Practical examples of modeling choices and their consequences for risk assessment

EPA Science Inventory

Although benchmark dose (BMD) modeling has become the preferred approach to identifying a point of departure (POD) over the No Observed Adverse Effect Level, there remain challenges to its application in human health risk assessment. BMD modeling, as currently implemented by the...

What is a food and what is a medicinal product in the European Union? Use of the benchmark dose (BMD) methodology to define a threshold for "pharmacological action".

PubMed

Lachenmeier, Dirk W; Steffen, Christian; el-Atma, Oliver; Maixner, Sibylle; Löbell-Behrends, Sigrid; Kohl-Himmelseher, Matthias

2012-11-01

The decision criterion for the demarcation between foods and medicinal products in the EU is the significant "pharmacological action". Based on six examples of substances with ambivalent status, the benchmark dose (BMD) method is evaluated to provide a threshold for pharmacological action. Using significant dose-response models from literature clinical trial data or epidemiology, the BMD values were 63mg/day for caffeine, 5g/day for alcohol, 6mg/day for lovastatin, 769mg/day for glucosamine sulfate, 151mg/day for Ginkgo biloba extract, and 0.4mg/day for melatonin. The examples for caffeine and alcohol validate the approach because intake above BMD clearly exhibits pharmacological action. Nevertheless, due to uncertainties in dose-response modelling as well as the need for additional uncertainty factors to consider differences in sensitivity within the human population, a "borderline range" on the dose-response curve remains. "Pharmacological action" has proven to be not very well suited as binary decision criterion between foods and medicinal product. The European legislator should rethink the definition of medicinal products, as the current situation based on complicated case-by-case decisions on pharmacological action leads to an unregulated market flooded with potentially illegal food supplements. Copyright © 2012 Elsevier Inc. All rights reserved.

Benchmark dose for cadmium exposure and elevated N-acetyl-β-D-glucosaminidase: a meta-analysis.

PubMed

Liu, CuiXia; Li, YuBiao; Zhu, ChunShui; Dong, ZhaoMin; Zhang, Kun; Zhao, YanBin; Xu, YiLu

2016-10-01

Cadmium (Cd) is a well-known nephrotoxic contaminant, and N-acetyl-β-D-glucosaminidase (NAG) is considered to be an early and sensitive marker of tubular dysfunction. The link between Cd exposure and NAG level enables us to derive the benchmark dose (BMD) of Cd. Although several reports have already documented urinary Cd (UCd)-NAG relationships and BMD estimations, high heterogeneities arise due to the sub-populations (age, gender, and ethnicity) and BMD methodologies being employed. To clarify the influences that these variables exert, firstly, a random effect meta-analysis was performed in this study to correlate the UCd and NAG based on 92 datasets collected from 30 publications. Later, this established correlation (Ln(NAG) = 0.51 × Ln(UCd) + 0.83) was applied to derive the UCd BMD 5 of 1.76 μg/g creatinine and 95 % lower confidence limit of BMD 5 (BMDL 5 ) of 1.67 μg/g creatinine. While the regressions for different age groups and genders differed slightly, it is age and not gender that significantly affects BMD estimations. Ethnic differences may require further investigation given that limited data is currently available. Based on a comprehensive and systematic literature review, this study is a new attempt to quantify the UCd-NAG link and estimate BMD.

Potential uncertainty reduction in model-averaged benchmark dose estimates informed by an additional dose study.

PubMed

Shao, Kan; Small, Mitchell J

2011-10-01

A methodology is presented for assessing the information value of an additional dosage experiment in existing bioassay studies. The analysis demonstrates the potential reduction in the uncertainty of toxicity metrics derived from expanded studies, providing insights for future studies. Bayesian methods are used to fit alternative dose-response models using Markov chain Monte Carlo (MCMC) simulation for parameter estimation and Bayesian model averaging (BMA) is used to compare and combine the alternative models. BMA predictions for benchmark dose (BMD) are developed, with uncertainty in these predictions used to derive the lower bound BMDL. The MCMC and BMA results provide a basis for a subsequent Monte Carlo analysis that backcasts the dosage where an additional test group would have been most beneficial in reducing the uncertainty in the BMD prediction, along with the magnitude of the expected uncertainty reduction. Uncertainty reductions are measured in terms of reduced interval widths of predicted BMD values and increases in BMDL values that occur as a result of this reduced uncertainty. The methodology is illustrated using two existing data sets for TCDD carcinogenicity, fitted with two alternative dose-response models (logistic and quantal-linear). The example shows that an additional dose at a relatively high value would have been most effective for reducing the uncertainty in BMA BMD estimates, with predicted reductions in the widths of uncertainty intervals of approximately 30%, and expected increases in BMDL values of 5-10%. The results demonstrate that dose selection for studies that subsequently inform dose-response models can benefit from consideration of how these models will be fit, combined, and interpreted. © 2011 Society for Risk Analysis.

BMDExpress Data Viewer: A Visualization Tool to Analyze BMDExpress Datasets(SoTC)

EPA Science Inventory

Background: Benchmark Dose (BMD) modelling is a mathematical approach used to determine where a dose-response change begins to take place relative to controls following chemical exposure. BMDs are being increasingly applied in regulatory toxicology to estimate acceptable exposure...

BMDExpress Data Viewer: A Visualization Tool to Analyze BMDExpress Datasets (STC symposium)

EPA Science Inventory

Background: Benchmark Dose (BMD) modelling is a mathematical approach used to determine where a dose-response change begins to take place relative to controls following chemical exposure. BMDs are being increasingly applied in regulatory toxicology to estimate acceptable exposure...

Developing chemical criteria for wildlife: The benchmark dose versus NOAEL approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linder, G.

1995-12-31

Wildlife may be exposed to a wide variety of chemicals in their environment, and various strategies for evaluating wildlife risk for these chemicals have been developed. One, a ``no-observable-adverse-effects-level`` or NOAEL-approach has increasingly been applied to develop chemical criteria for wildlife. In this approach, the NOAEL represents the highest experimental concentration at which there is no statistically significant change in some toxicity endpoint relative to a control. Another, the ``benchmark dose`` or BMD-approach relies on the lower confidence limit for a concentration that corresponds to a small, but statistically significant, change in effect over some reference condition. Rather than correspondingmore » to a single experimental concentration as does the NOAEL, the BMD-approach considers the full concentration response curve for derivation of the BMD. Here, using a variety of vertebrates and an assortment of chemicals (including carbofuran, paraquat, methylmercury, cadmium, zinc, and copper), the NOAEL-approach will be critically evaluated relative to the BMD approach. Statistical models used in the BMD approach suggest these methods are potentially available for eliminating safety factors in risk calculations. A reluctance to recommend this, however, stems from the uncertainty associated with the shape of concentration-response curves at low concentrations. Also, with existing data the derivation of BMDs has shortcomings when sample size is small (10 or fewer animals per treatment). The success of BMD models clearly depends upon the continued collection of wildlife data in the field and laboratory, the design of toxicity studies sufficient for BMD calculations, and complete reporting of these results in the literature. Overall, the BMD approach for developing chemical criteria for wildlife should be given further consideration, since it more fully evaluates concentration-response data.« less

DOSE-RESPONSE ASSESSMENT FOR DEVELOPMENTAL TOXICITY III. STATISTICAL MODELS

EPA Science Inventory

Although quantitative modeling has been central to cancer risk assessment for years, the concept of do@e-response modeling for developmental effects is relatively new. he benchmark dose (BMD) approach has been proposed for use with developmental (as well as other noncancer) endpo...

BMDExpress Data Viewer - A visualization Tool to Analyze BMDExpress Datasets (Health Canada Science Forum)

EPA Science Inventory

Benchmark Dose (BMD) modelling is a mathematical approach used to determine where a dose-response change begins to take place relative to controls following chemical exposure. BMDs are being increasingly applied in regulatory toxicology to determine points of departure. BMDExpres...

Evaluating MoE and its Uncertainty and Variability for Food Contaminants (EuroTox presentation)

EPA Science Inventory

Margin of Exposure (MoE), is a metric for quantifying the relationship between exposure and hazard. Ideally, it is the ratio of the dose associated with hazard and an estimate of exposure. For example, hazard may be characterized by a benchmark dose (BMD), and, for food contami...

75 FR 40729 - Residues of Quaternary Ammonium Compounds, N-Alkyl (C12-14

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-14

.... Systemic toxicity occurs after absorption and distribution of the chemical to tissues in the body. Such... identified (the LOAEL) or a Benchmark Dose (BMD) approach is sometimes used for risk assessment. Uncertainty.... No systemic effects observed up to 20 mg/ kg/day, highest dose of technical that could be tested...

Mechanism-based risk assessment strategy for drug-induced cholestasis using the transcriptional benchmark dose derived by toxicogenomics.

PubMed

Kawamoto, Taisuke; Ito, Yuichi; Morita, Osamu; Honda, Hiroshi

2017-01-01

Cholestasis is one of the major causes of drug-induced liver injury (DILI), which can result in withdrawal of approved drugs from the market. Early identification of cholestatic drugs is difficult due to the complex mechanisms involved. In order to develop a strategy for mechanism-based risk assessment of cholestatic drugs, we analyzed gene expression data obtained from the livers of rats that had been orally administered with 12 known cholestatic compounds repeatedly for 28 days at three dose levels. Qualitative analyses were performed using two statistical approaches (hierarchical clustering and principle component analysis), in addition to pathway analysis. The transcriptional benchmark dose (tBMD) and tBMD 95% lower limit (tBMDL) were used for quantitative analyses, which revealed three compound sub-groups that produced different types of differential gene expression; these groups of genes were mainly involved in inflammation, cholesterol biosynthesis, and oxidative stress. Furthermore, the tBMDL values for each test compound were in good agreement with the relevant no observed adverse effect level. These results indicate that our novel strategy for drug safety evaluation using mechanism-based classification and tBMDL would facilitate the application of toxicogenomics for risk assessment of cholestatic DILI.

Benchmark concentrations for methyl mercury obtained from the 9-year follow-up of the Seychelles Child Development Study.

PubMed

van Wijngaarden, Edwin; Beck, Christopher; Shamlaye, Conrad F; Cernichiari, Elsa; Davidson, Philip W; Myers, Gary J; Clarkson, Thomas W

2006-09-01

Methyl mercury (MeHg) is highly toxic to the developing nervous system. Human exposure is mainly from fish consumption since small amounts are present in all fish. Findings of developmental neurotoxicity following high-level prenatal exposure to MeHg raised the question of whether children whose mothers consumed fish contaminated with background levels during pregnancy are at an increased risk of impaired neurological function. Benchmark doses determined from studies in New Zealand, and the Faroese and Seychelles Islands indicate that a level of 4-25 parts per million (ppm) measured in maternal hair may carry a risk to the infant. However, there are numerous sources of uncertainty that could affect the derivation of benchmark doses, and it is crucial to continue to investigate the most appropriate derivation of safe consumption levels. Earlier, we published the findings from benchmark analyses applied to the data collected on the Seychelles main cohort at the 66-month follow-up period. Here, we expand on the main cohort analyses by determining the benchmark doses (BMD) of MeHg level in maternal hair based on 643 Seychellois children for whom 26 different neurobehavioral endpoints were measured at 9 years of age. Dose-response models applied to these continuous endpoints incorporated a variety of covariates and included the k-power model, the Weibull model, and the logistic model. The average 95% lower confidence limit of the BMD (BMDL) across all 26 endpoints varied from 20.1 ppm (range=17.2-22.5) for the logistic model to 20.4 ppm (range=17.9-23.0) for the k-power model. These estimates are somewhat lower than those obtained after 66 months of follow-up. The Seychelles Child Development Study continues to provide a firm scientific basis for the derivation of safe levels of MeHg consumption.

Benchmark Dose Modeling Estimates of the Concentrations of Inorganic Arsenic That Induce Changes to the Neonatal Transcriptome, Proteome, and Epigenome in a Pregnancy Cohort.

PubMed

Rager, Julia E; Auerbach, Scott S; Chappell, Grace A; Martin, Elizabeth; Thompson, Chad M; Fry, Rebecca C

2017-10-16

Prenatal inorganic arsenic (iAs) exposure influences the expression of critical genes and proteins associated with adverse outcomes in newborns, in part through epigenetic mediators. The doses at which these genomic and epigenomic changes occur have yet to be evaluated in the context of dose-response modeling. The goal of the present study was to estimate iAs doses that correspond to changes in transcriptomic, proteomic, epigenomic, and integrated multi-omic signatures in human cord blood through benchmark dose (BMD) modeling. Genome-wide DNA methylation, microRNA expression, mRNA expression, and protein expression levels in cord blood were modeled against total urinary arsenic (U-tAs) levels from pregnant women exposed to varying levels of iAs. Dose-response relationships were modeled in BMDExpress, and BMDs representing 10% response levels were estimated. Overall, DNA methylation changes were estimated to occur at lower exposure concentrations in comparison to other molecular endpoints. Multi-omic module eigengenes were derived through weighted gene co-expression network analysis, representing co-modulated signatures across transcriptomic, proteomic, and epigenomic profiles. One module eigengene was associated with decreased gestational age occurring alongside increased iAs exposure. Genes/proteins within this module eigengene showed enrichment for organismal development, including potassium voltage-gated channel subfamily Q member 1 (KCNQ1), an imprinted gene showing differential methylation and expression in response to iAs. Modeling of this prioritized multi-omic module eigengene resulted in a BMD(BMDL) of 58(45) μg/L U-tAs, which was estimated to correspond to drinking water arsenic concentrations of 51(40) μg/L. Results are in line with epidemiological evidence supporting effects of prenatal iAs occurring at levels <100 μg As/L urine. Together, findings present a variety of BMD measures to estimate doses at which prenatal iAs exposure influences neonatal outcome-relevant transcriptomic, proteomic, and epigenomic profiles.

Multiple exposures to indoor contaminants: Derivation of benchmark doses and relative potency factors based on male reprotoxic effects.

PubMed

Fournier, K; Tebby, C; Zeman, F; Glorennec, P; Zmirou-Navier, D; Bonvallot, N

2016-02-01

Semi-Volatile Organic Compounds (SVOCs) are commonly present in dwellings and several are suspected of having effects on male reproductive function mediated by an endocrine disruption mode of action. To improve knowledge of the health impact of these compounds, cumulative toxicity indicators are needed. This work derives Benchmark Doses (BMD) and Relative Potency Factors (RPF) for SVOCs acting on the male reproductive system through the same mode of action. We included SVOCs fulfilling the following conditions: detection frequency (>10%) in French dwellings, availability of data on the mechanism/mode of action for male reproductive toxicity, and availability of comparable dose-response relationships. Of 58 SVOCs selected, 18 induce a decrease in serum testosterone levels. Six have sufficient and comparable data to derive BMDs based on 10 or 50% of the response. The SVOCs inducing the largest decrease in serum testosterone concentration are: for 10%, bisphenol A (BMD10 = 7.72E-07 mg/kg bw/d; RPF10 = 7,033,679); for 50%, benzo[a]pyrene (BMD50 = 0.030 mg/kg bw/d; RPF50 = 1630), and the one inducing the smallest one is benzyl butyl phthalate (RPF10 and RPF50 = 0.095). This approach encompasses contaminants from diverse chemical families acting through similar modes of action, and makes possible a cumulative risk assessment in indoor environments. The main limitation remains the lack of comparable toxicological data. Copyright © 2015 Elsevier Inc. All rights reserved.

A health risk benchmark for the neurologic effects of styrene: comparison with NOAEL/LOAEL approach.

PubMed

Rabovsky, J; Fowles, J; Hill, M D; Lewis, D C

2001-02-01

Benchmark dose (BMD) analysis was used to estimate an inhalation benchmark concentration for styrene neurotoxicity. Quantal data on neuropsychologic test results from styrene-exposed workers [Mutti et al. (1984). American Journal of Industrial Medicine, 5, 275-286] were used to quantify neurotoxicity, defined as the percent of tested workers who responded abnormally to > or = 1, > or = 2, or > or = 3 out of a battery of eight tests. Exposure was based on previously published results on mean urinary mandelic- and phenylglyoxylic acid levels in the workers, converted to air styrene levels (15, 44, 74, or 115 ppm). Nonstyrene-exposed workers from the same region served as a control group. Maximum-likelihood estimates (MLEs) and BMDs at 5 and 10% response levels of the exposed population were obtained from log-normal analysis of the quantal data. The highest MLE was 9 ppm (BMD = 4 ppm) styrene and represents abnormal responses to > or = 3 tests by 10% of the exposed population. The most health-protective MLE was 2 ppm styrene (BMD = 0.3 ppm) and represents abnormal responses to > or = 1 test by 5% of the exposed population. A no observed adverse effect level/lowest observed adverse effect level (NOAEL/LOAEL) analysis of the same quantal data showed workers in all styrene exposure groups responded abnormally to > or = 1, > or = 2, or > or = 3 tests, compared to controls, and the LOAEL was 15 ppm. A comparison of the BMD and NOAEL/LOAEL analyses suggests that at air styrene levels below the LOAEL, a segment of the worker population may be adversely affected. The benchmark approach will be useful for styrene noncancer risk assessment purposes by providing a more accurate estimate of potential risk that should, in turn, help to reduce the uncertainty that is a common problem in setting exposure levels.

BMDExpress Data Viewer: A Visualization Tool to Analyze ...

EPA Pesticide Factsheets

Regulatory agencies increasingly apply benchmark dose (BMD) modeling to determine points of departure in human risk assessments. BMDExpress applies BMD modeling to transcriptomics datasets and groups genes to biological processes and pathways for rapid assessment of doses at which biological perturbations occur. However, graphing and analytical capabilities within BMDExpress are limited, and the analysis of output files is challenging. We developed a web-based application, BMDExpress Data Viewer, for visualization and graphical analyses of BMDExpress output files. The software application consists of two main components: ‘Summary Visualization Tools’ and ‘Dataset Exploratory Tools’. We demonstrate through two case studies that the ‘Summary Visualization Tools’ can be used to examine and assess the distributions of probe and pathway BMD outputs, as well as derive a potential regulatory BMD through the modes or means of the distributions. The ‘Functional Enrichment Analysis’ tool presents biological processes in a two-dimensional bubble chart view. By applying filters of pathway enrichment p-value and minimum number of significant genes, we showed that the Functional Enrichment Analysis tool can be applied to select pathways that are potentially sensitive to chemical perturbations. The ‘Multiple Dataset Comparison’ tool enables comparison of BMDs across multiple experiments (e.g., across time points, tissues, or organisms, etc.). The ‘BMDL-BM

Editor's Highlight: Application of Gene Set Enrichment Analysis for Identification of Chemically Induced, Biologically Relevant Transcriptomic Networks and Potential Utilization in Human Health Risk Assessment.

PubMed

Dean, Jeffry L; Zhao, Q Jay; Lambert, Jason C; Hawkins, Belinda S; Thomas, Russell S; Wesselkamper, Scott C

2017-05-01

The rate of new chemical development in commerce combined with a paucity of toxicity data for legacy chemicals presents a unique challenge for human health risk assessment. There is a clear need to develop new technologies and incorporate novel data streams to more efficiently inform derivation of toxicity values. One avenue of exploitation lies in the field of transcriptomics and the application of gene expression analysis to characterize biological responses to chemical exposures. In this context, gene set enrichment analysis (GSEA) was employed to evaluate tissue-specific, dose-response gene expression data generated following exposure to multiple chemicals for various durations. Patterns of transcriptional enrichment were evident across time and with increasing dose, and coordinated enrichment plausibly linked to the etiology of the biological responses was observed. GSEA was able to capture both transient and sustained transcriptional enrichment events facilitating differentiation between adaptive versus longer term molecular responses. When combined with benchmark dose (BMD) modeling of gene expression data from key drivers of biological enrichment, GSEA facilitated characterization of dose ranges required for enrichment of biologically relevant molecular signaling pathways, and promoted comparison of the activation dose ranges required for individual pathways. Median transcriptional BMD values were calculated for the most sensitive enriched pathway as well as the overall median BMD value for key gene members of significantly enriched pathways, and both were observed to be good estimates of the most sensitive apical endpoint BMD value. Together, these efforts support the application of GSEA to qualitative and quantitative human health risk assessment. Published by Oxford University Press on behalf of the Society of Toxicology 2017. This work is written by US Government employees and is in the public domain in the US.

Quantitative comparison between in vivo DNA adduct formation from exposure to selected DNA-reactive carcinogens, natural background levels of DNA adduct formation and tumour incidence in rodent bioassays.

PubMed

Paini, Alicia; Scholz, Gabriele; Marin-Kuan, Maricel; Schilter, Benoît; O'Brien, John; van Bladeren, Peter J; Rietjens, Ivonne M C M

2011-09-01

This study aimed at quantitatively comparing the occurrence/formation of DNA adducts with the carcinogenicity induced by a selection of DNA-reactive genotoxic carcinogens. Contrary to previous efforts, we used a very uniform set of data, limited to in vivo rat liver studies in order to investigate whether a correlation can be obtained, using a benchmark dose (BMD) approach. Dose-response data on both carcinogenicity and in vivo DNA adduct formation were available for six compounds, i.e. 2-acetylaminofluorene, aflatoxin B1, methyleugenol, safrole, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and tamoxifen. BMD(10) values for liver carcinogenicity were calculated using the US Environmental Protection Agency BMD software. DNA adduct levels at this dose were extrapolated assuming linearity of the DNA adduct dose response. In addition, the levels of DNA adducts at the BMD(10) were compared to available data on endogenous background DNA damage in the target organ. Although for an individual carcinogen the tumour response increases when adduct levels increase, our results demonstrate that when comparing different carcinogens, no quantitative correlation exists between the level of DNA adduct formation and carcinogenicity. These data confirm that the quantity of DNA adducts formed by a DNA-reactive compound is not a carcinogenicity predictor but that other factors such as type of adduct and mutagenic potential may be equally relevant. Moreover, comparison to background DNA damage supports the notion that the mere occurrence of DNA adducts above or below the level of endogenous DNA damage is neither correlated to development of cancer. These data strongly emphasise the need to apply the mode of action framework to understand the contribution of other biological effect markers playing a role in carcinogenicity.

Hepatic transcriptomic alterations for N,N-dimethyl-p-toluidine (DMPT) and p-toluidine after 5-day exposure in rats.

PubMed

Dunnick, June K; Shockley, Keith R; Morgan, Daniel L; Brix, Amy; Travlos, Gregory S; Gerrish, Kevin; Michael Sanders, J; Ton, T V; Pandiri, Arun R

2017-04-01

N,N-dimethyl-p-toluidine (DMPT), an accelerant for methyl methacrylate monomers in medical devices, was a liver carcinogen in male and female F344/N rats and B6C3F1 mice in a 2-year oral exposure study. p-Toluidine, a structurally related chemical, was a liver carcinogen in mice but not in rats in an 18-month feed exposure study. In this current study, liver transcriptomic data were used to characterize mechanisms in DMPT and p-toluidine liver toxicity and for conducting benchmark dose (BMD) analysis. Male F344/N rats were exposed orally to DMPT or p-toluidine (0, 1, 6, 20, 60 or 120 mg/kg/day) for 5 days. The liver was examined for lesions and transcriptomic alterations. Both chemicals caused mild hepatic toxicity at 60 and 120 mg/kg and dose-related transcriptomic alterations in the liver. There were 511 liver transcripts differentially expressed for DMPT and 354 for p-toluidine at 120 mg/kg/day (false discovery rate threshold of 5 %). The liver transcriptomic alterations were characteristic of an anti-oxidative damage response (activation of the Nrf2 pathway) and hepatic toxicity. The top cellular processes in gene ontology (GO) categories altered in livers exposed to DMPT or p-toluidine were used for BMD calculations. The lower confidence bound benchmark doses for these chemicals were 2 mg/kg/day for DMPT and 7 mg/kg/day for p-toluidine. These studies show the promise of using 5-day target organ transcriptomic data to identify chemical-induced molecular changes that can serve as markers for preliminary toxicity risk assessment.

A Signal-to-Noise Crossover Dose as the Point of Departure for Health Risk Assessment

PubMed Central

Portier, Christopher J.; Krewski, Daniel

2011-01-01

Background: The U.S. National Toxicology Program (NTP) cancer bioassay database provides an opportunity to compare both existing and new approaches to determining points of departure (PoDs) for establishing reference doses (RfDs). Objectives: The aims of this study were a) to investigate the risk associated with the traditional PoD used in human health risk assessment [the no observed adverse effect level (NOAEL)]; b) to present a new approach based on the signal-to-noise crossover dose (SNCD); and c) to compare the SNCD and SNCD-based RfD with PoDs and RfDs based on the NOAEL and benchmark dose (BMD) approaches. Methods: The complete NTP database was used as the basis for these analyses, which were performed using the Hill model. We determined NOAELs and estimated corresponding extra risks. Lower 95% confidence bounds on the BMD (BMDLs) corresponding to extra risks of 1%, 5%, and 10% (BMDL01, BMDL05, and BMDL10, respectively) were also estimated. We introduce the SNCD as a new PoD, defined as the dose where the additional risk is equal to the “background noise” (the difference between the upper and lower bounds of the two-sided 90% confidence interval on absolute risk) or a specified fraction thereof. Results: The median risk at the NOAEL was approximately 10%, and the default uncertainty factor (UF = 100) was considered most applicable to the BMDL10. Therefore, we chose a target risk of 1/1,000 (0.1/100) to derive an SNCD-based RfD by linear extrapolation. At the median, this approach provided the same RfD as the BMDL10 divided by the default UF. Conclusions: Under a standard BMD approach, the BMDL10 is considered to be the most appropriate PoD. The SNCD approach, which is based on the lowest dose at which the signal can be reliably detected, warrants further development as a PoD for human health risk assessment. PMID:21813365

Transcriptional responses in the rat nasal epithelium following subchronic inhalation of naphthalene vapor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clewell, H.J., E-mail: hclewell@thehamner.org; Efremenko, A.; Campbell, J.L.

Male and female Fischer 344 rats were exposed to naphthalene vapors at 0 (controls), 0.1, 1, 10, and 30 ppm for 6 h/d, 5 d/wk, over a 90-day period. Following exposure, the respiratory epithelium and olfactory epithelium from the nasal cavity were dissected separately, RNA was isolated, and gene expression microarray analysis was conducted. Only a few significant gene expression changes were observed in the olfactory or respiratory epithelium of either gender at the lowest concentration (0.1 ppm). At the 1.0 ppm concentration there was limited evidence of an oxidative stress response in the respiratory epithelium, but not in themore » olfactory epithelium. In contrast, a large number of significantly enriched cellular pathway responses were observed in both tissues at the two highest concentrations (10 and 30 ppm, which correspond to tumorigenic concentrations in the NTP bioassay). The nature of these responses supports a mode of action involving oxidative stress, inflammation and proliferation. These results are consistent with a dose-dependent transition in the mode of action for naphthalene toxicity/carcinogenicity between 1.0 and 10 ppm in the rat. In the female olfactory epithelium (the gender/site with the highest incidences of neuroblastomas in the NTP bioassay), the lowest concentration at which any signaling pathway was significantly affected, as characterized by the median pathway benchmark dose (BMD) or its 95% lower bound (BMDL) was 6.0 or 3.7 ppm, respectively, while the lowest female olfactory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 16.1, 11.1, and 8.4 ppm, respectively. In the male respiratory epithelium (the gender/site with the highest incidences of adenomas in the NTP bioassay), the lowest pathway BMD and BMDL were 0.4 and 0.3 ppm, respectively, and the lowest male respiratory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 0.5, 0.7, and 0.9 ppm, respectively. Using a published physiologically based pharmacokinetic (PBPK) model to estimate target tissue dose relevant to the proposed mode of action (total naphthalene metabolism per gram nasal tissue), the lowest transcriptional BMDLs from this analysis equate to human continuous naphthalene exposure at approximately 0.3 ppm. It is unlikely that significant effects of naphthalene or its metabolites will occur at exposures below this concentration. - Highlights: • We investigated mode of action for carcinogenicity of inhaled naphthalene in rats. • Gene expression changes were measured in rat nasal tissues after 90 day exposures. • Support a non-linear mode of action (oxidative stress, inflammation, and proliferation) • Suggest a dose-dependent transition in the mode of action between 1.0 and 10 ppm • Transcriptional benchmark doses could inform point of departure for risk assessment.« less

Comparing BMD‐derived genotoxic potency estimations across variants of the transgenic rodent gene mutation assay

PubMed Central

Johnson, George E.; Battaion, Hannah L.; Slob, Wout; Gollapudi, B.

2017-01-01

There is growing interest in quantitative analysis of in vivo genetic toxicity dose‐response data, and use of point‐of‐departure (PoD) metrics such as the benchmark dose (BMD) for human health risk assessment (HHRA). Currently, multiple transgenic rodent (TGR) assay variants, employing different rodent strains and reporter transgenes, are used for the assessment of chemically‐induced genotoxic effects in vivo. However, regulatory issues arise when different PoD values (e.g., lower BMD confidence intervals or BMDLs) are obtained for the same compound across different TGR assay variants. This study therefore employed the BMD approach to examine the ability of different TGR variants to yield comparable genotoxic potency estimates. Review of over 2000 dose‐response datasets identified suitably‐matched dose‐response data for three compounds (ethyl methanesulfonate or EMS, N‐ethyl‐N‐nitrosourea or ENU, and dimethylnitrosamine or DMN) across four commonly‐used murine TGR variants (Muta™Mouse lacZ, Muta™Mouse cII, gpt delta and BigBlue® lacI). Dose‐response analyses provided no conclusive evidence that TGR variant choice significantly influences the derived genotoxic potency estimate. This conclusion was reliant upon taking into account the importance of comparing BMD confidence intervals as opposed to directly comparing PoD values (e.g., comparing BMDLs). Comparisons with earlier works suggested that with respect to potency determination, tissue choice is potentially more important than choice of TGR assay variant. Scoring multiple tissues selected on the basis of supporting toxicokinetic information is therefore recommended. Finally, we used typical within‐group variances to estimate preliminary endpoint‐specific benchmark response (BMR) values across several TGR variants/tissues. We discuss why such values are required for routine use of genetic toxicity PoDs for HHRA. Environ. Mol. Mutagen. 58:632–643, 2017. © 2017 Her Majesty the Queen in Right of Canada. Environmental and Molecular Mutagenesis Published by Wiley Periodicals, Inc. PMID:28945287

Cumulative organophosphate pesticide exposure and risk assessment among pregnant women living in an agricultural community: a case study from the CHAMACOS cohort.

PubMed Central

Castorina, Rosemary; Bradman, Asa; McKone, Thomas E; Barr, Dana B; Harnly, Martha E; Eskenazi, Brenda

2003-01-01

Approximately 230,000 kg of organophosphate (OP) pesticides are applied annually in California's Salinas Valley. These activities have raised concerns about exposures to area residents. We collected three spot urine samples from pregnant women (between 1999 and 2001) enrolled in CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas), a longitudinal birth cohort study, and analyzed them for six dialkyl phosphate metabolites. We used urine from 446 pregnant women to estimate OP pesticide doses with two deterministic steady-state modeling methods: method 1, which assumed the metabolites were attributable entirely to a single diethyl or dimethyl OP pesticide; and method 2, which adapted U.S. Environmental Protection Agency (U.S. EPA) draft guidelines for cumulative risk assessment to estimate dose from a mixture of OP pesticides that share a common mechanism of toxicity. We used pesticide use reporting data for the Salinas Valley to approximate the mixture to which the women were exposed. Based on average OP pesticide dose estimates that assumed exposure to a single OP pesticide (method 1), between 0% and 36.1% of study participants' doses failed to attain a margin of exposure (MOE) of 100 relative to the U.S. EPA oral benchmark dose(10) (BMD(10)), depending on the assumption made about the parent compound. These BMD(10) values are doses expected to produce a 10% reduction in brain cholinesterase activity compared with background response in rats. Given the participants' average cumulative OP pesticide dose estimates (method 2) and regardless of the index chemical selected, we found that 14.8% of the doses failed to attain an MOE of 100 relative to the BMD(10) of the selected index. An uncertainty analysis of the pesticide mixture parameter, which is extrapolated from pesticide application data for the study area and not directly quantified for each individual, suggests that this point estimate could range from 1 to 34%. In future analyses, we will use pesticide-specific urinary metabolites, when available, to evaluate cumulative OP pesticide exposures. PMID:14527844

Is multidetector CT-based bone mineral density and quantitative bone microstructure assessment at the spine still feasible using ultra-low tube current and sparse sampling?

PubMed

Mei, Kai; Kopp, Felix K; Bippus, Rolf; Köhler, Thomas; Schwaiger, Benedikt J; Gersing, Alexandra S; Fehringer, Andreas; Sauter, Andreas; Münzel, Daniela; Pfeiffer, Franz; Rummeny, Ernst J; Kirschke, Jan S; Noël, Peter B; Baum, Thomas

2017-12-01

Osteoporosis diagnosis using multidetector CT (MDCT) is limited to relatively high radiation exposure. We investigated the effect of simulated ultra-low-dose protocols on in-vivo bone mineral density (BMD) and quantitative trabecular bone assessment. Institutional review board approval was obtained. Twelve subjects with osteoporotic vertebral fractures and 12 age- and gender-matched controls undergoing routine thoracic and abdominal MDCT were included (average effective dose: 10 mSv). Ultra-low radiation examinations were achieved by simulating lower tube currents and sparse samplings at 50%, 25% and 10% of the original dose. BMD and trabecular bone parameters were extracted in T10-L5. Except for BMD measurements in sparse sampling data, absolute values of all parameters derived from ultra-low-dose data were significantly different from those derived from original dose images (p<0.05). BMD, apparent bone fraction and trabecular thickness were still consistently lower in subjects with than in those without fractures (p<0.05). In ultra-low-dose scans, BMD and microstructure parameters were able to differentiate subjects with and without vertebral fractures, suggesting osteoporosis diagnosis is feasible. However, absolute values differed from original values. BMD from sparse sampling appeared to be more robust. This dose-dependency of parameters should be considered for future clinical use. • BMD and quantitative bone parameters are assessable in ultra-low-dose in vivo MDCT scans. • Bone mineral density does not change significantly when sparse sampling is applied. • Quantitative trabecular bone microstructure measurements are sensitive to dose reduction. • Osteoporosis subjects could be differentiated even at 10% of original dose. • Radiation exposure should be considered when comparing quantitative bone parameters.

Short-term, high-dose glucocorticoid treatment does not contribute to reduced bone mineral density in patients with multiple sclerosis.

PubMed

Olsson, A; Oturai, D B; Sørensen, P S; Oturai, P S; Oturai, A B

2015-10-01

Patients with multiple sclerosis (MS) are at increased risk of reduced bone mineral density (BMD). A contributing factor might be treatment with high-dose glucocorticoids (GCs). The objective of this paper is to assess bone mass in patients with MS and evaluate the importance of short-term, high-dose GC treatment and other risk factors that affect BMD in patients with MS. A total of 260 patients with MS received short-term high-dose GC treatment and had their BMD measured by dual x-ray absorptiometry. BMD was compared to a healthy age-matched reference population (Z-scores). Data regarding GCs, age, body mass index (BMI), serum 25(OH)D, disease duration and severity were collected retrospectively and analysed in a multiple linear regression analysis to evaluate the association between each risk factor and BMD. Osteopenia was present in 38% and osteoporosis in 7% of the study population. Mean Z-score was significantly below zero, indicating a decreased BMD in our MS patients. Multiple linear regression analysis showed no significant association between GCs and BMD. In contrast, age, BMI and disease severity were independently associated with both lumbar and femoral BMD. Reduced BMD was prevalent in patients with MS. GC treatment appears not to be the primary underlying cause of secondary osteoporosis in MS patients. © The Author(s), 2015.

Selection of appropriate tumour data sets for Benchmark Dose Modelling (BMD) and derivation of a Margin of Exposure (MoE) for substances that are genotoxic and carcinogenic: considerations of biological relevance of tumour type, data quality and uncertainty assessment.

PubMed

Edler, Lutz; Hart, Andy; Greaves, Peter; Carthew, Philip; Coulet, Myriam; Boobis, Alan; Williams, Gary M; Smith, Benjamin

2014-08-01

This article addresses a number of concepts related to the selection and modelling of carcinogenicity data for the calculation of a Margin of Exposure. It follows up on the recommendations put forward by the International Life Sciences Institute - European branch in 2010 on the application of the Margin of Exposure (MoE) approach to substances in food that are genotoxic and carcinogenic. The aims are to provide practical guidance on the relevance of animal tumour data for human carcinogenic hazard assessment, appropriate selection of tumour data for Benchmark Dose Modelling, and approaches for dealing with the uncertainty associated with the selection of data for modelling and, consequently, the derived Point of Departure (PoD) used to calculate the MoE. Although the concepts outlined in this article are interrelated, the background expertise needed to address each topic varies. For instance, the expertise needed to make a judgement on biological relevance of a specific tumour type is clearly different to that needed to determine the statistical uncertainty around the data used for modelling a benchmark dose. As such, each topic is dealt with separately to allow those with specialised knowledge to target key areas of guidance and provide a more in-depth discussion on each subject for those new to the concept of the Margin of Exposure approach. Copyright © 2013 ILSI Europe. Published by Elsevier Ltd.. All rights reserved.

Chronic use of low-dose aspirin is not associated with lower bone mineral density in the general population.

PubMed

Bonten, T N; de Mutsert, R; Rosendaal, F R; Jukema, J W; van der Bom, J G; de Jongh, R T; den Heijer, M

2017-10-01

Low-dose aspirin is the cornerstone of secondary prevention of cardiovascular disease. Previous studies suggested that the use of aspirin is associated with an increased fracture risk. However, there is uncertainty whether this is due to an effect of aspirin on bone mineral density (BMD). Between 2008 and 2012, information on medication use and dual X-ray absorptiometry measured vertebral and femoral BMD of 916 participants was collected in the Netherland Epidemiology of Obesity study. The cross-sectional association between chronic low-dose aspirin use and BMD was estimated using linear regression, controlling for demography, body composition, comorbidity and other medication use which could affect BMD. A subgroup analysis in postmenopausal women (n=329) was conducted. After full adjustment, there was no difference between aspirin users and non-users for vertebral BMD (adjusted mean difference: 0.036 (95% CI -0.027 to 0.100) g/cm 2 ) and femoral BMD (adjusted mean difference: 0.001 (-0.067 to 0.069) g/cm 2 ). Also in the subgroup of postmenopausal women, aspirin use was not associated with lower vertebral (adjusted mean difference: 0.069 (-0.046 to 0.184) g/cm 2 ) or femoral BMD (adjusted mean difference: -0.055 (-0.139;0.029) g/cm 2 ). Chronic use of low-dose aspirin is not associated with lower BMD in the general population. The increased risk of fractures observed in aspirin users in previous studies is therefore more likely to be the result of common causes of aspirin use and fractures, but not of direct effects of aspirin on BMD. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

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ABSTRACT:Only a fraction of chemicals in commerce have been fully assessed for their potential hazards to human health due to difficulties involved in conventional regulatory tests. It has recently been proposed that quantitative transcriptomic data can be used to determine benchmark dose (BMD) and estimate a point of departure (POD). Several studies have shown that transcriptional PODs correlate with PODs derived from analysis of pathological changes, but there is no consensus on how the genes that are used to derive a transcriptional POD should be selected. Because of very large number of unrelated genes in gene expression data, the process of selecting subsets of informative genes is a major challenge. We used published microarray data from studies on rats exposed orally to multiple doses of six chemicals for 5, 14, 28, and 90 days. We evaluated eight different approaches to select genes for POD derivation and compared them to three previously proposed approaches. The relationship between transcriptional BMDs derived using these 11 approaches were compared with PODs derived from apical data that might be used in a human health risk assessment. We found that transcriptional benchmark dose values for all 11 approaches were remarkably aligned with different apical PODs, while a subset of between 3 and 8 of the approaches met standard statistical criteria across the 5-, 14-, 28-, and 90-day time points and thus qualify as effective estimates of apical PODs. Our r

Using early biomarker data to predict long-term bone mineral density: application of semi-mechanistic bone cycle model on denosumab data.

PubMed

Zheng, Jenny; van Schaick, Erno; Wu, Liviawati Sutjandra; Jacqmin, Philippe; Perez Ruixo, Juan Jose

2015-08-01

Osteoporosis is a chronic skeletal disease characterized by low bone strength resulting in increased fracture risk. New treatments for osteoporosis are still an unmet medical need because current available treatments have various limitations. Bone mineral density (BMD) is an important endpoint for evaluating new osteoporosis treatments; however, the BMD response is often slower and less profound than that of bone turnover markers (BTMs). If the relationship between BTMs and BMD can be quantified, the BMD response can be predicted by the changes in BTM after a single dose; therefore, a decision based on BMD changes can be informed early. We have applied a bone cycle model to a phase 2 denosumab dose-ranging study in osteopenic women to quantitatively link serum denosumab pharmacokinetics, BTMs, and lumbar spine (LS) BMD. The data from two phase 3 denosumab studies in patients with low bone mass, FREEDOM and DEFEND, were used for external validation. Both internal and external visual predictive checks demonstrated that the model was capable of predicting LS BMD at the denosumab regimen of 60 mg every 6 months. It has been demonstrated that the model, in combination with the changes in BTMs observed from a single-dose study in men, is capable of predicting long-term BMD outcomes (e.g., LS BMD response in men after 1 year of treatment) in different populations. We propose that this model can be used to inform drug development decisions for osteoporosis treatment early via evaluating LS BMD response when BTM data become available in early trials.

The soy isoflavones for reducing bone loss study: 3-yr effects on pQCT bone mineral density and strength measures in postmenopausal women.

PubMed

Shedd-Wise, Kristine M; Alekel, D Lee; Hofmann, Heike; Hanson, Kathy B; Schiferl, Dan J; Hanson, Laura N; Van Loan, Marta D

2011-01-01

Soy isoflavones exert inconsistent bone density-preserving effects, but the bone strength-preserving effects in humans are unknown. Our double-blind randomized controlled trial examined 2 soy isoflavone doses (80 or 120mg/d) vs placebo tablets on volumetric bone mineral density (vBMD) and strength (by means of peripheral quantitative computed tomography) in healthy postmenopausal women (46-63yr). We measured 3-yr changes in cortical BMD (CtBMD), cortical thickness (CtThk), periosteal circumference (PC), endosteal circumference (EC), and strength-strain index (SSI) at 1/3 midshaft femur (N=171), and trabecular BMD (TbBMD), PC, and SSI at 4% distal tibia (N=162). We found no treatment effect on femur CtThk, PC, or EC, or tibia TbBMD or PC. The strongest predictors (negative) of tibia TbBMD and SSI and femur CtBMD were timepoint and bone resorption; whole-body fat mass was protective of SSI. As time since last menstrual period (TLMP) increased (p=0.012), 120-mg/d dose was protective of CtBMD. The strongest predictors of femur SSI were timepoint, bone resorption, and TLMP (protective). Isoflavone tablets were negative predictors of SSI, but 80-mg/d dose became protective as bone turnover increased (p=0.011). Soy isoflavone treatment for 3yr was modestly beneficial for midshaft femur vBMD as TLMP increased and for midshaft femur SSI as bone turnover increased. Copyright © 2011 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Oral toxicity of 3-nitro-1,2,4-triazol-5-one in rats.

PubMed

Crouse, Lee C B; Lent, Emily May; Leach, Glenn J

2015-01-01

3-Nitro-1,2,4-triazol-5-one (NTO), an insensitive explosive, was evaluated to assess potential environmental and human health effects. A 14-day oral toxicity study in Sprague-Dawley rats was conducted with NTO in polyethylene glycol -200 by gavage at doses of 0, 250, 500, 1000, 1500, or 2000 mg/kg-d. Body mass and food consumption decreased in males (2000 mg/kg-d), and testes mass was reduced at doses of 500 mg/kg-d and greater. Based on the findings in the 14-day study, a 90-day study was conducted at doses of 0, 30, 100, 315, or 1000 mg/kg-d NTO. There was no effect on food consumption, body mass, or neurobehavioral parameters. Males in the 315 and 1000 mg/kg-d groups had reduced testes mass with associated tubular degeneration and atrophy. The testicular effects were the most sensitive adverse effect and were used to derive a benchmark dose (BMD) of 70 mg/kg-d with a 10% effect level (BMDL10) of 40 mg/kg-d. © The Author(s) 2015.

Application of low-tube current with iterative model reconstruction on Philips Brilliance iCT Elite FHD in the accuracy of spinal QCT using a European spine phantom.

PubMed

Wu, Yan; Jiang, Yaojun; Han, Xueli; Wang, Mingyue; Gao, Jianbo

2018-02-01

To investigate the repeatability and accuracy of quantitative CT (QCT) measurement of bone mineral density (BMD) by low-mAs using iterative model reconstruction (IMR) technique based on phantom model. European spine phantom (ESP) was selected and measured on the Philips Brilliance iCT Elite FHD machine for 10 times. Data were transmitted to the QCT PRO workstation to measure BMD (mg/cm 3 ) of the ESP (L1, L2, L3). Scanning method: the voltage of X-ray tube is 120 kV, the electric current of X-ray tube output in five respective groups A-E were: 20, 30, 40, 50 and 60 mAs. Reconstruction: all data were reconstructed using filtered back projection (FBP), IR levels of hybrid iterative reconstruction (iDose 4 , levels 1, 2, 3, 4, 5, 6 were used) and IMR (levels 1, 2, 3 were used). ROIs were placed in the middle of L1, L2 and L3 spine phantom in each group. CT values, noise and contrast-to-noise ratio (CNR) were measured and calculated. One-way analysis of variance (ANOVA) was used to compare BMD values of different mAs and different IMR. Radiation dose [volume CT dose index (CTDI vol ) and dose length product (DLP)] was positively correlated with tube current. In L1 with low BMD, different mAs in FBP showed P<0.05, indicating statistically significant BMD in ESP. In other iterative algorithms, different mAs under same iterative algorithms showed P>0.05, indicating no difference in BMD. And P>0.05 was observed among BMD of spine phantom in L1, L2 and L3 under same mAs joined with varied iterative reconstruction. The BMD in L1 varied greatly during FBP reconstruction, and less variation was observed in reconstruction of IMR [1] and IMR [2]. The BMD of L2 changed more during FBP reconstruction, where less was observed in IMR [2]. The BMD of L3 varied greatly during FBP reconstruction, and was less varied in all levels of iDose 4 and reconstruction of IMR [2]. In addition, along with continuous mAs incensement, the CNRs in various algorithms continued to increase. Among them, CNR with the FBP algorithm is the lowest, and CNR of the IMR [3] algorithm is the highest. Repeated measurements of BMD with QCT in the ESP multicenter showed that BMD changes in L1-L3 are the least varied at IMR [2] algorithm. It is recommended to scan at 120 kV with 20 mAs combined with IMR [2] algorithm. In this way, the BMD of spine by QCT could be accurately measured, while radiation dosage significantly reduced and imaging quality improved at the same time.

Exercise frequency and bone mineral density development in exercising postmenopausal osteopenic women. Is there a critical dose of exercise for affecting bone? Results of the Erlangen Fitness and Osteoporosis Prevention Study.

PubMed

Kemmler, Wolfgang; von Stengel, Simon; Kohl, Matthias

2016-08-01

Due to older people's low sports participation rates, exercise frequency may be the most critical component for designing exercise protocols that address bone. The aims of the present article were to determine the independent effect of exercise frequency (ExFreq) and its corresponding changes on bone mineral density (BMD) and to identify the minimum effective dose that just relevantly affects bone. Based on the 16-year follow-up of the intense, consistently supervised Erlangen Fitness and Osteoporosis Prevention-Study, ExFreq was retrospectively determined in the exercise-group of 55 initially early-postmenopausal females with osteopenia. Linear mixed-effect regression analysis was conducted to determine the independent effect of ExFreq on BMD changes at lumbar spine and total hip. Minimum effective dose of ExFreq based on BMD changes less than the 90% quantile of the sedentary control-group (n=43). Cut-offs were determined after 4, 8, 12 and 16years using bootstrap with 5000 replications. After 16years, average ExFreq ranged between 1.02 and 2.96sessions/week (2.28±0.40sessions/week). ExFreq has an independent effect on LS-BMD (p<.001) and hip-BMD (p=.005) changes. Bootstrap analysis detected a minimum effective dose at about 2sessions/week/16years (cut-off LS-BMD: 2.11, 95% CI: 2.06-2.12; total hip-BMD: 2.22, 95% CI: 2.00-2.78sessions/week/16years). In summary, the minimum effective dose of exercise frequency that relevantly addresses BMD is quite high, at least compared with the low sport participation rate of older adults. This result might not be generalizable across all exercise types, protocols and cohorts, but it does indicate at least that even when applying high impact/high intensity programs, exercise frequency and its maintenance play a key role in bone adaptation. Copyright © 2016 Elsevier Inc. All rights reserved.

Bone and bone turnover.

PubMed

Crofton, Patricia M

2009-01-01

Children with cancer are exposed to multiple influences that may adversely affect bone health. Some treatments have direct deleterious effects on bone whilst others may have indirect effects mediated through various endocrine abnormalities. Most clinical outcome studies have concentrated on survivors of acute lymphoblastic leukaemia (ALL). There is now good evidence that earlier treatment protocols that included cranial irradiation with doses of 24 Gy or greater may result in growth hormone deficiency and low bone mineral density (BMD) in the lumbar spine and femoral neck. Under current protocols, BMD decreases during intensive chemotherapy and fracture risk increases. Although total body BMD may eventually return to normal after completion of chemotherapy, lumbar spine trabecular BMD may remain low for many years. The implications for long-term fracture risk are unknown. Risk factors for low BMD include high dose methotrexate, higher cumulative doses of glucocorticoids, male gender and low physical activity. BMD outcome in non-ALL childhood cancers has been less well studied but there is evidence that survivors of childhood brain or bone tumours, and survivors of bone marrow transplants for childhood malignancy, all have a high risk of long-term osteopenia. Long-term follow-up is required, with appropriate treatment of any endocrine abnormalities identified. Copyright (c) 2009 S. Karger AG, Basel.

Exploratory analysis of the potential relationship between urinary molybdenum and bone mineral density among adult men and women from NHANES 2007-2010.

PubMed

Lewis, Ryan C; Johns, Lauren E; Meeker, John D

2016-12-01

Human exposure to molybdenum (Mo) may play a role in reducing bone mineral density (BMD) by interfering with steroid sex hormone levels. To begin to address gaps in the literature on this topic, the potential relationship between urinary Mo (U-Mo) and BMD at the femoral neck (FN-BMD) and lumbar spine (LS-BMD) was explored in a sample of 1496 adults participating in the 2007-2010 cycles of the National Health and Nutrition Examination Survey. Associations were assessed using multiple linear regression models stratified on sex and age. In adjusted models for 50-80+ year-old women, there was a statistically significant inverse relationship between natural log-U-Mo and LS-BMD (p-value: 0.002), and a statistically significant dose-dependent decrease in LS-BMD with increasing U-Mo quartiles (trend p-value: 0.002). A suggestive (trend p-value: 0.08), dose-dependent decrease in FN-BMD with increasing U-Mo quartiles was noted in this group of women as well. All other adjusted models revealed no statistically significant or suggestive relationships between U-Mo and FN-BMD or LS-BMD. Bone health is important for overall human health and well-being and, given the exploratory nature of this work, additional studies are needed to confirm the results in other populations, and clarify the potential underlying mechanisms of Mo on BMD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intake of dehydrated nopal (Opuntia ficus indica) improves bone mineral density and calciuria in adult Mexican women.

PubMed

Aguilera-Barreiro, María de Los Angeles; Rivera-Márquez, José Alberto; Trujillo-Arriaga, Héctor Miguel; Tamayo Y Orozco, Juan Alfredo; Barreira-Mercado, Eduardo; Rodríguez-García, Mario E

2013-01-01

The intake of dehydrated nopal (DN) at a high stage of maturity along with high calcium content could improve bone mineral density (BMD) and calciuria and thus prevent osteoporosis. To evaluate the effect of calcium intake from a vegetable source (DN) on BMD and calciuria covering a 2-year period in menopausal and non-menopausal women with low bone mass (LBM). The study was quasi-experimental, blinded, and randomized, and included 131 Mexican women aged 35-55. Urinary calcium/creatinine index (CCI) was determined; BMD was analyzed on lumbar spine and total hip regions. Four groups were studied: Control group (CG), women with normocalciuria and a minimum dose of DN; experimental group 1 (EG1), women with hypercalciuria and a minimum dose of DN; experimental group 2 (EG2), women with hypercalciuria, and a maximum dose of DN; and normal group (NG) for reference in BMD. After the first semester of treatment, calciuria levels in women from both experimental groups returned to normal, remaining constant for the rest of the treatment. The percentage difference in BMD increased in the total hip region in the CG (pre 4.5% and post 2.1%) and EG2 (pre 1.8% and post 2.5%) groups significantly in comparison to NG and EG1, which exhibited a significant decrease in their BMD. BMD increased only for the lumbar region in the EG2 group (premenopausal). The use of a vegetable calcium source such as nopal improves BMD in women with LBM in the total hip and lumbar spine regions principally in the premenopausal women, maintaining constant and normal calciuria levels.

Intake of dehydrated nopal (Opuntia ficus indica) improves bone mineral density and calciuria in adult Mexican women

PubMed Central

Aguilera-Barreiro, María de los Angeles; Rivera-Márquez, José Alberto; Trujillo-Arriaga, Héctor Miguel; Tamayo y Orozco, Juan Alfredo; Barreira-Mercado, Eduardo; Rodríguez-García, Mario E

2013-01-01

Background The intake of dehydrated nopal (DN) at a high stage of maturity along with high calcium content could improve bone mineral density (BMD) and calciuria and thus prevent osteoporosis. Objective To evaluate the effect of calcium intake from a vegetable source (DN) on BMD and calciuria covering a 2-year period in menopausal and non-menopausal women with low bone mass (LBM). Methods The study was quasi-experimental, blinded, and randomized, and included 131 Mexican women aged 35–55. Urinary calcium/creatinine index (CCI) was determined; BMD was analyzed on lumbar spine and total hip regions. Four groups were studied: Control group (CG), women with normocalciuria and a minimum dose of DN; experimental group 1 (EG1), women with hypercalciuria and a minimum dose of DN; experimental group 2 (EG2), women with hypercalciuria, and a maximum dose of DN; and normal group (NG) for reference in BMD. Results After the first semester of treatment, calciuria levels in women from both experimental groups returned to normal, remaining constant for the rest of the treatment. The percentage difference in BMD increased in the total hip region in the CG (pre 4.5% and post 2.1%) and EG2 (pre 1.8% and post 2.5%) groups significantly in comparison to NG and EG1, which exhibited a significant decrease in their BMD. BMD increased only for the lumbar region in the EG2 group (premenopausal). Conclusion The use of a vegetable calcium source such as nopal improves BMD in women with LBM in the total hip and lumbar spine regions principally in the premenopausal women, maintaining constant and normal calciuria levels. PMID:23704856

Physiologic Estrogen Replacement Increases Bone Density in Adolescent Girls with Anorexia Nervosa

PubMed Central

Misra, Madhusmita; Katzman, Debra; Miller, Karen K.; Mendes, Nara; Snelgrove, Deirdre; Russell, Melissa; Goldstein, Mark; Ebrahimi, Seda; Clauss, Laura; Weigel, Thomas; Mickley, Diane; Schoenfeld, David; Herzog, David B.; Klibanski, Anne

2011-01-01

Background Anorexia nervosa (AN) is prevalent in adolescents and is associated with decreased bone mineral accrual at a time critical for optimizing bone mass. Low bone mineral density (BMD) in AN is a consequence of nutritional and hormonal alterations, including hypogonadism and low estradiol levels. Effective therapeutic strategies to improve BMD in adolescents with AN have not been identified. Specifically, high estrogen doses given as an oral contraceptive do not improve BMD. The impact of physiological estrogen doses that mimic puberty on BMD has not been examined. Subjects and Methods We enrolled 110 girls with AN and 40 normal-weight controls (C) 12–18y of similar maturity. Subjects were studied for 18 months. Mature AN [bone age (BA) ≥15 y; n=96] were randomized to transdermal 100mcg 17β-estradiol (with cyclic progesterone) or placebo for 18m. Immature AN (BA <15y; n=14) were randomized to incremental low dose oral ethinyl-estradiol (3.75mcg daily from 0–6m, 7.5mcg from 6–12m, 11.25mcg from 12–18m) to mimic pubertal estrogen increases, or placebo for the 18m duration. Results All BMD measures assessed by dual energy x-ray absorptiometry (DXA) were lower in AN than C. At baseline, AN randomized to estrogen (AN E+) did not differ from those randomized to placebo (AN E−) for age, maturity, height, BMI, amenorrhea duration and BMD parameters. Spine and hip BMD Z-scores increased over time in the AN E+ compared with AN E− group, even after controlling for baseline age and weight. Conclusion Physiological estradiol replacement increases spine and hip BMD in girls with AN. PMID:21698665

A randomized phase II trial evaluating different schedules of zoledronic acid on bone mineral density in patients with prostate cancer beginning androgen deprivation therapy.

PubMed

Lang, Joshua M; Wallace, Marianne; Becker, Jordan T; Eickhoff, Jens C; Buehring, Bjoern; Binkley, Neil; Staab, Mary Jane; Wilding, George; Liu, Glenn; Malkovsky, Miroslav; McNeel, Douglas G

2013-12-01

To assess the effects of timing and schedule of zoledronic acid (ZA) administration on bone mineral density (BMD) in patients beginning androgen deprivation therapy (ADT) for the treatment of recurrent prostate cancer. In this randomized, 3-arm trial, we evaluated changes in BMD after 3 different ZA administration schedules in men with recurrent prostate cancer who were beginning ADT. Forty-four patients were enrolled and randomized to receive a single dose of ZA given 1 week before beginning ADT (arm 1), a single dose of ZA given 6 months after beginning ADT (arm 2), or monthly administration of ZA starting 6 months after beginning ADT, for a total of 6 doses (arm 3). Patients who received ZA before ADT had a significant improvement in BMD at the total proximal femur and trochanter after 6 months compared with the other groups. In addition, only patients in the arm that received multiple doses improved lumbar spine BMD while on ADT, with these findings persisting to 24 months. However, this group also experienced more grade 1 adverse events. Analysis of these data suggests that ZA administration before initiation of ADT was superior to treatment 6 months after starting ADT in maintaining BMD. In addition, monthly ZA administration can increase BMD above baseline but is associated with more adverse events. Further study is needed to examine whether the timing and frequency of ZA therapy in patients on ADT can reduce fracture risk. Copyright © 2013 Elsevier Inc. All rights reserved.

The evaluation of bone metabolism in children with renal transplantation.

PubMed

Büyükkaragöz, Bahar; Bakkaloglu, Sevcan A; Kandur, Yaşar; Isiyel, Emel; Akcaboy, Meltem; Buyan, Necla; Hasanoglu, Enver

2015-06-01

This study aims to evaluate BMD and bone biomarkers and to investigate the effects of immunosuppressives on bone disease after RTx. Thirty-three RTR aged 16.7 ± 3.7 yr and healthy controls (n = 32) were enrolled. There was no difference between pre-RTx BMD and BMD at the time of study (45.9 ± 30.9 months after RTx), while both values were lower than controls (p < 0.01 and p < 0.05, respectively). Worst BMD scores were obtained at sixth month after RTx (-0.2 ± 0.9) and best at fourth year (1.4 ± 1.3). 25-hydroxy-(OH) vitamin D and OPG were higher in RTR (p < 0.001). BMD z scores negatively correlated with OPG and cumulative CS doses at the time of study (r = -0.344, p < 0.05 and r = -0.371, p < 0.05, respectively). Regression analysis revealed OPG as the only predictor of BMD (β -0.78, 95% CI -0.004 to -0.013, p < 0.001). The increase in OPG, a significant predictor of BMD, could either be secondary to graft dysfunction or for protection against bone loss. CS doses should be minimized to avoid their untoward effects on bone metabolism. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Anemia risk in relation to lead exposure in lead-related manufacturing.

PubMed

Hsieh, Nan-Hung; Chung, Shun-Hui; Chen, Szu-Chieh; Chen, Wei-Yu; Cheng, Yi-Hsien; Lin, Yi-Jun; You, Su-Han; Liao, Chung-Min

2017-05-05

Lead-exposed workers may suffer adverse health effects under the currently regulated blood lead (BPb) levels. However, a probabilistic assessment about lead exposure-associated anemia risk is lacking. The goal of this study was to examine the association between lead exposure and anemia risk among factory workers in Taiwan. We first collated BPb and indicators of hematopoietic function data via health examination records that included 533 male and 218 female lead-exposed workers between 2012 and 2014. We used benchmark dose (BMD) modeling to estimate the critical effect doses for detection of abnormal indicators. A risk-based probabilistic model was used to characterize the potential hazard of lead poisoning for job-specific workers by hazard index (HI). We applied Bayesian decision analysis to determine whether BMD could be implicated as a suitable BPb standard. Our results indicated that HI for total lead-exposed workers was 0.78 (95% confidence interval: 0.50-1.26) with risk occurrence probability of 11.1%. The abnormal risk of anemia indicators for male and female workers could be reduced, respectively, by 67-77% and 86-95% by adopting the suggested BPb standards of 25 and 15 μg/dL. We conclude that cumulative exposure to lead in the workplace was significantly associated with anemia risk. This study suggests that current BPb standard needs to be better understood for the application of lead-exposed population protection in different scenarios to provide a novel standard for health management. Low-level lead exposure risk is an occupational and public health problem that should be paid more attention.

Rapid Loss of Bone Mass and Strength in Mice after Abdominal Irradiation

PubMed Central

Jia, Dan; Gaddy, Dana; Suva, Larry J.; Corry, Peter M.

2011-01-01

Localized irradiation is a common treatment modality for malignancies in the pelvic-abdominal cavity. We report here on the changes in bone mass and strength in mice 7–14 days after abdominal irradiation. Male C57BL/6 mice of 10–12 weeks of age were given a single-dose (0, 5, 10, 15 or 20 Gy) or fractionated (3 Gy × 2 per day × 7.5 days) X rays to the abdomen and monitored daily for up to 14 days. A decrease in the serum bone formation marker and ex vivo osteoblast differentiation was detected 7 days after a single dose of radiation, with little change in the serum bone resorption marker and ex vivo osteoclast formation. A single dose of radiation elicited a loss of bone mineral density (BMD) within 14 days of irradiation. The BMD loss was up to 4.1% in the whole skeleton, 7.3% in tibia, and 7.7% in the femur. Fractionated abdominal irradiation induced similar extents of BMD loss 10 days after the last fraction: 6.2% in the whole skeleton, 5.1% in tibia, and 13.8% in the femur. The loss of BMD was dependent on radiation dose and was more profound in the trabecula-rich regions of the long bones. Moreover, BMD loss in the total skeleton and the femurs progressed with time. Peak load and stiffness in the mid-shaft tibia from irradiated mice were 11.2–14.2% and 11.5–25.0% lower, respectively, than sham controls tested 7 days after a single-dose abdominal irradiation. Our data demonstrate that abdominal irradiation induces a rapid loss of BMD in the mouse skeleton. These effects are bone type- and region-specific but are independent of radiation fractionation. The radiation-induced abscopal damage to the skeleton is manifested by the deterioration of biomechanical properties of the affected bone. PMID:21859327

Prevalence and associated factors of low bone mass in adults with systemic lupus erythematosus.

PubMed

Cramarossa, G; Urowitz, M B; Su, J; Gladman, D; Touma, Z

2017-04-01

Background Systemic lupus erythematosus (SLE) patients are often treated with glucocorticoids, which place them at risk of bone loss. Objectives The objectives of this article are to determine: (1) the prevalence of low bone mineral density (BMD) and factors associated with low BMD and (2) the prevalence of symptomatic fragility fractures in inception patients of the Toronto Lupus Cohort (TLC). Methods Prospectively collected data from the TLC (1996-2015) of inception patients' first BMD were analyzed. For pre-menopausal women/males <50 years, BMD 'below expected range for age' was defined by Z-score ≤ -2.0 SD. For post-menopausal women/males age 50 or older, osteoporosis was defined by T-score ≤ -2.5 SD and low bone mass by T-score between -1.0 and -2.5 SD. Patients' BMDs were defined as abnormal if Z-score ≤ -2.0 or T-score < -1.0 SD, and the remainder as normal. Descriptive analysis and logistic regression were employed. Results Of 1807 patients, 286 are inception patients with BMD results (mean age 37.9 ± 13.7 years); 88.8% are female. The overall prevalence of abnormal BMD is 31.5%. In pre-menopausal women ( n = 173), the prevalence of BMD below expected range is 17.3%. In post-menopausal women ( n = 81), the prevalence of osteoporosis and low BMD are 12.3% and 43.2%, respectively. Age and cumulative dose of glucocorticoids are statistically significantly associated with abnormal BMD in multivariate analysis. Of 769 inception patients from TLC, 11.1% experienced symptomatic fragility fractures (peripheral and vertebral) over the course of their disease. Conclusion The prevalence of low BMD is high in SLE patients, and is associated with older age and higher cumulative glucocorticoid dose.

Duration of antiresorptive activity of zoledronate in postmenopausal women with osteopenia: a randomized, controlled multidose trial

PubMed Central

Grey, Andrew; Bolland, Mark J.; Horne, Anne; Mihov, Borislav; Gamble, Greg; Reid, Ian R.

2017-01-01

BACKGROUND: Intravenous zoledronate 5 mg annually reduces fracture risk, and 5 mg every 2 years prevents bone loss, but the optimal dosing regimens for these indications are uncertain. METHODS: We conducted a 3-year open-label extension of a 2-year randomized, placebo-controlled, double-blind study. Late postmenopausal women with osteopenia were assigned to receive a single baseline dose of 1 mg, 2.5 mg or 5 mg of zoledronate or placebo. The primary outcome was change in spine bone mineral density (BMD). Secondary outcomes were changes in hip BMD and serum markers of bone turnover. RESULTS: The study involved 160 women. Zoledronate increased BMD and reduced markers of bone turnover in a dose-dependent manner. After 2 years, the 1-mg, 2.5-mg and 5-mg zoledronate doses increased spine BMD over placebo by 5.0% (95% confidence interval [CI] 3.0% to 7.0%), 5.7% (95% CI 3.7% to 7.7%) and 5.7% (95% CI 3.7% to 7.6%), respectively; after 5 years, the respective increases were 2.0% (95% CI −1.1% to 5.0%), 2.2% (95% CI −1.0% to 5.4%) and 5.1% (95% CI 2.2% to 8.1%). After 2 years, the 1-mg, 2.5-mg and 5-mg zoledronate doses increased total hip BMD over placebo by 2.6% (95% CI 1.3% to 3.9%), 4.1% (95% CI 2.9% to 5.4%) and 4.7% (95% CI 3.4% to 5.9%), respectively; after 5 years, the respective increases were 1.8% (95% CI −0.1% to 3.8%), 2.8% (95% CI 0.8% to 4.8%) and 5.4% (95% CI 3.5% to 7.3%). BMD remained above baseline values for 2–3 years in the 1-mg group, 3–4 years in the 2.5-mg group and at least 5 years in the 5-mg group. INTERPRETATION: The antiresorptive activity of single zoledronate doses of 1–5 mg persist for at least 3 years in postmenopausal women with osteopenia. Clinical trials would be justified to evaluate the effects on fracture risk of less frequent or lower doses of zoledronate than are currently recommended. Trial registration: www.anzctr.org.au, no. ACTRN12607000576426 PMID:28893875

Reversing sex steroid deficiency and optimizing skeletal development in the adolescent with gonadal failure.

PubMed

Vanderschueren, Dirk; Vandenput, Liesbeth; Boonen, Steven

2005-01-01

During puberty, the acquisition of skeletal mass and areal bone mineral density (BMD) mainly reflects an increase in bone size (length and perimeters) and not true volumetric BMD. Sexual dimorphism in bone mass and areal BMD is also explained by differences in bone size (longer and wider bones in males) and not by differences in volumetric BMD. Androgens stimulate skeletal growth by activation of the androgen receptor, whereas estrogens (following aromatization of androgens and stimulation of estrogen receptors) have a biphasic effect on skeletal growth during puberty. Recent evidence from clinical cases has shown that many of the growth-promoting effects of the sex steroids are mediated through estrogens rather than androgens. In addition, skeletal maturation and epiphyseal fusion are also estrogen-dependent in both sexes. Nevertheless, independent actions of androgens in these processes also occur. Both sex steroids maintain volumetric BMD during puberty. Androgens interact with the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis neonatally, resulting in a sexual dimorphic GH pattern during puberty, whereas estrogens stimulate GH and hereby IGF-I in both sexes. Hypogonadism in adolescents impairs not only bone size but also maintenance of volumetric BMD, hereby severely reducing peak areal BMD. Delayed puberty in boys and Turner's syndrome in women impair both bone length and size, reducing areal BMD. Whether volumetric BMD is also reduced and whether fracture risk is increased in these conditions remains controversial. Replacing sex steroids according to a biphasic pattern (starting at low doses and ending at high-normal doses) seems the safest approach to reach targeted height and to optimize bone development.

Correlation of In Vivo Versus In Vitro Benchmark Doses (BMDs) Derived From Micronucleus Test Data: A Proof of Concept Study.

PubMed

Soeteman-Hernández, Lya G; Fellows, Mick D; Johnson, George E; Slob, Wout

2015-12-01

In this study, we explored the applicability of using in vitro micronucleus (MN) data from human lymphoblastoid TK6 cells to derive in vivo genotoxicity potency information. Nineteen chemicals covering a broad spectrum of genotoxic modes of action were tested in an in vitro MN test using TK6 cells using the same study protocol. Several of these chemicals were considered to need metabolic activation, and these were administered in the presence of S9. The Benchmark dose (BMD) approach was applied using the dose-response modeling program PROAST to estimate the genotoxic potency from the in vitro data. The resulting in vitro BMDs were compared with previously derived BMDs from in vivo MN and carcinogenicity studies. A proportional correlation was observed between the BMDs from the in vitro MN and the BMDs from the in vivo MN assays. Further, a clear correlation was found between the BMDs from in vitro MN and the associated BMDs for malignant tumors. Although these results are based on only 19 compounds, they show that genotoxicity potencies estimated from in vitro tests may result in useful information regarding in vivo genotoxic potency, as well as expected cancer potency. Extension of the number of compounds and further investigation of metabolic activation (S9) and of other toxicokinetic factors would be needed to validate our initial conclusions. However, this initial work suggests that this approach could be used for in vitro to in vivo extrapolations which would support the reduction of animals used in research (3Rs: replacement, reduction, and refinement). © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology.

Transdermal Nitroglycerin Therapy May Not Prevent Early Postmenopausal Bone Loss

PubMed Central

Wimalawansa, Sunil J.; Grimes, Julia P.; Wilson, Alan C.; Hoover, Donald R.

2009-01-01

Context: Osteoporosis is common among postmenopausal women; animal studies and human pilot studies support the concept of nitric oxide (NO) donors reducing bone mineral density loss. Objective: The objective of the study was to evaluate whether NO donor, nitroglycerin, prevents postmenopausal bone loss. Design: This was a 3-yr randomized, double blinded, single-center, placebo-controlled clinical trial. Setting: The single-center study was conducted at the University of Medicine and Dentistry-Robert Wood Johnson Medical School (New Brunswick, NJ). Participants: Participants included 186 postmenopausal women aged 40–65 yr, with lumbar bone mineral density (BMD) T-scores of 0 to −2.5. Intervention: Women, stratified by lumbar T-score (<−1.50 and ≥−1.50) and years since menopause (≤5 and >5 yr), were randomized to receive nitroglycerin ointment (22.5 mg as Nitro-Bid) or placebo ointment received daily for 3 yr. Both groups took 630 mg daily calcium plus 400 IU vitamin D supplements. Measurements: BMD was measured at 6 months and annually by dual-energy x-ray absorptiometry. Percent change in lumbar vertebrae BMD was the primary outcome. Hip BMD, total body bone mineral content, and height were secondary outcomes. Results: After 36 months of therapy, changes of −2.1% in the active group (n = 88) and −2.5% in the placebo group (n = 82) in lumbar spine BMD were seen (P = 0.59; 95% confidence interval −1.001, 1.975). Secondary outcomes also did not differ by intervention arm. The active group reported more headaches compared with the placebo group (57 vs. 14%, P < 0.001). Other adverse and serious adverse events were not different. Conclusions: BMD changes did not substantially differ between postmenopausal women who received the dose of nitroglycerin tested, in comparison with a placebo. Once-daily dosing with 22.5 mg of transdermal-administered nitroglycerin was not effective (compliance adjusted dose was only ∼16 mg/d); a sub-therapeutic dose. PMID:19549739

Initial analyses of the relationship between 'Thresholds' of toxicity for individual chemicals and 'Interaction Thresholds' for chemical mixtures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Raymond S.H.; Dennison, James E.

2007-09-01

The inter-relationship of 'Thresholds' between chemical mixtures and their respective component single chemicals was studied using three sets of data and two types of analyses. Two in vitro data sets involve cytotoxicity in human keratinocytes from treatment of metals and a metal mixture [Bae, D.S., Gennings, C., Carter, Jr., W.H., Yang, R.S.H., Campain, J.A., 2001. Toxicological interactions among arsenic, cadmium, chromium, and lead in human keratinocytes. Toxicol. Sci. 63, 132-142; Gennings, C., Carter, Jr., W.H., Campain, J.A., Bae, D.S., Yang, R.S.H., 2002. Statistical analysis of interactive cytotoxicity in human epidermal keratinocytes following exposure to a mixture of four metals. J.more » Agric. Biol. Environ. Stat. 7, 58-73], and induction of estrogen receptor alpha (ER-{alpha}) reporter gene in MCF-7 human breast cancer cells by estrogenic xenobiotics [Gennings, C., Carter, Jr., W.H., Carney, E.W., Charles, G.D., Gollapudi, B.B., Carchman, R.A., 2004. A novel flexible approach for evaluating fixed ratio mixtures of full and partial agonists. Toxicol. Sci. 80, 134-150]. The third data set came from PBPK modeling of gasoline and its components in the human. For in vitro cellular responses, we employed Benchmark Dose Software (BMDS) to obtain BMD{sub 01}, BMD{sub 05}, and BMD{sub 10}. We then plotted these BMDs against exposure concentrations for the chemical mixture and its components to assess the ranges and slopes of these BMD-concentration lines. In doing so, we consider certain BMDs to be 'Interaction Thresholds' or 'Thresholds' for mixtures and their component single chemicals and the slope of the line must be a reflection of the potency of the biological effects. For in vivo PBPK modeling, we used 0.1x TLVs, TLVs, and 10x TLVs for gasoline and six component markers as input dosing for PBPK modeling. In this case, the venous blood levels under the hypothetical exposure conditions become our designated 'Interaction Thresholds' or 'Thresholds' for gasoline and its component single chemicals. Our analyses revealed that the mixture 'Interaction Thresholds' appear to stay within the bounds of the 'Thresholds' of its respective component single chemicals. Although such a trend appears to be emerging, nevertheless, it should be emphasized that our analyses are based on limited data sets and further analyses on data sets, preferably the more comprehensive experimental data sets, are needed before a definitive conclusion can be drawn.« less

Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia: a randomized controlled trial.

PubMed

Amstrup, Anne Kristine; Sikjaer, Tanja; Heickendorff, Lene; Mosekilde, Leif; Rejnmark, Lars

2015-09-01

Melatonin is known for its regulation of circadian rhythm. Recently, studies have shown that melatonin may have a positive effect on the skeleton. By increasing age, the melatonin levels decrease, which may lead to a further imbalanced bone remodeling. We aimed to investigate whether treatment with melatonin could improve bone mass and integrity in humans. In a double-blind RCT, we randomized 81 postmenopausal osteopenic women to 1-yr nightly treatment with melatonin 1 mg (N = 20), 3 mg (N = 20), or placebo (N = 41). At baseline and after 1-yr treatment, we measured bone mineral density (BMD) by dual X-ray absorptiometry, quantitative computed tomography (QCT), and high-resolution peripheral QCT (HR-pQCT) and determined calciotropic hormones and bone markers. Mean age of the study subjects was 63 (range 56-73) yr. Compared to placebo, femoral neck BMD increased by 1.4% in response to melatonin (P < 0.05) in a dose-dependent manner (P < 0.01), as BMD increased by 0.5% in the 1 mg/day group (P = 0.55) and by 2.3% (P < 0.01) in the 3 mg/day group. In the melatonin group, trabecular thickness in tibia increased by 2.2% (P = 0.04), and volumetric bone mineral density (vBMD) in the spine, by 3.6% (P = 0.04) in the 3 mg/day. Treatment did not significantly affect BMD at other sites or levels of bone turnover markers; however, 24-hr urinary calcium was decreased in response to melatonin by 12.2% (P = 0.02). In conclusion, 1-yr treatment with melatonin increased BMD at femoral neck in a dose-dependent manner, while high-dose melatonin increased vBMD in the spine. Further studies are needed to assess the mechanisms of action and whether the positive effect of nighttime melatonin will protect against fractures. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Impact of Calcium and Two Doses of Vitamin D on Bone Metabolism in the Elderly: A Randomized Controlled Trial.

PubMed

Rahme, Maya; Sharara, Sima Lynn; Baddoura, Rafic; Habib, Robert H; Halaby, Georges; Arabi, Asma; Singh, Ravinder J; Kassem, Moustapha; Mahfoud, Ziyad; Hoteit, Maha; Daher, Rose T; Bassil, Darina; El Ferkh, Karim; El-Hajj Fuleihan, Ghada

2017-07-01

The optimal dose of vitamin D to optimize bone metabolism in the elderly is unclear. We tested the hypothesis that vitamin D, at a dose higher than recommended by the Institute of Medicine (IOM), has a beneficial effect on bone remodeling and mass. In this double-blind trial we randomized 257 overweight elderly subjects to receive 1000 mg of elemental calcium citrate/day, and the daily equivalent of 3750 IU/day or 600 IU/day of vitamin D3 for 1 year. The subjects' mean age was 71 ± 4 years, body mass index 30 ± 4 kg/m 2 , 55% were women, and 222 completed the 12-month follow-up. Mean serum 25 hydroxyvitamin D (25OHD) was 20 ng/mL, and rose to 26 ng/mL in the low-dose arm, and 36 ng/mL in the high-dose arm, at 1 year (p < 0.05). Plasma parathyroid hormone, osteocalcin, and C-terminal telopeptide (Cross Laps) levels decreased significantly by 20% to 22% in both arms, but there were no differences between the two groups for any variable, at 6 or 12 months, with the exception of serum calcitriol, which was higher in the high-dose group at 12 months. Bone mineral density (BMD) increased significantly at the total hip and lumbar spine, but not the femoral neck, in both study arms, whereas subtotal body BMD increased in the high-dose group only, at 1 year. However, there were no significant differences in percent change BMD between the two study arms at any skeletal site. Subjects with serum 25OHD <20 ng/mL and PTH level >76 pg/mL showed a trend for higher BMD increments at all skeletal sites, in the high-dose group, that reached significance at the hip. Adverse events were comparable in the two study arms. This controlled trial shows little additional benefit in vitamin D supplementation at a dose exceeding the IOM recommendation of 600 IU/day on BMD and bone markers, in overweight elderly individuals. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Glyphosate in the general population and in applicators: a critical review of studies on exposures.

PubMed

Solomon, Keith R

2016-09-01

The recent classification of glyphosate as a probable human carcinogen by the International Agency for Research on Cancer (IARC) was arrived at without a detailed assessment of exposure. Glyphosate is widely used as an herbicide, which might result in exposures of the general public and applicators. Exposures were estimated from information in the open literature and unpublished reports provided by Monsanto Company. Based on the maximum measured concentration in air, an exposure dose of 1.04 × 10  -   6  mg/kg body mass (b.m.)/d was estimated. Assuming consumption of surface water without treatment, the 90th centile measured concentration would result in a consumed dose of 2.25 × 10  -   5  mg/kg b.m./d. Estimates by the Food and Agriculture Organization of the United Nations (FAO) of consumed doses in food provided a median exposure of 0.005 mg/kg b.m./d (range 0.002-0.013). Based on tolerance levels, the conservative estimate by the US Environmental Protection Agency (US EPA) for exposure of the general population via food and water was 0.088 mg/kg b.m./d (range 0.058-0.23). For applicators, 90th centiles for systemic exposures based on biomonitoring and dosimetry (normalized for penetration through the skin) were 0.0014 and 0.021 mg/kg b.m./d, respectively. All of these exposures are less than the reference dose and the acceptable daily intakes proposed by several regulatory agencies, thus supporting a conclusion that even for these highly exposed populations the exposures were within regulatory limits.

BONE MINERAL DENSITY IN PATIENTS WITH ADDISON DISEASE ON REPLACEMENT THERAPY WITH PREDNISOLONE.

PubMed

Chandy, David D; Bhatia, Eesh

2016-04-01

In primary adrenal insufficiency (PAI), replacement with prednisolone may result in lower bone mineral density (BMD) compared with hydrocortisone therapy. However, the number of patients studied on prednisolone is small and the results are conflicting. We conducted a cross-sectional study to determine BMD and its relation with therapy in patients on physiologic doses of prednisolone replacement. Forty-one consecutive patients (31 males, age [mean ± SD] 50.9 ± 13.0 years), receiving prednisolone (hydrocortisone equivalent [HCE] 13.0 ± 3.0 mg/m(2)) for 104 ± 95 months were studied. BMD was evaluated by dual-energy X-ray absorptiometry and compared with an age- and sex-matched reference group of healthy Indian subjects (n = 677). Among males, BMD Z-scores (mean [95% confidence interval {CI}]) at lumbar spine (-0.42 [-0.80, -0.04]), femoral neck (-0.50 [-0.95, -0.06]) and total hip (-0.58 [-0.90, -0.26]) were significantly lower than the reference population. Z-scores in female patients did not differ from controls. Among postmenopausal females and males >50 years, 43% had osteoporosis (T-score ≤-2.5), as compared with 25% in the reference group (P = .04). There was no correlation between BMD Z-scores and HCE dose or duration of therapy. On multivariate regression analysis, body mass index was the only significant predictor of BMD. A high proportion of males (45%) had low serum testosterone (<300 ng/dL), but there was no correlation between testosterone and BMD. Male patients with PAI receiving physiologic prednisolone replacement had a small but significant diminution in BMD at all sites.

The Impact of Low-Dose Disease-modifying Anti-rheumatics Drugs (DMARDs) on Bone Mineral Density of Premenopausal Women in Early Rheumatoid Arthritis.

PubMed

Rexhepi, Sylejman; Rexhepi, Mjellma; Sahatçiu-Meka, Vjollca; Mahmutaj, Vigan; Boshnjaku, Shkumbin

2016-04-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetrical polyarthritis and multisystemic involvement. The aim of this study was to assess the impact of low dose of methotrexate on bone mineral density (BMD) in patients with early rheumatoid arthritis (RA). This paper follows a retrospective study, which involves 60 female patients with early onset RA diagnosed according to the American Rheumatism Association Criteria (ACR/EULAR 2010). The patients were divided into two groups group I was composed of thirty patients treated with dose of 7.5 mg/weekly methotrexate (MTX), while group II included thirty patients treated with dose of 2 g/daily sulfasalazine (SSZ). The Disease Activity was measured by a combination of Erythrocyte Sedimentation Rate (ESR) and Disease Activity Score (DAS-28). Bone mineral density of the lumbar spine (L2-4), and femoral neck, was measured by dual energy X-ray absorptiometry (DEXA) (Stratos 800). Laboratory findings included: In this study, we found no negative effect on BMD in RA patients treated with low dose MTX in comparison to patients treated with SSZ. There was not observed significant difference in BMD of the lumbar spine, femur neck or trochanter, of MTX and SSZ patients in the pretreatment phase, nor after 12 months of treatment. No significant change in the biochemical parameters of the both groups. Based on the results of our study, low dose of methotrexate has no negative effect on BMD in premenopausal RA patients. We believe that these results might provide new insights and that further longitudinal studies with larger groups of premenopausal RA patients are required.

The Impact of Low-Dose Disease-modifying Anti-rheumatics Drugs (DMARDs) on Bone Mineral Density of Premenopausal Women in Early Rheumatoid Arthritis

PubMed Central

Rexhepi, Sylejman; Rexhepi, Mjellma; Sahatçiu-Meka, Vjollca; Mahmutaj, Vigan; Boshnjaku, Shkumbin

2016-01-01

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetrical polyarthritis and multisystemic involvement. Objective: The aim of this study was to assess the impact of low dose of methotrexate on bone mineral density (BMD) in patients with early rheumatoid arthritis (RA). Materials and methods: This paper follows a retrospective study, which involves 60 female patients with early onset RA diagnosed according to the American Rheumatism Association Criteria (ACR/EULAR 2010). The patients were divided into two groups group I was composed of thirty patients treated with dose of 7.5 mg/weekly methotrexate (MTX), while group II included thirty patients treated with dose of 2 g/daily sulfasalazine (SSZ). The Disease Activity was measured by a combination of Erythrocyte Sedimentation Rate (ESR) and Disease Activity Score (DAS-28). Bone mineral density of the lumbar spine (L2–4), and femoral neck, was measured by dual energy X-ray absorptiometry (DEXA) (Stratos 800). Laboratory findings included: In this study, we found no negative effect on BMD in RA patients treated with low dose MTX in comparison to patients treated with SSZ. There was not observed significant difference in BMD of the lumbar spine, femur neck or trochanter, of MTX and SSZ patients in the pretreatment phase, nor after 12 months of treatment. No significant change in the biochemical parameters of the both groups. Conclusion: Based on the results of our study, low dose of methotrexate has no negative effect on BMD in premenopausal RA patients. We believe that these results might provide new insights and that further longitudinal studies with larger groups of premenopausal RA patients are required. PMID:27147781

Negative impact of high cumulative glucocorticoid dose on bone metabolism of patients with myasthenia gravis.

PubMed

Braz, Nayara Felicidade Tomaz; Rocha, Natalia Pessoa; Vieira, Érica Leandro Marciano; Gomez, Rodrigo Santiago; Barbosa, Izabela Guimarães; Malheiro, Olívio Brito; Kakehasi, Adriana Maria; Teixeira, Antonio Lucio

2017-08-01

This current study aimed to evaluate the frequency of low bone mass, osteopenia, and osteoporosis in patients with myasthenia gravis (MG) and to investigate the possible association between bone mineral density (BMD) and plasma levels of bone metabolism markers. Eighty patients with MG and 62 controls BMD were measured in the right femoral neck and lumbar spine by dual-energy X-ray absorptiometry. Plasma concentrations of osteocalcin, osteopontin, osteoprotegerin, tumor necrosis factor (TNF-α), interleukin (IL)-1β, IL-6, dickkopf (DKK-1), sclerostin, insulin, leptin, adrenocorticotropic hormone, parathyroid hormone, and fibroblast growth factor (FGF-23) were analyzed by Luminex®. The mean age of patients was 41.9 years, with 13.5 years of length of illness, and a mean cumulative dose of glucocorticoids 38,123 mg. Patients had significant reduction in BMD of the lumbar, the femoral neck, and in the whole body when compared with controls. Fourteen percent MG patients had osteoporosis at the lumbar spine and 2.5% at the femoral neck. In comparison with controls, patients with MG presented lower levels of osteocalcin, adrenocorticotropic hormone, parathyroid hormone, sclerostin, TNF-α, and DKK-1 and higher levels of FGF-23, leptin, and IL-6. There was a significant negative correlation between cumulative glucocorticoid dose and serum calcium, lumbar spine T-score, femoral neck BMD, T-score, and Z-score. After multivariate analysis, higher TNF-α levels increased the likelihood of presenting low bone mass by 2.62. MG patients under corticotherapy presented low BMD and altered levels of bone markers.

BMI levels with MS Bone mineral density levels in adults with multiple sclerosis: a meta-analysis.

PubMed

Huang, Zhongming; Qi, Yiying; Du, Shaohua; Chen, Guangnan; Yan, Weiqi

2015-01-01

Multiple sclerosis (MS) and osteoporosis (OP) affect a substantial proportion of the population. Accumulating evidence suggests that MS patients are at high risk for OP. We performed a meta-analysis to identify risk factors for lowered bone mineral density (BMD) in MS patients. We searched for articles within the Medline, Embase and Cochrane Library databases, published up to March 2014, pertaining to associations between MS and BMD. A total of 11 studies was included in the meta-analysis. The analysis indicated that MS patients have reduced lumbar spine, femur neck, and hip BMD compared with healthy controls (lumbar spine, standardized mean difference (SMD) = -0.76, 95% CI: -1.07, -0.45; femur neck, SMD = -0.56, 95% CI: -0.84, -0.29; and hip, SMD = -0.62, 95% CI: -0.96, -0.29). Further subgroup analysis revealed that a disease duration of >7 years, total steroid dose during the disease of >15 g, and an Expanded Disability Status Scale (EDSS) score of > 3, increased the risk of reduced BMD in the lumbar spine and femoral neck, but not in the hip. Meta-regression analysis did not explain the heterogeneity in the clinical characteristics or outcome definitions. Our meta-analysis suggests that MS patients have reduced overall BMD compared with healthy controls. Furthermore, disease duration (>7 years), total steroid dose (>15 g), and EDSS score (>3) are risk factors for reduced BMD in MS patients.

Effects of 16-month treatment with the cathepsin K inhibitor ONO-5334 on bone markers, mineral density, strength and histomorphometry in ovariectomized cynomolgus monkeys.

PubMed

Yamada, Hiroyuki; Ochi, Yasuo; Mori, Hiroshi; Nishikawa, Satoshi; Hashimoto, Yasuaki; Nakanishi, Yasutomo; Tanaka, Makoto; Bruce, Mark; Deacon, Steve; Kawabata, Kazuhito

2016-05-01

We examined the effects of ONO-5334, a cathepsin K inhibitor, on bone markers, BMD, strength and histomorphometry in ovariectomized (OVX) cynomolgus monkeys. ONO-5334 (1.2, 6 and 30mg/kg/day, p.o.), alendronate (0.05mg/kg/2weeks, i.v.), or vehicle was administered to OVX monkeys (all groups N=20) for 16months. A concurrent Sham group (N=20) was also treated with vehicle for 16months. OVX significantly increased bone resorption and formation markers and decreased BMD in lumbar vertebra, femoral neck, proximal tibia and distal radius. Alendronate suppressed these parameters to a level similar to that in the Sham-operated monkeys. ONO-5334 at doses 6 and 30mg/kg decreased bone resorption markers to a level roughly half of that in the Sham group, while keeping bone formation markers level above that in the Sham monkeys. Changes in DXA BMD confirmed that ONO-5334 at doses 6 and 30mg/kg increased BMD to a level greater than that in the Sham group in all examined sites. In the proximal tibia, in vivo pQCT analysis showed that ONO-5334 at doses 6 and 30mg/kg suppressed trabecular BMD loss to the sham level. However, ONO-5334 increased cortical BMD, cortical area and cortical thickness to a level greater than that in the Sham group, suggesting that ONO-5334 improves both cortical BMD and cortical geometry. Histomorphometric analysis revealed that ONO-5334 suppressed bone formation rate (BFR) at osteonal site in the midshaft femur but did not influence OVX-induced increase in BFR at either the periosteal or endocortical surfaces. Unlike alendronate, ONO-5334 increased osteoclasts surface (Oc.S/BS) and serum tartrate-resistant acid phosphatise 5b (TRAP5b) activity, highlighting the difference in the mode of action between these two drugs. Our results suggest that ONO-5334 has therapeutic potential not only in vertebral bones, but also in non-vertebral bones. Copyright © 2016 Elsevier Inc. All rights reserved.

[Using fractional polynomials to estimate the safety threshold of fluoride in drinking water].

PubMed

Pan, Shenling; An, Wei; Li, Hongyan; Yang, Min

2014-01-01

To study the dose-response relationship between fluoride content in drinking water and prevalence of dental fluorosis on the national scale, then to determine the safety threshold of fluoride in drinking water. Meta-regression analysis was applied to the 2001-2002 national endemic fluorosis survey data of key wards. First, fractional polynomial (FP) was adopted to establish fixed effect model, determining the best FP structure, after that restricted maximum likelihood (REML) was adopted to estimate between-study variance, then the best random effect model was established. The best FP structure was first-order logarithmic transformation. Based on the best random effect model, the benchmark dose (BMD) of fluoride in drinking water and its lower limit (BMDL) was calculated as 0.98 mg/L and 0.78 mg/L. Fluoride in drinking water can only explain 35.8% of the variability of the prevalence, among other influencing factors, ward type was a significant factor, while temperature condition and altitude were not. Fractional polynomial-based meta-regression method is simple, practical and can provide good fitting effect, based on it, the safety threshold of fluoride in drinking water of our country is determined as 0.8 mg/L.

Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial.

PubMed

El-Hajj Fuleihan, Ghada; Nabulsi, Mona; Tamim, Hala; Maalouf, Joyce; Salamoun, Mariana; Khalife, Hassan; Choucair, Mahmoud; Arabi, Asma; Vieth, Reinhold

2006-02-01

Despite the high prevalence of hypovitaminosis D in children and adolescents worldwide, the impact of vitamin D deficiency on skeletal health is unclear. One hundred seventy-nine girls, ages 10-17 yr, were randomly assigned to receive weekly oral vitamin D doses of 1,400 IU (equivalent to 200 IU/d) or 14,000 IU (equivalent to 2,000 IU/d) in a double-blind, placebo-controlled, 1-yr protocol. Areal bone mineral density (BMD) and bone mineral content (BMC) at the lumbar spine, hip, forearm, total body, and body composition were measured at baseline and 1 yr. Serum calcium, phosphorus, alkaline phosphatase, and vitamin D metabolites were measured during the study. In the overall group of girls, lean mass increased significantly in both treatment groups (P < or = 0.05); bone area and total hip BMC increased in the high-dose group (P < 0.02). In premenarcheal girls, lean mass increased significantly in both treatment groups, and there were consistent trends for increments in BMD and/or BMC at several skeletal sites, reaching significance at lumbar spine BMD in the low-dose group and at the trochanter BMC in both treatment groups. There was no significant change in lean mass, BMD, or BMC in postmenarcheal girls. Vitamin D replacement had a positive impact on musculoskeletal parameters in girls, especially during the premenarcheal period.

Effects of whole body vibration on bone mineral density in postmenopausal women: a systematic review and meta-analysis.

PubMed

Oliveira, L C; Oliveira, R G; Pires-Oliveira, D A A

2016-10-01

This systematic review and meta-analysis of randomized controlled trials (RCTs) identified significant effects of whole body vibration (WBV) on bone mineral density (BMD) of the lumbar spine (in the sensitivity analysis and seven subgroup analyses), femoral neck (in one subgroup analysis), and trochanter (four subgroup analyses) in postmenopausal women, but not other measurements of BMD. Interventions using WBV training have been conducted in postmenopausal women, aimed at increasing BMD; however, the results are contradictory. Our objective is to conduct a systematic review and meta-analysis of RCTs examining WBV effect on BMD. RCTs were considered eligible, with follow-up ≥6 months, which verified the effects of WBV on the BMD of postmenopausal women. The calculations of the meta-analysis were performed through the weighted mean difference between the WBV and control groups, or the WBV and combined training, through the absolute change between pre- and post-intervention in the areal bone mineral density (aBMD) or trabecular volumetric bone mineral density (vBMDt). Fifteen RCTs were included in the meta-analysis. No differences were observed in the primary analysis. WBV was found to improve aBMD compared with the control group, after exclusion of studies with low quality methodological (lumbar spine), when excluding the studies which combined WBV with medication or combined training (lumbar spine), with the use of low frequency and high magnitude (lumbar spine and trochanter), high frequency and low magnitude (lumbar spine), high cumulative dose and low magnitude (lumbar spine), low cumulative dose and high magnitude (lumbar spine and trochanter), with semi-flexed knee (lumbar spine, femoral neck, and trochanter), and side-alternating type of vibration (lumbar spine and trochanter). Despite WBV presenting potential to act as a coadjuvant in the prevention or treatment of osteoporosis, especially for aBMD of the lumbar spine, the ideal intervention is not yet clear. Our subgroup analyses helped to demonstrate the various factors which appear to influence the effects of WBV on BMD, contributing to clinical practice and the definition of protocols for future interventions.

Effects of eight-month treatment with ONO-5334, a cathepsin K inhibitor, on bone metabolism, strength and microstructure in ovariectomized cynomolgus monkeys.

PubMed

Ochi, Yasuo; Yamada, Hiroyuki; Mori, Hiroshi; Nakanishi, Yasutomo; Nishikawa, Satoshi; Kayasuga, Ryoji; Kawada, Naoki; Kunishige, Akiko; Hashimoto, Yasuaki; Tanaka, Makoto; Sugitani, Masafumi; Kawabata, Kazuhito

2014-08-01

This study examined the effect of ONO-5334, a cathepsin K inhibitor, on bone turnover, mineral density (BMD), mechanical strength and microstructure in ovariectomized (OVX) cynomolgus monkeys. Vehicle, ONO-5334 (3, 10 or 30 mg/kg) or alendronate (0.5 mg/kg) was orally administered for eight months to sham- and OVX-operated monkeys. ONO-5334 dose-dependently suppressed OVX-induced increase in bone turnover markers (urinary C-terminal cross-linking telopeptide of type I collagen (CTX) and serum osteocalcin). At the dose of 30 mg/kg, ONO-5334 maintained urinary CTX at nearly zero level and kept serum osteocalcin around the level of the sham animals. Marker levels in the alendronate-treated animals were similar to those in the sham animals throughout the study. ONO-5334 dose-dependently reversed the effect of OVX on vertebral BMD as measured by dual-energy X-ray absorptiometry (DXA) with improvement of bone mechanical strength. Both ONO-5334 and alendronate suppressed OVX-induced changes in vertebral microstructure and turnover state. In the femoral neck, peripheral quantitative computed tomography (pQCT) analysis showed that ONO-5334 increased total and cortical BMD. In particular, ONO-5334 significantly increased cortical BMD with improvement of bone mechanical strength. In microstructural analysis, alendronate suppressed OVX-induced increase in femoral mid-shaft osteonal bone formation rate (BFR) to a level below that recorded in the sham group, whereas ONO-5334 at 30 mg/kg did not suppress periosteal, osteonal and endocortical BFR. This finding supports the significant effect of ONO-5334 on cortical BMD and mechanical strength in the femoral neck. The results of this study suggest that ONO-5334 has good therapeutic potential for the treatment of osteoporosis. Copyright © 2014 Elsevier Inc. All rights reserved.

Oral contraceptive use and bone density in adolescent and young adult women

PubMed Central

Scholes, Delia; Ichikawa, Laura; LaCroix, Andrea Z.; Spangler, Leslie; Beasley, Jeannette M.; Reed, Susan; Ott, Susan M.

2009-01-01

Background Most of the millions of oral contraceptive (OC) users are under age 30 years and in the critical period for bone mass accrual. Study Design This cross-sectional study of 606 women aged 14–30 years examined both OC duration and estrogen dose and their association with bone mineral density (BMD) at the hip, spine, and whole-body (DEXA). Results Of 389 OC users and 217 nonusers enrolled, 50% were adolescents (14–18 years). Of OC users, 38% used “low-dose” OCs [<30 mcg ethinyl estradiol (EE)]. In adolescents, mean BMD differed by neither OC duration nor EE dose. However, 19–30 year-old women’s mean BMD was lower with longer OC use for spine and whole-body (p=0.004, p=0.02, respectively) and lowest for >12 months of low-dose OCs for the hip, spine and whole-body (p=0.02, 0.003 and 0.002, respectively). Conclusions Prolonged use of today’s OCs, particularly <30 mcg EE, may adversely impact young adult women’s bone density while ingesting these agents. PMID:20004271

Denosumab in Postmenopausal Osteoporosis: What the Clinician Needs to Know

PubMed Central

Lewiecki, E. Michael

2009-01-01

Denosumab is a subcutaneously (SC) administered investigational fully human monoclonal antibody to receptor activator of nuclear factor-kB ligand (RANKL), a cytokine member of the tumor necrosis factor family that is the principal mediator of osteoclastic bone resorption. RANKL stimulates the formation, activity, and survival of osteoclasts, and is implicated in the pathogenesis of postmenopausal osteoporosis and other skeletal disorders associated with increased bone remodeling. Denosumab binds RANKL, preventing it from binding to RANK, thereby reducing the formation, activity, and survival of osteoclasts and slowing the rate of bone resorption. Postmenopausal women with low bone mineral density (BMD) treated with denosumab have a reduction of bone turnover markers and an increase in BMD that is rapid, sustained, and reversible. In postmenopausal women with osteoporosis, denosumab reduces the risk of vertebral, hip, and nonvertebral fractures. In postmenopausal women with low BMD randomized to receive denosumab or alendronate, denosumab is associated with a significantly greater increase in BMD and further reduction in bone turnover markers compared with alendronate. In postmenopausal women with low BMD who were previously treated with alendronate, those who switched to denosumab have a significantly greater BMD increase and further reduction in bone turnover markers compared with those continuing alendronate. Denosumab is well tolerated with a favorable safety profile. It is a promising emerging drug for the prevention and treatment of osteoporosis, offering a long dosing interval of every 6 months and convenient SC dosing, with the potential of improving long-term adherence to therapy compared with current oral treatments. PMID:22870424

The Role of Monocyte Percentage in Osteoporosis in Male Rheumatic Diseases.

PubMed

Su, Yu-Jih; Chen, Chao Tung; Tsai, Nai-Wen; Huang, Chih-Cheng; Wang, Hung-Chen; Kung, Chia-Te; Lin, Wei-Che; Cheng, Ben-Chung; Su, Chih-Min; Hsiao, Sheng-Yuan; Lu, Cheng-Hsien

2017-11-01

Osteoporosis is easily overlooked in male patients, especially in the field of rheumatic diseases mostly prevalent with female patients, and its link to pathogenesis is still lacking. Attenuated monocyte apoptosis from a transcriptome-wide expression study illustrates the role of monocytes in osteoporosis. This study tested the hypothesis that the monocyte percentage among leukocytes could be a biomarker of osteoporosis in rheumatic diseases. Eighty-seven males with rheumatic diseases were evaluated in rheumatology outpatient clinics for bone mineral density (BMD) and surrogate markers, such as routine peripheral blood parameters and autoantibodies. From the total number of 87 patients included in this study, only 15 met the criteria for diagnosis of osteoporosis. Both age and monocyte percentage remained independently associated with the presence of osteoporosis. Steroid dose (equivalent prednisolone dose) was negatively associated with BMD of the hip area and platelet counts were negatively associated with BMD and T score of the spine area. Besides age, monocyte percentage meets the major requirements for osteoporosis in male rheumatic diseases. A higher monocyte percentage in male rheumatic disease patients, aged over 50 years in this study, and BMD study should be considered in order to reduce the risk of osteoporosis-related fractures.

Dose and Effect Thresholds for Early Key Events in a Mode of ...

EPA Pesticide Factsheets

ABSTRACT Strategies for predicting adverse health outcomes of environmental chemicals are centered on early key events in toxicity pathways. However, quantitative relationships between early molecular changes in a given pathway and later health effects are often poorly defined. The goal of this study was to evaluate short-term key event indicators using qualitative and quantitative methods in an established pathway of mouse liver tumorigenesis mediated by peroxisome proliferator-activated receptor-alpha (PPARα). Male B6C3F1 mice were exposed for 7 days to di(2-ethylhexyl) phthalate (DEHP), di-n-octyl phthalate (DNOP), and n-butyl benzyl phthalate (BBP), which vary in PPARα activity and liver tumorigenicity. Each phthalate increased expression of select PPARα target genes at 7 days, while only DEHP significantly increased liver cell proliferation labeling index (LI). Transcriptional benchmark dose (BMDT) estimates for dose-related genomic markers stratified phthalates according to hypothetical tumorigenic potencies, unlike BMDs for non-genomic endpoints (liver weights or proliferation). The 7-day BMDT values for Acot1 as a surrogate measure for PPARα activation were 29, 370, and 676 mg/kg-d for DEHP, DNOP, and BBP, respectively, distinguishing DEHP (liver tumor BMD of 35 mg/kg-d) from non-tumorigenic DNOP and BBP. Effect thresholds were generated using linear regression of DEHP effects at 7 days and 2-year tumor incidence values to anchor early response molec

Antiresorptive effect of a cathepsin K inhibitor ONO-5334 and its relationship to BMD increase in a phase II trial for postmenopausal osteoporosis.

PubMed

Tanaka, Makoto; Hashimoto, Yoshitaka; Hasegawa, Chihiro; Deacon, Steve; Eastell, Richard

2017-06-19

ONO-5334 is a cathepsin K inhibitor that induced bone mineral density (BMD) gain in a phase II study in postmenopausal osteoporosis patients. Even though the antiresorptive effect could only be monitored in the morning during the study, simulation can allow the antiresorptive effect to be assessed over 24 h, with assessment of the relationship to BMD gain. Inhibition of the serum C-telopeptide of type I collagen (sCTX) level at doses of ONO-5334 of 100 mg once daily (QD), 300 mg QD, and 50 mg twice daily (BID) was simulated using plasma ONO-5334 pharmacokinetic (PK) data for repeated dose administration in a phase I study and corresponding sCTX inhibition from the PK-pharmacodynamic (PK/PD) relationship. sCTX was selected because it has a high signal-to-noise ratio compared to other telopeptides. A negative sigmoidal shape for the PK/PD relationship between plasma ONO-5334 and sCTX levels was obtained in our previous study. The simulated sCTX inhibition reached >99% of the maximal inhibitory effect (Emax) at 0.5 h in all treatment groups, and decreased to <80% Emax at 8 and 12 h at 50 mg BID and 100 mg QD, respectively. However, sCTX inhibition at 300 mg QD was maintained at ≥82% Emax over 24 h. The mean sCTX inhibition rates for 24 h at 100 mg QD, 300 mg QD and 50 mg BID were 63, 95 and 80% Emax, respectively. There was a positive linear relationship by treatment group between mean sCTX inhibition over 24 h and observed BMD gain in the phase II study. The dose response for BMD with ONO-5334 at 100 and 300 mg QD and higher BMD gain at 50 mg BID vs. 100 mg QD can be explained by sCTX inhibition over 24 h. The simulation gave the antiresorptive effect of ONO-5334 over 24 h and allowed prediction of BMD gain due to ONO-5334. The registration number in The European Union Clinical Trials Register is 2007-002417-39 . The date of registration was August 31, 2007.

Bone architecture adaptations after spinal cord injury: impact of long-term vibration of a constrained lower limb.

PubMed

Dudley-Javoroski, S; Petrie, M A; McHenry, C L; Amelon, R E; Saha, P K; Shields, R K

2016-03-01

This study examined the effect of a controlled dose of vibration upon bone density and architecture in people with spinal cord injury (who eventually develop severe osteoporosis). Very sensitive computed tomography (CT) imaging revealed no effect of vibration after 12 months, but other doses of vibration may still be useful to test. The purposes of this report were to determine the effect of a controlled dose of vibratory mechanical input upon individual trabecular bone regions in people with chronic spinal cord injury (SCI) and to examine the longitudinal bone architecture changes in both the acute and chronic state of SCI. Participants with SCI received unilateral vibration of the constrained lower limb segment while sitting in a wheelchair (0.6g, 30 Hz, 20 min, three times weekly). The opposite limb served as a control. Bone mineral density (BMD) and trabecular micro-architecture were measured with high-resolution multi-detector CT. For comparison, one participant was studied from the acute (0.14 year) to the chronic state (2.7 years). Twelve months of vibration training did not yield adaptations of BMD or trabecular micro-architecture for the distal tibia or the distal femur. BMD and trabecular network length continued to decline at several distal femur sub-regions, contrary to previous reports suggesting a "steady state" of bone in chronic SCI. In the participant followed from acute to chronic SCI, BMD and architecture decline varied systematically across different anatomical segments of the tibia and femur. This study supports that vibration training, using this study's dose parameters, is not an effective anti-osteoporosis intervention for people with chronic SCI. Using a high-spatial-resolution CT methodology and segmental analysis, we illustrate novel longitudinal changes in bone that occur after spinal cord injury.

High vitamin D3 diet administered during active colitis negatively affects bone metabolism in an adoptive T cell transfer model

PubMed Central

Larmonier, C. B.; McFadden, R.-M. T.; Hill, F. M.; Schreiner, R.; Ramalingam, R.; Besselsen, D. G.; Ghishan, F. K.

2013-01-01

Decreased bone mineral density (BMD) represents an extraintestinal complication of inflammatory bowel disease (IBD). Vitamin D3 has been considered a viable adjunctive therapy in IBD. However, vitamin D3 plays a pleiotropic role in bone modeling and regulates the bone formation-resorption balance, depending on the physiological environment, and supplementation during active IBD may have unintended consequences. We evaluated the effects of vitamin D3 supplementation during the active phase of disease on colonic inflammation, BMD, and bone metabolism in an adoptive IL-10−/− CD4+ T cell transfer model of chronic colitis. High-dose vitamin D3 supplementation for 12 days during established disease had negligible effects on mucosal inflammation. Plasma vitamin D3 metabolites correlated with diet, but not disease, status. Colitis significantly reduced BMD. High-dose vitamin D3 supplementation did not affect cortical bone but led to a further deterioration of trabecular bone morphology. In mice fed a high vitamin D3 diet, colitis more severely impacted bone formation markers (osteocalcin and bone alkaline phosphatase) and increased bone resorption markers, ratio of receptor activator of NF-κB ligand to osteoprotegrin transcript, plasma osteoprotegrin level, and the osteoclast activation marker tartrate-resistant acid phosphatase (ACp5). Bone vitamin D receptor expression was increased in mice with chronic colitis, especially in the high vitamin D3 group. Our data suggest that vitamin D3, at a dose that does not improve inflammation, has no beneficial effects on bone metabolism and density during active colitis or may adversely affect BMD and bone turnover. These observations should be taken into consideration in the planning of further clinical studies with high-dose vitamin D3 supplementation in patients with active IBD. PMID:23639807

High vitamin D3 diet administered during active colitis negatively affects bone metabolism in an adoptive T cell transfer model.

PubMed

Larmonier, C B; McFadden, R-M T; Hill, F M; Schreiner, R; Ramalingam, R; Besselsen, D G; Ghishan, F K; Kiela, P R

2013-07-01

Decreased bone mineral density (BMD) represents an extraintestinal complication of inflammatory bowel disease (IBD). Vitamin D₃ has been considered a viable adjunctive therapy in IBD. However, vitamin D₃ plays a pleiotropic role in bone modeling and regulates the bone formation-resorption balance, depending on the physiological environment, and supplementation during active IBD may have unintended consequences. We evaluated the effects of vitamin D₃ supplementation during the active phase of disease on colonic inflammation, BMD, and bone metabolism in an adoptive IL-10-/- CD4⁺ T cell transfer model of chronic colitis. High-dose vitamin D₃ supplementation for 12 days during established disease had negligible effects on mucosal inflammation. Plasma vitamin D₃ metabolites correlated with diet, but not disease, status. Colitis significantly reduced BMD. High-dose vitamin D₃ supplementation did not affect cortical bone but led to a further deterioration of trabecular bone morphology. In mice fed a high vitamin D₃ diet, colitis more severely impacted bone formation markers (osteocalcin and bone alkaline phosphatase) and increased bone resorption markers, ratio of receptor activator of NF-κB ligand to osteoprotegrin transcript, plasma osteoprotegrin level, and the osteoclast activation marker tartrate-resistant acid phosphatase (ACp5). Bone vitamin D receptor expression was increased in mice with chronic colitis, especially in the high vitamin D₃ group. Our data suggest that vitamin D₃, at a dose that does not improve inflammation, has no beneficial effects on bone metabolism and density during active colitis or may adversely affect BMD and bone turnover. These observations should be taken into consideration in the planning of further clinical studies with high-dose vitamin D₃ supplementation in patients with active IBD.

BENCHMARK DOSE TECHNICAL GUIDANCE DOCUMENT ...

EPA Pesticide Factsheets

The purpose of this document is to provide guidance for the Agency on the application of the benchmark dose approach in determining the point of departure (POD) for health effects data, whether a linear or nonlinear low dose extrapolation is used. The guidance includes discussion on computation of benchmark doses and benchmark concentrations (BMDs and BMCs) and their lower confidence limits, data requirements, dose-response analysis, and reporting requirements. This guidance is based on today's knowledge and understanding, and on experience gained in using this approach.

Calcium and cholecalciferol supplementation provides no added benefit to nutritional counseling to improve bone mineral density in survivors of childhood acute lymphoblastic leukemia (ALL).

PubMed

Kaste, S C; Qi, A; Smith, K; Surprise, H; Lovorn, E; Boyett, J; Ferry, R J; Relling, M V; Shurtleff, S A; Pui, C H; Carbone, L; Hudson, M M; Ness, K K

2014-05-01

We sought to improve lumbar spine bone mineral density (LS-BMD) in long-term survivors of childhood acute lymphoblastic leukemia (ALL) using calcium and cholecalciferol supplementation. This double-blind, placebo-controlled trial randomized 275 participants (median age, 17 [9-36.1] years) with age- and gender-specific LS-BMD Z-scores <0 to receive nutritional counseling with supplementation of 1,000 mg/day calcium and 800 International Unit cholecalciferol or placebo for 2 years. The primary outcome was change in LS-BMD assessed by quantitative computerized tomography (QCT) at 24 months. Linear regression models were employed to identify the baseline risk factors for low LS-BMD and to compare LS-BMD outcomes. Pre-randomization LS-BMD below the mean was associated with male gender (P = 0.0024), White race (P = 0.0003), lower body mass index (P < 0.0001), and cumulative glucocorticoid doses of ≥ 5,000 mg (P = 0.0012). One hundred eighty-eight (68%) participants completed the study; 77% adhered to the intervention. Mean LS-BMD change did not differ between survivors randomized to supplements (0.33 ± 0.57) or placebo (0.28 ± 0.56). Participants aged 9-13 years and those 22-35 years had the greatest mean increases in LS-BMD (0.50 ± 0.66 and 0.37 ± 0.23, respectively). Vitamin D insufficiency (serum 25[OH]D <30 ng/ml) found in 296 (75%), was not associated with LS-BMD outcomes (P = 0.78). Cholecalciferol and calcium supplementation provides no added benefit to nutritional counseling for improving LS-BMD among adolescent and young adult survivors of ALL (93% of whom had LS-BMD Z-scores above the mean at study entry). © 2014 Wiley Periodicals, Inc.

Effect of alendronate on early bone loss of renal transplant recipients.

PubMed

Abediazar, S; Nakhjavani, M R

2011-03-01

Renal transplant recipients (RTRs) are at risk of developing osteoporosis and osteopenia due to underlying renal osteodystrophy, hypophosphatemia, and immunosuppression. This process occurs more frequently in the first year after renal transplantation (RTX), resulting in eventual bone loss and fractures. The purpose of this study was to evaluate the effect of low-dose alendronate to prevent early bone loss after RTX. We prospectively studied 43 successful RTR including 22 men and 21-women with a mean overall age of 39.16±11.73 years, mean body mass index of 23.6±3.73, and mean dialysis duration of 25.73±17.67 months. We matched them based on age and sex: the alendronate-treated group received vitamin D (Vit D) during the study plus 30 mg alendronate weekly from 1 month after RTX. The control group only received Vit D. We measured serum calcium, phosphate, alkaline phosphatase, blood urea, creatinine, and intact parathyroid hormone (iPTH) at the pretransplant baseline and monthly thereafter as well as BMD of the lumbar spine, femur, and radius pretransplant baseline versus 3 and 6 months after RTX. At 6 month after RTX, the lumbar BMD in the alendronate group increased significantly from 0.819±0.11 to 0.863±0.14 (P<.01), while it decreased in the control group from 0.897±0.17 to 0.817±0.16 (P<.001). There was also a significant increase in radius BMD (P<.001) and a nonsignificant increase in femoral BMD in the alendronate versus a significant decrease of femoral and radius BMD (P<.001) in the control group at 6 months. Upon multivariate analysis, there was a significant correlation between alendronate and spine BMD (r=.45, P<.001) but no linear regression between age, sex, BMI, dialysis duration of or iPTH with femoral, spine, or radius BMD changes at month 6. Low-dose alendronate was significantly useful to mitigate fast bone loss and increase BMD immediately after RTX. Copyright © 2011. Published by Elsevier Inc.

Perioperative alendronate, risedronate, calcitonin and indomethacin treatment alters femoral stem fixation and periprosthetic bone mineral density in ovariectomized rats.

PubMed

Cankaya, Deniz; Tabak, Yalcin; Ozturk, Akif Muhtar; Gunay, Muhammed Cuneyd

2015-07-01

Many factors affect implant stability and periprosthetic bone mineral density (BMD) following total joint arthroplasty. We asked whether perioperative alendronate, risedronate, calcitonin and indomethacine administration altered (1) femoral stem shear strength and periprosthetic bone mineral density BMD in ovariectomized rats and (2) whether there were differences in the effect of these drugs. Thirty overiectomized rats were divided into five groups and implanted with intramedullary mini-cortical screws in the femur. Four groups were treated with alendronate, risedronate, salmon calcitonin and indomethacin for 4 weeks preoperatively and 8 weeks postoperatively. Although alendronate and risedronate increased the periprosthetic BMD more than calcitonin, they did not alter implant fixation compared to calcitonin. Indomethacin significantly decreased the BMD around the stem and implant stability compared to all other groups. This study showed that perioperative treatment with bisphosphonates and calcitonin improved the BMD around the stems and implant stability. Although bisphosphonates increased the BMD more than calcitonin, there was no difference in implant stability. Indomethacin markedly decreased the periprosthetic BMD and implant stability. The main clinical significance of our study was the finding about the need to strictly avoid long-term use of high-dose nonsteroidal antiinflammatory drugs for patients who have major joint arthritis and a previous history of arthroplasty.

77 FR 36533 - Notice of Availability of the Benchmark Dose Technical Guidance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-19

... ENVIRONMENTAL PROTECTION AGENCY [FRL-9688-7] Notice of Availability of the Benchmark Dose Technical Guidance AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of Availability. SUMMARY: The U.S. Environmental Protection Agency is announcing the availability of Benchmark Dose Technical...

A Candidate Gene Association Study of Bone Mineral Density in an Iranian Population.

PubMed

Dastgheib, Seyed Alireza; Gartland, Alison; Tabei, Seyed Mohammad Bagher; Omrani, Gholamhossein Ranjbar; Teare, Marion Dawn

2016-01-01

The genetic epidemiology of variation in bone mineral density (BMD) and osteoporosis is not well studied in Iranian populations and needs more research. We report a candidate gene association study of BMD variation in a healthy cross-sectional study of 501 males and females sampled from the Iranian Multi-Centre Osteoporosis Study, Shiraz, Iran. We selected to study the association with 21 single nucleotide polymorphisms (SNPs) located in the 7 candidate genes LRP5, RANK, RANKL, OPG, P2RX7, VDR , and ESR1 . BMD was measured at the three sites L2-L4, neck of femur, and total hip. Association between BMD and each SNP was assessed using multiple linear regression assuming an allele dose (additive effect) on BMD (adjusted for age and sex). Statistically significant (at the unadjusted 5% level) associations were seen with seven SNPs in five of the candidate genes. Two SNPs showed statistically significant association with more than one BMD site. Significant association was seen between BMD at all the three sites with the VDR SNP rs731246 (L2-L4 p  = 0.038; neck of femur p  = 0.001; and total hip p  < 0.001). The T allele was consistently associated with lower BMD than the C allele. Significant association was also seen for the P2RX7 SNP rs3751143, where the G allele was consistently associated with lower BMD than the T allele (L2-L4 p  = 0.069; neck of femur p  = 0.024; and total hip p  = 0.045).

A Consumer's Guide to Benchmark Dose Models: Results of U.S. EPA Testing of 14 Dichotomous, 8 Continuous, and 6 Developmental Models (Presentation)

EPA Science Inventory

Benchmark dose risk assessment software (BMDS) was designed by EPA to generate dose-response curves and facilitate the analysis, interpretation and synthesis of toxicological data. Partial results of QA/QC testing of the EPA benchmark dose software (BMDS) are presented. BMDS pr...

Bone mineral density loss in thoracic and lumbar vertebrae following radiation for abdominal cancers.

PubMed

Wei, Randy L; Jung, Brian C; Manzano, Wilfred; Sehgal, Varun; Klempner, Samuel J; Lee, Steve P; Ramsinghani, Nilam S; Lall, Chandana

2016-03-01

To investigate the relationship between abdominal chemoradiation (CRT) for locally advanced cancers and bone mineral density (BMD) reduction in the vertebral spine. Data from 272 patients who underwent abdominal radiation therapy from January 1997 to May 2015 were retrospectively reviewed. Forty-two patients received computed tomography (CT) scans of the abdomen prior to initiation and at least twice after radiation therapy. Bone attenuation (in Hounsfield unit) (HU) measurements were collected for each vertebral level from T7 to L5 using sagittal CT images. Radiation point dose was obtained at each mid-vertebral body from the radiation treatment plan. Percent change in bone attenuation (Δ%HU) between baseline and post-radiation therapy were computed for each vertebral body. The Δ%HU was compared against radiation dose using Pearson's linear correlation. Abdominal radiotherapy caused significant reduction in vertebral BMD as measured by HU. Patients who received only chemotherapy did not show changes in their BMD in this study. The Δ%HU was significantly correlated with the radiation point dose to the vertebral body (R=-0.472, P<0.001) within 4-8 months following RT. The same relationship persisted in subsequent follow up scans 9 months following RT (R=-0.578, P<0.001). Based on the result of linear regression, 5 Gy, 15 Gy, 25 Gy, 35 Gy, and 45 Gy caused 21.7%, 31.1%, 40.5%, 49.9%, and 59.3% decrease in HU following RT, respectively. Our generalized linear model showed that pre-RT HU had a positive effect (β=0.830) on determining post-RT HU, while number of months post RT (β=-0.213) and radiation point dose (β=-1.475) had a negative effect. A comparison of the predicted versus actual HU showed significant correlation (R=0.883, P<0.001) with the slope of the best linear fit=0.81. Our model's predicted HU were within ±20 HU of the actual value in 53% of cases, 70% of the predictions were within ±30 HU, 81% were within ±40 HU, and 90% were within ±50 HU of the actual post-RT HU. Four of 42 patients were found to have vertebral body compression fractures in the field of radiation. Patients who receive abdominal chemoradiation develop significant BMD loss in the thoracic and lumbar vertebrae. Treatment-related BMD loss may contribute to the development of vertebral compression fractures. A predictive model for post-CRT BMD changes may inform bone protective strategies in patients planned for abdominal CRT. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Soy Isoflavones for Reducing Bone Loss (SIRBL) Study: Three year effects on pQCT bone mineral density and strength measures in postmenopausal women

PubMed Central

SHEDD-WISE, KRISTINE M.; ALEKEL, D. LEE; HOFMANN, HEIKE; HANSON, KATHY B.; SCHIFERL, DAN J.; HANSON, LAURA N.; VAN LOAN, MARTA D.

2011-01-01

Soy isoflavones exert inconsistent bone density-preserving effects, but the bone strength-preserving effects in humans are unknown. Our double-blind randomized controlled trial examined two soy isoflavone doses (80 or 120 mg/d) vs placebo tablets on volumetric bone mineral density (vBMD) and strength (via peripheral quantitative computed tomography) in healthy postmenopausal women (46–63 y). We measured 3 y change in cortical (Ct) BMD, cortical thickness (CtThk), periosteal circumference (PC), endosteal circumference (EC), and strength-strain index (SSI) at 1/3 midshaft femur (N=171) and trabecular (Tb) BMD, PC, and SSI at 4% distal tibia (N=162). We found no treatment effect on femur CtThk, PC, or EC, or tibia TbBMD or PC. Strongest predictors (negative) of tibia TbBMD and SSI and femur CtBMD were timepoint and bone resorption; whole body fat mass was protective of SSI. As time since last menstrual period (TLMP) increased (p=0.012), 120 mg/d was protective of CtBMD. Strongest predictors of femur SSI were timepoint, bone resorption, and TLMP (protective). Isoflavone tablets were negative predictors of SSI, but 80 mg/d became protective as bone turnover increased (p=0.011). Soy isoflavone treatment for 3 y was modestly beneficial for midshaft femur vBMD as TLMP increased, and for midshaft femur SSI as bone turnover increased. PMID:21295742

A Mode-of-Action Approach for the Identification of Genotoxic Carcinogens

PubMed Central

Hernández, Lya G.; van Benthem, Jan; Johnson, George E.

2013-01-01

Distinguishing between clastogens and aneugens is vital in cancer risk assessment because the default assumption is that clastogens and aneugens have linear and non-linear dose-response curves, respectively. Any observed non-linearity must be supported by mode of action (MOA) analyses where biological mechanisms are linked with dose-response evaluations. For aneugens, the MOA has been well characterised as disruptors of mitotic machinery where chromosome loss via micronuclei (MN) formation is an accepted endpoint used in risk assessment. In this study we performed the cytokinesis-block micronucleus assay and immunofluorescence mitotic machinery visualisation in human lymphoblastoid (AHH-1) and Chinese Hamster fibroblast (V79) cell lines after treatment with the aneugen 17-β-oestradiol (E2). Results were compared to previously published data on bisphenol-A (BPA) and Rotenone data. Two concentration-response approaches (the threshold-[Td] and benchmark-dose [BMD] approaches) were applied to derive a point of departure (POD) for in vitro MN induction. BMDs were also derived from the most sensitive carcinogenic endpoint. Ranking comparisons of the PODs from the in vitro MN and the carcinogenicity studies demonstrated a link between these two endpoints for BPA, E2 and Rotenone. This analysis was extended to include 5 additional aneugens, 5 clastogens and 3 mutagens and further concentration and dose-response correlations were observed between PODs from the in vitro MN and carcinogenicity. This approach is promising and may be further extended to other genotoxic carcinogens, where MOA and quantitative information from the in vitro MN studies could be used in a quantitative manner to further inform cancer risk assessment. PMID:23675539

Recent advances in mathematical modeling of developmental abnormalities using mechanistic information.

PubMed

Kavlock, R J

1997-01-01

During the last several years, significant changes in the risk assessment process for developmental toxicity of environmental contaminants have begun to emerge. The first of these changes is the development and beginning use of statistically based dose-response models [the benchmark dose (BMD) approach] that better utilize data derived from existing testing approaches. Accompanying this change is the greater emphasis placed on understanding and using mechanistic information to yield more accurate, reliable, and less uncertain risk assessments. The next stage in the evolution of risk assessment will be the use of biologically based dose-response (BBDR) models that begin to build into the statistically based models factors related to the underlying kinetic, biochemical, and/or physiologic processes perturbed by a toxicant. Such models are now emerging from several research laboratories. The introduction of quantitative models and the incorporation of biologic information into them has pointed to the need for even more sophisticated modifications for which we offer the term embryologically based dose-response (EBDR) models. Because these models would be based upon the understanding of normal morphogenesis, they represent a quantum leap in our thinking, but their complexity presents daunting challenges both to the developmental biologist and the developmental toxicologist. Implementation of these models will require extensive communication between developmental toxicologists, molecular embryologists, and biomathematicians. The remarkable progress in the understanding of mammalian embryonic development at the molecular level that has occurred over the last decade combined with advances in computing power and computational models should eventually enable these as yet hypothetical models to be brought into use.

Low bone density risk is higher in exercising women with multiple triad risk factors.

PubMed

Gibbs, Jenna C; Nattiv, Aurelia; Barrack, Michelle T; Williams, Nancy I; Rauh, Mitchell J; Nichols, Jeanne F; De Souza, Mary Jane

2014-01-01

The cumulative effect of the female athlete triad (Triad) risk factors on the likelihood of low bone mineral density (BMD) in exercising women is unclear. This study aimed to determine the risk of low BMD in exercising women with multiple Triad risk factors. We retrospectively examined cross-sectional data from 437 exercising women (mean ± SD age of 18.0 ± 3.5 yr, weighed 57.5 ± 7.1 kg with 24.5% ± 6.1% body fat) obtained at baseline from 4 prospective cohort studies examining Triad risk factors. Questionnaires were completed to obtain information on demographic characteristics, self-reported eating attitudes/behaviors, menstrual function, sport/activity participation, and medication use. Height and body weight were measured. BMD was measured using dual energy x-ray absorptiometry. Low BMD was defined as z-scores of <-1 and ≤-2. Chi-square tests were performed to determine the percentage of women with low BMD who met the criteria for individual (current oligo/amenorrhea, late menarche, low body mass index (BMI), elevated dietary restraint, lean sport/activity participation) or multiple (2, 3, 4, or 5) Triad risk factors. Late menarche and low BMI were associated with the highest percentage of low BMD (z-score < -1), 55% and 54%, respectively, and low BMD (z-score ≤-2), 14% and 16%, respectively. The percentage of participants with low BMD (z-score < -1 and ≤-2) increased from 10% to 62% and from 2% to 18%, respectively, as women met the criteria for an increasing number of Triad risk factors. A cumulative number of Triad risk factors were associated with an increased risk of low BMD, suggesting a dose-response association between the number of Triad risk factors and BMD in exercising women. Further research should be conducted to develop a user-friendly algorithm integrating these indicators of risk for low BMD in exercising women (particularly factors associated with low BMI/body weight, menstrual dysfunction, lean sport/activity participation, and elevated dietary restraint).

Bone architecture adaptations after spinal cord injury: impact of long-term vibration of a constrained lower limb

PubMed Central

Dudley-Javoroski, S.; Petrie, M. A.; McHenry, C. L.; Amelon, R. E.; Saha, P. K.

2015-01-01

Summary This study examined the effect of a controlled dose of vibration upon bone density and architecture in people with spinal cord injury (who eventually develop severe osteoporosis). Very sensitive computed tomography (CT) imaging revealed no effect of vibration after 12 months, but other doses of vibration may still be useful to test. Introduction The purposes of this report were to determine the effect of a controlled dose of vibratory mechanical input upon individual trabecular bone regions in people with chronic spinal cord injury (SCI) and to examine the longitudinal bone architecture changes in both the acute and chronic state of SCI. Methods Participants with SCI received unilateral vibration of the constrained lower limb segment while sitting in a wheelchair (0.6g, 30 Hz, 20 min, three times weekly). The opposite limb served as a control. Bone mineral density (BMD) and trabecular micro-architecture were measured with high-resolution multi-detector CT. For comparison, one participant was studied from the acute (0.14 year) to the chronic state (2.7 years). Results Twelve months of vibration training did not yield adaptations of BMD or trabecular micro-architecture for the distal tibia or the distal femur. BMD and trabecular network length continued to decline at several distal femur sub-regions, contrary to previous reports suggesting a “steady state” of bone in chronic SCI. In the participant followed from acute to chronic SCI, BMD and architecture decline varied systematically across different anatomical segments of the tibia and femur. Conclusions This study supports that vibration training, using this study’s dose parameters, is not an effective antiosteoporosis intervention for people with chronic SCI. Using a high-spatial-resolution CT methodology and segmental analysis, we illustrate novel longitudinal changes in bone that occur after spinal cord injury. PMID:26395887

Effect of low-dose calcium supplements on bone loss in perimenopausal and postmenopausal Asian women: a randomized controlled trial.

PubMed

Nakamura, Kazutoshi; Saito, Toshiko; Kobayashi, Ryosaku; Oshiki, Rieko; Kitamura, Kaori; Oyama, Mari; Narisawa, Sachiko; Nashimoto, Mitsue; Takahashi, Shunsuke; Takachi, Ribeka

2012-11-01

Current standard-dose calcium supplements (eg, 1000 mg/d) may increase the risk for cardiovascular events. Effectiveness of lower-dose supplements in preventing bone loss should thus be considered. This study aimed to assess whether calcium supplements of 500 or 250 mg/d effectively prevent bone loss in perimenopausal and postmenopausal Japanese women. We recruited 450 Japanese women between 50 and 75 years of age. They were randomly assigned to receive 500 mg of calcium (as calcium carbonate), 250 mg of calcium, or placebo daily. Medical examinations conducted three times over a 2-year follow-up period assessed bone mineral density (BMD) of the lumbar spine and femoral neck. One-factor repeated measures ANOVA was used for statistical tests. Subgroup analyses were also conducted. Average total daily calcium intake at baseline for the 418 subjects who underwent follow-up examinations was 493 mg/d. Intention-to-treat analysis showed less dramatic decreases in spinal BMD for the 500-mg/d calcium supplement group compared to the placebo group (1.2% difference over 2 years, p = 0.027). Per-protocol analysis (≥80% compliance) revealed that spinal BMD for the 500-mg/d and 250-mg/d calcium supplement groups decreased less than the placebo group (1.6%, p = 0.010 and 1.0%, p = 0.078, respectively), and that femoral neck BMD for the 500-mg/d calcium supplement group decreased less relative to the placebo group (1.0%, p = 0.077). A low-dose calcium supplement of 500 mg/d can effectively slow lumbar spine bone loss in perimenopausal and postmenopausal women with habitually low calcium intake, but its effect on the femoral neck is less certain. Calcium supplementation dosage should thus be reassessed. (Clinical Trials Registry number: UMIN000001176). Copyright © 2012 American Society for Bone and Mineral Research.

Low-dose combined oral contraceptive use is associated with lower bone mineral content variation in adolescents over a 1-year period.

PubMed

Biason, Talita Poli; Goldberg, Tamara Beres Lederer; Kurokawa, Cilmery Suemi; Moretto, Maria Regina; Teixeira, Altamir Santos; Nunes, Hélio Rubens de Carvalho

2015-04-03

Low-dose combined oral contraceptives (COCs) can interfere with bone mass acquisition during adolescence. This study aimed to evaluate bone mineral density (BMD) and bone mineral content (BMC) in female adolescents taking a standard low-dose COC (ethinylestradiol 20 μg/desogestrel 150 μg) over a 1-year period and to compare their data with those of healthy adolescents from the same age group not taking COCs. This was a non-randomized parallel-control study with a 1-year follow-up. Sixty-seven adolescents aged from 12 to 19 years, divided into COC users (n = 41) taking 20 μg ethinylestradiol/150 μg desogestrel and COC non-user controls (n = 26), were evaluated by bone densitometry examinations at baseline and after 12 months. Comparisons between the groups at the study onset were performed using the Mann-Whitney test with the significance level fixed at 5% or p < 0.05. Comparisons between the groups at the study onset and after 12 months were based on variations in the median percentages for bone mass variables. The COC users presented with low bone mass acquisition in the lumbar spine, and had BMD and BMC median variations of 2.07% and +1.57%, respectively, between the measurements at baseline and 12 months. The control group had median variations of +12.16% and +16.84% for BMD and BMC, respectively, over the same period. The total body BMD and BMC showed similar evolutions during the study in both groups. Statistical significance (p < 0.05) was seen for the BMC percentage variation between COC users and non-users. Use of a low-dose COC (ethinylestradiol 20 μg/desogestrel 150 μg) was associated with lower bone mass acquisition in adolescents during the study period. Registry Number, RBR-5h9b3c.

Asymmetric bone adaptations to soleus mechanical loading after spinal cord injury

PubMed Central

Dudley-Javoroski, S.; Shields, R.K.

2009-01-01

The purpose of this report is to examine longitudinal bone mineral density (BMD) changes in individuals with spinal cord injury (SCI) who began unilateral soleus electrical stimulation early after injury. Twelve men with SCI and seven without SCI underwent peripheral quantitative computed tomography assessment of distal tibia BMD. After 4.5 to 6 years of training, average trained limb BMD was 27.5% higher than untrained limb BMD. The training effect was more pronounced in the central core of the tibia cross-section (40.5% between-limb difference). No between-limb difference emerged in the anterior half of the tibia (19.2 mg/cm3 difference, p>0.05). A robust between-limb difference emerged in the posterior half of the tibia (76.1 mg/cm3 difference, p=0.0439). The posterior tibia BMD of one subject remained within the range of non-SCI values for 3.8 years post-SCI. The results support that the constrained orientation of soleus mechanical loads, administered over several years, elicited bone-sparing effects in the posterior tibia. This study provides a demonstration of the bone-protective potential of a carefully controlled dose of mechanical load. The specific orientation of applied mechanical loads may strongly influence the manifestation of BMD adaptations in humans with SCI. PMID:18799855

Metabolic and skeletal effects of low and high doses of calcium acetate in patients with preterminal chronic renal failure.

PubMed

Phelps, Kenneth R; Stern, Marc; Slingerland, Alice; Heravi, Mahin; Strogatz, David S; Haqqie, Syed S

2002-01-01

Secondary hyperparathyroidism commonly evolves, as the glomerular filtration rate falls. The metabolic and skeletal effects of a possible remedy, calcium acetate, have not been studied in patients with preterminal chronic renal failure. Men with a mean creatinine clearance of approximately 30 ml/min took calcium acetate for 24 weeks at doses which provided 507 or 1,521 mg calcium/day with meals. Metabolic determinations were made at intervals of 4-8 weeks, and the bone mineral density (BMD) was measured at the beginning and at the end of the trial. The low-dose regimen produced no metabolic or skeletal effect. In subjects prescribed the high-dose regimen, the 24-hour urine phosphorus excretion fell from 0.53 mg/mg creatinine to values ranging from 0.34 to 0.41 mg/mg creatinine. The theoretical phosphorus threshold concentration rose by a maximum of 38.6%, and the serum phosphorus concentration did not change. The mean serum calcium concentration rose by a maximum of 7.2%. The mean fractional changes in parathyroid hormone and 1,25-dihydroxyvitamin D concentrations ranged from -27.0 to -39.6% and from -5.0 to -20.3%, respectively. The BMD increased at L1, L3, and L4. Calcium acetate prescribed to deliver 1,521 mg calcium/day with meals reduced parathyroid hormone and 1,25-dihydroxyvitamin D concentrations and increased lumbar BMD in men with preterminal chronic renal failure. Copyright 2002 S. Karger AG, Basel

Nonparametric estimation of benchmark doses in environmental risk assessment

PubMed Central

Piegorsch, Walter W.; Xiong, Hui; Bhattacharya, Rabi N.; Lin, Lizhen

2013-01-01

Summary An important statistical objective in environmental risk analysis is estimation of minimum exposure levels, called benchmark doses (BMDs), that induce a pre-specified benchmark response in a dose-response experiment. In such settings, representations of the risk are traditionally based on a parametric dose-response model. It is a well-known concern, however, that if the chosen parametric form is misspecified, inaccurate and possibly unsafe low-dose inferences can result. We apply a nonparametric approach for calculating benchmark doses, based on an isotonic regression method for dose-response estimation with quantal-response data (Bhattacharya and Kong, 2007). We determine the large-sample properties of the estimator, develop bootstrap-based confidence limits on the BMDs, and explore the confidence limits’ small-sample properties via a short simulation study. An example from cancer risk assessment illustrates the calculations. PMID:23914133

Bone mineral density during pregnancy in women participating in a randomized controlled trial of vitamin D supplementation.

PubMed

Wei, Wei; Shary, Judith R; Garrett-Mayer, Elizabeth; Anderson, Betsy; Forestieri, Nina E; Hollis, Bruce W; Wagner, Carol L

2017-12-01

Background: Little is known about bone mineral density (BMD) during pregnancy. Advances in technology with lower radiation emissions by dual-energy X-ray absorptiometry instruments now permit the safe measurement of BMD during pregnancy. Objective: We evaluated maternal BMD during pregnancy as a function of vitamin D status in women of diverse racial/ethnic backgrounds. Design: A total of 301 women who underwent BMD measurements at 12-20 wk of gestation and again at 0-14 wk postpartum were included in this analysis. Women were a subset of subjects who were recruited for a randomized, controlled, double-blind trial of vitamin D supplementation in pregnancy (400, 2000, or 4000 IU/d). Results: Treatment had no significant effect on changes in BMD that occurred between 12-20 wk of gestation and 0-14 wk postpartum. Similarly, changes in spine and femoral neck bone mineral contents (BMCs) were not significantly different in the treatment groups. In addition, vitamin D inadequacy (serum 25-hydroxyvitamin D concentration, averaged across pregnancy, <50 nmol/L) was not associated with changes in BMD or BMC. There were significant racial/ethnic differences in spine BMD. African Americans lost more spine BMD than did Caucasians (-0.04 ± 0.04 compared with -0.02 ± 0.04 g/cm 2 ; P = 0.033). In addition, baseline obesity was associated with a greater loss of femoral neck BMD. The means ± SDs of femoral neck BMD loss were -0.02 ± 0.05 and 0.0 ± 0.03 g/cm 2 for groups with baseline body mass index (BMI; in kg/m 2 ) ≥30 and <30, respectively. Conclusion: These findings do not support a dose effect of vitamin D supplementation on bone health and suggest that race/ethnicity and BMI play an important role in pregnancy bone health. This trial was registered at clinicaltrials.gov as NCT00292591. © 2017 American Society for Nutrition.

Testosterone Dose Dependently Prevents Bone and Muscle Loss in Rodents after Spinal Cord Injury

PubMed Central

Conover, Christine F.; Beggs, Luke A.; Beck, Darren T.; Otzel, Dana M.; Balaez, Alexander; Combs, Sarah M.; Miller, Julie R.; Ye, Fan; Aguirre, J. Ignacio; Neuville, Kathleen G.; Williams, Alyssa A.; Conrad, Bryan P.; Gregory, Chris M.; Wronski, Thomas J.; Bose, Prodip K.; Borst, Stephen E.

2014-01-01

Abstract Androgen administration protects against musculoskeletal deficits in models of sex-steroid deficiency and injury/disuse. It remains unknown, however, whether testosterone prevents bone loss accompanying spinal cord injury (SCI), a condition that results in a near universal occurrence of osteoporosis. Our primary purpose was to determine whether testosterone-enanthate (TE) attenuates hindlimb bone loss in a rodent moderate/severe contusion SCI model. Forty (n=10/group), 14 week old male Sprague-Dawley rats were randomized to receive: (1) Sham surgery (T9 laminectomy), (2) moderate/severe (250 kdyne) SCI, (3) SCI+Low-dose TE (2.0 mg/week), or (4) SCI+High-dose TE (7.0 mg/week). Twenty-one days post-injury, SCI animals exhibited a 77–85% reduction in hindlimb cancellous bone volume at the distal femur (measured via μCT) and proximal tibia (measured via histomorphometry), characterized by a >70% reduction in trabecular number, 13–27% reduction in trabecular thickness, and increased trabecular separation. A 57% reduction in cancellous volumetric bone mineral density (vBMD) at the distal femur and a 20% reduction in vBMD at the femoral neck were also observed. TE dose dependently prevented hindlimb bone loss after SCI, with high-dose TE fully preserving cancellous bone structural characteristics and vBMD at all skeletal sites examined. Animals receiving SCI also exhibited a 35% reduction in hindlimb weight bearing (triceps surae) muscle mass and a 22% reduction in sublesional non-weight bearing (levator ani/bulbocavernosus [LABC]) muscle mass, and reduced prostate mass. Both TE doses fully preserved LABC mass, while only high-dose TE ameliorated hindlimb muscle losses. TE also dose dependently increased prostate mass. Our findings provide the first evidence indicating that high-dose TE fully prevents hindlimb cancellous bone loss and concomitantly ameliorates muscle loss after SCI, while low-dose TE produces much less profound musculoskeletal benefit. Testosterone-induced prostate enlargement, however, represents a potential barrier to the clinical implementation of high-dose TE as a means of preserving musculoskeletal tissue after SCI. PMID:24378197

Lead toxicity: does the critical level of lead resulting in adverse effects differ between adults and children?

PubMed

Murata, Katsuyuki; Iwata, Toyoto; Dakeishi, Miwako; Karita, Kanae

2009-01-01

The Scientific Committee on Neurotoxicology and Psychophysiology and the Scientific Committee on the Toxicology of Metals of the International Commission on Occupational Health in 2006 recommended that the standard for blood lead (BPb) levels be reduced to 30 microg/dl for industrial workers and 5 microg/dl for children. To examine whether the critical level of lead producing adverse effects truly differs between workers and children, we provided an overview of studies addressing the critical level of lead in workers, together with a perspective on lead toxicity in children. In 25 reports published in English with keywords of "benchmark dose (BMD)," "lead" and "humans," only five studies proved to be relevant to lead toxicity. Four more studies with figures illustrating significant relationships between lead and neurotoxic outcomes were selected. Based on data from previous reports using a BMD approach, the critical organ of lead in workers was thought to be the nervous system and the critical BPb level (number-weighted mean) was between 10.7 and 17.5 microg/dl. The neurotoxic effects of lead exposure at such levels seemed reversible. The BPb level at which lead-associated intellectual deficits occurred in children was as low as the critical level of BPb (below 5 microg/dl) for inhibited heme synthesis in workers. The neurotoxic effects of lead in workers appear to be initiated at BPb levels below 18 microg/dl, which are somewhat higher than the critical level of lead neurotoxicity in children. Each national institute for risk management should take evidence-based preventive action against subclinical lead poisoning in workers, as well as in children.

[The replacement therapy of rPTH(1-84) in established rat model of hypothyroidism].

PubMed

Ding, Zhiwei; Li, Tiancheng; Liu, Yuhe; Xiao, Shuifang

2015-12-01

To investigate the replacement therapy of rPTH(1-84) (recombinant human parathyroid hormone (1-84)) to hypothyroidism in established rat model. Rat model of hypothyroidism was established by resecting parathyroids. A total of 30 rats with removal of parathyroids were divided into 6 groups randomly, 5 in each group, and applied respectively with saline injection (negative control group), calcitriol treatment (positive control group) and quadripartite PTH administration with dose of 20, 40, 80 and 160 µg/kg (experimental groups). Saline and rPTH(1-84) were injected subcutaneously daily. Calcitriol was gavaged once a day. Sham-operation was conducted in 5 rats of negative control group. To verify the authenticity of the rat model with hypothyroidism, the serum was insolated centrifugally from rat blood that was obtained from angular vein at specific time to measure calcium and phosphorus concentration. Urine in 12 hours was collected by metabolic cages and the calcium concentration was measured. After 10-week drug treatment, the experiment was terminated and bilateral femoral bone and L2-5 lumbar vertebra were removed from rats. Bone mineral density (BMD)of bilateral femoral bone and lumbar vertebra was analyzed by dual X-ray absorptiometry (DXA). The concentration of bone alkaline phosphatase (BALP) in serum was determined by radioimmunoassay. The rat model with hypothyroidism was obtained by excising parathyroid gland and was verified by monitoring calcium and phosphorus concentration subsequently. Administration of rPTH(1-84) in the dose of 80 or 160 µg/kg made serum calcium and phosphorus back to normal levels, with no significant difference between the doses (P>0.05). The BMD in each group of rats with rPTH(1-84) administration was increased significantly (P<0.05). The levels of urinary calcium and serum BALP in rats of maximum rPTH(1-84) injection group (160 µg/kg) were higher than those of normal control group (P<0.05). The rats treated with calcitriol had normal calcium levels and showed the increase of BMD and phosphorus concentration compared with normal control group (P<0.05). The amount of urinary calcium also exceeded the other groups (P<0.05), but no with significant difference in BMD of bilateral femoral bone and lumbar vertebra between negative control group and normal control group (P>0.05). Calcium and phosphorus return to normal level by administration of rPTH(1-84) in the dose of 80 µg/kg or 160 µg/kg, with increase in BMD. Calcitriol can return the level of calcium to normal and increase BMD, but can not correspondingly decrease the phosphorus concentration and increase the excretion of calcium in urine.

A MULTIMODEL APPROACH FOR CALCULATING BENCHMARK DOSE

EPA Science Inventory

A Multimodel Approach for Calculating Benchmark Dose
Ramon I. Garcia and R. Woodrow Setzer

In the assessment of dose response, a number of plausible dose- response models may give fits that are consistent with the data. If no dose response formulation had been speci...

Adverse events, bone mineral density and discontinuation associated with generic alendronate among postmenopausal women previously tolerant of brand alendronate: a retrospective cohort study

PubMed Central

2010-01-01

Background A rise in gastrointestinal (GI) adverse events (AEs) and a decline in bone mineral density (BMD) was observed in patients previously tolerant to brand alendronate shortly after generic versions were introduced in July 2005 to the Canadian market. The objective of our study was to quantify changes in AE rates and BMD scores, as well as associated alendronate discontinuation among patients before and after switch from brand to generic alendronate. Methods A chart review of postmenopausal women 50 years of age and older between 2003 and 2007 was conducted in two specialized tertiary care referral centers. Patients on alendronate both before and after July 2005 were included. The change in the number of AEs, changes in BMD and associated alendronate discontinuation was compared before and after the switch from brand to generic alendronate. Results 301 women with an average age of 67.6 years (standard deviation (SD) = 9.5) had a total of 47 AEs between July 2003 and December 2007 that resulted in discontinuation of the medication. There was a significant increase in the rate of AEs per patient-months-at-risk from 0.0001 before to 0.0044 after October 2005 (p < 0.001). The most common AEs were GI in nature (stomach pain, GI upset, nausea, and reflux). In addition, 23 patients discontinued alendronate due to BMD reduction after January 2006. In these patients, BMD scores were significantly reduced from their prior BMD measures (change of -0.0534, p < 0.001 for spine BMD and change of -0.0338, p = 0.01 for femur BMD). Among patients who discontinued due to BMD reduction, BMD was stable in the period prior to January 2006 (change of -0.0066, p = 0.5 for spine BMD and change of 0.0011, p = 0.9 for femur BMD); however, testing for reduction after January 2006 in BMD measures (one-sided T-test) revealed there was a significant reduction in BMD scores for both anatomic sites (change of -0.0321, p = .005 for spine, change of -0.0205, p = 0.05 for femur). Conclusions Patients who were previously stable on doses of brand alendronate experienced an increase in AEs causing discontinuation after introduction of automatic substitution to generic alendronate. In addition, reductions in BMD were observed in some patients who had stable BMDs before January 2006. Given the substantial increase in AEs, generic alendronate may not be as well tolerated as brand alendronate. PMID:20388226

Calcium and Vitamin D Supplementation and Loss of Bone Mineral Density in Women Undergoing Breast Cancer Therapy

PubMed Central

Datta, Mridul; Schwartz, Gary G.

2013-01-01

An unintended consequence of breast cancer therapies is an increased risk of osteoporosis due to accelerated bone loss. We conducted a systematic review of calcium and/or vitamin D (Ca±D) supplementation trials for maintaining bone mineral density (BMD) in women with breast cancer using the “before-after” data from the Ca±D supplemented comparison group of trials evaluating the effect of drugs such as bisphosphonates on BMD. Whether Ca±D supplements increase BMD in women undergoing breast cancer therapy has never been tested against an unsupplemented control group. However, results from 16 trials indicate that the Ca±D doses tested (500-1500 mg calcium; 200-1000 IU vitamin D) were inadequate to prevent BMD loss in these women. Cardiovascular disease is the main cause of mortality in women with breast cancer. Because calcium supplements may increase cardiovascular disease risk, future trials should evaluate the safety and efficacy of Ca±D supplementation in women undergoing breast cancer therapy. PMID:23932583

Effect of zoledronic acid on bone density and markers of bone turnover in a community clinic.

PubMed

Lim, Ria; Zailskas, Susan; Goldsby, Tashauna U; Lukens, Carrie; Muravev, Rostislav; Dulipsingh, Latha

2013-01-01

This study aims to document the efficacy of zoledronic acid by comparing bone densities and markers of bone turnover, in patients with osteoporosis. Bone mineral density (BMD) and urinary N-telopeptide, a marker of bone turnover, were compared before and after treatment with intravenous zoledronic acid. 52 participants had atleast two doses of zoledronic acid over 36 months. Significant increases in BMD were found in the spine (t=4.38, P<0.01) and decrease in bone turnover marker N-telopeptide (t=3.30, P=0.002). Small but significant correlations were determined between prior steroid use and change in BMD in the spine (r=0.35, P<0.05), and family history of osteoporosis and change in BMD in the right femur (r=0.38, P<0.05). Annual infusions of zoledronic acid for at least two years, revealed a significant increase in bone density at the spine and a decrease in urinary N-telopeptide in patients treated at our center.

Effect of carbamezapine and valproic acid on bone mineral density, IGF-I and IGFBP-3.

PubMed

Kumandas, Sefer; Koklu, Esad; Gümüs, Hakan; Koklu, Selmin; Kurtoglu, Selim; Karakukcu, Musa; Keskin, Mehmet

2006-04-01

To examine the effect of carbamezapine and valproate on bone mineral density (BMD), IGF-I and IGFBP-3 levels in children. The effects of at least 2 years valproic acid and carbamazepine therapy on BMD were evaluated in a cross-sectional and retrospective study. All children were ambulatory, prepubertal, and had normal activity and nutritionally adequate diets. Ambulatory epileptic patients were divided into two groups. Thirty-three patients (group 1; 17 boys, 16 girls; mean age: 8.8 +/- 2.0 years) were treated with valproic acid and 33 patients were treated with carbamazepine (group 2; 20 boys, 13 girls; mean age: 9.7 +/- 1.6 years). The control group consisted of 22 healthy children (13 boys, 9 girls; mean age: 8.9 +/- 2.3 years), who were age- and sex-matched with the patient groups. Children with metabolic bone disease, growth and neurological impairment, signs of malnutrition, or any chronic disease were excluded from the study. BMD values at lumbar spine in both the carbamazepine (-1.69 +/- 0.85 mean L1-4 BMD z-scores, mean 35.5 +/- 12.8 months treatment, and 19,478.6 +/- 6,301.3 mg/kg cumulative dose) and valproic acid (-1.28 +/- 0.80 mean L1-4 BMD z-scores, mean 33.7 +/- 15.0 months treatment, and 22,852.4 +/- 12,477.4 mg/kg cumulative dose) groups were significantly lower than that of the control group (-0.23 +/- 0.87 mean L1-4 BMD z-score). Serum ALP and PTH levels were significantly higher in the carbamazepine-treated group (65.4 +/- 21.1 pg/ml, 767 +/- 267 U/l, respectively) than those of the valproic acid-treated (39.1 +/- 12.8 pg/ml, 561 +/- 166 U/l, respectively) and control groups (36.3 +/- 4.9 pg/ml, 487 +/- 82 U/l, respectively). Serum 25-hydroxyvitamin D of the carbamazepine-treated group (9.8 +/- 3.2 microg/l) was significantly lower than the other groups (15.1 +/- 3.5, 16.6 +/- 4.7 microg/l, respectively). There were eight and 13 patients with plasma intact PTH above reference values in groups 1 and 2, respectively. Valproic acid and carbamazepine therapy results in a hyperparathyroid state and altered vitamin D metabolism, respectively. BMD values at lumbar spine were significantly reduced in both carbamezapine and valproic acid treated groups. Valproic acid and carbamazepine therapy do not change IGF-I and IGFBP-3 levels. Altering the hepatic conversion of vitamin D may be the mechanism of carbamazepine-associated reduction in BMD, but the mechanism of decreased BMD in valproate therapy remains unclear.

Effect of odanacatib on bone turnover markers, bone density and geometry of the spine and hip of ovariectomized monkeys: a head-to-head comparison with alendronate.

PubMed

Williams, Donald S; McCracken, Paul J; Purcell, Mona; Pickarski, Maureen; Mathers, Parker D; Savitz, Alan T; Szumiloski, John; Jayakar, Richa Y; Somayajula, Sangeetha; Krause, Stephen; Brown, Keenan; Winkelmann, Christopher T; Scott, Boyd B; Cook, Lynn; Motzel, Sherri L; Hargreaves, Richard; Evelhoch, Jeffrey L; Cabal, Antonio; Dardzinski, Bernard J; Hangartner, Thomas N; Duong, Le T

2013-10-01

Odanacatib (ODN) is a selective and reversible Cathepsin K (CatK) inhibitor currently being developed as a once weekly treatment for osteoporosis. Here, effects of ODN compared to alendronate (ALN) on bone turnover, DXA-based areal bone mineral density (aBMD), QCT-based volumetric BMD (vBMD) and geometric parameters were studied in ovariectomized (OVX) rhesus monkeys. Treatment was initiated 10 days after ovariectomy and continued for 20 months. The study consisted of four groups: L-ODN (2 mg/kg, daily p.o.), H-ODN (8/4 mg/kg daily p.o.), ALN (15 μg/kg, twice weekly, s.c.), and VEH (vehicle, daily, p.o.). L-ODN and ALN doses were selected to approximate the clinical exposures of the ODN 50-mg and ALN 70-mg once-weekly, respectively. L-ODN and ALN effectively reduced bone resorption markers uNTx and sCTx compared to VEH. There was no additional efficacy with these markers achieved with H-ODN. Conversely, ODN displayed inversely dose-dependent reduction of bone formation markers, sP1NP and sBSAP, and L-ODN reduced formation to a lesser degree than ALN. At month 18 post-OVX, L-ODN showed robust increases in lumbar spine aBMD (11.4%, p<0.001), spine trabecular vBMD (13.7%, p<0.001), femoral neck (FN) integral (int) vBMD (9.0%, p<0.001) and sub-trochanteric proximal femur (SubTrPF) int vBMD, (6.4%, p<0.001) compared to baseline. L-ODN significantly increased FN cortical thickness (Ct.Th) and cortical bone mineral content (Ct.BMC) by 22.5% (p<0.001) and 21.8% (p<0.001), respectively, and SubTrPF Ct.Th and Ct.BMC by 10.9% (p<0.001) and 11.3% (p<0.001) respectively. Compared to ALN, L-ODN significantly increased FN Ct. BMC by 8.7% (p<0.05), and SubTrPF Ct.Th by 7.6% (p<0.05) and Ct.BMC by 6.2% (p<0.05). H-ODN showed no additional efficacy compared to L-ODN in OVX-monkeys in prevention mode. Taken together, the results from this study have demonstrated that administration of ODN at levels which approximate clinical exposure in OVX-monkeys had comparable efficacy to ALN in DXA-based aBMD and QCT-based vBMD. However, FN cortical mineral content clearly demonstrated superior efficacy of ODN versus ALN in this model of estrogen-deficient non-human primates. © 2013 Elsevier Inc. All rights reserved.

Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Mulligan, Kathleen; Glidden, David V.; Anderson, Peter L.; Liu, Albert; McMahan, Vanessa; Gonzales, Pedro; Ramirez-Cardich, Maria Esther; Namwongprom, Sirianong; Chodacki, Piotr; de Mendonca, Laura Maria Carvalo; Wang, Furong; Lama, Javier R.; Chariyalertsak, Suwat; Guanira, Juan Vicente; Buchbinder, Susan; Bekker, Linda-Gail; Schechter, Mauro; Veloso, Valdilea G.; Grant, Robert M.; Vargas, Lorena; Sanchez, Jorge; Mai, Chiang; Saokhieo, Pongpun; Murphy, Kerry; Gilmore, Hailey; Holland, Sally; Faber, Elizabeth; Duda, John; Bewerunge, Linda; Batist, Elizabeth; Hoskin, Christine; Brown, Ben; de Janeiro, Rio; Beppu-Yoshida, Carina; da Costa, Marcellus Dias; Assis de Jesus, Sergio Carlos; Grangeiro da Silva, Jose Roberto; Millan, Roberta; de Siqueira Hoagland, Brenda Regina; Martinez Fernandes, Nilo; da Silva Freitas, Lucilene; Grinsztejn, Beatriz; Pilotto, Jose; Bushman, Lane; Zheng, Jia-Hua; Anthony Guida, Louis; Kline, Brandon; Goicochea, Pedro; Manzo, Jonathan; Hance, Robert; McConnell, Jeff; Defechereux, Patricia; Levy, Vivian; Robles, Malu; Postle, Brian; Burns, David; Rooney, James

2015-01-01

Background. Daily preexposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) decreases the risk of human immunodeficiency virus (HIV) acquisition. Initiation of TDF decreases bone mineral density (BMD) in HIV-infected people. We report the effect of FTC/TDF on BMD in HIV-seronegative men who have sex with men and in transgender women. Methods. Dual-energy X-ray absorptiometry was performed at baseline and 24-week intervals in a substudy of iPrEx, a randomized, double-blind, placebo-controlled trial of FTC/TDF PrEP. Plasma and intracellular tenofovir concentrations were measured in participants randomized to FTC/TDF. Results. In 498 participants (247 FTC/TDF, 251 placebo), BMD in those randomized to FTC/TDF decreased modestly but statistically significantly by 24 weeks in the spine (net difference, −0.91% [95% confidence interval {CI}, −1.44% to −.38%]; P = .001) and hip (−0.61% [95% CI, −.96% to −.27%], P = .001). Changes within each subsequent 24-week interval were not statistically significant. Changes in BMD by week 24 correlated inversely with intracellular tenofovir diphosphate (TFV-DP), which was detected in 53% of those randomized to FTC/TDF. Net BMD loss by week 24 in participants with TFV-DP levels indicative of consistent dosing averaged −1.42% ± 29% and −0.85% ± 19% in the spine and hip, respectively (P < .001 vs placebo). Spine BMD tended to rebound following discontinuation of FTC/TDF. There were no differences in fractures (P = .62) or incidence of low BMD. Conclusions. In HIV-uninfected persons, FTC/TDF PrEP was associated with small but statistically significant decreases in BMD by week 24 that inversely correlated with TFV-DP, with more stable BMD thereafter. Clinical Trials Registration. NCT00458393. PMID:25908682

The effect of locally delivered recombinant human bone morphogenetic protein-2 with hydroxyapatite/tri-calcium phosphate on the biomechanical properties of bone in diabetes-related osteoporosis.

PubMed

Liporace, Frank A; Breitbart, Eric A; Yoon, Richard S; Doyle, Erin; Paglia, David N; Lin, Sheldon

2015-06-01

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is particularly effective in improving osteogenesis in patients with diminished bone healing capabilities, such as individuals with type 1 diabetes mellitus (T1DM) who have impaired bone healing capabilities and increased risk of developing osteoporosis. This study measured the effects of rhBMP-2 treatment on osteogenesis by observing the dose-dependent effect of localized delivery of rhBMP-2 on biomechanical parameters of bone using a hydroxyapatite/tri-calcium phosphate (HA/TCP) carrier in a T1DM-related osteoporosis animal model. Two different doses of rhBMP-2 (LD low dose, HD high dose) with a HA/TCP carrier were injected into the femoral intramedullary canal of rats with T1DM-related osteoporosis. Two more diabetic rat groups were injected with saline alone and with HA/TCP carrier alone. Radiographs and micro-computed tomography were utilized for qualitative assessment of bone mineral density (BMD). Biomechanical testing occurred at 4- and 8-week time points; parameters tested included torque to failure, torsional rigidity, shear stress, and shear modulus. At the 4-week time point, the LD and HD groups both exhibited significantly higher BMD than controls; at the 8-week time point, the HD group exhibited significantly higher BMD than controls. Biomechanical testing revealed dose-dependent, higher trends in all parameters tested at the 4- and 8-week time points, with minimal significant differences. Groups treated with rhBMP-2 demonstrated improved bone mineral density at both 4 and 8 weeks compared to control saline groups, in addition to strong trends towards improvement of intrinsic and extrinsic biomechanical properties when compared to control groups. Data revealed trends toward dose-dependent increases in peak torque, torsional rigidity, shear stress, and shear modulus 4 weeks after rhBMP-2 treatment. Not applicable.

Vitamin K3 increased BMD at 1 and 2 months post-surgery and the maximum stress of the middle femur in the rat.

PubMed

Hong, You-jia; Liu, Sheng; Jiang, Ning-yi; Jiang, Sen; Liang, Jiu-gen

2015-02-01

The therapeutic effects of vitamin K3 (VK3) on osteoporosis are still unknown. In this study, we hypothesized that VK3 possesses therapeutic effects on osteoporosis; to verify this hypothesis, the ovariectomized rat was used as an osteoporosis model. Fifty-six Sprague-Dawley female rats aged 8 to 9 months were randomly assigned to 4 groups: sham surgery, ovariectomy with saline, ovariectomy with low-dose VK3, and ovariectomy with high-dose VK3. Intramuscular injection of VK3 was performed every other day beginning 1 month postoperatively. The therapeutic effects of VK3 on osteoporosis were evaluated by measurement of bone mineral density (BMD), bone biochemical markers, biomechanical properties, and bone morphometric parameters. The overall average BMD in VK3-treated groups increased to a level between those of the ovariectomy group and the sham surgery group. The procollagen I N-terminal peptide level peaked at 2 months after surgery in all groups except in the group that had undergone ovariectomy with low-dose VK3. The tartrate-resistant acid phosphatase 5b level increased more slowly at 4 months after surgery than at 2 months after surgery in the VK3-treated groups. The ovariectomy with high-dose VK3 group had the highest maximum stress of the middle femur of all groups. With VK3 treatment, the trabecular bone area percentage increased. All morphometric indicators for the middle tibia in the VK3-treated groups reached the levels found in the sham surgery group. In summary, VK3 therapy increased BMD at 1 and 2 months postsurgery and the maximum stress of the middle femur. In addition, VK3 therapy slowed the increase in bone turnover in ovariectomized rats. Furthermore, VK3 can improve morphometric indicators for the middle tibia. Our preliminary study indicates that VK3 has a potential therapeutic effect on osteoporosis and is worthy of further investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

Associations between vitamin D metabolites, antiretroviral therapy and bone mineral density in people with HIV.

PubMed

Klassen, K M; Kimlin, M G; Fairley, C K; Emery, S; Anderson, P H; Ebeling, P R

2016-05-01

To see if vitamin D and antiretroviral therapy are associated with bone mineral density (BMD) in people with HIV. Lower hip BMD was associated with tenofovir (an antiretroviral medicine) in those with 25(OH)D ≥50 nmol/L. The relationship between antiretroviral therapy and hip BMD differs depending on vitamin D status. People with HIV have an increased risk of low BMD and fractures. Antiretroviral therapy contributes to this increased risk. The aim of this study was to evaluate associations between vitamin D metabolites and antiretroviral therapy on BMD. The simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir-lamivudine trial (STEAL) was an open-label, prospective randomised non-inferiority study that compared simplification of current nucleoside reverse transcriptase inhibitors (NRTIs) to fixed-dose combination tenofovir-emtricitabine (TDF-FTC) or abacavir-lamivudine. Serum 25(OH)D and 1,25(OH)2D were measured in 160 individuals (90 receiving TDF-FTC, 70 receiving other NRTIs) at baseline from this study. Multivariable linear regression models were constructed to evaluate the covariates of 1,25(OH)2D and BMD. Protease inhibitor use (p = 0.02) and higher body mass index (BMI) (p = 0.002) were associated with lower 1,25(OH)2D levels in those with 25(OH)D <50 nmol/L. However, TDF-FTC use (p = 0.01) was associated with higher 1,25(OH)2D levels, but only in those with 25(OH)D ≥50 nmol/L. White ethnicity (p = 0.02) and lower BMI (p < 0.001) in those with 25(OH)D <50 nmol/L and with TDF-FTC use (p = 0.008) in those with 25(OH)D ≥50 nmol/L were associated with lower hip BMD. TDF-FTC use, higher serum calcium and serum βCTX, winter, and lower bone-specific alkaline phosphatase (BALP) and BMI were associated with lower lumbar spine BMD. TDF-FTC use (versus non-TDF-FTC use) was associated with lower hip BMD, and this difference was more pronounced in those with 25(OH)D ≥50 nmol/L. Serum 25(OH)D <50 nmol/L was associated with lower hip BMD in all participants. Therefore, the associations between antiretroviral therapy and hip BMD differ depending on vitamin D status.

Role of the standard deviation in the estimation of benchmark doses with continuous data.

PubMed

Gaylor, David W; Slikker, William

2004-12-01

For continuous data, risk is defined here as the proportion of animals with values above a large percentile, e.g., the 99th percentile or below the 1st percentile, for the distribution of values among control animals. It is known that reducing the standard deviation of measurements through improved experimental techniques will result in less stringent (higher) doses for the lower confidence limit on the benchmark dose that is estimated to produce a specified risk of animals with abnormal levels for a biological effect. Thus, a somewhat larger (less stringent) lower confidence limit is obtained that may be used as a point of departure for low-dose risk assessment. It is shown in this article that it is important for the benchmark dose to be based primarily on the standard deviation among animals, s(a), apart from the standard deviation of measurement errors, s(m), within animals. If the benchmark dose is incorrectly based on the overall standard deviation among average values for animals, which includes measurement error variation, the benchmark dose will be overestimated and the risk will be underestimated. The bias increases as s(m) increases relative to s(a). The bias is relatively small if s(m) is less than one-third of s(a), a condition achieved in most experimental designs.

Bone mineral density in patients with alopecia areata treated with long-term intralesional corticosteroids.

PubMed

Samrao, Aman; Fu, Jennifer M; Harris, Steven T; Price, Vera H

2013-02-01

Intralesional corticosteroid injections are a common treatment for patchy alopecia areata, the most prevalent subtype of this autoimmune hair disorder. To date, no studies have examined the potential adverse effects of this therapy on bone mineral density (BMD). In this retrospective, cross-sectional case series, 18 patients with patchy alopecia areata treated at 4- to 8-week intervals with intralesional triamcinolone acetonide for at least 20 months were evaluated for BMD using dual-energy x-ray absorptiometry (DXA). Follow-up DXA measurements were obtained in those with abnormal findings. Nine out of 18 patients (50%) had abnormal DXA results. Patients with the following risk factors were more likely to have abnormal BMD: age older than 50 years, body mass index less than 18.5 kg/m2, lack of weight-bearing exercise, smoking history, postmenopausal status, past stress fracture, family history of osteopenia or osteoporosis, and a cumulative intralesional triamcinolone acetonide dose of greater than 500 mg. Patients with patchy alopecia areata who receive chronic intralesional triamcinolone acetonide therapy should be counseled on preventive measures for osteoporosis and monitored for effects on BMD.

Performance of clinical referral criteria for bone densitometry in patients under 65 years of age assessed by spine bone mineral density

PubMed Central

Kayan, K; de Takats, D; Ashford, R; Kanis, J; McCloskey, E

2003-01-01

Background: A case finding strategy based on a number of established risk factors has been suggested by Royal College of Physicians' (RCP) guidelines to optimise bone densitometry referrals for assessment of osteoporosis. Objective: The performance of clinical referral criteria was examined in women and men aged <65 years referred for bone mineral density (BMD) assessment. Study design: Cross sectional observational study over six months. Results: Though BMD tended to be lower in patients with multiple criteria for referral, differences from those referred with a single criterion were not statistically significant. The overall prevalence of osteoporosis was higher than expected in both sexes, 11.6% in women and 27.5% in men (expected prevalences were 8% and <1% respectively). BMD was significantly lower in patients referred with a single criterion compatible with the RCP guidelines than in age matched controls or in those patients referred with non-RCP criteria (mean (SD) Z score –0.47(1.38) v 0.35(1.41), p<0.001). Low body mass index was also significantly associated with a lower than expected BMD. In contrast, spine BMD was higher than expected in those with self reported back pain, loss of height, or spinal curvature (p = NS). Conclusion: Most of the criteria recommended by the RCP performed well in identifying relatively younger patients with low BMD and osteoporosis. However, prior fractures and corticosteroid use did not reach statistical significance probably due to inclusion of all energy fractures, and current or past steroid use of unspecified dose or duration. Criteria like loss of height and/or spine curvature perform relatively poorly, reflecting the need for further investigation to better identify those needing BMD assessment. PMID:14612601

Do 6 months of whole-body vibration training improve lean mass and bone mass acquisition of adolescent swimmers?

PubMed

Gómez-Bruton, A; González-Agüero, A; Matute-Llorente, A; Julián, C; Lozano-Berges, G; Gómez-Cabello, A; Casajús, J A; Vicente-Rodríguez, G

2017-12-01

Swimming has little effect on bone mass. Therefore, adolescent swimmers should complement their water training with a short and intense weight-bearing training, aiming to increase their bone acquisition. Forty swimmers performed a six-month whole-body vibration (WBV) training. WBV had no effect on adolescent swimmers' bone mass or lean mass. The aims of the present study were to evaluate the effects of a whole-body vibration (WBV) intervention on bone mineral density (BMD), bone mineral content (BMC) and lean mass (LM) in adolescent swimmers. Forty male and female adolescent swimmers (VIB; mean age 14.2 ± 1.9 years) completed the WBV protocol that consisted of 15 min of training 3 days per week during a 6-month period (ranging from 3.6 to 11.6 g), while 23 swimmers (SWI; mean age 15.0 ± 2.2 years) continued with their regular swimming training alone. VIB were divided into tertiles according to training compliance in order to evaluate if any dose-effect relation existed. BMD, BMC and LM were measured longitudinally by dual energy X-ray at the whole body, lumbar-spine and hip. No group by time interactions and no differences in change percentage were found for BMD, BMC or LM in any of the measured variables. The mean change percentage of the subtotal body (whole body minus the head) for VIB and SWI, respectively, was 2.3 vs. 2.4% for BMD, 5.7 vs 5.7% for BMC and 7.3 vs. 8.0% for lean mass. Moreover, no indication for dose-response was observed. The proposed WBV protocol had no effect on BMD, BMC and LM in adolescent swimmers. Other types of training should be used in this population to improve both bone and lean mass.

Effects on vitamin D, bone and the kidney of switching from fixed-dose tenofovir disoproxil fumarate/emtricitabine/efavirenz to darunavir/ritonavir monotherapy: a randomized, controlled trial (MIDAS).

PubMed

Hamzah, Lisa; Tiraboschi, Juan M; Iveson, Helen; Toby, Martina; Mant, Christine; Cason, John; Burling, Keith; Wandolo, Emily; Jendrulek, Isabelle; Taylor, Chris; Ibrahim, Fowzia; Kulasegaram, Ranjababu; Teague, Alastair; Post, Frank A; Fox, Julie

2016-01-01

Efavirenz (EFV) has been associated with reductions in vitamin D (25[OH]D) and tenofovir (TDF) with increased bone turnover, reductions in bone mineral density (BMD) and renal tubular dysfunction. We hypothesized that switching from fixed-dose TDF/emtricitabine (FTC)/EFV to darunavir/ritonavir monotherapy (DRV/r) might increase 25(OH)D and BMD, and improve renal tubular function. Subjects with HIV RNA <50 copies/ml on TDF/FTC/EFV for ≥6 months were randomized 1:1 to ongoing TDF/FTC/EFV or DRV/r (800/100 mg once daily) for 48 weeks. The primary end point was change from baseline in 25(OH)D at week 48. Secondary end points included changes in BMD, bone turnover markers and renal tubular function. A total of 64 subjects (86% male, 66% white, mean [sd] CD4(+) T-cell count 537.3 [191.5]/mm(3)) were analysed. After adjustment for baseline 25(OH)D and demographics, at week 48 DRV/r monotherapy was associated with a +3.6 (95% CI 0.6, 6.6) ng/ml increase in 25(OH)D compared to TDF/FTC/EFV (P=0.02). DRV/r monotherapy was associated with an increase in BMD (+2.9% versus -0.003% at the neck of femur and +2.6% versus +0.008% at the lumbar spine for DRV/r versus TDF/FTC/EFV; P<0.05 for all) and reductions in bone biomarkers compared with those remaining on TDF/FTC/EFV. No significant difference in renal tubular function was observed. Reasons for discontinuation in the DRV/r arm included side effects (n=4) and viral load rebound (n=3), all of which resolved with DRV/r discontinuation or regimen intensification. Switching from TDF/FTC/EFV to DRV/r in patients with suppressed HIV RNA resulted in significant improvements in 25(OH)D and bone biomarkers, and a 2-3% increase in BMD.

Administration of growth hormone in selectively protein-deprived rats decreases BMD and bone strength.

PubMed

Ammann, Patrick; Brennan, Tara C; Mekraldi, Samia; Aubert, Michel L; Rizzoli, René

2010-06-01

Isocaloric protein undernutrition is associated with decreased bone mass and decreased bone strength, together with lower IGF-I levels. It remains unclear whether administration of growth hormone (GH) corrects these alterations in bone metabolism. Six-month-old female rats were fed isocaloric diets containing either 2.5% or 15% casein for 2 weeks. Bovine growth hormone (bGH, 0.5 or 2.5mg/kg of body weight) or vehicle was then administered as subcutaneous injections, twice daily, to rats on either diet for 4 weeks. At the proximal tibia, analysis of bone mineral density (BMD), maximal load and histomorphometry were performed. In addition, urinary deoxypyridinoline, plasma osteocalcin and IGF-I concentrations were measured. Weight was monitored weekly. bGH caused a dose-dependent increase in plasma IGF-I regardless of the dietary protein content. However, bGH dose-dependently decreased BMD and bone strength in rats fed the low-protein diet. There was no significant effect of bGH on BMD in rats fed the normal protein diet within this short-term treatment period, however bone formation as detected by histomorphometry was improved in this group but not the low-protein group. Osteoclast surface was increased in the low-protein bGH-treated animals only. Changes in bone turnover markers were detectable under both normal and low-protein diets. These results emphasize the major importance of dietary protein intake in the bone response to short-term GH administration, and highlight the need for further investigation into the effects of GH treatment in patients with reduced protein intake. Copyright 2010 Elsevier Inc. All rights reserved.

Fully automated bone mineral density assessment from low-dose chest CT

NASA Astrophysics Data System (ADS)

Liu, Shuang; Gonzalez, Jessica; Zulueta, Javier; de-Torres, Juan P.; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.

2018-02-01

A fully automated system is presented for bone mineral density (BMD) assessment from low-dose chest CT (LDCT). BMD assessment is central in the diagnosis and follow-up therapy monitoring of osteoporosis, which is characterized by low bone density and is estimated to affect 12.3 million US population aged 50 years or older, creating tremendous social and economic burdens. BMD assessment from DXA scans (BMDDXA) is currently the most widely used and gold standard technique for the diagnosis of osteoporosis and bone fracture risk estimation. With the recent large-scale implementation of annual lung cancer screening using LDCT, great potential emerges for the concurrent opportunistic osteoporosis screening. In the presented BMDCT assessment system, each vertebral body is first segmented and labeled with its anatomical name. Various 3D region of interest (ROI) inside the vertebral body are then explored for BMDCT measurements at different vertebral levels. The system was validated using 76 pairs of DXA and LDCT scans of the same subject. Average BMDDXA of L1-L4 was used as the reference standard. Statistically significant (p-value < 0.001) strong correlation is obtained between BMDDXA and BMDCT at all vertebral levels (T1 - L2). A Pearson correlation of 0.857 was achieved between BMDDXA and average BMDCT of T9-T11 by using a 3D ROI taking into account of both trabecular and cortical bone tissue. These encouraging results demonstrate the feasibility of fully automated quantitative BMD assessment and the potential of opportunistic osteoporosis screening with concurrent lung cancer screening using LDCT.

Modeling corticosteroid effects in a rat model of rheumatoid arthritis II: mechanistic pharmacodynamic model for dexamethasone effects in Lewis rats with collagen-induced arthritis.

PubMed

Earp, Justin C; Dubois, Debra C; Molano, Diana S; Pyszczynski, Nancy A; Almon, Richard R; Jusko, William J

2008-08-01

A mechanism-based model for pharmacodynamic effects of dexamethasone (DEX) was incorporated into our model for arthritis disease progression in the rat to aid in identification of the primary factors responsible for edema and bone loss. Collagen-induced arthritis was produced in male Lewis rats after injection of type II porcine collagen. DEX was given subcutaneously in single doses of 0.225 or 2.25 mg/kg or 7-day multiple doses of 0.045 or 0.225 mg/kg at 21 days postdisease induction. Effects on disease progression were measured by paw swelling, bone mineral density (BMD), body weights, plasma corticosterone (CST), and tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and glucocorticoid receptor (GR) mRNA expression in paw tissue. Lumbar and femur BMD was determined by PIXImus II dual-energy X-ray absorptiometry. Plasma CST was assayed by high-performance liquid chromatography. Cytokine and GR mRNA were assayed by quantitative real-time polymerase chain reaction. Indirect response models, drug interaction models, transduction processes, and the fifth-generation model of corticosteroid dynamics were integrated and applied using S-ADAPT software to describe how dexamethasone binding to GR can regulate diverse processes. Cytokine mRNA, GR mRNA, plasma CST, and paw edema were suppressed after DEX administration. TNF-alpha mRNA expression and BMD seemed to increase immediately after dosing but were ultimately reduced. Model parameters indicated that IL-6 and IL-1beta were most sensitive to inhibition by DEX. TNF-alpha seemed to primarily influence edema, whereas IL-6 contributed the most to bone loss. Lower doses of corticosteroids may be sufficient to suppress the cytokines most relevant to bone erosion.

[Long-term effects of 7-year growth hormone substitution on bone metabolism, bone density, and bone quality in growth hormone-deficient adults].

PubMed

Wilhelm, Birgit; Kann, Peter Herbert

2004-10-15

Subnormal bone mineral density (BMD) and increased fracture risk are described in patients with growth hormone deficiency (GHD). Growth hormone (GH) has been reported to have beneficial effects on bone in GHD. The aim of this study was to investigate the long-term effects of GH replacement therapy on bone metabolism, BMD, and bone quality in patients with GHD. 20 adult patients with GHD (eleven male, nine female, mean age 42.5 years) were included in the study and randomized to either GH or placebo in a dose of 0.25 U/kg body weight/week. After 6 months all patients received GH. After a 1-year double-blind, placebo-controlled study the patients were followed for another 72 months in an open study. The patients were compared to 20 age- und sex-matched healthy controls. Bone turnover was determined by ICTP (type I collagen carboxyterminal cross-linked telopeptide) as parameter of bone resorption and PICP (carboxyterminal propeptide of type I procollagen) as marker of bone formation. BMD was measured at the lumbar spine by dual-photon absorptiometry (DPA) and at the forearm by single-photon absorptiometry (SPA). Apparent phalangeal ultrasound transmission velocity (APU) was assessed as parameter of bone quality independent of BMD. At the beginning of the study BMD at both measuring sites was lower in patients with GHD than in healthy controls. During the 1st year of GH replacement therapy BMD decreased, followed by a continuous increase in BMD (about 12%) up to 60 months which remained unchanged thereafter, building up a plateau. After 72 months no significant difference between the patients and the healthy controls could be detected. Concerning parameters of bone turnover, first ICTP as marker of bone resorption showed a significant increase, later on the marker of bone formation increased as well. APU decreased during the first 6 months of treatment, but had returned to its baseline value after 24 months and remained unchanged throughout the rest of the study. BMD is subnormal in adults with GHD. GH replacement therapy stimulates bone turnover in patients with GHD and in the long term such stimulation results in an increased BMD. Thereby, GH shows a triphasic action on BMD: an initial decrease in BMD during the 1st year, followed by a continuous increase in BMD with buildup of a stable plateau after 60 months. The newly formed bone seems to have normal bone elasticity.

RESULTS OF QA/QC TESTING OF EPA BENCHMARK DOSE SOFTWARE VERSION 1.2

EPA Science Inventory

EPA is developing benchmark dose software (BMDS) to support cancer and non-cancer dose-response assessments. Following the recent public review of BMDS version 1.1b, EPA developed a Hill model for evaluating continuous data, and improved the user interface and Multistage, Polyno...

Quality Assurance Testing of Version 1.3 of U.S. EPA Benchmark Dose Software (Presentation)

EPA Science Inventory

EPA benchmark dose software (BMDS) issued to evaluate chemical dose-response data in support of Agency risk assessments, and must therefore be dependable. Quality assurance testing methods developed for BMDS were designed to assess model dependability with respect to curve-fitt...

Screening-Level Risk Assessment for Styrene-Acrylonitrile (SAN) Trimer Detected in Soil and Groundwater

PubMed Central

Kirman, C. R.; Gargas, M. L.; Collins, J. J.; Rowlands, J. C.

2012-01-01

A screening-level risk assessment was conducted for styrene-acrylonitrile (SAN) Trimer detected at the Reich Farm Superfund site in Toms River, NJ. Consistent with a screening-level approach, on-site and off-site exposure scenarios were evaluated using assumptions that are expected to overestimate actual exposures and hazards at the site. Environmental sampling data collected for soil and groundwater were used to estimate exposure point concentrations. Several exposure scenarios were evaluated to assess potential on-site and off-site exposures, using parameter values for exposures to soil (oral, inhalation of particulates, and dermal contact) and groundwater (oral, dermal contact) to reflect central tendency exposure (CTE) and reasonable maximum exposure (RME) conditions. Three reference dose (RfD) values were derived for SAN Trimer for short-term, subchronic, and chronic exposures, based upon its effects on the liver in exposed rats. Benchmark (BMD) methods were used to assess the relationship between exposure and response, and to characterize appropriate points of departure (POD) for each RfD. An uncertainty factor of 300 was applied to each POD to yield RfD values of 0.1, 0.04, and 0.03 mg/kg-d for short-term, subchronic, and chronic exposures, respectively. Because a chronic cancer bioassay for SAN Trimer in rats (NTP 2011a) does not provide evidence of carcinogenicity, a cancer risk assessment is not appropriate for this chemical. Potential health hazards to human health were assessed using a hazard index (HI) approach, which considers the ratio of exposure dose (i.e., average daily dose, mg/kg-d) to toxicity dose (RfD, mg/kg-d) for each scenario. All CTE and RME HI values are well below 1 (where the average daily dose is equivalent to the RfD), indicating that there is no concern for potential noncancer effects in exposed populations even under the conservative assumptions of this screening-level assessment. PMID:23030654

Choline-stabilized orthosilicic acid supplementation as an adjunct to Calcium/Vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial

PubMed Central

Spector, Tim D; Calomme, Mario R; Anderson, Simon H; Clement, Gail; Bevan, Liisa; Demeester, Nathalie; Swaminathan, Rami; Jugdaohsingh, Ravin; Berghe, Dirk A Vanden; Powell, Jonathan J

2008-01-01

Background Mounting evidence supports a physiological role for silicon (Si) as orthosilicic acid (OSA, Si(OH)4) in bone formation. The effect of oral choline-stabilized orthosilicic acid (ch-OSA) on markers of bone turnover and bone mineral density (BMD) was investigated in a double-blind placebo-controlled trial. Methods Over 12-months, 136 women out of 184 randomized (T-score spine < -1.5) completed the study and received, daily, 1000 mg Ca and 20 μg cholecalciferol (Vit D3) and three different ch-OSA doses (3, 6 and 12 mg Si) or placebo. Bone formation markers in serum and urinary resorption markers were measured at baseline, and after 6 and 12 months. Femoral and lumbar BMD were measured at baseline and after 12 months by DEXA. Results Overall, there was a trend for ch-OSA to confer some additional benefit to Ca and Vit D3 treatment, especially for markers of bone formation, but only the marker for type I collagen formation (PINP) was significant at 12 months for the 6 and 12 mg Si dose (vs. placebo) without a clear dose response effect. A trend for a dose-corresponding increase was observed in the bone resorption marker, collagen type I C-terminal telopeptide (CTX-I). Lumbar spine BMD did not change significantly. Post-hoc subgroup analysis (baseline T-score femur < -1) however was significant for the 6 mg dose at the femoral neck (T-test). There were no ch-OSA related adverse events observed and biochemical safety parameters remained within the normal range. Conclusion Combined therapy of ch-OSA and Ca/Vit D3 had a potential beneficial effect on bone collagen compared to Ca/Vit D3 alone which suggests that this treatment is of potential use in osteoporosis. NTR 1029 PMID:18547426

Strontium ranelate for preventing and treating postmenopausal osteoporosis.

PubMed

O'Donnell, S; Cranney, A; Wells, G A; Adachi, J D; Reginster, J Y

2006-10-18

Strontium ranelate is a new treatment for osteoporosis therefore, its benefits and harms need to be known. To determine the efficacy and safety of strontium ranelate for the treatment and prevention of postmenopausal osteoporosis. We searched MEDLINE (1996 to March 2005), EMBASE (1996 to week 9 2005), the Cochrane Library (1996 to Issue 1 2005), reference lists of relevant articles and conference proceedings from the last two years. Additional data was sought from authors. We included randomized controlled trials (RCTs) of at least one year duration comparing strontium ranelate versus placebo reporting fracture incidence, bone mineral density (BMD), health related quality of life or safety in postmenopausal women. Treatment (versus prevention) population was defined as women with prevalent vertebral fractures and/or lumbar spine BMD T score < -2.5 SD. Two reviewers independently determined study eligibility, assessed trial quality and extracted the relevant data. Disagreements were resolved by consensus. RCTs were grouped by dose of strontium ranelate and treatment duration. Where possible, meta-analysis was conducted using the random effects model. Four trials met the inclusion criteria. Three included a treatment population (0.5 to 2 g of strontium ranelate daily) and one a prevention population (0.125 g, 0.5 g and 1 g daily). A 37% reduction in vertebral fractures (RR 0.63, 95% CI 0.56, 0.71) and a 14% reduction in non-vertebral fractures (RR 0.86, 95% CI 0.75, 0.98) were demonstrated over three years with 2 g of strontium ranelate daily in a treatment population. An increase in BMD was shown at all BMD sites after two to three years in both populations. Lower doses of strontium ranelate were superior to placebo and the highest dose demonstrated the greatest reduction in vertebral fractures and increase in BMD. An increased risk of diarrhea with 2 g of strontium ranelate was found; however, adverse events did not affect the risk of discontinuing treatment nor did it increase the risk of serious side effects, gastritis or death. Additional data suggests that the risk of vascular and nervous system side-effects is slightly increased with taking 2 g of strontium ranelate daily over three to four years. There is silver level evidence (www.cochranemsk.org) to support the efficacy of strontium ranelate for the reduction of fractures (vertebral and to a lesser extent non-vertebral) in postmenopausal osteoporotic women and an increase in BMD in postmenopausal women with/without osteoporosis. Diarrhea may occur however, adverse events leading to study withdrawal were not significantly increased with taking 2 g of strontium ranelate daily. Potential vascular and neurological side-effects need to be further explored.

A single injection of the anabolic bone agent, parathyroid hormone-collagen binding domain (PTH-CBD), results in sustained increases in bone mineral density for up to 12 months in normal female mice.

PubMed

Ponnapakkam, Tulasi; Katikaneni, Ranjitha; Suda, Hirofumi; Miyata, Shigeru; Matsushita, Osamu; Sakon, Joshua; Gensure, Robert C

2012-09-01

Parathyroid hormone (PTH) is the most effective osteoporosis treatment, but it is only effective if administered by daily injections. We fused PTH(1-33) to a collagen binding domain (PTH-CBD) to extend its activity, and have shown an anabolic bone effect with monthly dosing. We tested the duration of action of this compound with different routes of administration. Normal young C57BL/6J mice received a single intraperitoneal injection of PTH-CBD (320 μg/kg). PTH-CBD treated mice showed a 22.2 % increase in bone mineral density (BMD) at 6 months and 12.8 % increase at 12 months. When administered by subcutaneous injection, PTH-CBD again caused increases in BMD, 15.2 % at 6 months and 14.3 % at 12 months. Radiolabeled PTH-CBD was concentrated in bone and skin after either route of administration. We further investigated skin effects of PTH-CBD, and histological analysis revealed an apparent increase in anagen VI hair follicles. A single dose of PTH-CBD caused sustained increases in BMD by >10 % for 1 year in normal mice, regardless of the route of administration, thus showing promise as a potential osteoporosis therapy.

Comparison of the effects of three oral bisphosphonate therapies on the peripheral skeleton in postmenopausal osteoporosis: the TRIO study.

PubMed

Paggiosi, M A; Peel, N; McCloskey, E; Walsh, J S; Eastell, R

2014-12-01

We compared the effects of oral alendronate, ibandronate and risedronate on the central and peripheral skeleton over 2 years. We report differences in effect on the central skeleton but not on the peripheral skeleton. Greater effects were observed for ibandronate (and alendronate) than risedronate at the spine but not the hip. Generally, comparative clinical trials of bisphosphonates have examined changes in bone within central skeletal regions. We have examined the effects of bisphosphonate treatment on the peripheral skeleton. We conducted a 2-year, open-label, parallel randomised control trial of three orally administered bisphosphonates, at their licensed dose, to examine and compare their effects on the peripheral skeleton using multiple modes of measurement. We studied 172 postmenopausal women (53-84 years) who had either a bone mineral density (BMD) T-score of  ≤ -2.5 at the spine and/or total hip or  < -1.0 at either site plus a previous low trauma fracture. Participants were randomised to receive either (i) ibandronate 150 mg/month, (ii) alendronate 70 mg/week or (iii) risedronate 35 mg/week, plus calcium (1,200 mg/day) and vitamin D (800 IU/day), for 2 years. Premenopausal women (33-40 years, n = 226) were studied to monitor device stability. We measured central BMD of the lumbar spine, total hip, total body and forearm using dual-energy X-ray absorptiometry. We measured calcaneus BMD (using dual-energy X-ray absorptiometry plus laser), radius and tibia BMD (using peripheral quantitative computed tomography), finger BMD (using radiographic absorptiometry), and phalangeal and calcaneal ultrasound variables (using quantitative ultrasound). Mixed effects regression models were used to evaluate effects of time and treatment allocation on BMD change. By 2 years, there were significant increases (p < 0.05) in central BMD sites (lumbar spine, total hip). In the peripheral skeleton, only significant changes in calcaneus BMD, 33 % total radius BMD and quantitative ultrasound (QUS)-2 broadband ultrasound attenuation (BUA) were evident for women receiving oral bisphosphonates. The increases in lumbar spine and total body BMD were greater with ibandronate and alendronate than with risedronate. Treatment effects on peripheral measurements did not differ between the three bisphosphonates.

Effects of flaxseed lignan and oil on bone health of breast-tumor-bearing mice treated with or without tamoxifen.

PubMed

Chen, Jianmin; Saggar, Jasdeep K; Ward, Wendy E; Thompson, Lilian U

2011-01-01

Previous studies showed that flaxseed lignan (secoisolariciresinol diglucoside, SDG) and oil (FO) inhibit established breast tumor growth in athymic mice with or without tamoxifen (TAM) treatment. TAM was found to increase bone mineral content (BMC) and density (BMD) in breast cancer patients. It is not known whether SDG or FO alone or combined with TAM affects bone health. Hence, the effects of SDG and FO, alone or in combination, on BMC, BMD, and biomechanical bone strength in ovariectomized athymic mice with established human breast tumors (MCF-7) treated with or without TAM were studied. In a factorial design, mice were divided into four non-TAM and four TAM groups. Each group consisted of mice fed a basal diet (BD), SDG (1 g/kg), FO (38.5 g/kg) or SDG + FO (combination) diets. The TAM group had TAM implants that provide a 5-mg TAM dose released over 60 d. TAM exerted an overall significant effect in increasing BMC, BMD, and biomechanical strength in femurs and lumbar vertebra. Without TAM treatment, SDG produced significant lower femur BMD (6%) while FO produced lower vertebrae BMC (8%) and BMD (6%). With TAM treatment, SDG and FO did not exert an effect on BMC and BMD at the femur or vertebra. SDG and FO produced no marked effect on biomechanical bone strength with or without TAM treatment. In conclusion, FS components did not significantly attenuate the positive effects on bone induced by TAM in this model system, indicating no apparent adverse effects on bone health.

Exercise Frequency and Fracture Risk in Older Adults-How Often Is Enough?

PubMed

Kemmler, Wolfgang; von Stengel, Simon; Kohl, Matthias

2017-12-01

Due to older people's low sports participation rates, exercise frequency may be the most critical component for designing exercise protocols that address fracture risk. The aims of the present article were to review and summarize the independent effect of exercise frequency (ExFreq) on the main determinants of fracture prevention, i.e., bone strength, fall frequency, and fall impact in older adults. Evidence collected last year suggests that there is a critical dose of ExFreq that just affects bone (i.e., BMD). Corresponding data for fall-related fracture risk are still sparse and inconsistent, however. The minimum effective dose (MED) of ExFreq that just favorably affects BMD at the lumbar spine and femoral neck has been found to vary between 2.1 and 2.5 sessions/week. Although this MED cannot necessarily be generalized to other cohorts, we speculate that this "critical exercise frequency" might not significantly vary among adult cohorts.

Determination of a site-specific reference dose for methylmercury for fish-eating populations.

PubMed

Shipp, A M; Gentry, P R; Lawrence, G; Van Landingham, C; Covington, T; Clewell, H J; Gribben, K; Crump, K

2000-11-01

Environmental risk-management decisions in the U.S. involving potential exposures to methylmercury currently use a reference dose (RfD) developed by the U.S. Environmental Protection Agency (USEPA). This RfD is based on retrospective studies of an acute poisoning incident in Iraq in which grain contaminated with a methylmercury fungicide was inadvertently used in the baking of bread. The exposures, which were relatively high but lasted only a few months, were associated with neurological effects in both adults (primarily paresthesia) and infants (late walking, late talking, etc.). It is generally believed that the developing fetus represents a particularly sensitive subpopulation for the neurological effects of methylmercury. The USEPA derived an RfD of 0.1 microg/kg/day based on benchmark dose (BMD) modeling of the combined neurological endpoints reported for children exposed in utero. This RfD included an uncertainty factor of 10 to consider human pharmacokinetic variability and database limitations (lack of data on multigeneration effects or possible long-term sequelae of perinatal exposure). Alcoa signed an Administrative Order of Consent for the conduct of a remedial investigation/feasibility study (RI/FS) at their Point Comfort Operations and the adjacent Lavaca Bay in Texas to address the effects of historical discharges of mercury-containing wastewater. In cooperation with the Texas Natural Resource Conservation Commission and USEPA Region VI, Alcoa conducted a baseline risk assessment to assess potential risk to human health and the environment. As a part of this assessment. Alcoa pursued the development of a site-specific RfD for methylmercury to specifically address the potential human health effects associated with the ingestion of contaminated finfish and shellfish from Lavaca Bay. Application of the published USEPA RfD to this site is problematic; while the study underlying the RfD represented acute exposure to relatively high concentrations of methylmercury, the exposures of concern for the Point Comfort site are from the chronic consumption of relatively low concentrations of methylmercury in fish. Since the publication of the USEPA RfD, several analyses of chronic exposure to methylmercury in fish-eating populations have been reported. The purpose of the analysis reported here was to evaluate the possibility of deriving an RfD for methylmercury, specifically for the case of fish ingestion, on the basis of these new studies. In order to better support the risk-management decisions associated with developing a remediation approach for the site in question, the analysis was designed to provide information on the distribution of acceptable ingestion rates across a population, which could reasonably be expected to be consistent with the results of the epidemiological studies of other fish-eating populations. Based on a review of the available literature on the effects of methylmercury, a study conducted with a population in the Seychelles Islands was selected as the critical study for this analysis. The exposures to methylmercury in this population result from chronic, multigenerational ingestion of contaminated fish. This prospective study was carefully conducted and analyzed, included a large cohort of mother-infant pairs, and was relatively free of confounding factors. The results of this study are essentially negative, and a no-observed-adverse-effect level (NOAEL) derived from the estimated exposures has recently been used by the Agency for Toxic Substances and Disease Registry (ATSDR) as the basis for a chronic oral minimal risk level (MRL) for methylmercury. In spite of the fact that no statistically significant effects were observed in this study, the data as reported are suitable for dose-response analysis using the BMD method. Evaluation of the BMD method used in this analysis, as well as in the current USEPA RfD, has demonstrated that the resulting 95% lower bound on the 10% benchmark dose (BMDL) represents a conservative estimate of the traditional NOAEL, and that it is superior to the use of "average" or "grouped" exposure estimates when dose-response information is available, as is the case for the Seychelles study. A more recent study in the Faroe Islands, which did report statistically significant associations between methylmercury exposure and neurological effects, could not be used for dose-response modeling due to inadequate reporting of the data and confounding from co-exposure to polychlorinated biphenyls (PCBs). BMD modeling over the wide range of neurological endpoints reported in the Seychelles study yielded a lowest BMDL for methylmercury in maternal hair of 21 ppm. This BMDL was then converted to an expected distribution of daily ingestion rates across a population using Monte Carlo analysis with a physiologically based pharmacokinetic (PBPK) model to evaluate the impact of interindividual variability. The resulting distribution of ingestion rates at the BMDL had a geometric mean of 1.60 microg/kg/day with a geometric standard deviation of 1.33; the 1st, 5th, and 10th percentiles of the distribution were 0.86, 1.04, and 1.15 microg/kg/day. In place of the use of an uncertainty factor of 3 for pharmacokinetic variability, as is done in the current RfD, one of these lower percentiles of the daily ingestion rate distribution provides a scientifically based, conservative basis for taking into consideration the impact of pharmacokinetic variability across the population. On the other hand, it was felt that an uncertainty factor of 3 for database limitations should be used in the current analysis. Although there can be high confidence in the benchmark-estimated NOAEL of 21 ppm in the Seychelles study, some results in the New Zealand and Faroe Islands studies could be construed to suggest the possibility of effects at maternal hair concentrations below 10 ppm. In addition, while concerns regarding the possibility of chronic sequelae are not supported by the available data, neither can they be absolutely ruled out. The use of an uncertainty factor of 3 is equivalent to using a NOAEL of 7 ppm in maternal hair, which provides additional protection against the possibility that effects could occur at lower concentrations in some populations. Based on the analysis described above, the distribution of acceptable daily ingestion rates (RfDs) recommended to serve as the basis for site-specific risk-management decisions at Alcoa's Point Comfort Operations ranges from approximately 0.3 to 1.1 microg/kg/day, with a population median (50th percentile) of 0.5 microg/kg/day. By analogy with USEPA guidelines for the use of percentiles in applications of distributions in exposure assessments, the 10th percentile provides a reasonably conservative measure. On this basis, a site-specific RfD of 0.4 microg/kg/day is recommended.

Evaluation of Insulin-Like Growth Factor Acid-Labile Subunit as a Potential Biomarker of Effect for Deoxynivalenol-Induced Proinflammatory Cytokine Expression

PubMed Central

Flannery, Brenna M.; Amuzie, Chidozie J.; Pestka, James J.

2013-01-01

Consumption of the trichothecene deoxynivalenol (DON) suppresses growth in experimental animals - an adverse effect that was used to establish the tolerable daily intake for this toxin. DON ingestion has been recently found to suppress plasma insulin-like growth factor acid-labile subunit (IGFALS), a protein essential for growth. Studies were conducted to explore the feasibility of using plasma IGFALS as a biomarker of effect for DON. In the first study, weanling mice were fed 0, 1, 2.5, 5 and 10 ppm DON and weight and plasma IGFALS determined at intervals over 9 wk. Reduced body weight gains were detectable beginning at wk 5 in the 10 ppm dose and wk 7 at the 5 ppm dose. Plasma IGFALS was significantly depressed at wk 5 in the 5 and 10 ppm groups at wk 9 in the 10 ppm group. Depressed IGFALS significantly correlated with reduced body weight at wk 5 and 9. Benchmark dose modeling revealed the BMDL and BMD for plasma IGFALS reduction were 1.1 and 3.0 ppm DON and for weight reduction were 2.1 and 4.5 ppm DON. In the second study, it was demonstrated that mice fed 15 ppm DON diet had significantly less plasma IGFALS than mice fed identical amounts of control diet. Thus DON’s influence on IGFALS likely reflects the combined effects of reduced food intake as well as its physiological action involving suppressors of cytokine signaling. Taken together, these findings suggest that plasma IGFALS might be a useful biomarker for DON’s adverse effects on growth. PMID:23298694

Dose-dependent transitions in Nrf2-mediated adaptive response and related stress responses to hypochlorous acid in mouse macrophages

PubMed Central

Woods, Courtney G.; Fu, Jingqi; Xue, Peng; Hou, Yongyong; Pluta, Linda J.; Yang, Longlong; Zhang, Qiang; Thomas, Russell S.; Andersen, Melvin E.; Pi, Jingbo

2009-01-01

Hypochlorous acid (HOCl) is potentially an important source of cellular oxidative stress. Human HOCl exposure can occur from chlorine gas inhalation or from endogenous sources of HOCl, such as respiratory burst by phagocytes. Transcription factor Nrf2 is a key regulator of cellular redox status and serves as a primary source of defense against oxidative stress. We recently demonstrated that HOCl activates Nrf2-mediated antioxidant response in cultured mouse macrophages in a biphasic manner. In an effort to determine whether Nrf2 pathways overlap with other stress pathways, gene expression profiling was performed in RAW 264.7 macrophages exposed to HOCl using whole genome mouse microarrays. Benchmark dose (BMD) analysis on gene expression data revealed that Nrf2-mediated antioxidant response and protein ubiquitination were the most sensitive biological pathways that were activated in response to low concentrations of HOCl (< 0.35 mM). Genes involved in chromatin architecture maintenance and DNA-dependent transcription were also sensitive to very low doses. Moderate concentrations of HOCl (0.35 to 1.4 mM) caused maximal activation of the Nrf2-pathway and innate immune response genes, such as IL-1β, IL-6, IL-10 and chemokines. At even higher concentrations of HOCl (2.8 to 3.5 mM) there was a loss of Nrf2-target gene expression with increased expression of numerous heat shock and histone cluster genes, AP-1-family genes, cFos and Fra1 and DNA damage-inducible Gadd45 genes. These findings confirm an Nrf2-centric mechanism of action of HOCl in mouse macrophages and provide evidence of interactions between Nrf2, inflammatory, and other stress pathways. PMID:19376150

Cross-sex testosterone therapy in ovariectomized mice: addition of low-dose estrogen preserves bone architecture.

PubMed

Goetz, Laura G; Mamillapalli, Ramanaiah; Devlin, Maureen J; Robbins, Amy E; Majidi-Zolbin, Masoumeh; Taylor, Hugh S

2017-11-01

Cross-sex hormone therapy (XHT) is widely used by transgender people to alter secondary sex characteristics to match their desired gender presentation. Here, we investigate the long-term effects of XHT on bone health using a murine model. Female mice underwent ovariectomy at either 6 or 10 wk and began weekly testosterone or vehicle injections. Dual-energy X-ray absorptiometry (DXA) was performed (20 wk) to measure bone mineral density (BMD), and microcomputed tomography was performed to compare femoral cortical and trabecular bone architecture. The 6-wk testosterone group had comparable BMD with controls by DXA but reduced bone volume fraction, trabecular number, and cortical area fraction and increased trabecular separation by microcomputed tomography. Ten-week ovariectomy/XHT maintained microarchitecture, suggesting that estrogen is critical for bone acquisition during adolescence and that late, but not early, estrogen loss can be sufficiently replaced by testosterone alone. Given these findings, we then compared effects of testosterone with effects of weekly estrogen or combined testosterone/low-dose estrogen treatment after a 6-wk ovariectomy. Estrogen treatment increased spine BMD and microarchitecture, including bone volume fraction, trabecular number, trabecular thickness, and connectivity density, and decreased trabecular separation. Combined testosterone-estrogen therapy caused similar increases in femur and spine BMD and improved architecture (increased bone volume fraction, trabecular number, trabecular thickness, and connectivity density) to estrogen therapy and were superior compared with mice treated with testosterone only. These results demonstrate estradiol is critical for bone acquisition and suggest a new cross-sex hormone therapy adding estrogens to testosterone treatments with potential future clinical implications for treating transgender youth or men with estrogen deficiency. Copyright © 2017 the American Physiological Society.

Significant and continuous improvement in bone mineral density among type 1 Gaucher disease patients treated with velaglucerase alfa: 69-month experience, including dose reduction.

PubMed

Elstein, Deborah; Foldes, A Joseph; Zahrieh, David; Cohn, Gabriel M; Djordjevic, Maja; Brutaru, Costin; Zimran, Ari

2011-06-15

Since bone pathology is a major concern in type 1 Gaucher disease (GD1), we evaluated bone mineral density (BMD) in adults receiving velaglucerase alfa in the seminal Phase I/II and extension trial. Ten treatment-naïve symptomatic patients with GD1 (four men, six women; median age 35years, range 18-62years) were included; of these, four patients were receiving bisphosphonates at enrollment. Using WHO criteria to classify the lumbar spine (LS) and femoral neck (FN) BMD T-scores, respectively, one (10%) and four (40%) patients had osteoporosis; eight (80%) and five (50%) had osteopenia; and one each (10%) was in the normal range, at baseline. By Month 69, two LS and one FN osteopenic patients normalized and one FN osteoporotic patient became osteopenic; change was seen only in patients not receiving bisphosphonates. Significant improvements in BMD Z-scores were seen at the LS by Month 24 and at the FN by Month 33 and were continuous thereafter. In linear mixed models, Z-scores were significantly lower than the reference population at baseline and improved significantly with treatment (LS and FN both P<0.01); analysis of the subgroup of patients not receiving bisphosphonates showed similar results. In conclusion, in this small cohort, velaglucerase alfa was associated with clinically meaningful and statistically significant LS and FN BMD improvements as early as Month 24 (LS) and 33 (FN), despite dose reduction and significant baseline skeletal pathology. These results suggest that velaglucerase alfa may hold promise in the management of skeletal pathology associated with GD1. Copyright © 2011 Elsevier Inc. All rights reserved.

Gradually increasing ethinyl estradiol for Turner syndrome may produce good final height but not ideal BMD.

PubMed

Hasegawa, Yukihiro; Ariyasu, Daisuke; Izawa, Masako; Igaki-Miyamoto, Junko; Fukuma, Mami; Hatano, Megumi; Yagi, Hiroko; Goto, Masahiro

2017-02-27

Estrogen replacement therapy in Turner syndrome should theoretically mimic the physiology of healthy girls. The objective of this study was to describe final height and bone mineral density (BMD) in a group of 17 Turner syndrome patients (group E) who started their ethinyl estradiol therapy with an ultra-low dosage (1-5 ng/kg/day) from 9.8-13.7 years. The subjects in group E had been treated with GH 0.35 mg/kg/week since the average age of 7.4 years. The 30 subjects in group L, one of the historical groups, were given comparable doses of GH, and conjugated estrogen 0.3125 mg/week ∼0.3125 mg/day was initiated at 12.2-18.7 years. The subjects in group S, the other historical group, were 21 patients who experienced breast development and menarche spontaneously. Final height (height gain < 2 cm/year) in group E was 152.4 ± 3.4 cm and the standard deviation (SD) was 2.02 ± 0.62 for Turner syndrome. The final height in group L was 148.5 ± 3.0 cm with a SD of 1.30 ± 0.55, which was significantly different from the values for group E. The volumetric BMD of group S (0.290 ± 0.026 g/cm 3 ) was significantly different from that of group L or E (0.262 or 0.262 g/cm 3 as a mean, respectively). This is the first study of patients with Turner syndrome where estrogen was administered initially in an ultra-low dose and then increased gradually. Our estrogen therapy in group E produced good final height but not ideal BMD.

Transient Increased Calcium and Calcitriol Requirements After Discontinuation of Human Synthetic Parathyroid Hormone 1-34 (hPTH 1-34) Replacement Therapy in Hypoparathyroidism.

PubMed

Gafni, Rachel I; Guthrie, Lori C; Kelly, Marilyn H; Brillante, Beth A; Christie, C Michele; Reynolds, James C; Yovetich, Nancy A; James, Robert; Collins, Michael T

2015-11-01

Synthetic human PTH 1-34 (hPTH 1-34) replacement therapy in hypoparathyroidism maintains eucalcemia and converts quiescent bone to high-turnover bone. However, the skeletal and metabolic effects of drug discontinuation have not been reported. Nine subjects with hypoparathyroidism received subcutaneous injections of hPTH 1-34 two to three times daily for 19.8 to 61.3 months and then transitioned back to calcium and calcitriol. Biochemistries and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) were assessed at baseline, while on treatment, and at follow-up 3 to 12 months after drug discontinuation. Two subjects developed hypocalcemia when hPTH 1-34 was abruptly discontinued. Thus, to avoid hypocalcemia, subjects were slowly weaned from hPTH 1-34 over several weeks. When hPTH 1-34 was stopped, subjects were requiring two to three times pretreatment doses of calcitriol and calcium to maintain blood calcium levels. Doses were gradually reduced over many weeks until calcium levels were stable on doses similar to baseline. Bone-specific alkaline phosphatase (BSAP), N-telopeptide (NTX), and osteocalcin (OC) increased significantly with hPTH 1-34; at follow-up, BSAP and NTX had returned to baseline while OC was still slightly elevated. During treatment, BMD was unchanged at the hip and lateral spine but declined at the anterior-posterior (AP) spine, radius, and total body. During weaning, BMD increased, with the hip and lateral spine exceeding pre-hPTH 1-34 values and the whole body returning to baseline. AP spine was increased non-significantly compared to baseline at follow-up. hPTH 1-34 must be gradually weaned in hypoparathyroid patients with high doses of oral medications given to avoid hypocalcemia. The transient increased requirements accompanied by increased BMD after long-term hPTH 1-34 therapy suggest a reversal of the expanded remodeling space favoring bone formation as the skeleton returns to a low-turnover state, reminiscent of the hungry bone syndrome. Further study and close monitoring is required to ensure safe transition to conventional therapy and to elucidate the physiological mechanism of this phenomenon. © 2015 American Society for Bone and Mineral Research.

Nano-risk Science: application of toxicogenomics in an adverse outcome pathway framework for risk assessment of multi-walled carbon nanotubes.

PubMed

Labib, Sarah; Williams, Andrew; Yauk, Carole L; Nikota, Jake K; Wallin, Håkan; Vogel, Ulla; Halappanavar, Sabina

2016-03-15

A diverse class of engineered nanomaterials (ENMs) exhibiting a wide array of physical-chemical properties that are associated with toxicological effects in experimental animals is in commercial use. However, an integrated framework for human health risk assessment (HHRA) of ENMs has yet to be established. Rodent 2-year cancer bioassays, clinical chemistry, and histopathological endpoints are still considered the 'gold standard' for detecting substance-induced toxicity in animal models. However, the use of data derived from alternative toxicological tools, such as genome-wide expression profiling and in vitro high-throughput assays, are gaining acceptance by the regulatory community for hazard identification and for understanding the underlying mode-of-action. Here, we conducted a case study to evaluate the application of global gene expression data in deriving pathway-based points of departure (PODs) for multi-walled carbon nanotube (MWCNT)-induced lung fibrosis, a non-cancer endpoint of regulatory importance. Gene expression profiles from the lungs of mice exposed to three individual MWCNTs with different physical-chemical properties were used within the framework of an adverse outcome pathway (AOP) for lung fibrosis to identify key biological events linking MWCNT exposure to lung fibrosis. Significantly perturbed pathways were categorized along the key events described in the AOP. Benchmark doses (BMDs) were calculated for each perturbed pathway and were used to derive transcriptional BMDs for each MWCNT. Similar biological pathways were perturbed by the different MWCNT types across the doses and post-exposure time points studied. The pathway BMD values showed a time-dependent trend, with lower BMDs for pathways perturbed at the earlier post-exposure time points (24 h, 3d). The transcriptional BMDs were compared to the apical BMDs derived by the National Institute for Occupational Safety and Health (NIOSH) using alveolar septal thickness and fibrotic lesions endpoints. We found that regardless of the type of MWCNT, the BMD values for pathways associated with fibrosis were 14.0-30.4 μg/mouse, which are comparable to the BMDs derived by NIOSH for MWCNT-induced lung fibrotic lesions (21.0-27.1 μg/mouse). The results demonstrate that transcriptomic data can be used to as an effective mechanism-based method to derive acceptable levels of exposure to nanomaterials in product development when epidemiological data are unavailable.

Permissible Exposure Level for Lunar Dusts: Gaps are Closing

NASA Technical Reports Server (NTRS)

James, John T.; Lam, Chiu-Wing; Scully Robert; Santana, Patricia; Cooper, Bonnie; McKay, David; Zeidler-Erdely, Patti C.; Castranova, Vincent

2010-01-01

Space faring nations plan to return human explorers to the moon within the next decade. Experience during the Apollo flights suggests that lunar dust will invariably get into the habitat where the finest portion (less than 5 micrometers) could be inhaled by the crew before it is cleared from the atmosphere. NASA is developing a database from which a 6-month, episodic exposure standard for lunar dust can be set. Three kinds of moon dust were prepared from a parent sample of Apollo 14 regolith #14003,96. Our goal was to prepare each type of dust sample with a mean diameter less than 2 m, which is suitable for instillation into the lungs of rats. The three samples were prepared as follows: separation from the parent sample using a fluidized bed, grinding using a jet mill grinder, or grinding with a ball-mill grinder. Grinding simulated restoration of surface activation of dust expected to occur at the surface of the moon on native lunar dust. We used two grinding methods because they seemed to produce different modes of activation. The effects of grinding were preserved by maintaining the dust in ultra-pure nitrogen until immediately before it was placed in suspension for administration to rats. The dust was suspended in physiological saline with 10% Survanta, a lung surfactant. Rats were given intratrachael instillations of the dust suspension at three doses. In addition to the three moon dusts (A, C and E), we instilled the same amount of a negative control (TiO2, B) and a highly-toxic, positive control (quartz, D). These additional mineral dusts were selected because they have well-established and very different permissible exposure levels (PELs). Our goal was to determine where lunar dusts fit between these extremes, and then estimate a PEL for each lunar dust. We evaluated many indices of toxicity to the lung. The figure shows the changes in lactate dehydrogenase (LDH), a marker of cell death, for the five dusts. Benchmark dose software (Version 2.1.2) from the Environmental Protection Agency was used to estimate the 10% effect levels (BMD(sub 10)) using five models. The best-fitting model was used to estimate the optimal BMD(sub 10) (table)

Can bone loss be reversed by antithyroid drug therapy in premenopausal women with Graves' disease?

PubMed Central

2010-01-01

Context Hyperthyroidism can lead to reduced bone mineral density (BMD) and increased fracture risk particularly in postmenopausal women, but the mechanism behind is still unclear. Objective Prospective examination of the influence of thyroid hormones and/or thyroid autoantibodies on BMD in premenopause. Design We have examined 32 premenopausal women with untreated active Graves' disease from time of diagnosis, during 18 months of antithyroid drug therapy (ATD) and additionally 18 months after discontinuing ATD. Variables of thyroid metabolism, calcium homeostasis and body composition were measured every 3 months. BMD of lumbar spine and femoral neck were measured at baseline, 18 ± 3 and 36 ± 3 months. Data were compared to base line, a sex- and age matched control group and a group of patients with Hashimoto's thyroiditis treated with non-suppressive doses of levothyroxine. Results The study showed significantly (p < 0.002) lower BMD in the thyrotoxic state compared to the control group with subsequent significant improvement during 18 ± 3 months of ATD compared to baseline (p < 0.001). However, during the following 18 months after stopping ATD femoral neck BMD decreased again unrelated to age (more than 0.4% per year, p < 0,002). The wellestablished effect of thyrotoxicosis on calcium homeostasis was confirmed. The positive predictor for best BMD was TSH receptor antibodies (TRAb) while free T4 correlated negatively in the thyrotoxic female Graves' patients (p < 0.02 and p < 0.003). In healthy controls and patients with treated Graves' disease both TSH and T4 correlated negatively to the bone mass (BMC) (p < 0.003). Conclusion The results indicated a clinically relevant impact of thyroid function on bone modulation also in premenopausal women with Graves' disease, and further indicated the possibility for a direct action of TRAb on bones. PMID:20807449

A rational use of glucocorticoids in patients with early arthritis has a minimal impact on bone mass

PubMed Central

2010-01-01

Introduction Glucocorticoid (GC)-induced osteoporosis is a frequent complication in patients with rheumatoid arthritis. However, little information exists about the consequences of GC use in patients with early arthritis. Here we describe the variables underlying the use of GC in early arthritis, as well as its effect on bone-mineral density. Methods Data from 116 patients in our early arthritis register were analyzed (90 women; median age, 52.5 years, interquartile range (IQR, 38.5-66); 6-month median disease duration at entry (IQR, 4-9)). In this register, the clinical and treatment information was recorded systematically, including the cumulative GC dose. Lumbar spine, hip, and forearm bone-mineral density (BMD) measurements were performed at entry and after a 2-year follow-up. A multivariate analysis was performed to establish the variables associated with the use of GCs, as well as those associated with variations in BMD. Results Of the patients with early arthritis studied, 67% received GCs during the 2-year follow-up. GCs were more frequently prescribed to elderly patients, those with higher basal disease activity and disability, and patients with positive rheumatoid factor. When adjusted for these variables, GCs were less frequently prescribed to female patients. The use of GCs was associated with an increase of BMD in the ultradistal region of the forearm, although it induced a significant loss of BMD in the medial region of the forearm. No relevant effect of GC was noted on the BMD measured at other locations. Conclusions The frequent use of GCs as a "bridge therapy" in patients with early arthritis does not seem to be associated with relevant loss of bone mass. Moreover, cumulative GC administration might be associated with an increase of juxtaarticular BMD. PMID:20331862

Effects of Radiation and a High Iron Load on Bone Mineral Density

NASA Technical Reports Server (NTRS)

Yuen, E.; Morgan, J. L. L.; Zwart, S. R.; Gonzales, E.; Camp, K.; Smith, S. M.; Bloomfield, S. A.

2012-01-01

Astronauts on long duration space flight missions to the moon or mars are exposed to radiation and have increase iron (Fe) stores, both of which can independently induce oxidative stress and may exacerbate bone mass loss and strength. We hypothesize a high Fe diet and a fractionated gamma radiation exposure would increase oxidative stress and lower bone mass. Three mo-old, SD rats (n=32) were randomized to receive an adequate Fe diet (45 mg Fe/kg diet) or a high Fe diet (650 mg Fe/kg diet) for 4 wks and either a cumulative 3 Gy dose (fractionated 8 x 0.375 Gy) of gamma radiation (Cs-137) or sham exposure starting on day 14. Elisa kit assessed serum catalase, clinical analyzer assessed serum Fe status and ex vivo pQCT scans measured bone parameters in the proximal/midshaft tibia and femoral neck. Mechanical strength was assessed by 3-pt bending and femoral neck test. There is a significant decrease in trabecular bone mineral density (BMD) from radiation (p less than 0.05) and a trend in diet (p=0.05) at the proximal tibia. There is a significant interaction in cortical BMD from the combined treatments at the midshaft tibia (p less than 0.05). There is a trending decrease in total BMD from diet (p=0.07) at the femoral neck. In addition, high serum Fe was correlated to low trabecular BMD (p less than 0.05) and high serum catalase was correlated to low BMD at all 3 bone sites (p less than 0.05). There was no difference in the max load of the tibia or femoral neck. Radiation and a high iron diet increases iron status and catalase in the serum and decreases BMD.

Bone Mineral Density and Growth in Children Having Undergone Liver Transplantation With Corticosteroid-Free Immunosuppressive Protocol.

PubMed

Mager, Diana; Al-Zaben, Abeer Salman; Robert, Cheri; Gilmour, Susan; Yap, Jason

2017-05-01

Children post-liver transplantation (post-LTX) are at risk of growth delay and decreased bone mineral density (BMD) secondary to corticosteroid (CS) therapy and suboptimal intake of nutrients important for bone health. The pediatric LTX program at Stollery Children's Hospital introduced a CS-free LTX regimen in 2003. This retrospective study investigated whether the implementation of a CS-free protocol resulted in improvements in BMD (dual x-ray absorptiometry) and growth following LTX. A retrospective chart review of all children undergoing LTX was conducted. The parameters included repeated measures of anthropometric (weight, weight z score, height, height z score), BMD/bone mineral content (BMC), laboratory variables, graft function (number/severity of rejection), and CS therapy (dose, duration). A total of 39 patients met study inclusion (20 male; n = 28 on CS; n = 11 CS-free). Mean duration of follow-up was 5.5 ± 3.3 years. The mean weight and height z scores were -0.31 ± 0.14 (CS) and 0.22 ± 0.23 (CS-free; P = .09) and -0.71 ± 0.13 (CS) and 0.23 ± 0.22 (CS-free; P = .002), respectively. Lumbar and whole-body BMD z score less than -2 were present in 15% and 8% of the cohort, respectively. There were no significant differences between CS and CS-free in lumbar BMC (22.2 ± 1.4 and 23.4 ± 2.02 g; P = .165) and lumbar BMD (0.57 ± 0.02 and 0.80 ± 0.22 g/cm 2 ; P = .152), respectively. Lumbar BMC ( r 2 = 0.89, P < .05) and whole-body BMC ( r 2 = 0.93, P < .05) were inversely related to CS dose >0.2 mg/kg/d and positively related to bone age ( P < .01). CS therapy in children post-LTX is associated with reduced BMC and delayed linear growth. Understanding the clinical and nutrition factors influencing bone health is important to optimizing growth and bone health in children post-LTX.

Effects of the combination of vitamin K and teriparatide on the bone metabolism in ovariectomized rats.

PubMed

Nagura, Nana; Komatsu, Jun; Iwase, Hideaki; Hosoda, Hiroshi; Ohbayashi, Osamu; Nagaoka, Isao; Kaneko, Kazuo

2015-05-01

The purpose of the present study was to evaluate the combined effects of vitamin K (VK) and teriparatide (TPTD) on bone mineral density (BMD), mechanical strength and other parameters for bone metabolism using a rat ovariectomized osteoporosis model. Ovariectomized female Sprague-Dawley rats were administered with VK (an oral dose of 30 mg/kg/day), TPTD (a subcutaneous dose of 30 µg/kg, three times a week) or a combination for 8 weeks. Thereafter, serum levels of γ-carboxylated osteocalcin (Gla-OC) were quantitated by ELISA; BMD and mechanical strength were measured by computed tomography and biomechanical testing, respectively at the femoral metaphysis. Additionally, histomorphometry was performed using the toluidine blue-stained coronal sections of distal femur. The combination of VK and TPTD clearly increased the serum levels of Gla-OC (a specific marker for bone formation) and osteoblast surface (the number of osteoblasts attaching with the surface of cancellous bone), compared to VK or TPTD alone. In addition, the combination of the two agents improved the BMD and bone strength of the femur in the ovariectomized rats, compared to VK or TPTD alone. Taken together, these findings suggest that the treatment with VK and TPTD may have a therapeutic advantage over VK or TPTD monotherapy for postmenopausal osteoporosis, possibly by enhancing the bone formation through the actions on OC and osteoblasts.

Effects of the combination of vitamin K and teriparatide on the bone metabolism in ovariectomized rats

PubMed Central

NAGURA, NANA; KOMATSU, JUN; IWASE, HIDEAKI; HOSODA, HIROSHI; OHBAYASHI, OSAMU; NAGAOKA, ISAO; KANEKO, KAZUO

2015-01-01

The purpose of the present study was to evaluate the combined effects of vitamin K (VK) and teriparatide (TPTD) on bone mineral density (BMD), mechanical strength and other parameters for bone metabolism using a rat ovariectomized osteoporosis model. Ovariectomized female Sprague-Dawley rats were administered with VK (an oral dose of 30 mg/kg/day), TPTD (a subcutaneous dose of 30 µg/kg, three times a week) or a combination for 8 weeks. Thereafter, serum levels of γ-carboxylated osteocalcin (Gla-OC) were quantitated by ELISA; BMD and mechanical strength were measured by computed tomography and biomechanical testing, respectively at the femoral metaphysis. Additionally, histomorphometry was performed using the toluidine blue-stained coronal sections of distal femur. The combination of VK and TPTD clearly increased the serum levels of Gla-OC (a specific marker for bone formation) and osteoblast surface (the number of osteoblasts attaching with the surface of cancellous bone), compared to VK or TPTD alone. In addition, the combination of the two agents improved the BMD and bone strength of the femur in the ovariectomized rats, compared to VK or TPTD alone. Taken together, these findings suggest that the treatment with VK and TPTD may have a therapeutic advantage over VK or TPTD monotherapy for postmenopausal osteoporosis, possibly by enhancing the bone formation through the actions on OC and osteoblasts. PMID:26137225

Categorical Regression and Benchmark Dose Software 3.0

EPA Science Inventory

The objective of this full-day course is to provide participants with interactive training on the use of the U.S. Environmental Protection Agency’s (EPA) Benchmark Dose software (BMDS, version 3.0, released fall 2018) and Categorical Regression software (CatReg, version 3.1...

Physiologically based kinetic modeling of bioactivation and detoxification of the alkenylbenzene methyleugenol in human as compared with rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Subeihi, Ala' A.A., E-mail: ala.alsubeihi@wur.nl; BEN-HAYYAN-Aqaba International Laboratories, Aqaba Special Economic Zone Authority; Spenkelink, Bert

2012-05-01

This study defines a physiologically based kinetic (PBK) model for methyleugenol (ME) in human based on in vitro and in silico derived parameters. With the model obtained, bioactivation and detoxification of methyleugenol (ME) at different doses levels could be investigated. The outcomes of the current model were compared with those of a previously developed PBK model for methyleugenol (ME) in male rat. The results obtained reveal that formation of 1′-hydroxymethyleugenol glucuronide (1′HMEG), a major metabolic pathway in male rat liver, appears to represent a minor metabolic pathway in human liver whereas in human liver a significantly higher formation of 1′-oxomethyleugenolmore » (1′OME) compared with male rat liver is observed. Furthermore, formation of 1′-sulfooxymethyleugenol (1′HMES), which readily undergoes desulfonation to a reactive carbonium ion (CA) that can form DNA or protein adducts (DA), is predicted to be the same in the liver of both human and male rat at oral doses of 0.0034 and 300 mg/kg bw. Altogether despite a significant difference in especially the metabolic pathways of the proximate carcinogenic metabolite 1′-hydroxymethyleugenol (1′HME) between human and male rat, the influence of species differences on the ultimate overall bioactivation of methyleugenol (ME) to 1′-sulfooxymethyleugenol (1′HMES) appears to be negligible. Moreover, the PBK model predicted the formation of 1′-sulfooxymethyleugenol (1′HMES) in the liver of human and rat to be linear from doses as high as the benchmark dose (BMD{sub 10}) down to as low as the virtual safe dose (VSD). This study shows that kinetic data do not provide a reason to argue against linear extrapolation from the rat tumor data to the human situation. -- Highlights: ► A PBK model is made for bioactivation and detoxification of methyleugenol in human. ► Comparison to the PBK model in male rat revealed species differences. ► PBK results support linear extrapolation from high to low dose and from rat to human.« less

Reduced bone mineral density in Japanese premenopausal women with systemic lupus erythematosus treated with glucocorticoids.

PubMed

Banno, S; Matsumoto, Y; Naniwa, T; Hayami, Y; Sugiura, Y; Yoshinouchi, T; Ueda, R

2002-12-01

Abstract We evaluated bone mineral density (BMD) in Japanese female patients with systemic lupus erythematosus (SLE) and assessed the influence of the use of glucocorticoids. Lumbar BMD was measured by dual x-ray absorptiometry (DXA) in 60 premenopausal females who previously had been receiving glucocorticoid therapy. Therapeutic- and disease-related variables for SLE were analyzed and bone resorption or formation markers were measured. Osteoporosis was defined as a T-score below 2.5 SD by DXA; 12 patients (20%) showed osteoporosis, and 30 (50%) had osteopenia. Compared with the nonosteoporotic group (n = 48), the osteoporotic group (n = 12) had a significantly longer duration of glucocorticoid treatment (P = 0.01), a cumulative prednisolone dose (P = 0.002), and an SLE damage index (SLICC/ACR). There was no difference in the incidence of osteoporosis either with or without the previous use of methyl-prednisolone pulse or immunosuppressive drugs. There was a significant positive correlation between urinary type I collagen cross-linked N-telopeptides (NTx) and serum bone-specific alkaline phosphatase (BAP) (r = 0.404, P = 0.002), but these bone metabolic markers showed no difference between the osteoporotic and nonosteoporotic groups. A good significant negative correlation was shown between BMD and the cumulative glucocorticoid dose (r = -0.351, P = 0.007). Stepwise logistic regression analysis showed that the cumulative glucocorticoid intake was independently associated with osteoporosis. Glucocorticoid-induced osteoporosis was frequently observed in Japanese SLE patients, as in Caucasian populations. The cumulative glucocorticoid dose was associated with an increased risk for osteoporosis. Bone metabolic markers such as NTx and BAP were not influenced by glucocorticoid treatment and could not predict current osteoporosis in SLE patients.

High doses of vitamin C plus E reduce strength training-induced improvements in areal bone mineral density in elderly men.

PubMed

Stunes, Astrid Kamilla; Syversen, Unni; Berntsen, Sveinung; Paulsen, Gøran; Stea, Tonje H; Hetlelid, Ken J; Lohne-Seiler, Hilde; Mosti, Mats Peder; Bjørnsen, Thomas; Raastad, Truls; Haugeberg, Glenn

2017-06-01

Resistance training is beneficial for maintaining bone mass. We aimed to investigate the skeletal effects of high doses of antioxidants [vitamin C + E (α-tocopherol)] supplementation during 12-week supervised strength training in healthy, elderly men METHODS: Design: double-blinded randomized placebo-controlled study. Participants followed a supervised, undulating periodic exercise program with weekly adjusted load: 3 sessions/week and 3-15 repetitions maximum (RM) sets/exercise. The control group (CG, n = 17, 67 ± 5 years) received placebo and the antioxidant group (AO, n = 16, 70 ± 7 years) 1000 mg vitamin C + 235 mg vitamin E, daily. Areal bone mineral density (aBMD) at whole body, lumbar spine (L1-L4), total hip, and femoral neck were measured by dual energy X-ray absorptiometry and muscle strength by 1RM. Serum analyses of bone-related factors and adipokines were performed. In the CG, total hip aBMD increased by 1.0% (CI: 0.3-1.7) versus pretest and lumbar spine aBMD increased by 0.9% (CI: -0.2 to 2.0) compared to the AO. In the CG, there was an increase in serum concentrations of insulin-like growth factor 1 [+27.3% (CI: -0.3 to 54.9)] and leptin [+31.2% (CI: 9.8-52.6)) versus pretest, and a decrease in sclerostin [-9.9% (CI: 4.4-15.3)] versus pretest and versus AO. Serum bone formation markers P1NP and osteocalcin increased in both groups, while the bone resorption marker CTX-1 remained unchanged. High doses of antioxidant supplementations may constrain the favorable skeletal benefits of 12 weeks of resistance exercise in healthy elderly men.

Improved efficacy of intramuscular weekly administration of clodronate 200 mg (100 mg twice weekly) compared with 100 mg (once weekly) for increasing bone mineral density in postmenopausal osteoporosis.

PubMed

Frediani, Bruno; Bertoldi, Ilaria; Pierguidi, Serena; Nicosia, Antonella; Picerno, Valentina; Filippou, Georgios; Cantarini, Luca; Galeazzi, Mauro

2013-03-01

Clodronate is a bisphosphonate used for the treatment of postmenopausal osteoporosis and all conditions characterized by excess bone resorption. We have previously reported that intramuscular (IM) therapy with clodronate at a dose of 100 mg/week displays significant effects on bone mineral density (BMD) although a plateau effect is observed after 1 year of treatment. Previous reports indicate that the densitometric effects of bisphosphonates directly correlate with the drug dosage and suggest that using IM clodronate at doses higher than 100 mg/week may result in improved efficacy. However, to the best of our knowledge, this has never been proved. The primary endpoint of the study was the effect on BMD of IM clodronate 100 mg once weekly or 100 mg twice weekly in patients with postmenopausal osteoporosis. The incidence of non-traumatic vertebral fractures and adverse events was also reported. The present study was a randomized, open-label, parallel-group trial conducted between January 2007 and December 2009 in the Osteoporosis and Osteoarticular Instrumental Diagnosis Centre (University of Siena, Siena, Italy). The study involved 60 women, aged 57-78 years, with a history of postmenopausal osteoporosis for more than 5 years. Patients were randomized to receive IM clodronate 100 mg once weekly (Group A, 30 patients) or 100 mg twice weekly (Group B, 30 patients), for 2 years. Significant increases compared with baseline in BMD were observed for both groups at 1 and 2 years, with significantly higher increases for Group B compared with Group A. Group B displayed a BMD increase (± SD) at the lumbar spine of +4.0 % (± 2.1) and +5.9 % (± 2.0) at 1 and 2 year(s), respectively, compared with +2.8 % (± 1.7) and +3.5 % (± 2.2), respectively, observed for Group A. Similarly, Group B showed better performance compared with Group A for BMD increase at the femoral neck, with an observed increase of +3.5 % (± 1.7) and +5.4 % (± 1.8) at 1 and 2 year(s), respectively, compared with a change of +2.3 % (± 1.9) and +2.5 % (± 1.9), respectively, registered in Group A. Consistently, the BMD increase measured at the total femur was significantly higher for Group B [+3.4 % (± 1.9) and +4.9 % (± 2.1) at years 1 and 2, respectively] compared with Group A [+1.6 % (± 0.9) and +2.4 % (± 1.9) at years 1 and 2, respectively]. When the change in BMD from year 1 to year 2 was compared, a significant increase of BMD was seen in Group B in all the analysed regions, contrary to that observed for Group A where a plateau effect resulted in no significant change from year 1 to year 2. Three non-traumatic vertebral fractures occurred during the study: two in Group A and one in Group B. The present study indicates the superior performance of IM clodronate 200 mg weekly (100 mg twice weekly) compared with 100 mg once weekly in BMD in women with postmenopausal osteoporosis. This work demonstrated that administration of twice the drug dosage in a week significantly improved the efficacy of the treatment without inducing serious adverse events. Therefore, IM clodronate 200 mg weekly may be considered a valid therapeutic choice for the treatment of postmenopausal osteoporosis.

Lycopene intake facilitates the increase of bone mineral density in growing female rats.

PubMed

Iimura, Yuki; Agata, Umon; Takeda, Satoko; Kobayashi, Yuki; Yoshida, Shigeki; Ezawa, Ikuko; Omi, Naomi

2014-01-01

Intake of the antioxidant lycopene has been reported to decrease oxidative stress and have beneficial effects on bone health. However, few in vivo studies have addressed these beneficial effects in growing female rodents or young women. The aim of this study was to investigate the effect of lycopene intake on bone metabolism through circulating oxidative stress in growing female rats. Six-week-old Sprague-Dawley female rats were randomly divided into 3 groups according to the lycopene content in their diet: 0, 50, and 100 ppm. The bone mineral density (BMD) of the lumbar spine and the tibial proximal metaphysis increased with lycopene content in a dose-dependent manner; the BMD in 100 ppm group was significantly higher than in the 0 ppm group. The urine deoxypyridinoline concentrations were significantly lower in the 50 and 100 ppm groups than in the 0 ppm group, and the serum bone-type alkaline phosphatase activity was significantly higher in 100 ppm group than in the 0 ppm group. No difference in systemic oxidative stress level was observed; however, the oxidative stress level inversely correlated with the tibial BMD. Our findings suggested that lycopene intake facilitates bone formation and inhibits bone resorption, leading to an increase of BMD in growing female rats.

Three doses of vitamin D, bone mineral density, and geometry in older women during modest weight control in a 1-year randomized controlled trial.

PubMed

Pop, L C; Sukumar, D; Schneider, S H; Schlussel, Y; Stahl, T; Gordon, C; Wang, X; Papathomas, T V; Shapses, S A

2017-01-01

The effects of higher than recommended vitamin D doses on bone mineral density (BMD) and quality are not known. In this study, higher intakes, in postmenopausal women undergoing weight control over 1 year, had no effect on areal or volumetric BMD but prevented the deterioration in cortical bone geometry. Studies examining how bone responds to a standard dose of vitamin D supplementation have been inconsistent. In addition, the effects of higher doses on BMD and quality are not known. Postmenopausal women undergoing weight control to improve health outcomes are particularly at risk for bone loss and might benefit from supplemental vitamin D intake above the recommended allowance. This 1-year-long, randomized, double-blind controlled study addresses whether vitamin D supplementation, in healthy overweight/obese older women, affects BMD and bone structural parameters. In addition, bone turnover and serum total, free, and bioavailable 25-hydroxyvitamin D (25OHD) responses to one of three daily levels of vitamin D 3 (600, 2000, 4000 IU) with 1.2 Ca g/day during weight control were examined. Fifty-eight women (age, 58 ± 6 years; body mass index, 30.2 ± 3.8 kg/m 2 , serum 25OHD, 27.3 ± 4.4 ng/mL) were randomized to treatment. After 1 year, serum 25OHD concentrations increased to 26.5 ± 4.4, 35.9 ± 4.5, and 41.5 ± 6.9 ng/mL, in groups 600, 2000, and 4000 IU, respectively, and differed between groups (p < 0.01). Weight change was similar between groups (-3.0 ± 4.1 %). Cortical (Ct) thickness of the tibia changed by -1.5 ± 5.1 %, +0.6 ± 3.2 %, and +2.0 ± 4.5 % in groups 600, 2000, and 4000 IU, respectively, and each group was significantly different from each other (p < 0.05). The decline in Ct thickness was prevented with higher vitamin D 3 supplementation, but there were no other significant changes due to treatment over 1 year. Whether these findings translate to changes in biomechanical properties leading to reduced fracture risk should be addressed in future studies.

Influence of different susceptibility testing methods and media on determination of the relevant fluconazole minimum inhibitory concentrations for heavy trailing Candida isolates with low-high phenotype.

PubMed

Alp, Sehnaz; Sancak, Banu; Hascelik, Gulsen; Arikan, Sevtap

2010-11-01

We investigated the incidence of trailing growth with fluconazole in 101 clinical Candida isolates (49 C. albicans and 52 C. tropicalis) and tried to establish the convenient susceptibility testing method and medium for fluconazole minimum inhibitory concentration (MIC) determination. MICs were determined by CLSI M27-A2 broth microdilution (BMD) and Etest methods on RPMI-1640 agar supplemented with 2% glucose (RPG) and on Mueller-Hinton agar supplemented with 2% glucose and 0.5 μg ml(-1) methylene blue (GMB). BMD and Etest MICs were read at 24 and 48 h, and susceptibility categories were compared. All isolates were determined as susceptible with BMD, Etest-RPG and Etest-GMB at 24 h. While all isolates were interpreted as susceptible at 48 h on Etest-RPG and Etest-GMB, one C. albicans isolate was interpreted as susceptible-dose dependent (S-DD) and two C. tropicalis isolates were interpreted as resistant with BMD. On Etest-RPG, trailing growth caused widespread microcolonies within the inhibition zone and resulted in confusion in MIC determination. On Etest-GMB, because of the nearly absence of microcolonies within the zone of inhibition, MICs were evaluated more easily. We conclude that, for the determination of fluconazole MICs of trailing Candida isolates, the Etest method has an advantage over BMD and can be used along with this reference method. Moreover, GMB appears more beneficial than RPG for the fluconazole Etest. © 2009 Blackwell Verlag GmbH.

Avoiding Pitfalls in the Use of the Benchmark Dose Approach to Chemical Risk Assessments; Some Illustrative Case Studies (Presentation)

EPA Science Inventory

The USEPA's benchmark dose software (BMDS) version 1.2 has been available over the Internet since April, 2000 (epa.gov/ncea/bmds.htm), and has already been used in risk assessments of some significant environmental pollutants (e.g., diesel exhaust, dichloropropene, hexachlorocycl...

Strontium ranelate for preventing and treating postmenopausal osteoporosis.

PubMed

O'Donnell, S; Cranney, A; Wells, G A; Adachi, J D; Reginster, J Y

2006-07-19

Strontium ranelate is a new anti-osteoporosis therapy therefore, its benefits and harms need to be known. To determine the efficacy and safety of strontium ranelate for the treatment and prevention of postmenopausal osteoporosis. We searched MEDLINE (1996 to March 2005), EMBASE (1996 to week 9 2005), the Cochrane Library (1996 to Issue 1 2005), reference lists of relevant articles and conference proceedings from the last two years. Additional data was sought from authors and industry sponsors. We included randomized controlled trials (RCTs) of at least one year duration comparing strontium ranelate versus placebo reporting fracture incidence, bone mineral density (BMD), health related quality of life and/or safety outcomes in postmenopausal women. Treatment (versus prevention) population was defined as women with prevalent vertebral fractures and/or lumbar spine BMD T score < -2.5 SD. Two reviewers independently determined study eligibility, assessed trial quality and extracted the relevant data. Disagreements were resolved by consensus. RCTs were grouped by dose of strontium ranelate and treatment duration. Where possible, meta-analysis was conducted using the random effects model. A total of four trials met our inclusion criteria, three of which investigated the effects of strontium ranelate compared to placebo in a treatment population (doses ranged from 0.5 to 2 g daily) and one, in a prevention population (doses 0.125, 0.5 and 1 g daily). In osteoporotic, postmenopausal women a 37% reduction in vertebral fractures (two trials, n = 5082, RR 0.63, 95% CI 0.56 to 0.71) and a 14% reduction in non-vertebral fractures (two trials, n = 6572, RR 0.86, 95% CI 0.75 to 0.98) was demonstrated over a three year period with 2 g of strontium ranelate daily. An increase in BMD at all sites was shown with the same dose: lumbar spine BMD (two trials, n = 1614, WMD adjusted for strontium content 5.44, 95% CI 3.41 to 7.46 and WMD not adjusted 11.29, 95% CI 10.22 to 12.37 over two years), femoral neck and total hip (two trials, n = 4230, WMD 8.25, 95% CI 7.84 to 8.66 and WMD 9.83, 95% CI 9.39 to 10.26 respectively over three years). One gram of strontium ranelate daily in postmenopausal women without osteoporosis increased BMD at all sites over a two year period: lumbar spine (one trial, n = 59, WMD adjusted for strontium content 2.39, 95% CI 0.15 to 4.63 and WMD not adjusted 6.68, 95% CI 5.16 to 8.20), femoral neck (one trial, n= 60, WMD 2.52, 95%CI 0.96 to 4.09) and total hip (one trial, n = 60, WMD 1.02, 95% CI 0.48 to 1.56). In both the treatment and prevention populations, lower doses of strontium ranelate were superior to placebo with the highest dose of strontium ranelate demonstrating the greatest reduction in vertebral fractures and increase in BMD. There is some evidence to suggest that 2 g of strontium ranelate daily compared to placebo may have a beneficial effect on health related quality of life in postmenopausal women after three years of treatment. Two grams of strontium ranelate daily increased the risk of diarrhea (RR 1.38%, 95% CI 1.02 to 1.87); however, adverse events did not affect the risk of discontinuing strontium ranelate nor did it increase the risk of serious side effects, gastritis or death. Additional data obtained suggests that the risk of vascular system disorders including venous thromboembolism (two trials, n = 6669, 2.2% versus 1.5%, OR 1.5, 95% CI 1.1 to 2.1) and pulmonary embolism (two trials, n = 6669, 0.8% versus 0.4%, OR 1.7, 95% CI 1.0 to 3.1) as well as nervous system disorders such as headaches (3.9% versus 2.9%), seizures (0.3% versus 0.1%), memory loss (2.4% versus 1.9%) and disturbance in consciousness (2.5% versus 2.0%) is slightly increased with taking 2 g of strontium ranelate daily over a 3 to 4 year period. There is silver level evidence to support the efficacy of strontium ranelate for the reduction of vertebral fractures (and to a lesser extent non-vertebral fractures) in postmenopausal osteoporotic women and an increase in BMD (all sites) in postmenopausal women with and without osteoporosis. Diarrhea may occur however, adverse events leading to study withdrawal were not significantly increased in the strontium ranelate group. Potential risks to the vascular and neurological system associated with taking 2 g of strontium ranelate daily need to be further explored and quantified.

The effect of lysophosphatidic acid using a hydrogel or collagen sponge carrier on bone healing in dogs.

PubMed

Might, Kelly R; Martinez, Steven A; Karin, Norman; Lin, Genyao; Tarasevich, Barbara; Pool, Roy R

2016-07-19

The purposes of this study were to determine: 1) the efficacy of polycaprolactone-g-polyethylene glycol (PCL-g-PEG) and polylactic-co-glycolic acid (PLGA-g-PEG) hydrogels and an absorbable collagen sponge (ACS) as carriers for lysophosphatidic acid (LPA), 2) the effect of LPA on bone healing in dogs, and 3) the ideal dose of LPA to maximally stimulate bone healing. Bilateral ulnar ostectomies were performed on purpose bred dogs. Control defects were filled with a PCL-g-PEG or PLGA-g-PEG hydrogel, or a saline soaked ACS. Contralateral defects were filled with a PCL-g-PEG or PLGA-g-PEG hydrogel, or an ACS with each carrying differing concentrations of an LPA solution. Dual-energy X-ray absorptiometry (DXA) was performed. Total bone area (TBA), mineral density (BMD), and mineral content (BMC) were determined at each time point. Relationships between the effect of treatment over time on TBA, BMC and BMD were determined. Phase 1 - There was no significant difference in DXA-based TBA (p = 0.09), BMC (p = 0.33), or BMD (p = 0.74) over time between LPA treatments, or between the LPA treated and control groups TBA (p = 0.95), BMC (p = 0.99), or BMD (p = 0.46). Phase 2 - There was no significant difference over time between LPA treatments in DXA-based TBA (p = 0.33), BMC (p = 0.45), or BMD (p = 0.43), or between the LPA treated and control groups TBA (p = 0.94), BMC (p = 0.38), or BMD (p = 0.17). Phase 3 - There was no significant difference over time between LPA treatments in DXA-based TBA (p = 0.78), BMC (p = 0.88), or BMD (p = 0.35), or between the LPA treated and control groups TBA (p = 0.07), BMC (p = 0.85), or BMD (p = 0.06). There was a significant increase in TBA (p <0.0001) and BMC (p = 0.0014), but a significant decrease in BMD (p <0.0001) was noted over time when all groups were combined. Although LPA has shown promise as an osteoinductive agent in research, its performance as a bone graft substitute, as utilized in this study, is unsupported. Further studies are necessary to determine the incorporation and elution kinetics of LPA from the PLGA-g-PEG hydrogel and from an ACS. Hydrogels may have clinical applications for delaying or preventing bone formation.

Vertebral and femoral bone mineral density and bone strength in prostate cancer patients assessed in phantomless PET/CT examinations.

PubMed

Schwaiger, Benedikt J; Kopperdahl, David L; Nardo, Lorenzo; Facchetti, Luca; Gersing, Alexandra S; Neumann, Jan; Lee, Kwang J; Keaveny, Tony M; Link, Thomas M

2017-08-01

Bone fracture risk assessed ancillary to positron emission tomography with computed tomography co-registration (PET/CT) could provide substantial clinical value to oncology patients with elevated fracture risk without introducing additional radiation dose. The purpose of our study was to investigate the feasibility of obtaining valid measurements of bone mineral density (BMD) and finite element analysis-derived bone strength of the hip and spine using PET/CT examinations of prostate cancer patients by comparing against values obtained using routine multidetector-row computed tomography (MDCT) scans-as validated in previous studies-as a reference standard. Men with prostate cancer (n=82, 71.6±8.3 years) underwent Fluorine-18 NaF PET/CT and routine MDCT within three months. Femoral neck and total hip areal BMD, vertebral trabecular BMD and femur and vertebral strength based on finite element analysis were assessed in 63 paired PET/CT and MDCT examinations using phantomless calibration and Biomechanical-CT analysis. Men with osteoporosis or fragile bone strength identified at either the hip or spine (vertebral trabecular BMD ≤80mg/cm 3 , femoral neck or total hip T-score ≤-2.5, vertebral strength ≤6500N and femoral strength ≤3500N, respectively) were considered to be at high risk of fracture. PET/CT- versus MDCT-based BMD and strength measurements were compared using paired t-tests, linear regression and by generating Bland-Altman plots. Agreement in fracture-risk classification was assessed in a contingency table. All measurements from PET/CT versus MDCT were strongly correlated (R 2 =0.93-0.97; P<0.0001 for all). Mean differences for total hip areal BMD (0.001g/cm 2 , 1.1%), femoral strength (-60N, 1.3%), vertebral trabecular BMD (2mg/cm 3 , 2.6%) and vertebral strength (150N; 1.7%) measurements were not statistically significant (P>0.05 for all), whereas the mean difference in femoral neck areal BMD measurements was small but significant (-0.018g/cm 2 ; -2.5%; P=0.007). The agreement between PET/CT and MDCT for fracture-risk classification was 97% (0.89 kappa for repeatability). Ancillary analyses of BMD, bone strength, and fracture risk agreed well between PET/CT and MDCT, suggesting that PET/CT can be used opportunistically to comprehensively assess bone integrity. In subjects with high fracture risk such as cancer patients this may serve as an additional clinical tool to guide therapy planning and prevention of fractures. Copyright © 2017 Elsevier Inc. All rights reserved.

Experimental benchmarking of a Monte Carlo dose simulation code for pediatric CT

NASA Astrophysics Data System (ADS)

Li, Xiang; Samei, Ehsan; Yoshizumi, Terry; Colsher, James G.; Jones, Robert P.; Frush, Donald P.

2007-03-01

In recent years, there has been a desire to reduce CT radiation dose to children because of their susceptibility and prolonged risk for cancer induction. Concerns arise, however, as to the impact of dose reduction on image quality and thus potentially on diagnostic accuracy. To study the dose and image quality relationship, we are developing a simulation code to calculate organ dose in pediatric CT patients. To benchmark this code, a cylindrical phantom was built to represent a pediatric torso, which allows measurements of dose distributions from its center to its periphery. Dose distributions for axial CT scans were measured on a 64-slice multidetector CT (MDCT) scanner (GE Healthcare, Chalfont St. Giles, UK). The same measurements were simulated using a Monte Carlo code (PENELOPE, Universitat de Barcelona) with the applicable CT geometry including bowtie filter. The deviations between simulated and measured dose values were generally within 5%. To our knowledge, this work is one of the first attempts to compare measured radial dose distributions on a cylindrical phantom with Monte Carlo simulated results. It provides a simple and effective method for benchmarking organ dose simulation codes and demonstrates the potential of Monte Carlo simulation for investigating the relationship between dose and image quality for pediatric CT patients.

Risedronate therapy for the prevention of steroid-induced osteoporosis in patients with minimal-change nephrotic syndrome.

PubMed

Takei, Takashi; Itabashi, Mitsuyo; Tsukada, Misao; Sugiura, Hidekazu; Moriyama, Takahito; Kojima, Chiari; Shiohira, Shunji; Shimizu, Ari; Karasawa, Kazunori; Amemiya, Nobuyuki; Kawanishi, Kunio; Ogawa, Tetsuya; Uchida, Keiko; Tsuchiya, Ken; Nitta, Kosaku

2010-01-01

Minimal-change nephrotic syndrome (MCNS) is treated by the administration of prednisolone (PSL) at high doses. Steroid-induced osteoporosis is a serious adverse effect of this drug. Patients with MCNS were randomly assigned to two groups, the risedronate (2.5 mg/day) + alfacalcidol (0.25 µg/day) group (n=20) and the alfacalcidol (0.25 µg/day)-alone group (n=20). All the patients had received PSL and the clinical characteristics were compared between the two groups at baseline and at 12 months. A significant decrease of the mean bone mineral density (BMD) of the lumbar spine from 0.710±0.162 (g/cm(2)) to 0.588±0.125 was observed in the alfacalcidol-alone group (p=0.02), while no such decrease of the bone mineral density was found in the risedronate + alfacalcidol group (0.663±0.169 at baseline and 0.626±0.129 at 12 months). No significant differences in the results of other biochemical tests performed at the baseline and at 12 months were observed between the two groups. The likelihood of development of steroid-induced osteoporosis was influenced by the cumulative dose of PSL, the mean BMD at the baseline, occurrence of disease relapse, and risedronate therapy. Risedronate appears to be effective in preventing steroid-induced osteoporosis. It is necessary to use bisphosphonates to maintain the BMD in patients with MCNS receiving prolonged steroid therapy.

Bone density loss after allogeneic hematopoietic stem cell transplantation: a prospective study.

PubMed

Stern, J M; Sullivan, K M; Ott, S M; Seidel, K; Fink, J C; Longton, G; Sherrard, D J

2001-01-01

The incidence and course of bone density abnormalities following hematopoietic stem cell transplantation are poorly understood and complicated by the impact of multiple factors. Hip, spine, and wrist bone mineral densities (BMDs) were measured in 104 adults (54 women, 54 men; mean age, 40 years [range, 18-64 years]) at 3 and 12 months after allogeneic transplantation. Clinical and laboratory variables were evaluated using univariate and multivariate analyses to determine risk factors for osteoporosis, fracture, and avascular necrosis. At 3 months posttransplantation, combined (male and female) hip, spine, and wrist z scores were -0.35, -0.42, and +0.04 standard deviations, respectively. At 12 months both men and women experienced significant loss of hip BMD (4.2%, P < .0001); changes in the spine and wrist were minimal. The cumulative dose and number of days of glucocorticoid therapy and the number of days of cyclosporine or tacrolimus therapy showed significant associations with loss of BMD; age, total body irradiation, diagnosis, and donor type did not. Nontraumatic fractures occurred in 10.6% of patients and avascular necrosis in 9.6% within 3 years posttransplantation. The decrease in height between pretransplantation and 12 months posttransplantation was significant (P = .0001). Results indicate that loss of BMD after allogeneic stem cell transplantation is common and accelerated by the length of immunosuppressive therapy and cumulative dose of glucocorticoid. An increased incidence of fracture and avascular necrosis may adversely impact long-term quality of life. Prevention of bone demineralization appears warranted after stem cell transplantation.

Whole Body Vibration Treatments in Postmenopausal Women Can Improve Bone Mineral Density: Results of a Stimulus Focussed Meta-Analysis.

PubMed

Fratini, Antonio; Bonci, Tecla; Bull, Anthony M J

2016-01-01

Whole body vibration treatment is a non-pharmacological intervention intended to stimulate muscular response and increase bone mineral density, particularly for postmenopausal women. The literature related to this topic is controversial, heterogeneous, and unclear despite the prospect of a major clinical effect.The aim of this study was to identify and systematically review the literature to assess the effect of whole body vibration treatments on bone mineral density (BMD) in postmenopausal women with a specific focus on the experimental factors that influence the stimulus. Nine studies fulfilled the inclusion criteria, including 527 postmenopausal women and different vibration delivery designs. Cumulative dose, amplitudes and frequency of treatments as well as subject posture during treatment vary widely among studies. Some of the studies included an associated exercise training regime. Both randomized and controlled clinical trials were included. Whole body vibration was shown to produce significant BMD improvements on the hip and spine when compared to no intervention. Conversely, treatment associated with exercise training resulted in negligible outcomes when compared to exercise training or to placebo. Moreover, side-alternating platforms were more effective in improving BMD values than synchronous platforms and mechanical oscillations of magnitude higher than 3 g and/or frequency lower than 25 Hz were also found to be effective. Treatments with a cumulative dose over 1000 minutes in the follow-up period were correlated to positive outcomes.Our conclusion is that whole body vibration treatments in elderly women can reduce BMD decline.However, many factors (e.g., amplitude, frequency and subject posture) affect the capacity of the vibrations to propagate to the target site; the adequate level of stimulation required to produce these effects has not yet been defined. Further biomechanical analyses to predict the propagation of the vibration waves along the body and assess the stimulation levels are required.

Whole Body Vibration Treatments in Postmenopausal Women Can Improve Bone Mineral Density: Results of a Stimulus Focussed Meta-Analysis

PubMed Central

Bonci, Tecla; Bull, Anthony M. J.

2016-01-01

Whole body vibration treatment is a non-pharmacological intervention intended to stimulate muscular response and increase bone mineral density, particularly for postmenopausal women. The literature related to this topic is controversial, heterogeneous, and unclear despite the prospect of a major clinical effect.The aim of this study was to identify and systematically review the literature to assess the effect of whole body vibration treatments on bone mineral density (BMD) in postmenopausal women with a specific focus on the experimental factors that influence the stimulus. Nine studies fulfilled the inclusion criteria, including 527 postmenopausal women and different vibration delivery designs. Cumulative dose, amplitudes and frequency of treatments as well as subject posture during treatment vary widely among studies. Some of the studies included an associated exercise training regime. Both randomized and controlled clinical trials were included. Whole body vibration was shown to produce significant BMD improvements on the hip and spine when compared to no intervention. Conversely, treatment associated with exercise training resulted in negligible outcomes when compared to exercise training or to placebo. Moreover, side-alternating platforms were more effective in improving BMD values than synchronous platforms and mechanical oscillations of magnitude higher than 3 g and/or frequency lower than 25 Hz were also found to be effective. Treatments with a cumulative dose over 1000 minutes in the follow-up period were correlated to positive outcomes.Our conclusion is that whole body vibration treatments in elderly women can reduce BMD decline.However, many factors (e.g., amplitude, frequency and subject posture) affect the capacity of the vibrations to propagate to the target site; the adequate level of stimulation required to produce these effects has not yet been defined. Further biomechanical analyses to predict the propagation of the vibration waves along the body and assess the stimulation levels are required. PMID:27907000

Effect of high-dose vitamin D supplementation on bone density in youth with osteogenesis imperfecta: A randomized controlled trial.

PubMed

Plante, Laura; Veilleux, Louis-Nicolas; Glorieux, Francis H; Weiler, Hope; Rauch, Frank

2016-05-01

Osteogenesis imperfecta (OI) is a heritable condition characterized by fragile bones. Our previous studies indicated that serum 25-hydroxyvitamin D (25OHD) concentrations were positively associated with lumbar spine areal bone mineral density (LS-aBMD) in children and adolescents with OI. Here we assessed whether one year of high-dose vitamin D supplementation results in higher LS-aBMD z-scores in youth with OI. A one-year double-blind randomized controlled trial conducted at a pediatric orthopedic hospital in Montreal, Canada. Sixty patients (age: 6.0 to 18.9years; 35 female) were randomized in equal numbers to receive either 400 or 2000international units (IU) of vitamin D, stratified according to baseline bisphosphonate treatment status and pubertal stage. At baseline, the average serum 25OHD concentration was 65.6nmol/L (SD 20.4) with no difference between treatment groups (p=0.77); 21% of patients had results <50nmol/L. Vitamin D supplementation was associated with higher serum 25OHD concentrations in 90% of participants. The increase in mean 25OHD was significantly higher (p=0.02) in the group receiving 2000IU of vitamin D (mean [95% CI]=30.5nmol/L [21.3; 39.6]) than in the group receiving 400IU (15.2nmol/L [6.4; 24.1]). No significant differences in LS-aBMD z-score changes were detected between treatment groups. Thus, supplementation with vitamin D at 2000IU increased serum 25OHD concentrations in children with OI more than supplementation with 400IU. However, in this study where about 80% of participants had baseline serum 25OHD concentrations ≥50nmol/L, this difference had no detectable effect on LS-aBMD z-scores. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparative Effects of Teriparatide and Risedronate in Glucocorticoid-Induced Osteoporosis in Men: 18-Month Results of the EuroGIOPs Trial

PubMed Central

Glüer, Claus-C; Marin, Fernando; Ringe, Johann D; Hawkins, Federico; Möricke, Rüdiger; Papaioannu, Nikolaos; Farahmand, Parvis; Minisola, Salvatore; Martínez, Guillermo; Nolla, Joan M; Niedhart, Christopher; Guañabens, Nuria; Nuti, Ranuccio; Martín-Mola, Emilio; Thomasius, Friederike; Kapetanos, Georgios; Peña, Jaime; Graeff, Christian; Petto, Helmut; Sanz, Beatriz; Reisinger, Andreas; Zysset, Philippe K

2013-01-01

Data on treatment of glucocorticoid-induced osteoporosis (GIO) in men are scarce. We performed a randomized, open-label trial in men who have taken glucocorticoids (GC) for ≥3 months, and had an areal bone mineral density (aBMD) T-score ≤ –1.5 standard deviations. Subjects received 20 μg/d teriparatide (n = 45) or 35 mg/week risedronate (n = 47) for 18 months. Primary objective was to compare lumbar spine (L1–L3) BMD measured by quantitative computed tomography (QCT). Secondary outcomes included BMD and microstructure measured by high-resolution QCT (HRQCT) at the 12th thoracic vertebra, biomechanical effects for axial compression, anterior bending, and axial torsion evaluated by finite element (FE) analysis from HRQCT data, aBMD by dual X-ray absorptiometry, biochemical markers, and safety. Computed tomography scans were performed at 0, 6, and 18 months. A mixed model repeated measures analysis was performed to compare changes from baseline between groups. Mean age was 56.3 years. Median GC dose and duration were 8.8 mg/d and 6.4 years, respectively; 39.1% of subjects had a prevalent fracture, and 32.6% received prior bisphosphonate treatment. At 18 months, trabecular BMD had significantly increased for both treatments, with significantly greater increases with teriparatide (16.3% versus 3.8%; p = 0.004). HRQCT trabecular and cortical variables significantly increased for both treatments with significantly larger improvements for teriparatide for integral and trabecular BMD and bone surface to volume ratio (BS/BV) as a microstructural measure. Vertebral strength increases at 18 months were significant in both groups (teriparatide: 26.0% to 34.0%; risedronate: 4.2% to 6.7%), with significantly higher increases in the teriparatide group for all loading modes (0.005 < p < 0.015). Adverse events were similar between groups. None of the patients on teriparatide but five (10.6%) on risedronate developed new clinical fractures (p = 0.056). In conclusion, in this 18-month trial in men with GIO, teriparatide showed larger improvements in spinal BMD, microstructure, and FE-derived strength than risedronate. PMID:23322362

Association of stressful life events with accelerated bone loss in older men: the Osteoporotic Fractures in Men (MrOS) Study

PubMed Central

Fink, Howard A.; Kuskowski, Michael A.; Cauley, Jane A.; Taylor, Brent C.; Schousboe, John T.; Cawthon, Peggy M.; Ensrud, Kristine E.

2015-01-01

Purpose/Introduction Prior studies suggest that stressful life events may increase adverse health outcomes, including falls and possibly fractures. The current study builds on these findings and examines whether stressful life events are associated with increased bone loss. Methods 4388 men aged ≥65 years in the Osteoporotic Fractures in Men study completed total hip bone mineral density (BMD) measures at baseline and visit 2, approximately 4.6 years later, and self-reported stressful life events data mid-way between baseline and visit 2, and at visit 2. We used linear regression to model the association of stressful life events with concurrent annualized total hip BMD loss, and log binomial regression or Poisson regression to model risk of concurrent accelerated BMD loss (>1 SD more than mean annualized change). Results 75.3% of men reported ≥1 type of stressful life event, including 43.3% with ≥2 types of stressful life events. Mean annualized BMD loss was −0.36% (SD 0.88) and 13.9% of men were categorized with accelerated BMD loss (about 5.7% or more total loss). Rate of annualized BMD loss increased with the number of types of stressful life events after adjustment for age (p<0.001), but not after multivariable adjustment (p=0.07). Multivariable-adjusted risk of accelerated BMD loss increased with the number of types of stressful life events (RR, 1.10 [95% CI, 1.04–1.16]) per increase of 1 type of stressful life event). Fracture risk was not significantly different between stressful life event-accelerated bone loss subgroups (p=0.08). Conclusions In these older men, stressful life events were associated with a small, dose-related increase in risk of concurrent accelerated hip bone loss. Low frequency of fractures limited assessment of whether rapid bone loss mediates any association of stressful life events with incident fractures. Future studies are needed to confirm these findings and to investigate the mechanism that may underlie this association. PMID:25169421

Evaluation of Automated Fracture Risk Assessment Based on the Canadian Association of Radiologists and Osteoporosis Canada Assessment Tool.

PubMed

Allin, Sonya; Bleakney, Robert; Zhang, Julie; Munce, Sarah; Cheung, Angela M; Jaglal, Susan

2016-01-01

Fracture risk assessments are not always clearly communicated on bone mineral density (BMD) reports; evidence suggests that structured reporting (SR) tools may improve report clarity. The aim of this study is to compare fracture risk assessments automatically assigned by SR software in accordance with Canadian Association of Radiologists and Osteoporosis Canada (CAROC) recommendations to assessments from experts on narrative BMD reports. Charts for 500 adult patients who recently received a BMD exam were sampled from across University of Toronto's Joint Department of Medical Imaging. BMD measures and clinical details were manually abstracted from charts and were used to create structured reports with assessments generated by a software implementation of CAROC recommendations. CAROC calculations were statistically compared to experts' original assessments using percentage agreement (PA) and Krippendorff's alpha. Canadian FRAX calculations were also compared to experts', where possible. A total of 25 (5.0%) reported assessments did not conform to categorizations recommended by Canadian guidelines. Across the remainder, the Krippendorff's alpha relating software assigned assessments to physicians was high at 0.918; PA was 94.3%. Lower agreement was associated with reports for patients with documented modifying factors (alpha = 0.860, PA = 90.2%). Similar patterns of agreement related expert assessments to FRAX calculations, although statistics of agreement were lower. Categories of disagreement were defined by (1) gray areas in current guidelines, (2) margins of assessment categorizations, (3) dictation/transcription errors, (4) patients on low doses of steroids, and (5) ambiguous documentation of modifying factors. Results suggest that SR software can produce fracture risk assessments that agree with experts on most routine, adult BMD exams. Results also highlight situations where experts tend to diverge from guidelines and illustrate the potential for SR software to (1) reduce variability in, (2) ameliorate errors in, and (3) improve clarity of routine adult BMD exam reports. Copyright © 2016 International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Therapy of Hypoparathyroidism With PTH(1–84): A Prospective Six Year Investigation of Efficacy and Safety

PubMed Central

Cusano, Natalie E.; Fan, Wen-Wei; Delgado, Yasmine; Zhang, Chengchen; Costa, Aline G.; Cremers, Serge; Dworakowski, Elzbieta; Bilezikian, John P.

2016-01-01

Context: Human recombinant (rh)PTH(1–84) was recently approved for the treatment of refractory hypoparathyroidism, based upon a short-term phase 3 clinical trial. Long-term data are needed, because no time limit was placed on the treatment period. Objective: We studied the effect of long-term rhPTH(1–84) treatment in hypoparathyroidism for up to 6 years. Design: Prospective open-label study. Setting: Referral center. Patients: A total of 33 subjects with hypoparathyroidism. Interventions: rhPTH(1–84) treatment was initiated at a starting dose of 100 μg every other day for 6 years. Due to the availability of new dosages during the 6-year time period of the study, the dose could be and was adjusted for most patients to a daily dosing regimen. Main Outcome Measures: Supplemental calcium and vitamin D requirements, serum and urinary calcium (monthly for 6 mo and then biannually), serum phosphorus, bone turnover markers, and bone mineral density (BMD) biannually. Results: Treatment with rhPTH(1–84) progressively reduced supplemental calcium requirements over 6 years by 53% (P < .0001) and 1,25-dihydroxyvitamin D requirements by 67% (P < .0001). Sixteen subjects (48%) were able to eliminate 1,25-dihydroxyvitamin D supplementation completely. Serum calcium concentration remained stable, and urinary calcium excretion fell. Lumbar spine BMD increased (3.8 ± 1%, P = .004) as did total hip BMD (2.4 ± 1%, P = .02), whereas femoral neck BMD remained stable and the distal one third radius decreased (−4.4 ±1%, P < .0001). Bone turnover markers increased significantly, reaching a 3-fold peak above baseline values at 1 year and subsequently declining but remaining higher than pretreatment values. Hypercalcemia was uncommon (12 episodes over 6 y; 2.5% of all values). Conclusions: Long-term, continuous therapy of hypoparathyroidism for 6 years with rhPTH(1–84) is associated with reductions in supplemental calcium and calcitriol requirements, stable serum calcium concentration, and reduced urinary calcium excretion. The safety profile remains good. These data represent the longest experience with the therapeutic use of PTH for any condition and demonstrate its long-term efficacy and safety in hypoparathyroidism. PMID:27144931

Benchmarking pediatric cranial CT protocols using a dose tracking software system: a multicenter study.

PubMed

De Bondt, Timo; Mulkens, Tom; Zanca, Federica; Pyfferoen, Lotte; Casselman, Jan W; Parizel, Paul M

2017-02-01

To benchmark regional standard practice for paediatric cranial CT-procedures in terms of radiation dose and acquisition parameters. Paediatric cranial CT-data were retrospectively collected during a 1-year period, in 3 different hospitals of the same country. A dose tracking system was used to automatically gather information. Dose (CTDI and DLP), scan length, amount of retakes and demographic data were stratified by age and clinical indication; appropriate use of child-specific protocols was assessed. In total, 296 paediatric cranial CT-procedures were collected. Although the median dose of each hospital was below national and international diagnostic reference level (DRL) for all age categories, statistically significant (p-value < 0.001) dose differences among hospitals were observed. The hospital with lowest dose levels showed smallest dose variability and used age-stratified protocols for standardizing paediatric head exams. Erroneous selection of adult protocols for children still occurred, mostly in the oldest age-group. Even though all hospitals complied with national and international DRLs, dose tracking and benchmarking showed that further dose optimization and standardization is possible by using age-stratified protocols for paediatric cranial CT. Moreover, having a dose tracking system revealed that adult protocols are still applied for paediatric CT, a practice that must be avoided. • Significant differences were observed in the delivered dose between age-groups and hospitals. • Using age-adapted scanning protocols gives a nearly linear dose increase. • Sharing dose-data can be a trigger for hospitals to reduce dose levels.

Dose specification for hippocampal sparing whole brain radiotherapy (HS WBRT): considerations from the UK HIPPO trial QA programme.

PubMed

Megias, Daniel; Phillips, Mark; Clifton-Hadley, Laura; Harron, Elizabeth; Eaton, David J; Sanghera, Paul; Whitfield, Gillian

2017-03-01

The HIPPO trial is a UK randomized Phase II trial of hippocampal sparing (HS) vs conventional whole-brain radiotherapy after surgical resection or radiosurgery in patients with favourable prognosis with 1-4 brain metastases. Each participating centre completed a planning benchmark case as part of the dedicated radiotherapy trials quality assurance programme (RTQA), promoting the safe and effective delivery of HS intensity-modulated radiotherapy (IMRT) in a multicentre trial setting. Submitted planning benchmark cases were reviewed using visualization for radiotherapy software (VODCA) evaluating plan quality and compliance in relation to the HIPPO radiotherapy planning and delivery guidelines. Comparison of the planning benchmark data highlighted a plan specified using dose to medium as an outlier by comparison with those specified using dose to water. Further evaluation identified that the reported plan statistics for dose to medium were lower as a result of the dose calculated at regions of PTV inclusive of bony cranium being lower relative to brain. Specification of dose to water or medium remains a source of potential ambiguity and it is essential that as part of a multicentre trial, consideration is given to reported differences, particularly in the presence of bone. Evaluation of planning benchmark data as part of an RTQA programme has highlighted an important feature of HS IMRT dosimetry dependent on dose being specified to water or medium, informing the development and undertaking of HS IMRT as part of the HIPPO trial. Advances in knowledge: The potential clinical impact of differences between dose to medium and dose to water are demonstrated for the first time, in the setting of HS whole-brain radiotherapy.

The association between serum dehydroepiandrosterone Sulphate (DHEA-S) level and bone mineral density in Korean men.

PubMed

Lee, Dain; Kim, Hyeonmok; Ahn, Seong Hee; Lee, Seung Hun; Bae, Sung Jin; Kim, Eun Hee; Kim, Hong-Kyu; Choe, Jae Won; Kim, Beom-Jun; Koh, Jung-Min

2015-08-01

Many lines of evidence indicate that dehydroepiandrosterone (DHEA) plays a distinct role in bone metabolism and that its sulphated form (DHEA-S), which is easily measured in blood, may be a potential biomarker of osteoporosis-related phenotypes. However, most previous epidemiologic studies focused on postmenopausal women and reported conflicting results. We aimed to investigate the association between the serum DHEA-S level and bone mass in men. This large cross-sectional study included 1089 healthy Korean men who participated in a routine health screening examination. Bone mineral density (BMD) at the lumbar spine, total femur, femur neck, and trochanter and serum DHEA-S level were obtained in all subjects. After adjustment for age, body mass index, lifestyle factors and serum levels of calcium, phosphorus, testosterone, 25-OH-vitamin D3 and cortisol, higher serum DHEA-S concentrations were associated with higher BMD values at all skeletal sites. Consistently, compared to the subjects in the highest DHEA-S quartile (Q4), those in the lowest DHEA-S quartile (Q1) showed significantly lower BMD values. Multiple logistic regression analyses revealed that the odds ratios for the risk of lower BMD (T-score <-1) increased in a dose-dependent manner across decreasing DHEA-S quartiles and the odds for the risk of lower BMD were 2·59-fold higher in Q1 than in Q4. These findings support previous evidences that DHEA-S has favourable effects on bone mass in men and suggest that a low serum DHEA-S level may be a potential risk factor for male osteoporosis. © 2015 John Wiley & Sons Ltd.

Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy.

PubMed

Martin, Elizabeth A; Barresi, Rita; Byrne, Barry J; Tsimerinov, Evgeny I; Scott, Bryan L; Walker, Ashley E; Gurudevan, Swaminatha V; Anene, Francine; Elashoff, Robert M; Thomas, Gail D; Victor, Ronald G

2012-11-28

Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. Like Duchenne muscular dystrophy (DMD), BMD is caused by mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the muscle sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires certain spectrin-like repeats in dystrophin's rod domain and the adaptor protein α-syntrophin to be targeted to the sarcolemma. When healthy skeletal muscle is subjected to exercise, sarcolemmal nNOSμ-derived NO attenuates local α-adrenergic vasoconstriction, thereby optimizing perfusion of muscle. We found previously that this protective mechanism is defective-causing functional muscle ischemia-in dystrophin-deficient muscles of the mdx mouse (a model of DMD) and of children with DMD, in whom nNOSμ is mislocalized to the cytosol instead of the sarcolemma. We report that this protective mechanism also is defective in men with BMD in whom the most common dystrophin mutations disrupt sarcolemmal targeting of nNOSμ. In these men, the vasoconstrictor response, measured as a decrease in muscle oxygenation, to reflex sympathetic activation is not appropriately attenuated during exercise of the dystrophic muscles. In a randomized placebo-controlled crossover trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation is fully restored in the muscles of men with BMD by boosting NO-cGMP (guanosine 3',5'-monophosphate) signaling with a single dose of the drug tadalafil, a phosphodiesterase 5A inhibitor. These results further support an essential role for sarcolemmal nNOSμ in the normal modulation of sympathetic vasoconstriction in exercising human skeletal muscle and implicate the NO-cGMP pathway as a putative new target for treating BMD.

Effects of atorvastatin on bone mineral density (BMD) and bone metabolism in elderly males with osteopenia and mild dyslipidemia: a 1-year randomized trial.

PubMed

Chen, Zhi-guo; Cai, Hua-jie; Jin, Xian; Lu, Jin-hua; Wang, Jing; Fang, Ning-yuan

2014-01-01

We explored the effects of atorvastatin on BMD and biochemical markers of bone metabolism in a 1-year, prospective, randomized controlled study. 64 male patients with osteopenia and mild dyslipidemia (mean age 80.1±6.6 years) were randomized to a 1-year atorvastatin treatment or control. BMD of hip and lumbar spine was measured with dual-energy X-ray absorptionmetry (DXA). Bone metabolic markers including resorption markers β-c-terminal telopeptide of type I collagen (CTx), formative markers osteocalcin (OC), 25-hydroxyvitamin D (25(OH)D) were measured with electrochemiluminescence immunoassay (ECLIA). Other bone metabolism markers including intact parathyroid hormone (iPTH) and testosterone were measured with chemiluminescence enzyme immunoassay (CLEIA). Levels of serum lipid and biochemical parameters were measured with automatic biochemical analyzer. All the parameters were recorded at baseline, and at 6 and 12 months, respectively. Compared with the control group, the atorvastatin treatment group showed significant reduction of triglyceride (TG, P<0.01) and low-density lipoprotein cholesterol (LDL-C, P<0.01). At 12 month, total hip BMD in atorvastatin group was significantly higher (P<0.01) compared with the control group, while there were no similar effect on femoral neck or lumbar spine between the two groups (P=0.48 and 0.53 respectively). Meanwhile, CTx significantly reduced in atorvastatin treatment group (P<0.001) compared with baseline. Our findings suggest that in elderly male patients with osteopenia and mild dyslipidemia, therapeutic doses of atorvastatin were associated with positive effects on BMD, probably mediated by suppressed bone resorption. Copyright © 2014. Published by Elsevier Ireland Ltd.

Subclinical hypervitaminosis A in rat: measurements of bone mineral density (BMD) do not reveal adverse skeletal changes.

PubMed

Lind, P M; Johansson, S; Rönn, M; Melhus, H

2006-01-05

We have previously shown that subclinical hypervitaminosis A in rats causes fragile bones. To begin to investigate possible mechanisms for Vitamin A action we extended our previous study. Forty-five mature female Sprague-Dawley rats were divided into three groups, each with 15 animals. They were fed a standard diet containing 12IU Vitamin A per g pellet (control, C), or a standard diet supplemented with 120 IU ("10xC") or 600 IU ("50xC") Vitamin A/g pellet for 12 weeks. At the end of the study, serum retinyl esters were elevated 4- and 20-fold. Although neither average food intake nor final body weights were significantly different between groups, a dose-dependent reduction in serum levels of Vitamin D and E, but not Vitamin K, was found. In the 50xC-group the length of the humerus was the same as in controls, but the diameter was reduced (-4.1%, p<0.05). Peripheral quantitative computed tomography (pQCT) at the diaphysis showed that bone mineral density (BMD) was unchanged and that periosteal circumference had decreased significantly (-3.7%, p<0.05). Ash weight of the humerus was not affected, but since bone volume decreased, volumetric BMD, as measured by the bone ash method, even increased (+2.5%, p<0.05). In conclusion, interference with other fat-soluble Vitamins is a possible indirect mechanism of Vitamin A action. Moreover, BMD measurements do not reveal early adverse skeletal changes induced by moderate excesses of Vitamin A in rats. Since the WHO criterium for osteoporosis is based on BMD, further studies are warranted to examine whether this is also true in humans.

Early myocardial damage assessment in dystrophinopathies using (99)Tc(m)-MIBI gated myocardial perfusion imaging.

PubMed

Zhang, Li; Liu, Zhe; Hu, Ke-You; Tian, Qing-Bao; Wei, Ling-Ge; Zhao, Zhe; Shen, Hong-Rui; Hu, Jing

2015-01-01

Early detection of muscular dystrophy (MD)-associated cardiomyopathy is important because early medical treatment may slow cardiac remodeling and attenuate symptoms of cardiac dysfunction; however, no sensitive and standard diagnostic method for MD at an earlier stage has been well-recognized. Thus, the aim of this study was to test the early diagnostic value of technetium 99m-methoxyisobutylisonitrile ((99)Tc(m)-MIBI) gated myocardial perfusion imaging (G-MPI) for MD. Ninety-one patients underwent (99)Tc(m)-MIBI G-MPI examinations when they were diagnosed with Duchenne muscular dystrophy (DMD) (n=77) or Becker muscular dystrophy (BMD; n=14). (99)Tc(m)-MIBI G-MPI examinations were repeated in 43 DMD patients who received steroid treatments for 2 years as a follow-up examination. Myocardial defects were observed in nearly every segment of the left ventricular wall in both DMD and BMD patients compared with controls, especially in the inferior walls and the apices by using (99)Tc(m)-MIBI G-MPI. Cardiac wall movement impairment significantly correlated with age in the DMD and BMD groups (r s=0.534 [P<0.05] and r s=0.784 [P<0.05], respectively). Intermittent intravenous doses of glucocorticoids and continuation with oral steroid treatments significantly improved myocardial function in DMD patients (P<0.05), but not in BMD patients. (99)Tc(m)-MIBI G-MPI is a sensitive and safe approach for early evaluation of cardiomyopathy in patients with DMD or BMD, and can serve as a candidate method for the evaluation of progression, prognosis, and assessment of the effect of glucocorticoid treatment in these patients.

Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy

PubMed Central

Martin, Elizabeth A.; Barresi, Rita; Byrne, Barry J.; Tsimerinov, Evgeny I.; Scott, Bryan L.; Walker, Ashley E.; Gurudevan, Swaminatha V.; Anene, Francine; Elashoff, Robert M.; Thomas, Gail D.; Victor, Ronald G.

2013-01-01

Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. Like Duchenne muscular dystrophy (DMD), BMD is caused by mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the muscle sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires certain spectrin-like repeats in dystrophin’s rod domain and the adaptor protein α-syntrophin to be targeted to the sarcolemma. When healthy skeletal muscle is subjected to exercise, sarcolemmal nNOSμ-derived nitric oxide (NO) attenuates local α-adrenergic vasoconstriction thereby optimizing perfusion of muscle. We found previously that this protective mechanism is defective—causing functional muscle ischemia—in dystrophin-deficient muscles of the mdx mouse (a model of DMD) and of children with DMD, in whom nNOSμ is mislocalized to the cytosol instead of the sarcolemma. Here, we report that this protective mechanism also is defective in men with BMD in whom the most common dystrophin mutations disrupt sarcolemmal targeting of nNOSμ. In these men, the vasoconstrictor response, measured as a decrease in muscle oxygenation, to reflex sympathetic activation is not appropriately attenuated during exercise of the dystrophic muscles. In a randomized placebo-controlled cross-over trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation fully restored in the muscles of men with BMD by boosting NO-cGMP signaling with a single dose of the drug tadalafil, a phosphodiesterase (PDE5A) inhibitor. These results further support an essential role for sarcolemmal nNOSμ in the normal modulation of sympathetic vasoconstriction in exercising human skeletal muscle and implicate the NO-cGMP pathway as a putative new target for treating BMD. PMID:23197572

Meeting The Joint Commission's Dose Incident Identification and External Benchmarking Requirements Using the ACR's Dose Index Registry.

PubMed

Bohl, Michael A; Goswami, Roopa; Strassner, Brett; Stanger, Paula

2016-08-01

The purpose of this investigation was to evaluate the potential of using the ACR's Dose Index Registry(®) to meet The Joint Commission's requirements to identify incidents in which the radiation dose index from diagnostic CT examinations exceeded the protocol's expected dose index range. In total, 10,970 records in the Dose Index Registry were statistically analyzed to establish both an upper and lower expected dose index for each protocol. All 2015 studies to date were then retrospectively reviewed to identify examinations whose total examination dose index exceeded the protocol's defined upper threshold. Each dose incident was then logged and reviewed per the new Joint Commission requirements. Facilities may leverage their participation in the ACR's Dose Index Registry to fully meet The Joint Commission's dose incident identification review and external benchmarking requirements. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Effects of Bisphosphonates and Calcium plus Vitamin-D Supplements on Cognitive Function in Postmenopausal Osteoporosis§.

PubMed

Safer, Umut; Safer, Vildan Binay; Demir, Sibel Ozbudak; Yanikoglu, Inci

2016-01-01

Postmenopausal osteoporosis has been linked to accelerated cognitive decline; however, little is known about the effects of medical treatment on cognitive functions. In this prospective study, we evaluated the effects of bisphosphonate treatment and calcium plus vitamin D supplementation on cognitive functions in 45 women with postmenopausal osteoporosis who were started on medical treatment. The medications included alendronate, zoledronic acid, risedronate, or ibandronic acid along with a low or high dose of calcium plus vitamin D supplements. The cognitive function was assessed by the mini-mental state examination (MMSE) test. All subjects underwent bone mineral density (BMD) measurement via dual-energy X-ray absorptiometry at baseline and at study completion. The mean T-score improved significantly at 1 year, except for neck of the femur area. The mean MMSE score did not change significantly at 12 months (26.40 ± 2.07 vs. 26.48 ± 2.07; p = 0.513), with no difference among bisphosphonates combined with calcium plus vitamin D. Higher dose (1200 mg/800 U/day) of calcium plus vitamin D supplementation tended to have a greater improvement as compared with lower dose (600 mg/400 U/day) (Δ MMSE: 0.11 ± 0.72 vs. -0.14 ± 0.69). Cognitive functions in the women remained unaltered, whereas bone BMD T-scores were significantly improved at the 12(th) month after the administration of bisphosphonates and calcium plus vitamin D supplements. Higher doses of calcium plus vitamin D supplements were likely to have better cognitive effects as compared with lower doses.

ORANGE: a Monte Carlo dose engine for radiotherapy.

PubMed

van der Zee, W; Hogenbirk, A; van der Marck, S C

2005-02-21

This study presents data for the verification of ORANGE, a fast MCNP-based dose engine for radiotherapy treatment planning. In order to verify the new algorithm, it has been benchmarked against DOSXYZ and against measurements. For the benchmarking, first calculations have been done using the ICCR-XIII benchmark. Next, calculations have been done with DOSXYZ and ORANGE in five different phantoms (one homogeneous, two with bone equivalent inserts and two with lung equivalent inserts). The calculations have been done with two mono-energetic photon beams (2 MeV and 6 MeV) and two mono-energetic electron beams (10 MeV and 20 MeV). Comparison of the calculated data (from DOSXYZ and ORANGE) against measurements was possible for a realistic 10 MV photon beam and a realistic 15 MeV electron beam in a homogeneous phantom only. For the comparison of the calculated dose distributions and dose distributions against measurements, the concept of the confidence limit (CL) has been used. This concept reduces the difference between two data sets to a single number, which gives the deviation for 90% of the dose distributions. Using this concept, it was found that ORANGE was always within the statistical bandwidth with DOSXYZ and the measurements. The ICCR-XIII benchmark showed that ORANGE is seven times faster than DOSXYZ, a result comparable with other accelerated Monte Carlo dose systems when no variance reduction is used. As shown for XVMC, using variance reduction techniques has the potential for further acceleration. Using modern computer hardware, this brings the total calculation time for a dose distribution with 1.5% (statistical) accuracy within the clinical range (less then 10 min). This means that ORANGE can be a candidate for a dose engine in radiotherapy treatment planning.

Doping dose of salbutamol and exercise training: impact on the skeleton of ovariectomized rats.

PubMed

Bonnet, N; Laroche, N; Beaupied, H; Vico, L; Dolleans, E; Benhamou, C L; Courteix, D

2007-08-01

Previous studies in healthy rats have demonstrated a deleterious bone impact of beta-agonist treatment. The purpose of this study was to examine the trabecular and cortical effects of beta(2)-agonists at doping dose on treadmill exercising rats with estrogen deficiency. Adult female rats were ovariectomized (OVX; n = 44) or sham operated (n = 12). Then, OVX rats received a subcutaneous injection of salbutamol (SAB) or vehicle with (EXE) or without treadmill exercise for 10 wk. Bone mineral density (BMD) was analyzed by densitometry. Microcomputed tomography and histomorphometric analysis were performed to study trabecular bone structure and bone cell activities. After 10 wk, SAB rats presented a much more marked decrease of BMD and trabecular parameters. Exercise did not change the high level of bone resorption in OVX EXE SAB compared with OVX SAB group (both on COOH-terminal collagen cross-links and osteoclast number). These results confirm the deleterious effect of beta(2)-agonists on bone quantity (femoral BMD gain: OVX EXE, +6.8%, vs. OVX EXE SAB, -1.8%; P < 0.01) and quality (-8.0% of femoral trabecular thickness in OVX EXE SAB vs. OVX EXE), indicating that SAB suppresses the effect of EXE in OVX rats. Furthermore, we notice that the slight beneficial effect of exercise was mainly localized in the tibia. These findings indicate the presence of a bone alteration threshold below which there is no more alteration in structural bone quantity and quality. The negative effects of SAB on bone observed in this study in trained rats may indicate potential complications in doping female athletes with exercise-induced amenorrhea.

A comparison of DXA and CT based methods for estimating the strength of the femoral neck in post-menopausal women

PubMed Central

Danielson, Michelle E.; Beck, Thomas J.; Karlamangla, Arun S.; Greendale, Gail A.; Atkinson, Elizabeth J.; Lian, Yinjuan; Khaled, Alia S.; Keaveny, Tony M.; Kopperdahl, David; Ruppert, Kristine; Greenspan, Susan; Vuga, Marike; Cauley, Jane A.

2013-01-01

Purpose Simple 2-dimensional (2D) analyses of bone strength can be done with dual energy x-ray absorptiometry (DXA) data and applied to large data sets. We compared 2D analyses to 3-dimensional (3D) finite element analyses (FEA) based on quantitative computed tomography (QCT) data. Methods 213 women participating in the Study of Women’s Health across the Nation (SWAN) received hip DXA and QCT scans. DXA BMD and femoral neck diameter and axis length were used to estimate geometry for composite bending (BSI) and compressive strength (CSI) indices. These and comparable indices computed by Hip Structure Analysis (HSA) on the same DXA data were compared to indices using QCT geometry. Simple 2D engineering simulations of a fall impacting on the greater trochanter were generated using HSA and QCT femoral neck geometry; these estimates were benchmarked to a 3D FEA of fall impact. Results DXA-derived CSI and BSI computed from BMD and by HSA correlated well with each other (R= 0.92 and 0.70) and with QCT-derived indices (R= 0.83–0.85 and 0.65–0.72). The 2D strength estimate using HSA geometry correlated well with that from QCT (R=0.76) and with the 3D FEA estimate (R=0.56). Conclusions Femoral neck geometry computed by HSA from DXA data corresponds well enough to that from QCT for an analysis of load stress in the larger SWAN data set. Geometry derived from BMD data performed nearly as well. Proximal femur breaking strength estimated from 2D DXA data is not as well correlated with that derived by a 3D FEA using QCT data. PMID:22810918

Intermittent minodronic acid treatment with sufficient bone resorption inhibition prevents reduction in bone mass and strength in ovariectomized rats with established osteopenia comparable with daily treatment.

PubMed

Kimoto, Aishi; Tanaka, Makoto; Nozaki, Kazutoshi; Mori, Masamichi; Fukushima, Shinji; Mori, Hiroshi; Shiroya, Tsutomu; Nakamura, Toshitaka

2013-07-01

This study examined and compared the effects of four-week intermittent and daily administrations of minodronic acid, a highly potent nitrogen-containing bisphosphonate, on bone mineral density (BMD), bone strength, bone turnover, and histomorphometry on established osteopenia in ovariectomized (OVX) rats. Fourteen-week-old female F344 rats were OVX or sham-operated. At 12 weeks post surgery, minodronic acid was orally administered once every 4 weeks at 0.2, 1, and 5 mg/kg and once daily at 0.006, 0.03, and 0.15 mg/kg for 12 months. The total dosing amount was comparable between the two dosing regimens. The levels of urinary deoxypyridinoline and serum osteocalcin were measured to assess bone turnover. BMD as assessed via dual-energy X-ray absorptiometry, bone structure and dynamical changes in vertebral trabecula and biomechanical properties were measured ex vivo at 12 months to assess bone content and material properties. Minodronic acid dose-dependently ameliorated the decrease in BMD of lumbar vertebrae and the femur in both treatment regimens similarly. Minodronic acid suppressed elevated urinary levels of deoxypyridinoline, a bone resorption marker, and reduced the serum levels of osteocalcin, a bone formation marker. In the mechanical test at 12 months of treatment, minodronic acid dose-dependently ameliorated the reduction in bone strength in femur and vertebral body. There is no significant difference in parameters between the two regimens except maximal load of lower doses in lumbar vertebral body and absorption energy of middle doses in femur. With these parameters with significant differences, values of the intermittent regimen were significantly lower than that of daily repeated regimen. Bone histomorphometric analysis of the lumbar vertebral body showed that minodronic acid significantly ameliorated the decrease in bone mass, trabecular thickness and number, and the increase in trabecular separation, bone resorption indices (Oc.S/BS and N.Oc/BS), and bone formation indices (BFR/BS, MAR and OV/BV) in both regimens. Minodronic acid suppressed OVX-induced increases in bone turnover at the tissue level and ameliorated all structural indices, thereby improving the deterioration of bone quality under osteoporotic disease conditions regardless of the regimen. In conclusion, a four-week intermittent treatment of minodronic acid suppressed increased bone resorption as daily treatment when considering the total administered dose in OVX rats with established osteopenia. The improvement of microarchitectural destruction in low dose of intermittent treatment was weaker than that observed in a daily repeated regimen; however the effects of high and middle doses of intermittent treatment were equivalent to that observed in daily repeated regimen accompanied by sufficient bone resorption inhibition in rats. These findings suggest that minodronic acid at an appropriate dose in an intermittent regimen may be as clinically useful in osteoporosis therapy as in daily treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

High-energy neutron depth-dose distribution experiment.

PubMed

Ferenci, M S; Hertel, N E

2003-01-01

A unique set of high-energy neutron depth-dose benchmark experiments were performed at the Los Alamos Neutron Science Center/Weapons Neutron Research (LANSCE/WNR) complex. The experiments consisted of filtered neutron beams with energies up to 800 MeV impinging on a 30 x 30 x 30 cm3 liquid, tissue-equivalent phantom. The absorbed dose was measured in the phantom at various depths with tissue-equivalent ion chambers. This experiment is intended to serve as a benchmark experiment for the testing of high-energy radiation transport codes for the international radiation protection community.

Site-Specific Variations in Bone Mineral Density under Systemic Conditions Inducing Osteoporosis in Minipigs.

PubMed

Schulz, Matthias C; Kowald, Jan; Estenfelder, Sven; Jung, Roland; Kuhlisch, Eberhard; Eckelt, Uwe; Mai, Ronald; Hofbauer, Lorenz C; Stroszczynski, Christian; Stadlinger, Bernd

2017-01-01

Osteoporosis is a systemic bone disease with an increasing prevalence in the elderly population. There is conflicting opinion about whether osteoporosis affects the alveolar bone of the jaws and whether it poses a risk to the osseointegration of dental implants. The aim of the present study was to evaluate the effects of systemic glucocorticoid administration on the jaw bone density of minipigs. Thirty-seven adult female minipigs were randomly divided into two groups. Quantitative computed tomography (QCT) was used to assess bone mineral density BMD of the lumbar spine as well as the mandible and maxilla, and blood was drawn. One group of minipigs initially received 1.0 mg prednisolone per kg body weight daily for 2 months. The dose was tapered to 0.5 mg per kg body weight per day thereafter. The animals in the other group served as controls and received placebo. QCT and blood analysis were repeated after 6 and 9 months. BMD was compared between the two groups by measuring Hounsfield units, and serum levels of several bone metabolic markers were also assessed. A decrease in BMD was observed in the jaws from baseline to 9 months. This was more pronounced in the prednisolone group. Statistically significant differences were reached for the mandible ( p < 0.001) and the maxilla ( p < 0.001). The administration of glucocorticoids reduced the BMD in the jaws of minipigs. The described model shows promise in the evaluation of osseointegration of dental implants in bone that is compromised by osteoporosis.

Optimizing Radiation Doses for Computed Tomography Across Institutions: Dose Auditing and Best Practices.

PubMed

Demb, Joshua; Chu, Philip; Nelson, Thomas; Hall, David; Seibert, Anthony; Lamba, Ramit; Boone, John; Krishnam, Mayil; Cagnon, Christopher; Bostani, Maryam; Gould, Robert; Miglioretti, Diana; Smith-Bindman, Rebecca

2017-06-01

Radiation doses for computed tomography (CT) vary substantially across institutions. To assess the impact of institutional-level audit and collaborative efforts to share best practices on CT radiation doses across 5 University of California (UC) medical centers. In this before/after interventional study, we prospectively collected radiation dose metrics on all diagnostic CT examinations performed between October 1, 2013, and December 31, 2014, at 5 medical centers. Using data from January to March (baseline), we created audit reports detailing the distribution of radiation dose metrics for chest, abdomen, and head CT scans. In April, we shared reports with the medical centers and invited radiology professionals from the centers to a 1.5-day in-person meeting to review reports and share best practices. We calculated changes in mean effective dose 12 weeks before and after the audits and meeting, excluding a 12-week implementation period when medical centers could make changes. We compared proportions of examinations exceeding previously published benchmarks at baseline and following the audit and meeting, and calculated changes in proportion of examinations exceeding benchmarks. Of 158 274 diagnostic CT scans performed in the study period, 29 594 CT scans were performed in the 3 months before and 32 839 CT scans were performed 12 to 24 weeks after the audit and meeting. Reductions in mean effective dose were considerable for chest and abdomen. Mean effective dose for chest CT decreased from 13.2 to 10.7 mSv (18.9% reduction; 95% CI, 18.0%-19.8%). Reductions at individual medical centers ranged from 3.8% to 23.5%. The mean effective dose for abdominal CT decreased from 20.0 to 15.0 mSv (25.0% reduction; 95% CI, 24.3%-25.8%). Reductions at individual medical centers ranged from 10.8% to 34.7%. The number of CT scans that had an effective dose measurement that exceeded benchmarks was reduced considerably by 48% and 54% for chest and abdomen, respectively. After the audit and meeting, head CT doses varied less, although some institutions increased and some decreased mean head CT doses and the proportion above benchmarks. Reviewing institutional doses and sharing dose-optimization best practices resulted in lower radiation doses for chest and abdominal CT and more consistent doses for head CT.

Differential effect of predictors of bone mineral density and hip geometry in postmenopausal women: a cross-sectional study.

PubMed

Singh, Rekha; Gupta, Sushil; Awasthi, Ashish

2015-01-01

Osteoporosis is an important health problem in postmenopausal women. Lactation duration (LD), parity, menopause duration (MD), and body mass index (BMI) are important predictors of bone mineral density (BMD) and osteoporotic fractures in them. In addition, they have site-specific effects on BMD. Osteoporosis is especially prevalent in postmenopausal women. The aim of the study was to determine the effects of age, parity, LD, MD, and BMI on BMD at different sites and hip geometry in postmenopausal women. In this cross-sectional study, 87 women (45 years and above and at least 5 years postmenopausal) were enrolled. Subjects were divided into three parity groups (group 1: ≤ 2 children, group: 3-4 children, and group 3: > 4 children) and three LD groups (group 1: < 4 years, group 2: 4-8 years, and group 3: > 8 years). BMD was measured at neck of femur (BMD-NF), trochanter (BMD-TR), inter-trochanter (BMD-IT), spine (BMD-LS), and forearm (BMD-FA). Hip geometry was analyzed based on dual energy X-ray absorptiometry. One way ANOVA was used for comparisons of groups, and Bonferroni correction was used as post-hoc test. p value < 0.05 was considered significant. A significant difference in mean BMD was found between parity groups 1 and 3 at BMD-NF, BMD-TR, and BMD-LS, and between LD groups 1 and 3 at BMD-NF, BMD-TR, BMD-IT, and BMD-LS. Mean buckling ratio (BR) at IT was significantly different between parity groups 1 and 3, and LD groups 1 and 3. In multivariate regression analysis, BMI, age, and parity were significant predictors for BMD-NF; parity, BMI, and MD for BMD-TR; BMI, MD, and LD for BMD-IT; BMI and LD for BMD-LS; and age, LD, and BMI for BMD-FA. BMI and LD were significant predictors of IT-BR, while MD and BMI of narrow neck BR. MD, LD, parity, BMI, and age are important factors influencing BMD at hip and spine in postmenopausal women, and have site-specific effects on BMD.

Dienogest 2 mg Daily in the Treatment of Adolescents with Clinically Suspected Endometriosis: The VISanne Study to Assess Safety in ADOlescents.

PubMed

Ebert, Andreas D; Dong, Liying; Merz, Martin; Kirsch, Bodo; Francuski, Maja; Böttcher, Bettina; Roman, Horace; Suvitie, Pia; Hlavackova, Olga; Gude, Kerstin; Seitz, Christian

2017-10-01

To study the safety and efficacy of dienogest 2 mg in adolescents with suspected endometriosis. A 52-week, open-label, single-arm study. In 21 study centers, in 6 European countries. Adolescents aged 12 to younger than 18 years with clinically suspected or laparoscopically confirmed endometriosis. Dienogest 2 mg once daily. The primary end point was relative change in lumbar spine (L2-L4) bone mineral density (BMD) measured using dual-energy x-ray absorptiometry. A key secondary end point was change in endometriosis-associated pain assessed using a visual analogue scale. Of 120 patients screened, 111 comprised the full-analysis set (ie, patients who took ≥1 dose of study drug and had ≥1 post-treatment observation) and 97 (87.4%) completed the study. Mean lumbar BMD at baseline was 1.1046 (SD, 0.1550) g/cm 2 . At the end of dienogest treatment (EOT; defined as at 52 weeks or premature study discontinuation), mean relative change in BMD from baseline was -1.2% (SD, 2.3%; n = 103). Follow-up measurement 6 months after EOT in the subgroup with decreased BMD at EOT (n = 60) showed partial recovery in lumbar BMD (mean change from baseline: -2.3% at EOT, -0.6% 6 months after EOT). Mean endometriosis-associated pain score was 64.3 (SD, 19.1) mm at baseline and decreased to 9.0 (SD, 13.9) mm by week 48. In adolescents with suspected endometriosis, dienogest 2 mg for 52 weeks was associated with a decrease in lumbar BMD, followed by partial recovery after treatment discontinuation. Endometriosis-associated pain was substantially reduced during treatment. Because bone accretion is critical during adolescence, results of the VISanne study to assess safety in ADOlescents (VISADO) study highlights the need for tailored treatment in this population, taking into account the expected efficacy on endometriosis-associated pain and an individual's risk factors for osteoporosis. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

High degree of discordance between three-dimensional and two-dimensional lumbar spine bone mineral density in Turner's syndrome.

PubMed

Lage, Andrea Z; Brandão, Cynthia A; Mendes, Judite R T; Huayllas, Martha K; Liberman, Bernardo; Mendonça, Berenice B; Costa, Elaine M F; Verreschi, Ieda T; Lazaretti-Castro, Marise

2005-01-01

Low bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) has been described in Turner's syndrome (TS). One of the error factors of DXA is short stature, a common finding in TS patients. Aimed to evaluate the influence of a low stature on BMD, we compared the two-dimensional (2D) or conventional BMD (cBMD) with three-dimensional (3D) or volumetric BMD (vBMD) in 62 females (10 to 48 yr old) with TS diagnosis in a case control study. They were compared to 102 normal females (7 to 45 yr old) grouped by age-ranges. All patients were subjected to a lumbar spine densitometry by DXA in the PA and lateral projections, obtained the cBMD and vBMD and calculated for the apparent BMD (appBMD). In TS, the mean of Z-score for cBMD was significantly lower than that for vBMD and for appBMD (-2.31 +/- 1.42; -0.64 +/- 1.55; and -1.72 +/- 1.5; respectively). Most of the patients (83.8%) had a Z-score <-1 for cBMD, whereas the majority (58.1%) had a Z-score <-1 for vBMD. Concluding, the cBMD underestimates the bone mass of the lumbar spine in patients with TS inducing to false diagnoses of bone fragility. Volumetric BMD approached the bone mass of control patients, while appBMD just partially do that.

Effects of PTH (1-84) on bone quality in a validated model of osteoporosis due to androgenic deprivation.

PubMed

Martín-Fernández, Marta; Martínez, Elena; Díaz-Curiel, Manuel; Guede, David; Caeiro, José Ramón; De la Piedra, Concepción

2014-03-01

The purpose of this study was to evaluate the effect of parathyroid hormone (PTH) (1-84) in a model of male osteoporosis induced by orchidectomy in rats. Six-month-old Wistar rats were used as follows: SHAM (simulated orchidectomy), orchidectomized (ORX), ORX + PTH1 (ORX and treated with 10 µg/Kg/d of PTH 1-84) and ORX + PTH2 (ORX and treated with 50 µg/Kg/d of PTH 1-84) over 3 months, with treatment beginning three months after orchidectomy. Orchidectomy resulted in a decreased of femoral and lumbar bone mineral density (BMD), a worsening of trabecular and cortical microarchitecture and a decrease in biomechanical properties. Both doses of PTH (1-84) partially (low dose) or totally (high dose) restored the ORX-induced changes. Serum C-telopeptide of type I collagen/5b isoenzyme of tartrate-resistant acid phosphatase (CTX/TRAP) resorption index increased after orchidectomy. Osteocalcin (bone Gla protein; BGP) levels were not affected by orchidectomy. PTH (1-84) treatment did not produce any changes in the levels of CTX/TRAP with respect to the ORX group. BGP levels increased with PTH treatment. PTH (1-84) is able to restore the adverse effects of orchidectomy on bone as measured by BMD, microstructural and biomechanical properties and bone remodeling markers.

Gender disparity in BMD conversion: a comparison between Lunar and Hologic densitometers.

PubMed

Ganda, Kirtan; Nguyen, Tuan V; Pocock, Nicholas

2014-01-01

Female-derived inter-conversion and standardised BMD equations at the lumbar spine and hip have not been validated in men. This study of 110 male subjects scanned on Hologic and Lunar densitometers demonstrates that published equations may not applicable to men at the lumbar spine. Male inter-conversion equations have also been derived. Currently, available equations for inter-manufacturer conversion of bone mineral density (BMD) and calculation of standardised BMD (sBMD) are used in both males and females, despite being derived and validated only in women. Our aim was to test the validity of the published equations in men. One hundred ten men underwent lumbar spine (L2-4), femoral neck (FN) and total hip (TH) dual X-ray absorptiometry (DXA) using Hologic and Lunar scanners. Hologic BMD was converted to Lunar using published equations derived from women for L2-4 and FN. Actual Lunar BMD (A-Lunar) was compared to converted (Lunar equivalent) Hologic BMD values (H-Lunar). sBMD was calculated separately using Hologic (sBMD-H) and Lunar BMD (sBMD-L) at L2-4, FN and TH. Conversion equations in men for Hologic to Lunar BMD were derived using Deming regression analysis. There was a strong linear correlation between Lunar and Hologic BMD at all skeletal sites. A-Lunar BMD was however significantly higher than derived H-Lunar BMD (p < 0.001) at L2-L4 (mean difference, 0.07 g/cm(2)). There was no significant difference at the FN (mean difference, 0.01 g/cm(2)). sBMD-L at the spine was significantly higher than sBMD-H (mean difference, 0.06 g/cm(2), p < 0.001), whilst there was little difference at the FN and TH (mean difference, 0.01 g/cm(2)). Published conversion equations for Lunar BMD to Hologic BMD, and formulae for lumbar spine sBMD, derived in women may not be applicable to men.

Shock wave treatment shows dose-dependent enhancement of bone mass and bone strength after fracture of the femur.

PubMed

Wang, Ching-Jen; Yang, Kuender D; Wang, Feng-Sheng; Hsu, Chia-Chen; Chen, Hsiang-Ho

2004-01-01

Shock wave treatment is believed to improve bone healing after fracture. The purpose of this study was to evaluate the effect of shock wave treatment on bone mass and bone strength after fracture of the femur in a rabbit model. A standardized closed fracture of the right femur was created with a three-point bending method in 24 New Zealand white rabbits. Animals were randomly divided into three groups: (1) control (no shock wave treatment), (2) low-energy (shock wave treatment at 0.18 mJ/mm2 energy flux density with 2000 impulses), and (3) high-energy (shock wave treatment at 0.47 mJ/mm2 energy flux density with 4000 impulses). Bone mass (bone mineral density (BMD), callus formation, ash and calcium contents) and bone strength (peak load, peak stress and modulus of elasticity) were assessed at 12 and 24 weeks after shock wave treatment. While the BMD values of the high-energy group were significantly higher than the control group (P = 0.021), the BMD values between the low-energy and control groups were not statistically significant (P = 0.358). The high-energy group showed significantly more callus formation (P < 0.001), higher ash content (P < 0.001) and calcium content (P = 0.003) than the control and low-energy groups. With regard to bone strength, the high-energy group showed significantly higher peak load (P = 0.012), peak stress (P = 0.015) and modulus of elasticity (P = 0.011) than the low-energy and control groups. Overall, the effect of shock wave treatment on bone mass and bone strength appears to be dose dependent in acute fracture healing in rabbits.

The Soy Isoflavones to Reduce Bone Loss (SIRBL) Study: Three Year Effects on pQCT Bone Mineral Density and Strength Measures in Postmenopausal Women

USDA-ARS?s Scientific Manuscript database

Soy isoflavones exert inconsistent bone density preserving effects, but the bone strength preserving effects in humans are unknown. Our double-blind randomized controlled trial examined 2 soy isoflavone doses (80 or 120 mg/d) vs placebo tablets on volumetric bone mineral density (vBMD) and strength ...

The skeletal consequences of thyrotoxicosis.

PubMed

Nicholls, Jonathan J; Brassill, Mary Jane; Williams, Graham R; Bassett, J H Duncan

2012-06-01

Euthyroid status is essential for normal skeletal development and the maintenance of adult bone structure and strength. Established thyrotoxicosis has long been recognised as a cause of high bone turnover osteoporosis and fracture but more recent studies have suggested that subclinical hyperthyroidism and long-term suppressive doses of thyroxine (T4) may also result in decreased bone mineral density (BMD) and an increased risk of fragility fracture, particularly in postmenopausal women. Furthermore, large population studies of euthyroid individuals have demonstrated that a hypothalamic-pituitary-thyroid axis set point at the upper end of the normal reference range is associated with reduced BMD and increased fracture susceptibility. Despite these findings, the cellular and molecular mechanisms of thyroid hormone action in bone remain controversial and incompletely understood. In this review, we discuss the role of thyroid hormones in bone and the skeletal consequences of hyperthyroidism.

Benchmarking B-Cell Epitope Prediction with Quantitative Dose-Response Data on Antipeptide Antibodies: Towards Novel Pharmaceutical Product Development

PubMed Central

Caoili, Salvador Eugenio C.

2014-01-01

B-cell epitope prediction can enable novel pharmaceutical product development. However, a mechanistically framed consensus has yet to emerge on benchmarking such prediction, thus presenting an opportunity to establish standards of practice that circumvent epistemic inconsistencies of casting the epitope prediction task as a binary-classification problem. As an alternative to conventional dichotomous qualitative benchmark data, quantitative dose-response data on antibody-mediated biological effects are more meaningful from an information-theoretic perspective in the sense that such effects may be expressed as probabilities (e.g., of functional inhibition by antibody) for which the Shannon information entropy (SIE) can be evaluated as a measure of informativeness. Accordingly, half-maximal biological effects (e.g., at median inhibitory concentrations of antibody) correspond to maximally informative data while undetectable and maximal biological effects correspond to minimally informative data. This applies to benchmarking B-cell epitope prediction for the design of peptide-based immunogens that elicit antipeptide antibodies with functionally relevant cross-reactivity. Presently, the Immune Epitope Database (IEDB) contains relatively few quantitative dose-response data on such cross-reactivity. Only a small fraction of these IEDB data is maximally informative, and many more of them are minimally informative (i.e., with zero SIE). Nevertheless, the numerous qualitative data in IEDB suggest how to overcome the paucity of informative benchmark data. PMID:24949474

Effects of pioglitazone on bone in postmenopausal women with impaired fasting glucose or impaired glucose tolerance: a randomized, double-blind, placebo-controlled study.

PubMed

Bone, Henry G; Lindsay, Robert; McClung, Michael R; Perez, Alfonso T; Raanan, Marsha G; Spanheimer, Robert G

2013-12-01

Meta-analyses of clinical studies have suggested an increased incidence of peripheral fractures in postmenopausal women with type 2 diabetes mellitus taking pioglitazone. The mechanism behind this apparent increase is unknown. The objective of the study was to examine the effects of pioglitazone on bone mineral density (BMD) and turnover. Twenty-five sites (in the United States) enrolled participants in this randomized, double-blind, placebo-controlled study. Postmenopausal women (n = 156) with impaired fasting glucose or impaired glucose tolerance participated in the study. The intervention consisted of pioglitazone 30 mg/d (n = 78) or placebo (n = 78), increased to 45 mg/d after 1 month, for 12 months of treatment total, followed by 6 months of washout/follow-up. Percentage changes from baseline to month 12 and from month 12 to month18 in BMD in total proximal femur (primary end point), total body, femoral neck, lumbar spine, and radius were measured. Least squares mean changes from baseline to month 12 in total proximal femur BMD were -0.69% for pioglitazone and -0.14% for placebo (P = .170). No statistically significant between-group differences were observed for any BMD or bone remodeling marker end point. We observed improved glycemic control and insulin sensitivity with pioglitazone treatment. In addition, pioglitazone appeared to increase body fat, which may affect bone density measurements, especially in the lumbar spine. One pioglitazone-treated and three placebo-treated women experienced confirmed fractures. Over 18 months, one pioglitazone-treated (1.3%) and eight placebo-treated women (10.3%) developed overt type 2 diabetes mellitus. The pattern and incidence of adverse events with pioglitazone were consistent with clinical experience with thiazolidinediones. Maximal-dose pioglitazone had no effects on BMD or bone turnover, while improving glycemic control as expected, in postmenopausal women with impaired fasting glucose or impaired glucose tolerance.

No evidence that the skeletal non-response to potassium alkali supplements in healthy postmenopausal women depends on blood pressure or sodium chloride intake.

PubMed

Frassetto, L A; Hardcastle, A C; Sebastian, A; Aucott, L; Fraser, W D; Reid, D M; Macdonald, H M

2012-12-01

In vitro studies demonstrate that bone is degraded in an acidic environment due to chemical reactions and through effects on bone cells. Clinical evidence is insufficient to unequivocally resolve whether the diet net acid or base load bone affects breakdown in humans. Increasing dietary salt (sodium chloride, NaCl) mildly increases blood acidity in humans and in rats with increased sensitivity to the blood pressure effects of salt, whereas increased potassium (K) intake can decrease blood pressure. Blood pressure responses to NaCl or K may potentially be a marker for increased bone turnover or lower bone mineral density (BMD) in women at higher risk for osteoporosis and fracture. We retrospectively analysed data from two data sets (California and NE Scotland) of postmenopausal women (n=266) enrolled in long-term randomized, placebo-controlled studies of the effects of administration of low- or high-dose dietary K alkali supplementation on bone turnover in relation to sodium or chloride excretion (a marker of dietary salt intake). Mean arterial pressure (MAP) was calculated from blood pressure measures, MAP was divided into tertiles and its influence on the effect of dietary NaCl and K alkali supplementation on deoxypyridinoline markers of bone resorption and BMD by DEXA was tested. Data was analysed for each data set separately and then combined. Percentage change in BMD after 24 months was less for California compared with North East Scotland (hip: -0.6 ± 2.8% and -1.5 ± 2.4%, respectively (P=0.027); spine: -0.5 ± 3.4% and -2.6 ± 3.5%, (P<0.001). We found no effect of dietary alkali treatment on BMD change or bone resorption for either centre. Adjusting for the possible calcium- or potassium-lowering effects on blood pressure did not alter the results. Blood pressure responses to Na, Cl or K intake did not help predict a BMD response to diet alkali therapy.

SU-E-T-466: Implementation of An Extension Module for Dose Response Models in the TOPAS Monte Carlo Toolkit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramos-Mendez, J; Faddegon, B; Perl, J

2015-06-15

Purpose: To develop and verify an extension to TOPAS for calculation of dose response models (TCP/NTCP). TOPAS wraps and extends Geant4. Methods: The TOPAS DICOM interface was extended to include structure contours, for subsequent calculation of DVH’s and TCP/NTCP. The following dose response models were implemented: Lyman-Kutcher-Burman (LKB), critical element (CE), population based critical volume (CV), parallel-serials, a sigmoid-based model of Niemierko for NTCP and TCP, and a Poisson-based model for TCP. For verification, results for the parallel-serial and Poisson models, with 6 MV x-ray dose distributions calculated with TOPAS and Pinnacle v9.2, were compared to data from the benchmarkmore » configuration of the AAPM Task Group 166 (TG166). We provide a benchmark configuration suitable for proton therapy along with results for the implementation of the Niemierko, CV and CE models. Results: The maximum difference in DVH calculated with Pinnacle and TOPAS was 2%. Differences between TG166 data and Monte Carlo calculations of up to 4.2%±6.1% were found for the parallel-serial model and up to 1.0%±0.7% for the Poisson model (including the uncertainty due to lack of knowledge of the point spacing in TG166). For CE, CV and Niemierko models, the discrepancies between the Pinnacle and TOPAS results are 74.5%, 34.8% and 52.1% when using 29.7 cGy point spacing, the differences being highly sensitive to dose spacing. On the other hand, with our proposed benchmark configuration, the largest differences were 12.05%±0.38%, 3.74%±1.6%, 1.57%±4.9% and 1.97%±4.6% for the CE, CV, Niemierko and LKB models, respectively. Conclusion: Several dose response models were successfully implemented with the extension module. Reference data was calculated for future benchmarking. Dose response calculated for the different models varied much more widely for the TG166 benchmark than for the proposed benchmark, which had much lower sensitivity to the choice of DVH dose points. This work was supported by National Cancer Institute Grant R01CA140735.« less

Benchmark Credentialing Results for NRG-BR001: The First National Cancer Institute-Sponsored Trial of Stereotactic Body Radiation Therapy for Multiple Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Hallaq, Hania A., E-mail: halhallaq@radonc.uchicago.edu; Chmura, Steven J.; Salama, Joseph K.

Purpose: The NRG-BR001 trial is the first National Cancer Institute–sponsored trial to treat multiple (range 2-4) extracranial metastases with stereotactic body radiation therapy. Benchmark credentialing is required to ensure adherence to this complex protocol, in particular, for metastases in close proximity. The present report summarizes the dosimetric results and approval rates. Methods and Materials: The benchmark used anonymized data from a patient with bilateral adrenal metastases, separated by <5 cm of normal tissue. Because the planning target volume (PTV) overlaps with organs at risk (OARs), institutions must use the planning priority guidelines to balance PTV coverage (45 Gy in 3 fractions) againstmore » OAR sparing. Submitted plans were processed by the Imaging and Radiation Oncology Core and assessed by the protocol co-chairs by comparing the doses to targets, OARs, and conformity metrics using nonparametric tests. Results: Of 63 benchmarks submitted through October 2015, 94% were approved, with 51% approved at the first attempt. Most used volumetric arc therapy (VMAT) (78%), a single plan for both PTVs (90%), and prioritized the PTV over the stomach (75%). The median dose to 95% of the volume was 44.8 ± 1.0 Gy and 44.9 ± 1.0 Gy for the right and left PTV, respectively. The median dose to 0.03 cm{sup 3} was 14.2 ± 2.2 Gy to the spinal cord and 46.5 ± 3.1 Gy to the stomach. Plans that spared the stomach significantly reduced the dose to the left PTV and stomach. Conformity metrics were significantly better for single plans that simultaneously treated both PTVs with VMAT, intensity modulated radiation therapy, or 3-dimensional conformal radiation therapy compared with separate plans. No significant differences existed in the dose at 2 cm from the PTVs. Conclusions: Although most plans used VMAT, the range of conformity and dose falloff was large. The decision to prioritize either OARs or PTV coverage varied considerably, suggesting that the toxicity outcomes in the trial could be affected. Several benchmarks met the dose-volume histogram metrics but produced unacceptable plans owing to low conformity. Dissemination of a frequently-asked-questions document improved the approval rate at the first attempt. Benchmark credentialing was found to be a valuable tool for educating institutions about the protocol requirements.« less

Benchmark Credentialing Results for NRG-BR001: The First National Cancer Institute-Sponsored Trial of Stereotactic Body Radiation Therapy for Multiple Metastases.

PubMed

Al-Hallaq, Hania A; Chmura, Steven J; Salama, Joseph K; Lowenstein, Jessica R; McNulty, Susan; Galvin, James M; Followill, David S; Robinson, Clifford G; Pisansky, Thomas M; Winter, Kathryn A; White, Julia R; Xiao, Ying; Matuszak, Martha M

2017-01-01

The NRG-BR001 trial is the first National Cancer Institute-sponsored trial to treat multiple (range 2-4) extracranial metastases with stereotactic body radiation therapy. Benchmark credentialing is required to ensure adherence to this complex protocol, in particular, for metastases in close proximity. The present report summarizes the dosimetric results and approval rates. The benchmark used anonymized data from a patient with bilateral adrenal metastases, separated by <5 cm of normal tissue. Because the planning target volume (PTV) overlaps with organs at risk (OARs), institutions must use the planning priority guidelines to balance PTV coverage (45 Gy in 3 fractions) against OAR sparing. Submitted plans were processed by the Imaging and Radiation Oncology Core and assessed by the protocol co-chairs by comparing the doses to targets, OARs, and conformity metrics using nonparametric tests. Of 63 benchmarks submitted through October 2015, 94% were approved, with 51% approved at the first attempt. Most used volumetric arc therapy (VMAT) (78%), a single plan for both PTVs (90%), and prioritized the PTV over the stomach (75%). The median dose to 95% of the volume was 44.8 ± 1.0 Gy and 44.9 ± 1.0 Gy for the right and left PTV, respectively. The median dose to 0.03 cm 3 was 14.2 ± 2.2 Gy to the spinal cord and 46.5 ± 3.1 Gy to the stomach. Plans that spared the stomach significantly reduced the dose to the left PTV and stomach. Conformity metrics were significantly better for single plans that simultaneously treated both PTVs with VMAT, intensity modulated radiation therapy, or 3-dimensional conformal radiation therapy compared with separate plans. No significant differences existed in the dose at 2 cm from the PTVs. Although most plans used VMAT, the range of conformity and dose falloff was large. The decision to prioritize either OARs or PTV coverage varied considerably, suggesting that the toxicity outcomes in the trial could be affected. Several benchmarks met the dose-volume histogram metrics but produced unacceptable plans owing to low conformity. Dissemination of a frequently-asked-questions document improved the approval rate at the first attempt. Benchmark credentialing was found to be a valuable tool for educating institutions about the protocol requirements. Copyright © 2016 Elsevier Inc. All rights reserved.

The effect of topiramate and lamotrigine on rat bone mass, structure and metabolism.

PubMed

Simko, Julius; Fekete, Sona; Gradosova, Iveta; Malakova, Jana; Zivna, Helena; Valis, Martin; Palicka, Vladimir; Zivny, Pavel

2014-05-15

There is only limited data concerning the effect of the newer antiepileptic drugs on bone. The objective of this study was to determine the effect of topiramate (TPM) and lamotrigine (LTG) monotherapy on bone mineral density (BMD), mineral content (BMC), bone markers, body composition and bone mechanical strength in the orchidectomized (ORX) rat model. 24 orchidectomized Wistar rats were divided into control and test groups, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed with SLD enriched with LTG or TPM for 12 weeks. Dual energy X-ray absorptiometry was used to measure bone mineral density. The concentrations of bone metabolism markers were assayed in bone homogenate. In addition, both femurs were measured and used for biomechanical testing. Compared to the control group, both test groups had significantly lower weight, fat mass, whole body and femur BMD, BMC and reduced mechanical strength of bone. All of these changes were more pronounced in rats exposed to LTG. In conclusion, both LTG and TPM significantly reduce BMD and body weight and impair mechanical strength of bone. A question arises as to the degree of dependence of the effect on the dose. Further studies are warranted to establish whether LTG and TPM may have a clinically significant effect on BMD exclusively in the model of gonadectomized rats, or whether the effect applies also in the model of gonadally intact animals, and in the respective human models. Copyright © 2014 Elsevier B.V. All rights reserved.

Genome-wide association study of coronary and aortic calcification in lung cancer screening CT

NASA Astrophysics Data System (ADS)

de Vos, Bob D.; van Setten, Jessica; de Jong, Pim A.; Mali, Willem P.; Oudkerk, Matthijs; Viergever, Max A.; Išgum, Ivana

2016-03-01

Arterial calcification has been related to cardiovascular disease (CVD) and osteoporosis. However, little is known about the role of genetics and exact pathways leading to arterial calcification and its relation to bone density changes indicating osteoporosis. In this study, we conducted a genome-wide association study of arterial calcification burden, followed by a look-up of known single nucleotide polymorphisms (SNPs) for coronary artery disease (CAD) and myocardial infarction (MI), and bone mineral density (BMD) to test for a shared genetic basis between the traits. The study included a subcohort of the Dutch-Belgian lung cancer screening trial comprised of 2,561 participants. Participants underwent baseline CT screening in one of two hospitals participating in the trial. Low-dose chest CT images were acquired without contrast enhancement and without ECG-synchronization. In these images coronary and aortic calcifications were identified automatically. Subsequently, the detected calcifications were quantified using coronary artery calcium Agatston and volume scores. Genotype data was available for these participants. A genome-wide association study was conducted on 10,220,814 SNPs using a linear regression model. To reduce multiple testing burden, known CAD/MI and BMD SNPs were specifically tested (45 SNPs from the CARDIoGRAMplusC4D consortium and 60 SNPS from the GEFOS consortium). No novel significant SNPs were found. Significant enrichment for CAD/MI SNPs was observed in testing Agatston and coronary artery calcium volume scores. Moreover, a significant enrichment of BMD SNPs was shown in aortic calcium volume scores. This may indicate genetic relation of BMD SNPs and arterial calcification burden.

[Benchmark experiment to verify radiation transport calculations for dosimetry in radiation therapy].

PubMed

Renner, Franziska

2016-09-01

Monte Carlo simulations are regarded as the most accurate method of solving complex problems in the field of dosimetry and radiation transport. In (external) radiation therapy they are increasingly used for the calculation of dose distributions during treatment planning. In comparison to other algorithms for the calculation of dose distributions, Monte Carlo methods have the capability of improving the accuracy of dose calculations - especially under complex circumstances (e.g. consideration of inhomogeneities). However, there is a lack of knowledge of how accurate the results of Monte Carlo calculations are on an absolute basis. A practical verification of the calculations can be performed by direct comparison with the results of a benchmark experiment. This work presents such a benchmark experiment and compares its results (with detailed consideration of measurement uncertainty) with the results of Monte Carlo calculations using the well-established Monte Carlo code EGSnrc. The experiment was designed to have parallels to external beam radiation therapy with respect to the type and energy of the radiation, the materials used and the kind of dose measurement. Because the properties of the beam have to be well known in order to compare the results of the experiment and the simulation on an absolute basis, the benchmark experiment was performed using the research electron accelerator of the Physikalisch-Technische Bundesanstalt (PTB), whose beam was accurately characterized in advance. The benchmark experiment and the corresponding Monte Carlo simulations were carried out for two different types of ionization chambers and the results were compared. Considering the uncertainty, which is about 0.7 % for the experimental values and about 1.0 % for the Monte Carlo simulation, the results of the simulation and the experiment coincide. Copyright © 2015. Published by Elsevier GmbH.

Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment.

PubMed

Kemp, John P; Medina-Gomez, Carolina; Estrada, Karol; St Pourcain, Beate; Heppe, Denise H M; Warrington, Nicole M; Oei, Ling; Ring, Susan M; Kruithof, Claudia J; Timpson, Nicholas J; Wolber, Lisa E; Reppe, Sjur; Gautvik, Kaare; Grundberg, Elin; Ge, Bing; van der Eerden, Bram; van de Peppel, Jeroen; Hibbs, Matthew A; Ackert-Bicknell, Cheryl L; Choi, Kwangbom; Koller, Daniel L; Econs, Michael J; Williams, Frances M K; Foroud, Tatiana; Zillikens, M Carola; Ohlsson, Claes; Hofman, Albert; Uitterlinden, André G; Davey Smith, George; Jaddoe, Vincent W V; Tobias, Jonathan H; Rivadeneira, Fernando; Evans, David M

2014-06-01

Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg) and residual (re) correlations between BMD measured at the upper limbs (UL-BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of ∼ 4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78) between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43). Likewise, the residual correlation between BMD at appendicular sites (r(e) = 0.55) was higher than the residual correlation between SK-BMD and BMD at appendicular sites (r(e) = 0.20-0.24). To explore the basis for the observed differences in rg and re, genome-wide association meta-analyses were performed (n ∼ 9,395), combining data from ALSPAC and the Generation R Study identifying 15 independent signals from 13 loci associated at genome-wide significant level across different skeletal regions. Results suggested that previously identified BMD-associated variants may exert site-specific effects (i.e. differ in the strength of their association and magnitude of effect across different skeletal sites). In particular, variants at CPED1 exerted a larger influence on SK-BMD and UL-BMD when compared to LL-BMD (P = 2.01 × 10(-37)), whilst variants at WNT16 influenced UL-BMD to a greater degree when compared to SK- and LL-BMD (P = 2.31 × 10(-14)). In addition, we report a novel association between RIN3 (previously associated with Paget's disease) and LL-BMD (rs754388: β = 0.13, SE = 0.02, P = 1.4 × 10(-10)). Our results suggest that BMD at different skeletal sites is under a mixture of shared and specific genetic and environmental influences. Allowing for these differences by performing genome-wide association at different skeletal sites may help uncover new genetic influences on BMD.

Phenotypic Dissection of Bone Mineral Density Reveals Skeletal Site Specificity and Facilitates the Identification of Novel Loci in the Genetic Regulation of Bone Mass Attainment

PubMed Central

Estrada, Karol; St Pourcain, Beate; Heppe, Denise H. M.; Warrington, Nicole M.; Oei, Ling; Ring, Susan M.; Kruithof, Claudia J.; Timpson, Nicholas J.; Wolber, Lisa E.; Reppe, Sjur; Gautvik, Kaare; Grundberg, Elin; Ge, Bing; van der Eerden, Bram; van de Peppel, Jeroen; Hibbs, Matthew A.; Ackert-Bicknell, Cheryl L.; Choi, Kwangbom; Koller, Daniel L.; Econs, Michael J.; Williams, Frances M. K.; Foroud, Tatiana; Carola Zillikens, M.; Ohlsson, Claes; Hofman, Albert; Uitterlinden, André G.; Davey Smith, George; Jaddoe, Vincent W. V.; Tobias, Jonathan H.; Rivadeneira, Fernando; Evans, David M.

2014-01-01

Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg) and residual (re) correlations between BMD measured at the upper limbs (UL-BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of ∼4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78) between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43). Likewise, the residual correlation between BMD at appendicular sites (re = 0.55) was higher than the residual correlation between SK-BMD and BMD at appendicular sites (re = 0.20–0.24). To explore the basis for the observed differences in rg and re, genome-wide association meta-analyses were performed (n∼9,395), combining data from ALSPAC and the Generation R Study identifying 15 independent signals from 13 loci associated at genome-wide significant level across different skeletal regions. Results suggested that previously identified BMD-associated variants may exert site-specific effects (i.e. differ in the strength of their association and magnitude of effect across different skeletal sites). In particular, variants at CPED1 exerted a larger influence on SK-BMD and UL-BMD when compared to LL-BMD (P = 2.01×10−37), whilst variants at WNT16 influenced UL-BMD to a greater degree when compared to SK- and LL-BMD (P = 2.31×10−14). In addition, we report a novel association between RIN3 (previously associated with Paget's disease) and LL-BMD (rs754388: β = 0.13, SE = 0.02, P = 1.4×10−10). Our results suggest that BMD at different skeletal sites is under a mixture of shared and specific genetic and environmental influences. Allowing for these differences by performing genome-wide association at different skeletal sites may help uncover new genetic influences on BMD. PMID:24945404

Comparative Benchmark Dose Modeling as a Tool to Make the First Estimate of Safe Human Exposure Levels to Lunar Dust

NASA Technical Reports Server (NTRS)

James, John T.; Lam, Chiu-wing; Scully, Robert R.

2013-01-01

Brief exposures of Apollo Astronauts to lunar dust occasionally elicited upper respiratory irritation; however, no limits were ever set for prolonged exposure ot lunar dust. Habitats for exploration, whether mobile of fixed must be designed to limit human exposure to lunar dust to safe levels. We have used a new technique we call Comparative Benchmark Dose Modeling to estimate safe exposure limits for lunar dust collected during the Apollo 14 mission.

Determinants of bone mineral density in patients on haemodialysis or peritoneal dialysis--a cross-sectional, longitudinal study.

PubMed

Nybo, Mads; Jespersen, Bente; Aarup, Michael; Ejersted, Charlotte; Hermann, Anne Pernille; Brixen, Kim

2013-01-01

The aim of the study was to identify biomarkers of alteration in bone mineral density (BMD) in patients on haemodialysis (HD) and peritoneal dialysis (PD). In a cross-sectional, longitudinal study dual-energy X-ray absorptiometry scans were performed in 146 HD-patients and 28 PD-patients. Follow-up after 14 months (mean) was conducted in 73 patients. As potential biomarkers we investigated parathyroid hormone (PTH), 25-hydroxy vitamin-D, ionised calcium, albumin, phosphate, and total alkaline phosphatases (t-ALP). Both groups of dialysis patients had lower BMD in the femoral neck (BMD(neck)) (P < 0.001) and forearm (BMD(forearm)) (P < 0.001) compared to healthy controls, but comparable BMD in the lumbar spine (BMD(spine)). BMD did not differ between dialysis types, but patients ever-treated with glucocorticoids had significantly lower BMD, while patients with polycystic kidney disease had higher BMD. BMD correlated with body weight, actual age, age at initiation of dialysis, duration of dialysis and levels of PTH and t-ALP. However, t-ALP only remained associated with low BMD(spine) after adjusting for other factors (P = 0.001). In the follow-up study all patients had decreased BMD in all three locations, but only for the lumbar spine there was a significant association between BMD and the bone markers t-ALP (P = 0.009) and PTH (P = 0.013). Both HD and PD patients have low BMD, and increased concentrations of t-ALP is associated BMD(spine) after adjustment, while PTH and t-ALP is associated with decrease in BMD(spine) over time. This substantiates the use of these biomarkers in both types of dialysis patients.

The relationship between angiotensin-converting enzyme (ACE) insertion (I) / deletion (D) polymorphism, serum ACE activity and bone mineral density (BMD) in older Chinese.

PubMed

Zhang, Ya-Feng; Wang, Hong; Cheng, Qiong; Qin, Ling; Tang, Nelson Ls; Leung, Ping-Chong; Kwok, Timothy Cy

2017-01-01

In this study, we set out to investigate the relationship between angiotensin-converting enzyme ( ACE) I/D polymorphism, serum ACE activity and bone mineral density (BMD) in older Chinese. A standardized, structured, face-to-face interview was performed to collect demographic information. BMD was measured using dual-energy X-ray absorptiometry (DXA). I/D genotypes of ACE were determined by polymerase chain reaction (PCR) amplification. Serum ACE activity was determined photometrically by a commercially available kinetic kit. Multiple linear regression analysis was used to examine the relationship between ACE I/D polymorphism, serum ACE activity and BMD. A total of 1567 males and 1760 females were selected for analyzing the relationship between ACE I/D polymorphism and BMD. There was no significant difference in spine BMD, total hip BMD and femur neck BMD among different ACE I/D genotypes both in males and females. A total of 1699 males and 1739 females were selected for analyzing the relationship between serum ACE activity and BMD. There was also no significant difference in spine BMD, total hip BMD and femur neck BMD among different serum ACE activity groups both in males and females. There was no relationship between ACE I/D polymorphism, serum ACE activity and BMD in older Chinese.

Development of a Food Group-Based Diet Score and Its Association with Bone Mineral Density in the Elderly: The Rotterdam Study.

PubMed

de Jonge, Ester A L; Kiefte-de Jong, Jessica C; de Groot, Lisette C P G M; Voortman, Trudy; Schoufour, Josje D; Zillikens, M Carola; Hofman, Albert; Uitterlinden, André G; Franco, Oscar H; Rivadeneira, Fernando

2015-08-18

No diet score exists that summarizes the features of a diet that is optimal for bone mineral density (BMD) in the elderly. Our aims were (a) to develop a BMD-Diet Score reflecting a diet that may be beneficial for BMD based on the existing literature, and (b) to examine the association of the BMD-Diet Score and the Healthy Diet Indicator, a score based on guidelines of the World Health Organization, with BMD in Dutch elderly participating in a prospective cohort study, the Rotterdam Study (n = 5144). Baseline dietary intake, assessed using a food frequency questionnaire, was categorized into food groups. Food groups that were consistently associated with BMD in the literature were included in the BMD-Diet Score. BMD was measured repeatedly and was assessed using dual energy X-ray absorptiometry. The BMD-Diet Score considered intake of vegetables, fruits, fish, whole grains, legumes/beans and dairy products as "high-BMD" components and meat and confectionary as "low-BMD" components. After adjustment, the BMD-Diet Score was positively associated with BMD (β (95% confidence interval) = 0.009 (0.005, 0.012) g/cm(2) per standard deviation). This effect size was approximately three times as large as has been observed for the Healthy Diet Indicator. The food groups included in our BMD-Diet Score could be considered in the development of future dietary guidelines for healthy ageing.

Multiscale benchmarking of drug delivery vectors.

PubMed

Summers, Huw D; Ware, Matthew J; Majithia, Ravish; Meissner, Kenith E; Godin, Biana; Rees, Paul

2016-10-01

Cross-system comparisons of drug delivery vectors are essential to ensure optimal design. An in-vitro experimental protocol is presented that separates the role of the delivery vector from that of its cargo in determining the cell response, thus allowing quantitative comparison of different systems. The technique is validated through benchmarking of the dose-response of human fibroblast cells exposed to the cationic molecule, polyethylene imine (PEI); delivered as a free molecule and as a cargo on the surface of CdSe nanoparticles and Silica microparticles. The exposure metrics are converted to a delivered dose with the transport properties of the different scale systems characterized by a delivery time, τ. The benchmarking highlights an agglomeration of the free PEI molecules into micron sized clusters and identifies the metric determining cell death as the total number of PEI molecules presented to cells, determined by the delivery vector dose and the surface density of the cargo. Copyright © 2016 Elsevier Inc. All rights reserved.

Greater Intake of Fruit and Vegetables Is Associated with Greater Bone Mineral Density and Lower Osteoporosis Risk in Middle-Aged and Elderly Adults

PubMed Central

Tian, Hui-yuan; He, Juan; Chen, Geng-dong; Chen, Yu-ming

2017-01-01

Objective A few studies have suggested that the consumption of fruit and vegetables (FV) may benefit bone health, but limited data are available in Asian subjects. We examined the association between FV intake and bone mineral density (BMD) and osteoporosis in Chinese adults. Methods This population-based cross-sectional study involved 2083 women and 1006 men aged 40–75 years in Guangzhou, China. Habitual dietary data was collected from a 79-item food frequency questionnaire by face-to-face interviews. The BMD was measured for the whole body (WB), lumbar spine (LS), total hip (TH) and femur neck (FN) with dual-energy X-ray absorptiometry. Results After adjustment for potential covariates, we observed dose-dependent associations between total FV intake and BMD and osteoporosis risk. The mean BMD was higher in tertile 3 vs. tertile 1 by 1.33% (TH) and 1.31% (FN) for FV, and 1.10% (WB), 1.57% (TH), and 2.05% (FN) for fruit (all P-trends < 0.05). Significant beneficial associations with BMD at some sites were also found in most fruit categories but not in total vegetables or their subgroups. The odds ratios (95% confidence interval) of osteoporosis (T-score ≤ −2.5) in tertile 3 (vs. 1) were 0.73 (0.58–0.92), 0.37 (0.22–0.60), and 0.71 (0.52–0.97) for FV; 0.82 (0.66–1.03), 0.48 (0.30–0.77) and 0.89 (0.61–1.12) for fruit; and 0.80 (0.64–1.01), 0.57 (0.35–0.92) and 0.76 (0.55–1.05) for vegetables at the LS, TH, and FN, respectively. The favorable association between FV intake and the occurrence of osteoporosis was evident only in subjects with lower BMI (<24.0 kg/m2, P-trends < 0.05). Conclusions Greater intake of FV was independently associated with a higher BMD and a lower presence of osteoporosis in middle-aged and elderly Chinese subjects with lower BMI. Fruit tended to have more contribution to the favorable association than vegetables. PMID:28045945

The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups.

PubMed

George, Jaya A; Micklesfield, L K; Norris, S A; Crowther, N J

2014-06-01

There are few data on the contribution of body composition to bone mineral density (BMD) in non-Caucasian populations. We therefore studied the contribution of body composition, and possible confounding of 25-hydroxyvitamin D and PTH, to BMD at various skeletal sites in black African (BA) and Asian Indian (AI) subjects. This was a cross-sectional study in Johannesburg, South Africa. BMD, body fat, and lean mass were measured using dual x-ray absorptiometry and abdominal fat distribution by ultrasound in 714 healthy subjects, aged 18-65 years. Whole-body (subtotal), hip, femoral neck, and lumbar spine (lumbar) BMD were significantly higher in BA than AI subjects (P < .001 for all). Whole-body lean mass positively associated with BMD at all sites in both ethnic groups (P < .001 for all) and partially explained the higher BMD in BA females compared with AI females. Whole-body fat mass correlated positively with lumbar BMD in BA (P = .001) and inversely with subtotal BMD in AI subjects (P < .0001). Visceral adiposity correlated inversely with subtotal BMD in the BA (P = .037) and with lumbar BMD in the AI group (P = .005). No association was found between serum 25-hydroxyvitamin D and BMD. PTH was inversely associated with hip BMD in the BA group (P = .01) and with subtotal (P = .002), hip (P = .001), and femoral BMD (P < .0001) in the AI group. Significant differences in whole-body and site-specific BMD between the BA and AI groups were observed, with lean mass the major contributor to BMD at all sites in both groups. The contribution of other components of body composition differed by site and ethnic group.

Benchmark studies of induced radioactivity produced in LHC materials, Part II: Remanent dose rates.

PubMed

Brugger, M; Khater, H; Mayer, S; Prinz, A; Roesler, S; Ulrici, L; Vincke, H

2005-01-01

A new method to estimate remanent dose rates, to be used with the Monte Carlo code FLUKA, was benchmarked against measurements from an experiment that was performed at the CERN-EU high-energy reference field facility. An extensive collection of samples of different materials were placed downstream of, and laterally to, a copper target, intercepting a positively charged mixed hadron beam with a momentum of 120 GeV c(-1). Emphasis was put on the reduction of uncertainties by taking measures such as careful monitoring of the irradiation parameters, using different instruments to measure dose rates, adopting detailed elemental analyses of the irradiated materials and making detailed simulations of the irradiation experiment. The measured and calculated dose rates are in good agreement.

SU-E-T-148: Benchmarks and Pre-Treatment Reviews: A Study of Quality Assurance Effectiveness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lowenstein, J; Nguyen, H; Roll, J

Purpose: To determine the impact benchmarks and pre-treatment reviews have on improving the quality of submitted clinical trial data. Methods: Benchmarks are used to evaluate a site’s ability to develop a treatment that meets a specific protocol’s treatment guidelines prior to placing their first patient on the protocol. A pre-treatment review is an actual patient placed on the protocol in which the dosimetry and contour volumes are evaluated to be per protocol guidelines prior to allowing the beginning of the treatment. A key component of these QA mechanisms is that sites are provided timely feedback to educate them on howmore » to plan per the protocol and prevent protocol deviations on patients accrued to a protocol. For both benchmarks and pre-treatment reviews a dose volume analysis (DVA) was performed using MIM softwareTM. For pre-treatment reviews a volume contour evaluation was also performed. Results: IROC Houston performed a QA effectiveness analysis of a protocol which required both benchmarks and pre-treatment reviews. In 70 percent of the patient cases submitted, the benchmark played an effective role in assuring that the pre-treatment review of the cases met protocol requirements. The 35 percent of sites failing the benchmark subsequently modified there planning technique to pass the benchmark before being allowed to submit a patient for pre-treatment review. However, in 30 percent of the submitted cases the pre-treatment review failed where the majority (71 percent) failed the DVA. 20 percent of sites submitting patients failed to correct their dose volume discrepancies indicated by the benchmark case. Conclusion: Benchmark cases and pre-treatment reviews can be an effective QA tool to educate sites on protocol guidelines and to minimize deviations. Without the benchmark cases it is possible that 65 percent of the cases undergoing a pre-treatment review would have failed to meet the protocols requirements.Support: U24-CA-180803.« less

Preferential reduction of bone mineral density at the femur reflects impairment of physical activity in patients with low-activity rheumatoid arthritis.

PubMed

Sugiguchi, Shigeru; Goto, Hitoshi; Inaba, Masaaki; Nishizawa, Yoshiki

2010-02-01

Bone mineral density (BMD) and factors influencing BMD in rheumatoid arthritis (RA) under good or moderate control were examined to assess management of osteoporosis in RA. BMD of the lumbar spine, femur, and distal radius was measured in 105 female patients with well-controlled RA. Laboratory and clinical variables associated with disease activity were measured in the same subjects, and correlations between these variables and BMD were evaluated. The RA patients showed a greater decrease in BMD of the femoral neck than of the lumbar spine. Age, Health Assessment Questionnaire (HAQ) score, and Larsen damage score had negative correlations with BMD of the femoral neck. In multiple regression analysis of the parameters associated with BMD of the femoral neck in simple regression analysis, an increase in HAQ score showed a negative correlation with BMD of the femoral neck. After initiation of treatment with alendronate (ALN), BMD of the femoral neck increased and correlated with improvement in HAQ score. A decrease in BMD of the femoral neck is a characteristic of RA. This suggests that muscle tonus has more effect than weight-bearing activity on BMD in patients with RA. BMD of the femoral neck is a useful index for general evaluation of RA patients.

Cortical bone is more sensitive to alcohol dose effects than trabecular bone in the rat.

PubMed

Maurel, Delphine B; Boisseau, Nathalie; Benhamou, Claude-Laurent; Jaffré, Christelle

2012-10-01

While chronic alcohol consumption is known to decrease bone mineral content (BMC), bone mineral density (BMD), and negatively modify trabecular bone microarchitecture, the impact of alcohol on cortical microarchitecture is still unclear. The aim of this study was to investigate the effects of various doses of alcohol on bone density, trabecular and cortical parameters and bone strength in rats. Forty-eight male Wistar rats were divided into four groups: control (C), alcohol 25% v/v (A25), alcohol 30% v/v (A30) and alcohol 35% v/v (A35). Rats in the alcohol groups were fed a solution composed of ethanol and water for 17 weeks while the control group drank only water. Bone quality and quantity were evaluated through the analysis of density, trabecular and cortical bone microarchitectural parameters, osteocalcin and N-Telopeptide concentrations and a 3-point bending test. Bone density along with trabecular and cortical thickness were lower in alcohol groups compared to C. BMD was lower in A35 vs. A30 and cortical thickness was lower in A35 vs. A25 and A30. Pore number was increased by alcohol and the porosity was greater in A35 compared to C. N-Telopeptide concentration was decreased in alcohol groups compared to control whereas no differences were observed in osteocalcin concentrations. Maximal energy to failure was lower in A25 and A35 compared to C. Chronic ethanol consumption increases cortical bone damage in rats and may have detrimental effects on bone strength. These effects were dose-dependent, with greater negative effects proportionate to greater alcohol doses. Copyright © 2011 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Hip bone loss is attenuated with 1000 IU but not 400 IU daily vitamin D3: a 1-year double-blind RCT in postmenopausal women.

PubMed

Macdonald, Helen M; Wood, Adrian D; Aucott, Lorna S; Black, Alison J; Fraser, William D; Mavroeidi, Alexandra; Reid, David M; Secombes, Karen R; Simpson, William G; Thies, Frank

2013-10-01

Few year-long vitamin D supplementation trials exist that match seasonal changes. The aim of this study was to determine whether daily oral vitamin D3 at 400 IU or 1000 IU compared with placebo affects annual bone mineral density (BMD) change in postmenopausal women in a 1-year double-blind placebo controlled trial in Scotland. White women aged 60 to 70 years (n = 305) were randomized to one of two doses of vitamin D or placebo. All participants started simultaneously in January/February 2009, attending visits at bimonthly intervals with 265 (87%) women attending the final visit and an additional visit 1 month after treatment cessation. BMD (Lunar iDXA) and 1,25-dihydroxyvitamin D[1,25(OH)2 D], N-terminal propeptide of type 1 collagen [P1NP], C-terminal telopeptide of type I collagen [CTX], and fibroblast growth factor-23 [FGF23] were measured by immunoassay at the start and end of treatment. Circulating PTH, serum Ca, and total 25-hydroxyvitamin D [25(OH)D] (latter by tandem mass spectrometry) were measured at each visit. Mean BMD loss at the hip was significantly less for the 1000 IU vitamin D group (0.05% ± 1.46%) compared with the 400 IU vitamin D or placebo groups (0.57% ± 1.33% and 0.60% ± 1.67%, respectively) (p < 0.05). Mean (± SD) baseline 25(OH)D was 33.8 ± 14.6 nmol/L; comparative 25(OH)D change for the placebo, 400 IU, and 1000 IU vitamin D groups was -4.1 ± 11.5 nmol/L, +31.6 ± 19.8 nmol/L, and +42.6 ± 18.9 nmol/L, respectively. Treatment did not change markers of bone metabolism, except for a small reduction in PTH and an increase in serum calcium (latter with 1000 IU dose only). The discordance between the incremental increase in 25(OH)D between the 400 IU and 1000 IU vitamin D and effect on BMD suggests that 25(OH)D may not accurately reflect clinical outcome, nor how much vitamin D is being stored. © 2013 American Society for Bone and Mineral Research.

Corticosteroid use and bone mineral accretion in children with asthma: effect modification by vitamin D.

PubMed

Tse, Sze Man; Kelly, H William; Litonjua, Augusto A; Van Natta, Mark L; Weiss, Scott T; Tantisira, Kelan G

2012-07-01

The adverse effects of corticosteroids on bone mineral accretion (BMA) have been well documented. Vitamin D insufficiency, a prevalent condition in the pediatric population, has also been associated with decreased bone mineral density (BMD). We sought to determine whether children with asthma who have lower vitamin D levels are more susceptible to the negative effects of corticosteroids on BMD over time. Children aged 5 to 12 years with mild-to-moderate asthma who participated in the Childhood Asthma Management Program were followed for a mean of 4.3 years. Total doses of inhaled corticosteroids and oral corticosteroids (OCSs) were recorded, serum 25-hydroxyvitamin D3 levels were measured at the beginning of the trial, and serial dual-energy x-ray absorptiometry scans of the lumbar spine were performed. Annual BMA rates were defined as follows: [(BMD at 4 years' follow-up - BMD at baseline)/4 years]. BMA was calculated for 780 subjects. In boys baseline vitamin D levels significantly modified the relationship between OCSs and BMA (vitamin D × OCS interaction, P= .023). Stratification by vitamin D levels showed a decrease in BMA with increased use of OCSs in vitamin D-insufficient boys only (P< .001). Compared with vitamin D-sufficient boys, vitamin D-insufficient boys exposed to more than 2 courses of OCSs per year had twice the decrease in BMA rate (relative to boys who were OCS unexposed). Vitamin D levels significantly modified the effect of OCSs on BMA in boys. Further research is needed to examine whether vitamin D supplementation in children with poorly controlled asthma might confer benefits to bone health. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Corticosteroid use and bone mineral accretion in children with asthma: effect modification by vitamin D

PubMed Central

Tse, Sze Man; Kelly, H. William; Litonjua, Augusto; Van Natta, Mark L.; Weiss, Scott T.; Tantisira, Kelan

2012-01-01

Background The adverse effects of corticosteroids on bone mineral accretion (BMA) have been well documented. Vitamin D insufficiency, a prevalent condition in the pediatric population, has also been associated with decreased bone mineral density (BMD). Objective To determine whether children with asthma who have lower vitamin D levels are more susceptible to the negative effects of corticosteroids on BMD over time. Methods Children aged 5–12 years with mild-to-moderate asthma who participated in the Childhood Asthma Management Program were followed for a mean of 4.3 years. Total doses of inhaled and oral corticosteroids (OCS) were recorded, serum 25-hydroxyvitamin D3 levels were measured at the beginning of the trial and serial DEXA scans of the lumbar spine were performed. Annual BMA rates were defined as: [(BMD at 4 years follow-up − BMD at baseline)/4 years]. Results BMA was calculated for 780 subjects. In boys, baseline vitamin D levels significantly modified the relationship between OCS and BMA (vitamin D x OCS interaction, p=0.023). Stratification by vitamin D levels showed a decrease in BMA with increased use of OCS in vitamin D insufficient boys only (p<0.001). Compared to vitamin D sufficient boys, vitamin D insufficient boys exposed to more than 2 courses of oral corticosteroids per year had twice the decrease in BMA rate (relative to boys who were OCS-unexposed). Conclusions Vitamin D levels significantly modified the effect of oral corticosteroids on bone mineral accretion in boys. Further research is needed to examine whether vitamin D supplementation in children with poorly controlled asthma may confer benefits to bone health. PMID:22608570

Effects of long-term administration of omeprazole on bone mineral density and the mechanical properties of the bone.

PubMed

Yanagihara, Gabriela Rezende; de Paiva, Aline Goulart; Neto, Maurílio Pacheco; Torres, Larissa Helena; Shimano, Antônio Carlos; Louzada, Mário Jefferson Quirino; Annoni, Raquel; de Oliveira Penoni, Álvaro César

2015-01-01

Epidemiological studies have shown a relationship between long-term use of proton pump inhibitors and bone metabolism. However, this relationship has not yet become established. The aim of the present study was to analyze the mechanical properties and bone mineral density (BMD) of rats that were subjected to long-term omeprazole use. Fifty Wistar rats weighing between 200 and 240 g were divided equally into five groups: OMP300 (omeprazole intake at a dose of 300 μmoL/kg/day); OMP200 (200 μmoL/kg/day); OMP40 (40 μmoL/kg/day); OMP10 (10 μmoL/kg/day); and Cont (control group; intake of dilution vehicle). The solutions were administered for 90 consecutive days. After the rats had been sacrificed, their BMD, the mechanical properties of the dissected femurs and their serum Ca++ levels were analyzed. The BMD of the OMP300 group was lower than that of the controls (p = 0.006). There was no difference on comparing the OMP200, OMP40 and OMP10 groups with the controls. The maximum strength and rigidity of the femur did not differ in the experimental groups in comparison with the controls. The OMP300 group had a statistically lower serum Ca++ concentration than that of the controls (p = 0.049), but the other groups did not show any difference in relation to the controls. Daily intake of 300 μmoL/kg/day of omeprazole decreased the BMD of the femur, but without changes to the rigidity and strength of the femur in adult rats.

Effects of vitamin K in postmenopausal women: mini review.

PubMed

Guralp, Onur; Erel, Cemal Tamer

2014-03-01

Possible benefits of vitamin K on bone health, fracture risk, markers of bone formation and resorption, cardiovascular health, and cancer risk in postmenopausal women have been investigated for over three decades; yet there is no clear evidence-based universal recommendation for its use. Interventional studies showed that vitamin K1 provided significant improvement in undercarboxylated osteocalcin (ucOC) levels in postmenopausal women with normal bone mineral density (BMD); however, there are inconsistent results in women with low BMD. There is no study showing any improvement in bone-alkaline-phosphatase (BAP), n-telopeptide of type-1 collagen (NTX), 25-hydroxy-vitamin D, and urinary markers. Improvement in BMD could not be shown in the majority of the studies; there is no interventional study evaluating the fracture risk. Studies evaluating the isolated effects of menatetrenone (MK-4) showed significant improvement in osteocalcin (OC); however, there are inconsistent results on BAP, NTX, and urinary markers. BMD was found to be significantly increased in the majority of studies. The fracture risk was assessed in three studies, which showed decreased fracture risk to some extent. Although there are proven beneficial effects on some of the bone formation markers, there is not enough evidence-based data to support a role for vitamin K supplementation in osteoporosis prevention among healthy, postmenopausal women receiving vitamin D and calcium supplementation. Interventional studies investigating the isolated role of vitamin K on cardiovascular health are required. Longterm clinical trials are required to evaluate the effect of vitamin K on gynecological cancers. MK-4 seems safe even at doses as high as 45 mg/day. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Evaluation of mandibular bone mineral density using the dual-energy X-ray absorptiometry technique in edentulous subjects living in an endemic fluorosis region.

PubMed

Buyukkaplan, U S; Guldag, M U

2012-07-01

Fluoride is one of the biological trace elements with a strong affinity for osseous, cartilaginous and dental tissue. The dental and skeletal effects of high fluoride intake have already been studied in the literature, but little is known about the effects of high fluoride intake on edentulous mandibles. The purpose of this study was to evaluate the effects of high fluoride intake on mandibular bone mineral density (BMD) measured by the dual-energy X-ray absorptiometry (DXA) technique in edentulous individuals with systemic fluorosis. 32 people who were living in an endemic fluorosis area since birth and 31 people who were living in a non-endemic fluorosis area since birth (control group) participated in this study. Systemic fluorosis was diagnosed in the patients using the sialic acid (NANA)/glycosaminoglycan (GAG) ratio. The BMDs of the mandibles were determined by the DXA technique. The serum NANA/GAG ratios in the fluorosis group were significantly lower than those in the control group (p < 0.001). There was also a statistically significant difference in mandibular BMD measurements (p < 0.05) between the systemic fluorosis and control groups, as measured by the DXA technique. Mandibular body BMD measurements were higher in the fluorosis group (1.25 ± 0.24 g cm(-2)) than in the control group (1.01 ± 0.31 g cm(-2)). The results of the study showed that fluoride intake higher than the optimum level causes increased mandibular BMD in edentulous individuals. Further dose-related studies are needed to determine the effects of high fluoride intake on bony structures of the stomatognathic system.

Bone mineral content and bone mineral density in adolescent girls with anorexia nervosa--a longitudinal study.

PubMed

Jagielska, G; Wolańczyk, T; Komender, J; Tomaszewicz-Libudzic, C; Przedlacki, J; Ostrowski, K

2001-08-01

Total body and lumbar spine bone mineral density (BMD-TB, BMD-L) and total body bone mineral content (BMC-TB) were measured to establish the course of bone demineralization in anorexia nervosa and the clinical factors influencing BMC-TB and BMD changes during treatment. Forty-two girls with DSM III-R anorexia nervosa, age 14.7+/-2.4 years. BMC-TB, BMD-TB and BMD-L were measured in approximately 7-month intervals for 27.8+/-4.1 months using DXA. Despite nutritional improvement, there was an initial decrease of BMD-L, and no change in BMC-TB and BMD-TB. an increase in BMC-TB and BMD was observed after approx. 21 months from the beginning of the study. The improvement in BMC-TB and BMD was related to changes in nutritional status and was significantly marked in younger patients, with earlier anorexia onset and before menarche.

Genetic and environmental determinants of volumetric and areal BMD in multi-generational families of African ancestry: the Tobago Family Health Study.

PubMed

Wang, Xiaojing; Kammerer, Candace M; Wheeler, Victor W; Patrick, Alan L; Bunker, Clareann H; Zmuda, Joseph M

2007-04-01

BMD is higher and fracture risk is lower among individuals of African versus European descent, but little is known about the genetic architecture of BMD in the former group. Heritabilities of areal and volumetric BMD were moderate in our large families of African descent but differed for trabecular and cortical BMD. Populations of African ancestry have lower osteoporotic fracture risk and higher BMD than other ethnic groups. However, there is a paucity of information regarding the genetic and environmental influences on bone health among populations of African heritage. We dissected the genetic architecture of areal BMD measured by DXA at the proximal femur, lumbar spine, and whole body and volumetric BMD measured by pQCT at the distal and proximal radius and tibia in 283 women and 188 men > or =18 years of age (mean, 43 years) from eight multigenerational Afro-Caribbean families (mean family size > 50). Using quantitative genetic methods, we estimated the residual heritability and the effects of anthropometric, demographic, lifestyle, and medical variables on areal and volumetric BMD. Compared with U.S. non-Hispanic blacks and whites, areal BMD at the femoral neck was highest in the Afro-Caribbean men and women at all ages. Trabecular volumetric BMD decreased linearly with increasing age, whereas cortical volumetric BMD did not decrease until age 40-49, especially in women. Anthropometric, lifestyle, and medical factors accounted for 12-32% of the variation in areal and volumetric BMD, and residual heritabilities (range, 0.23-0.52) were similar to those reported in other ethnic groups. Heritability of cortical BMD was substantially lower than that of areal or trabecular volumetric BMD, although the measured covariates accounted for a similar proportion of the total phenotypic variation. Our study is the first comprehensive genetic epidemiologic analysis of volumetric BMD measured by QCT and the first analysis of these traits in extended families of African descent. Genes account for as much or more of the total variation in areal and volumetric BMD than do environmental factors, but these effects seem to differ for trabecular and cortical bone.

Influence of Contrast Media on Bone Mineral Density (BMD) Measurements from Routine Contrast-Enhanced MDCT Datasets using a Phantom-less BMD Measurement Tool.

PubMed

Toelly, Andrea; Bardach, Constanze; Weber, Michael; Gong, Rui; Lai, Yanbo; Wang, Pei; Guo, Yulin; Kirschke, Jan; Baum, Thomas; Gruber, Michael

2017-06-01

Aim  To evaluate the differences in phantom-less bone mineral density (BMD) measurements in contrast-enhanced routine MDCT scans at different contrast phases, and to develop an algorithm for calculating a reliable BMD value. Materials and Methods  112 postmenopausal women from the age of 40 to 77 years (mean age: 57.31 years; SD 9.61) who underwent a clinically indicated MDCT scan, consisting of an unenhanced, an arterial, and a venous phase, were included. A retrospective analysis of the BMD values of the Th12 to L4 vertebrae in each phase was performed using a commercially available phantom-less measurement tool. Results  The mean BMD value in the unenhanced MDCT scans was 79.76 mg/cm³ (SD 31.20), in the arterial phase it was 85.09 mg/cm³ (SD 31.61), and in the venous phase it was 86.18 mg/cm³ (SD 31.30). A significant difference (p < 0.001) was found between BMD values on unenhanced and contrast-enhanced MDCT scans. There was no significant difference between BMD values in the arterial and venous phases (p = 0.228). The following conversion formulas were calculated using linear regression: unenhanced BMD = -2.287 + 0.964 * [arterial BMD value] and -4.517 + 0.978 * [venous BMD value]. The intrarater agreement of BMD measurements was calculated with an intraclass correlation (ICC) of 0.984 and the interobserver reliability was calculated with an ICC of 0.991. Conclusion  Phantom-less BMD measurements in contrast-enhanced MDCT scans result in increased mean BMD values, but, with the formulas applied in our study, a reliable BMD value can be calculated. However, the mean BMD values did not differ significantly between the arterial and venous phases. Key points   · BMD can be assessed on routine CT scans using a phantom-less tool.. · i. v. contrast agent significantly elevates BMD values measured on routine CT scans.. · BMD values measured in the arterial and venous phase did not differ significantly.. · Conversion formulas were defined for the calculation of a reliable BMD.. · The phantom-less tool showed good reliability and is a promising method.. Citation Format · Toelly A, Bardach C, Weber M et al. Influence of Contrast Media on Bone Mineral Density (BMD) Measurements from Routine Contrast-Enhanced MDCT Datasets using a Phantom-less BMD Measurement Tool. Fortschr Röntgenstr 2017; 189: 537 - 543. © Georg Thieme Verlag KG Stuttgart · New York.

Diagnostic reference levels of paediatric computed tomography examinations performed at a dedicated Australian paediatric hospital.

PubMed

Bibbo, Giovanni; Brown, Scott; Linke, Rebecca

2016-08-01

Diagnostic Reference Levels (DRL) of procedures involving ionizing radiation are important tools to optimizing radiation doses delivered to patients and in identifying cases where the levels of doses are unusually high. This is particularly important for paediatric patients undergoing computed tomography (CT) examinations as these examinations are associated with relatively high-dose. Paediatric CT studies, performed at our institution from January 2010 to March 2014, have been retrospectively analysed to determine the 75th and 95th percentiles of both the volume computed tomography dose index (CTDIvol ) and dose-length product (DLP) for the most commonly performed studies to: establish local diagnostic reference levels for paediatric computed tomography examinations performed at our institution, benchmark our DRL with national and international published paediatric values, and determine the compliance of CT radiographer with established protocols. The derived local 75th percentile DRL have been found to be acceptable when compared with those published by the Australian National Radiation Dose Register and two national children's hospitals, and at the international level with the National Reference Doses for the UK. The 95th percentiles of CTDIvol for the various CT examinations have been found to be acceptable values for the CT scanner Dose-Check Notification. Benchmarking CT radiographers shows that they follow the set protocols for the various examinations without significant variations in the machine setting factors. The derivation of DRL has given us the tool to evaluate and improve the performance of our CT service by improved compliance and a reduction in radiation dose to our paediatric patients. We have also been able to benchmark our performance with similar national and international institutions. © 2016 The Royal Australian and New Zealand College of Radiologists.

Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial.

PubMed

Campbell, Craig; McMillan, Hugh J; Mah, Jean K; Tarnopolsky, Mark; Selby, Kathryn; McClure, Ty; Wilson, Dawn M; Sherman, Matthew L; Escolar, Diana; Attie, Kenneth M

2017-04-01

ACE-031 is a fusion protein of activin receptor type IIB and IgG1-Fc, which binds myostatin and related ligands. It aims to disrupt the inhibitory effect on muscle development and provide potential therapy for myopathies like Duchenne muscular dystrophy (DMD). ACE-031 was administered subcutaneously every 2-4 weeks to DMD boys in a randomized, double-blind, placebo-controlled, ascending-dose trial. The primary objective was safety evaluation. Secondary objectives included characterization of pharmacokinetics and pharmacodynamics. ACE-031 was not associated with serious or severe adverse events. The study was stopped after the second dosing regimen due to potential safety concerns of epistaxis and telangiectasias. A trend for maintenance of the 6-minute walk test (6MWT) distance in the ACE-031 groups compared with a decline in the placebo group (not statistically significant) was noted, as was a trend for increased lean body mass and bone mineral density (BMD) and reduced fat mass. ACE-031 use demonstrated trends for pharmacodynamic effects on lean mass, fat mass, BMD, and 6MWT. Non-muscle-related adverse events contributed to the decision to discontinue the study. Myostatin inhibition is a promising therapeutic approach for DMD. Muscle Nerve 55: 458-464, 2017. © 2016 Wiley Periodicals, Inc.

Follicle-stimulating hormone is independently associated with lean mass but not BMD in younger postmenopausal women

PubMed Central

Gourlay, Margaret L.; Specker, Bonny L.; Li, Chenxi; Hammett-Stabler, Catherine A.; Renner, Jordan B.; Rubin, Janet E.

2011-01-01

Purpose Increased follicle-stimulating hormone (FSH) has been associated with lower bone mineral density (BMD) in animal models and longitudinal studies of women, but a direct effect has not been demonstrated. Methods We tested associations between FSH, non-bone body composition measures and BMD in 94 younger (aged 50 to 64 years) postmenopausal women without current use of hormone therapy, adjusting for sex hormone concentrations and clinical risk factors for osteoporosis. Lean mass, fat mass and areal BMD (aBMD) at the spine, femoral neck and total hip were measured using dual energy X-ray absorptiometry (DXA). Volumetric BMD (vBMD) was measured at the distal radius using peripheral quantitative computed tomography (pQCT). Results: FSH was inversely correlated with lean and fat mass, bioavailable estradiol, spine and hip aBMD, and vBMD at the ultradistal radius. In the multivariable analysis, FSH was independently associated with lean mass (β= −0.099, p=0.005) after adjustment for age, race, years since menopause, bioavailable estradiol, bioavailable testosterone, LH, PTH, SHBG and urine N-telopeptide. FSH showed no statistically significant association with aBMD at any site or pQCT measures at the distal radius in adjusted models. Race was independently associated with aBMD, and race and urine N-telopeptide were independently associated with bone area and vBMD. Conclusions After adjustment for hormonal measures and osteoporosis risk factors, higher concentrations of FSH were independently associated with lower lean mass, but not with BMD. Previously reported correlations between FSH and BMD might have been due to indirect associations via lean mass or weight. PMID:22086136

Germline variation in the MTHFR and MTRR genes determines the nadir of bone density in pediatric acute lymphoblastic leukemia: a prospective study.

PubMed

te Winkel, M L; de Muinck Keizer-Schrama, S M P F; de Jonge, R; van Beek, R D; van der Sluis, I M; Hop, W C J; Pieters, R; van den Heuvel-Eibrink, M M

2011-03-01

This study aims to identify folate-metabolism-related genetic risk factors for low bone mineral density (BMD) during/after pediatric acute lymphoblastic leukemia (ALL) treatment. We investigated the influence of methylenetetrahydrofolate reductase (MTHFR 677C > T and 1298A > C) and methionine synthase reductase (MTRR 66A > G) single nucleotide polymorphisms (SNPs) on total body BMD (BMD(TB)) and lumbar spine BMD (BMD(LS)) in 83 patients. Homocysteine, folate and vitamin B12 were determined. BMD was measured repeatedly using dual-energy X-ray absorptiometry in patients ≥ 4 years (n = 68). Carriers of the MTHFR 677 T-allele showed a lower baseline BMD(TB) than non-carriers (-0.38 SDS vs. +0.55 SDS, p = 0.01) and BMD(TB) remained lower during/after treatment. MTHFR 677C>T did not influence treatment-related loss of BMD(TB) (p = 0.39). The MTRR 66 G-allele carriers showed a trend towards a lower BMD(TB) compared with non-carriers. Combining these two SNPs, patients carrying ≥ 2 risk alleles had a significantly lower BMD(TB) (-1.40 SDS) than patients with one (-0.80 SDS) or no risk alleles (-0.31 SDS). Although carriers of the MTHFR 1298A > C had higher homocysteine levels, this SNP was not related to BMD(TB). BMD(LS) of carriers was similar to non-carriers of the investigated SNPs. The MTHFR 677C>T SNP and the MTRR 66A >G SNP were identified as determinants of impaired BMD(TB) in childhood ALL patients. Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.

Correlates of Trabecular and Cortical Volumetric Bone Mineral Density of the Radius and Tibia in Older Men: The Osteoporotic Fractures in Men Study

PubMed Central

Barbour, Kamil E; Zmuda, Joseph M; Strotmeyer, Elsa S; Horwitz, Mara J; Boudreau, Robert; Evans, Rhobert W; Ensrud, Kristine E; Petit, Moira A; Gordon, Christopher L; Cauley, Jane A

2010-01-01

Quantitative computed tomography (QCT) can estimate volumetric bone mineral density (vBMD) and distinguish trabecular from cortical bone. Few comprehensive studies have examined correlates of vBMD in older men. This study evaluated the impact of demographic, anthropometric, lifestyle, and medical factors on vBMD in 1172 men aged 69 to 97 years and enrolled in the Osteoporotic Fractures in Men Study (MrOS). Peripheral quantitative computed tomography (pQCT) was used to measure vBMD of the radius and tibia. The multivariable linear regression models explained up to 10% of the variance in trabecular vBMD and up to 9% of the variance in cortical vBMD. Age was not correlated with radial trabecular vBMD. Correlates associated with both cortical and trabecular vBMD were age (−), caffeine intake (−), total calcium intake (+), nontrauma fracture (−), and hypertension (+). Higher body weight was related to greater trabecular vBMD and lower cortical vBMD. Height (−), education (+), diabetes with thiazolidinedione (TZD) use (+), rheumatoid arthritis (+), using arms to stand from a chair (−), and antiandrogen use (−) were associated only with trabecular vBMD. Factors associated only with cortical vBMD included clinic site (−), androgen use (+), grip strength (+), past smoker (−), and time to complete five chair stands (−). Certain correlates of trabecular and cortical vBMD differed among older men. An ascertainment of potential risk factors associated with trabecular and cortical vBMD may lead to better understanding and preventive efforts for osteoporosis in men. © 2010 American Society for Bone and Mineral Research. PMID:20200975

Case study on the utility of hepatic global gene expression profiling in the risk assessment of the carcinogen furan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jackson, Anna Francina, E-mail: Francina.Jackson@hc-sc.gc.ca; Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa K1S 5B6; Williams, Andrew, E-mail: Andrew.Williams@hc-sc.gc.ca

2014-01-01

Furan is a chemical hepatocarcinogen in mice and rats. Its previously postulated cancer mode of action (MOA) is chronic cytotoxicity followed by sustained regenerative proliferation; however, its molecular basis is unknown. To this end, we conducted toxicogenomic analysis of B3C6F1 mouse livers following three week exposures to non-carcinogenic (0, 1, 2 mg/kg bw) or carcinogenic (4 and 8 mg/kg bw) doses of furan. We saw enrichment for pathways responsible for cytotoxicity: stress-activated protein kinase (SAPK) and death receptor (DR5 and TNF-alpha) signaling, and proliferation: extracellular signal-regulated kinases (ERKs) and TNF-alpha. We also noted the involvement of NF-kappaB and c-Jun inmore » response to furan, which are genes that are known to be required for liver regeneration. Furan metabolism by CYP2E1 produces cis-2-butene-1,4-dial (BDA), which is required for ensuing cytotoxicity and oxidative stress. NRF2 is a master regulator of gene expression during oxidative stress and we suggest that chronic NFR2 activity and chronic inflammation may represent critical transition events between the adaptive (regeneration) and adverse (cancer) outcomes. Another objective of this study was to demonstrate the applicability of toxicogenomics data in quantitative risk assessment. We modeled benchmark doses for our transcriptional data and previously published cancer data, and observed consistency between the two. Margin of exposure values for both transcriptional and cancer endpoints were also similar. In conclusion, using furan as a case study we have demonstrated the value of toxicogenomics data in elucidating dose-dependent MOA transitions and in quantitative risk assessment. - Highlights: • Global gene expression changes in furan-exposed mouse livers were analyzed. • A molecular mode of action for furan-induced hepatocarcinogenesis is proposed. • Key pathways include NRF2, SAPK, ERK and death receptor signaling. • Important roles for TNF-alpha, c-Jun, and NF-κB in tumorigenesis are proposed. • BMD and MoE values from transcriptional and apical data are compared.« less

Change of urinary fluoride and bone metabolism indicators in the endemic fluorosis areas of southern china after supplying low fluoride public water

PubMed Central

2013-01-01

Background Few studies have evaluated health impacts, especially biomarker changes, following implementation of a new environmental policy. This study examined changes in water fluoride, urinary fluoride (UF), and bone metabolism indicators in children after supplying low fluoride public water in endemic fluorosis areas of Southern China. We also assessed the relationship between UF and serum osteocalcin (BGP), calcitonin (CT), alkaline phosphatase (ALP), and bone mineral density to identify the most sensitive bone metabolism indicators related to fluoride exposure. Methods Four fluorosis-endemic villages (intervention villages) in Guangdong, China were randomly selected to receive low-fluoride water. One non-endemic fluorosis village with similar socio-economic status, living conditions, and health care access, was selected as the control group. 120 children aged 6-12 years old were randomly chosen from local schools in each village for the study. Water and urinary fluoride content as well as serum BGP, CT, ALP and bone mineral density were measured by the standard methods and compared between the children residing in the intervention villages and the control village. Benchmark dose (BMD) and benchmark dose lower limit (BMDL) were calculated for each bone damage indicator. Results Our study found that after water source change, fluoride concentrations in drinking water in all intervention villages (A-D) were significantly reduced to 0.11 mg/l, similar to that in the control village (E). Except for Village A where water change has only been taken place for 6 years, urinary fluoride concentrations in children of the intervention villages were lower or comparable to those in the control village after 10 years of supplying new public water. The values of almost all bone indicators in children living in Villages B-D and ALP in Village A were either lower or similar to those in the control village after the intervention. CT and BGP are sensitive bone metabolism indicators related to UF. While assessing the temporal trend of different abnormal bone indicators after the intervention, bone mineral density showed the most stable and the lowest abnormal rates over time. Conclusions Our results suggest that supplying low fluoride public water in Southern China is successful as measured by the reduction of fluoride in water and urine, and changes in various bone indicators to normal levels. A comparison of four bone indicators showed CT and BGP to be the most sensitive indicators. PMID:23425550

Severe bone marrow edema on sacroiliac joint MRI increases the risk of low BMD in patients with axial spondyloarthritis.

PubMed

Kim, Ha Neul; Jung, Joon-Yong; Hong, Yeon Sik; Park, Sung-Hwan; Kang, Kwi Young

2016-03-02

To determine the association between inflammatory and structural lesions on sacroiliac joint (SIJ) MRI and BMD and to identify risk factors for low BMD in patients with axial spondyloarthritis (axSpA). Seventy-six patients who fulfilled the ASAS axSpA criteria were enrolled. All underwent SIJ MRI and BMD measurement at the lumbar spine, femoral neck, and total hip. Inflammatory and structural lesions on SIJ MRI were scored. Laboratory tests and assessment of radiographic and disease activity were performed at the time of MRI. The association between SIJ MRI findings and BMD was evaluated. Among the 76 patients, 14 (18%) had low BMD. Patients with low BMD showed significantly higher bone marrow edema (BME) and deep BME scores on MRI than those with normal BMD (p < 0.047 and 0.007, respectively). Inflammatory lesions on SIJ MRI correlated with BMD at the femoral neck and total hip. Multivariate analysis identified the presence of deep BME on SIJ MRI, increased CRP, and sacroiliitis on X-ray as risk factors for low BMD (OR = 5.6, 14.6, and 2.5, respectively). The presence of deep BME on SIJ MRI, increased CRP levels, and severity of sacroiliitis on X-ray were independent risk factors for low BMD.

[Analysis of risk factors for low bone mineral density in patients with inflammatory bowel disease].

PubMed

Park, Jae Jung; Jung, Sung Ae; Noh, Young Wook; Kang, Min Jung; Jung, Ji Min; Kim, Seong Eun; Jung, Hye Kyung; Shim, Ki Nam; Kim, Tae Hun; Yoo, Kwon; Moon, Il Hwan; Hong, Young Sun

2010-04-01

Several clinical risk factors for low bone mineral density (BMD) in the patients with inflammatory bowel disease (IBD) have been suggested. However, its prevalence and pathophysiology in Korean population have not been fully studied. The aim of this study was to investigate the prevalence and risk factors for low BMD in Korean IBD patient. BMD of the lumbar spine and femur was evaluated using dual-energy X-ray absorptiometry in 30 patients with IBD. Biochemical parameters of bone metabolism, such as serum calcium, phosphorus, osteocalcin, and deoxypyridinoline were measured. The associations between low BMD and clinical parameters such as disease duration, disease activity, drug history, body mass index (BMI), and others were evaluated retrospectively using medical records. Low BMD at the lumbar spine or femur was observed in 63.3% of the patients, and there was no significant difference between the patients with Crohns disease and ulcerative colitis. Clinical and biochemical parameters were irrelevant to BMD. In the patients without glucocorticoid treatment prior to BMD measurement, already 50.0% of patients had low BMD. Low BMD is a common feature in Korean IBD patients, even those who do not use glucocorticoid. The multiple factors may be involved in the pathogenesis of low BMD. Therefore, BMD should be examined in all IBD patients, irrespective of glucocorticoid treatment.

Analysis of LCT-13910 genotypes and bone mineral density in ancient skeletal materials.

PubMed

Mnich, Barbara; Spinek, Anna Elżbieta; Chyleński, Maciej; Sommerfeld, Aleksandra; Dabert, Miroslawa; Juras, Anna; Szostek, Krzysztof

2018-01-01

The relation of LCT-13910 genotypes and bone mineral density (BMD) has been the subject of modern-day human population studies, giving inconsistent results. In the present study we analyze for the first time a relation of LCT-13910 genotypes and BMD in historical skeletal individuals. Ancient population might be a model for testing this association due to elimination of non-natural factors affecting bone density. Among 22 medieval individuals from Sanok churchyard (South-Eastern Poland; dated from XIV to XVII c. AD) we identified 4 individuals with osteoporosis (mean BMD = 0.468 g/cm2, SD = 0.090), 10 individuals with osteopenia (mean BMD = 0.531 g/cm2, SD = 0.066) and 8 individuals with normal BMD values (mean BMD = 0,642 g/cm2, SD = 0.060). Analyses of BMD and LCT-13910 genotypes revealed that mean BMD was the highest (0.583 g/cm2, SD = 0.065) in the individuals with lactose tolerance genotypes (TT and CT). We also found possible association of lower BMD at the radius and CC genotypes due to higher but not statistically significant frequency of osteoporosis in the lactose intolerant group (p = 0.60). Statistically significant correlation was found between BMD and females aged 20-35 years, with tendency to reduce BMD with age (p = 0.02).

Heterogeneity in Spinal Bone Mineral Density Among Young Adults From Three Eastern Provincial Capital Cities in Mainland China.

PubMed

Cheng, Xiao-Guang; Li, Kai; Ou, Shan-Xing; Tang, Guang-Yu; Wang, Qian-Qian; Wang, Chao; Wang, Ling; Tian, Wei

This study compares spinal volumetric bone mineral density (vBMD) with spinal areal bone mineral density (aBMD) among young adults from 3 eastern provincial capital cities in Mainland China. A total of 416 young adults (age range: 20-40 yr) from 3 eastern provincial capital cities (Beijing, Shanghai, and Guangzhou) in Mainland China were recruited in this study. From each subject, the vBMD of the lumbar spine was measured by the Mindways quantitative computed tomography system. Moreover, the aBMD of the lumbar spine, measured by the dual-energy X-ray absorptiometry, was extracted from a previous multicenter large-scale study, and the 420 participants were matched by age, gender, height, weight, as well as geographic territory. The vBMD and the aBMD values were further compared and analyzed. Generally, the bone mineral density (BMD) results were significantly different among participants from the 3 cities (p <0.05). Specifically, both vBMD and aBMD values of participants from Beijing were significantly different from those from Guangzhou (p <0.05). Additionally, a statistically significant difference in aBMD values was also found between participants from Beijing and Shanghai (p <0.05). However, no significant differences were found between participants from Shanghai and Guangzhou in terms of the aBMD and vBMD values (p 1  > 0.05 and p 2  > 0.05). Interestingly, the overall mean vBMD value was 5.9% greater in women than those in men for all the 3 cities (p <0.001). This study demonstrated an overall heterogeneity in spinal BMD among young adults from 3 eastern provincial capital cities in Mainland China. Specifically, the taller and heavier young adults from the northern part of China have smaller spinal vBMD but higher spinal aBMD values than those who were shorter and lighter from the southern part of China. Copyright © 2016 International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Opposite Effects of GSTM1 – and GSTT1 – Gene Deletion Variants on Bone Mineral Density

PubMed Central

Mlakar, Simona Jurkovic; Osredkar, Josko; Prezelj, Janez; Marc, Janja

2011-01-01

Oxidative stress is associated with osteoporosis. The glutathione S-transferases form the major detoxifying group of enzymes responsible for eliminating products of oxidative stress. We have therefore proposed GSTM1 and GSTT1 genes as candidates for studying the genetics of osteoporosis. The aim of the present study was to examine possible association of GSTM1 and GSTT1 gene deletion polymorphisms, alone or in combination, with bone mineral density at femoral neck (BMD_fn), lumbar spine (BMD_ls) and total hip (BMD_th) in Slovenian elderly women and men. GSTM1 and GSTT1 gene deletion polymorphisms in 712 elderly people were analyzed using the triplex PCR method for the presence of GSTM1 and GSTT1 gene segments. BMD_fn, BMD_ls and BMD_th were measured by the dual-energy X-ray absorptiometry (DEXA) method. Results were analyzed using univariate statistic model adjusted for sex, body mass index (BMI) and age. Our results showed the significant differences in BMD_th, BMD_ls and BMD_fn values (p = 0.031, 0.017 and 0.023, respectively) in subgroups of GSTT1 gene deletion polymorphism. For GSTM1 gene deletion polymorphism borderline significant association was found with BMD_ls (p = 0.100). Furthermore, subjects with homozygous deletion of GSTT1 gene showed higher BMD values on all measured skeletal sites and, in contrast, subjects with homozygous deletion of GSTM1 gene showed lower BMD values. Moreover, a gene-gene interaction study showed significant association of GSTM1-null and GSTT1-null polymorphisms with BMD_ls values (p = 0.044). Carriers with a combination of the presence of GSTT1 gene and the homozygous absence of GSTM1 gene fragment were associated with the lower BMD values at all skeletal sites. The significant association of combination of GSTT1 gene presence and homozygous absence of GSTM1 gene with BMD was demonstrated, suggesting that it could be used, if validated in other studies, as genetic marker for low BMD. PMID:22048269

Opposite effects of GSTM1--and GSTT1: gene deletion variants on bone mineral density.

PubMed

Mlakar, Simona Jurkovic; Osredkar, Josko; Prezelj, Janez; Marc, Janja

2011-01-01

Oxidative stress is associated with osteoporosis. The glutathione S-transferases form the major detoxifying group of enzymes responsible for eliminating products of oxidative stress. We have therefore proposed GSTM1 and GSTT1 genes as candidates for studying the genetics of osteoporosis. The aim of the present study was to examine possible association of GSTM1 and GSTT1 gene deletion polymorphisms, alone or in combination, with bone mineral density at femoral neck (BMD_fn), lumbar spine (BMD_ls) and total hip (BMD_th) in Slovenian elderly women and men.GSTM1 and GSTT1 gene deletion polymorphisms in 712 elderly people were analyzed using the triplex PCR method for the presence of GSTM1 and GSTT1 gene segments. BMD_fn, BMD_ls and BMD_th were measured by the dual-energy X-ray absorptiometry (DEXA) method. Results were analyzed using univariate statistic model adjusted for sex, body mass index (BMI) and age. Our results showed the significant differences in BMD_th, BMD_ls and BMD_fn values (p=0.031, 0.017 and 0.023, respectively) in subgroups of GSTT1 gene deletion polymorphism. For GSTM1 gene deletion polymorphism borderline significant association was found with BMD_ls (p=0.100). Furthermore, subjects with homozygous deletion of GSTT1 gene showed higher BMD values on all measured skeletal sites and, in contrast, subjects with homozygous deletion of GSTM1 gene showed lower BMD values. Moreover, a gene-gene interaction study showed significant association of GSTM1-null and GSTT1-null polymorphisms with BMD_ls values (p=0.044). Carriers with a combination of the presence of GSTT1 gene and the homozygous absence of GSTM1 gene fragment were associated with the lower BMD values at all skeletal sites. The significant association of combination of GSTT1 gene presence and homozygous absence of GSTM1 gene with BMD was demonstrated, suggesting that it could be used, if validated in other studies, as genetic marker for low BMD.

Effects of obesity and diabetes on rate of bone density loss.

PubMed

Leslie, W D; Morin, S N; Majumdar, S R; Lix, L M

2018-01-01

In this large registry-based study, women with diabetes had marginally greater bone mineral density (BMD) loss at the femoral neck but not at other measurement sites, whereas obesity was not associated with greater BMD loss. Our data do not support the hypothesis that rapid BMD loss explains the increased fracture risk associated with type 2 diabetes and obesity observed in prior studies. Type 2 diabetes and obesity are associated with higher bone mineral density (BMD) which may be less protective against fracture than previously assumed. Inconsistent data suggest that rapid BMD loss may be a contributing factor. We examined the rate of BMD loss in women with diabetes and/or obesity in a population-based BMD registry for Manitoba, Canada. We identified 4960 women aged ≥ 40 years undergoing baseline and follow-up BMD assessments (mean interval 4.3 years) without confounding medication use or large weight fluctuation. We calculated annualized rate of BMD change for the lumbar spine, total hip, and femoral neck in relation to diagnosed diabetes and body mass index (BMI) category. Baseline age-adjusted BMD was greater in women with diabetes and for increasing BMI category (all P < 0.001). In women with diabetes, unadjusted BMD loss was less at the lumbar spine (P = 0.017), non-significantly greater at the femoral neck (P = 0.085), and similar at the total hip (P = 0.488). When adjusted for age and BMI, diabetes was associated with slightly greater femoral neck BMD loss (- 0.0018 g/cm 2 /year, P = 0.012) but not at the lumbar spine or total hip. There was a strong linear effect of increasing BMI on attenuated BMI loss at the lumbar spine with negligible effects on hip BMD. Diabetes was associated with slightly greater BMD loss at the femoral neck but not at other measurement sites. BMD loss at the lumbar spine was reduced in overweight and obese women but BMI did not significantly affect hip BMD loss.

Concordance of transcriptional and apical benchmark dose levels for conazole-induced liver effects in mice.

PubMed

Bhat, Virunya S; Hester, Susan D; Nesnow, Stephen; Eastmond, David A

2013-11-01

The ability to anchor chemical class-based gene expression changes to phenotypic lesions and to describe these changes as a function of dose and time informs mode-of-action determinations and improves quantitative risk assessments. Previous global expression profiling identified a 330-probe cluster differentially expressed and commonly responsive to 3 hepatotumorigenic conazoles (cyproconazole, epoxiconazole, and propiconazole) at 30 days. Extended to 2 more conazoles (triadimefon and myclobutanil), the present assessment encompasses 4 tumorigenic and 1 nontumorigenic conazole. Transcriptional benchmark dose levels (BMDL(T)) were estimated for a subset of the cluster with dose-responsive behavior and a ≥ 5-fold increase or decrease in signal intensity at the highest dose. These genes primarily encompassed CAR/RXR activation, P450 metabolism, liver hypertrophy- glutathione depletion, LPS/IL-1-mediated inhibition of RXR, and NRF2-mediated oxidative stress pathways. Median BMDL(T) estimates from the subset were concordant (within a factor of 2.4) with apical benchmark doses (BMDL(A)) for increased liver weight at 30 days for the 5 conazoles. The 30-day median BMDL(T) estimates were within one-half order of magnitude of the chronic BMDLA for hepatocellular tumors. Potency differences seen in the dose-responsive transcription of certain phase II metabolism, bile acid detoxification, and lipid oxidation genes mirrored each conazole's tumorigenic potency. The 30-day BMDL(T) corresponded to tumorigenic potency on a milligram per kilogram day basis with cyproconazole > epoxiconazole > propiconazole > triadimefon > myclobutanil (nontumorigenic). These results support the utility of measuring short-term gene expression changes to inform quantitative risk assessments from long-term exposures.

Development of a Food Group-Based Diet Score and Its Association with Bone Mineral Density in the Elderly: The Rotterdam Study

PubMed Central

de Jonge, Ester A. L.; Kiefte-de Jong, Jessica C.; de Groot, Lisette C. P. G. M.; Voortman, Trudy; Schoufour, Josje D.; Zillikens, M. Carola; Hofman, Albert; Uitterlinden, André G.; Franco, Oscar H.; Rivadeneira, Fernando

2015-01-01

No diet score exists that summarizes the features of a diet that is optimal for bone mineral density (BMD) in the elderly. Our aims were (a) to develop a BMD-Diet Score reflecting a diet that may be beneficial for BMD based on the existing literature, and (b) to examine the association of the BMD-Diet Score and the Healthy Diet Indicator, a score based on guidelines of the World Health Organization, with BMD in Dutch elderly participating in a prospective cohort study, the Rotterdam Study (n = 5144). Baseline dietary intake, assessed using a food frequency questionnaire, was categorized into food groups. Food groups that were consistently associated with BMD in the literature were included in the BMD-Diet Score. BMD was measured repeatedly and was assessed using dual energy X-ray absorptiometry. The BMD-Diet Score considered intake of vegetables, fruits, fish, whole grains, legumes/beans and dairy products as “high-BMD” components and meat and confectionary as “low-BMD” components. After adjustment, the BMD-Diet Score was positively associated with BMD (β (95% confidence interval) = 0.009 (0.005, 0.012) g/cm2 per standard deviation). This effect size was approximately three times as large as has been observed for the Healthy Diet Indicator. The food groups included in our BMD-Diet Score could be considered in the development of future dietary guidelines for healthy ageing. PMID:26295256

Alendronate for the Treatment of Osteoporosis in Men: A Meta-Analysis of Randomized Controlled Trials.

PubMed

Xu, Zhiguo

Alendronate has been widely used in the treatment of osteoporosis. However, the effect of alendronate in the male osteoporosis remains controversial. We conducted a meta-analysis to assess the efficacy of alendronate in the treatment of men with osteoporosis. PubMed, Embase, and Web of Science were searched from their inception to October 25, 2015. Eligible studies were randomized controlled trials that evaluated the effect of alendronate in the male osteoporosis. The outcomes included mean percentage changes in bone mineral density (BMD) of lumbar spine, femoral neck, total hip, trochanter, and total body, and the incidence of new vertebral fractures. Results were expressed with weighted mean difference (WMD), and risk ratio with 95% CIs. A fixed-effects model or random-effects model was used for the meta-analysis according to heterogeneity. Eight studies involving 988 patients met the inclusion criteria. Alendronate significantly increased the mean percentage BMD at the lumbar spine (WMD = 4.95, 95% CI, 2.40-7.49; P < 0.001), femoral neck (WMD = 2.59, 95% CI, 1.52-3.66; P < 0.001), and total hip (WMD = 2.39, 95% CI, 1.05-3.27; P < 0.001), but not at the trochanter (WMD = 1.76, 95% CI, -0.69 to 4.21; P = 0.158) and total body (WMD = 3.29, 95% CI, -0.04 to 6.62; P = 0.053). Moreover, alendronate was also decreased the incidence of vertebral fractures (risk ratio = 0.46, 95% CI, 0.28-0.77; P = 0.003). Subgroup analysis showed that among the male osteoporosis, greater increase in the lumbar spine BMD (WMD = 5.99, 95% CI, 3.42-8.56; P < 0.001) and femoral neck BMD (WMD = 3.66, 95% CI, 2.57-4.76; P = 0.023) was observed when the alendronate was administrated with a dose of 10 mg. Based on current evidence, alendronate shows beneficial effect on the lumbar spine, femoral neck, and total hip BMD, and the incidence of new vertebral fractures.

The balance between soluble receptors regulating IL-6 trans-signaling is predictive for the RANKL/osteoprotegerin ratio in postmenopausal women with rheumatoid arthritis.

PubMed

Oelzner, Peter; Franke, Sybille; Lehmann, Gabriele; Eidner, Thorsten; Hein, Gert; Wolf, Gunter

2012-01-01

The objective of this study is to investigate the relationship between soluble components of the interleukin 6 (IL-6) system mediating and modifying IL-6 trans-signaling and the RANKL-RANK-osteoprotegerin system in postmenopausal women with rheumatoid arthritis (RA). The following parameters were investigated in 126 postmenopausal women with RA: IL-6, soluble IL-6-receptor (sIL-6R), soluble glycoprotein 130 (sgp130), sRANKL, osteoprotegerin (OPG), osteocalcin, erythrocyte sedimentation rate and C-reactive protein in sera, pyridinolin and desoxypyridinolin crosslinks in the morning urine. Bone mineral density (BMD) was measured by dual X-ray absorptiometry at the lumbar spine (BMD-LS) and at the femoral neck (BMD-FN). Predictors of RANKL/OPG ratio and BMD were evaluated by multiple linear regression analysis. The following determinants of the RANKL/OPG ratio were identified: sIL-6R/sgp130 ratio and daily glucocorticoid (GC) dose as positive determinants in the whole group (R (2) = 0.56; P = 0.001), sIL-6R/sgp130 ratio as the exclusive positive determinant in patients with GC therapy (R (2) = 0.48; P = 0.001) and sgp130 as negative determinant in patients without GC (R (2) = 0.42; P = 0.031). Sgp130 was highly significantly positively correlated with OPG in the whole group (P < 0.001) as well as in patients with (n = 70; P < 0.05) and without GC therapy (n = 56; P < 0.01). sIL-6R was the main negative predictor of BMD-LS (R (2) = 0.41; P = 0.019). High sIL-6R/sgp130 ratio and/or low sgp130 are associated with a high sRANKL/OPG ratio in sera of postmenopausal women with RA indicating the critical significance of IL-6 trans-signaling for an increase in the RANKL/OPG ratio and of bone resorption. Inhibition of IL-6 trans-signaling may be an effective bone-protecting principle in postmenopausal women with RA.

25-Hydroxyvitamin D Threshold for the Effects of Vitamin D Supplements on Bone Density Secondary Analysis of a Randomized Controlled Trial.

PubMed

Macdonald, Helen M; Reid, Ian R; Gamble, Gregory D; Fraser, William D; Tang, Jonathan C; Wood, Adrian D

2018-04-17

Most trials of vitamin D supplementation have shown no benefits on bone density (BMD), though severe vitamin D deficiency causes osteomalacia which is associated with profound BMD deficits. Recently, the ViDA-BMD study from New Zealand demonstrated a threshold of baseline 25-hydroxyvitamin D (30 nmol/L) below which vitamin D supplementation did benefit BMD. We have now re-examined data from a similar trial in Aberdeen to determine whether a baseline 25-hydroxyvitamin D threshold of 30 nmol/L is also observed in that database. The Aberdeen study recruited 305 postmenopausal women in late winter and randomized them to receive placebo, vitamin D 400 IU/day or vitamin D 1000 IU/day over one year. As previously reported, BMD loss at the hip was reduced by vitamin D 1000 IU/day only, and there was no significant treatment effect of either dose at the lumbar spine. In the present analysis, when the trial participants were grouped according to whether their baseline 25-hydroxyvitamin D was ≤30 nmol/L or above this threshold, significant treatment effects were apparent at both the spine and hip in those with baseline 25-hydroxyvitamin D ≤30 nmol/L, but no significant effects were apparent in those with baseline 25-hydroxyvitamin D above this level. There was evidence of a similar threshold for effects on parathyroid hormone, but no groups showed changes in bone turnover markers during the study. It is concluded that vitamin D supplements only increase bone density in adults with nadir 25-hydroxyvitamin D ≤30 nmol/L. This moves us further towards a trial-based definition of vitamin D deficiency in adults with adequate calcium intakes, and suggests that supplement use should be targeted accordingly. Future trials of vitamin D supplementation should focus on individuals with 25-hydroxyvitamin D concentrations in this range. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Bone mineral density, chemical composition and biomechanical properties of the tibia of female rats exposed to cadmium since weaning up to skeletal maturity.

PubMed

Brzóska, M M; Majewska, K; Moniuszko-Jakoniuk, J

2005-10-01

The influence of exposure to cadmium (Cd) during skeletal development on the risk of bone fractures at the stage of skeletal maturity was investigated on a female rat model of human exposure. The tibias of rats treated with 1, 5 or 50 mg Cd/l in drinking water for 3, 6, 9 and 12 months (since weaning) were used. The exposure to Cd dose- and time-dependently influenced the tibia bone mineral density (BMD) and chemical composition. In skeletally matured animals, at each level of the exposure to Cd, the BMD at the whole tibia and its diaphysis as well as the percentage of minerals content in the bone, including the content of zinc, copper and iron, were decreased compared to control. Moreover, in the 50 mg Cd/l group, the percentage of organic components content increased. The Cd-induced changes, at all levels of exposure, resulted in weakening in the yield strength and fracture strength of the tibia (a three-point bending test of the diaphysis and compression test with vertical loading) of the skeletally matured females. A very important and clinically useful finding of this study is that a decrease (even by several percent) in the tibia BMD results in weakness in the bone biomechanical properties and that the BMD may predict the risk of its fracture at the exposure to Cd. Moreover, the results together with our previous findings seem to suggest that tibia, due to higher vulnerability of its diaphysis, compared to the femoral diaphysis, to damage by Cd may be more useful than femur to investigate the effect of Cd on the cortical bone. The present study revealed that a low exposure to Cd (1 mg Cd/l), corresponding to low human environmental exposure, during the skeletal development affects the tibia mineral status leading to weakening in its mechanical properties at the skeletal maturity. The findings allow for the conclusion that environmental exposure to Cd during childhood and adolescence may enhance the risk of low BMD and fractures at adulthood.

Associations between bone-alkaline phosphatase and bone mineral density in adults with and without diabetes

PubMed Central

Chen, Hailing; Li, Jufen; Wang, Qian

2018-01-01

Abstract Insufficient evidence is available to reliably compare the roles of bone alkaline phosphatase (BAP) and bone mineral density (BMD) in diabetes. This study aimed to compare associations between BAP and BMD in adults with and without diabetes to elucidate fracture risk in diabetes. Data were extracted from the National Health and Nutrition Examination Survey (NHANES), 2001–2004, including 4197 adults aged 20 to 49 years, 143 with diabetes (DM group), and 4054 without (non-DM group). Main outcome measure was BMD and regression analyses were performed to identify serum BAP and other covariates associated with total BMD. BMD decreased significantly in DM patients when BAP was increased. In the non-DM group, all BMD results were significantly decreased when BAP was increased. Factors associated with total BMD varied with DM status. Lifestyle measures such as smoking and physical activity were also associated with BMD in the non-DM group. BAP and BMD are inversely associated in DM and non-DM patients. BAP is significantly associated with BMD after controlling for other variables, suggesting that BAP may interact with other factors altering bone metabolism in DM patients. PMID:29702995

Low bone mineral density in children and adolescents with inflammatory bowel disease: a population-based study from Western Sweden.

PubMed

Schmidt, Susanne; Mellström, Dan; Norjavaara, Ensio; Sundh, S Valter; Saalman, Robert

2009-12-01

Low bone mineral density (BMD) has been recognized as a potential problem in children with inflammatory bowel disease (IBD). The aim of the study was to investigate BMD in Swedish children and adolescents with IBD and to evaluate possible factors affecting BMD. To evaluate BMD, all patients (n = 144) underwent a dual-energy X-ray absorptiometry (DXA) of the whole body and the spine. BMD values were expressed as Z-scores using normative pediatric data from Lunar (GE Medical Systems). In this population-based study, the lowest BMD values were found in the lumbar spine. The entire IBD group showed significantly lower BMD Z-scores of the lumbar spine (L2-L4) in comparison to healthy references (-0.8 standard deviation [SD], range -5.9 to 3.7 SD, P < 0.001). Decreased BMD with a Z-score < -1 SD occurred in 46.7% of the individuals with Crohn's disease (CD) and in 47.0% of those with ulcerative colitis (UC). Low BMD with a Z-score ≤ -2 SD was present in 26.7% of the patients with CD and in 24.1% of the UC patients. In a multiple regression model with BMD lumbar spine as the depending variable, possible factors associated with lower BMD were male gender, low body mass index (BMI), and treatment with azathioprine. Low BMD is prevalent in Swedish pediatric patients with IBD. Possible risk factors for lower BMD are male gender, low BMI, and treatment with azathioprine, as a probable marker of disease course severity. Copyright © 2009 Crohn's & Colitis Foundation of America, Inc.

Evaluation of bone mineral density and related parameters in patients with haemophilia: a single center cross-sectional study

PubMed Central

Kiper Unal, Hatice Demet; Comert Ozkan, Melda; Atilla, Fatos Dilan; Demirci, Zuhal; Soyer, Nur; Yildirim Simsir, Ilgin; Omur, Ozgur; Capaci, Kazim; Saydam, Guray; Sahin, Fahri

2017-01-01

Haemophilia has been associated with low bone mineral density (BMD) probably due to some predisposing factors. The aim of this study was to evaluate the relationship between BMD and potential clinical predictors in adult haemophilic patients. Fortynine patients with moderate and severe haemophilia were enrolled. BMD was measured by Dual Energy X-Ray Absorptiometry (DXA) and blood tests were performed for vitamin D, calcium, phosphore, alkaline phosphatase and parathormone levels. Functional Independence Score in Haemophilia (FISH) and Haemophilia Joint Health Score (HJHS) were used to assess musculoskeletal functions. Body mass index (BMI), Hepatitis C virus (HCV)/Human immunodeficiency virus (HIV) seropositivity and smoking status were also recorded. BMD was found lower than expected for reference age in 34.8% of patients of less than 50 years old. In patients older than 50 years, 66.6% of them had osteoporosis and 33.3% of them had normal BMD. FISH score was statistically significant correlated with BMD of total hip (TH) and femur neck (FN) but not with lumbar spine (LS). In eligible patients, there was also a statistically significant correlation between BMD of TH and HJHS. Vitamine D deficiency was common and found in 77.5% of patients, although there was no significant correlation with BMD. Also no correlation was found between BMD and blood tests, HCV/HIV status, BMI and smoking. This study confirmed that patients with haemophilia have an increased prevelance of low BMD even in younger group. Our results showed that there are significant correlations between FISH score and BMD of TH and FN and also between HJHS score and BMD of TH. Thus, using scoring systems may be beneficial as a simple predictors of BMD to reflect the severity of haemophilic arthropathy. PMID:29181264

Bone mineral density and bone turnover among young women in Chiang Mai, Thailand.

PubMed

Iwasaki, Eriko; Morakote, Nuntana; Chaovistsaree, Somsak; Matsuo, Hiroya

2014-03-12

The present study was carried out to investigate the influence of lifestyle on bone mineral density (BMD) and bone turnover among young women in Chiang Mai, Thailand. A total of 177 young women affiliated with Chiang Mai University hospital were enrolled. Firstly, questionnaires about their lifestyle and the Osteoporosis Knowledge Test (OKT) were examined. The measurement of BMD was assessed by Quantitative Ultrasound (QUS). Secondly, based on the measurement of BMD, the subjects were divided into 2 groups, a Low BMD group (L group: less than YAM-1.0SD) and a Normal BMD group (N group: more than YAM-1.0SD). L group (n=23) and N group (n=23) were examined using Osteocalcine (OC), type 1 collagen cross-linked N-telopeptide (NTx) and undercarboxylated osteocalcin (ucOC) as bone turnover markers, and serum Ca, 1,25-(OH)2Vitamin D, Vitamin K1 and Vitamin K2 (MK-4) as bone turnover related factors. Based on the results, the percentage of Low BMD group was 23.2%. Concerning lifestyle and BMD, the BMD of the low cheese intake group was 99.7± 17.0 and the BMD of the high cheese intake one was 110.0± 23.3 (p<0.05). The BMD of the fracture experience group was 82.5± 11.6 and the BMD of no-fracture group was 103.3± 19.6 (p<0.05). These were significant differences in ucOC and 1,25-(OH)2Vitamin D between L and N groups (p<0.05). It was suggested that BMI, food and fracture experience might affect BMD level and suppression of bone formation might have contributed to the low BMD group among young women in Chiang Mai, Thailand.

Evaluation of bone mineral density and related parameters in patients with haemophilia: a single center cross-sectional study.

PubMed

Kiper Unal, Hatice Demet; Comert Ozkan, Melda; Atilla, Fatos Dilan; Demirci, Zuhal; Soyer, Nur; Yildirim Simsir, Ilgin; Omur, Ozgur; Capaci, Kazim; Saydam, Guray; Sahin, Fahri

2017-01-01

Haemophilia has been associated with low bone mineral density (BMD) probably due to some predisposing factors. The aim of this study was to evaluate the relationship between BMD and potential clinical predictors in adult haemophilic patients. Fortynine patients with moderate and severe haemophilia were enrolled. BMD was measured by Dual Energy X-Ray Absorptiometry (DXA) and blood tests were performed for vitamin D, calcium, phosphore, alkaline phosphatase and parathormone levels. Functional Independence Score in Haemophilia (FISH) and Haemophilia Joint Health Score (HJHS) were used to assess musculoskeletal functions. Body mass index (BMI), Hepatitis C virus (HCV)/Human immunodeficiency virus (HIV) seropositivity and smoking status were also recorded. BMD was found lower than expected for reference age in 34.8% of patients of less than 50 years old. In patients older than 50 years, 66.6% of them had osteoporosis and 33.3% of them had normal BMD. FISH score was statistically significant correlated with BMD of total hip (TH) and femur neck (FN) but not with lumbar spine (LS). In eligible patients, there was also a statistically significant correlation between BMD of TH and HJHS. Vitamine D deficiency was common and found in 77.5% of patients, although there was no significant correlation with BMD. Also no correlation was found between BMD and blood tests, HCV/HIV status, BMI and smoking. This study confirmed that patients with haemophilia have an increased prevelance of low BMD even in younger group. Our results showed that there are significant correlations between FISH score and BMD of TH and FN and also between HJHS score and BMD of TH. Thus, using scoring systems may be beneficial as a simple predictors of BMD to reflect the severity of haemophilic arthropathy.

Risk of Fracture in Women with Sarcopenia, Low Bone Mass, or Both.

PubMed

Harris, Rebekah; Chang, Yuefang; Beavers, Kristen; Laddu-Patel, Deepika; Bea, Jennifer; Johnson, Karen; LeBoff, Meryl; Womack, Catherine; Wallace, Robert; Li, Wenjun; Crandall, Carolyn; Cauley, Jane

2017-12-01

To determine whether women with sarcopenia and low bone mineral density (BMD) are at greater risk of clinical fractures than those with sarcopenia or low BMD alone. Women's Health Initiative (WHI) Observational and Clinical trials. Three U.S. clinical centers (Pittsburgh, PA; Birmingham, AL; Phoenix/Tucson, AZ). Women (mean age 63.3 ± 0.07) with BMD measurements (N = 10,937). Sarcopenia was defined as appendicular lean mass values corrected for height and fat mass. Low BMD was defined as a femoral neck T-score less than -1.0 based on the Third National Health and Nutrition Examination Survey reference database for white women. Cox proportional hazards analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). We followed women for incident fractures over a median of 15.9 years. Participants were classified into mutually exclusive groups based on BMD and sarcopenia status: normal BMD and no sarcopenia (n = 3,857, 35%), sarcopenia alone (n = 774, 7%), low BMD alone (n = 4,907, 45%), and low BMD and sarcopenia (n = 1,399, 13%). Women with low BMD, with (HR = 1.72, 95% CI = 1.44-2.06) or without sarcopenia (HR = 1.58, 95% CI = 1.37-1.83), had greater risk of fracture than women with normal BMD; the difference remained statistically significant after adjustment for important covariates. Women with low BMD, with (HR = 2.78, 95% CI = 1.78-4.30 and without (HR = 2.42, 95% CI = 1.63-3.59) sarcopenia had higher risk of hip fractures. Women with sarcopenia alone had similar HRs to women with normal BMD. Compared to women with normal BMD. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

The effect of two doses of dried plum on bone density and bone biomarkers in osteopenic postmenopausal women: a randomized, controlled trial.

PubMed

Hooshmand, S; Kern, M; Metti, D; Shamloufard, P; Chai, S C; Johnson, S A; Payton, M E; Arjmandi, B H

2016-07-01

Daily consumption of 50 g of dried plum (equivalent to 5-6 dried plums) for 6 months may be as effective as 100 g of dried plum in preventing bone loss in older, osteopenic postmenopausal women. To some extent, these results may be attributed to the inhibition of bone resorption with the concurrent maintenance of bone formation. The objective of our current study was to examine the possible dose-dependent effects of dried plum in preventing bone loss in older osteopenic postmenopausal women. Forty-eight osteopenic women (65-79 years old) were randomly assigned into one of three treatment groups for 6 months: (1) 50 g of dried plum; (2) 100 g of dried plum; and (3) control. Total body, hip, and lumbar bone mineral density (BMD) were evaluated at baseline and 6 months using dual-energy X-ray absorptiometry. Blood biomarkers including bone-specific alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRAP-5b), high-sensitivity C-reactive protein (hs-CRP), insulin-like growth factor-1 (IGF-1), and sclerostin were measured at baseline, 3 months, and 6 months. Osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), calcium, phosphorous, and vitamin D were measured at baseline and 6 months. Both doses of dried plum were able to prevent the loss of total body BMD compared with that of the control group (P < 0.05). TRAP-5b, a marker of bone resorption, decreased at 3 months and this was sustained at 6 months in both 50 and 100 g dried plum groups (P < 0.01 and P < 0.04, respectively). Although there were no significant changes in BAP for either of the dried plum groups, the BAP/TRAP-5b ratio was significantly (P < 0.05) greater at 6 months in both dried plum groups whereas there were no changes in the control group. These results confirm the ability of dried plum to prevent the loss of total body BMD in older osteopenic postmenopausal women and suggest that a lower dose of dried plum (i.e., 50 g) may be as effective as 100 g of dried plum in preventing bone loss in older, osteopenic postmenopausal women. This may be due, in part, to the ability of dried plums to inhibit bone resorption. This clinical trial was registered at ClinicalTrials.gov: NCT02325895 .

Preadipocyte factor-1 levels are higher in women with hypothalamic amenorrhea and are associated with bone mineral content and bone mineral density through a mechanism independent of leptin.

PubMed

Aronis, Konstantinos N; Kilim, Holly; Chamberland, John P; Breggia, Anne; Rosen, Clifford; Mantzoros, Christos S

2011-10-01

Preadipocyte factor 1 (pref-1) is increased in anorexia nervosa and is associated negatively with bone mineral density (BMD). No previous studies exist on pref-1 in women with exercise-induced hypothalamic amenorrhea (HA), which similar to anorexia nervosa, is an energy-deficiency state associated with hypoleptinemia. Our objective was to evaluate whether pref-1 levels are also elevated and associated with low BMD and to assess whether leptin regulates pref-1 levels in women with HA. Study 1 was a double-blinded, placebo-controlled randomized clinical trial of metreleptin administration in women with HA. Study 2 was an open-label study of metreleptin administration in low physiological, supraphysiological, and pharmacological doses in healthy women volunteers. At Beth Israel Deaconess Medical Center, 20 women with HA and leptin levels higher than 5 ng/ml and nine healthy control women participated in study 1, and five healthy women participated in study 2. For study 1, 20 HA subjects were randomized to receive either 0.08 mg/kg metreleptin (n = 11) or placebo (n = 9). For study 2, five healthy subjects received 0.01, 0.1, and 0.3 mg/kg metreleptin in both fed and fasting conditions for 1 and 3 d, respectively. Circulating pref-1 and leptin levels were measured. Pref-1 was significantly higher in HA subjects vs. controls (P = 0.035) and negatively associated with BMD (ρ = -0.38; P < 0.01) and bone mineral content (ρ = -0.32; P < 0.05). Metreleptin administration did not alter pref-1 levels in any study reported herein. Pref-1 is higher in HA subjects than controls. Metreleptin administration at low physiological, supraphysiological, and pharmacological doses does not affect pref-1 levels, suggesting that hypoleptinemia is not responsible for higher pref-1 levels and that leptin does not regulate pref-1.

Low Preoperative BMD Is Related to High Migration of Tibia Components in Uncemented TKA-92 Patients in a Combined DEXA and RSA Study With 2-Year Follow-Up.

PubMed

Andersen, Mikkel R; Winther, Nikkolaj S; Lind, Thomas; Schrøder, Henrik M; Flivik, Gunnar; Petersen, Michael M

2017-07-01

The fixation of uncemented tibia components in total knee arthroplasty may rely on the bone quality of the tibia; however, no previous studies have shown convincing objective proof of this. Component migration is relevant as it has been shown to predict aseptic loosening. We performed 2-year follow-up of 92 patients who underwent total knee arthroplasty surgery with an uncemented tibia component. Bone mineral density (BMD; g/cm 2 ) of the tibia host bone was measured preoperatively using dual energy X-ray absorptiometry. The proximal tibia was divided into 2 regions of interest (ROI) in the part of the tibia bone where the components were implanted. Radiostereometric analysis was performed postoperatively and after 3, 6, 12, and 24 months. The primary outcome was maximum total point motion (MTPM; mm). Regression analysis was performed to evaluate the relation between preoperative BMD and MTPM. We found low preoperative BMD in ROI1 to be significantly related to high MTPM at all follow-ups: after 3 months (R 2  = 20%, P BMD  = 0.017), 6 months (R 2  = 29%, P BMD  = 0.003), 12 months (R 2  = 33%, P BMD  = 0.001), and 24 months (R 2  = 27%, P BMD  = 0.001). We also found a significant relation for low BMD in ROI2 and high MTPM: 3 months (R 2  = 19%, P BMD  = 0.042), 6 months (R 2  = 28%, P BMD  = 0.04), 12 months (R 2  = 32%, P BMD  = 0.004), and 24 months (R 2  = 24%, P BMD  = 0.005). Low preoperative BMD in the tibia is related to high MTPM. Thus, high migration of uncemented tibia components is to be expected in patients with poor bone quality. Copyright © 2017 Elsevier Inc. All rights reserved.

Vertebral Volumetric Bone Density and Strength Are Impaired in Women With Low-Weight and Atypical Anorexia Nervosa

PubMed Central

Bachmann, Katherine N.; Schorr, Melanie; Bruno, Alexander G.; Bredella, Miriam A.; Lawson, Elizabeth A.; Gill, Corey M.; Singhal, Vibha; Meenaghan, Erinne; Gerweck, Anu V.; Slattery, Meghan; Eddy, Kamryn T.; Ebrahimi, Seda; Koman, Stuart L.; Greenblatt, James M.; Keane, Robert J.; Weigel, Thomas; Misra, Madhusmita; Bouxsein, Mary L.; Klibanski, Anne

2017-01-01

Context: Areal bone mineral density (BMD) is lower, particularly at the spine, in low-weight women with anorexia nervosa (AN). However, little is known about vertebral integral volumetric BMD (Int.vBMD) or vertebral strength across the AN weight spectrum, including “atypical” AN [body mass index (BMI) ≥18.5 kg/m2]. Objective: To investigate Int.vBMD and vertebral strength, and their determinants, across the AN weight spectrum Design: Cross-sectional observational study Setting: Clinical research center Participants: 153 women (age 18 to 45): 64 with low-weight AN (BMI <18.5 kg/m2; 58% amenorrheic), 44 with atypical AN (18.5≤BMI<23 kg/m2; 30% amenorrheic), 45 eumenorrheic controls (19.2≤BMI<25 kg/m2). Measures: Int.vBMD and cross-sectional area (CSA) by quantitative computed tomography of L4; estimated vertebral strength (derived from Int.vBMD and CSA) Results: Int.vBMD and estimated vertebral strength were lowest in low-weight AN, intermediate in atypical AN, and highest in controls. CSA did not differ between groups; thus, vertebral strength (calculated using Int.vBMD and CSA) was driven by Int.vBMD. In AN, Int.vBMD and vertebral strength were associated positively with current BMI and nadir lifetime BMI (independent of current BMI). Int.vBMD and vertebral strength were lower in AN with current amenorrhea and longer lifetime amenorrhea duration. Among amenorrheic AN, Int.vBMD and vertebral strength were associated positively with testosterone. Conclusions: Int.vBMD and estimated vertebral strength (driven by Int.vBMD) are impaired across the AN weight spectrum and are associated with low BMI and endocrine dysfunction, both current and previous. Women with atypical AN experience diminished vertebral strength, partially due to prior low-weight and/or amenorrhea. Lack of current low-weight or amenorrhea in atypical AN does not preclude compromise of vertebral strength. PMID:27732336

Combat sports practice favors bone mineral density among adolescent male athletes.

PubMed

Nasri, Raouf; Hassen Zrour, Saoussen; Rebai, Haithem; Neffeti, Fadoua; Najjar, Mohamed Fadhel; Bergaoui, Naceur; Mejdoub, Hafedh; Tabka, Zouhair

2015-01-01

The aim of this study was to determine the impact of combat sports practice on bone mineral density (BMD) and to analyze the relationship between bone parameters and anthropometric measurements, bone markers, and activity index (AI). In other words, to detect the most important determinant of BMD in the adolescent period among combat sports athletes. Fifty athletes engaged in combat sports, mean age 17.1±0.2 yr, were compared with 30 sedentary subjects who were matched for age, height, and pubertal stage. For all subjects, the whole-body BMD, lumbar spine BMD (L2-L4), and BMD in the pelvis, arms, and legs was measured by dual-energy X-ray absorptiometry, and anthropometric measurements were evaluated. Daily calcium intake, bone resorption, and formation markers were measured. BMD measurements were greater in the combat sports athletes than in the sedentary group (p<0.01). Weight, body mass index, and lean body mass were significantly correlated with BMD in different sites. Daily calcium consumption lower than daily calcium intake recommended in both athletes and sedentary group. AI was strongly correlated with all BMD measurements particularly with the whole body, legs, and arms. Negative correlations were observed between bone markers and BMD in different sites. The common major predictor of BMD measurements was AI (p<0.0001). AI associated to lean body mass determined whole-body BMD until 74%. AI explained both BMD in arms and L2-L4 at 25%. AI associated to height can account for 63% of the variance in BMD legs. These observations suggested that the best model predicting BMD in different sites among adolescent combat sports athletes was the AI. Children and adolescents should be encouraged to participate in combat sports to maximize their bone accrual. Copyright © 2015 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

The relationship of depression, anxiety and stress with low bone mineral density in post-menopausal women.

PubMed

Erez, Hany Burstein; Weller, Aron; Vaisman, Nachum; Kreitler, Shulamith

2012-01-01

The goal of the present study was to examine the relationships of depression, anxiety and stress with bone mineral density (BMD). We hypothesized negative relations between those mood variables and BMD in three assessed areas. The study showed association between depression and decreased BMD. The hypothesis regarding anxiety and stress was partially confirmed. In the last decade, the relationship of osteoporosis to psychological variables has been increasingly studied. The accumulating evidence from these studies supports the conclusion that depression is related to decreased BMD. Nevertheless, several studies found no support for this relationship. Moreover, only a small number of studies examined the association between anxiety or stress and decreased BMD. The goal of the present study was to examine the relationships of depression, anxiety and stress with BMD by means of adequate measuring instruments, while controlling for background factors known to be related to BMD decrease (e.g., body mass index, family history). The study included 135 post-menopausal female participants, who arrived for BMD screening, between the years 2006 and 2009. Several days prior to the examination, participants completed a series of questionnaires assessing depression and anxiety. BMD was measured using DXA, in spine, right and left hip. The study showed negative associations between depression and BMD variables in the three assessed areas. There were negative correlations between anxiety, stress and spine BMD, as well as a tendency towards negative relations in the right and left hip BMD. Concurrent hierarchical regressions showed that the addition of the three psychological variables increased the explained variance by 6–8 %. In addition, depression was found to have a unique significant contribution to the explained variance in right and left hip BMD. The findings provide supporting evidence for the existence of associations between mood variables and decreased BMD. Further research is required for gaining deeper insight into these relationships.

Vertebral Volumetric Bone Density and Strength Are Impaired in Women With Low-Weight and Atypical Anorexia Nervosa.

PubMed

Bachmann, Katherine N; Schorr, Melanie; Bruno, Alexander G; Bredella, Miriam A; Lawson, Elizabeth A; Gill, Corey M; Singhal, Vibha; Meenaghan, Erinne; Gerweck, Anu V; Slattery, Meghan; Eddy, Kamryn T; Ebrahimi, Seda; Koman, Stuart L; Greenblatt, James M; Keane, Robert J; Weigel, Thomas; Misra, Madhusmita; Bouxsein, Mary L; Klibanski, Anne; Miller, Karen K

2017-01-01

Areal bone mineral density (BMD) is lower, particularly at the spine, in low-weight women with anorexia nervosa (AN). However, little is known about vertebral integral volumetric BMD (Int.vBMD) or vertebral strength across the AN weight spectrum, including "atypical" AN [body mass index (BMI) ≥18.5 kg/m2]. To investigate Int.vBMD and vertebral strength, and their determinants, across the AN weight spectrum. Cross-sectional observational study. Clinical research center. 153 women (age 18 to 45): 64 with low-weight AN (BMI <18.5 kg/m2; 58% amenorrheic), 44 with atypical AN (18.5≤BMI<23 kg/m2; 30% amenorrheic), 45 eumenorrheic controls (19.2≤BMI<25 kg/m2). Int.vBMD and cross-sectional area (CSA) by quantitative computed tomography of L4; estimated vertebral strength (derived from Int.vBMD and CSA). Int.vBMD and estimated vertebral strength were lowest in low-weight AN, intermediate in atypical AN, and highest in controls. CSA did not differ between groups; thus, vertebral strength (calculated using Int.vBMD and CSA) was driven by Int.vBMD. In AN, Int.vBMD and vertebral strength were associated positively with current BMI and nadir lifetime BMI (independent of current BMI). Int.vBMD and vertebral strength were lower in AN with current amenorrhea and longer lifetime amenorrhea duration. Among amenorrheic AN, Int.vBMD and vertebral strength were associated positively with testosterone. Int.vBMD and estimated vertebral strength (driven by Int.vBMD) are impaired across the AN weight spectrum and are associated with low BMI and endocrine dysfunction, both current and previous. Women with atypical AN experience diminished vertebral strength, partially due to prior low-weight and/or amenorrhea. Lack of current low-weight or amenorrhea in atypical AN does not preclude compromise of vertebral strength. Copyright © 2017 by the Endocrine Society

Height adjustment in assessing dual energy x-ray absorptiometry measurements of bone mass and density in children.

PubMed

Zemel, Babette S; Leonard, Mary B; Kelly, Andrea; Lappe, Joan M; Gilsanz, Vicente; Oberfield, Sharon; Mahboubi, Soroosh; Shepherd, John A; Hangartner, Thomas N; Frederick, Margaret M; Winer, Karen K; Kalkwarf, Heidi J

2010-03-01

In children, bone mineral content (BMC) and bone mineral density (BMD) measurements by dual-energy x-ray absorptiometry (DXA) are affected by height status. No consensus exists on how to adjust BMC or BMD (BMC/BMD) measurements for short or tall stature. The aim of this study was to compare various methods to adjust BMC/BMD for height in healthy children. Data from the Bone Mineral Density in Childhood Study (BMDCS) were used to develop adjustment methods that were validated using an independent cross-sectional sample of healthy children from the Reference Data Project (RDP). We conducted the study in five clinical centers in the United States. We included 1546 BMDCS and 650 RDP participants (7 to 17 yr of age, 50% female). No interventions were used. We measured spine and whole body (WB) BMC and BMD Z-scores for age (BMC/BMD(age)), height age (BMC/BMD(height age)), height (BMC(height)), bone mineral apparent density (BMAD(age)), and height-for-age Z-score (HAZ) (BMC/BMD(haz)). Spine and WB BMC/BMD(age)Z and BMAD(age)Z were positively (P < 0.005; r = 0.11 to 0.64) associated with HAZ. Spine BMD(haz) and BMC(haz)Z were not associated with HAZ; WB BMC(haz)Z was modestly associated with HAZ (r = 0.14; P = 0.0003). All other adjustment methods were negatively associated with HAZ (P < 0.005; r = -0.20 to -0.34). The deviation between adjusted and BMC/BMD(age) Z-scores was associated with age for most measures (P < 0.005) except for BMC/BMD(haz). Most methods to adjust BMC/BMD Z-scores for height were biased by age and/or HAZ. Adjustments using HAZ were least biased relative to HAZ and age and can be used to evaluate the effect of short or tall stature on BMC/BMD Z-scores.

Analysis of LCT-13910 genotypes and bone mineral density in ancient skeletal materials

PubMed Central

Mnich, Barbara; Spinek, Anna Elżbieta; Chyleński, Maciej; Sommerfeld, Aleksandra; Dabert, Miroslawa; Szostek, Krzysztof

2018-01-01

The relation of LCT-13910 genotypes and bone mineral density (BMD) has been the subject of modern-day human population studies, giving inconsistent results. In the present study we analyze for the first time a relation of LCT-13910 genotypes and BMD in historical skeletal individuals. Ancient population might be a model for testing this association due to elimination of non-natural factors affecting bone density. Among 22 medieval individuals from Sanok churchyard (South-Eastern Poland; dated from XIV to XVII c. AD) we identified 4 individuals with osteoporosis (mean BMD = 0.468 g/cm2, SD = 0.090), 10 individuals with osteopenia (mean BMD = 0.531 g/cm2, SD = 0.066) and 8 individuals with normal BMD values (mean BMD = 0,642 g/cm2, SD = 0.060). Analyses of BMD and LCT-13910 genotypes revealed that mean BMD was the highest (0.583 g/cm2, SD = 0.065) in the individuals with lactose tolerance genotypes (TT and CT). We also found possible association of lower BMD at the radius and CC genotypes due to higher but not statistically significant frequency of osteoporosis in the lactose intolerant group (p = 0.60). Statistically significant correlation was found between BMD and females aged 20–35 years, with tendency to reduce BMD with age (p = 0.02). PMID:29708972

Cross-sex pattern of bone mineral density in early onset gender identity disorder.

PubMed

Haraldsen, I R; Haug, E; Falch, J; Egeland, T; Opjordsmoen, S

2007-09-01

Hormonally controlled differences in bone mineral density (BMD) between males and females are well studied. The effects of cross-sex hormones on bone metabolism in patients with early onset gender identity disorder (EO-GID), however, are unclear. We examined BMD, total body fat (TBF) and total lean body mass (TLBM) in patients prior to initiation of sex hormone treatment and during treatment at months 3 and 12. The study included 33 EO-GID patients who were approved for sex reassignment and a control group of 122 healthy Norwegians (males, n=77; females, n=45). Male patients (n=12) received an oral dose of 50 mug ethinylestradiol daily for the first 3 months and 100 mug daily thereafter. Female patients (n=21) received 250 mg testosterone enantate intramuscularly every third week. BMD, TBF and TLBM were estimated using dual energy X-ray absorptiometry (DXA). In male patients, the DXA measurements except TBF were significantly lower compared to their same-sex control group at baseline and did not change during treatment. In female patients, the DXA measurements were slightly higher than in same-sex controls at baseline and also remained unchanged during treatment. In conclusion, this study reports that body composition and bone density of EO-GID patients show less pronounced sex differences compared to controls and that bone density was unaffected by cross-sex hormone treatment.

Intake of Novel Red Clover Supplementation for 12 Weeks Improves Bone Status in Healthy Menopausal Women

PubMed Central

Thorup, Anne Cathrine; Lambert, Max Norman; Kahr, Henriette Strøm; Bjerre, Mette; Jeppesen, Per Bendix

2015-01-01

Objective. To investigate the effect by which daily consumption of a novel red clover (RC) extract influences bone health, inflammatory status, and cardiovascular health in healthy menopausal women. Design. A 12-week randomized, double-blinded, placebo-controlled trial involving 60 menopausal women receiving a daily dose of 150 mL RC extract containing 37.1 mg isoflavones (33.8 mg as aglycones) or placebo. Methods. Bone parameters were changes in bone mineral density (BMD), bone mineral content (BMC), and T-score at the lumbar spine and femoral neck. Bone turnover (CTx) and inflammatory markers were measured in plasma and finally blood pressure (BP) was evaluated. Results. RC extract had positive effect on bone health, and only the women receiving the placebo experienced a decline in BMD (p < 0.01) at the lumbar spine. T-score at the lumbar spine only decreased in the placebo group (p < 0.01). CTx decreased in the RC group with −9.94 (±4.93)%, although not significant. Conclusion. Daily consumption of RC extract over a 12-week period was found to have a beneficial effect on bone health in menopausal women based on BMD and T-score at the lumbar spine and plasma CTx levels. No changes in BP or inflammation markers were found and no side effects were observed. PMID:26265926

A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy.

PubMed

Mendell, Jerry R; Sahenk, Zarife; Malik, Vinod; Gomez, Ana M; Flanigan, Kevin M; Lowes, Linda P; Alfano, Lindsay N; Berry, Katherine; Meadows, Eric; Lewis, Sarah; Braun, Lyndsey; Shontz, Kim; Rouhana, Maria; Clark, Kelly Reed; Rosales, Xiomara Q; Al-Zaidy, Samiah; Govoni, Alessandra; Rodino-Klapac, Louise R; Hogan, Mark J; Kaspar, Brian K

2015-01-01

Becker muscular dystrophy (BMD) is a variant of dystrophin deficiency resulting from DMD gene mutations. Phenotype is variable with loss of ambulation in late teenage or late mid-life years. There is currently no treatment for this condition. In this BMD proof-of-principle clinical trial, a potent myostatin antagonist, follistatin (FS), was used to inhibit the myostatin pathway. Extensive preclinical studies, using adeno-associated virus (AAV) to deliver follistatin, demonstrated an increase in strength. For this trial, we used the alternatively spliced FS344 to avoid potential binding to off target sites. AAV1.CMV.FS344 was delivered to six BMD patients by direct bilateral intramuscular quadriceps injections. Cohort 1 included three subjects receiving 3 × 10(11) vg/kg/leg. The distance walked on the 6MWT was the primary outcome measure. Patients 01 and 02 improved 58 meters (m) and 125 m, respectively. Patient 03 showed no change. In Cohort 2, Patients 05 and 06 received 6 × 10(11) vg/kg/leg with improved 6MWT by 108 m and 29 m, whereas, Patient 04 showed no improvement. No adverse effects were encountered. Histological changes corroborated benefit showing reduced endomysial fibrosis, reduced central nucleation, more normal fiber size distribution with muscle hypertrophy, especially at high dose. The results are encouraging for treatment of dystrophin-deficient muscle diseases.

A Phase 1/2a Follistatin Gene Therapy Trial for Becker Muscular Dystrophy

PubMed Central

Mendell, Jerry R; Sahenk, Zarife; Malik, Vinod; Gomez, Ana M; Flanigan, Kevin M; Lowes, Linda P; Alfano, Lindsay N; Berry, Katherine; Meadows, Eric; Lewis, Sarah; Braun, Lyndsey; Shontz, Kim; Rouhana, Maria; Clark, Kelly Reed; Rosales, Xiomara Q; Al-Zaidy, Samiah; Govoni, Alessandra; Rodino-Klapac, Louise R; Hogan, Mark J; Kaspar, Brian K

2015-01-01

Becker muscular dystrophy (BMD) is a variant of dystrophin deficiency resulting from DMD gene mutations. Phenotype is variable with loss of ambulation in late teenage or late mid-life years. There is currently no treatment for this condition. In this BMD proof-of-principle clinical trial, a potent myostatin antagonist, follistatin (FS), was used to inhibit the myostatin pathway. Extensive preclinical studies, using adeno-associated virus (AAV) to deliver follistatin, demonstrated an increase in strength. For this trial, we used the alternatively spliced FS344 to avoid potential binding to off target sites. AAV1.CMV.FS344 was delivered to six BMD patients by direct bilateral intramuscular quadriceps injections. Cohort 1 included three subjects receiving 3 × 1011 vg/kg/leg. The distance walked on the 6MWT was the primary outcome measure. Patients 01 and 02 improved 58 meters (m) and 125 m, respectively. Patient 03 showed no change. In Cohort 2, Patients 05 and 06 received 6 × 1011 vg/kg/leg with improved 6MWT by 108 m and 29 m, whereas, Patient 04 showed no improvement. No adverse effects were encountered. Histological changes corroborated benefit showing reduced endomysial fibrosis, reduced central nucleation, more normal fiber size distribution with muscle hypertrophy, especially at high dose. The results are encouraging for treatment of dystrophin-deficient muscle diseases. PMID:25322757

Studies of indirect and direct effects of hypervitaminosis A on rat bone by comparing free access to food and pair-feeding.

PubMed

Lind, Thomas; Lind, P Monica; Hu, Lijuan; Melhus, Håkan

2018-04-26

The most prominent features of hypervitaminosis A in rats are spontaneous fractures and anorexia. Since caloric restriction induces alterations in bone, some effects could be secondary to loss of appetite. To clarify the mechanisms behind vitamin A-induced bone fragility it is necessary to distinguish between direct and indirect effects. In this study we compared rats fed high doses of vitamin A both with pair-fed controls, which were fed the same amount of chow as that consumed by the vitamin A group to keep food intake the same, and to controls with free access to food. In contrast to the pair-fed animals, rats in the free access group fed high doses of vitamin A for 7 days had 13% lower food intake, 15% lower body weight, and 2.7% shorter femurs compared with controls. In addition, serum biomarkers of bone turnover were reduced. Peripheral quantitative computed tomography of the femurs showed that the bone mineral content, cross sectional area, and periosteal circumference were similarly reduced in the pair-fed and free access groups. However, bone mineral density (BMD) and cortical parameters were only significantly decreased in the free access group. Our data indicate that the major direct short-term effect of high doses of vitamin A on rat bone is a reduced bone diameter, whereas the effects on bone length, serum biomarkers of bone turnover, BMD, and bone cortex appear to be mainly indirect, caused by a systemic toxicity with loss of appetite, reduced food intake, and general effects on growth.

Modifications in Bone Matrix of Estrogen-Deficient Rats Treated with Intermittent PTH

PubMed Central

Campos, Jenifer Freitas; Katchburian, Eduardo; de Medeiros, Valquíria Pereira; Nader, Helena Bonciani; Nonaka, Keico Okino; Plotkin, Lilian Irene; Reginato, Rejane Daniele

2015-01-01

Bone matrix dictates strength, elasticity, and stiffness to the bone. Intermittent parathyroid hormone (iPTH), a bone-forming treatment, is widely used as a therapy for osteoporosis. We investigate whether low doses of intermittent PTH (1-34) change the profile of organic components in the bone matrix after 30 days of treatment. Forty 6-month-old female Wistar rats underwent ovariectomy and after 3 months received low doses of iPTH administered for 30 days: daily at 0.3 µg/kg/day (PTH03) or 5 µg/kg/day (PTH5); or 3 times per week at 0.25 µg/kg/day (PTH025). After euthanasia, distal femora were processed for bone histomorphometry, histochemistry for collagen and glycosaminoglycans, biochemical quantification of sulfated glycosaminoglycans, and hyaluronan by ELISA and TUNEL staining. Whole tibiae were used to estimate the bone mineral density (BMD). Histomorphometric analysis showed that PTH5 increased cancellous bone volume by 6% over vehicle-treated rats. In addition, PTH5 and PTH03 increased cortical thickness by 21% and 20%, respectively. Tibial BMD increased in PTH5-treated rats and this group exhibited lower levels of chondroitin sulfate; on the other hand, hyaluronan expression was increased. Hormonal administration in the PTH5 group led to decreased collagen maturity. Further, TUNEL-positive osteocytes were decreased in the cortical compartment of PTH5 whereas administration of PTH025 increased the osteocyte death. Our findings suggest that daily injections of PTH at low doses alter the pattern of organic components from the bone matrix, favoring the increase of bone mass. PMID:25695082

Friend or foe: high bone mineral density on routine bone density scanning, a review of causes and management.

PubMed

Gregson, Celia L; Hardcastle, Sarah A; Cooper, Cyrus; Tobias, Jonathan H

2013-06-01

A finding of high BMD on routine DXA scanning is not infrequent and most commonly reflects degenerative disease. However, BMD increases may also arise secondary to a range of underlying disorders affecting the skeleton. Although low BMD increases fracture risk, the converse may not hold for high BMD, since elevated BMD may occur in conditions where fracture risk is increased, unaffected or reduced. Here we outline a classification for the causes of raised BMD, based on identification of focal or generalized BMD changes, and discuss an approach to guide appropriate investigation by clinicians after careful interpretation of DXA scan findings within the context of the clinical history. We will also review the mild skeletal dysplasia associated with the currently unexplained high bone mass phenotype and discuss recent advances in osteoporosis therapies arising from improved understanding of rare inherited high BMD disorders.

Friend or foe: high bone mineral density on routine bone density scanning, a review of causes and management

PubMed Central

Hardcastle, Sarah A.; Cooper, Cyrus; Tobias, Jonathan H.

2013-01-01

A finding of high BMD on routine DXA scanning is not infrequent and most commonly reflects degenerative disease. However, BMD increases may also arise secondary to a range of underlying disorders affecting the skeleton. Although low BMD increases fracture risk, the converse may not hold for high BMD, since elevated BMD may occur in conditions where fracture risk is increased, unaffected or reduced. Here we outline a classification for the causes of raised BMD, based on identification of focal or generalized BMD changes, and discuss an approach to guide appropriate investigation by clinicians after careful interpretation of DXA scan findings within the context of the clinical history. We will also review the mild skeletal dysplasia associated with the currently unexplained high bone mass phenotype and discuss recent advances in osteoporosis therapies arising from improved understanding of rare inherited high BMD disorders. PMID:23445662

SU-E-J-30: Benchmark Image-Based TCP Calculation for Evaluation of PTV Margins for Lung SBRT Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, M; Chetty, I; Zhong, H

2014-06-01

Purpose: Tumor control probability (TCP) calculated with accumulated radiation doses may help design appropriate treatment margins. Image registration errors, however, may compromise the calculated TCP. The purpose of this study is to develop benchmark CT images to quantify registration-induced errors in the accumulated doses and their corresponding TCP. Methods: 4DCT images were registered from end-inhale (EI) to end-exhale (EE) using a “demons” algorithm. The demons DVFs were corrected by an FEM model to get realistic deformation fields. The FEM DVFs were used to warp the EI images to create the FEM-simulated images. The two images combined with the FEM DVFmore » formed a benchmark model. Maximum intensity projection (MIP) images, created from the EI and simulated images, were used to develop IMRT plans. Two plans with 3 and 5 mm margins were developed for each patient. With these plans, radiation doses were recalculated on the simulated images and warped back to the EI images using the FEM DVFs to get the accumulated doses. The Elastix software was used to register the FEM-simulated images to the EI images. TCPs calculated with the Elastix-accumulated doses were compared with those generated by the FEM to get the TCP error of the Elastix registrations. Results: For six lung patients, the mean Elastix registration error ranged from 0.93 to 1.98 mm. Their relative dose errors in PTV were between 0.28% and 6.8% for 3mm margin plans, and between 0.29% and 6.3% for 5mm-margin plans. As the PTV margin reduced from 5 to 3 mm, the mean TCP error of the Elastix-reconstructed doses increased from 2.0% to 2.9%, and the mean NTCP errors decreased from 1.2% to 1.1%. Conclusion: Patient-specific benchmark images can be used to evaluate the impact of registration errors on the computed TCPs, and may help select appropriate PTV margins for lung SBRT patients.« less

A Normal Reference of Bone Mineral Density (BMD) Measured by Dual Energy X-Ray Absorptiometry in Healthy Thai Children and Adolescents Aged 5–18 Years: A New Reference for Southeast Asian Populations

PubMed Central

Nakavachara, Pairunyar; Pooliam, Julaporn; Weerakulwattana, Linda; Kiattisakthavee, Pornpimol; Chaichanwattanakul, Katharee; Manorompatarasarn, Racahnee; Chokephaibulkit, Kulkanya; Viprakasit, Vip

2014-01-01

Ethnic-specific normative data of bone mineral density (BMD) is essential for the accurate interpretation of BMD measurement. There have been previous reports of normative BMD data for Caucasian and Asian children including Japanese, Chinese, Korean and Indian. However, the normative BMD data for Southeast Asian including Thai children and adolescents are not currently available. The goals of our study were 1) to establish normative data of BMD, bone mineral content (BMC), bone area (BA) and lean body mass (LBM) for healthy Thai children and adolescents; aged 5–18 years measured by dual energy X-ray absorptiometry (DXA, Lunar Prodigy) and 2) to evaluate the relationships between BMD vs. age, sex, puberty, weight, height, calcium intake and the age of menarche in our population. Gender and age-specific BMD (L2-4; LS and total body; TB), BMADLS (apparent BMD of the lumbar spine), BMC (L2-4 and total body), BA (L2-4 and total body) and LBM were evaluated in 367 children (174 boys and 193 girls). All parameters increased progressively with age. A rapid increase in BMD, BMC and BMADLS was observed at earlier ages in girls. Gender and Tanner stage-specific BMD normative data were also generated. The dynamic changes of BMD values from childhood to early and late puberty of Thai children appeared to be consistent with those of Caucasian and Asian populations. Using a multiple-regression, weight and Tanner stage significantly affected BMDLS, BMDTB and BMADLS in both genders. Only in girls, height was found to have significant influence on BMDTB and BMADLS. The positive correlation between BMD and several demographic parameters, except the calcium intake, was observed. In summary, we established a normal BMD reference for Thai children and adolescents and this will be of useful for clinicians and researchers to appropriately assess BMD in Thais and other Southeast Asian children. PMID:24847716

Areal and volumetric bone mineral density and risk of multiple types of fracture in older men.

PubMed

Chalhoub, Didier; Orwoll, Eric S; Cawthon, Peggy M; Ensrud, Kristine E; Boudreau, Robert; Greenspan, Susan; Newman, Anne B; Zmuda, Joseph; Bauer, Douglas; Cummings, Steven; Cauley, Jane A

2016-11-01

Although many studies have examined the association between low bone mineral density (BMD) and fracture risk in older men, none have simultaneously studied the relationship between multiple BMD sites and risk of different types of fractures. Using data from the Osteoporotic Fractures in Men study, we evaluated the association between areal BMD (aBMD) by dual-energy X-ray absorptiometry (DXA) and volumetric BMD (vBMD) by quantitative computed tomography (QCT) measurements, and different types of fractures during an average of 9.7years of follow-up. Men answered questionnaires about fractures every 4months (>97% completions). Fractures were confirmed by centralized review of radiographic reports; pathological fractures were excluded. Risk of fractures was assessed at the hip, spine, wrist, shoulder, rib/chest/sternum, ankle/foot/toe, arm, hand/finger, leg, pelvis/coccyx, skull/face and any non-spine fracture. Age and race adjusted Cox proportional-hazards modeling was used to assess the risk of fracture in 3301 older men with both aBMD (at the femoral neck (FN) and lumbar spine) and vBMD (at the trabecular spine and FN, and cortical FN) measurements, with hazard ratios (HRs) expressed per standard deviation (SD) decrease. Lower FN and spine aBMD were associated with an increased risk of fracture at the hip, spine, wrist, shoulder, rib/chest/sternum, arm, and any non-spine fracture (statistically significant HRs per SD decrease ranged from 1.24-3.57). Lower trabecular spine and FN vBMD were associated with increased risk of most fractures with statistically significant HRs ranging between 1.27 and 3.69. There was a statistically significant association between FN cortical vBMD and fracture risk at the hip (HR=1.55) and spine sites (HR=1.26), but no association at other fracture sites. In summary, both lower aBMD and vBMD were associated with increased fracture risk. The stronger associations observed for trabecular vBMD than cortical vBMD may reflect the greater metabolic activity of the trabecular compartment. Copyright © 2016 Elsevier Inc. All rights reserved.

Areal and volumetric Bone Mineral Density and risk of multiple types of fracture in older men

PubMed Central

Chalhoub, Didier; Orwoll, Eric S.; Cawthon, Peggy M.; Ensrud, Kristine E.; Boudreau, Robert; Greenspan, Susan; Newman, Anne B.; Zmuda, Joseph; Bauer, Douglas; Cummings, Steven; Cauley, Jane A.

2016-01-01

Although many studies have examined the association between low bone mineral density (BMD) and fracture risk in older men, none have simultaneously studied the relationship between multiple BMD sites and risk of different types of fractures. Using data from the Osteoporotic Fractures in Men study, we evaluated the association between areal BMD (aBMD) by dual-energy X-ray absorptiometry (DXA) and volumetric BMD (vBMD) by quantitative computed tomography (QCT) measurements, and different types of fractures during an average of 9.7 years of follow up. Men answered questionnaires about fractures every 4 months (>97% completions). Fractures were confirmed by centralized review of radiographic reports; pathological fractures were excluded. Risk of fractures was assessed at the hip, spine, wrist, shoulder, rib/chest/sternum, ankle/foot/toe, arm, hand/finger, leg, pelvis/coccyx, skull/face and any non-spine fracture. Age and race adjusted Cox proportional-hazards modeling was used to assess the risk of fracture in 3301 older men with both aBMD (at the femoral neck (FN) and lumbar spine) and vBMD (at the trabecular spine and FN, and cortical FN) measurements, with hazard ratios (HRs) expressed per standard deviation (SD) decrease. Lower FN and spine aBMD were associated with an increased risk of fracture at the hip, spine, wrist, shoulder, rib/chest/sternum, arm, and any non-spine fracture (statistically significant HRs per SD decrease ranged from 1.24 - 3.57). Lower trabecular spine and FN vBMD were associated with increased risk of most fractures with statistically significant HRs ranging between 1.27 and 3.69. There was a statistically significant association between FN cortical vBMD and fracture risk at the hip (HR=1.55) and spine sites (HR=1.26), but no association at other fracture sites. In summary, both lower aBMD and vBMD were associated with increased fracture risk. The stronger associations observed for trabecular vBMD than cortical vBMD may reflect the greater metabolic activity of the trabecular compartment. PMID:27554426

Evaluation of triclosan in Minnesota lakes and rivers: Part II - human health risk assessment.

PubMed

Yost, Lisa J; Barber, Timothy R; Gentry, P Robinan; Bock, Michael J; Lyndall, Jennifer L; Capdevielle, Marie C; Slezak, Brian P

2017-08-01

Triclosan, an antimicrobial compound found in consumer products, has been detected in low concentrations in Minnesota municipal wastewater treatment plant (WWTP) effluent. This assessment evaluates potential health risks for exposure of adults and children to triclosan in Minnesota surface water, sediments, and fish. Potential exposures via fish consumption are considered for recreational or subsistence-level consumers. This assessment uses two chronic oral toxicity benchmarks, which bracket other available toxicity values. The first benchmark is a lower bound on a benchmark dose associated with a 10% risk (BMDL 10 ) of 47mg per kilogram per day (mg/kg-day) for kidney effects in hamsters. This value was identified as the most sensitive endpoint and species in a review by Rodricks et al. (2010) and is used herein to derive an estimated reference dose (RfD (Rodricks) ) of 0.47mg/kg-day. The second benchmark is a reference dose (RfD) of 0.047mg/kg-day derived from a no observed adverse effect level (NOAEL) of 10mg/kg-day for hepatic and hematopoietic effects in mice (Minnesota Department of Health [MDH] 2014). Based on conservative assumptions regarding human exposures to triclosan, calculated risk estimates are far below levels of concern. These estimates are likely to overestimate risks for potential receptors, particularly because sample locations were generally biased towards known discharges (i.e., WWTP effluent). Copyright © 2017 Elsevier Inc. All rights reserved.

Longitudinal change in bone mineral density in a population-based cohort of patients with inflammatory bowel disease.

PubMed

Targownik, Laura E; Leslie, William D; Carr, Rachel; Clara, Ian; Miller, Norine; Rogala, Linda; Graff, Lesley A; Walker, John R; Bernstein, Charles N

2012-11-01

Persons with inflammatory bowel disease (IBD) are reported to have a high prevalence of osteoporosis and reduced bone mineral density (BMD) and to be at higher risk of fracture. The course of BMD loss over time is poorly characterized in persons with IBD. Eighty-six persons, stratified by age, were enrolled from a population-based longitudinal IBD cohort study to undergo BMD testing at baseline, with final BMD testing a mean of 4.3 years later. The proportion of subjects with significant change in BMD at the lumbar spine, total hip, and femoral neck was assessed, as were clinical, biochemical, and anthropomorphic changes. Vertebral radiographs were also obtained at baseline and at the end of follow-up in those aged 50 years and above to detect vertebral fractures. The change in BMD seen in this cohort of IBD patients was similar to the expected rate of BMD loss in the general population. Age >50 years, decreasing body mass index (BMI), and corticosteroid use were most notably correlated with BMD loss. Subjects aged <50 years did not have statistically significant declines in BMD. IBD symptom activity scores correlated poorly with BMD loss. Vertebral fractures were uncommon, with only two subjects out of 41 >50 years old developing a definite radiographic fracture over the course of follow-up. No major nonvertebral fractures were observed. Patients with IBD do not appear to have significantly accelerated BMD loss. Older age, decreasing BMI, and corticosteroid use may identify IBD patients at greater risk for BMD loss.

S219. RISK FACTORS FOR LOW BONE MINERAL DENSITY IN PATIENTS TAKING ANTIPSYCHOTICS

PubMed Central

Jhon, Min; Hong, Ji-Eun; Park, Cheol; Lee, Ju-Yeon; Jo, Anna; Kim, Jae-Min; Shin, Il-Seon; Williams, Lana; Berk, Michael; Yoon, Jin-Sang; Kim, Sung-Wan

2018-01-01

Abstract Background The aim of this study is to explore potentially modifiable risk factors for low bone mineral density (BMD) in adults with psychotic disorders. Furthermore, we sought to identify gender-specific risk factors. Methods The study included 285 community-dwelling patients with psychotic disorders. Dual-energy x-ray absorptiometry was used to measure BMD. Laboratory examinations included vitamin D and prolactin levels. Low BMD was defined as<1 standard deviation below the mean for young adults. Clinical characteristics associated with low BMD were identified with logistic regression analysis in total population and each gender. Results Fifty-eight (20.4%) subjects had low BMD. Low BMD was more common in men and in patients with low body mass indices (BMIs), as well as in those with shorter treatment durations, those on Medicaid, and patients using serotonergic antidepressants. Logistic regression analysis revealed that low BMD was negatively associated with BMI and treatment duration and positively with gender (male) and serotonergic antidepressants use in the overall population. In men, low BMD was associated with treatment duration and BMI; in women, low BMD was associated with BMI, prolactin level, vitamin D, and serotonergic antidepressant use. Discussion Low BMI was risk factor for reduced BMD in both genders. Shorter treatment duration was associated with low BMD in men, whereas higher prolactin levels, lower vitamin D, and the use of serotonergic antidepressants were associated with low BMD in women. Psychotropic agents should be prescribed mindful of their effects on bone, as use of these medications is a modifiable risk factor for osteoporosis in women with psychotic disorders.

Influence of lean and fat mass on bone mineral density (BMD) in postmenopausal women with osteoporosis.

PubMed

Dytfeld, Joanna; Ignaszak-Szczepaniak, Magdalena; Gowin, Ewelina; Michalak, Michał; Horst-Sikorska, Wanda

2011-01-01

Despite known positive association between body mass and bone mineral density (BMD), relative contribution of fat and lean tissue to BMD remains under debate. We aimed at investigating the effect of selected anthropometric parameters, including fat content and lean body mass (LBM) on BMD in postmenopausal, osteoporotic women with body mass index (BMI) > 20 kg/m(2). The study involved 92 never-treated women (mean age 69.5 ± 7.3). L1-L4 and femoral neck (FN) BMD were measured by dual energy X-ray absorptiometry (DEXA). Absolute (kg) and relative (%) fat and LBM were assessed by means of electric bioimpedance method. We showed both FN and L1-L4 BMD were positively correlated with body mass, waist circumference (WC), hip circumference (HC) and LBM (kg). Fat content correlated with FN BMD (r = 0.36, p < 0.001). Regression analysis revealed the only predictor of L1-L4 BMD was LBM (R(2) = 0.18, p < 0.05), for FN--both LBM and fat (R(2) = 0.18, p < 0.05 and p < 0.001, respectively). Of the women, 44.5% were overweight, 18.4% obese. Obese women displayed the highest BMD. Both L1-L4 and FN BMD were higher in women with WC > 80 cm. In postmenopausal osteoporotic women with BMI > 20 kg/m(2) both fat and lean tissue might contribute to BMD. Positive association between body mass and BMD does not make obesity and osteoporosis mutually exclusive. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

MRI-measured bone marrow adipose tissue is inversely related to DXA-measured bone mineral in Caucasian women.

PubMed

Shen, W; Chen, J; Punyanitya, M; Shapses, S; Heshka, S; Heymsfield, S B

2007-05-01

Recent studies suggest that bone marrow adipose tissue (BMAT) might play a role in the pathogenesis of osteoporosis. Previous research using regional magnetic resonance spectroscopy methods to measure BMAT has reported inconsistent findings on the relationship between BMAT and dual-energy absorptiometry (DXA)-measured bone mineral density (BMD). In the present study, total body and pelvic BMAT were evaluated in 56 healthy women (age 18-88 yrs, mean +/- SD, 47.4 +/- 17.6 yrs; BMI, 24.3 +/- 4.2 kg/m(2)) with T1-weighted whole-body magnetic resonance imaging (MRI). BMD was measured using the whole-body DXA mode (GE Lunar DPX, software version 4.7). A strong negative correlation was observed between pelvic BMAT and BMD (total-body BMD, R = -0.743, P < 0.001; pelvic BMD, R = -0.646, P < 0.001), and between total-body BMAT and BMD (total-body BMD, R = -0.443, P < 0.001; pelvic BMD, R = -0.308, P < 0.001). The inverse association between pelvic BMAT and BMD remained strong after adjusting for age, weight, total body fat, and menopausal status (partial correlation: total-body BMD, R = -0.553, P < 0.001; pelvic BMD, R = -0.513, P < 0.001). BMAT was also highly correlated with age (pelvic BMAT, R = 0.715, P < 0.001; total-body BMAT, R = 0.519, P < 0.001). MRI-measured BMAT is thus strongly inversely correlated with DXA-measured BMD independent of other predictor variables. These observations, in the context of DXA technical concerns, support the growing evidence linking BMAT with low bone density.

Comparative risk assessment of alcohol, tobacco, cannabis and other illicit drugs using the margin of exposure approach.

PubMed

Lachenmeier, Dirk W; Rehm, Jürgen

2015-01-30

A comparative risk assessment of drugs including alcohol and tobacco using the margin of exposure (MOE) approach was conducted. The MOE is defined as ratio between toxicological threshold (benchmark dose) and estimated human intake. Median lethal dose values from animal experiments were used to derive the benchmark dose. The human intake was calculated for individual scenarios and population-based scenarios. The MOE was calculated using probabilistic Monte Carlo simulations. The benchmark dose values ranged from 2 mg/kg bodyweight for heroin to 531 mg/kg bodyweight for alcohol (ethanol). For individual exposure the four substances alcohol, nicotine, cocaine and heroin fall into the "high risk" category with MOE < 10, the rest of the compounds except THC fall into the "risk" category with MOE < 100. On a population scale, only alcohol would fall into the "high risk" category, and cigarette smoking would fall into the "risk" category, while all other agents (opiates, cocaine, amphetamine-type stimulants, ecstasy, and benzodiazepines) had MOEs > 100, and cannabis had a MOE > 10,000. The toxicological MOE approach validates epidemiological and social science-based drug ranking approaches especially in regard to the positions of alcohol and tobacco (high risk) and cannabis (low risk).

Comparative risk assessment of tobacco smoke constituents using the margin of exposure approach: the neglected contribution of nicotine

PubMed Central

Baumung, Claudia; Rehm, Jürgen; Franke, Heike; Lachenmeier, Dirk W.

2016-01-01

Nicotine was not included in previous efforts to identify the most important toxicants of tobacco smoke. A health risk assessment of nicotine for smokers of cigarettes was conducted using the margin of exposure (MOE) approach and results were compared to literature MOEs of various other tobacco toxicants. The MOE is defined as ratio between toxicological threshold (benchmark dose) and estimated human intake. Dose-response modelling of human and animal data was used to derive the benchmark dose. The MOE was calculated using probabilistic Monte Carlo simulations for daily cigarette smokers. Benchmark dose values ranged from 0.004 mg/kg bodyweight for symptoms of intoxication in children to 3 mg/kg bodyweight for mortality in animals; MOEs ranged from below 1 up to 7.6 indicating a considerable consumer risk. The dimension of the MOEs is similar to those of other tobacco toxicants with high concerns relating to adverse health effects such as acrolein or formaldehyde. Owing to the lack of toxicological data in particular relating to cancer, long term animal testing studies for nicotine are urgently necessary. There is immediate need of action concerning the risk of nicotine also with regard to electronic cigarettes and smokeless tobacco. PMID:27759090

Comparative risk assessment of alcohol, tobacco, cannabis and other illicit drugs using the margin of exposure approach

PubMed Central

Lachenmeier, Dirk W.; Rehm, Jürgen

2015-01-01

A comparative risk assessment of drugs including alcohol and tobacco using the margin of exposure (MOE) approach was conducted. The MOE is defined as ratio between toxicological threshold (benchmark dose) and estimated human intake. Median lethal dose values from animal experiments were used to derive the benchmark dose. The human intake was calculated for individual scenarios and population-based scenarios. The MOE was calculated using probabilistic Monte Carlo simulations. The benchmark dose values ranged from 2 mg/kg bodyweight for heroin to 531 mg/kg bodyweight for alcohol (ethanol). For individual exposure the four substances alcohol, nicotine, cocaine and heroin fall into the “high risk” category with MOE < 10, the rest of the compounds except THC fall into the “risk” category with MOE < 100. On a population scale, only alcohol would fall into the “high risk” category, and cigarette smoking would fall into the “risk” category, while all other agents (opiates, cocaine, amphetamine-type stimulants, ecstasy, and benzodiazepines) had MOEs > 100, and cannabis had a MOE > 10,000. The toxicological MOE approach validates epidemiological and social science-based drug ranking approaches especially in regard to the positions of alcohol and tobacco (high risk) and cannabis (low risk). PMID:25634572

Translational benchmark risk analysis

PubMed Central

Piegorsch, Walter W.

2010-01-01

Translational development – in the sense of translating a mature methodology from one area of application to another, evolving area – is discussed for the use of benchmark doses in quantitative risk assessment. Illustrations are presented with traditional applications of the benchmark paradigm in biology and toxicology, and also with risk endpoints that differ from traditional toxicological archetypes. It is seen that the benchmark approach can apply to a diverse spectrum of risk management settings. This suggests a promising future for this important risk-analytic tool. Extensions of the method to a wider variety of applications represent a significant opportunity for enhancing environmental, biomedical, industrial, and socio-economic risk assessments. PMID:20953283

Frequency, risk factors, and adverse sequelae of bone loss in patients with ostomy for inflammatory bowel diseases.

PubMed

Gupta, Supriya; Wu, Xianrui; Moore, Travis; Shen, Bo

2014-02-01

Bone loss in patients with inflammatory bowel disease (IBD) with ostomy has not been systemically studied. The aims of the study were to evaluate the frequency, risk factors, and sequelae of bone loss in patients with IBD and stomas and to monitor the change in bone mineral density (BMD) over time after ostomy. A total of 126 patients met the inclusion criteria (i.e., those with IBD diagnosis and stoma), including ileostomy (N = 120), colostomy (N = 3), and jejunostomy (N = 3). BMD was measured on dual-energy X-ray absorptiometry (DEXA). Patients were classified as having normal or low BMD based on the International Society for Clinical Densitometry criteria. Thirty-two demographic and clinical variables were evaluated with logistic regression models. At a median of 6.6 years (interquartile range, 2-18.7 yr) after stoma, 37 (29.4%) patients had a low BMD. On univariate analysis, there were no significant differences between the normal and low BMD groups in the following variables: gender, race, age at diagnosis of IBD, prevalence of Crohn's disease and ulcerative colitis, age at ostomy, duration from diagnosis to DEXA and from ostomy to DEXA, menopausal age, diabetes, hypothyroidism, renal stones, short bowel syndrome, history of smoking or excessive alcohol use, family history of IBD or osteoporosis, daily calcium and vitamin D supplement, estrogen replacement, and steroid use. Body mass index was significantly lower in the low BMD group than the normal BMD group (23.3 ± 5.5 versus 26.0 ± 5.2, P = 0.013). Fragility fracture occurred in 8 (21.6%) patients in low BMD group and 4 (4.5%) patients in normal BMD group (P = 0.006). In a multivariate analysis, low body mass index was the only covariate-adjusted factor associated with low BMD. In patients with multiple DEXA scans available over time after ostomy, hip BMD was found to improve marginally, and the lumbar and femoral BMD remained stable. Low BMD was common in patients with IBD after ostomy, largely based on the findings in patients with CD with ileostomy. Fragility fracture was 5 times more frequent in patients with ostomy with low BMD compared with those with normal BMD. The low BMD was associated with a low body mass index. Screening and surveillance of BMD should routinely be performed, particularly in these patients at risk. Bone mass tends to stabilize over time after stoma.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Grace L.; Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, Texas; Jiang, Jing

Purpose: High-quality treatment for intact cervical cancer requires external radiation therapy, brachytherapy, and chemotherapy, carefully sequenced and completed without delays. We sought to determine how frequently current treatment meets quality benchmarks and whether new technologies have influenced patterns of care. Methods and Materials: By searching diagnosis and procedure claims in MarketScan, an employment-based health care claims database, we identified 1508 patients with nonmetastatic, intact cervical cancer treated from 1999 to 2011, who were <65 years of age and received >10 fractions of radiation. Treatments received were identified using procedure codes and compared with 3 quality benchmarks: receipt of brachytherapy, receipt ofmore » chemotherapy, and radiation treatment duration not exceeding 63 days. The Cochran-Armitage test was used to evaluate temporal trends. Results: Seventy-eight percent of patients (n=1182) received brachytherapy, with brachytherapy receipt stable over time (Cochran-Armitage P{sub trend}=.15). Among patients who received brachytherapy, 66% had high–dose rate and 34% had low–dose rate treatment, although use of high–dose rate brachytherapy steadily increased to 75% by 2011 (P{sub trend}<.001). Eighteen percent of patients (n=278) received intensity modulated radiation therapy (IMRT), and IMRT receipt increased to 37% by 2011 (P{sub trend}<.001). Only 2.5% of patients (n=38) received IMRT in the setting of brachytherapy omission. Overall, 79% of patients (n=1185) received chemotherapy, and chemotherapy receipt increased to 84% by 2011 (P{sub trend}<.001). Median radiation treatment duration was 56 days (interquartile range, 47-65 days); however, duration exceeded 63 days in 36% of patients (n=543). Although 98% of patients received at least 1 benchmark treatment, only 44% received treatment that met all 3 benchmarks. With more stringent indicators (brachytherapy, ≥4 chemotherapy cycles, and duration not exceeding 56 days), only 25% of patients received treatment that met all benchmarks. Conclusion: In this cohort, most cervical cancer patients received treatment that did not comply with all 3 benchmarks for quality treatment. In contrast to increasing receipt of newer radiation technologies, there was little improvement in receipt of essential treatment benchmarks.« less

Association of unipedal standing time and bone mineral density in community-dwelling Japanese women.

PubMed

Sakai, A; Toba, N; Takeda, M; Suzuki, M; Abe, Y; Aoyagi, K; Nakamura, T

2009-05-01

Bone mineral density (BMD) and physical performance of the lower extremities decrease with age. In community-dwelling Japanese women, unipedal standing time, timed up and go test, and age are associated with BMD while in women aged 70 years and over, unipedal standing time is associated with BMD. The aim of this study was to clarify whether unipedal standing time is significantly associated with BMD in community-dwelling women. The subjects were 90 community-dwelling Japanese women aged 54.7 years. BMD of the second metacarpal bone was measured by computed X-ray densitometry. We measured unipedal standing time as well as timed up and go test to assess physical performance of the lower extremities. Unipedal standing time decreased with increased age. Timed up and go test significantly correlated with age. Low BMD was significantly associated with old age, short unipedal standing time, and long timed up and go test. Stepwise regression analysis revealed that age, unipedal standing time, and timed up and go test were significant factors associated with BMD. In 21 participants aged 70 years and over, body weight and unipedal standing time, but not age, were significantly associated with BMD. BMD and physical performance of the lower extremities decrease with older age. Unipedal standing time, timed up and go test, and age are associated with BMD in community-dwelling Japanese women. In women aged 70 years and over, unipedal standing time is significantly associated with BMD.

[Prevalence of low bone mineral density in postmenopausal breast cancer survivors].

PubMed

Poloni, Priscila Ferreira; Omodei, Michelle Sako; Nahas-Neto, Jorge; Uemura, Gilberto; Véspoli, Heloisa De Luca; Nahas, Eliana Aguiar Petri

2015-01-01

To evaluate the prevalence of low bone mineral density (BMD) in postmenopausal breast cancer survivors. In this cross-sectional study, 115 breast cancer survivors, seeking healthcare at a University Hospital in Brazil, were evaluated. Eligibility criteria included women with amenorrhea ≥ 12 months and age ≥ 45 years, treated for breast cancer and metastasis-free for at least five years. BMD was measured by DEXA at the lumbar spine (L1-L4) and femoral neck. Low BMD was considered when total-spine and/or femoral-neck T-score values were <-1.0 Delphi Score (DP) (osteopenia and osteoporosis). The risk factors for low BMD were assessed by interview. Data were analyzed statistically by the χ(2) test and Fisher's exact test. The mean age of breast cancer survivors was 61.6 ± 10.1 years and time since menopause was 14.2 ± 5.6 years, with a mean follow-up of 10.1 ± 3.9 years. Considering spine and femoral neck, 60% of breast cancer survivors had low BMD. By evaluating the risk factors for low BMD, a significant difference was found in the percent distribution for age (higher % of women >50 years with low BMD), personal history of previous fracture (11.6% with low BMD versus 0% with normal BMD) and BMI. A higher frequency of obesity was observed among women with normal BMD (63%) compared to those with low BMD (26.1%) (p<0.05). Postmenopausal breast cancer survivors had a high prevalence of osteopenia and osteoporosis.

Unipedal standing exercise and hip bone mineral density in postmenopausal women: a randomized controlled trial.

PubMed

Sakai, Akinori; Oshige, Toshihisa; Zenke, Yukichi; Yamanaka, Yoshiaki; Nagaishi, Hitoshi; Nakamura, Toshitaka

2010-01-01

The aim of this study was to test the effect of unipedal standing exercise on bone mineral density (BMD) of the hip in postmenopausal women. Japanese postmenopausal women (n = 94) were assigned at random to an exercise or control group (no exercise). The 6-month exercise program consisted of standing on a single foot for 1 min per leg 3 times per day. BMD of the hip was measured by dual-energy X-ray absorptiometry. There was no significant difference in age and baseline hip BMD between the exercise group (n = 49) and control group (n = 45). Exercise did not improve hip BMD compared with the control group. Stepwise regression analysis identified old age as a significant determinant (p = 0.034) of increased hip total BMD at 6 months after exercise. In 31 participants aged >/=70 years, the exercise group (n = 20) showed significant increase in the values of hip BMD at the areas of total (p = 0.008), intertrochanteric (p = 0.023), and Ward's triangle (p = 0.032). The same parameters were decreased in the control group (n = 11). The percent changes in hip BMD of the exercise group were not significantly different from those of the control group either in the participants with low baseline hip total BMD (<80% of the young adult mean) or high baseline hip total BMD (> or =80% of the young adult mean). In conclusion, unipedal standing exercise for 6 months did not improve hip BMD in Japanese postmenopausal women. Effect of exercise on hip total BMD was age dependent. In participants aged > or =70 years, the exercise significantly increased hip total BMD.

Quantitative trait locus on chromosome 1q influences bone loss in young Mexican American adults

PubMed Central

Shaffer, John R.; Kammerer, Candace M.; Bruder, Jan M.; Cole, Shelley A.; Dyer, Thomas D.; Almasy, Laura; MacCluer, Jean W.; Blangero, John; Bauer, Richard L.; Mitchell, Braxton D.

2009-01-01

Introduction Bone loss occurs as early as the third decade and its cumulative effect throughout adulthood may impact risk for osteoporosis in later life, however the genes and environmental factors influencing early bone loss are largely unknown. We investigated the role of genes in the change in bone mineral density (BMD) in participants of the San Antonio Family Osteoporosis Study. Materials and Methods BMD change in 327 Mexican Americans (ages 25–45 years) from 32 extended pedigrees was calculated from DXA measurements at baseline and follow-up (3.5 to 8.9 years later). Family-based likelihood methods were used to estimate heritability (h2) and perform autosome-wide linkage analysis for BMD change of the proximal femur and forearm, and estimate heritability for BMD change of lumbar spine. Results BMD change was significantly heritable for total hip, ultradistal radius and 33% radius (h2 = 0.34, 0.34, 0.27, respectively, p < 0.03 for all), modestly heritable for femoral neck (h2 = 0.22, p = 0.06) and not heritable for spine BMD. Covariates associated with BMD change included age, sex, baseline BMD, menopause, body mass index, and interim BMI change, and accounted for 6% to 24% of phenotype variation. A significant quantitative trait locus (LOD = 3.6) for femoral neck BMD change was observed on chromosome 1q23. Conclusions We observed that change in BMD in young adults is heritable, and performed one of the first linkage studies for BMD change. Linkage to chromosome 1q23 suggests this region may harbor one or more genes involved in regulating early BMD change of the femoral neck. PMID:19067020

Bone Parameters in Anorexia Nervosa and Athletic Amenorrhea: Comparison of Two Hypothalamic Amenorrhea States.

PubMed

Kandemir, Nurgun; Slattery, Meghan; Ackerman, Kathryn E; Tulsiani, Shreya; Bose, Amita; Singhal, Vibha; Baskaran, Charumathi; Ebrahimi, Seda; Goldstein, Mark; Eddy, Kamryn; Klibanski, Anne; Misra, Madhusmita

2018-04-05

We have reported low bone mineral density (BMD), impaired bone structure, and increased fracture risk in anorexia nervosa (AN) and normal-weight, oligo-amenorrheic athletes (OA). However, data directly comparing compartment-specific bone parameters in AN, OA and controls are lacking. 426 females 14-21.9 years old were included; 231 AN, 94 OA and 101 normal-weight eumenorrheic controls. Dual energy x-ray absorptiometry was used to assess areal BMD (aBMD) of the whole body less head (WBLH), spine, and hip. High resolution peripheral quantitative CT was used to assess volumetric BMD (vBMD), bone geometry and structure at the non-weight bearing distal radius and weight-bearing distal tibia. AN had lower WBLH and hip aBMD Z-scores than OA and controls (p<0.0001). AN and OA had lower spine aBMD Z-scores than controls (p<0.01). At the radius, total and cortical vBMD, percent cortical area and thickness were lower in AN and OA vs. controls (p≤0.04); trabecular vBMD was lower in AN than controls. At the tibia, AN had lower measures for most parameters vs. OA and controls (p<0.05); OA had lower cortical vBMD than controls (p=0.002). AN and OA had higher fracture rates vs. controls. Stress fracture prevalence was highest in OA (p<0.0001); non-stress fracture prevalence was highest in AN (p<0.05). AN is deleterious to bone at all sites and both bone compartments. A high stress fracture rate in OA, who have comparable WBLH and hip aBMD measures to controls, indicates that BMD in these women may need to be even higher to avoid fractures.

Linkage Screen for BMD Phenotypes in Male and Female COP and DA Rat Strains

PubMed Central

Koller, Daniel L; Liu, Lixiang; Alam, Imranul; Sun, Qiwei; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

2008-01-01

Because particular inbred strains of experimental animals are informative for only a subset of the genes underlying variability in BMD, we undertook a genome screen to identify quantitative trait loci (QTLs) in 828 F2 progeny (405 males and 423 females) derived from the Copenhagen 2331 (COP) and dark agouti (DA) strains of rats. This screen was performed to complement our study in female Fischer 344 (F344) and Lewis (LEW) rats and to further delineate the factors underlying the complex genetic architecture of BMD in the rat model. Microsatellite genotyping was performed using markers at an average density of 20 cM. BMD was measured by pQCT and DXA. These data were analyzed in the R/qtl software to detect QTLs acting in both sexes as well as those having sex-specific effects. A QTL was detected in both sexes on chromosome 18 for midfemur volumetric BMD (vBMD; genome-wide, p < 0.01). On distal chromosome 1, a QTL was found for femur and vertebral aBMD as well as distal femur vBMD, and this QTL appears distinct from the proximal chromosome 1 QTL impacting BMD in our F344/LEW cross. Additional aBMD and vBMD QTLs and several sex-specific QTLs were also detected. These included a male-specific QTL (p < 0.01) on chromosome 8 and a female-specific QTL on chromosomes 7 and 14 (p < 0.01). Few of the QTLs identified showed overlap with the significant QTLs from the F344/LEW cross. These results confirm that the genetic influence on BMD in the rat model is quite complex and would seem to be influenced by a number of different genes, some of which have sex-specific effects. PMID:18707222

Trabecular bone deficits among Vietnamese immigrants.

PubMed

Melton, L J; Marquez, M A; McCready, L K; Achenbach, S J; Riggs, B L; Amin, S; Khosla, S

2011-05-01

Compared to white women, lower areal bone mineral density (aBMD) in middle-aged Vietnamese immigrants is due to reduced trabecular volumetric bone mineral density (vBMD), which in turn is associated with greater trabecular separation along with lower estrogen levels. The epidemiology of osteoporosis in Asian populations is still poorly known, but we previously found a deficit in lumbar spine aBMD among postmenopausal Southeast Asian women, compared to white women, that persisted after correction for bone size. This issue was revisited using more sophisticated imaging techniques. Twenty Vietnamese immigrants (age, 44-79 years) were compared to 162 same-aged white women with respect to aBMD at the hip, spine and wrist, vBMD at the hip and spine by quantitative computed tomography and vBMD and bone microstructure at the ultradistal radius by high-resolution pQCT. Bone turnover and sex steroid levels were assessed in a subset (20 Vietnamese and 40 white women). The aBMD was lower at all sites among the Vietnamese women, but femoral neck vBMD did not differ from middle-aged white women. Significant differences in lumbar spine and ultradistal radius vBMD in the Vietnamese immigrants were due to lower trabecular vBMD, which was associated with increased trabecular separation. Bone resorption was elevated and bone formation depressed among the Vietnamese immigrants, although trends were not statistically significant. Serum estradiol was positively associated with trabecular vBMD in the Vietnamese women, but their estrogen levels were dramatically lower compared to white women. Although reported discrepancies in aBMD among Asian women are mainly an artifact of smaller bone size, we identified a specific deficit in the trabecular bone among a sample of Vietnamese immigrants that may be related to low estrogen levels and which needs further study.

Trabecular bone deficits among Vietnamese immigrants

PubMed Central

Marquez, M. A.; McCready, L. K.; Achenbach, S. J.; Riggs, B. L.; Amin, S.; Khosla, S.

2011-01-01

Summary Compared to white women, lower areal bone mineral density (aBMD) in middle-aged Vietnamese immigrants is due to reduced trabecular volumetric bone mineral density (vBMD), which in turn is associated with greater trabecular separation along with lower estrogen levels. Introduction The epidemiology of osteoporosis in Asian populations is still poorly known, but we previously found a deficit in lumbar spine aBMD among postmenopausal Southeast Asian women, compared to white women, that persisted after correction for bone size. This issue was revisited using more sophisticated imaging techniques. Methods Twenty Vietnamese immigrants (age, 44–79 years) were compared to 162 same-aged white women with respect to aBMD at the hip, spine and wrist, vBMD at the hip and spine by quantitative computed tomography and vBMD and bone microstructure at the ultradistal radius by high-resolution pQCT. Bone turnover and sex steroid levels were assessed in a subset (20 Vietnamese and 40 white women). Results The aBMD was lower at all sites among the Vietnamese women, but femoral neck vBMD did not differ from middle-aged white women. Significant differences in lumbar spine and ultradistal radius vBMD in the Vietnamese immigrants were due to lower trabecular vBMD, which was associated with increased trabecular separation. Bone resorption was elevated and bone formation depressed among the Vietnamese immigrants, although trends were not statistically significant. Serum estradiol was positively associated with trabecular vBMD in the Vietnamese women, but their estrogen levels were dramatically lower compared to white women. Conclusions Although reported discrepancies in aBMD among Asian women are mainly an artifact of smaller bone size, we identified a specific deficit in the trabecular bone among a sample of Vietnamese immigrants that may be related to low estrogen levels and which needs further study. PMID:20658128

Antioxidant enzymes GSR, SOD1, SOD2, and CAT gene variants and bone mineral density values in postmenopausal women: a genetic association analysis.

PubMed

Mlakar, Simona Jurkovic; Osredkar, Josko; Prezelj, Janez; Marc, Janja

2012-03-01

Oxidative stress participates in decreasing bone formation and stimulating bone resorption. Furthermore, antioxidant enzymes have been observed to have low protective activity in women with osteoporosis.The aim of the present study was to examine any association of selected gene polymorphisms of the glutathione S-reductase (GSR), superoxide dismutase (SOD1 and SOD2), and catalase (CAT) genes, alone or in combination, with the bone mineral density (BMD) values of femoral neck (fn), lumbar spine (ls), and total hip (th) in Slovenian postmenopausal women. The gene polymorphisms of CAT, GSR, SOD1, and SOD2 genes in 468 postmenopausal women were analyzed using restriction fragment length polymorphism and a fluorescent 5'-exonuclease genotyping method. BMD_fn, BMD_ls, and BMD_th were measured using dual-energy x-ray absorptiometry. Moreover, univariate statistic analysis and two-way analysis of variance for interaction testing were performed. A significant association of BMD_th values (P = 0.027) was found in genotype subgroups of 423-287G>A GSR polymorphism located in the third intron among postmenopausal women. Furthermore, women with at least one G allele showed significantly higher levels of BMD_fn (P = 0.044), BMD_th (P = 0.009), and BMD_ls (P = 0.043) than those that are AA homozygotes. Interestingly, the 423-287G>A_GSR*1154-393T>A_GSR combination was significantly associated with BMD_fn (P = 0.013) and BMD_th (P = 0.002) in postmenopausal women. The results of our study demonstrate for the first time that antioxidant enzyme GSR gene polymorphisms are significantly associated with BMD, suggesting that the A allele of 423-287G>A GSR polymorphism could contribute to decreased BMD values in postmenopausal women.

Bone mineral density and vertebral fractures in patients with systemic lupus erythematosus: A systematic review and meta-regression.

PubMed

Mendoza-Pinto, Claudia; Rojas-Villarraga, Adriana; Molano-González, Nicolás; Jiménez-Herrera, Erick A; León-Vázquez, María de la Luz; Montiel-Jarquín, Álvaro; García-Carrasco, Mario; Cervera, Ricard

2018-01-01

Observational studies have indicated a high but heterogeneous prevalence of low bone mineral density (BMD) and vertebral fractures (VF) in patients with systemic lupus erythematosus (SLE). Therefore, the objectives of this systematic review and meta-regression were: 1) to compare BMD between SLE patients and healthy controls and 2) to evaluate the relationship between BMD and glucocorticoid therapy and VF in SLE patients. Articles were identified from electronic databases (PubMed, Embase, VHL, SciELO and the Cochrane Library). Prospective longitudinal and cross-sectional studies were considered for review. We evaluated the quality of the evidence included using the Oxford Centre for evidence-based medicine (EBM) Levels of Evidence. In total, 38 articles were identified and analyzed (3442 SLE cases and 6198 controls) in the analysis of BMD (9232 women and 408 men). There were significant differences in mean BMD between SLE patients and controls. BMD mean difference in cases/controls: -0.0566 95% CI (-0.071, -0.0439; p = < 0.0001). When only SLE patients were analyzed, the BMD did not significantly differ between patients who had or had not received glucocorticoid (GCT) therapy. 694 SLE patients were included in the analysis of VF (189 with VF vs. 505 without VF). Patients with VF had lower BMD than patients without VF (BMD mean difference without VF/with VF: 0.033 (95%CI: 0.006-0.060); p-value: 0.0156). Patients with SLE had lower BMD than healthy controls. Moreover, SLE patients with VF had lower BMD than patients without VF. However, our data did not show that GCT therapy had an impact on BMD.

MRI-measured bone marrow adipose tissue is inversely related to DXA-measured bone mineral in Caucasian women

PubMed Central

Chen, J.; Punyanitya, M.; Shapses, S.; Heshka, S.; Heymsfield, S. B.

2007-01-01

Introduction Recent studies suggest that bone marrow adipose tissue (BMAT) might play a role in the pathogenesis of osteoporosis. Previous research using regional magnetic resonance spectroscopy methods to measure BMAT has reported inconsistent findings on the relationship between BMAT and dual-energy absorptiometry (DXA)-measured bone mineral density (BMD). Methods In the present study, total body and pelvic BMAT were evaluated in 56 healthy women (age 18–88 yrs, mean±SD, 47.4±17.6 yrs; BMI, 24.3±4.2 kg/m2) with T1-weighted whole-body magnetic resonance imaging (MRI). BMD was measured using the whole-body DXA mode (GE Lunar DPX, software version 4.7). Results A strong negative correlation was observed between pelvic BMAT and BMD (total-body BMD, R=− 0.743, P<0.001; pelvic BMD, R=− 0.646, P<0.001), and between total-body BMAT and BMD (total-body BMD, R=− 0.443, P<0.001; pelvic BMD, R=− 0.308, P < 0.001). The inverse association between pelvic BMAT and BMD remained strong after adjusting for age, weight, total body fat, and menopausal status (partial correlation: total-body BMD, R=− 0.553, P< 0.001; pelvic BMD, R=− 0.513, P<0.001). BMAT was also highly correlated with age (pelvic BMAT, R=0.715, P< 0.001; total-body BMAT, R=0.519, P<0.001). Conclusion MRI-measured BMAT is thus strongly inversely correlated with DXA-measured BMD independent of other predictor variables. These observations, in the context of DXA technical concerns, support the growing evidence linking BMAT with low bone density. PMID:17139464

Muscle and bone plasticity after spinal cord injury: Review of adaptations to disuse and to electrical muscle stimulation

PubMed Central

Dudley-Javoroski, Shauna; Shields, Richard K.

2009-01-01

The paralyzed musculoskeletal system retains a remarkable degree of plasticity after spinal cord injury (SCI). In response to reduced activity, muscle atrophies and shifts toward a fast-fatigable phenotype arising from numerous changes in histochemistry and metabolic enzymes. The loss of routine gravitational and muscular loads removes a critical stimulus for maintenance of bone mineral density (BMD), precipitating neurogenic osteoporosis in paralyzed limbs. The primary adaptations of bone to reduced use are demineralization of epiphyses and thinning of the diaphyseal cortical wall. Electrical stimulation of paralyzed muscle markedly reduces deleterious post-SCI adaptations. Recent studies demonstrate that physiological levels of electrically induced muscular loading hold promise for preventing post-SCI BMD decline. Rehabilitation specialists will be challenged to develop strategies to prevent or reverse musculoskeletal deterioration in anticipation of a future cure for SCI. Quantifying the precise dose of stress needed to efficiently induce a therapeutic effect on bone will be paramount to the advancement of rehabilitation strategies. PMID:18566946

Eating disorders, menstrual dysfunction, weight change and DMPA use predict bone density change in college-aged women.

PubMed

Nieves, Jeri W; Ruffing, Jamie A; Zion, Marsha; Tendy, Susan; Yavorek, Trudy; Lindsay, Robert; Cosman, Felicia

2016-03-01

There are limited longitudinal studies that have evaluated bone mineral density (BMD) changes in college-aged women. Our objective was to simultaneously evaluate factors influencing 4-year BMD change. This was a longitudinal cohort study of healthy, physically active women in the US Military Academy (n=91; average age=18.4years). Assessments over four years included: height, weight, calcium intake, physical fitness, menstrual function (annual number cycles), oral contraceptives (OCs) or depot-medroxyprogesterone acetate (DMPA) use, and eating disorder behavior (Eating Disorder Inventory; (EDI)). BMD was measured annually at the lumbar spine and total hip by dual X-ray absorptiometry and calcaneal BMD by PIXI. Slope of 4year BMD change at each skeletal site (spine total hip and calcaneus) was calculated for each woman. BMD gains occurred at the spine in 50% and the hip in 36% of women. In unadjusted analyses, spine bone gain was positively related to menstrual cycle frequency (p=0.04). Spine and hip BMD loss occurred in those using DMPA (p<0.01) and those with the highest EDI quartile scores (p<0.05). BMD change was unrelated to OC use. Hip and calcaneus BMD decreased with weight loss (average 4.8+2.2lb/year) as compared to those with stable weight/weight gain (p<0.05). In multivariable analysis, spine BMD increase was significantly related to African American (AA) race, normal EDI score and normal menses. Hip BMD increase was related to AA race, weight increase and normal menses. DMPA use was associated with spine, hip, and calcaneus bone loss. On average, BMD may modestly increase in college-aged women, in the absence of risk factors. However, risk factors including subclinical eating disorders, weight loss, menstrual dysfunction and DMPA use can have significant detrimental effects on BMD in young healthy physically active women. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of calcium and vitamin D supplementation on bone mineral density in children with inflammatory bowel disease.

PubMed

Benchimol, Eric I; Ward, Leanne M; Gallagher, J C; Rauch, Frank; Barrowman, Nick; Warren, Jaime; Beedle, Susan; Mack, David R

2007-11-01

The purpose of this study was to evaluate the effect of calcium and vitamin D2 supplementation on bone mineral density (BMD) in children with inflammatory bowel disease (IBD). This was an open-label, prospective study conducted over a 12-month period. Seventy-two patients were divided into 2 groups based on lumbar spine areal BMD (L2-4 aBMD). Patients with an L2-4 aBMD z score of -1 or higher were assigned to the control group (n = 33; mean age, 11.0 +/- 3.5 years; 20 boys). Patients with an L2-4 aBMD of less than -1 (n = 39; mean age 11.8 +/- 2.5 years; 25 boys) were allocated to the intervention group and received 1000 mg of supplemental elemental calcium daily for 12 months (n = 19) or supplemental calcium for 12 months and 50,000 IU of vitamin D2 monthly for 6 months (n = 20). The 2 groups differed in L2-4 aBMD z scores (intervention, -1.9 +/- 0.6; control, -0.2 +/- 0.6; P < 0.001) and volumetric L2-4 BMD (vBMD; intervention, 0.29 +/- 0.04; control, 0.33 +/- 0.06; P < 0.001). After 1 year of therapy, the control and intervention groups had similar changes in height z scores, L2-4 aBMD, L2-4 vBMD (z score change, L2-4 aBMD: control 0.2 +/- 0.6 [n = 21], intervention 0.4 +/- 0.6; P = 0.4 [n = 26]; z score change, L2-4 vBMD: control 0.1 +/- 0.4, intervention 0.2 +/- 0.6; P = 0.74). The changes in these parameters were similar between patients who had received calcium only or calcium plus vitamin D. These results suggest that, in children with IBD, supplementation of calcium and vitamin D does not accelerate accrual in L2-4 BMD.

Lumbar disc degeneration was not related to spine and hip bone mineral densities in Chinese: facet joint osteoarthritis may confound the association.

PubMed

Pan, Jianjiang; Lu, Xuan; Yang, Ge; Han, Yongmei; Tong, Xiang; Wang, Yue

2017-12-01

A sample of 512 Chinese was studied and we observed that greater disc degeneration on MRI was associated with greater spine DXA BMD. Yet, this association may be confounded by facet joint osteoarthritis. BMD may not be a risk factor for lumbar disc degeneration in Chinese. Evidence suggested that lumbar vertebral bone and intervertebral disc interact with each other in multiple ways. The current paper aims to determine the association between bone mineral density (BMD) and lumbar disc degeneration using a sample of Chinese. We studied 165 patients with back disorders and 347 general subjects from China. All subjects had lumbar spine magnetic resonance (MR) imaging and dual- energy X-ray absorptiometry (DXA) spine BMD studies, and a subset of general subjects had additional hip BMD measurements. On T2-weighted MR images, Pfirrmann score was used to evaluate the degree of lumbar disc degeneration and facet joint osteoarthritis was assessed as none, slight-moderate, and severe. Regression analyses were used to examine the associations between lumbar and hip BMD and disc degeneration, adjusting for age, gender, body mass index (BMI), lumbar region, and facet joint osteoarthritis. Greater facet joint osteoarthritis was associated with greater spine BMD (P < 0.01) in both patients and general subjects. For general subjects, greater spine BMD was associated with severe disc degeneration, controlling for age, gender, BMI, and lumbar region. When facet joint osteoarthritis entered the regression model, however, greater spine BMD was associated with greater facet joint osteoarthritis (P < 0.01) but not greater disc degeneration (P > 0.05). No statistical association was observed between spine BMD and lumbar disc degeneration in patients with back disorders (P > 0.05), and between hip BMD and disc degeneration in general subjects (P > 0.05). BMD may not be a risk factor for lumbar disc degeneration in Chinese. Facet joint osteoarthritis inflates DXA spine BMD measurements and therefore, may confound the association between spine BMD and disc degeneration.

Birth weight and adult bone metabolism are unrelated: results from birth weight-discordant monozygotic twins.

PubMed

Frost, Morten; Petersen, Inge; Andersen, Thomas L; Langdahl, Bente L; Buhl, Thora; Christiansen, Lene; Brixen, Kim; Christensen, Kaare

2013-12-01

Low birth weight (BW) has been associated with poor bone health in adulthood. The aim of this study was to investigate the association between BW and bone mass and metabolism in adult BW-discordant monozygotic (MZ) twins. A total of 153 BW-extremely discordant MZ twin pairs were recruited from the Danish Twin Registry. Serum vitamin D (25-hydroxyvitamin D [25OHD]) and bone turnover markers (BTMs) amino-terminal propeptide of type I procollagen (P1NP), pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (1CTP), and cross-linked C-telopeptide (CTX) were quantified. Femoral neck (FN), total hip (TH), lumbar spine (LS), and whole-body (WB) bone mineral density (BMD) (ie, FN-BMD, TH-BMD, LS-BMD, and WB-BMD, respectively) were measured using dual-energy X-ray absorptiometry (DXA). Twins were studied as single individuals using regression analyses with or without adjustment for height, weight, age, sex, and intrapair correlation. Within-pair differences were assessed using Student's t test and fixed-regression models. BW was not associated with BTMs, LS-BMD, TH-BMD, FN-BMD, or WB-BMD, but BW was associated with WB-BMC, and WB-Area after adjustments. Compared to the co-twin, twins with the highest BW were heavier and taller in adulthood (mean differences ± SD): 3.0 ± 10.5 kg; 1.6 ± 2.6 cm; both p < 0.001). Within-pair analyses showed that LS-BMD, TH-BMD, and FN-BMD tended to be higher in twins with highest BW (for all: mean difference 0.01 ± 0.1 g/cm(2) ; p = 0.08, 0.05, and 0.10, respectively). No difference was observed after adjustment for adult body size. Intrapair differences in BW were not associated with differences in any of the biochemical parameters or BMD. Small differences between twins in BMD were explained by dissimilarities in body size. These results suggest that BW and adult bone metabolism are unrelated. © 2013 American Society for Bone and Mineral Research.

Application of the World Health Organization Fracture Risk Assessment Tool to predict need for dual-energy X-ray absorptiometry scanning in postmenopausal women.

PubMed

Chao, An-Shine; Chen, Fang-Ping; Lin, Yu-Ching; Huang, Ting-Shuo; Fan, Chih-Ming; Yu, Yu-Wei

2015-12-01

To evaluate the efficacy of the World Health Organization Fracture Risk Assessment Tool, excluding bone mineral density (pre-BMD FRAX), in identifying Taiwanese postmenopausal women needing dual-energy X-ray absorptiometry (DXA) examination for further treatment. The pre-BMD FRAX score was calculated for 231 postmenopausal women who participated in public health education workshops in the local Keelung community, Taiwan. DXA scanning and vertebral fracture assessment (VFA) were arranged for women classified as intermediate or high risk for fracture using the pre-BMD FRAX fracture probability. Pre-BMD FRAX classified 26 women as intermediate risk and 37 as having high risk for fracture. Subsequent DXA scans for these 63 women showed that 36 were osteoporotic, 19 were osteopenic, and eight had normal bone density. Concurrent VFA revealed 25 spine factures in which 14 were osteoporotic, seven were osteopenic, and four had normal bone density. The efficacy of the pre-BMD FRAX score to identify those patients with low bone mass by DXA was 87.3% (55/63). When VFA was combined with BMD to identify those patients with high risk (osteopenia, osteoporosis, or spinal fracture), the efficacy of the pre-BMD score increased to 93.7% (59/63). According to the National Osteoporosis Foundation, the overall concordance between pre-BMD FRAX and BMD, expressed through the kappa index, was 0.967. Compared with the evaluation when BMD was used alone, there was a significant increase in efficacy in identifying women who need treatment using BMD plus VFA or FRAX plus BMD. Furthermore, the highest efficacy was achieved when FRAX with BMD and VFA was used. The pre-BMD FRAX score not only efficiently predicts postmenopausal patients who are potentially at risk and might require treatment but also reduces unnecessary DXA use. Concurrent VFA during DXA use increases spine fracture detection. This improvement in diagnostic efficacy allows clinicians to provide the most appropriate therapeutic recommendation. Copyright © 2015. Published by Elsevier B.V.

BMD Loci Contribute to Ethnic and Developmental Differences in Skeletal Fragility across Populations: Assessment of Evolutionary Selection Pressures

PubMed Central

Medina-Gómez, Carolina; Chesi, Alessandra; Heppe, Denise H.M.; Zemel, Babette S.; Yin, Jia-Lian; Kalkwarf, Heidi J.; Hofman, Albert; Lappe, Joan M.; Kelly, Andrea; Kayser, Manfred; Oberfield, Sharon E.; Gilsanz, Vicente; Uitterlinden, André G.; Shepherd, John A.; Jaddoe, Vincent W.V.; Grant, Struan F.A.; Lao, Oscar; Rivadeneira, Fernando

2015-01-01

Bone mineral density (BMD) is a highly heritable trait used both for the diagnosis of osteoporosis in adults and to assess bone health in children. Ethnic differences in BMD have been documented, with markedly higher levels in individuals of African descent, which partially explain disparity in osteoporosis risk across populations. To date, 63 independent genetic variants have been associated with BMD in adults of Northern-European ancestry. Here, we demonstrate that at least 61 of these variants are predictive of BMD early in life by studying their compound effect within two multiethnic pediatric cohorts. Furthermore, we show that within these cohorts and across populations worldwide the frequency of those alleles associated with increased BMD is systematically elevated in individuals of Sub-Saharan African ancestry. The amount of differentiation in the BMD genetic scores among Sub-Saharan and non-Sub-Saharan populations together with neutrality tests, suggest that these allelic differences are compatible with the hypothesis of selective pressures acting on the genetic determinants of BMD. These findings constitute an explorative contribution to the role of selection on ethnic BMD differences and likely a new example of polygenic adaptation acting on a human trait. PMID:26226985

Nonstandard Lumbar Region in Predicting Fracture Risk.

PubMed

Alajlouni, Dima; Bliuc, Dana; Tran, Thach; Pocock, Nicholas; Nguyen, Tuan V; Eisman, John A; Center, Jacqueline R

Femoral neck (FN) bone mineral density (BMD) is the most commonly used skeletal site to estimate fracture risk. The role of lumbar spine (LS) BMD in fracture risk prediction is less clear due to osteophytes that spuriously increase LS BMD, particularly at lower levels. The aim of this study was to compare fracture predictive ability of upper L1-L2 BMD with standard L2-L4 BMD and assess whether the addition of either LS site could improve fracture prediction over FN BMD. This study comprised a prospective cohort of 3016 women and men over 60 yr from the Dubbo Osteoporosis Epidemiology Study followed up for occurrence of minimal trauma fractures from 1989 to 2014. Dual-energy X-ray absorptiometry was used to measure BMD at L1-L2, L2-L4, and FN at baseline. Fracture risks were estimated using Cox proportional hazards models separately for each site. Predictive performances were compared using receiver operating characteristic curve analyses. There were 565 women and 179 men with a minimal trauma fracture during a mean of 11 ± 7 yr. L1-L2 BMD T-score was significantly lower than L2-L4 T-score in both genders (p < 0.0001). L1-L2 and L2-L4 BMD models had a similar fracture predictive ability. LS BMD was better than FN BMD in predicting vertebral fracture risk in women [area under the curve 0.73 (95% confidence interval, 0.68-0.79) vs 0.68 (95% confidence interval, 0.62-0.74), but FN was superior for hip fractures prediction in both women and men. The addition of L1-L2 or L2-L4 to FN BMD in women increased overall and vertebral predictive power compared with FN BMD alone by 1% and 4%, respectively (p < 0.05). In an elderly population, L1-L2 is as good as but not better than L2-L4 site in predicting fracture risk. The addition of LS BMD to FN BMD provided a modest additional benefit in overall fracture risk. Further studies in individuals with spinal degenerative disease are needed. Copyright © 2017 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Osteogenesis imperfecta type V: Genetic and clinical findings in eleven Chinese patients.

PubMed

Liu, Yi; Wang, Jiawei; Ma, Doudou; Lv, Fang; Xu, Xiaojie; Xia, Weibo; Jiang, Yan; Wang, Ou; Xing, Xiaoping; Zhou, Peiran; Wang, Jianyi; Yu, Wei; Li, Mei

2016-11-01

Osteogenesis imperfecta (OI) type V is a rare inherited disease characterized by multiple fractures, intraosseous membrane calcification, and hypercallus formation. We investigate the causative gene, phenotype and also observe the effects of zoledronic acid in Chinese OI type V patients. The clinical phenotype and causative gene mutation was investigated in eleven patients with type V OI. Patients were given a dose of zoledronic acid 5mg intravenously. Fracture incidence and Z-score of bone mineral density (BMD) were evaluated. Serum levels of biomarkers such as cross linked C-telopeptide of type I collagen (β-CTX) and safety parameters were assessed. The c.-14C>T mutation in the 5' untranslated region of IFITM5 was detected in all patients. The phenotype was largely variable, and no significant correlation of genotype and phenotype was found. After one dose of zoledronic acid infusion, fracture incidence significantly dropped from 2fractures/year before treatment to 0fracture/year after treatment (P=0.01). Z score of lumbar spine BMD elevated from -2.6 to -1.3 (P<0.001). Serum β-CTX level decreased by 50% (P<0.05). No serious adverse event was found. No obvious correlation was found between the genotype and phenotype. Zoledronic acid had significantly skeletal protective effects in OI of type V. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of a flattening filter free multiple source model for use as an independent, Monte Carlo, dose calculation, quality assurance tool for clinical trials.

PubMed

Faught, Austin M; Davidson, Scott E; Popple, Richard; Kry, Stephen F; Etzel, Carol; Ibbott, Geoffrey S; Followill, David S

2017-09-01

The Imaging and Radiation Oncology Core-Houston (IROC-H) Quality Assurance Center (formerly the Radiological Physics Center) has reported varying levels of compliance from their anthropomorphic phantom auditing program. IROC-H studies have suggested that one source of disagreement between institution submitted calculated doses and measurement is the accuracy of the institution's treatment planning system dose calculations and heterogeneity corrections used. In order to audit this step of the radiation therapy treatment process, an independent dose calculation tool is needed. Monte Carlo multiple source models for Varian flattening filter free (FFF) 6 MV and FFF 10 MV therapeutic x-ray beams were commissioned based on central axis depth dose data from a 10 × 10 cm 2 field size and dose profiles for a 40 × 40 cm 2 field size. The models were validated against open-field measurements in a water tank for field sizes ranging from 3 × 3 cm 2 to 40 × 40 cm 2 . The models were then benchmarked against IROC-H's anthropomorphic head and neck phantom and lung phantom measurements. Validation results, assessed with a ±2%/2 mm gamma criterion, showed average agreement of 99.9% and 99.0% for central axis depth dose data for FFF 6 MV and FFF 10 MV models, respectively. Dose profile agreement using the same evaluation technique averaged 97.8% and 97.9% for the respective models. Phantom benchmarking comparisons were evaluated with a ±3%/2 mm gamma criterion, and agreement averaged 90.1% and 90.8% for the respective models. Multiple source models for Varian FFF 6 MV and FFF 10 MV beams have been developed, validated, and benchmarked for inclusion in an independent dose calculation quality assurance tool for use in clinical trial audits. © 2017 American Association of Physicists in Medicine.

A Matter of Timing: Identifying Significant Multi-Dose Radiotherapy Improvements by Numerical Simulation and Genetic Algorithm Search

PubMed Central

Angus, Simon D.; Piotrowska, Monika Joanna

2014-01-01

Multi-dose radiotherapy protocols (fraction dose and timing) currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge. Building on our previous single-dose numerical simulation model of EMT6/Ro spheroids, a multi-dose irradiation response module is added and calibrated to the effective dose arising from 18 independent multi-dose treatment programs available in the experimental literature. With the developed model a constrained, non-linear, search for better performing cadidate protocols is conducted within the vicinity of two benchmarks by genetic algorithm (GA) techniques. After evaluating less than 0.01% of the potential benchmark protocol space, candidate protocols were identified by the GA which conferred an average of 9.4% (max benefit 16.5%) and 7.1% (13.3%) improvement (reduction) on tumour cell count compared to the two benchmarks, respectively. Noticing that a convergent phenomenon of the top performing protocols was their temporal synchronicity, a further series of numerical experiments was conducted with periodic time-gap protocols (10 h to 23 h), leading to the discovery that the performance of the GA search candidates could be replicated by 17–18 h periodic candidates. Further dynamic irradiation-response cell-phase analysis revealed that such periodicity cohered with latent EMT6/Ro cell-phase temporal patterning. Taken together, this study provides powerful evidence towards the hypothesis that even simple inter-fraction timing variations for a given fractional dose program may present a facile, and highly cost-effecitive means of significantly improving clinical efficacy. PMID:25460164

A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search.

PubMed

Angus, Simon D; Piotrowska, Monika Joanna

2014-01-01

Multi-dose radiotherapy protocols (fraction dose and timing) currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge. Building on our previous single-dose numerical simulation model of EMT6/Ro spheroids, a multi-dose irradiation response module is added and calibrated to the effective dose arising from 18 independent multi-dose treatment programs available in the experimental literature. With the developed model a constrained, non-linear, search for better performing cadidate protocols is conducted within the vicinity of two benchmarks by genetic algorithm (GA) techniques. After evaluating less than 0.01% of the potential benchmark protocol space, candidate protocols were identified by the GA which conferred an average of 9.4% (max benefit 16.5%) and 7.1% (13.3%) improvement (reduction) on tumour cell count compared to the two benchmarks, respectively. Noticing that a convergent phenomenon of the top performing protocols was their temporal synchronicity, a further series of numerical experiments was conducted with periodic time-gap protocols (10 h to 23 h), leading to the discovery that the performance of the GA search candidates could be replicated by 17-18 h periodic candidates. Further dynamic irradiation-response cell-phase analysis revealed that such periodicity cohered with latent EMT6/Ro cell-phase temporal patterning. Taken together, this study provides powerful evidence towards the hypothesis that even simple inter-fraction timing variations for a given fractional dose program may present a facile, and highly cost-effecitive means of significantly improving clinical efficacy.

Bone mineral density across a range of physical activity volumes: NHANES 2007-2010.

PubMed

Whitfield, Geoffrey P; Kohrt, Wendy M; Pettee Gabriel, Kelley K; Rahbar, Mohammad H; Kohl, Harold W

2015-02-01

The association between aerobic physical activity volume and bone mineral density (BMD) is not completely understood. The purpose of this study was to clarify the association between BMD and aerobic activity across a broad range of activity volumes, particularly volumes between those recommended in the 2008 Physical Activity Guidelines for Americans and those of trained endurance athletes. Data from the 2007-2010 National Health and Nutrition Examination Survey were used to quantify the association between reported physical activity and BMD at the lumbar spine and proximal femur across the entire range of activity volumes reported by US adults. Participants were categorized into multiples of the minimum guideline-recommended volume based on reported moderate- and vigorous-intensity leisure activity. Lumbar and proximal femur BMD were assessed with dual-energy x-ray absorptiometry. Among women, multivariable-adjusted linear regression analyses revealed no significant differences in lumbar BMD across activity categories, whereas proximal femur BMD was significantly higher among those who exceeded the guidelines by 2-4 times than those who reported no activity. Among men, multivariable-adjusted BMD at both sites neared its highest values among those who exceeded the guidelines by at least 4 times and was not progressively higher with additional activity. Logistic regression estimating the odds of low BMD generally echoed the linear regression results. The association between physical activity volume and BMD is complex. Among women, exceeding guidelines by 2-4 times may be important for maximizing BMD at the proximal femur, whereas among men, exceeding guidelines by ≥4 times may be beneficial for lumbar and proximal femur BMD.

Agreement between FRAX scores calculated with and without bone mineral density in women with osteopenia in Turkey.

PubMed

Olmez Sarikaya, Nese; Kapar Yavasi, Secil; Tan, Gulten; Satiroglu, Servet; Yildiz, Arife Hilal; Oz, Bengi; Yoleri, Ozlem; Memis, Asuman

2014-12-01

This study aimed to analyze the agreement between FRAX scores calculated with and without femoral neck (FN) bone mineral density (BMD) and to investigate the resultant treatment recommendations in women with osteopenia. A cross-sectional review of postmenopausal women who were referred for DXA evaluation was conducted. One hundred twenty-nine postmenopausal women aged 40 years and older with osteopenia [FN T-score between -1 and (-2.5)] were recruited for the study. Absolute agreement between FRAX scores calculated with and without BMD was analyzed by intraclass correlation analysis (ICC). Thresholds recommended by National Osteoporosis Foundation were used for treatment recommendations. Correlation between demographic factors and the difference in BMD+ and BMD- FRAX scores was analyzed by Spearman correlation test. Agreement levels and treatment recommendations were also analyzed in 112/129 patients without previous fracture. Agreement between BMD+ and BMD- MO and hip FRAX scores was good (ICC 0.867) and fair to good (ICC 0.641), respectively. In patients without previous fracture, agreement between MO and hip fracture probabilities was good (ICC = 0.838 and ICC = 0.778, respectively). Treatment recommendations with respect to treatment threshold of ≥3 for hip fracture probabilities were identical in 120/129 (93 %) cases. Difference between BMD+ and BMD- fracture probabilities was correlated with age and FN BMD. In most cases, FRAX without BMD provided the same treatment recommendations as FRAX with BMD in postmenopausal women with osteopenia. Exclusion of patients with previous fracture yielded better agreement levels.

Meniscal Damage Associated with Increased Local Subchondral Bone Mineral Density: A Framingham Study

PubMed Central

Lo, GH; Niu, J; McLennan, CE; DP, Kiel; McLean, RR; Guermazi, A; Genant, HK; McAlindon, TE; Hunter, DJ

2008-01-01

Objective Because menisci and the M:L BMD are associated with loading within the knee, we postulated there to be an association between compartment-specific meniscal damage and M:L BMD. We hypothesized that knees with higher M:L BMD, consistent with increased medial subchondral BMD, would be associated with medial meniscal damage, and lower ratios with lateral meniscal damage. Methods We conducted a cross-sectional study evaluating participants in the Framingham OA Cohort having MRIs, BMDs, and x-rays of the knee. Medial and lateral meniscal damage were defined on MRI. We performed a logistic regression with medial meniscal damage as the outcome testing M:L BMD groups as predictor variables. We adjusted for age and sex; we used GEE to adjust for correlation between knees. Identical analyses were performed evaluating lateral meniscal damage. Results When evaluating the relation of M:L BMD to medial meniscal damage, the odds ratios (ORs) of prevalent medial meniscal damage from lowest to highest quartile of M:L BMD were 1.0 (referent), 1.9, 2.4 and 8.9, p for trend <0.0001. When evaluating the relation of M:L BMD to lateral meniscal damage, the ORs of prevalent lateral meniscal damage from lowest to highest quartile of M:L BMD were 1.0 (referent), 0.3, 0.2, and 0.2, p for trend =0.001. Conclusions Meniscal damage is associated with higher regional tibial BMD in the same compartment. Our findings highlight the close relationship between meniscal integrity and regional tibial subchondral BMD. PMID:17825586

Interest of a prescreening questionnaire to reduce the cost of bone densitometry.

PubMed

Ben Sedrine, W; Broers, P; Devogelaer, J P; Depresseux, G; Kaufman, J M; Goemaere, S; Reginster, J Y

2002-05-01

Bone mineral density (BMD) measurement is widely recognized as the best single tool to identify patients with a high lifetime risk of developing an osteoporosis-related fracture. However, the cost/benefit value of screening the whole population has been repeatedly challenged and demonstrated to be rather poor. In many countries, BMD scan is not or no longer reimbursed because of lack of validated criteria to identify patients who should benefit from this procedure. Based on the proposals of a nationwide expert panel, a simple questionnaire identifying historical, clinical and behavioral risk factors for osteoporosis was developed. The aim of this study was to assess the diagnostic accuracy of the proposed criteria; to determine the extent to which this questionnaire could be useful for optimizing the use of densitometry tests; and, more specifically, to estimate the diagnostic costs per osteoporotic or osteopenic patient detected. For this purpose, we applied the questionnaire to 3998 consecutive individuals at least 20 years old, of both genders, either consulting spontaneously or referred for a BMD measurement to an outpatient osteoporosis center. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and at the hip (both total hip and femoral neck). Diagnostic accuracies were evaluated through measures of sensitivity, specificity, and positive and negative predictive values. After determining a benchmark value for age, different strategies were compared in order to identify the most cost-effective one in terms of cost per patient detected. According to the WHO operational definition of osteoporosis (T-score <-2.5), 31% of the subjects were classified as osteoporotic at one or more of the measured sites. If only patients with at least one of the proposed risk factors had been referred for scans, 33.3% of the BMD measurements would have been avoided. Among those, less than 5% were missclassified as they did have osteoporosis at the total hip and up to 23% at one or more of the considered sites. On the other hand, of the subjects who would be recommended for a densitometry test, only a small fraction were identified correctly (the positive predictive values varied from 11.3% at the total hip to 34.8% at any site). In this first setting, the suggested criteria seem useful chiefly for excluding subjects who do not need a DXA scan rather than selecting osteoporotic patients. When applied only to patients aged 61 years or more, the positive predictive values rose to 15.1% (total hip) and 42.9% (any site), whereas the corresponding negative predictive values were set at 93% and 68.6%. In comparison, with a mass screening scenario the estimated diagnostic costs (costs associated with the DXA procedure) per osteoporotic patient detected at any of the considered sites would be reduced by more than 9% (59.4 instead of 65.3 Euros) if the suggested indications are taken into account for prescreening patients. And when the questionnaire is applied only to women over the age of 60 years these costs would be further reduced to 50.6 Euros, representing a 23% decrease. Then, a prescreening strategy based on these indications concomitantly with an age-selective criterion could represent a promising way toward a more rational use of BMD measurement.

Generation of induced pluripotent stem cells from a Becker muscular dystrophy patient carrying a deletion of exons 45-55 of the dystrophin gene (CCMi002BMD-A-9 ∆45-55).

PubMed

Gowran, Aoife; Spaltro, Gabriella; Casalnuovo, Federica; Vigorelli, Vera; Spinelli, Pietro; Castiglioni, Elisa; Rovina, Davide; Paganini, Stefania; Di Segni, Marina; Gervasini, Cristina; Nigro, Patrizia; Pompilio, Giulio

2018-04-01

Becker muscular dystrophy (BMD) is a dystrophinopathy caused by mutations in the dystrophin gene on chromosome Xp21. BMD mutations result in truncated semi-functional dystrophin isoforms. Consequently, less severe clinical symptoms become apparent later in life compared to Duchenne muscular dystrophy. Dermal fibroblasts from a BMD patient were electroporated with episomal plasmids containing reprogramming factors to create the induced pluripotent stem cell line: CCMi002BMD-A-9 that showed pluripotent markers, were karyotypically normal and capable of trilineage differentiation. MLPA analyses performed on DNA extracted from CCMi002BMD-A-9 showed an in-frame deletion of exons 45 to 55 (CCMi002BMD-A-9 Δ45-55). Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures.

PubMed

Styrkarsdottir, Unnur; Thorleifsson, Gudmar; Gudjonsson, Sigurjon A; Sigurdsson, Asgeir; Center, Jacqueline R; Lee, Seung Hun; Nguyen, Tuan V; Kwok, Timothy C Y; Lee, Jenny S W; Ho, Suzanne C; Woo, Jean; Leung, Ping-C; Kim, Beom-Jun; Rafnar, Thorunn; Kiemeney, Lambertus A; Ingvarsson, Thorvaldur; Koh, Jung-Min; Tang, Nelson L S; Eisman, John A; Christiansen, Claus; Sigurdsson, Gunnar; Thorsteinsdottir, Unnur; Stefansson, Kari

2016-01-06

Bone mineral density (BMD) is a measure of osteoporosis and is useful in evaluating the risk of fracture. In a genome-wide association study of BMD among 20,100 Icelanders, with follow-up in 10,091 subjects of European and East-Asian descent, we found a new BMD locus that harbours the PTCH1 gene, represented by rs28377268 (freq. 11.4-22.6%) that associates with reduced spine BMD (P=1.0 × 10(-11), β=-0.09). We also identified a new spine BMD signal in RSPO3, rs577721086 (freq. 6.8%), that associates with increased spine BMD (P=6.6 × 10(-10), β=0.14). Importantly, both variants associate with osteoporotic fractures and affect expression of the PTCH1 and RSPO3 genes that is in line with their influence on BMD and known biological function of these genes. Additional new BMD signals were also found at the AXIN1 and SOST loci and a new lead SNP at the EN1 locus.

Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures

PubMed Central

Styrkarsdottir, Unnur; Thorleifsson, Gudmar; Gudjonsson, Sigurjon A.; Sigurdsson, Asgeir; Center, Jacqueline R.; Lee, Seung Hun; Nguyen, Tuan V.; Kwok, Timothy C.Y.; Lee, Jenny S.W.; Ho, Suzanne C.; Woo, Jean; Leung, Ping-C.; Kim, Beom-Jun; Rafnar, Thorunn; Kiemeney, Lambertus A.; Ingvarsson, Thorvaldur; Koh, Jung-Min; Tang, Nelson L.S.; Eisman, John A.; Christiansen, Claus; Sigurdsson, Gunnar; Thorsteinsdottir, Unnur; Stefansson, Kari

2016-01-01

Bone mineral density (BMD) is a measure of osteoporosis and is useful in evaluating the risk of fracture. In a genome-wide association study of BMD among 20,100 Icelanders, with follow-up in 10,091 subjects of European and East-Asian descent, we found a new BMD locus that harbours the PTCH1 gene, represented by rs28377268 (freq. 11.4–22.6%) that associates with reduced spine BMD (P=1.0 × 10−11, β=−0.09). We also identified a new spine BMD signal in RSPO3, rs577721086 (freq. 6.8%), that associates with increased spine BMD (P=6.6 × 10−10, β=0.14). Importantly, both variants associate with osteoporotic fractures and affect expression of the PTCH1 and RSPO3 genes that is in line with their influence on BMD and known biological function of these genes. Additional new BMD signals were also found at the AXIN1 and SOST loci and a new lead SNP at the EN1 locus. PMID:26733130

The first case of imported Borrelia miyamotoi disease concurrent with Lyme disease.

PubMed

Oda, Rentaro; Kutsuna, Satoshi; Sekikawa, Yoshiyuki; Hongo, Igen; Sato, Kozue; Ohnishi, Makoto; Kawabata, Hiroki

2017-05-01

Borrelia miyamotoi disease (BMD) is an emerging infectious disease caused by B. miyamotoi. Although BMD has been reported in the United States, Europe, and Japan, no case of imported BMD has been described in the world. Here, we report a 63-year-old American man living in Japan who presented with malaise, headache, myalgia, and arthralgia. We suspected Lyme disease because of his travel history to Minnesota and presence of erythema migrans. Serologic analysis supported our diagnosis, and doxycycline was administered for 14 days. However, we also suspected coinfection with BMD because of his fever, elevated liver function test results and his travel history. The patient was seropositive for the immunoglobulin M antibody to recombinant glycerophosphodiester phosphodiesterase, and was diagnosed with coinfection with BMD. This case suggests that BMD should be considered in febrile travelers returning from the Northeastern and Midwestern regions of the United States, and that BMD and Lyme disease coinfection should be considered to detect cases of imported BMD. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Comparison of volumetric bone mineral density in the tibial region of interest for ACL reconstruction.

PubMed

Klein, Scott A; Nyland, John; Caborn, David N M; Kocabey, Yavuz; Nawab, Akbar

2005-12-01

Adequate tibial bone mineral density (BMD) is essential to soft tissue graft fixation during anterior cruciate ligament (ACL) reconstruction. The purpose of this study was to compare volumetric bone plug density measurements at the tibial region of interest for ACL reconstruction using a standardized immersion technique and Archimedes' principle. Cancellous bone cores were harvested from the proximal, middle, and distal metaphyseal regions of the lateral tibia and from the standard tibial tunnel location used for ACL reconstruction of 18 cadaveric specimens. Proximal tibial cores displayed 32.6% greater BMD than middle tibial cores and 31.8% greater BMD than distal tibial cores, but did not differ from the BMD of the tibial tunnel cores. Correlational analysis confirmed that the cancellous BMD in the tibial tunnel related to the cancellous BMD of the proximal and distal lateral tibial metaphysis. In conjunction with its adjacent cortical bone, the cancellous BMD of the region used for standard tibial tunnel placement provides an effective foundation for ACL graft fixation. In tibia with poor BMD, bicortical fixation that incorporates cortical bone from the distal tibial tunnel region is recommended.

Cardiorespiratory fitness and hip bone mineral density in women: a 6-year prospective study.

PubMed

Tucker, Larry A; Nokes, Neil R; Bailey, Bruce W; Lecheminant, James D

2014-10-01

Cross-sectional studies and short term interventions focusing on fitness and bone mineral density (BMD) are common. However, few investigations have studied the effect of fitness on BMD over an extended period of time. The present study was conducted to determine the extent to which cardiorespiratory fitness influences risk of BMD loss at the hip over 6 yr. A prospective cohort design was used with 245 healthy, middle-aged women. Hip BMD was assessed using dual energy x-ray absorptiometry. Calcium and vitamin D were measured using the Block Food Frequency Questionnaire. Menopause status was measured by a questionnaire. Results showed that fit and unfit women experienced similar changes in hip BMD over time. Specifically, unfit women experienced a non-significant 7% increased risk of losing hip BMD compared to their counterparts (RR = 1.07, 95% CI = 0.66, 1.73). Adjusting statistically for differences in age, initial body weight, and hip BMD, weight change, menopause status, calcium and vitamin D intake, and time between assessments had little effect on the relationship. Fitness level did not influence risk of hip BMD loss over time.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faillace, E.R.; Cheng, J.J.; Yu, C.

A series of benchmarking runs were conducted so that results obtained with the RESRAD code could be compared against those obtained with six pathway analysis models used to determine the radiation dose to an individual living on a radiologically contaminated site. The RESRAD computer code was benchmarked against five other computer codes - GENII-S, GENII, DECOM, PRESTO-EPA-CPG, and PATHRAE-EPA - and the uncodified methodology presented in the NUREG/CR-5512 report. Estimated doses for the external gamma pathway; the dust inhalation pathway; and the soil, food, and water ingestion pathways were calculated for each methodology by matching, to the extent possible, inputmore » parameters such as occupancy, shielding, and consumption factors.« less

Benchmark Dose Software (BMDS) Development and ...

EPA Pesticide Factsheets

This report is intended to provide an overview of beta version 1.0 of the implementation of a model of repeated measures data referred to as the Toxicodiffusion model. The implementation described here represents the first steps towards integration of the Toxicodiffusion model into the EPA benchmark dose software (BMDS). This version runs from within BMDS 2.0 using an option screen for making model selection, as is done for other models in the BMDS 2.0 suite. This report is intended to provide an overview of beta version 1.0 of the implementation of a model of repeated measures data referred to as the Toxicodiffusion model.

Gender-specific risk factors for low bone mineral density in patients taking antipsychotics for psychosis.

PubMed

Jhon, Min; Yoo, Taeyoung; Lee, Ju-Yeon; Kim, Seon-Young; Kim, Jae-Min; Shin, Il-Seon; Williams, Lana; Berk, Michael; Yoon, Jin-Sang; Kim, Sung-Wan

2018-01-01

This study examined clinical and gender-specific risk factors for low bone mineral density (BMD) in adult patients with psychotic disorders. The study included 285 community-dwelling patients with psychotic disorders. Dual-energy X-ray absorptiometry was used to measure BMD. Clinical characteristics associated with low BMD were identified with logistic regression analysis in total population and each gender. Fifty-eight (20.4%) subjects had low BMD. Low BMD was more common in men and in patients with low body mass indices (BMIs), as well as in those with shorter treatment durations, those on Medicaid, and patients using serotonergic antidepressants. Logistic regression analysis revealed that low BMD was negatively associated with BMI and treatment duration and positively with gender (male) and serotonergic antidepressants use in the overall population. In men, low BMD was associated with treatment duration and BMI; in women, low BMD was associated with BMI, prolactin level, vitamin D, and serotonergic antidepressant use. Managing the risk factors associated with low BMD among patients with psychotic disorder should be done gender-specifically. Psychotropic agents should be prescribed mindful of their effects on bone, as use of these medications is a modifiable risk factor for osteoporosis in women with psychotic disorders. Copyright © 2018 John Wiley & Sons, Ltd.

Prevalence and clinical determinants of low bone mineral density in anorexia nervosa.

PubMed

Hofman, Marielle; Landewé-Cleuren, Sabine; Wojciechowski, Franz; Kruseman, Arie Nieuwenhuijzen

2009-01-01

To determine the prevalence of low bone mass in anorexia nervosa (AN) and the association with clinical parameters. A cross-sectional study on 286 Caucasian women with AN. Bone mineral density (BMD) was measured with DXA. Low BMD was defined as a Z-score

Loss of lean body mass affects low bone mineral density in patients with rheumatoid arthritis - results from the TOMORROW study.

PubMed

Okano, Tadashi; Inui, Kentaro; Tada, Masahiro; Sugioka, Yuko; Mamoto, Kenji; Wakitani, Shigeyuki; Koike, Tatsuya; Nakamura, Hiroaki

2017-11-01

Osteoporosis is one of the complications for patients with rheumatoid arthritis (RA). Rheumatoid cachexia, the loss of lean body mass, is another. However, the relationship between decreased lean body mass and reduced bone mineral density (BMD) in patients with RA has not been well studied. This study included 413 participants, comprising 208 patients with RA and 205 age- and sex-matched healthy volunteers. Clinical data, BMD, bone metabolic markers (BMM) and body composition, such as lean body mass and percent fat, were collected. Risk factors for osteoporosis in patients with RA including the relationship BMD and body composition were analyzed. Patients with RA showed low BMD and high BMM compared with controls. Moreover, lean body mass was lower and percent fat was higher in patients with RA. Lean body mass correlated positively and percent fat negatively with BMD. Lean body mass was a positive and disease duration was a negative independent factor for BMD in multivariate statistical analysis. BMD and lean body mass were significantly lower in patients with RA compared to healthy controls. Lean body mass correlated positively with BMD and decreased lean body mass and disease duration affected low BMD in patients with RA. [UMIN Clinical Trials Registry, http://www.umin.ac.jp/ctr/ , UMIN000003876].

Comparison of Vocal Vibration-Dose Measures for Potential-Damage Risk Criteria

ERIC Educational Resources Information Center

Titze, Ingo R.; Hunter, Eric J.

2015-01-01

Purpose: School-teachers have become a benchmark population for the study of occupational voice use. A decade of vibration-dose studies on the teacher population allows a comparison to be made between specific dose measures for eventual assessment of damage risk. Method: Vibration dosimetry is reformulated with the inclusion of collision stress.…

Low bone mineral density in achondroplasia and hypochondroplasia.

PubMed

Matsushita, Masaki; Kitoh, Hiroshi; Mishima, Kenichi; Kadono, Izumi; Sugiura, Hiroshi; Hasegawa, Sachi; Nishida, Yoshihiro; Ishiguro, Naoki

2016-08-01

Achondroplasia (ACH) and hypochondroplasia (HCH) are the most common form of short-limb skeletal dysplasias caused by activated fibroblast growth factor receptor 3 (FGFR3) signaling. Although decreased bone mass was reported in gain-of-function mutation in Fgfr3 mice, both disorders have never been described as osteoporotic. In the present study, we evaluated bone mineral density (BMD) in ACH and HCH patients. We measured spinal BMD (L1-L4) in 18 ACH and four HCH patients with an average age of 19.8 ± 7.5 years (range, 10-33 years). BMD Z-score in each individual was calculated for normalizing age and gender. Correlation between body mass index (BMI) and BMD was analyzed. Moreover, BMD and Z-score were compared between ACH patients and HCH patients. The average BMD of ACH/HCH patients was 0.805 ± 0.141 g/cm(2) (range, 0.554-1.056 g/cm(2) ), resulting in an average Z-score of -1.1 ± 0.8 (range, -2.4 to 0.6) of the standard value. A slightly positive correlation was observed between BMI and BMD (r = 0.45; P = 0.13). There was no significant difference in BMD and Z-score between ACH and HCH patients. Spinal BMD was reduced in ACH/HCH patients, and was mildly correlated with individual BMI. We should carefully monitor BMD and examine osteoporosis-related symptoms in adolescent and adult ACH/HCH patients. © 2016 Japan Pediatric Society. © 2015 Japan Pediatric Society.

High-Density Association Study of 383 Candidate Genes for Volumetric BMD at the Femoral Neck and Lumbar Spine Among Older Men

PubMed Central

Yerges, Laura M.; Klei, Lambertus; Cauley, Jane A.; Roeder, Kathryn; Kammerer, Candace M.; Moffett, Susan P.; Ensrud, Kristine E.; Nestlerode, Cara S.; Marshall, Lynn M.; Hoffman, Andrew R.; Lewis, Cora; Lang, Thomas F.; Barrett-Connor, Elizabeth; Ferrell, Robert E.; Orwoll, Eric S.

2009-01-01

Genetics is a well-established but poorly understood determinant of BMD. Whereas some genetic variants may influence BMD throughout the body, others may be skeletal site specific. We initially screened for associations between 4608 tagging and potentially functional single nucleotide polymorphisms (SNPs) in 383 candidate genes and femoral neck and lumbar spine volumetric BMD (vBMD) measured from QCT scans among 862 community-dwelling white men ≥65 yr of age in the Osteoporotic Fractures in Men Study (MrOS). The most promising SNP associations (p < 0.01) were validated by genotyping an additional 1156 white men from MrOS. This analysis identified 8 SNPs in 6 genes (APC, DMP1, FGFR2, FLT1, HOXA, and PTN) that were associated with femoral neck vBMD and 13 SNPs in 7 genes (APC, BMPR1B, FOXC2, HOXA, IGFBP2, NFATC1, and SOST) that were associated with lumbar spine vBMD in both genotyping samples (p < 0.05). Although most associations were specific to one skeletal site, SNPs in the APC and HOXA gene regions were associated with both femoral neck and lumbar spine BMD. This analysis identifies several novel and robust genetic associations for volumetric BMD, and these findings in combination with other data suggest the presence of genetic loci for volumetric BMD that are at least to some extent skeletal-site specific. PMID:19453261

Increased bone mineral density in Aboriginal and Torres Strait Islander Australians: impact of body composition differences.

PubMed

Maple-Brown, L J; Hughes, J; Piers, L S; Ward, L C; Meerkin, J; Eisman, J A; Center, J R; Pocock, N A; Jerums, G; O'Dea, K

2012-07-01

Bone mineral density (BMD) has been reported to be both higher and lower in Indigenous women from different populations. Body composition data have been reported for Indigenous Australians, but there are few published BMD data in this population. We assessed BMD in 161 Indigenous Australians, identified as Aboriginal (n=70), Torres Strait Islander (n=68) or both (n=23). BMD measurements were made on Norland-XR46 (n=107) and Hologic (n=90) dual-energy X-ray absorptiometry (DXA) machines. Norland BMD and body composition measurements in these individuals, and also in 36 Caucasian Australians, were converted to equivalent Hologic BMD (BMD(H)) and body composition measurements for comparison. Femoral neck (FN) and lumbar spine Z-scores were high in Indigenous participants (mean FN Z-score: Indigenous men +0.98, p<0.0001 vs. mean zero; Indigenous women +0.82, p<0.0001 vs. mean zero). FN BMD(H) was higher in Aboriginal and/or Torres Strait Islander than Caucasian participants, after adjusting for age, gender, diabetes and height and remained higher in men after addition of lean mass to the model. We conclude that FN BMD is higher in Aboriginal and/or Torres Strait Islander Australians than Caucasian Australian reference ranges and these differences still remained significant in men after adjustment for lean mass. It remains to be seen whether these BMD differences translate to differences in fracture rates. Copyright © 2012 Elsevier Inc. All rights reserved.

Longitudinal changes in femur bone mineral density after spinal cord injury: effects of slice placement and peel method

PubMed Central

Dudley-Javoroski, S.

2010-01-01

Summary Surveillance of femur metaphysis bone mineral density (BMD) decline after spinal cord injury (SCI) may be subject to slice placement error of 2.5%. Adaptations to anti-osteoporosis measures should exceed this potential source of error. Image analysis parameters likewise affect BMD output and should be selected strategically in longitudinal studies. Introduction Understanding the longitudinal changes in bone mineral density (BMD) after spinal cord injury (SCI) is important when assessing new interventions. We determined the longitudinal effect of SCI on BMD of the femur metaphysis. To facilitate interpretation of longitudinal outcomes, we (1) determined the BMD difference associated with erroneous peripheral quantitative computed tomography (pQCT) slice placement, and (2) determined the effect of operator-selected pQCT peel algorithms on BMD. Methods pQCT images were obtained from the femur metaphysis (12% of length from distal end) of adult subjects with and without SCI. Slice placement errors were simulated at 3 mm intervals and were processed in two ways (threshold-based vs. concentric peel). Results BMD demonstrated a rapid decline over 2 years post-injury. BMD differences attributable to operator-selected peel methods were large (17.3% for subjects with SCI). Conclusions Femur metaphysis BMD declines after SCI in a manner similar to other anatomic sites. Concentric (percentage-based) peel methods may be most appropriate when special sensitivity is required to detect BMD adaptations. Threshold-based methods may be more appropriate when asymmetric adaptations are observed. PMID:19707702

Racial/ethnic differences in bone mineral density among older women

PubMed Central

Nam, Hae-Sung; Kweon, Sun-Seog; Choi, Jin-Su; Zmuda, Joseph M.; Leung, P. C.; Lui, Li-Yung; Hill, Deanna D.; Patrick, Alan L.

2014-01-01

The epidemiologic information regarding international differences in bone mineral density (BMD) in women is currently insufficient. We compared BMD in older women across five racial/ethnic groups in four countries. The femoral neck, total hip, and lumbar spine BMD were measured in women (aged 65–74 years) from the Study of Osteoporotic Fractures (SOF) (5,035 Caucasian women and 256 African American women in the US), the Tobago Women’s Health Study (116 Afro-Caribbean women), the Ms Os Hong Kong Study (794 Hong Kong Chinese women) and the Namwon Study (1,377 South Korean women). BMD was corrected according to the cross-site calibration results for all scanners. When compared with US Caucasian women, the age adjusted mean BMD measurements at the hip sites were 21–31 % higher among Tobago Afro-Caribbean women and 13–23 % higher among African American women. The total hip and spine BMD values were 4–5 % lower among Hong Kong Chinese women and 4–7 % lower among South Korean women compared to US Caucasians. The femoral neck BMD was similar in Hong Kong Chinese women, but higher among South Korean women compared to US Caucasians. Current/past estrogen use was a significant contributing factor to the difference in BMD between US versus non-US women. Differences in body weight partially explained the difference in BMD between Asian versus non-Asian women. These findings show substantial racial/ethnic differences in BMD even within African or Asian origin individuals, and highlight the contributing role of body weight and estrogen use to the geographic and racial/ethnic variation in BMD. PMID:23143509

The Relationship Between Fractures and DXA Measures of BMD in the Distal Femur of Children and Adolescents With Cerebral Palsy or Muscular Dystrophy

PubMed Central

Henderson, Richard C; Berglund, Lisa M; May, Ryan; Zemel, Babette S; Grossberg, Richard I; Johnson, Julie; Plotkin, Horacio; Stevenson, Richard D; Szalay, Elizabeth; Wong, Brenda; Kecskemethy, Heidi H; Harcke, H Theodore

2010-01-01

Children with limited or no ability to ambulate frequently sustain fragility fractures. Joint contractures, scoliosis, hip dysplasia, and metallic implants often prevent reliable measures of bone mineral density (BMD) in the proximal femur and lumbar spine, where BMD is commonly measured. Further, the relevance of lumbar spine BMD to fracture risk in this population is questionable. In an effort to obtain bone density measures that are both technically feasible and clinically relevant, a technique was developed involving dual-energy X-ray absorptiometry (DXA) measures of the distal femur projected in the lateral plane. The purpose of this study is to test the hypothesis that these new measures of BMD correlate with fractures in children with limited or no ability to ambulate. The relationship between distal femur BMD Z-scores and fracture history was assessed in a cross-sectional study of 619 children aged 6 to 18 years with muscular dystrophy or moderate to severe cerebral palsy compiled from eight centers. There was a strong correlation between fracture history and BMD Z-scores in the distal femur; 35% to 42% of those with BMD Z-scores less than −5 had fractured compared with 13% to 15% of those with BMD Z-scores greater than −1. Risk ratios were 1.06 to 1.15 (95% confidence interval 1.04–1.22), meaning a 6% to 15% increased risk of fracture with each 1.0 decrease in BMD Z-score. In clinical practice, DXA measure of BMD in the distal femur is the technique of choice for the assessment of children with impaired mobility. © 2010 American Society for Bone and Mineral Research PMID:19821773

Dietary isoflavones and bone mineral density during midlife and the menopausal transition: cross-sectional and longitudinal results from the Study of Women's Health Across the Nation Phytoestrogen Study.

PubMed

Greendale, Gail A; Tseng, Chi-Hong; Han, Weijuan; Huang, Mei-Hua; Leung, Katherine; Crawford, Sybil; Gold, Ellen B; Waetjen, L Elaine; Karlamangla, Arun S

2015-03-01

This study aims to examine cross-sectional and longitudinal relations between dietary intake of isoflavones and bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) in black, white, Chinese, and Japanese women during the menopausal transition. We tested whether tertiles of isoflavone intake were associated with baseline BMD when all women were premenopausal or early perimenopausal. To analyze whether isoflavone intake was associated with longitudinal BMD, we fitted piecewise linear models to repeated measurements of baseline-normalized LS or FN BMD as functions of time before or after the final menstrual period (FMP) date. Multiply adjusted mean FN BMD values of premenopausal Japanese women were monotonically positively related to isoflavone consumption (P for trend = 0.0003). Otherwise, no statistically significant baseline associations were observed. During the period of 1 year before the FMP through 5 years after the FMP, all participants lost LS and FN BMD. Loss was unrelated to isoflavone intake, except for Japanese women during the period of 1 year before the FMP to 2 years after the FMP: higher tertiles of isoflavone intake were associated with greater annual LS BMD loss rates (P for trend = 0.01) and FN loss rates (P for trend = 0.04). In Japanese women, higher isoflavone intake is associated with higher peak FN BMD but also with greater rates of LS and FN BMD loss during the menopausal transition. Results for the other racial/ethnic groups did not support a relation between dietary intake of isoflavones and either peak BMD or BMD loss during the menopausal transition.

Thin healthy women have a similar low bone mass to women with anorexia nervosa.

PubMed

Fernández-García, D; Rodríguez, M; García Alemán, J; García-Almeida, J M; Picón, M J; Fernández-Aranda, F; Tinahones, F J

2009-09-01

An association between anorexia nerviosa (AN) and low bone mass has been demonstrated. Bone loss associated with AN involves hormonal and nutritional impairments, though their exact contribution is not clearly established. We compared bone mass in AN patients with women of similar weight with no criteria for AN, and a third group of healthy, normal-weight, age-matched women. The study included forty-eight patients with AN, twenty-two healthy eumenorrhoeic women with low weight (LW group; BMI < 18.5 kg/m2) and twenty healthy women with BMI >18.5 kg/m2 (control group), all of similar age. We measured lean body mass, percentage fat mass, total bone mineral content (BMC) and bone mineral density in lumbar spine (BMD LS) and in total (tBMD). We measured anthropometric parameters, leptin and growth hormone. The control group had greater tBMD and BMD LS than the other groups, with no differences between the AN and LW groups. No differences were found in tBMD, BMD LS and total BMC between the restrictive (n 25) and binge-purge type (n 23) in AN patients. In AN, minimum weight (P = 0.002) and percentage fat mass (P = 0.02) explained BMD LS variation (r2 0.48) and minimum weight (r2 0.42; P = 0.002) for tBMD in stepwise regression analyses. In the LW group, BMI explained BMD LS (r2 0.72; P = 0.01) and tBMD (r2 0.57; P = 0.04). We concluded that patients with AN had similar BMD to healthy thin women. Anthropometric parameters could contribute more significantly than oestrogen deficiency in the achievement of peak bone mass in AN patients.

Omentin Polymorphism and its Relations to Bone Mineral Density in Women.

PubMed

Boron, Dariusz; Czerny, Boguslaw; Bartkowiak-Wieczorek, Joanna; Sieron, Dominik; Wolski, Hubert

2015-04-01

Recognition of different genetic variants underlying development of osteoporosis would make it possible to administer individual symptomatic treatment as well as early prophylactics of osteoporosis. The aim of the study was to evaluate frequency of polymorphism 326A/T of gene ITLN-1 and assessment of its relations with the clinical parameters of osseous turnover and degree of postmenopausal osteoporosis. The study included 800 women at the postmenopausal (505) and reproductive (295) age throughout Wielkopolska region in Poland. The postmenopausal group included women with osteoporosis and osteopenia and the healthy ones. Women at the reproductive age were healthy. Frequency of the tested gene polymorphism was evaluated in the group where BMD was marked and in the control group. The analysis of the polymorphism A326T of gene ITLN-1 showed that in healthy postmenopausal female with genotype AA birth weight, BMD L2-L4 YA (%) and BMD L2-L4 AM (%) were significantly higher (BMD-bone mineral density; L2-L4-- lumbar vertebrae no 2, 4; YA--peak adult bone mass; AM--age-matched bone mass). In women with osteopenia BMD L2-L4 YA (%) and BMD L2-L4 AM (%) were significantly higher in women with genotype AA, but BMD L2-L4 was significantly higher in women with genotype TT. In women with osteoporosis with genotype AA T-score was significantly higher, but BMD L2-L4 and BMD L2-L4 YA (%) were significantly lower in this group. BMD L2-L4 AM (%) was significantly higher in women with AA genotype. In women with osteoporosis and osteopenia homozygous AA genotype may predispose to lower BMD in the lumbar spine. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

Prediction of bone strength at the distal tibia by HR-pQCT and DXA.

PubMed

Popp, Albrecht W; Windolf, Markus; Senn, Christoph; Tami, Andrea; Richards, R Geoff; Brianza, Stefano; Schiuma, Damiano

2012-01-01

Areal bone mineral density (aBMD) at the distal tibia, measured at the epiphysis (T-EPI) and diaphysis (T-DIA), is predictive for fracture risk. Structural bone parameters evaluated at the distal tibia by high resolution peripheral quantitative computed tomography (HR-pQCT) displayed differences between healthy and fracture patients. With its simple geometry, T-DIA may allow investigating the correlation between bone structural parameter and bone strength. Anatomical tibiae were examined ex vivo by DXA (aBMD) and HR-pQCT (volumetric BMD (vBMD) and bone microstructural parameters). Cortical thickness (CTh) and polar moment of inertia (pMOI) were derived from DXA measurements. Finally, an index combining material (BMD) and mechanical property (polar moment of inertia, pMOI) was defined and analyzed for correlation with torque at failure and stiffness values obtained by biomechanical testing. Areal BMD predicted the vBMD at T-EPI and T-DIA. A high correlation was found between aBMD and microstructural parameters at T-EPIas well as between aBMD and CTh at T-DIA. Finally, at T-DIA both indexes combining BMD and pMOI were strongly and comparably correlated with torque at failure and bone stiffness. Ex vivo, at the distal tibial diaphysis, a novel index combining BMD and pMOI, which can be calculated directly from a single DXA measurement, predicted bone strength and stiffness better than either parameter alone and with an order of magnitude comparable to that of HR-pQCT. Whether this index is suitable for better prediction of fracture risk in vivo deserves further investigation. Copyright © 2011 Elsevier Inc. All rights reserved.

Adipocytokine and ghrelin levels in relation to bone mineral density in prepubertal rhythmic gymnasts entering puberty: a 3-year follow-up study.

PubMed

Võsoberg, Kristel; Tillmann, Vallo; Tamm, Anna-Liisa; Jürimäe, Toivo; Maasalu, Katre; Jürimäe, Jaak

2016-04-01

To investigate changes in bone mineral density (BMD) in rhythmic gymnasts (RG) entering puberty and their age-matched untrained controls (UC) over the 36-month period, and associations with leptin, adiponectin and ghrelin over this period. Whole body (WB), lumbar spine (LS) and femoral neck (FN) BMD, WB bone mineral content (BMC), and leptin, adiponectin and ghrelin were measured in 35 RG and 33 UC girls at baseline and at 12-month intervals over the next 3 years. The change over the 36 months was calculated (∆ score). The pubertal development over the next 36 months was slower in RG compard to UC, while there was no difference in bone age development between the groups. BMD at all sites was higher in RG in comparison with UC at every measurement point. ∆LS BMD and ∆FN BMD, but not ∆WB BMD and ∆WB BMC, were higher in RG compared with UC. None of the measured hormones at baseline or their ∆ scores correlated with ∆BMD and ∆BMC in RG. Baseline fat free mass correlated with ∆WB BMD and ∆WB BMC in RG, while baseline leptin was related to ∆WB BMC, ∆WB BMD and ∆LS BMD in UC. Measured baseline hormones and their ∆ scores did not correlate with increases in bone mineral values in RG entering puberty. Although the pubertal development in RG was slower than in UC, high-intensity training appeared to increase BMD growth and counterbalance negative effects of slow pubertal develpment, lower fat mass and leptin in RG.

Evaluation of Glutathione-S-Transferase P1 Polymorphism and its Relation to Bone Mineral Density in Egyptian Children and Adolescents with Beta-Thalassemia Major

PubMed Central

Ragab, Seham M.; Badr, Eman A.; Ibrahim, Ahmed S.

2016-01-01

Background Osteoporosis is a major complication of beta thalassemia major (TM). Increased oxidative stress and its controlling genes were linked to osteoporosis. Ile105 Val variant is a functional polymorphism of Glutathione S-transferase P1 (GSTP1), with reduced anti-oxidative property. No data are available about this variant or its association with osteoporosis among thalassemia patients yet. Objectives To investigate Ile105Val polymorphism and its possible association with bone mineral density (BMD) values in a group of TM children. Methods Thirty five TM children and 30 age and sex matched healthy controls were included. Liver and renal functions, serum ferritin, calcium, phosphorous, alkaline phosphatase and osteocalcin were assayed. BMD was determined by DXA with calculation of Z-scores at lumbar spine (LS) and femoral neck (FN). Height for age Z- score (HAZ) adjusted BMD Z-scores were calculated. GSTP1 Ile105Val polymorphism was studied by polymerase chain reaction-restriction fragment length polymorphism. Results The relative frequency of 105 Val allele was significantly higher in TM patients than the controls (p<0.0001). Significant association between genotype subgroups and BMD parameters was detected. Compared to wild homozygotes, polymorphic homozygotes had lower LS-BMD (p =0.029), LS-BMD Z –score (p=0.008 ), LS- BMD haz - Z-score (p=0.011), FN- BMD (p= 0.001), FN- BMD Z –score (p=0.02) and FN-BMD haz - Z-score (p=0.001). They exhibited higher osteocalcin levels compared to heterozygotes and wild homozygotes (p=0.012, p=0.013, respectively). Conclusion Ile105Val polymorphism was frequent among TM patients and could increase their susceptibility to reduced BMD. Large sample studies are required to confirm these findings. PMID:26740865

Outcome of bone mineral density in anorexia nervosa patients 11.7 years after first admission.

PubMed

Herzog, W; Minne, H; Deter, C; Leidig, G; Schellberg, D; Wüster, C; Gronwald, R; Sarembe, E; Kröger, F; Bergmann, G

1993-05-01

Osteopenia is a typical finding in patients suffering from anorexia nervosa. Unfortunately, available longitudinal studies are limited by a relatively short follow-up period. Therefore cross-sectional long-term followup studies may help to determine both the outcome of this bone lesion and variables that influence its subsequent development. Of an initial 66 consecutive patients with anorexia nervosa, 51 (77.3%) could be further evaluated. After an average of 11.7 years following first admission, cross-sectional measurements of lumbar and proximal radial bone mineral density (BMD) were performed. The ability to predict BMD using variables obtained from anamnestic and clinical data was then determined by multiple-regression analysis. The BMD of both radial and lumbar bone in anorexic patients with poor disease outcome (as defined by the Morgan-Russell general outcome categories) deviated by -2.18 and -1.73 SD (Z score), respectively. In patients with a good disease outcome lumbar BMD was significantly less reduced compared with radial BMD (-0.26 versus -0.68 SD). Variables reflecting estrogen deficiency and nutritional status in the course of the disease, that is, relative estrogen exposure (for lumbar BMD) and years of anorexia nervosa (for radial BMD), allowed the best prediction of BMD. A marked reduction in cortical and trabecular BMD in anorexic patients with poor disease outcome suggests a higher risk of fractures in these patients. Furthermore, the finding of a persistently reduced cortical and a slightly reduced trabecular BMD, even in patients with good disease outcome, suggests that a recovery of trabecular BMD might be possible, at least in part. Recovery of cortical bone, if possible at all, seems to proceed more slowly.

Parathyroid hormone is predictive of low bone mass in Canadian aboriginal and white women.

PubMed

Weiler, Hope A; Leslie, William D; Bernstein, Charles N

2008-03-01

Canadian Aboriginal women have lower age- and weight-corrected bone mineral density (BMD) and lower vitamin D status than White women. This study was undertaken to describe the differences in biomarkers of bone metabolism and vitamin D in Aboriginal and non-Aboriginal women and to establish which biomarkers were predictive of BMD. In total, 41 rural Aboriginal, 212 urban Aboriginal and 182 urban White women were studied for BMD of the distal radius, calcaneus, lumbar spine, femoral neck, total hip and whole body using dual-energy X-ray absorptiometry. Serum biomarkers measured included calcium, phosphate, alkaline phosphatase (ALP), C-telopeptide of type 1 collagen (CTX), osteocalcin (OC), osteoprotegerin (OPG), parathyroid hormone (PTH) and 25(OH)D. Data were analyzed for differences among the three groups stratified by age (25 to 39, 40 to 59 and 60 to 75 y) using factorial ANOVA. Predictors of BMD including ethnicity, age and body weight were identified using step-wise regression. Unadjusted BMD of all sites declined with age regardless of ethnic grouping. Prediction models for 5 of 6 BMD sites included PTH accounting for age and body weight. Other predictors of BMD included OC for the radius and calcaneus; OPG for spine and total hip; and ALP for whole body and calcaneus. Serum 25(OH)D was not included in any model of BMD. After accounting for all variables in the regression equation, an average Aboriginal woman of 46 y and 79 kg was predicted to have 6% lower calcaneus BMD and 3% lower radius BMD compared to a White woman of the same age and weight. In conclusion, PTH is a better predictor of BMD than 25(OH)D in this population of Aboriginal and White women.

Increase in bone mineral density in strictly treated Crohn's disease patients with concomitant calcium and vitamin D supplementation.

PubMed

Bakker, Sjoerd F; Dik, Vincent K; Witte, Birgit I; Lips, Paul; Roos, Jan C; Van Bodegraven, Adriaan A

2013-06-01

Decreased bone mineral density (BMD) is common in Crohn's disease (CD) patients. This paper reports on the prevalence of decreased BMD in a referral cohort study of CD-patients next to the change of BMD over time in relation with CD-associated clinical characteristics. 205 CD patients of a referral hospital were enrolled between January1998-January 2010 when measurement of BMD by dual X-ray absorptiometry (DXA) was available. Follow-up DXA scan was performed in subjects with known risk factors besides Crohn indicative for low BMD. Treatment of CD patients was according to a protocol which is comparable to the current (inter)national guidelines. In osteopenic patients, supplemental vitamin D (800 IU) and Calcium (500-1000 mg) were prescribed. Mean BMD at baseline was 0.97 ± 0.16 gram/cm(2) in lumbar spine and 0.87 ± 0.12 gram/cm(2) in the total hip. At baseline, higher age and low Body Mass Index (BMI), were negatively correlated with BMD. Eighty-four patients underwent a second BMD assessment with a median interval period of 4 years (IQR 3-6). A mean annual increase of +0.76% (95%CI: -2.63%; +3.87%) in lumbar spine and +0.43% (95%CI: -2.65% ; +1.11%) in total hip was observed. Higher age, male sex, low BMI, and a higher age at diagnosis of CD were associated with low BMD. Follow-up of BMD in CD patients showed a contraintuitive small increase of BMD at lumbar spine and total hip in CD patients only using supplemental vitamin D and calcium next to strict treatment of CD. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Bone Mineral Density across a Range of Physical Activity Volumes: NHANES 2007–2010

PubMed Central

Whitfield, Geoffrey P.; Kohrt, Wendy M.; Pettee Gabriel, Kelley K.; Rahbar, Mohammad H.; Kohl, Harold W.

2014-01-01

Introduction The association between aerobic physical activity volume and bone mineral density (BMD) is not completely understood. The purpose of this study was to clarify the association between BMD and aerobic activity across a broad range of activity volumes, in particular volumes between those recommended in the 2008 Physical Activity Guidelines for Americans and those of trained endurance athletes. Methods Data from the 2007–2010 National Health and Nutrition Examination Survey were used to quantify the association between reported physical activity and BMD at the lumbar spine and proximal femur across the entire range of activity volumes reported by US adults. Participants were categorized into multiples of the minimum guideline-recommended volume based on reported moderate and vigorous intensity leisure activity. Lumbar and proximal femur BMD was assessed with dual-energy x-ray absorptiometry. Results Among women, multivariable-adjusted linear regression analyses revealed no significant differences in lumbar BMD across activity categories, while proximal femur BMD was significantly higher among those who exceeded guidelines by 2–4 times than those who reported no activity. Among men, multivariable-adjusted BMD at both sites neared its highest values among those who exceeded guidelines by at least 4 times and was not progressively higher with additional activity. Logistic regression estimating the odds of low BMD generally echoed the linear regression results. Conclusion The association between physical activity volume and BMD is complex. Among women, exceeding guidelines by 2–4 times may be important for maximizing BMD at the proximal femur, while among men, exceeding guidelines by 4+ times may be beneficial for lumbar and proximal femur BMD. PMID:24870584

Fracture risk among older men: osteopenia and osteoporosis defined using cut-points derived from female versus male reference data.

PubMed

Pasco, J A; Lane, S E; Brennan, S L; Timney, E N; Bucki-Smith, G; Dobbins, A G; Nicholson, G C; Kotowicz, M A

2014-03-01

We explored the effect of using male and female reference data in a male sample to categorise areal bone mineral density (BMD). Using male reference data, a large proportion of fractures arose from osteopenia, whereas using female reference data shifted the fracture burden into normal BMD. The purpose of this study was to describe fracture risk associated with osteopenia and osteoporosis in older men, defined by areal BMD and using cut-points derived from male and female reference data. As part of the Geelong Osteoporosis Study, we followed 619 men aged 60-93 years after BMD assessments (performed 2001-2006) until 2010, fracture, death or emigration. Post-baseline fractures were radiologically confirmed, and proportions of fractures in each BMD category were age-standardised to national profiles. Based on World Health Organization criteria, and using male reference data, 207 men had normal BMD at the femoral neck, 357 were osteopenic and 55 were osteoporotic. Using female reference data, corresponding numbers were 361, 227 and 31. During the study, 130 men died, 15 emigrated and 63 sustained at least one fracture. Using male reference data, most (86.5 %) of the fractures occurred in men without osteoporosis on BMD criteria (18.4 % normal BMD, 68.1 % osteopenia). The pattern differed when female reference data were used; while most fractures arose from men without osteoporosis (88.2 %), the burden shifted from those with osteopenia (34.8 %) to those with normal BMD (53.4 %). Decreasing BMD categories defined increasing risk of fracture. Although men with osteoporotic BMD were at greatest risk, they made a relatively small contribution to the total burden of fractures. Using male reference data, two-thirds of the fractures arose from men with osteopenia. However, using female reference data, approximately half of the fractures arose from those with normal BMD. Using female reference data to define osteoporosis in men does not appear to be the optimal approach.

Race/ethnic differences in bone mineral densities in older men

PubMed Central

Nam, H.-S.; Shin, M.-H.; Zmuda, J. M.; Leung, P. C.; Barrett-Connor, E.; Orwoll, E. S.

2010-01-01

Summary BMD was compared across race/ethnic groups. There were substantial race/ethnic differences in BMD even within African or Asian origin. Additional adjustment for body size greatly attenuated or reversed the differences between US Caucasian men vs Asian men. It illustrates the role of body size on the difference between these groups. Introduction There is insufficient epidemiologic information about men’s bone mineral density (BMD) levels across race/ethnic groups and geographic locations. Methods In a cross-sectional design, we compared BMD in older men across seven race/ethnic groups in four countries. Femoral neck, total hip, and lumbar spine BMD were measured in men (age 65 to 78 years) from the Osteoporotic Fractures in Men (MrOS) Study (4,074 Caucasian, 208 African-American, 157 Asian, and 116 Hispanic men in USA), Tobago Bone Health Study (422 Afro-Caribbean men), MrOS Hong Kong Study (1,747 Hong Kong Chinese men), and the Namwon Study (1,079 South Korean men). BMD was corrected according to the cross-site calibration results for all scanners. Results When compared with US Caucasian men, Afro-Caribbean and African-American men had, respectively, 8–20% and 6–11% higher age-adjusted mean BMD at all three bone sites. Hip BMD was similar in US Caucasian and Hispanic men, US Asian, Hong Kong Chinese, and Korean men had 3–14% lower BMD at all bone sites except femoral neck in Korean men. Additional adjustment for weight and height greatly attenuated or reversed the differences between US Caucasian men vs Asian men including US Asian, Hong Kong Chinese, and South Korean men. Among Asian groups, Korean men had higher femoral neck BMD and lower total hip BMD. Conclusion These findings show substantial race/ethnic differences in BMD even within African or Asian origin and illustrate the important role of body size on the difference between Asian men and others. PMID:20204598

Genome-wide association study in East Asians suggests UHMK1 as a novel bone mineral density susceptibility gene.

PubMed

Choi, Hyung Jin; Park, Hyojung; Zhang, Lei; Kim, Jung Hee; Kim, Ye An; Yang, Jae-Yeon; Pei, Yu-Fang; Tian, Qing; Shen, Hui; Hwang, Joo-Yeon; Deng, Hong-Wen; Cho, Nam H; Shin, Chan Soo

2016-10-01

To identify genetic variants that influence bone mineral density (BMD) in East Asians, we performed a quantitative trait analysis of lumbar spine, total hip and femoral neck BMD in a Korean population-based cohort (N=2729) and follow-up replication analysis in a Chinese Han population and two Caucasian populations (N=1547, 2250 and 987, respectively). From the meta-analysis of the stage 1 discovery analysis and stage 2 replication analysis, we identified four BMD loci that reached near-genome-wide significance level (P<5×10(-7)). One locus on 1q23 (UHMK1, rs16863247, P=4.1×10(-7) for femoral neck BMD and P=3.2×10(-6) for total hip BMD) was a novel BMD signal. Interestingly, rs16863247 was very rare in Caucasians (minor allele frequency<0.01), indicating that this association could be specific to East Asians. In gender specific analysis, rs1160574 on 1q32 (KCNH1) was associated with femoral neck BMD (P=2.1×10(-7)) in female subjects. rs9371538 in the known BMD region on 6q25 ESR1 was associated with lumbar spine BMD (P=5.6×10(-9)). rs7776725 in the known BMD region on 7q31 WTN16 was associated with total hip BMD (P=8.6×10(-9)). In osteoblasts, endogenous UHMK1 expression was increased during differentiation and UHMK1 knockdown decreased its differentiation, while UHMK1 overexpression increased its differentiation. In osteoclasts, endogenous UHMK1 expression was decreased during differentiation and UHMK1 knockdown increased its differentiation, while UHMK1 overexpression decreased its differentiation. In conclusion, our genome-wide association study identified the UHMK1 gene as a novel BMD locus specific to East Asians. Functional studies suggest a role of UHMK1 on regulation of osteoblasts and osteoclasts. Copyright © 2016 Elsevier Inc. All rights reserved.

Relation between obesity and bone mineral density and vertebral fractures in Korean postmenopausal women.

PubMed

Kim, Kyong-Chol; Shin, Dong-Hyuk; Lee, Sei-Young; Im, Jee-Aee; Lee, Duk-Chul

2010-11-01

The traditional belief that obesity is protective against osteoporosis has been questioned. Recent epidemiologic studies show that body fat itself may be a risk factor for osteoporosis and bone fractures. Accumulating evidence suggests that metabolic syndrome and the individual components of metabolic syndrome such as hypertension, increased triglycerides, and reduced high-density lipoprotein cholesterol are also risk factors for low bone mineral density. Using a cross sectional study design, we evaluated the associations between obesity or metabolic syndrome and bone mineral density (BMD) or vertebral fracture. A total of 907 postmenopausal healthy female subjects, aged 60-79 years, were recruited from woman hospitals in Seoul, South Korea. BMD, vetebral fracture, bone markers, and body composition including body weight, body mass index (BMI), percentage body fat, and waist circumference were measured. After adjusting for age, smoking status, alcohol consumption, total calcium intake, and total energy intake, waist circumference was negatively related to BMD of all sites (lumbar BMD p = 0.037, all sites of femur BMD p < 0.001) whereas body weight was still positively related to BMD of all sites (p < 0.001). Percentage body fat and waist circumference were much higher in the fracture group than the non-fracture group (p = 0.0383, 0.082 respectively). Serum glucose levels were positively correlated to lumbar BMD (p = 0.016), femoral neck BMD (p = 0.0335), and femoral trochanter BMD (p = 0.0082). Serum high density lipoprotein cholesterol (HDLC) was positively related to femoral trochanter BMD (p = 0.0366) and was lower in the control group than the fracture group (p = 0.011). In contrast to the effect favorable body weight on bone mineral density, high percentage body fat and waist circumference are related to low BMD and a vertebral fracture. Some components of metabolic syndrome were related to BMD and a vertebral fracture.

Temporal trends in obesity, osteoporosis treatment, bone mineral density, and fracture rates: a population-based historical cohort study.

PubMed

Leslie, William D; Lix, Lisa M; Yogendran, Marina S; Morin, Suzanne N; Metge, Colleen J; Majumdar, Sumit R

2014-04-01

Diverging international trends in fracture rates have been observed, with most reports showing that fracture rates have stabilized or decreased in North American and many European populations. We studied two complementary population-based historical cohorts from the Province of Manitoba, Canada (1996-2006) to determine whether declining osteoporotic fracture rates in Canada are attributable to trends in obesity, osteoporosis treatment, or bone mineral density (BMD). The Population Fracture Registry included women aged 50 years and older with major osteoporotic fractures, and was used to assess impact of changes in osteoporosis treatment. The BMD Registry included all women aged 50 years and older undergoing BMD tests, and was used to assess impact of changes in obesity and BMD. Model-based estimates of temporal changes in fracture rates (Fracture Registry) were calculated. Temporal changes in obesity and BMD and their association with fracture rates (BMD Registry) were estimated. In the Fracture Registry (n=27,341), fracture rates declined 1.6% per year (95% confidence interval [CI], 1.3% to 2.0%). Although osteoporosis treatment increased from 5.6% to 17.4%, the decline in fractures was independent of osteoporosis treatment. In the BMD Registry (n=36,587), obesity increased from 12.7% to 27.4%. Femoral neck BMD increased 0.52% per year and lumbar spine BMD increased 0.32% per year after covariate adjustment (p<0.001). Major osteoporotic fracture rates decreased in models that did not include femoral neck BMD (fully adjusted annual change -1.8%; 95% CI, -2.9 to -0.5), but adjusting for femoral neck BMD accounted for the observed reduction (annual change -0.5%; 95% CI, -1.8 to +1.0). In summary, major osteoporotic fracture rates declined substantially and linearly from 1996 to 2006, and this was explained by improvements in BMD rather than greater rates of obesity or osteoporosis treatment. © 2014 American Society for Bone and Mineral Research.

Ethnic and sex differences in bone marrow adipose tissue and bone mineral density relationship

PubMed Central

Chen, J.; Gantz, M.; Punyanitya, M.; Heymsfield, S. B.; Gallagher, D.; Albu, J.; Engelson, E.; Kotler, D.; Pi-Sunyer, X.; Shapses, S.

2012-01-01

Summary The relationship between bone marrow adipose tissue and bone mineral density is different between African Americans and Caucasians as well as between men and women. This suggests that the mechanisms that regulate the differentiation and proliferation of bone marrow stromal cells may differ in these populations. Introduction It has long been established that there are ethnic and sex differences in bone mineral density (BMD) and fracture risk. Recent studies suggest that bone marrow adipose tissue (BMAT) may play a role in the pathogenesis of osteoporosis. It is unknown whether ethnic and sex differences exist in the relationship between BMAT and BMD. Methods Pelvic BMAT was evaluated in 455 healthy African American and Caucasian men and women (age 18–88 years) using whole-body T1-weighted magnetic resonance imaging. BMD was measured using whole-body dual-energy X-ray absorptiometry. Results A negative correlation was observed between pelvic BMAT and total body BMD or pelvic BMD (r=−0.533, −0.576, respectively; P<0.001). In multiple regression analyses with BMD as the dependent variable, ethnicity significantly entered the regression models as either an individual term or an interaction with BMAT. Menopausal status significantly entered the regression model with total body BMD as the dependent variable. African Americans had higher total body BMD than Caucasians for the same amount of BMAT, and the ethnic difference for pelvic BMD was greater in those participants with a higher BMAT. Men and premeno-pausal women had higher total body BMD levels than postmenopausal women for the same amount of BMAT. Conclusions An inverse relationship exists between BMAT and BMD in African American and Caucasian men and women. The observed ethnic and sex differences between BMAT and BMD in the present study suggest the possibility that the mechanisms regulating the differentiation and proliferation of bone marrow stromal cells may differ in these populations. PMID:22173789

Ethnic and sex differences in bone marrow adipose tissue and bone mineral density relationship.

PubMed

Shen, W; Chen, J; Gantz, M; Punyanitya, M; Heymsfield, S B; Gallagher, D; Albu, J; Engelson, E; Kotler, D; Pi-Sunyer, X; Shapses, S

2012-09-01

The relationship between bone marrow adipose tissue and bone mineral density is different between African Americans and Caucasians as well as between men and women. This suggests that the mechanisms that regulate the differentiation and proliferation of bone marrow stromal cells may differ in these populations. It has long been established that there are ethnic and sex differences in bone mineral density (BMD) and fracture risk. Recent studies suggest that bone marrow adipose tissue (BMAT) may play a role in the pathogenesis of osteoporosis. It is unknown whether ethnic and sex differences exist in the relationship between BMAT and BMD. Pelvic BMAT was evaluated in 455 healthy African American and Caucasian men and women (age 18-88 years) using whole-body T1-weighted magnetic resonance imaging. BMD was measured using whole-body dual-energy X-ray absorptiometry. A negative correlation was observed between pelvic BMAT and total body BMD or pelvic BMD (r = -0.533, -0.576, respectively; P < 0.001). In multiple regression analyses with BMD as the dependent variable, ethnicity significantly entered the regression models as either an individual term or an interaction with BMAT. Menopausal status significantly entered the regression model with total body BMD as the dependent variable. African Americans had higher total body BMD than Caucasians for the same amount of BMAT, and the ethnic difference for pelvic BMD was greater in those participants with a higher BMAT. Men and premenopausal women had higher total body BMD levels than postmenopausal women for the same amount of BMAT. An inverse relationship exists between BMAT and BMD in African American and Caucasian men and women. The observed ethnic and sex differences between BMAT and BMD in the present study suggest the possibility that the mechanisms regulating the differentiation and proliferation of bone marrow stromal cells may differ in these populations.

Prior ankle fractures in postmenopausal women are associated with low areal bone mineral density and bone microstructure alterations.

PubMed

Biver, E; Durosier, C; Chevalley, T; Herrmann, F R; Ferrari, S; Rizzoli, R

2015-08-01

In a cross-sectional analysis in postmenopausal women, prior ankle fractures were associated with lower areal bone mineral density (BMD) and trabecular bone alterations compared to no fracture history. Compared to women with forearm fractures, microstructure alterations were of lower magnitude. These data suggest that ankle fractures are another manifestation of bone fragility. Whether ankle fractures represent fragility fractures associated with low areal bone mineral density (aBMD) and volumetric bone mineral density (vBMD) and/or bone microstructure alterations remains unclear, in contrast to the well-recognised association between forearm fractures and osteoporosis. The objective of this study was to investigate aBMD, vBMD and bone microstructure in postmenopausal women with prior ankle fracture in adulthood, compared with women without prior fracture or with women with prior forearm fractures, considered as typically of osteoporotic origin. In a cross-sectional analysis in the Geneva Retirees Cohort study, 63 women with ankle fracture and 59 with forearm fracture were compared to 433 women without fracture (mean age, 65 ± 1 years). aBMD was measured by dual-energy X-ray absorptiometry; distal radius and tibia vBMD and bone microstructure were measured by high-resolution peripheral quantitative computed tomography. Compared with women without fracture, those with ankle fractures had lower aBMD, radius vBMD (-7.9%), trabecular density (-10.7%), number (-7.3%) and thickness (-4.6%) and higher trabecular spacing (+14.5%) (P < 0.05 for all). Tibia trabecular variables were also altered. For 1 standard deviation decrease in total hip aBMD or radius trabecular density, odds ratios for ankle fractures were 2.2 and 1.6, respectively, vs 2.2 and 2.7 for forearm fracture, respectively (P ≤ 0.001 for all). Compared to women with forearm fractures, those with ankle fractures had similar spine and hip aBMD, but microstructure alterations of lower magnitude. Women with ankle fractures have lower aBMD and vBMD and trabecular bone alterations, suggesting that ankle fractures are another manifestation of bone fragility.

Milk and yogurt consumption are linked with higher bone mineral density but not with hip fracture: the Framingham Offspring Study.

PubMed

Sahni, Shivani; Tucker, Katherine L; Kiel, Douglas P; Quach, Lien; Casey, Virginia A; Hannan, Marian T

2013-01-01

Dairy foods are a complex source of essential nutrients. In this study, fluid dairy intake, specifically milk, and yogurt intakes were associated with hip but not spine bone mineral density (BMD), while cream may adversely influence BMD, suggesting that not all dairy products are equally beneficial for the skeleton. This study seeks to examine associations of milk, yogurt, cheese, cream, most dairy (total dairy without cream), and fluid dairy (milk + yogurt) with BMD at femoral neck (FN), trochanter (TR), and spine, and with incident hip fracture over 12-year follow-up in the Framingham Offspring Study. Three thousand two hundred twelve participants completed a food frequency questionnaire (1991–1995 or 1995–1998) and were followed for hip fracture until 2007 [corrected]. Two thousand five hundred and six participants had DXA BMD (1996-2001). Linear regression was used to estimate adjusted mean BMD while Cox-proportional hazards regression was used to estimate adjusted hazard ratios (HR) for hip fracture risk. Final models simultaneously included dairy foods adjusting for each other. Mean baseline age was 55 (±1.6) years, range 26-85. Most dairy intake was positively associated with hip and spine BMD. Intake of fluid dairy and milk was related with hip but not spine BMD. Yogurt intake was associated with TR-BMD alone. Cheese and cream intakes were not associated with BMD. In final models, yogurt intake remained positively associated with TR-BMD, while cream tended to be negatively associated with FN-BMD. Yogurt intake showed a weak protective trend for hip fracture [HR(95%CI), ≤4 serv/week, 0.46 (0.21-1.03) vs. >4 serv/week, 0.43 (0.06-3.27)]. No other dairy groups showed a significant association (HRs range, 0.53-1.47) with limited power (n, fractures = 43). Milk and yogurt intakes were associated with hip but not spine BMD, while cream may adversely influence BMD. Thus, not all dairy products are equally beneficial for the skeleton. Suggestive fracture results for milk and yogurt intakes need further confirmation.

Low Bone Mineral Density in Male Athletes Is Associated With Bone Stress Injuries at Anatomic Sites With Greater Trabecular Composition.

PubMed

Tenforde, Adam S; Parziale, Allyson L; Popp, Kristin L; Ackerman, Kathryn E

2018-01-01

While sports participation is often associated with health benefits, a subset of athletes may develop impaired bone health. Bone stress injuries (BSIs) are a common overuse injury in athletes; site of injury has been shown to relate to underlying bone health in female athletes. Hypothesis/Purpose: This case series characterizes the association of type of sports participation and anatomic site of BSIs with low bone mineral density (BMD), defined as BMD Z-score <-1.0. Similar to female athletes, it was hypothesized that male athletes who participate in running and sustain BSIs in sites of higher trabecular bone content would be more likely to have low BMD. Cohort study; Level of evidence, 3. Chart review identified 28 male athletes aged 14 to 36 years with history of ≥1 lower-extremity BSI who were referred for evaluation of overall bone health, including assessment of lumbar spine, hip, and/or total body less head BMD per dual-energy x-ray absorptiometry. BMD Z-scores were determined via age, sex, and ethnicity normative values. Prior BSIs were classified by anatomic site of injury into trabecular-rich locations (pelvis, femoral neck, and calcaneus) and cortical-rich locations (tibia, fibula, femur, metatarsal and tarsal navicular). Sport type and laboratory values were also assessed in relationship to BMD. The association of low BMD to anatomic site of BSI and sport were evaluated with P value <.05 as threshold of significance. Of 28 athletes, 12 (43%) met criteria for low BMD. Athletes with a history of trabecular-rich BSIs had a 4.6-fold increased risk for low BMD as compared with those with only cortical-rich BSIs (9 of 11 vs 3 of 17, P = .002). Within sport type, runners had a 6.1-fold increased risk for low BMD versus nonrunners (11 of 18 vs 1 of 10, P = .016). Laboratory values, including 25-hydroxy vitamin D, were not associated with BMD or BSI location. Low BMD was identified in 43% of male athletes in this series. Athletes participating in sports of running and with a history of trabecular-rich BSI were at increased risk for low BMD.

Self-reported recreational exercise combining regularity and impact is necessary to maximize bone mineral density in young adult women: a population-based study of 1,061 women 25 years of age.

PubMed

Callréus, M; McGuigan, F; Ringsberg, K; Akesson, K

2012-10-01

Recreational physical activity in 25-year-old women in Sweden increases bone mineral density (BMD) in the trochanter by 5.5% when combining regularity and impact. Jogging and spinning were especially beneficial for hip BMD (6.4-8.5%). Women who enjoyed physical education in school maintained their higher activity level at age 25. The aims of this study were to evaluate the effects of recreational exercise on BMD and describe how exercise patterns change with time in a normal population of young adult women. In a population-based study of 1,061 women, age 25 (±0.2), BMD was measured at total body (TB-BMD), femoral neck (FN-BMD), trochanter (TR-BMD), and spine (LS-BMD). Self-reported physical activity status was assessed by questionnaire. Regularity of exercise was expressed as recreational activity level (RAL) and impact load as peak strain score (PSS). A permutation (COMB-RP) was used to evaluate combined endurance and impacts on bone mass. More than half of the women reported exercising on a regular basis and the most common activities were running, strength training, aerobics, and spinning. Seventy percent participated in at least one activity during the year. Women with high RAL or PSS had higher BMD in the hip (2.6-3.5%) and spine (1.5-2.1%), with the greatest differences resulting from PSS (p < 0.001-0.02). Combined regularity and impact (high-COMB-RP) conferred the greatest gains in BMD (FN 4.7%, TR 5.5%, LS 3.1%; p < 0.001) despite concomitant lower body weight. Jogging and spinning were particularly beneficial for hip BMD (+6.4-8.5%). Women with high-COMB-RP scores enjoyed physical education in school more and maintained higher activity levels throughout compared to those with low scores. Self-reported recreational levels of physical activity positively influence BMD in young adult women but to maximize BMD gains, regular, high-impact exercise is required. Enjoyment of exercise contributes to regularity of exercising which has short- and long-term implications for bone health.

High bone mineral density in sickle cell disease: Prevalence and characteristics.

PubMed

De Luna, Gonzalo; Ranque, Brigitte; Courbebaisse, Marie; Ribeil, Jean-Antoine; Khimoud, Djamal; Dupeux, Sidonie; Silvera, Jonathan; Offredo, Lucile; Pouchot, Jacques; Arlet, Jean-Benoît

2018-05-01

Osteosclerosis (OSC) is a rarely studied complication of sickle cell disease (SCD). The objective of our study was to determine the prevalence and characteristics of high bone mineral density (BMD) and its radiological features in adult SCD patients. This prospective observational study was conducted from May 2007 to May 2016 in consecutive patients with steady-state SCD at two university hospitals. The BMD of the lumbar spine (L1-L4) and right femoral neck was determined by dual energy X-ray absorptiometry. Clinical, laboratory and radiographic data were recorded. High BMD was defined as a BMD Z-score of at least +2.5 standard deviations at the lumbar spine or hip. The characteristics of the patients with high BMD were compared to those of individuals with low or middle BMD, using multivariate ordinal logistic regression. 135 patients (86 women and 49 men) with a median age of 27 (IQR 23-33) years were included. High BMD was diagnosed in 20 (15%) patients with a median age of 33.5 (IQR 28-45) years. The SCD genotypes of these patients were SS in 11, SC in 5, S/beta+ in 3, and S/beta0 in 1. High BMD patients more frequently harbored the S/beta SCD genotype (21% vs 5% in non-high BMD patients; p=0.047) and were older (p=0.0007). Compared to patients with low or middle BMD, after adjustment for age and SCD genotype, high BMD patients had a higher prevalence of avascular necrosis history (p=0.009), higher BMI (p=0.007), and lower serum resorption marker CTX (p=0.04), bilirubin (p=0.02) and parathyroid hormone levels (p=0.02). There were no differences between groups regarding fracture history, H-shaped vertebrae or other biological variables. High-BMD values is a common manifestation in SCD patients, especially in those with the S/beta-thalassemia genotypes. The prevalence of high-BMD in SCD is associated with older age, suggesting that it will be more common in the future because the life span of patients with SCD is increasing thanks to significant progress in SCD treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

[Effect of vitamin D receptor gene polymorphism and lifestyle on bone mineral density and bone mineral density decrement rate].

PubMed

Yamagata, Z; Miyamura, T; Iijima, S; Asaka, A

1995-12-01

The effects of genetic and environmental factors on bone mineral density (BMD) were investigated in 108 healthy Japanese women. Of the 108 subjects, BMD (from the second to forth lumbar vertebrae) was measured in 1992 in 103, in 1993 in 100, and in both years in 95 by dual energy X-ray absorptiometry. Vitamin D receptor (VDR) gene polymorphism in intron 8 was used as a genetic marker. Information on menstruation, health status, lifestyle, quantities of nutrient intake and frequencies of food intake was obtained by questionnaire. The frequency of allele B (825bp), whose polymerase chain reaction (PCR) products cannot be cut with BsmI, was 0.259 and the frequency of allele b (650bp), whose PCR products can be cut with BsmI, was 0.741. The subjects in our study obeyed the Hardy-Weinberg law. While the frequency of allele B was 0.448 in European whites as reported by Morrison et al, it was 0.259 in our Japanese subjects, suggesting a racial difference. Z score values (average value 0, standard deviation 1) increased in the order BB, Bb and bb. This result indicates that allele B is associated with the lower BMD in Japanese, as in European whites. The BMD decrement rate increased in the order bb, Bb and BB, indicating that VDR gene polymorphism may be a regulatory factor for losing BMD. Most of lifestyle variables, calcium intake and vitamin D intake were not correlated with BMD, but the food frequency score (which was defined as values weighted in each of three food categories obtained by factor analysis) was significantly correlated with BMD. Multiple regression analysis showed significant influences of years after menopause, the food frequency score and VDR genotype on BMD. VDR genotype and years after menopause influenced the BMD decrement rate significantly in multiple regression analysis. Neither a relationship between BMD and calcium intake nor between BMD and vitamin D intake by VDR genotype was found. These results suggest that the VDR gene is a genetic factor in BMD and the BMD decrement rate in Japanese.

Changes in bone mineral density and body composition during pregnancy and postpartum. A controlled cohort study.

PubMed

Møller, U K; Við Streym, S; Mosekilde, L; Rejnmark, L

2012-04-01

In a controlled cohort study, bone mineral density (BMD) was measured in 153 women pre-pregnancy; during pregnancy; and 0.5, 4, 9, and 19 months postpartum. Seventy-five age-matched controls, without pregnancy plans, were followed in parallel. Pregnancy and breastfeeding cause a reversible bone loss, which, initially, is most pronounced at trabecular sites but also involves cortical sites during prolonged breastfeeding. Conflicting results have been reported on effects of pregnancy and breastfeeding on BMD and body composition (BC). In a controlled cohort study, we elucidate changes in BMD and BC during and following a pregnancy. We measured BMD and BC in 153 women planning pregnancy (n = 92 conceived), once in each trimester during pregnancy and 15, 129, and 280 days postpartum. Moreover, BMD was measured 19 months postpartum (n = 31). Seventy-five age-matched controls, without pregnancy plans, were followed in parallel. Compared with controls, BMD decreased significantly during pregnancy by 1.8 ± 0.5% at the lumbar spine, 3.2 ± 0.5% at the total hip, 2.4 ± 0.3% at the whole body, and 4.2 ± 0.7% at the ultra distal forearm. Postpartum, BMD decreased further with an effect of breastfeeding. At 9 months postpartum, women who had breastfed for <9 months had a BMD similar to that of the controls, whereas BMD at the lumbar spine and hip was decreased in women who were still breastfeeding. During prolonged breastfeeding, BMD at sites which consist of mostly trabecular bone started to be regained, whereas BMD at sites rich in cortical bone decreased further. At 19 months postpartum, BMD did not differ from baseline at any site. During pregnancy, fat- and lean-tissue mass increased by 19 ± 22% and 5 ± 6% (p < 0.001), respectively. Postpartum, changes in fat mass differed according to breastfeeding status with a slower decline in women who continued breastfeeding. Calcium and vitamin D intake was not associated with BMD changes. Pregnancy and breastfeeding cause a reversible bone loss. At 19 months postpartum, BMD has returned to pre-pregnancy level independently of breastfeeding length. Reversal of changes in fat mass depends on breastfeeding status.

Bone Mineral Content and Density Among Female NCAA Division I Athletes Across the Competitive Season and Over a Multi-Year Time Frame.

PubMed

Stanforth, Dixie; Lu, Tao; Stults-Kolehmainen, Matthew A; Crim, Brittany N; Stanforth, Philip R

2016-10-01

Stanforth, D, Lu, T, Stults-Kolehmainen, MA, Crim, BN, and Stanforth, PR. Bone mineral content and density among female NCAA Division I athletes across the competitive season and over a multi-year time frame. J Strength Cond Res 30(10): 2828-2838, 2016-Longitudinal and cross-sectional bone mineral content (BMC) and bone mineral density (BMD) comparisons were made among impact and nonimpact sports. Female collegiate athletes, 18-23 years of age, from basketball (BB; n = 38), soccer (SOC; n = 47), swimming (SW; n = 52), track sprinters and jumpers (TR; n = 49), and volleyball (VB; n = 26) had BMC/BMD measures preseason and postseason over 3 years. Control groups of 85 college females, 18-24 years of age, who completed 2 tests 1-3 years apart and of 170 college females, 18-20 years of age, were used for the longitudinal and cross-sectional analyses, respectively. A restricted maximum likelihood linear mixed model regression analysis with a compound symmetric heterogeneous variance-covariance matrix structure was used for all analyses (p ≤ 0.05). Increases from year-1 preseason to year-3 postseason included the following: total BMC (3.3%), total BMD (1.4%), and spine BMD (4.5%) for BB; total BMC (1.5%) and leg BMD (1.2%) for SOC; arm (1.8%), leg (1.9%), and total BMD (5.7%) for SW; total BMC (2.0%), arm (1.7%), leg (2.3%), pelvis (3.4%), spine (6.0%), and total BMD (2.3%) for TR; and arm (4.1%), leg (2.0%), pelvis (2.0%), spine (2.0%), and total BMD (2.7%) for VB. Comparisons among sports determined that BB had higher BMC and BMD values than all other sports for all variables except spine and total BMD; BB, SOC, TR, and VB had higher total BMC (11-29%), leg BMD (13-20%), and total BMD (9-15%) than SW and CON, and there were few differences among SOC, TR, and VB. In conclusion, small, significant increases in many BMC and BMD measures occur during female athlete's collegiate careers. The BMC and BMD differences between impact and nonimpact sports are large compared with smaller differences within impact sports.

Risk factors for low bone mineral density in children and adolescents with inflammatory bowel disease.

PubMed

Lopes, Letícia Helena Caldas; Sdepanian, Vera Lucia; Szejnfeld, Vera Lúcia; de Morais, Mauro Batista; Fagundes-Neto, Ulysses

2008-10-01

To evaluate bone mineral density of the lumbar spine in children and adolescents with inflammatory bowel disease, and to identify the clinical risk factors associated with low bone mineral density. Bone mineral density of the lumbar spine was evaluated using dual-energy X-ray absorptiometry (DXA) in 40 patients with inflammatory bowel disease. Patients were 11.8 (SD = 4.1) years old and most of them were male (52.5%). Multiple linear regression analysis was performed to identify potential associations between bone mineral density Z-score and age, height-for-age Z-score, BMI Z-score, cumulative corticosteroid dose in milligrams and in milligrams per kilogram, disease duration, number of relapses, and calcium intake according to the dietary reference intake. Low bone mineral density (Z-score bellow -2) was observed in 25% of patients. Patients with Crohn's disease and ulcerative colitis had equivalent prevalence of low bone mineral density. Multiple linear regression models demonstrated that height-for-age Z-score, BMI Z-score, and cumulative corticosteroid dose in mg had independent effects on BMD, respectively, beta = 0.492 (P = 0.000), beta = 0.460 (P = 0.001), beta = - 0.014 (P = 0.000), and these effects remained significant after adjustments for disease duration, respectively, beta = 0.489 (P = 0.013), beta = 0.467 (P = 0.001), and beta = - 0.005 (P = 0.015). The model accounted for 54.6% of the variability of the BMD Z-score (adjusted R2 = 0.546). The prevalence of low bone mineral density in children and adolescents with inflammatory bowel disease is considerably high and independent risk factors associated with bone mineral density are corticosteroid cumulative dose in milligrams, height-for-age Z-score, and BMI Z-score.

The effect of lamotrigine and phenytoin on bone turnover and bone strength: A prospective study in Wistar rats.

PubMed

Simko, Julius; Karesova, Iva; Kremlacek, Jan; Fekete, Sona; Zimcikova, Eva; Malakova, Jana; Zivna, Helena; Valis, Martin; Palicka, Vladimir

2016-12-01

Some data suggest that exposure to lamotrigine (LTG) might be associated with impaired bone health in an orchidectomized rat model. The aim of this study was to determine if LTG poses any significant risk for bone in a gonadally intact animals and to compare the effect of LTG with that of phenytoin (PHT). Twenty-four rats were divided into control and test groups, (n=8 per group). Control rats received a standard laboratory diet (SDL), while rats in the test groups were fed a SLD enriched with LTG or PHT for 12 weeks. Dual energy X-ray absorptiometry was used to measure bone mineral density (BMD). The concentrations of bone turnover markers (BTM) were assayed in bone homogenates. The femurs were measured and biomechanically tested. Treatment with either LTG or PHT had no significant effect on BMD or on the biomechanical strength of the bones. In contrast to the effect of LTG, we did find significant changes in BTM in the PHT group: a highly significant decrease in the osteoprotegerin/receptor activator of nuclear factor kappa B ratio (p<0.01) and highly significant increases in bone alkaline phosphatase and amino-terminal propeptide of procollagen type I (p<0.001, p˂0.01, respectively). In the LTG group, the only significant change was a decrease in sclerostin (p˂0.05). The PHT level was 19.0 (15.6-19.5) μmol/l, which represents the lower end of the therapeutic range used in humans. The level of LTG was 60.7 (58.5-61.8) μmol/l. LTG has no effect on the BMD, BTM or mechanical strength in gonadally intact animals. Although a low dose of PHT was associated with enhanced BTM, it did not affect BMD or the biomechanical properties of the bones, similar to the results observed for LTG. Copyright © 2016 Elsevier B.V. All rights reserved.

Combination of micellar casein with calcium and vitamins D2 and K2 improves bone status of ovariectomized mice.

PubMed

Boulier, A; Schwarz, J; Lespesailles, E; Baniel, A; Tomé, D; Blais, A

2016-10-01

Nutritional approaches may help to preserve bone quality. The purpose of our study was to demonstrate the efficiency of an innovative bone health product (BHP) including micellar casein rich in calcium, vitamin D2 and vitamin K2, to improve bone mineral density. The aim of postmenopausal osteoporosis treatment is to decrease bone resorption and/or increase bone formation. Because of the slow bone turnover, osteoporosis prevention and therapies are long-lasting, implying great costs and poor compliance. Even if the effects of nutrition on bone are not as marked as that of pharmaceutical agents, it can be of great help. The purpose of our study was to demonstrate the efficiency of an innovative bone health product (BHP) containing micellar casein rich in calcium, vitamin D2 and vitamin K2, for the improvement of bone mineral density (BMD). An ovariectomized mice model was used to study the effect of different concentrations of the ingredient on BMD and microarchitectural parameters. Blood concentrations of C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type 1 procollagene (PINP), alkaline phosphatase (ALP), osteocalcin (OC) and RANKL were also measured to evaluate bone remodelling, To evaluate the efficiency of the product to modulate osteoblast and osteoclast growth and differentiation, primary murine bone cells were used. In vivo studies showed that BMD and microarchitectural parameters were dose-dependently improved after ingestion of the supplement for 3 months. We also report increased osteoblast activity as shown by increased OC activity and decreased osteoclastogenesis as shown by reduced CTX activity. In vitro studies support that BHPs stimulate osteoblast differentiation and mineralization and inhibit osteoclast resorption activity. Our results show that, when chronically ingested, BHPs improve BMD of ovariectomized mice. This work supports that providing an ingredient including micellar casein rich in calcium, vitamin D2 and vitamin K2 is more efficient than the control diet to maintain bone quality.

A novel growth hormone receptor gene deletion mutation in a patient with primary growth hormone insensitivity syndrome (Laron syndrome).

PubMed

Yamamoto, Hiroyasu; Kouhara, Haruhiko; Iida, Keiji; Chihara, Kazuo; Kasayama, Soji

2008-04-01

Growth hormone (GH) insensitivity syndrome (Laron syndrome) is known to be caused by genetic disorders of the GH-IGF-1 axis. Although many mutations in the GH receptor have been identified, there have been only a few reports of deletions of the GH receptor gene. A Japanese adult female patient with Laron syndrome was subjected to chromosome analysis with basic G-banding and also with a high accuracy technique. Each exon of the GH receptor gene was amplified by means of PCR. Since this patient was diagnosed with osteoporosis, the effects of alendronate on bone mineral density (BMD) were also examined. The chromosome analysis with the high accuracy technique demonstrated a large deletion of the short arm in one allele of chromosome 5 from p11 to p13.1 [46, XX, del (5) (p11-p13.1)]. PCR amplification of exons of the GH receptor gene showed that only exons 2 and 3 were amplified. Low-dose IGF-1 administration (30microg/kg body weight) failed to increase her BMD, whereas alendronate administration resulted in an increase associated with a decrease in urinary deoxypyridinoline (DPD) and serum osteocalcin concentrations. The GH receptor gene of the patient was shown to lack exons 4-10. To the best of our knowledge, this is the third case report of Laron syndrome with large GH receptor deletion. Alendronate was effective for the enhancement of BMD.

Effects of Daily Intake of Calcium and Vitamin D-Enriched Milk in Healthy Postmenopausal Women: A Randomized, Controlled, Double-Blind Nutritional Study.

PubMed

Reyes-Garcia, Rebeca; Mendoza, Nicolas; Palacios, Santiago; Salas, Nancy; Quesada-Charneco, Miguel; Garcia-Martin, Antonia; Fonolla, Juristo; Lara-Villoslada, Federico; Muñoz-Torres, Manuel

2018-05-01

To determine the effect of the daily intake of calcium and vitamin D-enriched milk (with or without fructooligosaccharides [FOS]) on vitamin D, bone metabolism, and cardiovascular risk factors. Two-year randomized controlled study, including 500 healthy postmenopausal women, assigned to 500 mL/day of skimmed milk to one of three groups: Low-dose (L): (120 mg/100 mL calcium, vitamin D 3 30 UI/100 mL), group A: calcium and vitamin D (180 mg/100 mL and 120 UI/100 mL), and group B: calcium and vitamin D (180 mg/100 mL and 120 UI/100 mL) and FOS (5 g/L). We evaluated serum 25(OH)D, bone mineral density (BMD) by Dual Energy X-ray Absorptiometry, and biochemical data of glucose and lipid metabolism. After 24 months, vitamin D concentrations did not change in the control group, but increased in group A and group B, p < 0.001. We observed an increase in femoral neck BMD and an improvement in fasting plasma glucose, HbA 1c , total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B 100. Daily intake of milk enriched with calcium and vitamin D in postmenopausal healthy women induces a significant improvement in vitamin D status, a significant increase in BMD at femoral neck, and also favorable effects on glucose and lipid profile.

Accelerated bone mass senescence after hematopoietic stem cell transplantation.

PubMed

Serio, B; Pezzullo, L; Fontana, R; Annunziata, S; Rosamilio, R; Sessa, M; Giudice, V; Ferrara, I; Rocco, M; De Rosa, G; Ricci, P; Tauchmanovà, L; Montuori, N; Selleri, C

2013-01-01

Osteoporosis and avascular necrosis (AVN) are long-lasting and debilitating complications of hematopoietic stem cell transplantation (HSCT). We describe the magnitude of bone loss, AVN and impairment in osteogenic cell compartment following autologous (auto) and allogeneic (allo) HSCT, through the retrospective bone damage revaluation of 100 (50 auto- and 50 allo-HSCT) long-term survivors up to 15 years after transplant. Current treatment options for the management of these complications are also outlined. We found that auto- and allo-HSCT recipients show accelerated bone mineral loss and micro-architectural deterioration during the first years after transplant. Bone mass density (BMD) at the lumbar spine, but not at the femur neck, may improve in some patients after HSCT, suggesting more prolonged bone damage in cortical bone. Phalangeal BMD values remained low for even more years, suggesting persistent bone micro-architectural alterations after transplant. The incidence of AVN was higher in allo-HSCT recipients compared to auto-HSCT recipients. Steroid treatment length, but not its cumulative dose was associated with a higher incidence of bone loss. Allo-HSCT recipients affected by chronic graft versus host disease seem to be at greater risk of continuous bone loss and AVN development. Reduced BMD and higher incidence of AVN was partly related to a reduced regenerating capacity of the normal marrow osteogenic cell compartment. Our results suggest that all patients after auto-HSCT and allo-HSCT should be evaluated for their bone status and treated with anti-resorptive therapy as soon as abnormalities are detected.

Osteoporosis – a current view of pharmacological prevention and treatment

PubMed Central

Das, Subhajit; Crockett, Julie C

2013-01-01

Postmenopausal osteoporosis is the most common bone disease, associated with low bone mineral density (BMD) and pathological fractures which lead to significant morbidity. It is defined clinically by a BMD of 2.5 standard deviations or more below the young female adult mean (T-score =−2.5). Osteoporosis was a huge global problem both socially and economically – in the UK alone, in 2011 £6 million per day was spent on treatment and social care of the 230,000 osteoporotic fracture patients – and therefore viable preventative and therapeutic approaches are key to managing this problem within the aging population of today. One of the main issues surrounding the potential of osteoporosis management is diagnosing patients at risk before they develop a fracture. We discuss the current and future possibilities for identifying susceptible patients, from fracture risk assessment to shape modeling and in relation to the high heritability of osteoporosis now that a plethora of genes have been associated with low BMD and osteoporotic fracture. This review highlights the current therapeutics in clinical use (including bisphosphonates, anti-RANKL [receptor activator of NF-κB ligand], intermittent low dose parathyroid hormone, and strontium ranelate) and some of those in development (anti-sclerostin antibodies and cathepsin K inhibitors). By highlighting the intimate relationship between the activities of bone forming (osteoblasts) and bone-resorbing (osteoclasts) cells, we include an overview and comparison of the molecular mechanisms exploited in each therapy. PMID:23807838

Altered operant responding for motor reinforcement and the determination of benchmark doses following perinatal exposure to low-level 2,3,7,8-tetrachlorodibenzo-p-dioxin.

PubMed

Markowski, V P; Zareba, G; Stern, S; Cox, C; Weiss, B

2001-06-01

Pregnant Holtzman rats were exposed to a single oral dose of 0, 20, 60, or 180 ng/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the 18th day of gestation. Their adult female offspring were trained to respond on a lever for brief opportunities to run in specially designed running wheels. Once they had begun responding on a fixed-ratio 1 (FR1) schedule of reinforcement, the fixed-ratio requirement for lever pressing was increased at five-session intervals to values of FR2, FR5, FR10, FR20, and FR30. We examined vaginal cytology after each behavior session to track estrous cyclicity. Under each of the FR values, perinatal TCDD exposure produced a significant dose-related reduction in the number of earned opportunities to run, the lever response rate, and the total number of revolutions in the wheel. Estrous cyclicity was not affected. Because of the consistent dose-response relationship at all FR values, we used the behavioral data to calculate benchmark doses based on displacements from modeled zero-dose performance of 1% (ED(01)) and 10% (ED(10)), as determined by a quadratic fit to the dose-response function. The mean ED(10) benchmark dose for earned run opportunities was 10.13 ng/kg with a 95% lower bound of 5.77 ng/kg. The corresponding ED(01) was 0.98 ng/kg with a 95% lower bound of 0.83 ng/kg. The mean ED(10) for total wheel revolutions was calculated as 7.32 ng/kg with a 95% lower bound of 5.41 ng/kg. The corresponding ED(01) was 0.71 ng/kg with a 95% lower bound of 0.60. These values should be viewed from the perspective of current human body burdens, whose average value, based on TCDD toxic equivalents, has been calculated as 13 ng/kg.

Development of a chronic noncancer oral reference dose and drinking water screening level for sulfolane using benchmark dose modeling.

PubMed

Thompson, Chad M; Gaylor, David W; Tachovsky, J Andrew; Perry, Camarie; Carakostas, Michael C; Haws, Laurie C

2013-12-01

Sulfolane is a widely used industrial solvent that is often used for gas treatment (sour gas sweetening; hydrogen sulfide removal from shale and coal processes, etc.), and in the manufacture of polymers and electronics, and may be found in pharmaceuticals as a residual solvent used in the manufacturing processes. Sulfolane is considered a high production volume chemical with worldwide production around 18 000-36 000 tons per year. Given that sulfolane has been detected as a contaminant in groundwater, an important potential route of exposure is tap water ingestion. Because there are currently no federal drinking water standards for sulfolane in the USA, we developed a noncancer oral reference dose (RfD) based on benchmark dose modeling, as well as a tap water screening value that is protective of ingestion. Review of the available literature suggests that sulfolane is not likely to be mutagenic, clastogenic or carcinogenic, or pose reproductive or developmental health risks except perhaps at very high exposure concentrations. RfD values derived using benchmark dose modeling were 0.01-0.04 mg kg(-1) per day, although modeling of developmental endpoints resulted in higher values, approximately 0.4 mg kg(-1) per day. The lowest, most conservative, RfD of 0.01 mg kg(-1) per day was based on reduced white blood cell counts in female rats. This RfD was used to develop a tap water screening level that is protective of ingestion, viz. 365 µg l(-1). It is anticipated that these values, along with the hazard identification and dose-response modeling described herein, should be informative for risk assessors and regulators interested in setting health-protective drinking water guideline values for sulfolane. Copyright © 2012 John Wiley & Sons, Ltd.

Relationship of homocysteine levels with lumbar spine and femur neck BMD in postmenopausal women.

PubMed

Bahtiri, E; Islami, H; Rexhepi, S; Qorraj-Bytyqi, H; Thaçi, K; Thaçi, S; Karakulak, C; Hoxha, R

2015-01-01

The focus of several studies in recent years has been the association between increased plasma concentrations of homocysteine (Hcy), reduced bone mineral density and increased risk of bone fractures. Nevertheless, inconsistencies persist in the literature. Thus, the objective of this study was to investigate the possible relationship between serum Hcy and vitamin B12 status, and bone mineral density, on a group of post-menopausal women. One hundred thirty-nine postmenopausal women were recruited to enter this cross-sectional study. Bone mineral density (BMD) of total hip, femoral neck and lumbar spine was measured by dual-energy X-ray absorptiometry (DXA) and serum Hcy, vitamin B12, parathyroid hormone (PTH), total calcium and magnesium levels were determined. In addition, we investigated the relationship of Hcy and vitamin B12 and BMD using a meta-analysis approach. Serum Hcy levels were significantly higher in osteoporotic women when compared to other BMD groups, and were inversely related to lumbar spine BMD and femur neck BMD. Body mass index and serum Hcy levels were shown to be significant predictors of BMD at lumbar spine, femur neck and total hip. The performed meta-analysis showed that serum Hcy levels were significantly higher in osteoporotic subjects compared to normal BMD subjects. This study shows that Hcy status, but not vitamin B12 status, is associated with BMD in this cohort of postmenopausal women. We therefore confirm that high Hcy levels are an independent risk factor for osteoporosis. BMD evaluation in women at post menopause with high Hcy levels may be helpful in advising precautionary measures.

Sarcopenia is related to increased risk for low bone mineral density.

PubMed

Wu, Chia-Hung; Yang, Kun-Cheh; Chang, Hao-Hsiang; Yen, Jo-Fang; Tsai, Ko-Sung; Huang, Kuo-Chin

2013-01-01

Lean body mass is positively correlated with bone mineral density (BMD). The association between sarcopenia and BMD is less studied. The aim of the study is to investigate the association between sarcopenia and abnormal BMD. A total of 600 community residents aged 40-85 years (mean=63.63 ± 10.12) from Taipei, Taiwan were included. Abnormal and normal BMD groups were categorized by T-score of femoral neck and lumbar spine (L2-L4) measured by dual-energy X-ray absorptiometry. Skeletal muscle mass (SM) index (SMI) was obtained from SM divided by height squared using bioelectrical impedance analysis (BIA) method. Sarcopenia was defined as SMI less than 8.87 kg/m² in men and 6.42 kg/m² in women according to previous Taiwanese sarcopenia study. The association between BMD groups and sarcopenia was examined using binary logistic regression analyses after controlling potential confounders. Subjects with sarcopenia were at higher risk for low BMD (odds ratio (OR) = 1.59, 95% confidence interval (CI)=1.06-2.39 for femoral neck BMD and OR=1.72, 95% CI=1.09-2.72 for lumbar BMD) compared with the nonsarcopenia group. Even in different gender groups with age categorized, sarcopenia was still an important independent factor in female group. The least square (LS) means of BMD of femoral neck and lumbar spine were significantly lower in sarcopenia group. The risk of low BMD increased significantly with sarcopenia. Copyright © 2013 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Retreatment with teriparatide: our experience in three patients with severe secondary osteoporosis.

PubMed

Mana, D L; Zanchetta, M B; Zanchetta, J R

2017-04-01

Teriparatide is a drug for the treatment of osteoporosis which is licensed for use for up to 24 months. There is little experience with retreatment. The aim of this study was to evaluate, in three patients with severe secondary osteoporosis, the response to a second cycle of teriparatide regarding bone mineral density (BMD) and osteocalcin. Case 1 : A 62-year-old woman with multiple vertebral fractures has received corticoids for a long time. After starting teriparatide, her BMD and osteocalcin increased. She then received ibandronate for 3 years but her BMD declined. After a second treatment with teriparatide, her BMD increased again (18%). Case 2 : A 60-year-old woman with severe osteoporosis in lumbar spine (LS) (T-score - 4.5) had received corticoids for a long time and had celiac disease. After starting teriparatide, her BMD improved by 11.7%. She then received zoledronic acid for 15 months, but bone density decreased, so she was retreated with teriparatide. BMD had a slightly higher increase than after the first cycle (12.6%). Case 3 : A 60-year-old woman consulted for osteoporosis (LS T-score - 5.3), several fractures, and hyperthyroidism. She started teriparatide with improvement in BMD (39%). After 24 months, she received ibandronate for 1 year, but as her BMD declined, she was retreated with teriparatide. BMD showed an increase of 15%. The indication of a second cycle of treatment with teriparatide in three patients was effective in increasing BMD. Additional studies are needed to further identify the benefits and safety of retreatment with teriparatide.

Association between fibroblast growth factor 21 and bone mineral density in adults.

PubMed

Hao, Ruo-Han; Gao, Jun-Ling; Li, Meng; Huang, Wei; Zhu, Dong-Li; Thynn, Hlaing Nwe; Dong, Shan-Shan; Guo, Yan

2018-02-01

Animal-based studies have reported a decrease in bone mass resulting from high level of fibroblast growth factor 21 (FGF21). However, the correlation between plasma FGF21 levels and bone mineral density (BMD) is paradoxical in previous human-based studies, and the associations between FGF21 gene polymorphisms and BMD haven't been reported yet. Therefore, here, we evaluated plasma FGF21 levels with sufficient study samples, and performed genetic association test to reveal the physiological and genetic role of FGF21 on BMD in adults. Plasma and genetic samples containing 168 and 569 Han Chinese subjects, respectively, were employed in this study. Fasting plasma FGF21 levels were determined using enzyme-linked immunosorbent assay (ELISA). Regional BMD values were measured by dual energy X-ray absorptiometry (DXA). Five variants of FGF21 gene were successfully genotyped. Physiological association suggested that plasma FGF21 levels were inversely correlated with BMD in femoral neck (Neck-BMD: P = 0.039) and Ward's triangle (Ward's-BMD: P = 0.002) of hip region. A FGF21 gene variant, rs490942, was significantly associated with the increase of Ward's-BMD in total (P = 0.027) and female (P = 0.016) cohorts, as well as Neck-BMD in female cohort (P = 7.45 × 10 -3 ). Meanwhile, eQTL results indicated that this SNP was related to the decreased level of FGF21 gene expression. Taking together from both physiological and genetic levels, we suggest that FGF21 is inversely associated with regional BMD. And we haven't observed sex-specific effect in this study.

Optimal Serum Cholesterol Concentrations are Associated with Accelerated Bone Loss in African Ancestry Men

PubMed Central

Kuipers, Allison L.; Miljkovic, Iva; Evans, Rhobert; Bunker, Clareann H.; Patrick, Alan L.; Zmuda, Joseph M.

2016-01-01

Purpose Studies of lipid and lipoprotein cholesterol associations with bone mineral density (BMD) and bone loss have been inconclusive, and longitudinal data are sparse. Therefore, the aim of this study was to test if fasting serum lipid and lipoprotein cholesterol levels are associated with areal and volumetric BMD and BMD change, Methods We determined the association of serum triglycerides, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol concentrations with cross-sectional and longitudinal (mean follow-up: 6.1 years) measures of BMD in a cohort of 1289 in African ancestry men (mean age: 56.4 years). Fasting serum triglycerides, HDL and LDL were measured at baseline concurrent with BMD assessments. Dual-energy X-ray absorptiometry was used to quantify integral hip BMD and peripheral quantitative computed tomography at the radius and tibia was used to quantify volumetric BMD. Men were categorized as optimal, borderline or high-risk for triglyceride, HDL and LDL concentrations based on adult treatment panel III guidelines. Results Lower serum triglyceride or LDL and higher HDL concentrations were associated with lower trabecular BMD at baseline (all p<0.05). Similarly, men classified as having optimal levels of LDL, HDL or triglycerides at baseline experienced the greatest integral BMD loss at the hip and trabecular BMD loss at the tibia (all p<0.05), independent of potential confounding factors. Conclusions We found that clinically optimal serum lipid and lipoprotein cholesterol concentrations were associated with accelerated bone loss among Afro-Caribbean men. Further studies are needed to better understand the mechanisms involved and potential clinical significance of these findings. PMID:26602914

An Integrative Genetics Approach to Identify Candidate Genes Regulating BMD: Combining Linkage, Gene Expression, and Association

PubMed Central

Farber, Charles R; van Nas, Atila; Ghazalpour, Anatole; Aten, Jason E; Doss, Sudheer; Sos, Brandon; Schadt, Eric E; Ingram-Drake, Leslie; Davis, Richard C; Horvath, Steve; Smith, Desmond J; Drake, Thomas A; Lusis, Aldons J

2009-01-01

Numerous quantitative trait loci (QTLs) affecting bone traits have been identified in the mouse; however, few of the underlying genes have been discovered. To improve the process of transitioning from QTL to gene, we describe an integrative genetics approach, which combines linkage analysis, expression QTL (eQTL) mapping, causality modeling, and genetic association in outbred mice. In C57BL/6J × C3H/HeJ (BXH) F2 mice, nine QTLs regulating femoral BMD were identified. To select candidate genes from within each QTL region, microarray gene expression profiles from individual F2 mice were used to identify 148 genes whose expression was correlated with BMD and regulated by local eQTLs. Many of the genes that were the most highly correlated with BMD have been previously shown to modulate bone mass or skeletal development. Candidates were further prioritized by determining whether their expression was predicted to underlie variation in BMD. Using network edge orienting (NEO), a causality modeling algorithm, 18 of the 148 candidates were predicted to be causally related to differences in BMD. To fine-map QTLs, markers in outbred MF1 mice were tested for association with BMD. Three chromosome 11 SNPs were identified that were associated with BMD within the Bmd11 QTL. Finally, our approach provides strong support for Wnt9a, Rasd1, or both underlying Bmd11. Integration of multiple genetic and genomic data sets can substantially improve the efficiency of QTL fine-mapping and candidate gene identification. PMID:18767929

Determinants of low bone mineral density in children with epilepsy.

PubMed

Fong, Choong Yi; Kong, Ann Nie; Noordin, Mazidah; Poh, Bee Koon; Ong, Lai Choo; Ng, Ching Ching

2018-01-01

Children with epilepsy on long-term antiepileptic drugs (AEDs) are at risk of low bone mineral density (BMD). The aims of our study were to evaluate the prevalence and determinants of low BMD among Malaysian children with epilepsy. Cross-sectional study of ambulant children with epilepsy on long-term AEDs for >1 year seen in a tertiary hospital in Malaysia from 2014 to 2015. Detailed assessment of anthropometric measurements; environmental lifestyle risk factors; serum vitamin D, calcium and parathyroid hormone levels; genotyping of single nucleotide polymorphisms of genes in vitamin D and calcium metabolism; and lumbar spine BMD were obtained. Low BMD was defined as BMD Z-score ≤ -2.0 SD. Eighty-seven children with mean age of 11.9 years (56 males) participated in the study. The prevalence of low lumbar BMD was 21.8% (19 patients). Multivariate logistic regression analysis identified polytherapy >2 AEDs (OR: 7.86; 95% CI 1.03-59.96), small frame size with wrist breadth of <15th centile (OR 14.73; 95% CI 2.21-98.40), and body mass index Z-score < -2.0 (OR 8.73, 95% CI 1.17-65.19) as significant risk factors for low BMD. One-fifth of Malaysian children with epilepsy on long-term AEDs had low BMD. Targeted BMD should be performed for those who are on >2 AEDs, underweight or with small frame size as they are at higher risk of having low BMD. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

A comparison of swallowing dysfunction in Becker muscular dystrophy and Duchenne muscular dystrophy.

PubMed

Yamada, Yuka; Kawakami, Michiyuki; Wada, Ayako; Otsuka, Tomoyoshi; Muraoka, Kaori; Liu, Meigen

2018-06-01

Swallowing dysfunction has been reported in Duchenne muscular dystrophy (DMD), but has not been studied in Becker muscular dystrophy (BMD). The aims of this study were to report the characteristics of swallowing dysfunction in BMD compared with DMD. The study participants were 18 patients with BMD and 18 patients with DMD. All the patients were examined using videofluorography during swallowing of 5 mL of fluid. The penetration-aspiration scale (P-A scale) and the videofluorographic dysphagia scale (VDS) were used to evaluate dysphagia. Swinyard functional ability stage was not significantly different between the BMD and DMD groups. Rate of aspiration, P-A scale score, and total VDS score did not differ across groups, but the VDS item score for laryngeal elevation was lower in the BMD group than in the DMD group (median scores 4.5 and 9, respectively; p < 0.001). In the BMD group, total VDS score significantly correlated with Swinyard stage (r = 0.78, p < 0.001), but not with age or lung function. Patients with BMD have swallowing problems similar to those observed in patients with DMD when matched according to physical functional status. These patients should be evaluated and followed-up for the duration of their disease. Implications for rehabiliation Dysphagia is one of the most critical problems in patients with progressive neuromuscular disease but dysphagia in patients with Becker muscular dystrophy (BMD) was not well known. Eighteen patients with BMD and 18 patients with Duchenne muscular dystrophy were examined with videofluorography. Patients with BMD have swallowing problems similar to those observed in patients with DMD.

PPARG by Dietary Fat Interaction Influences Bone Mass in Mice and Humans

PubMed Central

Ackert-Bicknell, Cheryl L; Demissie, Serkalem; Marín de Evsikova, Caralina; Hsu, Yi-Hsiang; DeMambro, Victoria E; Karasik, David; Cupples, L Adrienne; Ordovas, Jose M; Tucker, Katherine L; Cho, Kelly; Canalis, Ernesto; Paigen, Beverly; Churchill, Gary A; Forejt, Jiri; Beamer, Wesley G; Ferrari, Serge; Bouxsein, Mary L; Kiel, Douglas P; Rosen, Clifford J

2008-01-01

Adult BMD, an important risk factor for fracture, is the result of genetic and environmental interactions. A quantitative trait locus (QTL) for the phenotype of volumetric BMD (vBMD), named Bmd8, was found on mid-distal chromosome (Chr) 6 in mice. This region is homologous to human Chr 3p25. The B6.C3H-6T (6T) congenic mouse was previously created to study this QTL. Using block haplotyping of the 6T congenic region, expression analysis in the mouse, and examination of nonsynonymous SNPs, peroxisome proliferator activated receptor γ (Pparg) was determined to be the most likely candidate gene for the Bmd8 QTL of the 630 genes located in the congenic region. Furthermore, in the C3H/HeJ (C3H) strain, which is the donor strain for the 6T congenic, several polymorphisms were found in the Pparg gene. On challenge with a high-fat diet, we found that the 6T mouse has a lower areal BMD (aBMD) and volume fraction of trabecular bone (BV/TV%) of the distal femur compared with B6 mice. Interactions between SNPs in the PPARG gene and dietary fat for the phenotype of BMD were examined in the Framingham Offspring Cohort. This analysis showed that there was a similar interaction of the PPARG gene and diet (fat intake) on aBMD in both men and women. These findings suggest that dietary fat has a significant influence on BMD that is dependent on the alleles present for the PPARG gene. PMID:18707223

Bone Lose of the Ancient Mediterranean lumbar vertebrae : Iasos, 6th century ad.

NASA Astrophysics Data System (ADS)

Kaya, Serdar; Solmaz, Ilker; Ilıca, A. Turan; Karaçalıoğlu, Özgür; Damla Yılmaz, Nalan; Başoğlu, Okşan; Kılıc, Selim; Izci, Yusuf

Evaluation of bone mineral density (BMD) of the ancient peoples has received great interest by anthropologists. The aims of this study are to investigate the lumbar vertebrae of the Iasos people during the Byzantine period, in order to determine the prevalence of bone loss and to interpret dietary conditions of ancient Mediterranean populations. Lumbar vertebrae belonging to twenty eight skeletons of the 6th c AD were analyzed by radiographs and dual energy X-ray absorptiometry. The BMD values for each biologic sex and age group were compared. The correlation between the BMD and radiological features was also analyzed. The mean BMD was 0.940 g/cm2. BMD was decreased by aging in both sexes, but it was not significant. Osteopenia was found in 11 (39%) and osteoporosis in 4 (14.3%) out 28 vertebrae. The BMD was normal in 13 (46%) out of 28 vertebrae. Osteopenia was present in 7 (38%) of 18 male vertebrae and 4 (40%) of 10 female vertebrae. The spine score was high in the male group and there was a strong positive correlation between the BMD and spine score for both sexes. This study revealed that the BMD decreased by aging and that osteopenia was a problem in both sexes of the Iasos people during the 6th c AD. There was no correlation between the BMD and radiological features for age groups and biological sexes.

[Bone mineral density, biochemical bone turnover markers and factors associated with bone health in young Korean women].

PubMed

Park, Young Joo; Lee, Sook Ja; Shin, Nah Mee; Shin, Hyunjeong; Kim, Yoo Kyung; Cho, Yunjung; Jeon, Songi; Cho, Inhae

2014-10-01

This study was done to assess the bone mineral density (BMD), biochemical bone turnover markers (BTMs), and factors associated with bone health in young Korean women. Participants were 1,298 women, ages 18-29, recruited in Korea. Measurements were BMD by calcaneus quantitative ultrasound, BTMs for Calcium, Phosphorus, Osteocalcin, and C-telopeptide cross-links (CTX), body composition by physical measurements, nutrients by food frequency questionnaire and psychosocial factors associated with bone health by self-report. The mean BMD (Z-score) was -0.94. 8.7% women had lower BMD (Z-score≤-2) and 14.3% women had higher BMD (Z-score≥0) than women of same age. BTMs were not significantly different between high-BMD (Z-score≥0) and low-BMD (Z-score<0) women. However, Osteocalcin and CTX were higher in women preferring caffeine intake, sedentary lifestyle and alcoholic drinks. Body composition and Calcium intake were significantly higher in high-BMD. Low-BMD women reported significantly higher susceptibility and barriers to exercise in health beliefs, lower bone health self-efficacy and promoting behaviors. Results of this study indicate that bone health of young Korean women is not good. Development of diverse strategies to intervene in factors such as exercise, nutrients, self-efficacy, health beliefs and behaviors, shown to be important, are needed to improve bone health.

Accounting for body size deviations when reporting bone mineral density variables in children.

PubMed

Webber, C E; Sala, A; Barr, R D

2009-01-01

In a child, bone mineral density (BMD) may differ from an age-expected normal value, not only because of the presence of disease, but also because of deviations of height or weight from population averages. Appropriate adjustment for body size deviations simplifies interpretation of BMD measurements. For children, a bone mineral density (BMD) measurement is normally expressed as a Z score. Interpretation is complicated when weight or height distinctly differ from age-matched children. We develop a procedure to allow for the influence of body size deviations upon measured BMD. We examined the relation between body size deviation and spine, hip and whole body BMD deviation in 179 normal children (91 girls). Expressions were developed that allowed derivation of an expected BMD based on age, gender and body size deviation. The difference between measured and expected BMD was expressed as a HAW score (Height-, Age-, Weight-adjusted score). In a second independent sample of 26 normal children (14 girls), measured spine, total femur and whole body BMD all fell within the same single normal range after accounting for age, gender and body size deviations. When traditional Z scores and HAW scores were compared in 154 children, 17.5% showed differences of more than 1 unit and such differences were associated with height and weight deviations. For almost 1 in 5 children, body size deviations influence BMD to an extent that could alter clinical management.

The effect of pregnancy and lactation on bone mineral density in fluoride-exposed rats.

PubMed

Yildiz, Mustafa; Oral, Baha

2006-06-01

Fluoride increases metabolic turnover of the bone in favour of bone formation. Excessive intake of fluoride may lead to pathological changes in teeth and bones: dental and skeletal fluorosis. In this study, we investigated the effect of pregnancy and lactation on bone mineral density (BMD) in fluoride-exposed rats. Female Wistar rats were given commercially available spring water with 100 ppm fluoride (N = 8), or without addition (N = 8) for 18 weeks. At 16 weeks of age, four female rats and one male rat were kept in a cage for 5 days; all females were successfully impregnated. BMD was measured at 16 weeks of age, on the first day postpartum, and at the end of lactation. Spinal BMD was significantly higher in fluoride-exposed rats than control (P < 0.05), but there were no differences in femoral BMD (P = 0.670). During pregnancy, spinal BMD and femoral BMD were not significantly changed in fluoride-exposed rats, whereas BMD of the spine was significantly decreased in the control rats (P = 0.013), but not in the femur. During lactation, BMD was significantly decreased at the two regions compared to initial values (P < 0.05) in both groups. This study shows that pregnancy has no effect on bone, but lactation has a decreasing effect on BMD in fluoride-exposed rats.

Bone mineral density in relation to body mass index among young women: a prospective cohort study.

PubMed

Elgán, Carina; Fridlund, Bengt

2006-08-01

To identify important predictors among lifestyle behaviours and physiological factors of bone mineral density (BMD) in relation to body mass index (BMI) among young women over a 2-year period. DESIGN, SAMPLE AND MEASUREMENTS: Data were collected in 1999 and 2001. Healthy young women (n=152) completed a questionnaire. BMD measurements were performed by DEXA in the calcaneus. The women were subdivided into three categories according to baseline BMI. Baseline bodyweight explained 25% of the variability in BMD at follow-up in the BMI<19 category, and high physical activity seemed to hinder BMD development. In the BMI>24 category, a difference in time spent outdoors during winter between baseline and follow-up was the single most important factor for BMD levels. Overweight women with periods of amenorrhoea had lower BMD than overweight women without such periods. Predictors and lifestyle behaviours associated with BMD are likely to be based on women of normal weight. BMI should be considered when advising on physical activity, since high physical activity seems to impair BMD development among underweight young women, possibly due to energy imbalance. Among overweight women, sleep satisfaction is the greatest predictor associated with BMD change and may indicate better bone formation conditions. Energy balance and sleep quality may be prerequisites of bone health and should be considered in prevention.

Baseline Vitamin D Status is Predictive of Longitudinal Change in Tibial BMD in Knee Osteoarthritis (OA)

USDA-ARS?s Scientific Manuscript database

With its lack of effective treatment and high prevalence, the public health impact of OA is substantial. Peri-articular bone in OA can be evaluated with the medial:lateral tibial BMD ratio (M:L BMD) obtained from dual x-ray absorptiometry (DXA). Higher M:L BMD is associated with medial OA features...

Serum serotonin concentration associated with bone mineral density in Chinese postmenopausal women.

PubMed

Wei, Qiu-Shi; Chen, Zhen-Qiu; Tan, Xin; Kang, Lu-Chen; Jiang, Xiao-Bing; Liang, Jiang; He, Wei; Deng, Wei-Min

2017-02-01

Recent studies have shown that circulating serotonin plays a potential role in bone metabolism. However, conflicting results have been reported for the relationship between serum serotonin concentrations and bone mineral density (BMD). We investigated whether the serum serotonin concentrations related to BMD in Chinese postmenopausal women. Serum serotonin and bone turnover concentrations of 117 premenopausal women and 262 asymptomatic postmenopausal women were analyzed by enzyme-linked immunosorbent assay. BMD at the lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry. The relationship between serotonin and BMD was investigated. The postmenopausal women had lower mean serum serotonin concentrations compared to the premenopausal women. Serotonin concentrations were negatively associated with age, weight, BMI, fat mass, and β-CTX concentrations in postmenopausal women. No significant correlations were found between serotonin and these parameters in premenopausal women. In postmenopausal women, age- and BMI-adjusted serotonin concentrations were positively correlated with BMD of the lumbar spine and femoral neck. Multiple regression analyses showed serum serotonin and β-CTX were the predictors for lumbar spine BMD. Only serum serotonin was the determinant for femoral neck BMD. In conclusion, lower serum serotonin concentrations are linked to low lumbar spine and femoral neck BMD in postmenopausal women.

Bone Density Following Three Years of Recovery from Long-Duration Space-Flight

NASA Technical Reports Server (NTRS)

Amin, S.; Achenbach, S. J.; Atkinson, E. J.; Sibonga, J.

2010-01-01

Bone loss during long-duration space flight is well recognized, but the long-term implications on bone health following return from flight remain unclear. Among US crew who were involved in long-duration missions in space (Mir and ISS), we have previously shown that at approximately 12 months following return, men, but not women, had BMD values at most sites that were still lower than would be expected had they not been exposed to a prolonged period of microgravity. We now extend our observations to 3 years of follow-up post-flight. Using their age, pre-flight BMD and follow-up time, post-flight BMD values for each US crew were predicted based on the model developed from the community sample. We found BMD measures to be either stable or improve by 3 years relative to their immediate post-flight BMD, however only total hip BMD still remains significantly lower than would be expected had they not been exposed to microgravity. Among male US crew, who have had their BMD measured following at least 3 years of recovery post long-duration flight, they continue to have lower BMD at the hip than would be expected, raising potential concerns regarding future hip fracture risk.

Thalassaemic osteopathy: a cross-sectional preliminary study from Sri Lanka.

PubMed

Dissanayake, Ruwangi; de Silva, Shamya; Lekamwasam, Sarath; Abeysekara, Gayan; Dissanayake, Vajira H W

2014-03-01

The objectives of this study were to demonstrate the presence of low bone mineral density (BMD) and to examine the association of known risk factors for low BMD in patients with beta thalassaemia major in Sri Lanka. Thirty-eight patients were studied. Their examination and laboratory investigation findings were recorded (haematology, biochemistry, hormonal profile, COL1A1 rs1800012G>T genotype, dual energy X-ray absorptiometry (DXA) scanning). Mean age was 10.95 years (range 5-21.4). 20 (52.6%) were male. BMD was low (z score ≤-2.0) in 12 (31.5%). Regression analysis of BMD on known risk factors (age, sex, pubertal stage, ferritin level, average pre-transfusion haemoglobin, serum calcium level and COL1A1 rs1800012G>T genotype) controlling for confounding factors on each comparison, showed that only age was significantly associated with low BMD (p=0.005). Approximately one-third of patients had a low BMD. Only age was significantly associated with a low BMD.

Multicenter analysis of CIREN occupant lumbar bone mineral density and correlation with age and fracture incidence.

PubMed

Saffarzadeh, Mona; Hightower, R Caresse; Talton, Jennifer W; Miller, Anna N; Stitzel, Joel D; Weaver, Ashley A

2016-09-01

This study aimed to quantify lumbar volumetric bone mineral density (vBMD) for 873 seriously injured Crash Injury Research and Engineering Network (CIREN) motor vehicle crash occupants (372 male, 501 female) from 8 centers using phantomless computed tomography scans and to associate vBMD with age, fracture incidence, and osteopenia/osteoporosis diagnoses. The novelty of this work is that it associates vBMD with region of injury by applying an established method for vBMD measurement using phantomless computed tomography (CT). A validated phantomless CT calibration method that uses patient-specific fat and muscle measurements to calibrate vBMD measured from the L1-L5 trabeculae was applied on 873 occupants from various CIREN centers. CT-measured lumbar vBMD < 145 mg/cc is indicative of osteopenia using a published threshold. CIREN occupant lumbar vBMD in milligrams per cubic centimeter was regressed against age, osteopenia/osteoporosis comorbidities, height, weight, body mass index (BMI), and the incidence of fracture in vertebral (cervical, thoracic, lumbar) and rib/sternum regions. Among the 873 occupants analyzed, 11% (92 occupants) were diagnosed as osteopenic in CIREN. Of these 92 occupants, 42% (39 occupants) had normal vBMD measures (≥145 mg/cc), suggesting possible misclassification in CIREN. Of the 134 occupants classified as osteopenic in vBMD analysis, 60% were not classified as osteopenic in CIREN, suggesting undiagnosed osteopenia, and 40% were correctly classified in CIREN. Age was negatively correlated with vBMD (P <.0001) and occupants with <145 mg/cc vBMD sustained a median number of 2 rib/sternum fractures compared to a median value of 0 rib/sternum fractures for the ≥145 mg/cc vBMD group (P <.0001). Vertebral fracture analysis revealed that the thoracolumbar region was the most common region of injury in the spine. Though the incidence of fracture was not significantly different in the thoracic (10% versus 6%, P =.122) and lumbar (16% versus 13%, P =.227) regions between the 2 bone quality groups, the proportion of thoracolumbar fractures was significantly higher in occupants with <145 mg/cc vBMD versus occupants with ≥145 mg/cc vBMD (24% versus 17%, P =.043). Low lumbar vertebral bone quality is associated with an increased number of rib/sternum fractures and a greater incidence of thoracolumbar vertebral body fractures within the CIREN population analyzed.

Factors affecting bone mineral density in postmenopausal women.

PubMed

Heidari, Behzad; Hosseini, Reza; Javadian, Yahya; Bijani, Ali; Sateri, Mohammad Hassan; Nouroddini, Haj Ghorban

2015-01-01

This study aimed to determine the relationship between bone mineral density (BMD) and demographic, biochemical, and clinical features according to BMD measurement sites. The results indicated that BMD correlates negatively with menopause duration, parity, and history of fractures but positively correlates with obesity, physical activity, education, and serum ferritin. Osteoporosis (OP) is an important cause of morbidity and mortality in the elderly people. The impacts of various factors on bone mineral density (BMD) differ across diverse population. We hypothesized that the influences of factors which affect BMD vary according to BMD measurement sites. The aim of this study was to determine the relationship between BMD in the femoral neck (FN) and lumbar spine (LS) with some common clinical, demographic, and biochemical parameters in postmenopausal women. In this cross-sectional case-control study, all postmenopausal women of the Amirkola Health and Ageing Project (AHAP) who performed bone densitometry were included. BMD at FN and LS was measured by DXA method. Data regarding clinical, demographic, and biochemical characteristics were provided. OP was diagnosed by the International Society for Clinical Densitometry criteria. Pearson correlation and multivariate regression analyses with simultaneous adjustment were performed to determine relationship. Five hundred thirty-seven women with mean age of 67.9 ± 6.7 years and mean menopause duration (MD) of 15.8 ± 5.1 years were studied. MD correlated negatively with FN-BMD and LS-BMD g/cm(2) (r = -0.405, p = 0.001 and r = -0.217, p = 0.001). Body mass index (BMI) correlated positively with FN and LS-BMD g/cm(2) (r = 0.397, p = 0.001 and r = 0.311, p = 0.001). The association of MD with risk of FN-OP was stronger than LS-OP. Obesity and metabolic syndrome (MS) and higher serum ferritin reduced the risk of OP at both LS and FN similarly, whereas the impacts of parity, prior fracture, high level of education, and physical activity were significantly different across BMD measurement sites. The results of this study indicated a significant association between OP and MD, obesity, parity, MS, history of fracture, serum ferritin, level of education, and physical activity. However, the direction and the strength of association varied across BMD measurement sites.

Bone Density in Peripubertal Boys with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Neumeyer, Ann M.; Gates, Amy; Ferrone, Christine; Lee, Hang; Misra, Madhusmita

2013-01-01

We determined whether bone mineral density (BMD) is lower in boys with autism spectrum disorders (ASD) than controls, and also assessed variables that may affect BMD in ASD. BMD was measured using dual energy X-ray absorptiometry (DXA) in 18 boys with ASD and 19 controls 8-14 years old. Boys with ASD had lower BMD Z-scores at the spine, hip and…

Are breast density and bone mineral density independent risk factors for breast cancer?

PubMed

Kerlikowske, Karla; Shepherd, John; Creasman, Jennifer; Tice, Jeffrey A; Ziv, Elad; Cummings, Steve R

2005-03-02

Mammographic breast density and bone mineral density (BMD) are markers of cumulative exposure to estrogen. Previous studies have suggested that women with high mammographic breast density or high BMD are at increased risk of breast cancer. We determined whether mammographic breast density and BMD of the hip and spine are correlated and independently associated with breast cancer risk. We conducted a cross-sectional study (N = 15,254) and a nested case-control study (of 208 women with breast cancer and 436 control subjects) among women aged 28 years or older who had a screening mammography examination and hip BMD measurement within 2 years. Breast density for 3105 of the women was classified using the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) categories, and percentage mammographic breast density among the case patients and control subjects was quantified with a computer-based threshold method. Spearman rank partial correlation coefficient and Pearson's correlation coefficient were used to examine correlations between BI-RADS breast density and BMD and between percentage mammographic breast density and BMD, respectively, in women without breast cancer. Logistic regression was used to examine the association of breast cancer with percentage mammographic breast density and BMD. All statistical tests were two-sided. Neither BI-RADS breast density nor percentage breast density was correlated with hip or spine BMD (correlation coefficient = -.02 and -.01 for BI-RADS, respectively, and -.06 and .01 for percentage breast density, respectively). Neither hip BMD nor spine BMD had a statistically significant relationship with breast cancer risk. Women with breast density in the highest sextile had an approximately threefold increased risk of breast cancer compared with women in the lowest sextile (odds ratio = 2.7, 95% confidence interval = 1.4 to 5.4); adjusting for hip or spine BMD did not change the association between breast density and breast cancer risk. Breast density is strongly associated with increased risk of breast cancer, even after taking into account reproductive and hormonal risk factors, whereas BMD, although a possible marker of lifetime exposure to estrogen, is not. Thus, a component of breast density that is independent of estrogen-mediated effects may contribute to breast cancer risk.

Bone density loss on computed tomography at 3-year follow-up in current compared to former male smokers.

PubMed

Pompe, E; Bartstra, J; Verhaar, H J; de Koning, H J; van der Aalst, C M; Oudkerk, M; Vliegenthart, R; Lammers, J-W J; de Jong, P A; Mohamed Hoesein, F A A

2017-04-01

Cigarette smoking negatively affects bone quality and increases fracture risk. Little is known on the effect of smoking cessation and computed tomography (CT)-derived bone mineral density (BMD) decline in the spine. We evaluated the association of current and former smoking with BMD decline after 3-year follow-up. Male current and former smokers participating in a lung cancer screening trial who underwent baseline and 3-year follow-up CT were included. BMD was measured by manual placement of a region of interest in the first lumbar vertebra and expressed in Hounsfield Unit (HU). Multiple linear regression analysis was used to evaluate the association between pack years smoked and smoking status with BMD decline. 408 participants were included with median (25th-75th percentile) age of 59.4 (55.9-63.5) years. At the start of the study, 197 (48.3%) participants were current smokers and 211 (51.7%) were former smokers and had a similar amount of pack years. Current smokers had quit smoking for 6 (4-8) years prior to inclusion. There was no difference in BMD between current and former smokers at baseline (109±34 HU vs. 108±32 HU, p=0.96). At 3-year follow-up, current smokers had a mean BMD decline of -3±13 HU (p=0.001), while BMD in former smokers did not change as compared to baseline (1±13 HU, p=0.34). After adjustment for BMD at baseline and body mass index, current smoking was independently associated with BMD decline (-3.8 HU, p=0.003). Age, pack years, and the presence of a fracture at baseline did not associate with BMD decline. Current smokers showed a more rapid BMD decline over a 3-year period compared to former smokers. This information might be important to identify subjects at risk for osteoporosis and emphasizes the importance of smoking cessation in light of BMD decline. Copyright © 2017 Elsevier B.V. All rights reserved.

Differential effect of obesity on bone mineral density in White, Hispanic and African American women: a cross sectional study

PubMed Central

Castro, Jonathan P; Joseph, Linda A; Shin, John J; Arora, Surender K; Nicasio, John; Shatzkes, Joshua; Raklyar, Irina; Erlikh, Irina; Pantone, Vincent; Bahtiyar, Gul; Chandler, Leon; Pabon, Lina; Choudhry, Sara; Ghadiri, Nilofar; Gosukonda, Pramodini; Muniyappa, Rangnath; von-Gicyzki, Hans; McFarlane, Samy I

2005-01-01

Osteoporosis is a major public health problem with low bone mass affecting nearly half the women aged 50 years or older. Evidence from various studies has shown that higher body mass index (BMI) is a protective factor for bone mineral density (BMD). Most of the evidence, however, is from studies with Caucasian women and it is unclear to what extent ethnicity plays a role in modifying the effect of BMI on BMD. A cross sectional study was performed in which records of postmenopausal women who presented for screening for osteoporosis at 2 urban medical centres were reviewed. Using logistic regression, we examined the interaction of race and BMI after adjusting for age, family history of osteoporosis, maternal fracture, smoking, and sedentary lifestyle on BMD. Low BMD was defined as T-score at the lumbar spine < -1. Among 3,206 patients identified, the mean age of the study population was 58.3 ± 0.24 (Years ± SEM) and the BMI was 30.6 kg/m2. 2,417 (75.4%) were African Americans (AA), 441(13.6%) were Whites and 348 (10.9%) were Hispanics. The AA women had lower odds of having low BMD compared to Whites [Odds ratio (OR) = 0.079 (0.03–0.24) (95% CI), p < 0.01]. The odds ratio of low BMD was not statistically significant between White and Hispanic women. We examined the interaction between race and BMD. For White women; as the BMI increases by unity, the odds of low BMD decreases [OR = 0.9 (0.87–0.94), p < 0.01; for every unit increase in BMI]. AA women had slightly but significantly higher odds of low BMD compared to Whites [OR 1.015 (1.007–1.14), p <0.01 for every unit increase in BMI]. This effect was not observed when Hispanic women were compared to Whites. There is thus a race-dependent effect of BMI on BMD. With each unit increase in BMI, BMD increases for White women, while a slight but significant decrease in BMD occurs in African American women. PMID:15817133

Differential effect of obesity on bone mineral density in White, Hispanic and African American women: a cross sectional study.

PubMed

Castro, Jonathan P; Joseph, Linda A; Shin, John J; Arora, Surender K; Nicasio, John; Shatzkes, Joshua; Raklyar, Irina; Erlikh, Irina; Pantone, Vincent; Bahtiyar, Gul; Chandler, Leon; Pabon, Lina; Choudhry, Sara; Ghadiri, Nilofar; Gosukonda, Pramodini; Muniyappa, Rangnath; von-Gicyzki, Hans; McFarlane, Samy I

2005-04-07

Osteoporosis is a major public health problem with low bone mass affecting nearly half the women aged 50 years or older. Evidence from various studies has shown that higher body mass index (BMI) is a protective factor for bone mineral density (BMD). Most of the evidence, however, is from studies with Caucasian women and it is unclear to what extent ethnicity plays a role in modifying the effect of BMI on BMD.A cross sectional study was performed in which records of postmenopausal women who presented for screening for osteoporosis at 2 urban medical centres were reviewed. Using logistic regression, we examined the interaction of race and BMI after adjusting for age, family history of osteoporosis, maternal fracture, smoking, and sedentary lifestyle on BMD. Low BMD was defined as T-score at the lumbar spine < -1.Among 3,206 patients identified, the mean age of the study population was 58.3 +/- 0.24 (Years +/- SEM) and the BMI was 30.6 kg/m2. 2,417 (75.4%) were African Americans (AA), 441(13.6%) were Whites and 348 (10.9%) were Hispanics. The AA women had lower odds of having low BMD compared to Whites [Odds ratio (OR) = 0.079 (0.03-0.24) (95% CI), p < 0.01]. The odds ratio of low BMD was not statistically significant between White and Hispanic women. We examined the interaction between race and BMD. For White women; as the BMI increases by unity, the odds of low BMD decreases [OR = 0.9 (0.87-0.94), p < 0.01; for every unit increase in BMI]. AA women had slightly but significantly higher odds of low BMD compared to Whites [OR 1.015 (1.007-1.14), p <0.01 for every unit increase in BMI]. This effect was not observed when Hispanic women were compared to Whites.There is thus a race-dependent effect of BMI on BMD. With each unit increase in BMI, BMD increases for White women, while a slight but significant decrease in BMD occurs in African American women.

Long-term changes in the density and structure of the human hip and spine after long-duration spaceflight

NASA Astrophysics Data System (ADS)

Dana Carpenter, R.; LeBlanc, Adrian D.; Evans, Harlan; Sibonga, Jean D.; Lang, Thomas F.

2010-07-01

To determine the long-term effects of long-duration spaceflight, we measured bone mineral density and bone geometry of International Space Station (ISS) crewmembers using quantitative computed tomography (QCT) before launch, immediately upon their return, one year after return, and 2-4.5 years after return from the ISS. Eight crew members (7 male, 1 female, mean age 45±4 years at start of mission) who spent an average of 181 days (range 161-196 days) aboard the ISS took part in the study. Integral bone mineral density (iBMD), trabecular BMD (tBMD), bone mineral content (BMC), and vertebral cross-sectional area (CSA) were measured in the lumbar spine, and iBMD, tBMD, cortical BMD (cBMD), BMC, CSA, volume, and femoral neck section modulus were measured in the hip. Spine iBMD was 95% of the average preflight value upon return from the ISS and reached its preflight value over the next 2-4.5 years. Spine tBMD was 97% of the average preflight value upon return from the ISS and tended to decrease throughout the course of the study. Vertebral CSA remained essentially unchanged throughout the study. Hip iBMD was 91% of the preflight value upon return from the ISS and was 95% of the preflight value after 2-4.5 years of recovery. Hip tBMD was 88% of the preflight value upon return and recovered to only 93% of the preflight value after 1 year. At the 2- to 4.5-year time point, average tBMD was 88% of the preflight value. During the recovery period the total volume and cortical bone volume in the hip reached values of 114% and 110% of their preflight values, respectively. The combination of age-related bone loss, long-duration spaceflight, and re-adaptation to the 1-g terrestrial environment presumably produced these changes. These long-term data suggest that skeletal changes that occur during long-duration spaceflight persist even after multiple years of recovery. These changes have important implications for the skeletal health of crew members, especially those who make repeat trips to space.

Attainment of peak bone mass at the lumbar spine, femoral neck and radius in men and women: relative contributions of bone size and volumetric bone mineral density.

PubMed

Henry, Yvette M; Fatayerji, Diana; Eastell, Richard

2004-04-01

The age at which peak bone mineral content (peak BMC) is reached remains controversial and the mechanism underlying bone mass "consolidation" is still undefined. The aims of this study were to investigate; (1) the timing of peak BMC by studying bone size and volumetric BMD (vBMD) as separate entities and (2) to determine the relative contributions of bone size and vBMD to bone mass "consolidation". A total of 132 healthy Caucasian children (63 boys and 69 girls, ages 11-19 years) and 134 healthy Caucasian adults (66 men and 68 women, ages 20-50 years) were studied. BMC was measured by DXA at the AP and lateral lumbar spine (LS) femoral neck (FN) and ultradistal radius (UDR). vBMD and bone volume (size) were estimated. Bone mass "consolidation" was examined between age 16 years to the age peak bone values were attained. During growth, BMC and bone size increased steeply with age and approximately 80-90% of peak values were achieved by late adolescence. vBMD at the spine and UDR (in women) increased gradually, but vBMD at the FN and UDR in men remained almost constant. During "consolidation", bone size continued to increase with little change in vBMD. Peak vBMD at the lumbar spine was reached at 22 and 29 years in men and women, respectively, but earlier at the FN at 12 years. At the UDR peak vBMD was achieved at age 19 years in women, with little change in men. In conclusion, peak vBMD and bone size are almost fully attained during late adolescence. Although speculative, the lack of change in vBMD during consolidation implies that the continued increase in bone mass may primarily be due to increases in bone size rather than increases in either trabecular volume, cortical thickness or the degree of mineralisation of existing bone matrix (vBMD). Skeletal growth and maturation is heterogeneous, but crucial in understanding how the origins of osteoporosis may begin during childhood and young adulthood.

The relationship between the bone mineral density and urinary cadmium concentration of residents in an industrial complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shin, Minah; Paek, Domyung; Yoon, Chungsik, E-mail: csyoon@snu.ac.kr

Background: An association between cadmium exposure and bone mineral density (BMD) has been demonstrated in elderly women, but has not been well studied in youths and men. Some studies report either no or a weak association between cadmium exposure and bone damage. Objectives: This study was designed to investigate the relationship between the urinary cadmium (U-Cd) levels and BMD of females and males of all ages. Methods: A total of 804 residents near an industrial complex were surveyed in 2007. U-Cd and BMD on the heel (non-dominant calcaneus) were analyzed with AAS-GTA and Dual-Energy X-ray absorptiometry, respectively. Demographic characteristics weremore » collected by structured questionnaires. Osteoporosis and osteopenia were defined by BMD cut-off values and T-scores set by the WHO; T score>-1, normal; -2.5=}1.0 {mu}g/g creatinine) in females (OR=2.92; 95% CI, 1.51-5.64) and in males (OR=3.37; 95% CI, 1.09-10.38). With the multiple linear regression model, the BMD of the adult group was negatively associated with U-Cd (<0.05), gender (female, p<0.001) and age (p<0.001). The BMD of participants who were {<=}19 years of age was negatively associated with gender (female, p<0.01), whereas it was positively associated with age and BMI (p<0.001). BMD was not associated with exercise, smoking habits, alcohol consumption, job or parental education. Conclusion: Results suggested that U-Cd might be associated with osteopenia as well as osteoporosis in both male and female adults. Age and female gender were negatively associated with BMD in the adult group, whereas age was positively associated with BMD in the youth group. Cadmium exposure may be a potential risk factor for lower-BMD and osteopenia symptoms as well as for osteoporosis symptoms. - Research Highlights: {yields} The relationship between the urinary cadmium levels and BMD was investigated. {yields} U-Cd was associated with osteopenia and osteoporosis in adults. {yields} Cadmium exposure may be a potential risk factor for lower-BMD and osteopenia.« less

Concordance of Transcriptional and Apical Benchmark Dose Levels for Conazole-Induced Liver Effects in Mice

EPA Science Inventory

ABSTRACT The ability to anchor chemical class-based gene expression changes to phenotypic lesions and to describe these changes as a function of dose and time informs mode of action determinations and improves quantitative risk assessments. Previous transcription-based microarra...

Quantitative regional and sub-regional analysis of femoral and tibial subchondral bone mineral density (sBMD) using computed tomography (CT): comparison of non-osteoarthritic (OA) and severe OA knees.

PubMed

Omoumi, P; Babel, H; Jolles, B M; Favre, J

2017-11-01

This study aimed to compare subchondral bone mineral density (sBMD) between non-radiographic osteoarthritic (OA) and medial femorotibial OA knees, using computed tomography (CT). CT exams from 16 non-radiographic OA (KL grade < 2) and 16 severe medial OA (KL grade ≥ 3) knees (average age of 61.7 ± 3 and 62.2 ± 5 years old respectively, 50% male in each group), were retrospectively analyzed. CT exams were segmented and 3D maps of sBMD based on the CT number in the most superficial 3 mm of femoral and tibial subchondral bone were computed. Average sBMD and medial-to-lateral sBMD ratios were calculated for total load-bearing regions and for sub-regions of interest in the femur and tibia. The analysis of total load-bearing regions did not reveal any significant difference between groups, except for the lateral tibia, where OA knees had lower sBMD. Sub-regional analysis unveiled differences with some sub-regions of the femur and tibia presenting significantly lower (in the lateral compartment) or higher (in the medial compartment) sBMD in OA knees compared to non-OA knees. The M/L sBMD ratios were significantly higher for OA knees compared to non-OA knees for all regions and sub-regions, except for the internal sub-regions. sBMD locally differs between non-OA and OA knees, in agreement with prior knowledge on biomechanics. CT proved to be a valuable tool for 3D analysis of femoral and tibial sBMD, which can be used in future studies to describe the chronology of sBMD alterations and improve our understanding of the role of subchondral bone in knee OA. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

The relations among upper-extremity loading characteristics and bone mineral density changes in young women.

PubMed

Wang, Man-Ying; Salem, George J

2004-06-01

The relations among the reaction forces engendered during an upper-extremity dynamic impact-loading exercise (DILE) program and bone mineral density adaptations (DeltaBMD) in the radius were investigated in 24 healthy premenopausal women (mean age = 29 +/- 6 years). Subjects performed DILE 36 cycles/day, 3 days/week for 24 weeks. The exercised arm was allocated randomly to either the dominant or the nondominant limb. In addition, subjects were assigned randomly into either damped or nondamped treatment arms to examine the effects of both higher- and lower-magnitude loading prescriptions. Measurements including anthropometrics, self-reported physical activity levels, hand-grip strength, radial BMD (DEXA, Hologic QDR1500, MA) at the ultradistal radius (UD), distal 1/3 radius (DR), and total distal radius (TOTAL), and exercise-related loading characteristics (impact load, loading rate, and impulse) were recorded at baseline and at 6 months. Simple linear regression models were used to fit the regional BMD changes to the reaction force, changes in hand-grip strength (DeltaGRIP), and changes in body weight (DeltaBW). Findings demonstrated that the damping condition utilized during DILE influenced the relations between loading events and BMD changes. Specifically, none of the reaction-force characteristics significantly predicted changes in BMD in participants performing DILE using the damped condition, whereas, in the nondamped condition, impact load accounted for 58% of the variance in BMD change at DR and 66% of the variance in BMD change at TOTAL. Thresholds of 345 and 285 N of impact force to promote BMD increases at DR and TOTAL, respectively, were obtained from the regression models in the nondamped group. Impulse was also an independent predictor of BMD changes at TOTAL, accounting for 56% of the variance. Neither DeltaGRIP nor DeltaBW significantly predicted DeltaBMD at any radial site. These findings, in young adult women, parallel previous reports identifying significant, regionally specific relations among external loading events and BMD changes in both animal and human models.

Milk and yogurt consumption are linked with higher bone mineral density but not with hip fracture: the Framingham Offspring Study

PubMed Central

Sahni, Shivani; Tucker, Katherine L.; Kiel, Douglas P.; Quach, Lien; Casey, Virginia A.; Hannan, Marian T.

2013-01-01

Purpose To examine associations of milk, yogurt, cheese, cream, most dairy (total dairy without cream) and fluid dairy (milk+yogurt) with bone density (BMD) at femoral neck (FN), trochanter (TR) and spine, and with incident hip fracture over 12-y follow-up in the Framingham Offspring Study. Methods 3,212 participants completed a food frequency questionnaire (1991–1995 or 1995–1998) and were followed for hip fracture until 2007. 2,506 participants had DXA BMD (1996–2001). Linear regression was used to estimate adjusted mean BMD while Cox-proportional hazards regression was used to estimate adjusted hazard ratios (HR) for hip fracture risk. Final models simultaneously included dairy foods adjusting for each other. Results Mean baseline age was 55 (±1.6)y, range: 26–85). Most dairy intake was positively associated with hip and spine BMD. Intake of fluid dairy and milk were related with hip but not spine BMD. Yogurt intake was associated with TR-BMD alone. Cheese and cream intakes were not associated with BMD. In final models, yogurt intake remained positively associated with TR-BMD, while cream tended to be negatively associated with FN-BMD. Yogurt intake showed a weak protective trend for hip fracture [HR(95%CI): ≤4 serv/wk: 0.46 (0.21–1.03) vs. >4 serv/wk: 0.43 (0.06–3.27)]. No other dairy groups showed a significant association (HRs range: 0.53–1.47) with limited power (n, fractures=43). Conclusion Milk and yogurt intakes were associated with hip but not spine BMD, while cream may adversely influence BMD. Thus, not all dairy products are equally beneficial for the skeleton. Suggestive fracture results for milk and yogurt intakes need further confirmation. PMID:23371478

Contributions of Caucasian-associated bone mass loci to the variation in bone mineral density in Vietnamese population.

PubMed

Ho-Pham, Lan T; Nguyen, Sing C; Tran, Bich; Nguyen, Tuan V

2015-07-01

Bone mineral density (BMD) is under strong genetic regulation, but it is not clear which genes are involved in the regulation, particularly in Asian populations. This study sought to determine the association between 29 genes discovered by Caucasian-based genome-wide association studies and BMD in a Vietnamese population. The study involved 564 Vietnamese men and women aged 18 years and over (average age: 47 years) who were randomly sampled from the Ho Chi Minh City. BMD at the femoral neck, lumbar spine, total hip and whole body was measured by DXA (Hologic QDR4500, Bedford, MA, USA). Thirty-two single nucleotide polymorphisms (SNPs) in 29 genes were genotyped using Sequenom MassARRAY technology. The magnitude of association between SNPs and BMD was analyzed by the linear regression model. The Bayesian model average method was used to identify SNPs that are independently associated with BMD. The distribution of genotypes of all, but two, SNPs was consistent with the Hardy-Weinberg equilibrium law. After adjusting for age, gender and weight, 3 SNPs were associated with BMD: rs2016266 (SP7 gene), rs7543680 (ZBTB40 gene), and rs1373004 (MBL2/DKK1 gene). Among the three genetic variants, the SNP rs2016266 had the strongest association, with each minor allele being associated with ~0.02 g/cm(2) increase in BMD at the femoral neck and whole body. Each of these genetic variant explained about 0.2 to 1.1% variance of BMD. All other SNPs were not significantly associated with BMD. These results suggest that genetic variants in the SP7, ZBTB40 and MBL2/DKK1 genes are associated with BMD in the Vietnamese population, and that the effect of these genes on BMD is likely to be modest. Copyright © 2015 Elsevier Inc. All rights reserved.

Organization and results of student pharmacist bone mineral density screenings in women.

PubMed

Harris, Adam C; Doucette, William R; Reist, Jeffery C; Nelson, Kathryn E

2011-01-01

To describe the organization and results of student pharmacist-run screenings of bone mineral density (BMD) among women living in the community. Iowa City from March 2008 to April 2009. Student pharmacists operated a BMD screening service at several community-based screening events, including university-sponsored health fairs and community pharmacy events. Interested individuals were invited to have their BMD screened; however, only women aged 21 years or older were asked to participate in the data collection. A risk factor form was completed by consenting participants before BMD screening using a quantitative ultrasound densitometer. Upon screening completion, T- and Z-scores were recorded and participants were counseled on their results. Student pharmacists worked to increase public awareness of bone health through the organization of BMD screenings. Working with faculty, a training process and screening-flow outline were developed to allow students to conduct the BMD screenings independently while adding to their education and increasing public health awareness in a community setting. T- and Z-scores from BMD screenings. Eight student pharmacist-organized BMD screenings were conducted during the course of 14 months. A total of 322 women participated in the screenings and data collection. The mean (±SD) T- and Z-scores for these participants were 0.03 ± 1.30 and 0.52 ± 1.13, respectively. A total of 62 (19.4%) women screened had an increased risk of fracture based on a T-score of -1 or less, whereas approximately two-thirds of all women had better-than-average BMD. Student pharmacists provided the community with free screenings that brought BMD scores to the attention of hundreds of women. Counseling sessions that accompanied the screenings contributed to the women learning more about their risks for osteoporosis. Based on these student pharmacist-run BMD screenings, we encourage other student pharmacist organizations to conduct similar screenings.

Bone mineral density and mortality in elderly men and women: the Rotterdam Study.

PubMed

Van Der Klift, M; Pols, H A P; Geleijnse, J M; Van Der Kuip, D A M; Hofman, A; De Laet, C E D H

2002-04-01

Recent studies have shown that a low bone mineral density (BMD) is associated with a higher risk of mortality. Most studies have investigated this relationship in women only and presented their risk estimates per standard deviation change in BMD. However, when using this approach, a BMD threshold might be missed when relative risks are presented in the traditional manner. Therefore, in this study our aim was to model the relation between BMD and all-cause mortality. In the Rotterdam Study, follow-up was complete for 5819 men and women aged > or =55 years for whom BMD data were available. During an average follow-up of 5.4 years, 399 men and 317 women died. We calculated BMD Z scores using measurements performed at the femoral neck. Cox proportional hazards regression was used to fit the model. An average BMD, reflected by a Z score = 0, was used as the reference. For women, no significant relationship between BMD and overall mortality was observed. For men, however, a cubic model best fitted the relationship under study, also after adjusting for age and body mass index (BMI). The risk of mortality increased when BMD was below average. Similar results were found when separate curves were made for diabetics and nondiabetics, smokers (ever or never), and tertiles of BMI. Excluding subjects who had suffered hip fractures, or adjusting for the number of drugs used and for lower limb disability, essentially did not change results. This suggests that low BMD is not mainly due to morbidity and impaired mobility in our cohort, which makes this a less likely explanation for the observed relation with mortality. The results of our study suggest that, in men, a nonlinear relationship between BMD and mortality exists, which is independent of comorbidity, whereas, in women, no significant relationship was observed.

Spinal Bone Texture Assessed by Trabecular Bone Score in Adolescent Girls With Anorexia Nervosa

PubMed Central

Donaldson, Abigail A.; Feldman, Henry A.; O'Donnell, Jennifer M.; Gopalakrishnan, Geetha

2015-01-01

Context: Trabecular bone score (TBS) is a bone assessment tool that offers information beyond that afforded by dual-energy x-ray absorptiometry (DXA) bone mineral density (BMD) measurements. Adolescents with anorexia nervosa (AN) are known to exhibit compromised bone density and skeletal strength. Objectives: This study aimed to determine TBS among adolescents with AN and evaluate the correlation with anthropometric, clinical and densitometric variables. Design: Areal BMD spinal measures were analyzed for TBS. Findings were compared with clinical (height, weight, body mass index [BMI], age, pubertal development, 25-hydroxyvitamin D) and self-reported data (illness duration, amenorrhea, exercise, fracture, family history of osteoporosis, and antidepressant use), and BMD measures by DXA and peripheral quantitative computed tomography (pQCT). Setting and Participants: This was an urban adolescent program consisting of 57 females with AN, age 11–18 y. Interventions: Interventions included DXA (absolute BMD and Z-score), pQCT (volumetric BMD [vBMD] and stress-strain index [SSI]), laboratory evaluation, and questionnaire administration. Main Outcome Measures: Main outcome measures included TBS, areal and vBMD, SSI, fracture history, disease duration. Results: The TBS of six participants (11%) showed degraded and 19 (33%) partially degraded microarchitecture. Spinal TBS was correlated (P < .05) with age, height, weight, BMI, pubertal stage, BMD, and body composition by DXA, and BMD and SSI by pQCT. TBS was not correlated with disease duration, fracture, vitamin D status, race, or ethnicity, and self-reported health data. Conclusions: TBS showed evidence of degraded microarchitecture in over 40% of this study sample, and strongly correlated with anthropometric data and measures of BMD and skeletal strength. TBS is a novel tool that captures another dimension of bone health in adolescents with AN. PMID:26108094

Socioeconomic status and bone mineral density in adults by race/ethnicity and gender: the Louisiana osteoporosis study.

PubMed

Du, Y; Zhao, L-J; Xu, Q; Wu, K-H; Deng, H-W

2017-05-01

Low bone mineral density (BMD) and osteoporosis have become a public health problem. We found that non-Hispanic white, black, and Asian adults with extremely low education and personal income are more likely to have lower BMD. This relationship is gender-specific. These findings are valuable to guide bone health interventions. The evidence is limited regarding the relationship between socioeconomic status (SES) and bone mineral density (BMD) for minority populations in the USA, as well as the relationship between SES and BMD for men. This study explored and examined the relationship between SES and BMD by race/ethnicity and gender. Data (n = 6568) from the Louisiana Osteoporosis Study (LOS) was examined, including data for non-Hispanic whites (n = 4153), non-Hispanic blacks (n = 1907), and non-Hispanic Asians (n = 508). General linear models were used to estimate the relationship of SES and BMD (total hip and lumbar spine) stratified by race/ethnicity and gender. Adjustments were made for physiological and behavioral factors. After adjusting for covariates, men with education levels below high school graduate experienced relatively low hip BMD than their counterparts with college or graduate education (p < 0.05). In addition, women reporting a personal annual income under $20,000 had relatively low hip and spine BMD than their counterparts with higher income level(s) (p < 0.05). Establishing a conclusive positive or negative association between BMD and SES proved to be difficult. However, individuals who are at an extreme SES disadvantage are the most vulnerable to have relatively low BMD in the study population. Efforts to promote bone health may benefit from focusing on men with low education levels and women with low individual income.

Body mass index is not a good predictor of bone density: results from WHI, CHS, and EPIDOS.

PubMed

Robbins, John; Schott, Anne-Marie; Azari, Rahman; Kronmal, Richard

2006-01-01

Body mass index (BMI) is often used to predict bone mineral density (BMD). This may be flawed. Large epidemiologic studies with BMI and BMD data were analyzed. Weight alone is a better predictor of BMD than BMI. Thus, when selecting individuals for dual-energy X-ray absorptiometry, weight should be used instead of BMI. Low body mass index (BMI) is frequently suggested as one of the factors that indicates the need for bone mineral density (BMD) screening for osteoporosis. The inclusion of the height-squared term in the denominator of this predictive factor is taken on faith or from other data, but it may not be reasonable in this case. We used data from three large epidemiologic studies to test the BMI, height, and weight as predictors of BMD: (1) the Women's Health Initiative (WHI) with 11,390 women; (2) the Cardiovascular Health Study (CHS) with 1,578 men and women; (3) and EPIDOS with 7,598 women. Dual-energy X-ray absorptiometry data on one or more BMD sites, the total hip, the femoral neck, and the lumbar spine from the three studies, as well as height and weight were examined. Correlation coefficients for BMI and weight with BMD were compared. Log transformed models were evaluated to compare the strengths of the models. The result of weight alone was a much better predictor of BMD for all sites in the three studies than BMI. Taller participants had larger BMDs than would have been predicted by BMI. In conclusion, BMIs should not be used to select individuals for BMD screening. A regression model using weight alone or weight and height is a better predictor of BMD in all three populations.

The utility of changes in serum levels of C-terminal telopeptide of type I collagen in predicting patient response to oral monthly ibandronate therapy.

PubMed

Hochberg, Marc C; Silverman, Stuart L; Barr, Charles E; Miller, Paul D

2010-01-01

Bone turnover markers may provide a more rapid indication of patient response to osteoporosis treatment than bone mineral density (BMD) measurements. This post hoc analysis of data from the MOBILE (Monthly Oral iBandronate In LadiEs) study assessed the relationship between increases in BMD at 12 mo from baseline after starting ibandronate treatment and changes in bone resorption marker serum C-terminal telopeptide of type I collagen (sCTX) from baseline at 3 and 6 mo. MOBILE enrolled postmenopausal women aged 55-80 yr with mean lumbar spine (LS) BMD T-score of -2.5 to -5.0. This analysis included women who received 150-mg monthly oral ibandronate (n=323). A high proportion of women were classified as BMD responders after 1 yr (BMD increase was >/=0%, i.e., 74-91% depending on skeletal site; BMD increase was >/=3%, i.e., 34-67%). Women with larger decreases in sCTX were more likely to be BMD responders. The percent increase in LS BMD at 12 mo was significantly associated with the percent decrease in sCTX at 3 mo from baseline (Pearson correlation coefficient: -0.19, p=0.0016). In linear regression models, percent decrease in sCTX at 3 mo from baseline was a significant predictor of 1-yr LS BMD response (R(2)=0.61, p=0.0007). These data suggest that 3-mo changes in sCTX levels are associated with 1-yr LS BMD increases in postmenopausal women treated with once-monthly oral ibandronate. The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Association of regional body composition with bone mineral density in HIV-infected and HIV-uninfected women: women's interagency HIV study.

PubMed

Sharma, Anjali; Tian, Fang; Yin, Michael T; Keller, Marla J; Cohen, Mardge; Tien, Phyllis C

2012-12-01

To understand how regional body composition affects bone mineral density (BMD) in HIV-infected and HIV-uninfected women. Dual energy x-ray absorptiometry was used to measure regional lean and fat mass and BMD at lumbar spine (LS), total hip (TH), and femoral neck (FN) in 318 HIV-infected and 122 HIV-uninfected Women's Interagency HIV Study participants at baseline and 2 and 5 years later. Total lean and fat mass were measured using bioimpedance analysis. Multivariate marginal linear regression models assessed the association of HIV status and body composition on BMD change. Compared with HIV-uninfected women, HIV-infected women were older (44 vs. 37 years), more likely to be Hepatitis C virus-infected (32% vs. 14%), and postmenopausal (26% vs. 3%) and had lower baseline total fat mass, trunk fat, and leg fat. In multivariate models, increased total lean mass was independently associated with increased BMD at LS, TH, and FN, and total fat mass was associated with increased BMD at TH and FN (all P < 0.05). When total fat was replaced in multivariate models with trunk fat and leg fat, increased trunk fat (and not leg fat) was associated with increased TH and FN BMD (P < 0.001). Total fat and lean mass are strong independent predictors of TH and FN BMD, and lean mass was associated with greater LS BMD. Regardless of HIV status, greater trunk fat (and not leg fat) was associated with increased TH and FN BMD, suggesting that weight-bearing fat may be a more important predictor of BMD in the hip.

BMD in elite female triathletes is related to isokinetic peak torque without any association to sex hormone concentrations.

PubMed

Wulff Helge, E; Melin, A; Waaddegaard, M; Kanstrup, I L

2012-10-01

Female endurance athletes suffering from low energy availability and reproductive hormonal disorders are at risk of low BMD. Muscle forces acting on bone may have a reverse site-specific effect. Therefore we wanted to test how BMD in female elite triathletes was associated to isokinetic peak torque (IPT) and reproductive hormone concentrations (RHC). A possible effect of oral contraceptives (OCON's) is taken into consideration. Eight female elite triathletes (training 8-24 hrs/wk) and seven sedentary controls, age 21-37 years, participated. Total body and regional BMD (g.cm-2) were measured by DXA. IPT were measured during knee extension, and trunk extension and flexion (Nm). Serum RHC and biochemical bone markers were evaluated. Energy balance was estimated from 7-days training-and weighed food records. Despite a high training volume, BMD in triathletes was not higher than in controls. In triathletes trunk flexion IPT, but not RHC, was a strong predictor of BMD in both total body and femur (0.70

Bone mineral density and mammographic density in Mexican women.

PubMed

Moseson, Heidi; Rice, Megan S; López-Ridaura, Ruy; Bertrand, Kimberly A; Torres, Gabriela; Blanco, Margarita; Tamayo-Orozco, Juan Alfredo; Lajous, Martin; Romieu, Isabelle

2016-01-01

Bone mineral density (BMD) is a putative marker for lifetime exposure to estrogen. Studies that have explored whether BMD is a determinant of mammographic density (MD) have observed inconsistent results. Therefore,we examined this potential association in a sample of women (n = 1,516) from the clinical sub-cohort in the Mexican teachers’ cohort (n = 115,315). We used multivariable linear regression to assess the association between quartiles of BMD and percent MD, as well as total dense and non-dense area of the breast, stratified by menopausal status. We also examined the associations by body mass index (BMI) (< 30 kg/m(2), ≥ 30 kg/m(2)). Overall, there was no association between BMD and MD among premenopausal women. However, when we stratified by BMI, there was a modest inverse association between BMD and percent MD (difference between extreme quartiles = -2.8, 95 % CI -5.9, 0.27, p trend = 0.04) among women with BMI < 30 kg/m(2), but a positive association among obese women (comparable difference = 5.1, 95 % CI 0.02, 10.1, p trend = 0.03;p interaction < 0.01). Among postmenopausal women, BMD and percent MD were positively associated after adjustment for BMI (p trend < 0.01). Postmenopausal women in the highest two quartiles of BMD had 4–5 % point higher percent MD compared to women in the lowest quartile. The association did not differ by BMI in postmenopausal women (p interaction = 0.76). Among obese premenopausal women as well as postmenopausal women, BMD was positively associated with percent MD. Among leaner premenopausal women, BMD and percent MD were modestly inversely associated. These findings support the hypothesis that cumulative exposure to estrogen (as measured by BMD) may influence MD.

A hospital based study of biochemical markers of bone turnovers & bone mineral density in north Indian women

PubMed Central

Kumar, Ashok; Devi, Salam Gyaneshwori; Mittal, Soniya; Shukla, Deepak Kumar; Sharma, Shashi

2013-01-01

Background & objectives: The osteoporotic risk for women increases soon after menopause. Bone turnover markers are known to be associated with bone loss and fracture risk. This study was aimed to assess bone turnover using bone markers and their correlation with bone mineral density (BMD) in pre- and post-menopausal women. Methods: A total of 255 healthy women (160 pre- and 95 post-menopausal) were enrolled. Serum bone alkaline phosphatase (sBAP) and serum N-terminal telopeptide of type I collagen (NTX) were measured to evaluate the bone formation and resorption, respectively. Bone mineral density was determined at lumbar spine (L2-L4) anteroposteriorly, femoral neck and Ward's triangle using Prodigy dual-energy X-ray absorptiometry (DXA) system. The comparison of years since menopause with respect to BMD and bone markers was also evaluated. Results: NTX and sBAP showed significant negative correlation with BMD of femur neck and Ward's triangle in postmenopausal women. BMD of all three sides were significant variables for NTX and BMD of femur neck and Ward's triangle for sBAP in postmenopausal women. BMD lumbar spine was a significant variable for sBAP in premenopausal women. The mean values of NTX increased significantly with increase in the duration of years since menopause. The BMD of all three sides decreased significantly with increase in the duration of years since menopause. Interpretation & conclusions: Serum NTX and sBAP were inversely correlated to BMD of femur neck and Ward's triangle in post-menopausal women. Simultaneous measurements of NTX and BMD in the north Indian women, suggest that bone resorption in women with low BMD remains high after menopause. PMID:23481051

Identification of a Linkage Disequilibrium Block in Chromosome 1q Associated With BMD in Premenopausal White Women

PubMed Central

Ichikawa, Shoji; Koller, Daniel L; Curry, Leah R; Lai, Dongbing; Xuei, Xiaoling; Pugh, Elizabeth W; Tsai, Ya-Yu; Doheny, Kimberly F; Edenberg, Howard J; Hui, Siu L; Foroud, Tatiana; Peacock, Munro; Econs, Michael J

2008-01-01

Osteoporosis is a complex disease with both genetic and environmental risk factors. A major determinant of osteoporotic fractures is peak BMD obtained during young adulthood. We previously reported linkage of chromosome 1q (LOD = 4.3) with variation in spinal areal BMD in healthy premenopausal white women. In this study, we used a two-stage genotyping approach to identify genes in the linked region that contributed to the variation of femoral neck and lumbar spine areal BMD. In the first stage, 654 SNPs across the linked region were genotyped in a sample of 1309 premenopausal white women. The most significant evidence of association for lumbar spine (p = 1.3 × 10−6) was found with rs1127091 in the GATAD2B gene. In the second stage, 52 SNPs around this candidate gene were genotyped in an expanded sample of 1692 white women. Significant evidence of association with spinal BMD (p < 10−5), and to a lesser extent with femoral neck BMD, was observed with eight SNPs within a single 230-kb linkage disequilibrium (LD) block. The most significant SNP (p = 3.4 × 10−7) accounted for >2.5% of the variation in spinal BMD in these women. The 230-kb LD block contains 11 genes, but because of the extensive LD, the specific gene(s) contributing to the variation in BMD could not be determined. In conclusion, the significant association between spinal BMD and SNPs in the 230-kb LD block in chromosome 1q indicates that genetic factor(s) in this block plays an important role in peak spinal BMD in healthy premenopausal white women. PMID:18505370

Defects in cortical microarchitecture among African-American women with type 2 diabetes

PubMed Central

Yu, Elaine W.; Putman, Melissa S.; Derrico, Nicolas; Abrishamanian-Garcia, Gabriela; Finkelstein, Joel S.; Bouxsein, Mary L.

2015-01-01

Introduction/Purpose Fracture risk is increased in patients with type 2 diabetes mellitus (DM2) despite normal areal bone mineral density (aBMD). DM2 is more common in African-Americans than in Caucasians. It is not known whether African-American women with DM2 have deficits in bone microstructure. Methods We measured aBMD at the spine and hip by DXA, and volumetric BMD (vBMD) and microarchitecture at the distal radius and tibia by HR-pQCT in 22 DM2 and 78 non-diabetic African-American women participating in the Study of Women Across the Nation (SWAN). We also measured fasting glucose and HOMA-IR. Results Age, weight, and aBMD at all sites were similar in both groups. At the radius, cortical porosity was 26% greater, while cortical vBMD and tissue mineral density were lower in women with DM2 than in controls. There were no differences in radius total vBMD or trabecular vBMD between groups. Despite inferior cortical bone properties at the radius, FEA-estimated failure load was similar between groups. Tibia vBMD and microarchitecture were also similar between groups. There were no significant associations between cortical parameters and duration of DM2 or HOMA-IR. However, among women with DM2, higher fasting glucose levels were associated with lower cortical vBMD (r=−0.54, p=0.018). Conclusions DM2 and higher fasting glucose are associated with unfavorable cortical bone microarchitecture at the distal radius in African-American women. These structural deficits may contribute to the increased fracture risk among women with DM2. Further our results suggest that hyperglycemia may be involved in mechanisms of skeletal fragility associated with DM2. PMID:25398431

Bone mineral density and mammographic density in Mexican women

PubMed Central

Moseson, Heidi; Rice, Megan S.; López-Ridaura, Ruy; Bertrand, Kimberly A.; Torres, Gabriela; Blanco, Margarita; Tamayo-Orozco, Juan Alfredo; Lajous, Martin; Romieu, Isabelle

2016-01-01

Background Bone mineral density (BMD) is a putative marker for lifetime exposure to estrogen. Studies that have explored whether BMD is a determinant of mammographic density (MD) have observed inconsistent results. Therefore, we examined this potential association in a sample of women (N=1,516) from the clinical sub-cohort in the Mexican Teachers’ Cohort (N=115,315). Methods We used multivariable linear regression to assess the association between quartiles of BMD and percent MD, as well as total dense and non-dense area of the breast, stratified by menopausal status. We also examined the associations by body mass index (BMI) (<30kg/m2,, ≥30kg/m2). Results Overall, there was no association between BMD and MD among premenopausal women. However, when we stratified by BMI, there was a modest inverse association between BMD and percent MD (difference between extreme quartiles= −2.8, 95%CI: −5.9, 0.27, p-trend=0.04) among women with BMI <30 kg/m2, but a positive association among obese women (comparable difference=5.1, 95%CI: 0.02, 10.1, p-trend=0.03; p-interaction<0.01). Among postmenopausal women, BMD and percent MD were positively associated after adjustment for BMI (p-trend<0.01). Postmenopausal women in the highest two quartiles of BMD had 4–5 percentage point higher percent MD compared to women in the lowest quartile. The association did not differ by BMI in postmenopausal women (p-interaction=0.76). Conclusion Among obese premenopausal women as well as postmenopausal women, BMD was positively associated with percent MD. Among leaner premenopausal women, BMD and percent MD were modestly inversely associated. These findings support the hypothesis that cumulative exposure to estrogen (as measured by BMD) may influence MD. PMID:26463740

Bone Strength and Arterial Stiffness Impact on Cardiovascular Mortality in a General Population

PubMed Central

Avramovska, Maja; Sikole, Aleksandar

2016-01-01

Osteoporosis and increased arterial stiffness independently have been found to be associated with higher cardiovascular events rates in the general population (GP). We examined 558 patients from GP by dual-energy X-ray absorptiometry (DXA) and pulse wave velocity (PWV) measurements at baseline, with 36-month follow-up period. DXA assessed bone mineral density of femoral neck (BMD FN) and lumbar spine (BMD LS). Carotid-femoral PWV was assessed by pulsed-Doppler. The aim of our study is to find correlation between bone strength and arterial stiffness and their impact on cardiovascular mortality in GP. The mean ± SD of BMD FN, BMD LS, and PWV was 0.852 ± 0.1432 g/cm2, 0.934 ± 0.1546 g/cm2, and 9.209 ± 1.9815 m/s. In multiple regression analysis we found BMD FN (βst = −6.0094, p < 0.0001), hypertension (βst = 1.7340, p < 0.0091), and diabetes (βst = 0.4595, p < 0.0046). With Cox-regression analysis, after 17 cardiovascular events, the significant covariates retained by the backward model were BMD FN (b = −2.4129, p = 0.015) and PWV (b = 0.2606, p = 0.0318). The cut-off values were PWV = 9.4 m/s, BMD FN = 0.783 g/cm2, and BMD LS = 0.992 g/cm2. The results for BMD FN and PWV hazard ratio risk were 1.116 and 1.297, respectively. BMD FN as a measure of bone strength and PWV as a measure of arterial stiffness are strong independent predictors of cardiovascular mortality in GP. PMID:27047700

Lean mass and fat mass predict bone mineral density in middle-aged individuals with noninsulin-requiring type 2 diabetes mellitus.

PubMed

Moseley, Kendall F; Dobrosielski, Devon A; Stewart, Kerry J; De Beur, Suzanne M Jan; Sellmeyer, Deborah E

2011-05-01

Despite high bone mineral density (BMD), persons with type 2 diabetes are at greater risk of fracture. The relationship between body composition and BMD in noninsulin-requiring diabetes is unclear. The aim was to examine how fat and lean mass independently affect the skeleton in this population. Subjects for this cross-sectional analysis were men (n = 78) and women (n = 56) aged 40-65 years (56 ± 6 years) with uncomplicated, noninsulin-requiring type 2 diabetes. Total body fat and lean mass, total body, hip and lumbar spine BMD were measured with dual energy X-ray absorptiometry. Magnetic resonance imaging measured total abdominal, visceral and subcutaneous (SQ) fat. Subjects had normal all-site BMD and were obese to overweight (body mass index 29-41 kg/m(2)) with controlled diabetes (HbA1c women 6·6 ± 1·2%, men 6·7 ± 1·6%). Lean mass was positively associated with total body, hip, femoral neck and hip BMD in both sexes. Fat mass, abdominal total and SQ fat were associated with total body and hip BMD in women. In multivariate analyses adjusted for sex, lean mass significantly predicted total, hip and femoral neck BMD in men and women. In unadjusted models, lean mass continued to predict BMD at these sites in men; fat mass also predicted total body, femoral and hip BMD in women. In men and women with uncomplicated, noninsulin-requiring diabetes, lean mass significantly predicted BMD at the total body, hip and femoral neck. Further research is needed to determine whether acquisition or maintenance of lean mass in T2DM can prevent hip fracture in this at-risk population. © 2011 Blackwell Publishing Ltd.

Influence of number of deliveries and total breast-feeding time on bone mineral density in premenopausal and young postmenopausal women.

PubMed

Tsvetov, Gloria; Levy, Sigal; Benbassat, Carlos; Shraga-Slutzky, Ilana; Hirsch, Dania

2014-03-01

Pregnancy and lactation have been associated with decline in bone mineral density (BMD). It is not clear if there is a full recovery of BMD to baseline. This study sought to determine if pregnancy or breast-feeding or both have a cumulative effect on BMD in premenopausal and early postmenopausal women. We performed single-center cohort analysis. Five hundred women aged 35-55 years underwent routine BMD screening from February to July 2011 at a tertiary medical center. Patients were questioned about number of total full-term deliveries and duration of breast-feeding and completed a background questionnaire on menarche and menopause, smoking, dairy product consumption, and weekly physical exercise. Weight and height were measured. Dual-energy X-ray absorptiometry was used to measure spinal, dual femoral neck, and total hip BMD. Associations between background characteristics and BMD values were analyzed. Sixty percent of the women were premenopausal. Mean number of deliveries was 2.5 and mean duration of breast-feeding was 9.12 months. On univariate analysis, BMD values were negatively correlated with patient age (p=0.006) and number of births (p=0.013), and positively correlated with body mass index (p<0.001). On multiple (adjusted) logistic regression analysis, prolonged breast-feeding duration, but not number of deliveries, was significantly correlated to a low BMD (p=0.008). An effect was noted only in postmenopausal women. The spine was the most common site of BMD decrease. Prolonged breast-feeding may have a deleterious long-term effect on BMD and may contribute to increased risk of osteoporosis later in life. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The scientists' opposition to SDI: How political views affect technical analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tait, G.E.

1989-01-01

This study examines the scientists' opposition to President Reagan's Strategic Defense Initiative (1983-1989) with a focus on the relationship between the scientists' political and strategic opposition to ballistic missile defenses (BMD) and their technical doubts about BMD technologies. The study begins with a review of the scientists' increased influence in United State's national security decision making because of the development of atomic weapons. The study then examines the scientists' role in developing and promoting a theory of arms control based upon mutual societal vulnerability. Because of this theory, a large segment of the American scientific community came to believe thatmore » the development of ballistic missile defenses would destabilize the strategic balance and therefore took the lead in arguing against BMD deployments. These background chapters conclude with an analysis of the scientists' involvement in the political campaign to stop the proposed Sentinel and Safeguard Anti-Ballistic Missile defense. The study then turns to the contemporary scientific opposition to BMD deployments and the SDI research program. After examining the polls and petitions that identify the scientists opposed to SDI, the study analyzes the tactics that three scientists use in their political effort to prevent BMD deployments. Next, an examination of the political and strategic assumptions behind the scientists' opposition to BMD reveals that a belief in the arms control process and deterrence by punishment, especially Assured Destruction deterrence, with a fear of an action-reaction arms race inspires much of the contemporary opposition to BMD. Finally, the scientists' technical doubts about BMD technologies are analyzed through the prism of peer critique. These critiques show that the scientists opposed to BMD deployments us pessimistic and unrealistic assumptions to skew their technical analysis of BMD technologies.« less

Depression, antidepressants, and bone mineral density in a population-based cohort.

PubMed

Mezuk, Briana; Eaton, William W; Golden, Sherita Hill; Wand, Gary; Lee, Hochang Benjamin

2008-12-01

It is uncertain whether depression and antidepressant use are associated with decreased bone mineral density (BMD) and whether these relationships differ for men and women. The study used a case-cohort design within the Baltimore Epidemiologic Catchment Area Study, a population-based sample of adults that recently completed its 23-year follow-up. Depression was measured at four time points during the follow-up period by the Diagnostic Interview Schedule. Lower spine BMD was measured at the fourth wave by dual-energy x-ray absorptiometry. The association of BMD with lifetime history of depression and antidepressant medication use was studied using linear regression with bootstrap standard errors. A history of depression was associated with lower spine BMD after controlling for age, sex, race, calcium intake, alcohol use, smoking status, level of physical activity, percent body fat, and antidepressant medication use (-0.140 g/cm(2); p <.002). After controlling for depression, antidepressant medication use was associated with decreased BMD in women but not in men (-0.218 g/cm(2); p <.016). A history of depression predicted decreased lumbar spine BMD in men and women, and antidepressant use predicted decreased BMD in women even after controlling for depression. The magnitude of the effect of depression on BMD was approximately equivalent to 1 standard deviation in BMD and was therefore clinically significant. Providers should be aware of the physiologic consequences of depression as well as the possible risks to bone strength associated with antidepressant use in older patients.

Osteoporosis risk factors and association with somatotypes in males.

PubMed

Saitoglu, Mahmut; Ardicoglu, Ozge; Ozgocmen, Salih; Kamanli, Ayhan; Kaya, Arzu

2007-10-01

Osteoporosis is a systemic and metabolic skeletal disease characterized by reduced bone mass, changes in microarchitecture, and consequential increased fracture risk. Previous reports described a relationship between bone content with fat mass and lean body mass. In this study, we assessed osteoporosis risk factors and the association with somatotypes in males aged 45-65 years. Standard axial spine and proximal femur bone mineral density (BMD) were measured using dual x-ray (DXA) absorptiometry in 70 healthy men. Heath-Carter procedure was followed to assess individual's somatotype. All body types were grouped as endomorphy, mesomorphy, and ectomorphy. Moderate to weak correlations were found between lumbar BMD with endomorphy and mesomorphy. Negative correlation was found between lumbar BMD and ectomorphy. Total femur BMD correlated positively with endomorphy and mesomorphy and negatively correlated with ectomorphy. Body mass index correlated weakly with lumbar, femur neck, and total femur BMD. Multiple regression analysis revealed that endomorphy was significantly related to BMD measurements at lumbar spine (standardized coefficient, SC = 0.51, p = 0.001), femur neck (SC = 0.52, p = 0.001), and total femur BMD (SC = 0.41, p = 0.01). Lumbar BMD and age, hand grip strength, smoking, tea and coffee consumption, calorie expenditure, calcium intake, PTH, albumin, total protein, sex hormone-binding globulin, and testosterone were not significantly correlated. Endomorphy seems related to high BMD values at the lumbar spine and the proximal femur in middle-aged men. Somatotype together with daily calorie expenditure may be taken into account when assessing risk factors for male osteoporosis.

Gene-dietary fat interaction, bone mineral density and bone speed of sound in Children: a twin study in China

PubMed Central

Huang, Tao; Liu, Huijuan; Zhao, Wei; Li, Ji; Wang, Youfa

2015-01-01

Scope Dietary fat correlates with bone mineral density (BMD). We tested the association between fat intake and BMD, and tested if fat intake modified the degree of genetic influence on BMD and bone speed of sound (SOS). Methods and results We included 622 twins aged 7–15 y from South China. Data on anthropometry, dietary intake, BMD, and SOS were collected. Quantitative genetic analyses of structural equation models were fit using the Mx statistical package. The within-pair intra-class correlations (ICC) for BMD in DZ twins were nearly half of that for MZ twins (ICC=0.39 vs 0.70). The heritability of BMD and SOS were 71% and 79%. Phenotypic correlation between fat intake and SOS was significant (r=−0.19, p=0.04). SOS was negatively correlated with fat intake in boys (r=−0.11, p=0.05), but not in girls. Full Cholesky decomposition models showed SOS has a strong genetic correlation with fat intake (rA =−0.88, 95% CI=−0.94, 0.01); the environmental correlation between fat intake and SOS was weak (rE =−0.04, 95% CI=−0.20, 0.13). Fat intake modified the additive genetic effects on BMD. Conclusion Genetic factors explained 71% and 79% of individual variance in BMD and SOS, respectively. Low fat intake counteracts genetic predisposition to low BMD. PMID:25546604

Replication of Previous Genome-wide Association Studies of Bone Mineral Density in Premenopausal American Women

PubMed Central

Ichikawa, Shoji; Koller, Daniel L; Padgett, Leah R; Lai, Dongbing; Hui, Siu L; Peacock, Munro; Foroud, Tatiana; Econs, Michael J

2010-01-01

Bone mineral density (BMD) achieved during young adulthood (peak BMD) is one of the major determinants of osteoporotic fracture in later life. Genetic variants associated with BMD have been identified by three recent genome-wide association studies. The most significant single-nucleotide polymorphisms (SNPs) from these studies were genotyped to test whether they were associated with peak BMD in premenopausal American women. Femoral neck and lumbar spine BMD were determined by dual-energy X-ray absorptiometry in two groups of premenopausal women: 1524 white women and 512 black women. In premenopausal white women, two SNPs in the C6orf97/ESR1 region were significantly associated with BMD (p < 4.8 × 10−4), with suggestive evidence for CTNNBL1 and LRP5 (p < .01). Evidence of association with one of the two SNPs in the C6orf97/ESR1 region also was observed in premenopausal black women. Furthermore, SNPs in SP7 and a chromosome 4 intergenic region showed suggestive association with BMD in black women. Detailed analyses of additional SNPs in the C6orf97/ESR1 region revealed multiple genomic blocks independently associated with femoral neck and lumbar spine BMD. Findings in the three published genome-wide association studies were replicated in independent samples of premenopausal American women, suggesting that genetic variants in these genes or regions contribute to peak BMD in healthy women in various populations. © 2010 American Society for Bone and Mineral Research. PMID:20200978

Bone Density and Cortical Structure after Pediatric Renal Transplantation

PubMed Central

Terpstra, Anniek M.; Kalkwarf, Heidi J.; Shults, Justine; Zemel, Babette S.; Wetzsteon, Rachel J.; Foster, Bethany J.; Strife, C. Frederic; Foerster, Debbie L.

2012-01-01

The impact of renal transplantation on trabecular and cortical bone mineral density (BMD) and cortical structure is unknown. We obtained quantitative computed tomography scans of the tibia in pediatric renal transplant recipients at transplantation and 3, 6, and 12 months; 58 recipients completed at least two visits. We used more than 700 reference participants to generate Z-scores for trabecular BMD, cortical BMD, section modulus (a summary measure of cortical dimensions and strength), and muscle and fat area. At baseline, compared with reference participants, renal transplant recipients had significantly lower mean section modulus and muscle area; trabecular BMD was significantly greater than reference participants only in transplant recipients younger than 13 years. After transplantation, trabecular BMD decreased significantly in association with greater glucocorticoid exposure. Cortical BMD increased significantly in association with greater glucocorticoid exposure and greater decreases in parathyroid hormone levels. Muscle and fat area both increased significantly, but section modulus did not improve. At 12 months, transplantation associated with significantly lower section modulus and greater fat area compared with reference participants. Muscle area and cortical BMD did not differ significantly between transplant recipients and reference participants. Trabecular BMD was no longer significantly elevated in younger recipients and was low in older recipients. Pediatric renal transplant associated with persistent deficits in section modulus, despite recovery of muscle, and low trabecular BMD in older recipients. Future studies should determine the implications of these data on fracture risk and identify strategies to improve bone density and structure. PMID:22282589

Preadipocyte Factor-1 Levels Are Higher in Women with Hypothalamic Amenorrhea and Are Associated with Bone Mineral Content and Bone Mineral Density through a Mechanism Independent of Leptin

PubMed Central

Aronis, Konstantinos N.; Kilim, Holly; Chamberland, John P.; Breggia, Anne; Rosen, Clifford

2011-01-01

Context: Preadipocyte factor 1 (pref-1) is increased in anorexia nervosa and is associated negatively with bone mineral density (BMD). No previous studies exist on pref-1 in women with exercise-induced hypothalamic amenorrhea (HA), which similar to anorexia nervosa, is an energy-deficiency state associated with hypoleptinemia. Objective: Our objective was to evaluate whether pref-1 levels are also elevated and associated with low BMD and to assess whether leptin regulates pref-1 levels in women with HA. Design: Study 1 was a double-blinded, placebo-controlled randomized clinical trial of metreleptin administration in women with HA. Study 2 was an open-label study of metreleptin administration in low physiological, supraphysiological, and pharmacological doses in healthy women volunteers. Setting and Patients: At Beth Israel Deaconess Medical Center, 20 women with HA and leptin levels higher than 5 ng/ml and nine healthy control women participated in study 1, and five healthy women participated in study 2. Intervention: For study 1, 20 HA subjects were randomized to receive either 0.08 mg/kg metreleptin (n = 11) or placebo (n = 9). For study 2, five healthy subjects received 0.01, 0.1, and 0.3 mg/kg metreleptin in both fed and fasting conditions for 1 and 3 d, respectively. Main Outcome Measures: Circulating pref-1 and leptin levels were measured. Results: Pref-1 was significantly higher in HA subjects vs. controls (P = 0.035) and negatively associated with BMD (ρ = −0.38; P < 0.01) and bone mineral content (ρ = −0.32; P < 0.05). Metreleptin administration did not alter pref-1 levels in any study reported herein. Conclusions: Pref-1 is higher in HA subjects than controls. Metreleptin administration at low physiological, supraphysiological, and pharmacological doses does not affect pref-1 levels, suggesting that hypoleptinemia is not responsible for higher pref-1 levels and that leptin does not regulate pref-1. PMID:21795455

Modification and benchmarking of SKYSHINE-III for use with ISFSI cask arrays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hertel, N.E.; Napolitano, D.G.

1997-12-01

Dry cask storage arrays are becoming more and more common at nuclear power plants in the United States. Title 10 of the Code of Federal Regulations, Part 72, limits doses at the controlled area boundary of these independent spent-fuel storage installations (ISFSI) to 0.25 mSv (25 mrem)/yr. The minimum controlled area boundaries of such a facility are determined by cask array dose calculations, which include direct radiation and radiation scattered by the atmosphere, also known as skyshine. NAC International (NAC) uses SKYSHINE-III to calculate the gamma-ray and neutron dose rates as a function of distance from ISFSI arrays. In thismore » paper, we present modifications to the SKYSHINE-III that more explicitly model cask arrays. In addition, we have benchmarked the radiation transport methods used in SKYSHINE-III against {sup 60}Co gamma-ray experiments and MCNP neutron calculations.« less

Bone mineral density and growth in children with coeliac disease on a gluten free-diet.

PubMed

Tuna Kırsaçlıoğlu, Ceyda; Kuloğlu, Zarife; Tanca, Aydan; Küçük, Nuriye Özlem; Aycan, Zehra; Öcal, Gönül; Ensari, Arzu; Kalaycı, Ayhan Gazi; Girgin, Nurten

2016-12-20

To evaluate changes in growth and bone metabolism during consumption of a gluten-free diet (GFD) in children with coeliac disease (CD). Thirty-seven children with CD (mean age of 8.8 ± 4.6 years, 21 girls) were enrolled. Anthropometric measurements, bone mineral density (BMD) in lumbar 2-4 vertebrae, and serum alkaline phosphatase, calcium, and phosphorus levels at diagnosis and at follow-up were recorded. The mean follow-up period was 3.5 ± 2.3 years. The BMD of patients was significantly lower than that of control subjects at the time of diagnosis but not after 1 year of the GFD. Incidence of low BMD with respect to z-scores for chronological age (CA) was significantly higher than z-scores for height age (HA) (P = 0.006). At the first year of GFD, BMD, BMD z-score, height-for-age z-scores, and weight-for-age z-scores were significantly increased compared with the baseline, but not after 1 year of the GFD. In CD, the first year of GFD is important in weight gain, linear growth, and improvement of BMD. A considerable relation of low BMD in children with CD, with respect to z-scores for CA, may be a result of misinterpretation of low BMD due to short stature.

Association of Insulin Resistance with Bone Strength and Bone Turnover in Menopausal Chinese-Singaporean Women without Diabetes.

PubMed

Kalimeri, Maria; Leek, Francesca; Wang, Nan Xin; Koh, Huann Rong; Roy, Nicole C; Cameron-Smith, David; Kruger, Marlena C; Henry, Christiani Jeyakumar; Totman, John J

2018-04-30

Insulin resistance (IR) is accompanied by increased areal or volumetric bone mineral density (aBMD or vBMD), but also higher fracture risk. Meanwhile, imbalances in bone health biomarkers affect insulin production. This study investigates the effect of IR on proximal femur and lumbar spine BMD, femoral neck bending, compressive and impact strength indices (Composite Strength Indices) and circulating levels of parathyroid hormone (PTH), C-telopeptide of Type I collagen (CTx-1) and 25(OH) Vitamin D₃, in a cohort of 97 healthy, non-obese, menopausal Chinese-Singaporean women. Lumbar spine aBMD was inversely associated with IR and dependent on lean body mass (LBM) and age. No such associations were found for vBMD of the third lumbar vertebra, aBMD and vBMD of the proximal femur, or circulating levels of PTH, CTx-1 and 25(OH) Vitamin D₃. Composite Strength Indices were inversely associated with IR and independent of LBM, but after adjusting for fat mass and age, this association remained valid only for the impact strength index. Composite Strength Indices were significantly lower in participants with a high degree of IR. Our findings on IR and Composite Strength Indices relationships were in agreement with previous studies on different cohorts, but those on IR and BMD associations were not.

Bone mineral density in girls with functional hypothalamic amenorrhea subjected to estroprogestagen treatment--a 4-year prospective study.

PubMed

Sowińska-Przepiera, Elżbieta; Chełstowski, Kornel; Friebe, Zbigniew; Syrenicz, Anhelli

2011-11-01

The aim of this study was to evaluate the effects of 4-year estroprogestagen therapy (EP) on the bone mineral density (BMD) of 16- to 17-year-old girls with functional hypothalamic amenorrhea (FHA, n = 78). Baseline values of hormonal parameters, bone fraction of alkaline phosphatase (BALP), and cross-linked n-telopeptide of type I collagen (Ntx) were taken along with BMD measurements. Follow-up measurements of laboratory parameters were performed after 6 months of EP treatment. BMD was measured on a yearly basis. Six-month treatment resulted in a marked increase in estradiol levels and a significant decrease in BALP and Ntx. The relative increase in BMD was highest after the second year of treatment. Based on the dynamics of BMD changes during the first year of treatment, we identified a subgroup with no or insignificant reactions to the treatment. It was characterized by significantly higher baseline BMD and markedly lower baseline Ntx compared to the patients who responded to 1-year therapy well or extremely well. Further follow-up proved, however, that this subgroup did not differ significantly in terms of the long-term prognosis for BMD normalization. In conclusion, this study showed that EP therapy is effective in the treatment of BMD disorders associated with FHA.

Association of Adenylate Cyclase 10 (ADCY10) Polymorphisms and Bone Mineral Density in Healthy Adults

PubMed Central

Ichikawa, Shoji; Koller, Daniel L.; Curry, Leah R.; Lai, Dongbing; Xuei, Xiaoling; Edenberg, Howard J.; Hui, Siu L.; Peacock, Munro; Foroud, Tatiana; Econs, Michael J.

2010-01-01

Phenotypic variation in bone mineral density (BMD) among healthy adults is influenced by both genetic and environmental factors. Genetic sequence variations in the adenylate cyclase 10 (ADCY10) gene, which is also called soluble adenylate cyclase, have previously been reported to be associated with low spinal BMD in hypercalciuric patients. Since ADCY10 is located in the region linked to spinal BMD in our previous linkage analysis, we tested whether polymorphisms in this gene are also associated with normal BMD variation in healthy adults. Sixteen single nucleotide polymorphisms (SNPs) distributed throughout ADCY10 were genotyped in two healthy groups of American whites: 1,692 premenopausal women and 715 men. Statistical analyses were performed in the two groups to test for association between these SNPs and femoral neck and lumbar spine areal BMD. We observed significant evidence of association (p<0.01) with one SNP each in men and women. Genotypes at these SNPs accounted for less than 1% of hip BMD variation in men, but 1.5% of spinal BMD in women. However, adjacent SNPs did not corroborate the association in either males or females. In conclusion, we found a modest association between an ADCY10 polymorphism and spinal areal BMD in premenopausal white women. PMID:19093065

Bone mineral density and insulin-like growth factor-1 in children with spastic cerebral palsy.

PubMed

Nazif, H; Shatla, R; Elsayed, R; Tawfik, E; Osman, N; Korra, S; Ibrahim, A

2017-04-01

Children with cerebral palsy (CP) have significant decrease linear growth rate and low bone mineral density (BMD). This study is to evaluate BMD in children with CP and its relation to the levels of insulin-like growth factor-1 (IGF-1). This cross-sectional study was carried out on 58 children suffering from spastic CP with the age range 4-12 years compared to 19 controls. All assessed by dual energy x-ray absorptiometry (DXA) to measure BMD, serum level of IGF-1, and serum vitamin D. The patients were classified according to their GMFCS. Fractures were reported in seven (12.1%) of cases. Our study demonstrated that, IGF-1 level and BMD decrease in correlation with the severity of CP. IGF-1correlates positively with serum vitamin D, BMI, and BMD. CP children with severe GMFCS level or who use anticonvulsive drugs are at a high risk for low BMD and low levels of IGF-1. Both BMD and IGF-1 were significantly in low children with spastic CP; IGF-1 negatively correlates with the severity of osteopenia in children with spastic. Children with CP who are not independently ambulant or with severe GMFCS level or who use anticonvulsive drugs are at a high risk for developing low BMD.

Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci

PubMed Central

Thompson, Wesley K.; McEvoy, Linda K.; Schork, Andrew J.; Zuber, Verena; LeBlanc, Marissa; Bettella, Francesco; Mills, Ian G.; Desikan, Rahul S.; Djurovic, Srdjan; Gautvik, Kaare M.; Dale, Anders M.; Andreassen, Ole A.

2015-01-01

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity. PMID:26695485

Lack of Association of Bone Morphogenetic Protein 2 Gene Haplotypes with Bone Mineral Density, Bone Loss, or Risk of Fractures in Men

PubMed Central

Varanasi, Satya S.; Tuck, Stephen P.; Mastana, Sarabjit S.; Dennison, Elaine; Cooper, Cyrus; Vila, Josephine; Francis, Roger M.; Datta, Harish K.

2011-01-01

Introduction. The association of bone morphogenetic protein 2 (BMP2) with BMD and risk of fracture was suggested by a recent linkage study, but subsequent studies have been contradictory. We report the results of a study of the relationship between BMP2 genotypes and BMD, annual change in BMD, and risk of fracture in male subjects. Materials and Methods. We tested three single-nucleotide polymorphisms (SNPs) across the BMP2 gene, including Ser37Ala SNP, in 342 Caucasian Englishmen, comprising 224 control and 118 osteoporotic subjects. Results. BMP2 SNP1 (Ser37Ala) genotypes were found to have similar low frequency in control subjects and men with osteoporosis. The major informative polymorphism, BMP2 SNP3 (Arg190Ser), showed no statistically significant association with weight, height, BMD, change in BMD at hip or lumbar spine, and risk of fracture. Conclusion. There were no genotypic or haplotypic effects of the BMP2 candidate gene on BMD, change in BMD, or fracture risk identified in this cohort. PMID:22013543

TH-A-19A-04: Latent Uncertainties and Performance of a GPU-Implemented Pre-Calculated Track Monte Carlo Method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Renaud, M; Seuntjens, J; Roberge, D

Purpose: Assessing the performance and uncertainty of a pre-calculated Monte Carlo (PMC) algorithm for proton and electron transport running on graphics processing units (GPU). While PMC methods have been described in the past, an explicit quantification of the latent uncertainty arising from recycling a limited number of tracks in the pre-generated track bank is missing from the literature. With a proper uncertainty analysis, an optimal pre-generated track bank size can be selected for a desired dose calculation uncertainty. Methods: Particle tracks were pre-generated for electrons and protons using EGSnrc and GEANT4, respectively. The PMC algorithm for track transport was implementedmore » on the CUDA programming framework. GPU-PMC dose distributions were compared to benchmark dose distributions simulated using general-purpose MC codes in the same conditions. A latent uncertainty analysis was performed by comparing GPUPMC dose values to a “ground truth” benchmark while varying the track bank size and primary particle histories. Results: GPU-PMC dose distributions and benchmark doses were within 1% of each other in voxels with dose greater than 50% of Dmax. In proton calculations, a submillimeter distance-to-agreement error was observed at the Bragg Peak. Latent uncertainty followed a Poisson distribution with the number of tracks per energy (TPE) and a track bank of 20,000 TPE produced a latent uncertainty of approximately 1%. Efficiency analysis showed a 937× and 508× gain over a single processor core running DOSXYZnrc for 16 MeV electrons in water and bone, respectively. Conclusion: The GPU-PMC method can calculate dose distributions for electrons and protons to a statistical uncertainty below 1%. The track bank size necessary to achieve an optimal efficiency can be tuned based on the desired uncertainty. Coupled with a model to calculate dose contributions from uncharged particles, GPU-PMC is a candidate for inverse planning of modulated electron radiotherapy and scanned proton beams. This work was supported in part by FRSQ-MSSS (Grant No. 22090), NSERC RG (Grant No. 432290) and CIHR MOP (Grant No. MOP-211360)« less

Latent uncertainties of the precalculated track Monte Carlo method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Renaud, Marc-André; Seuntjens, Jan; Roberge, David

Purpose: While significant progress has been made in speeding up Monte Carlo (MC) dose calculation methods, they remain too time-consuming for the purpose of inverse planning. To achieve clinically usable calculation speeds, a precalculated Monte Carlo (PMC) algorithm for proton and electron transport was developed to run on graphics processing units (GPUs). The algorithm utilizes pregenerated particle track data from conventional MC codes for different materials such as water, bone, and lung to produce dose distributions in voxelized phantoms. While PMC methods have been described in the past, an explicit quantification of the latent uncertainty arising from the limited numbermore » of unique tracks in the pregenerated track bank is missing from the paper. With a proper uncertainty analysis, an optimal number of tracks in the pregenerated track bank can be selected for a desired dose calculation uncertainty. Methods: Particle tracks were pregenerated for electrons and protons using EGSnrc and GEANT4 and saved in a database. The PMC algorithm for track selection, rotation, and transport was implemented on the Compute Unified Device Architecture (CUDA) 4.0 programming framework. PMC dose distributions were calculated in a variety of media and compared to benchmark dose distributions simulated from the corresponding general-purpose MC codes in the same conditions. A latent uncertainty metric was defined and analysis was performed by varying the pregenerated track bank size and the number of simulated primary particle histories and comparing dose values to a “ground truth” benchmark dose distribution calculated to 0.04% average uncertainty in voxels with dose greater than 20% of D{sub max}. Efficiency metrics were calculated against benchmark MC codes on a single CPU core with no variance reduction. Results: Dose distributions generated using PMC and benchmark MC codes were compared and found to be within 2% of each other in voxels with dose values greater than 20% of the maximum dose. In proton calculations, a small (≤1 mm) distance-to-agreement error was observed at the Bragg peak. Latent uncertainty was characterized for electrons and found to follow a Poisson distribution with the number of unique tracks per energy. A track bank of 12 energies and 60000 unique tracks per pregenerated energy in water had a size of 2.4 GB and achieved a latent uncertainty of approximately 1% at an optimal efficiency gain over DOSXYZnrc. Larger track banks produced a lower latent uncertainty at the cost of increased memory consumption. Using an NVIDIA GTX 590, efficiency analysis showed a 807 × efficiency increase over DOSXYZnrc for 16 MeV electrons in water and 508 × for 16 MeV electrons in bone. Conclusions: The PMC method can calculate dose distributions for electrons and protons to a statistical uncertainty of 1% with a large efficiency gain over conventional MC codes. Before performing clinical dose calculations, models to calculate dose contributions from uncharged particles must be implemented. Following the successful implementation of these models, the PMC method will be evaluated as a candidate for inverse planning of modulated electron radiation therapy and scanned proton beams.« less

Latent uncertainties of the precalculated track Monte Carlo method.

PubMed

Renaud, Marc-André; Roberge, David; Seuntjens, Jan

2015-01-01

While significant progress has been made in speeding up Monte Carlo (MC) dose calculation methods, they remain too time-consuming for the purpose of inverse planning. To achieve clinically usable calculation speeds, a precalculated Monte Carlo (PMC) algorithm for proton and electron transport was developed to run on graphics processing units (GPUs). The algorithm utilizes pregenerated particle track data from conventional MC codes for different materials such as water, bone, and lung to produce dose distributions in voxelized phantoms. While PMC methods have been described in the past, an explicit quantification of the latent uncertainty arising from the limited number of unique tracks in the pregenerated track bank is missing from the paper. With a proper uncertainty analysis, an optimal number of tracks in the pregenerated track bank can be selected for a desired dose calculation uncertainty. Particle tracks were pregenerated for electrons and protons using EGSnrc and geant4 and saved in a database. The PMC algorithm for track selection, rotation, and transport was implemented on the Compute Unified Device Architecture (cuda) 4.0 programming framework. PMC dose distributions were calculated in a variety of media and compared to benchmark dose distributions simulated from the corresponding general-purpose MC codes in the same conditions. A latent uncertainty metric was defined and analysis was performed by varying the pregenerated track bank size and the number of simulated primary particle histories and comparing dose values to a "ground truth" benchmark dose distribution calculated to 0.04% average uncertainty in voxels with dose greater than 20% of Dmax. Efficiency metrics were calculated against benchmark MC codes on a single CPU core with no variance reduction. Dose distributions generated using PMC and benchmark MC codes were compared and found to be within 2% of each other in voxels with dose values greater than 20% of the maximum dose. In proton calculations, a small (≤ 1 mm) distance-to-agreement error was observed at the Bragg peak. Latent uncertainty was characterized for electrons and found to follow a Poisson distribution with the number of unique tracks per energy. A track bank of 12 energies and 60000 unique tracks per pregenerated energy in water had a size of 2.4 GB and achieved a latent uncertainty of approximately 1% at an optimal efficiency gain over DOSXYZnrc. Larger track banks produced a lower latent uncertainty at the cost of increased memory consumption. Using an NVIDIA GTX 590, efficiency analysis showed a 807 × efficiency increase over DOSXYZnrc for 16 MeV electrons in water and 508 × for 16 MeV electrons in bone. The PMC method can calculate dose distributions for electrons and protons to a statistical uncertainty of 1% with a large efficiency gain over conventional MC codes. Before performing clinical dose calculations, models to calculate dose contributions from uncharged particles must be implemented. Following the successful implementation of these models, the PMC method will be evaluated as a candidate for inverse planning of modulated electron radiation therapy and scanned proton beams.

Adequate calcium intake during long periods improves bone mineral density in healthy children. Data from the Childhood Obesity Project.

PubMed

Closa-Monasterolo, Ricardo; Zaragoza-Jordana, Marta; Ferré, Natàlia; Luque, Veronica; Grote, Veit; Koletzko, Berthold; Verduci, Elvira; Vecchi, Fiammetta; Escribano, Joaquin

2018-06-01

Bone mineralization can be influenced by genetic factors, hormonal status, nutrition, physical activity and body composition. The association of higher calcium (Ca) intake or Ca supplementation with better bone mineral density (BMD) remains controversial. Furthermore, it has been speculated that maintaining long-term adequate Ca intake rather than having a brief supplementation period is more effective. The aim of the study was to prospectively analyse the influence of adequate Ca intake on BMD at 7 years of age in European children. Data from the Childhood Obesity Project were analysed in a prospective longitudinal cohort trial. Dietary intake was recorded using 3-day food records at 4, 5 and 6 years of age. The probability of adequate intake (PA) of Ca was calculated following the American Institute of Medicine guidelines for individual assessments, with FAO, WHO and United Nations University joint expert consultation dietary recommendations. Children were categorised as having high Ca PA (PA >95%) or not (PA <95%). At 7 years, whole body (WB) and lumbar spine (LS) BMD were measured in the Spanish subsample by dual-energy x-ray absorptiometry. Internal BMD z-scores were calculated; BMD below -1 z-score were considered to indicate osteopenia, and BMD z-scores below -2, "low bone mineral density for age". BMD was measured in 179 children. Ca intake at 6 years was positively correlated with LS BMD at 7 years (R = 0.205, p = 0.030). A Ca increase of 100 mg/day explained 19.4% (p = 0.011) of the LS BMD z-score variation, modifying it by 0.089 (0.021, 0.157) units. Children with Ca PA >95% at 5 and 6 or from 4 to 6 years of age showed higher BMD z-scores at the LS and WB levels than children with Ca PA <95% (p < 0.001 and p < 0.05 for LS and WB BMD, respectively). Ca PA >95% maintained over 2 years explained 26.3% of the LS BMD z-score variation (p < 0.001), increasing it by 0.669 (0.202, 1.137). PA >95% maintained over 3 years explained 24.9% of the LS BMD z-score variation, increasing it by 0.773 (0.282, 1.264). The effects of Ca adequacy on WB BMD were similar. Children with PA >95% over 2 years had an Odds ratio of 13.84 and 12 for osteopenia at the LS and WB levels, respectively (p = 0.001). Long periods of adequate Ca intake in childhood increase BMD and reduce osteopenia risk. The Childhood Obesity Project clinical trial (CHOP) was registered at clinicaltrials.gov as NCT00338689. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Meta-Analysis of Genome-Wide Scans Provides Evidence for Sex- and Site-Specific Regulation of Bone Mass

PubMed Central

Sham, Pak C; Zintzaras, Elias; Lewis, Cathryn M; Deng, Hong-Wen; Econs, Michael J; Karasik, David; Devoto, Marcella; Kammerer, Candace M; Spector, Tim; Andrew, Toby; Cupples, L Adrienne; Duncan, Emma L; Foroud, Tatiana; Kiel, Douglas P; Koller, Daniel; Langdahl, Bente; Mitchell, Braxton D; Peacock, Munro; Recker, Robert; Shen, Hui; Sol-Church, Katia; Spotila, Loretta D; Uitterlinden, Andre G; Wilson, Scott G; Kung, Annie WC; Ralston, Stuart H

2014-01-01

Several genome-wide scans have been performed to detect loci that regulate BMD, but these have yielded inconsistent results, with limited replication of linkage peaks in different studies. In an effort to improve statistical power for detection of these loci, we performed a meta-analysis of genome-wide scans in which spine or hip BMD were studied. Evidence was gained to suggest that several chromosomal loci regulate BMD in a site-specific and sex-specific manner. Introduction BMD is a heritable trait and an important predictor of osteoporotic fracture risk. Several genome-wide scans have been performed in an attempt to detect loci that regulate BMD, but there has been limited replication of linkage peaks between studies. In an attempt to resolve these inconsistencies, we conducted a collaborative meta-analysis of genome-wide linkage scans in which femoral neck BMD (FN-BMD) or lumbar spine BMD (LS-BMD) had been studied. Materials and Methods Data were accumulated from nine genome-wide scans involving 11,842 subjects. Data were analyzed separately for LS-BMD and FN-BMD and by sex. For each study, genomic bins of 30 cM were defined and ranked according to the maximum LOD score they contained. While various densitometers were used in different studies, the ranking approach that we used means that the results are not confounded by the fact that different measurement devices were used. Significance for high average rank and heterogeneity was obtained through Monte Carlo testing. Results For LS-BMD, the quantitative trait locus (QTL) with greatest significance was on chromosome 1p13.3-q23.3 (p = 0.004), but this exhibited high heterogeneity and the effect was specific for women. Other significant LS-BMD QTLs were on chromosomes 12q24.31-qter, 3p25.3-p22.1, 11p12-q13.3, and 1q32-q42.3, including one on 18p11-q12.3 that had not been detected by individual studies. For FN-BMD, the strongest QTL was on chromosome 9q31.1-q33.3 (p = 0.002). Other significant QTLs were identified on chromosomes 17p12-q21.33, 14q13.1-q24.1, 9q21.32-q31.1, and 5q14.3-q23.2. There was no correlation in average ranks of bins between men and women and the loci that regulated BMD in men and women and at different sites were largely distinct. Conclusions This large-scale meta-analysis provided evidence for replication of several QTLs identified in previous studies and also identified a QTL on chromosome 18p11-q12.3, which had not been detected by individual studies. However, despite the large sample size, none of the individual loci identified reached genome-wide significance. PMID:17228994

Utilization of DXA Bone Mineral Densitometry in Ontario

PubMed Central

2006-01-01

Executive Summary Issue Systematic reviews and analyses of administrative data were performed to determine the appropriate use of bone mineral density (BMD) assessments using dual energy x-ray absorptiometry (DXA), and the associated trends in wrist and hip fractures in Ontario. Background Dual Energy X-ray Absorptiometry Bone Mineral Density Assessment Dual energy x-ray absorptiometry bone densitometers measure bone density based on differential absorption of 2 x-ray beams by bone and soft tissues. It is the gold standard for detecting and diagnosing osteoporosis, a systemic disease characterized by low bone density and altered bone structure, resulting in low bone strength and increased risk of fractures. The test is fast (approximately 10 minutes) and accurate (exceeds 90% at the hip), with low radiation (1/3 to 1/5 of that from a chest x-ray). DXA densitometers are licensed as Class 3 medical devices in Canada. The World Health Organization has established criteria for osteoporosis and osteopenia based on DXA BMD measurements: osteoporosis is defined as a BMD that is >2.5 standard deviations below the mean BMD for normal young adults (i.e. T-score <–2.5), while osteopenia is defined as BMD that is more than 1 standard deviation but less than 2.5 standard deviation below the mean for normal young adults (i.e. T-score< –1 & ≥–2.5). DXA densitometry is presently an insured health service in Ontario. Clinical Need   Burden of Disease The Canadian Multicenter Osteoporosis Study (CaMos) found that 16% of Canadian women and 6.6% of Canadian men have osteoporosis based on the WHO criteria, with prevalence increasing with age. Osteopenia was found in 49.6% of Canadian women and 39% of Canadian men. In Ontario, it is estimated that nearly 530,000 Ontarians have some degrees of osteoporosis. Osteoporosis-related fragility fractures occur most often in the wrist, femur and pelvis. These fractures, particularly those in the hip, are associated with increased mortality, and decreased functional capacity and quality of life. A Canadian study showed that at 1 year after a hip fracture, the mortality rate was 20%. Another 20% required institutional care, 40% were unable to walk independently, and there was lower health-related quality of life due to attributes such as pain, decreased mobility and decreased ability to self-care. The cost of osteoporosis and osteoporotic fractures in Canada was estimated to be $1.3 billion in 1993. Guidelines for Bone Mineral Density Testing With 2 exceptions, almost all guidelines address only women. None of the guidelines recommend blanket population-based BMD testing. Instead, all guidelines recommend BMD testing in people at risk of osteoporosis, predominantly women aged 65 years or older. For women under 65 years of age, BMD testing is recommended only if one major or two minor risk factors for osteoporosis exist. Osteoporosis Canada did not restrict its recommendations to women, and thus their guidelines apply to both sexes. Major risk factors are age greater than or equal to 65 years, a history of previous fractures, family history (especially parental history) of fracture, and medication or disease conditions that affect bone metabolism (such as long-term glucocorticoid therapy). Minor risk factors include low body mass index, low calcium intake, alcohol consumption, and smoking. Current Funding for Bone Mineral Density Testing The Ontario Health Insurance Program (OHIP) Schedule presently reimburses DXA BMD at the hip and spine. Measurements at both sites are required if feasible. Patients at low risk of accelerated bone loss are limited to one BMD test within any 24-month period, but there are no restrictions on people at high risk. The total fee including the professional and technical components for a test involving 2 or more sites is $106.00 (Cdn). Method of Review This review consisted of 2 parts. The first part was an analysis of Ontario administrative data relating to DXA BMD, wrist and hip fractures, and use of antiresorptive drugs in people aged 65 years and older. The Institute for Clinical Evaluative Sciences extracted data from the OHIP claims database, the Canadian Institute for Health Information hospital discharge abstract database, the National Ambulatory Care Reporting System, and the Ontario Drug Benefit database using OHIP and ICD-10 codes. The data was analyzed to examine the trends in DXA BMD use from 1992 to 2005, and to identify areas requiring improvement. The second part included systematic reviews and analyses of evidence relating to issues identified in the analyses of utilization data. Altogether, 8 reviews and qualitative syntheses were performed, consisting of 28 published systematic reviews and/or meta-analyses, 34 randomized controlled trials, and 63 observational studies. Findings of Utilization Analysis Analysis of administrative data showed a 10-fold increase in the number of BMD tests in Ontario between 1993 and 2005. OHIP claims for BMD tests are presently increasing at a rate of 6 to 7% per year. Approximately 500,000 tests were performed in 2005/06 with an age-adjusted rate of 8,600 tests per 100,000 population. Women accounted for 90 % of all BMD tests performed in the province. In 2005/06, there was a 2-fold variation in the rate of DXA BMD tests across local integrated health networks, but a 10-fold variation between the county with the highest rate (Toronto) and that with the lowest rate (Kenora). The analysis also showed that: With the increased use of BMD, there was a concomitant increase in the use of antiresorptive drugs (as shown in people 65 years and older) and a decrease in the rate of hip fractures in people age 50 years and older. Repeat BMD made up approximately 41% of all tests. Most of the people (>90%) who had annual BMD tests in a 2-year or 3-year period were coded as being at high risk for osteoporosis. 18% (20,865) of the people who had a repeat BMD within a 24-month period and 34% (98,058) of the people who had one BMD test in a 3-year period were under 65 years, had no fracture in the year, and coded as low-risk. Only 19% of people age greater than 65 years underwent BMD testing and 41% received osteoporosis treatment during the year following a fracture. Men accounted for 24% of all hip fractures and 21 % of all wrist fractures, but only 10% of BMD tests. The rates of BMD tests and treatment in men after a fracture were only half of those in women. In both men and women, the rate of hip and wrist fractures mainly increased after age 65 with the sharpest increase occurring after age 80 years. Findings of Systematic Review and Analysis Serial Bone Mineral Density Testing for People Not Receiving Osteoporosis Treatment A systematic review showed that the mean rate of bone loss in people not receiving osteoporosis treatment (including postmenopausal women) is generally less than 1% per year. Higher rates of bone loss were reported for people with disease conditions or on medications that affect bone metabolism. In order to be considered a genuine biological change, the change in BMD between serial measurements must exceed the least significant change (variability) of the testing, ranging from 2.77% to 8% for precisions ranging from 1% to 3% respectively. Progression in BMD was analyzed, using different rates of baseline BMD values, rates of bone loss, precision, and BMD value for initiating treatment. The analyses showed that serial BMD measurements every 24 months (as per OHIP policy for low-risk individuals) is not necessary for people with no major risk factors for osteoporosis, provided that the baseline BMD is normal (T-score ≥ –1), and the rate of bone loss is less than or equal to 1% per year. The analyses showed that for someone with a normal baseline BMD and a rate of bone loss of less than 1% per year, the change in BMD is not likely to exceed least significant change (even for a 1% precision) in less than 3 years after the baseline test, and is not likely to drop to a BMD level that requires initiation of treatment in less than 16 years after the baseline test. Serial Bone Mineral Density Testing in People Receiving Osteoporosis Therapy Seven published meta-analysis of randomized controlled trials (RCTs) and 2 recent RCTs on BMD monitoring during osteoporosis therapy showed that although higher increases in BMD were generally associated with reduced risk of fracture, the change in BMD only explained a small percentage of the fracture risk reduction. Studies showed that some people with small or no increase in BMD during treatment experienced significant fracture risk reduction, indicating that other factors such as improved bone microarchitecture might have contributed to fracture risk reduction. There is conflicting evidence relating to the role of BMD testing in improving patient compliance with osteoporosis therapy. Even though BMD may not be a perfect surrogate for reduction in fracture risk when monitoring responses to osteoporosis therapy, experts advised that it is still the only reliable test available for this purpose. A systematic review conducted by the Medical Advisory Secretariat showed that the magnitude of increases in BMD during osteoporosis drug therapy varied among medications. Although most of the studies yielded mean percentage increases in BMD from baseline that did not exceed the least significant change for a 2% precision after 1 year of treatment, there were some exceptions. Bone Mineral Density Testing and Treatment After a Fragility Fracture A review of 3 published pooled analyses of observational studies and 12 prospective population-based observational studies showed that the presence of any prevalent fracture increases the relative risk for future fractures by approximately 2-fold or more. A review of 10 systematic reviews of RCTs and 3 additional RCTs showed that therapy with antiresorptive drugs significantly reduced the risk of vertebral fractures by 40 to 50% in postmenopausal osteoporotic women and osteoporotic men, and 2 antiresorptive drugs also reduced the risk of nonvertebral fractures by 30 to 50%. Evidence from observational studies in Canada and other jurisdictions suggests that patients who had undergone BMD measurements, particularly if a diagnosis of osteoporosis is made, were more likely to be given pharmacologic bone-sparing therapy. Despite these findings, the rate of BMD investigation and osteoporosis treatment after a fracture remained low (<20%) in Ontario as well as in other jurisdictions. Bone Mineral Density Testing in Men There are presently no specific Canadian guidelines for BMD screening in men. A review of the literature suggests that risk factors for fracture and the rate of vertebral deformity are similar for men and women, but the mortality rate after a hip fracture is higher in men compared with women. Two bisphosphonates had been shown to reduce the risk of vertebral and hip fractures in men. However, BMD testing and osteoporosis treatment were proportionately low in Ontario men in general, and particularly after a fracture, even though men accounted for 25% of the hip and wrist fractures. The Ontario data also showed that the rates of wrist fracture and hip fracture in men rose sharply in the 75- to 80-year age group. Ontario-Based Economic Analysis The economic analysis focused on analyzing the economic impact of decreasing future hip fractures by increasing the rate of BMD testing in men and women age greater than or equal to 65 years following a hip or wrist fracture. A decision analysis showed the above strategy, especially when enhanced by improved reporting of BMD tests, to be cost-effective, resulting in a cost-effectiveness ratio ranging from $2,285 (Cdn) per fracture avoided (worst-case scenario) to $1,981 (Cdn) per fracture avoided (best-case scenario). A budget impact analysis estimated that shifting utilization of BMD testing from the low risk population to high risk populations within Ontario would result in a saving of $0.85 million to $1.5 million (Cdn) to the health system. The potential net saving was estimated at $1.2 million to $5 million (Cdn) when the downstream cost-avoidance due to prevention of future hip fractures was factored into the analysis. Other Factors for Consideration There is a lack of standardization for BMD testing in Ontario. Two different standards are presently being used and experts suggest that variability in results from different facilities may lead to unnecessary testing. There is also no requirement for standardized equipment, procedure or reporting format. The current reimbursement policy for BMD testing encourages serial testing in people at low risk of accelerated bone loss. This review showed that biannual testing is not necessary for all cases. The lack of a database to collect clinical data on BMD testing makes it difficult to evaluate the clinical profiles of patients tested and outcomes of the BMD tests. There are ministry initiatives in progress under the Osteoporosis Program to address the development of a mandatory standardized requisition form for BMD tests to facilitate data collection and clinical decision-making. Work is also underway for developing guidelines for BMD testing in men and in perimenopausal women. Conclusion Increased use of BMD in Ontario since 1996 appears to be associated with increased use of antiresorptive medication and a decrease in hip and wrist fractures. Data suggest that as many as 20% (98,000) of the DXA BMD tests in Ontario in 2005/06 were performed in people aged less than 65 years, with no fracture in the current year, and coded as being at low risk for accelerated bone loss; this is not consistent with current guidelines. Even though some of these people might have been incorrectly coded as low-risk, the number of tests in people truly at low risk could still be substantial. Approximately 4% (21,000) of the DXA BMD tests in 2005/06 were repeat BMDs in low-risk individuals within a 24-month period. Even though this is in compliance with current OHIP reimbursement policies, evidence showed that biannual serial BMD testing is not necessary in individuals without major risk factors for fractures, provided that the baseline BMD is normal (T-score < –1). In this population, BMD measurements may be repeated in 3 to 5 years after the baseline test to establish the rate of bone loss, and further serial BMD tests may not be necessary for another 7 to 10 years if the rate of bone loss is no more than 1% per year. Precision of the test needs to be considered when interpreting serial BMD results. Although changes in BMD may not be the perfect surrogate for reduction in fracture risk as a measure of response to osteoporosis treatment, experts advised that it is presently the only reliable test for monitoring response to treatment and to help motivate patients to continue treatment. Patients should not discontinue treatment if there is no increase in BMD after the first year of treatment. Lack of response or bone loss during treatment should prompt the physician to examine whether the patient is taking the medication appropriately. Men and women who have had a fragility fracture at the hip, spine, wrist or shoulder are at increased risk of having a future fracture, but this population is presently under investigated and under treated. Additional efforts have to be made to communicate to physicians (particularly orthopaedic surgeons and family physicians) and the public about the need for a BMD test after fracture, and for initiating treatment if low BMD is found. Men had a disproportionately low rate of BMD tests and osteoporosis treatment, especially after a fracture. Evidence and fracture data showed that the risk of hip and wrist fractures in men rises sharply at age 70 years. Some counties had BMD utilization rates that were only 10% of that of the county with the highest utilization. The reasons for low utilization need to be explored and addressed. Initiatives such as aligning reimbursement policy with current guidelines, developing specific guidelines for BMD testing in men and perimenopausal women, improving BMD reports to assist in clinical decision making, developing a registry to track BMD tests, improving access to BMD tests in remote/rural counties, establishing mechanisms to alert family physicians of fractures, and educating physicians and the public, will improve the appropriate utilization of BMD tests, and further decrease the rate of fractures in Ontario. Some of these initiatives such as developing guidelines for perimenopausal women and men, and developing a standardized requisition form for BMD testing, are currently in progress under the Ontario Osteoporosis Strategy. PMID:23074491

SU-E-T-577: Commissioning of a Deterministic Algorithm for External Photon Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, T; Finlay, J; Mesina, C

Purpose: We report commissioning results for a deterministic algorithm for external photon beam treatment planning. A deterministic algorithm solves the radiation transport equations directly using a finite difference method, thus improve the accuracy of dose calculation, particularly under heterogeneous conditions with results similar to that of Monte Carlo (MC) simulation. Methods: Commissioning data for photon energies 6 – 15 MV includes the percentage depth dose (PDD) measured at SSD = 90 cm and output ratio in water (Spc), both normalized to 10 cm depth, for field sizes between 2 and 40 cm and depths between 0 and 40 cm. Off-axismore » ratio (OAR) for the same set of field sizes was used at 5 depths (dmax, 5, 10, 20, 30 cm). The final model was compared with the commissioning data as well as additional benchmark data. The benchmark data includes dose per MU determined for 17 points for SSD between 80 and 110 cm, depth between 5 and 20 cm, and lateral offset of up to 16.5 cm. Relative comparisons were made in a heterogeneous phantom made of cork and solid water. Results: Compared to the commissioning beam data, the agreement are generally better than 2% with large errors (up to 13%) observed in the buildup regions of the FDD and penumbra regions of the OAR profiles. The overall mean standard deviation is 0.04% when all data are taken into account. Compared to the benchmark data, the agreements are generally better than 2%. Relative comparison in heterogeneous phantom is in general better than 4%. Conclusion: A commercial deterministic algorithm was commissioned for megavoltage photon beams. In a homogeneous medium, the agreement between the algorithm and measurement at the benchmark points is generally better than 2%. The dose accuracy for a deterministic algorithm is better than a convolution algorithm in heterogeneous medium.« less

Parental attitudes toward newborn screening for Duchenne/Becker muscular dystrophy and spinal muscular atrophy.

PubMed

Wood, Molly F; Hughes, Sarah C; Hache, Lauren P; Naylor, Edwin W; Abdel-Hamid, Hoda Z; Barmada, M Michael; Dobrowolski, Steven F; Stickler, David E; Clemens, Paula R

2014-06-01

Disease inclusion in the newborn screening (NBS) panel should consider the opinions of those most affected by the outcome of screening. We assessed the level and factors that affect parent attitudes regarding NBS panel inclusion of Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and spinal muscular atrophy (SMA). The attitudes toward NBS for DMD, BMD, and SMA were surveyed and compared for 2 categories of parents, those with children affected with DMD, BMD, or SMA and expectant parents unselected for known family medical history. The level of support for NBS for DMD, BMD, and SMA was 95.9% among parents of children with DMD, BMD, or SMA and 92.6% among expectant parents. There was strong support for NBS for DMD, BMD, and SMA in both groups of parents. Given advances in diagnostics and promising therapeutic approaches, discussion of inclusion in NBS should continue. Copyright © 2013 Wiley Periodicals, Inc.

Risk assessment for consumer exposure to toluene diisocyanate (TDI) derived from polyurethane flexible foam.

PubMed

Arnold, Scott M; Collins, Michael A; Graham, Cynthia; Jolly, Athena T; Parod, Ralph J; Poole, Alan; Schupp, Thomas; Shiotsuka, Ronald N; Woolhiser, Michael R

2012-12-01

Polyurethanes (PU) are polymers made from diisocyanates and polyols for a variety of consumer products. It has been suggested that PU foam may contain trace amounts of residual toluene diisocyanate (TDI) monomers and present a health risk. To address this concern, the exposure scenario and health risks posed by sleeping on a PU foam mattress were evaluated. Toxicity benchmarks for key non-cancer endpoints (i.e., irritation, sensitization, respiratory tract effects) were determined by dividing points of departure by uncertainty factors. The cancer benchmark was derived using the USEPA Benchmark Dose Software. Results of previous migration and emission data of TDI from PU foam were combined with conservative exposure factors to calculate upper-bound dermal and inhalation exposures to TDI as well as a lifetime average daily dose to TDI from dermal exposure. For each non-cancer endpoint, the toxicity benchmark was divided by the calculated exposure to determine the margin of safety (MOS), which ranged from 200 (respiratory tract) to 3×10(6) (irritation). Although available data indicate TDI is not carcinogenic, a theoretical excess cancer risk (1×10(-7)) was calculated. We conclude from this assessment that sleeping on a PU foam mattress does not pose TDI-related health risks to consumers. Copyright © 2012 Elsevier Inc. All rights reserved.

Estrogen and peptide YY are associated with bone mineral density in premenopausal exercising women.

PubMed

Scheid, J L; Toombs, R J; Ducher, G; Gibbs, J C; Williams, N I; De Souza, M J

2011-08-01

In women with anorexia nervosa, elevated fasting peptide YY (PYY) is associated with decreased bone mineral density (BMD). Prior research from our lab has demonstrated that fasting total PYY concentrations are elevated in exercising women with amenorrhea compared to ovulatory exercising women. The purpose of this study was to assess the association between fasting total PYY, average monthly estrogen exposure and BMD in non-obese premenopausal exercising women. Daily urine samples were collected and assessed for metabolites of estrone 1-glucuronide (E1G) and pregnandiol glucuronide (PdG) for at least one menstrual cycle if ovulatory or a 28-day monitoring period if amenorrheic. Fasting serum samples were pooled over the measurement period and analyzed for total PYY and leptin. BMD and body composition were assessed by dual-energy X-ray absorptiometry. Multiple regression analyses were performed to determine whether measures of body composition, estrogen status, exercise minutes, leptin and PYY explained a significant amount of the variance in BMD at multiple sites. Premenopausal exercising women aged 23.8±0.9years with a mean BMI of 21.2±0.4kg/m(2) exercised 346±48min/week and had a peak oxygen uptake of 49.1±1.8mL/kg/min. Thirty-nine percent (17/44) of the women had amenorrhea. Fasting total PYY concentrations were negatively associated with total body BMD (p=0.033) and total hip BMD (p=0.043). Mean E1G concentrations were positively associated with total body BMD (p=0.033) and lumbar spine (L2-L4) BMD (p=0.047). The proportion of variance in lumbar spine (L2-L4) BMD explained by body weight and E1G cycle mean was 16.4% (R(2)=0.204, p=0.012). The proportion of variance in hip BMD explained by PYY cycle mean was 8.6% (R(2)=0.109, p=0.033). The proportion of variance in total body BMD explained by body weight and E1G cycle mean was 21.9% (R(2)=0.257, p=0.003). PYY, mean E1G and body weight are associated with BMD in premenopausal exercising women. Thus, elevated PYY and suppressed estrogen concentrations are associated with, and could be directly contributing to, low BMD in exercising women with amenorrhea, despite regular physical activity. Copyright © 2011 Elsevier Inc. All rights reserved.

Prevention of aromatase inhibitor-induced bone loss with alendronate in postmenopausal women: The BATMAN Trial.

PubMed

Lomax, Anna J; Yee Yap, Saw; White, Karen; Beith, Jane; Abdi, Ehtesham; Broad, Adam; Sewak, Sanjeev; Lee, Chooi; Sambrook, Philip; Pocock, Nicholas; Henry, Margaret J; Yeow, Elaine G; Bell, Richard

2013-12-01

Postmenopausal women on aromatase inhibitors (AI) are at risk of aromatase inhibitor-associated bone loss (AIBL) and fractures. In 2005 Osteoporosis Australia proposed an algorithm for bisphosphonate intervention. Three hundred and three postmenopausal women with early breast cancer (EBC) were enrolled (osteoporotic, n=25; osteopaenic, n=146; normal bone mineral density (BMD), n=126). Weekly alendronate (70 mg) treatment efficacy as triggered by the algorithm in preventing bone loss was evaluated. All patients received anastrozole (1 mg daily), calcium and vitamin D. All osteoporotic patients received alendronate at baseline. Eleven out of the 146 (7.5%) osteopaenic patients commenced alendronate within 18 months of participation and eleven commenced after. One hundred and twenty four out of the 146 (84.9%) osteopaenic patients and all 126 with normal baseline BMD did not trigger the algorithm. At three years, lumbar spine mean BMD increased (15.6%, p<0.01) in the osteoporotic group. BMD in the osteopaenic group with early intervention significantly increased at three years (6.3%, p=0.02). No significant change was seen in the late intervention group. No change was observed in those with osteopaenia without alendronate. There was a significant drop in lumbar spine (-5.4%) and hip (-4.5%) mean BMD, in the normal BMD group, none of whom received alendronate. Fracture data will be presented. In postmenopausal women with endocrine-responsive EBC, BMD improved over time when a bisphosphonate is administered with anastrozole in osteoporotic patients using an osteoporosis schedule. Subjects with normal baseline BMD experienced the greatest BMD loss, although none became osteoporotic.

Bone mineral density changes of lumbar spine and femur in osteoporotic patient treated with bisphosphonates and beta-hydroxy-beta-methylbutyrate (HMB): Case report.

PubMed

Tatara, Marcin R; Krupski, Witold; Majer-Dziedzic, Barbara

2017-10-01

Currently available approaches to osteoporosis treatment include application of antiresorptive and anabolic agents influencing bone tissue metabolism. The aim of the study was to present bone mineral density (BMD) changes of lumbar spine in osteoporotic patient treated with bisphosphonates such as ibandronic acid and pamidronic acid, and beta-hydroxy-beta-methylbutyrate (HMB). BMD and volumetric BMD (vBMD) of lumbar spine were measured during the 6 year observation period with the use of dual-energy X-ray absorptiometry (DEXA) and quantitative computed tomography (QCT). The described case report of osteoporotic patient with family history of severe osteoporosis has shown site-dependent response of bone tissue to antiosteoporotic treatment with bisphosphonates. Twenty-five-month treatment with ibandronic acid improved proximal femur BMD with relatively poor effects on lumbar spine BMD. Over 15-month therapy with pamidronic acid was effective to improve lumbar spine BMD, while in the proximal femur the treatment was not effective. A total of 61-week long oral administration with calcium salt of HMB improved vBMD of lumbar spine in the trabecular and cortical bone compartments when monitored by QCT. Positive effects of nearly 2.5 year HMB treatment on BMD of lumbar spine and femur in the patient were also confirmed using DEXA method. The results obtained indicate that HMB may be applied for the effective treatment of osteoporosis in humans. Further studies on wider human population are recommended to evaluate mechanisms influencing bone tissue metabolism by HMB.

Nutrition status, bone mass density, and selective serotonin reuptake inhibitors.

PubMed

Kindilien, Shannon; Goldberg, Elle M; Roberts, Melissa H; Gonzales-Pacheco, Diana

2018-05-07

The association between selective serotonin reuptake inhibitor (SSRI) use and bone mass density (BMD) has been debated. Inadequate diet, which may occur in depressed individuals prescribed SSRIs is also associated with decreased BMD. This study seeks to determine if SSRI use in adults is associated with lower than average BMD while controlling for nutrition related variables. Further, it investigates whether there are potential interactions between micronutrients and SSRI use on BMD. Adults, 655 with an SSRI prescription ≥180 days and 12,372 non-users, were identified in the 2005-2014 National Health and Nutrition Examination Survey (NHANES) data. Survey respondents were propensity score matched on propensity to have an SSRI prescription and compared on femoral neck BMD t-scores. A sub-analysis within SSRI users was conducted to calculate the odds ratio (OR) of having a low (osteopenia or osteoporosis) BMD t-score given SSRI exposure and inadequate daily micronutrient intake. Inadequate daily micronutrient intake was common; over half of SSRI users and non-users had inadequate calcium, vitamin d, and potassium. SSRI use was associated with an absolute reduction of 0.11 in BMD t-score. Inadequate daily vitamin D intake was associated with lower BMD t-scores in both SSRI users and non-users. The interaction of SSRI use and inadequate daily intake of zinc was also associated with low BMD (OR: 1.11, 95% CI: 1.01-1.23). Patient health may be improved by nutritional education, referral to a dietician, or by micronutrient monitoring by the prescribing physician. Copyright © 2017. Published by Elsevier Inc.

Bone mineral density, growth, pubertal development and other parameters in Brazilian children and young adults with sickle cell anaemia.

PubMed

Meeuwes, M; Souza de Carvalho, T F; Cipolotti, R; Gurgel, R Q; Ferrão, T O; Peters, M; Agyemang, C

2013-12-01

To evaluate the occurrence of low bone mineral density (BMD) and its relationship with clinical and laboratorial characteristics in children and young adults with sickle cell anaemia living in Northeast-Brazil, and to assess the role of radiography in diagnosing low BMD. Bone mineral density of lumbar spine was measured by dual energy X-ray absorptiometry (DXA) in 27 patients with Sickle cell anaemia (SCA) aged 7-28 years. Clinical history, calcium and calorie intake, laboratory measurements, anthropometrics and pubertal development were assessed, and X-rays were obtained. Z-scores and T-scores for weight, height, Body Mass Index (BMI) and BMD were calculated using age and gender matched reference data. Mean lumbar spine BMD Z-scores and T-scores were -1.81 SD in boys and -0.80 SD in girls. BMD Z-scores were below -2 SD in 33.3% of girls and in 46.7% of boys. Low BMD (<-2 SD) occurred significantly more in patients with low height-for-age (P = 0.02), low weight-for-age (P = 0.001) and low BMI-for-age (P = 0.006). No significant relationships were found between BMD and other clinical and laboratory parameters. Radiography had a sensitivity of 75% and a specificity of 36% to detect low BMD, and was considered not useful in this context. Patients with low height and/or low weight-for-age seem to be at high risk for developing low BMD. © 2013 John Wiley & Sons Ltd.

Higher prevalence of osteoporosis among female Holocaust survivors.

PubMed

Marcus, E-L; Menczel, J

2007-11-01

The prevalence of osteoporosis was statistically significantly higher among female Holocaust survivors than among those who were not exposed to the Holocaust. These findings support the importance of nutrition and environmental conditions during childhood and adolescence on BMD in older adults. Holocaust survivors during childhood and adolescence experienced undernutrition and lack of exercise and sunlight. The study aimed to establish if Holocaust survivors have higher prevalence of osteoporosis than subjects who were not Holocaust survivors. Seventy-three female Jewish Holocaust survivors > or = 60 years old and 60 female European-born Jews > or =60 years old who were not in the Holocaust were examined. BMD was measured using DXA of the lumbar spine and hips. The Cochran-Armitage trend test was used to test for an increasing trend in decreased BMD in the Holocaust survivors versus controls. Among Holocaust survivors 54.8% had osteoporosis, 39.7% osteopenia, and 5.5% normal BMD, whereas among controls 25.0% had osteoporosis, 55.0% osteopenia, and 20.0% normal BMD (p = 0.0001). In those who were <17 years old in 1945, among Holocaust survivors 58.0% had osteoporosis, 34.0% osteopenia, and 8.0% normal BMD, whereas among controls 20.0% had osteoporosis, 57.8% osteopenia, and 22.2% normal BMD (p = 0.0003). In those > or =17 years old in 1945, among Holocaust survivors 47.8% had osteoporosis, 52.2% osteopenia and none had normal BMD, whereas among controls 40.0% had osteoporosis, 46.7% osteopenia, and 13.3% normal BMD (p = 0.28). The prevalence of osteoporosis was significantly higher among Holocaust survivors.

The relationship between proton pump inhibitor use and longitudinal change in bone mineral density: a population-based study [corrected] from the Canadian Multicentre Osteoporosis Study (CaMos).

PubMed

Targownik, Laura E; Leslie, William D; Davison, K Shawn; Goltzman, David; Jamal, Sophie A; Kreiger, Nancy; Josse, Robert G; Kaiser, Stephanie M; Kovacs, Christopher S; Prior, Jerilynn C; Zhou, Wei

2012-09-01

Proton pump inhibitor (PPI) use has been identified as a risk factor for hip and vertebral fractures. Evidence supporting a relationship between PPI use and osteoporosis remains scant. Demonstrating that PPIs are associated with accelerated bone mineral density (BMD) loss would provide supportive evidence for a mechanism through which PPIs could increase fracture risk. We used the Canadian Multicentre Osteoporosis Study data set, which enrolled a population-based sample of Canadians who underwent BMD testing of the femoral neck, total hip, and lumbar spine (L1-L4) at baseline, and then again at 5 and 10 years. Participants also reported drug use and exposure to risk factors for osteoporosis and fracture. Multivariate linear regression was used to determine the independent association of PPI exposure and baseline BMD, and on change in BMD at 5 and 10 years. In all, 8,340 subjects were included in the baseline analysis, with 4,512 (55%) undergoing year 10 BMD testing. After adjusting for potential confounders, PPI use was associated with significantly lower baseline BMD at the femoral neck and total hip. PPI use was not associated with a significant acceleration in covariate-adjusted BMD loss at any measurement site after 5 and 10 years of follow-up. PPI users had lower BMD at baseline than PPI non-users, but PPI use over 10 years did not appear to be associated with accelerated BMD loss. The reasons for discordant findings between PPI use at baseline and during follow-up require further study.

Bone mineral density in midlife women: the Study of Women's Health in Qatar.

PubMed

Gerber, L M; Bener, A; Al-Ali, H M; Hammoudeh, M; Liu, L Q; Verjee, M

2015-04-01

The aim of this study is to investigate bone mineral density (BMD) for a large cross-section of midlife Arab women living in Qatar and to evaluate the association of body mass index (BMI), menopause status, and nationality, on BMD of the spine and femur. A cross-sectional study was conducted among women aged 40-60 years recruited from nine primary-care health centers in Qatar. BMD (g/m(2)) was assessed at the lumbar spine and the femur. The combined prevalence of osteopenia and osteoporosis was 4% at the femur and 16.2% at the spine. BMI and menstrual status were both independently associated with BMD at the spine and at the femur (all p values < 0.001). As BMI increased, BMD increased at both the spine and femur. Women who menstruated in the past 12 months had 0.82 g/cm(2) and 0.61 g/cm(2) greater BMD at the spine and femur, respectively, compared with women who had not menstruated in 12 months. Nationality was not associated with mean BMD of the spine or the femur. No significant differences were observed between Qatari and non-Qatari women in terms of mean BMD values at the spine and the femur except for the femur in the age group 55-60, where values were lower among non-Qataris (p = 0.04). Multivariable analyses showed that BMI and menstrual status were found to be strongly associated with BMD levels at the spine and femur. The high prevalence of obesity observed in this sample may explain the low levels of osteopenia and osteoporosis observed.

Plasma selenium, zinc, copper and lipid levels in postmenopausal Turkish women and their relation with osteoporosis.

PubMed

Arikan, Deniz Cemgil; Coskun, Ayhan; Ozer, Ali; Kilinc, Metin; Atalay, Filiz; Arikan, Tugba

2011-12-01

It has been shown that the trace elements and lipids play role in the growth, development and maintenance of bones. We aimed to investigate serum selenium (Se), zinc (Zn), copper (Cu) and lipid (total cholesterol, triglyceride (TG), high density lipoprotein-cholesterol, low-density lipoprotein-cholesterol) levels in postmenopausal women with osteoporosis, osteopenia and in healthy controls, and to determine the relationship between Se, Zn, Cu and lipid parameters and bone mineral density (BMD). The study included 107 postmenopausal women; 35 healthy (group 1), 37 osteopenic (group 2) and 35 osteoporotic (group 3). The women in all three groups were carefully matched for body mass index (BMI). Serum concentrations of Se, Zn and Cu were measured by atomic absorption spectrophotometry. Plasma Se, Cu, Zn and lipid levels were similar in all groups (p > 0.05). When we combined the women in each of the three groups, and considered them as one group (n = 107) we found a positive correlation between BMI and lumbar vertebra BMD, femur neck BMD, femur total BMD; a positive correlation between TG and femur neck BMD, femur total BMD; a positive correlation between Zn and lumbar vertebra BMD (total T score) (p < 0.05). There was no correlation between Se, Cu, Zn, P and lipid parameters (p > 0.05). Although BMI has a positive effect on BMD, trace elements and lipids, except Zn and TG, did not directly and correlatively influence BMD. Further studies are needed to clarify the role and relationship of trace elements and lipid parameters in postmenopausal osteoporosis.

Relationship between pre-sarcopenia, sarcopenia and bone mineral density in elderly men.

PubMed

Pereira, Fernando Borges; Leite, André Ferreira; de Paula, Ana Patrícia

2015-02-01

Analyze the influence of sarcopenia in bone health of elderly men. This cross-sectional study evaluated 198 men aged over 60 years. Body composition was measured by dual energy X-ray absorptiometry. The BMD was measured at the femoral neck, total hip, lumbar spine and 33% radius. The diagnosis of abnormal BMD was defined for men who presented densitometric diagnosis of osteopenia or osteoporosis defined by T-score of femoral neck, total hip and lumbar spine. The pre-sarcopenia and sarcopenia were defined according to the European Working Group on Sarcopenia in Older People. The group diagnosed with normal BMD, compared to the group of abnormal BMD, have significantly higher body weight, body mass index, grip strength, lean mass, fat mass, and relative appendicular skeletal muscle mass (RASM). However, after multiple linear regression analysis, we found that only the RASM, lean mass, and handgrip strength in the dominant hand influenced the variability of the BMD after adjustment for age and weight. Regression analyzes showed a positive association between greater appendicular lean mass and a smaller number of elderly patients with abnormal BMD diagnostic. The regression analyzes showed that elderly men diagnosed with pre-sarcopenia and sarcopenia had more abnormal BMD than non-sarcopenic elderly men. We concluded that pre-sarcopenia and sarcopenia were associated with abnormal BMD. The lean mass, compared to fat mass, has a greater positive influence on the BMD of elderly men. This result suggests the importance of the increase in lean mass for the bone health of elderly men.

Bone Mineral Density in Adolescent Girls with Hypogonadotropic and Hypergonadotropic Hypogonadism.

PubMed

Özbek, Mehmet Nuri; Demirbilek, Hüseyin; Baran, Rıza Taner; Baran, Ahmet

2016-06-05

Deficiency of sex steroids has a negative impact on bone mineral content. In studies conducted on postmenopausal women and animal studies, elevated follicle-stimulating hormone (FSH) levels were found to be correlated with a decrease in bone mineralization and osteoporosis. The aim of the present study was to evaluate bone mineral density (BMD) in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism and also to investigate the correlation between FSH level and BMD. The study group included 33 adolescent girls with hypogonadism (14 with hypogonadotropic hypogonadism and 19 with hypergonadotropic hypogonadism). FSH, luteinizing hormone, estradiol levels, and BMD (using dual energy x-ray absorptiometry) were measured. There were no statistically significant differences between the chronological age and bone age of the two patient groups, namely, with hypogonadotropic and hypergonadotropic hypogonadism. There was also no significant difference between BMD z-score values obtained from measurements from the spine and the femur neck of patients in the two groups (p-values were 0.841 and 0.281, respectively). In the hypergonadotropic group, a moderately negative correlation was detected between FSH level and BMD z-score measured from the femur neck (ρ=-0.69, p=0.001), whilst no correlation was observed between FSH levels and height adjusted BMD-z scores measured from the spine (ρ=0.17, p=0.493). FSH level was not found to be an independent variable affecting BMD z-score. BMD z-scores were detected to be similar in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism, and FSH levels were not found to have a clinically relevant impact on BMD.

Bone Mineral Density in Adolescent Girls with Hypogonadotropic and Hypergonadotropic Hypogonadism

PubMed Central

Özbek, Mehmet Nuri; Demirbilek, Hüseyin; Baran, Rıza Taner; Baran, Ahmet

2016-01-01

Objective: Deficiency of sex steroids has a negative impact on bone mineral content. In studies conducted on postmenopausal women and animal studies, elevated follicle-stimulating hormone (FSH) levels were found to be correlated with a decrease in bone mineralization and osteoporosis. The aim of the present study was to evaluate bone mineral density (BMD) in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism and also to investigate the correlation between FSH level and BMD. Methods: The study group included 33 adolescent girls with hypogonadism (14 with hypogonadotropic hypogonadism and 19 with hypergonadotropic hypogonadism). FSH, luteinizing hormone, estradiol levels, and BMD (using dual energy x-ray absorptiometry) were measured. Results: There were no statistically significant differences between the chronological age and bone age of the two patient groups, namely, with hypogonadotropic and hypergonadotropic hypogonadism. There was also no significant difference between BMD z-score values obtained from measurements from the spine and the femur neck of patients in the two groups (p-values were 0.841 and 0.281, respectively). In the hypergonadotropic group, a moderately negative correlation was detected between FSH level and BMD z-score measured from the femur neck (ρ=-0.69, p=0.001), whilst no correlation was observed between FSH levels and height adjusted BMD-z scores measured from the spine (ρ=0.17, p=0.493). FSH level was not found to be an independent variable affecting BMD z-score. Conclusion: BMD z-scores were detected to be similar in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism, and FSH levels were not found to have a clinically relevant impact on BMD. PMID:27087454

Hydroxychloroquine affects bone resorption both in vitro and in vivo.

PubMed

Both, Tim; Zillikens, M Carola; Schreuders-Koedam, Marijke; Vis, Marijn; Lam, Wai-Kwan; Weel, Angelique E A M; van Leeuwen, Johannes P T M; van Hagen, P Martin; van der Eerden, Bram C J; van Daele, Paul L A

2018-02-01

We recently showed that patients with primary Sjögren syndrome (pSS) have significantly higher bone mineral density (BMD) compared to healthy controls. The majority of those patients (69%) was using hydroxychloroquine (HCQ), which may have favorable effects on BMD. The aim of the study was to evaluate whether HCQ modulates osteoclast function. Osteoclasts were cultured from PBMC-sorted monocytes for 14 days and treated with different HCQ doses (controls 1 and 5 μg/ml). TRAP staining and resorption assays were performed to evaluate osteoclast differentiation and activity, respectively. Staining with an acidification marker (acridine orange) was performed to evaluate intracellular pH at multiple timepoints. Additionally, a fluorescent cholesterol uptake assay was performed to evaluate cholesterol trafficking. Serum bone resorption marker β-CTx was evaluated in rheumatoid arthritis patients. HCQ inhibits the formation of multinuclear osteoclasts and leads to decreased bone resorption. Continuous HCQ treatment significantly decreases intracellular pH and significantly enhanced cholesterol uptake in mature osteoclasts along with increased expression of the lowdensity lipoprotein receptor. Serum β-CTx was significantly decreased after 6 months of HCQ treatment. In agreement with our clinical data, we demonstrate that HCQ suppresses bone resorption in vitro and decreases the resorption marker β-CTx in vivo. We also showed that HCQ decreases the intracellular pH in mature osteoclasts and stimulates cholesterol uptake, suggesting that HCQ induces osteoclastic lysosomal membrane permeabilization (LMP) leading to decreased resorption without changes in apoptosis. We hypothesize that skeletal health of patients with increased risk of osteoporosis and fractures may benefit from HCQ by preventing BMD loss. © 2017 Wiley Periodicals, Inc.

Differential effects of raloxifene and estrogen on body composition in growth hormone-replaced hypopituitary women.

PubMed

Birzniece, Vita; Meinhardt, Udo J; Gibney, James; Johannsson, Gudmundur; Armstrong, Nicola; Baxter, Robert C; Ho, Ken K Y

2012-03-01

GH deficiency causes reduction in muscle and bone mass and an increase in fat mass (FM), the changes reversed by GH replacement. The beneficial effects of GH on fat oxidation and protein anabolism are attenuated more markedly by raloxifene, a selective estrogen receptor modulator, compared with 17β-estradiol. Whether this translates to a long-term detrimental effect on body composition is unknown. Our objective was to compare the effects of 17β-estradiol and raloxifene on FM, lean body mass (LBM), and bone mineral density (BMD) during GH replacement. This was an open-label randomized crossover study. Sixteen hypopituitary women received GH (0.5 mg/d) replacement for 24 months. One group received 17β-estradiol (2 mg/d) for the first 6 months before crossover to raloxifene (60 mg/d) for the remaining 18 months; the other received the reversed sequence. Serum IGF-I and IGF-binding protein-3 concentrations, and FM, LBM, lumbar spine and femoral neck BMD were analyzed at baseline and at 6, 12, and 24 months within and between subjects. GH therapy significantly increased mean IGF-I during 17β-estradiol and raloxifene cotreatments equally, but elevated IGF-binding protein-3 to a greater extent during raloxifene cotreatment. GH cotreatment with 17β-estradiol increased LBM and lumbar spine and femoral neck BMD and reduced FM to a greater extent than with raloxifene. In hypopituitary women, raloxifene at therapeutic doses significantly attenuated the beneficial effects of GH on body composition compared with 17β-estradiol. Raloxifene has no metabolic advantage over 17β-estradiol during GH replacement.

Incidence of Vertebral Fractures in Women with Systemic Lupus Erythematosus After 8 Years of Follow-Up.

PubMed

García-Carrasco, Mario; Mendoza-Pinto, Claudia; León-Vázquez, María de la Luz; Méndez-Martínez, Socorro; Etchegaray-Morales, Ivet; Montiel-Jarquín, Álvaro; Enriquez-Guerra, Miguel Angel; Muñóz-Guarneros, Margarita; Gálvez-Romero, José Luis; Soto-Santillán, Pamela; Cervera, Ricard

2017-09-01

The aim of this study was to evaluate possible associations between potential risk factors and the occurrence of established vertebral fractures (VF) in Mexican patients with systemic lupus erythematosus (SLE). Consecutive patients with SLE were enrolled in a prospective, observational study from 2006 to 2015. Information on potential risk factors, including demographics, clinical data, and bone mineral density (BMD) at the lumbar spine and hip on dual-energy X-ray absorptiometry was collected at baseline and follow-up. Semiquantitative analysis was used to determine incident VF on lateral thoracic and lumbar radiographs, defined as any vertebral body graded normal at baseline and at least mildly deformed (20-25% reduction or more in any vertebral height) during follow-up. Differences in baseline characteristics were assessed in patients with and without new radiographic VF. Of 110 SLE patients included, with a median follow-up of 8 (IQR 8-9) years, 22 (20%) had radiographic VF at baseline; 35 (32%) patients had a new VF. The annual incidence rate of new morphometric VF was 3.5 (95% CI 2.4-4.91) per 100 patient/years. Most fractures were mild or moderate and biconcave shaped. Incident VF were significantly associated with baseline BMD at the total hip and longer disease duration. Cumulative glucocorticoid dose, postmenopausal status, and previous prevalent VF were not associated with VF. In this SLE cohort in daily clinical practice, new VF were frequently present in SLE patients, especially those with longer disease duration and low-hip BMD.

Dietary Calcium Intake and Calcium Supplementation in Hungarian Patients with Osteoporosis

PubMed Central

Szamosujvári, Pál; Dombai, Péter; Csóré, Katalin; Mikófalvi, Kinga; Steindl, Tímea; Streicher, Ildikó; Tarsoly, Júlia; Zajzon, Gergely; Somogyi, Péter; Szamosújvári, Pál; Lakatos, Péter

2013-01-01

Purpose. Adequate calcium intake is the basis of osteoporosis therapy—when this proves insufficient, even specific antiosteoporotic agents cannot exert their actions properly. Methods. Our representative survey analyzed the dietary intake and supplementation of calcium in 8033 Hungarian female and male (mean age: 68 years) (68.01 (CI95: 67.81–68.21)) patients with osteoporosis. Results. Mean intake from dietary sources was 665 ± 7.9 mg (68.01 (CI95: 67.81–68.21)) daily. A significant positive relationship could be detected between total dietary calcium intake and lumbar spine BMD (P = 0.045), whereas such correlation could not be demonstrated with femoral T-score. Milk consumption positively correlated with femur (P = 0.041), but not with lumbar BMD. The ingestion of one liter of milk daily increased the T-score by 0.133. Average intake from supplementation was 558 ± 6.2 mg (68.01 (CI95: 67.81–68.21)) daily. The cumulative dose of calcium—from both dietary intake and supplementation—was significantly associated with lumbar (r = 0.024, P = 0.049), but not with femur BMD (r = 0.021, P = 0.107). The currently recommended 1000–1500 mg total daily calcium intake was achieved in 34.5% of patients only. It was lower than recommended in 47.8% of the cases and substantially higher in 17.7% of subjects. Conclusions. We conclude that calcium intake in Hungarian osteoporotic patients is much lower than the current recommendation, while routinely applied calcium supplementation will result in inappropriately high calcium intake in numerous patients. PMID:23737777

Protective effect of zoledronic acid on articular cartilage and subchondral bone of rabbits with experimental knee osteoarthritis

PubMed Central

She, Guorong; Zhou, Ziqi; Zha, Zhengang; Wang, Fei; Pan, Xiaoting

2017-01-01

Subchondral bone reabsorption and remodeling are responsible for the initiation and progression of osteoarthritis (OA). Zoledronic acid (ZOL), a third-generation bisphosphonate (BIS), is an inhibitor of bone reabsorption. However, the intervention effect of ZOL on OA has not been fully characterized and remains to be directly demonstrated in animal experiments. The present study examined the microscopic and macroscopic changes in the anterior cruciate ligament transection (ACLT) model of OA in rabbits and evaluated the effects of ZOL on cartilage degeneration and subchondral bone loss. A total of 32 New Zealand white rabbits were randomly divided into four groups: High-, medium- and low-dose ZOL groups, which received an intravenous injection of 250, 50 and 10 µg/kg ZOL, respectively, after modeling, as well as an untreated group. The bone mineral density (BMD) of the knee joint was evaluated by dual-energy X-ray absorptiometry scanning immediately after modeling and at 4 and 8 weeks. At week 8, quantitative measurement of cartilage was performed by a specialized magnetic resonance imaging (MRI) technique, including three-dimensional fat-suppressed spoil gradient-recalled sequence and T2 mapping. The rabbits were sacrificed by air embolism after anesthesia and both knee joints were harvested and evaluated by general and histological observation. Toluidine blue and hematoxylin and eosin staining were used to assess histological changes in the articular cartilage. Quantitative analysis of cartilage histopathology was performed according to the Mankin scoring system. The BMD of ACLT joints dropped after modeling, which was effectively suppressed by ZOL at the high and medium dose but not the low dose. MRI scans demonstrated that in the untreated group, articular cartilages on ACLT knees were thinner than those on normal knees. The high dose of ZOL preserved the cartilage tissue thickness more efficiently than the medium and low doses. Observation of specimens and pathological slices revealed that the articular cartilage degeneration in the high-dose ZOL group was lightest, while that in the medium- and low-dose ZOL group was moderate, and the untreated group exhibited the most severe defect. The untreated group had the highest Mankin score, whereas the high-dose ZOL group had the lowest score. In conclusion, ZOL increased the subchondral bone density, improved the microstructure and reduced the degeneration of articular cartilage in OA according to morphological as well as quantitative observation. ZOL exerted significant chondroprotective effects in a dose-dependent manner. A favorable chondroprotective effect was induced at the dose of 250 µg/kg. ZOL may represent a novel promising drug to complement the treatment of OA. PMID:29201194

Bone mineral density and correlation factor analysis in normal Taiwanese children.

PubMed

Shu, San-Ging

2007-01-01

Our aim was to establish reference data and linear regression equations for lumbar bone mineral density (BMD) in normal Taiwanese children. Several influencing factors of lumbar BMD were investigated. Two hundred fifty-seven healthy children were recruited from schools, 136 boys and 121 girls, aged 4-18 years were enrolled on a voluntary basis with written consent. Their height, weight, blood pressure, puberty stage, bone age and lumbar BMD (L2-4) by dual energy x-ray absorptiometry (DEXA) were measured. Data were analyzed using Pearson correlation and stepwise regression tests. All measurements increased with age. Prior to age 8, there was no gender difference. Parameters such as height, weight, and bone age (BA) in girls surpassed boys between ages 8-13 without statistical significance (p> or =0.05). This was reversed subsequently after age 14 in height (p<0.05). BMD difference had the same trend but was not statistically significant either. The influencing power of puberty stage and bone age over BMD was almost equal to or higher than that of height and weight. All the other factors correlated with BMD to variable powers. Multiple linear regression equations for boys and girls were formulated. BMD reference data is provided and can be used to monitor childhood pathological conditions. However, BMD in those with abnormal bone age or pubertal development could need modifications to ensure accuracy.

Normal Bone Mineral Density Associates with Duodenal Mucosa Healing in Adult Patients with Celiac Disease on a Gluten-Free Diet.

PubMed

Larussa, Tiziana; Suraci, Evelina; Imeneo, Maria; Marasco, Raffaella; Luzza, Francesco

2017-01-31

Impairment of bone mineral density (BMD) is frequent in celiac disease (CD) patients on a gluten-free diet (GFD). The normalization of intestinal mucosa is still difficult to predict. We aim to investigate the relationship between BMD and duodenal mucosa healing (DMH) in CD patients on a GFD. Sixty-four consecutive CD patients on a GFD were recruited. After a median period of a 6-year GFD (range 2-33 years), patients underwent repeat duodenal biopsy and dual-energy X-ray absorptiometry (DXA) scan. Twenty-four patients (38%) displayed normal and 40 (62%) low BMD, 47 (73%) DMH, and 17 (27%) duodenal mucosa lesions. All patients but one with normal BMD (23 of 24, 96%) showed DMH, while, among those with low BMD, 24 (60%) did and 16 (40%) did not. At multivariate analysis, being older (odds ratio (OR) 1.1, 95% confidence interval (CI) 1.03-1.18) and having diagnosis at an older age (OR 1.09, 95% CI 1.03-1.16) were associated with low BMD; in turn, having normal BMD was the only variable independently associated with DMH (OR 17.5, 95% CI 1.6-192). In older CD patients and with late onset disease, BMD recovery is not guaranteed, despite a GFD. A normal DXA scan identified CD patients with DMH; thus, it is a potential tool in planning endoscopic resampling.

Association of Insulin Resistance with Bone Strength and Bone Turnover in Menopausal Chinese-Singaporean Women without Diabetes

PubMed Central

Kalimeri, Maria; Leek, Francesca; Wang, Nan Xin; Koh, Huann Rong; Totman, John J.

2018-01-01

Insulin resistance (IR) is accompanied by increased areal or volumetric bone mineral density (aBMD or vBMD), but also higher fracture risk. Meanwhile, imbalances in bone health biomarkers affect insulin production. This study investigates the effect of IR on proximal femur and lumbar spine BMD, femoral neck bending, compressive and impact strength indices (Composite Strength Indices) and circulating levels of parathyroid hormone (PTH), C-telopeptide of Type I collagen (CTx-1) and 25(OH) Vitamin D3, in a cohort of 97 healthy, non-obese, menopausal Chinese-Singaporean women. Lumbar spine aBMD was inversely associated with IR and dependent on lean body mass (LBM) and age. No such associations were found for vBMD of the third lumbar vertebra, aBMD and vBMD of the proximal femur, or circulating levels of PTH, CTx-1 and 25(OH) Vitamin D3. Composite Strength Indices were inversely associated with IR and independent of LBM, but after adjusting for fat mass and age, this association remained valid only for the impact strength index. Composite Strength Indices were significantly lower in participants with a high degree of IR. Our findings on IR and Composite Strength Indices relationships were in agreement with previous studies on different cohorts, but those on IR and BMD associations were not. PMID:29710852

Identification of a gene module associated with BMD through the integration of network analysis and genome-wide association data.

PubMed

Farber, Charles R

2010-11-01

Bone mineral density (BMD) is influenced by a complex network of gene interactions; therefore, elucidating the relationships between genes and how those genes, in turn, influence BMD is critical for developing a comprehensive understanding of osteoporosis. To investigate the role of transcriptional networks in the regulation of BMD, we performed a weighted gene coexpression network analysis (WGCNA) using microarray expression data on monocytes from young individuals with low or high BMD. WGCNA groups genes into modules based on patterns of gene coexpression. and our analysis identified 11 gene modules. We observed that the overall expression of one module (referred to as module 9) was significantly higher in the low-BMD group (p = .03). Module 9 was highly enriched for genes belonging to the immune system-related gene ontology (GO) category "response to virus" (p = 7.6 × 10(-11)). Using publically available genome-wide association study data, we independently validated the importance of module 9 by demonstrating that highly connected module 9 hubs were more likely, relative to less highly connected genes, to be genetically associated with BMD. This study highlights the advantages of systems-level analyses to uncover coexpression modules associated with bone mass and suggests that particular monocyte expression patterns may mediate differences in BMD. © 2010 American Society for Bone and Mineral Research.

Normative Bone Mineral Density Z-Scores for Canadians Aged 16 to 24 Years: The Canadian Multicenter Osteoporosis Study

PubMed Central

Zhou, Wei; Langsetmo, Lisa; Berger, Claudie; Adachi, Jonathan D.; Papaioannou, Alexandra; Ioannidis, George; Webber, Colin; Atkinson, Stephanie A.; Olszynski, Wojciech P.; Brown, Jacques P.; Hanley, David A.; Josse, Robert; Kreiger, Nancy; Prior, Jerilynn; Kaiser, Stephanie; Kirkland, Susan; Goltzman, David; Davison, Kenneth Shawn

2016-01-01

The objectives of the study were to develop bone mineral density (BMD) reference norms and BMD Z-scores at various skeletal sites, to determine whether prior fracture and/or asthma were related to BMD, and to assess possible geographic variation of BMD among Canadian youth aged 16–24 yr. Z-Scores were defined as the number of standard deviations from the mean BMD of a healthy population of the same age, race, and sex. Z-Scores were calculated using the reference sample defined as Canadian Caucasian participants without asthma or prior fracture. Reference standards were created for lumbar spine (L1–L4), femoral neck, total hip, and greater trochanter, by each year of age (16–24 yr), and by sex. The Z-score norms were developed for groups noted earlier. Mean Z-scores between the asthma or fracture subgroups compared with the mean Z-scores in the reference sample were not different. There were minor differences in mean BMD across different Canadian geographic regions. This study provides age, sex, and skeletal site-specific Caucasian reference norms and formulae for the calculation of BMD Z-scores for Canadian youth aged 16–24 yr. This information will be valuable to help to identify individuals with clinically meaningful low BMD. PMID:20554232

Genetics of Bone Mass in Childhood and Adolescence: Effects of Sex and Maturation Interactions.

PubMed

Mitchell, Jonathan A; Chesi, Alessandra; Elci, Okan; McCormack, Shana E; Kalkwarf, Heidi J; Lappe, Joan M; Gilsanz, Vicente; Oberfield, Sharon E; Shepherd, John A; Kelly, Andrea; Zemel, Babette S; Grant, Struan F A

2015-09-01

We aimed to determine if adult bone mineral density (BMD) susceptibility loci were associated with pediatric bone mass and density, and if sex and pubertal stage influenced any association. We analyzed prospective areal BMD (aBMD) and bone mineral content (BMC) data from the Bone Mineral Density in Childhood Study (n = 603, European ancestry, 54% female). Linear mixed models were used to assess if 77 single-nucleotide polymorphisms (SNPs) near known adult BMD susceptibility loci interacted with sex and pubertal stage to influence the aBMD/BMC; adjusting for age, BMI, physical activity, and dietary calcium. The strongest main association was observed between an SNP near C7orf58 and distal radius aBMD. However, this association had a significant sex • SNP interaction, revealing a significant association only in females (b = -0.32, p = 1.8 × 10(-6)). Furthermore, the C12orf23 locus had significant interactions with both sex and pubertal stage, revealing associations in females during Tanner stage I for total hip aBMD (b = 0.24, p = 0.001) and femoral neck aBMD (b = 0.27, p = 3.0 × 10(-5)). In contrast, the sex • SNP interactions for loci near LRP5 and WNT16 uncovered associations that were only in males for total body less head BMC (b = 0.22, p = 4.4 × 10(-4)) and distal radius aBMD (b = 0.27, p = 0.001), respectively. Furthermore, the LRP5 locus interacted with both sex and pubertal stage, demonstrating associations that were exclusively in males during Tanner V for total hip aBMD (b = 0.29, p = 0.003). In total, significant sex • SNP interactions were found at 15 loci; pubertal stage • SNP interactions at 23 loci and 19 loci interacted with both sex and pubertal stage. In conclusion, variants originally associated with adult BMD influence bone mass in children of European ancestry, highlighting the fact that many of these loci operate early in life. However, the direction and magnitude of associations for a large number of SNPs only became evident when accounting for sex and maturation. © 2015 American Society for Bone and Mineral Research.

Association of genetic variants of MAOA and SH2B1 with bone mineral density in community-dwelling Japanese women.

PubMed

Yamada, Yoshiji; Ando, Fujiko; Shimokata, Hiroshi

2008-01-01

Although bone mineral density (BMD) is a complex trait that is influenced by both genetic and environmental factors, heritability studies in twins and families have shown that genetic factors account for 60-85% of its variance. We examined the relation of the variable number of tandem repeats (VNTR) polymorphism of the monoamine oxidase A gene (MAOA) and the A↷G (Thr484Ala) polymorphism of the SH2B adaptor protein 1 gene (SH2B1) to BMD in community-dwelling Japanese women and men. The 2235 subjects (1107 women, 1128 men) were aged 40-79 years and were randomly recruited for a population-based prospective cohort study of aging and age-related diseases in Japan. BMD at the distal and proximal radius was measured by peripheral quantitative computed tomography, and the BMD of the total body, lumbar spine (L2-L4), right femoral neck and right trochanter was measured by dual-energy X-ray absorptiometry. The genotypes of the VNTR polymorphism of MAOA were determined by DNA fragment analysis, and those of the A↷G (Thr484Ala) polymorphism of SH2B1 by melting curve analysis. The VNTR polymorphism of MAOA was associated with the BMD of the distal radius, total body, lumbar spine and trochanter in all women, and with the BMD of the total body and trochanter in postmenopausal ones, with the L (four repeats) and S (two or three repeats) alleles reflecting increased and decreased BMD, respectively. The A↷G (Thr484Ala) polymorphism of SH2B1 was associated with the BMD of the lumbar spine in all women, with the BMD of the proximal radius in premenopausal women and with the BMD of the lumbar spine, femoral neck and trochanter in postmenopausal women, with the variant G allele being related to increased BMD. These results suggest that MAOA and SH2B1 are determinative loci for bone mass in Japanese women, especially in postmenopausal ones.

Fracture discrimination by combined bone mineral density (BMD) and microarchitectural texture analysis.

PubMed

Touvier, J; Winzenrieth, R; Johansson, H; Roux, J P; Chaintreuil, J; Toumi, H; Jennane, R; Hans, D; Lespessailles, E

2015-04-01

The use of bone mineral density (BMD) for fracture discrimination may be improved by considering bone microarchitecture. Texture parameters such as trabecular bone score (TBS) or mean Hurst parameter (H) could help to find women who are at high risk of fracture in the non-osteoporotic group. The purpose of this study was to combine BMD and microarchitectural texture parameters (spine TBS and calcaneus H) for the detection of osteoporotic fractures. Two hundred and fifty five women had a lumbar spine (LS), total hip (TH), and femoral neck (FN) DXA. Additionally, texture analyses were performed with TBS on spine DXA and with H on calcaneus radiographs. Seventy-nine women had prevalent fragility fractures. The association with fracture was evaluated by multivariate logistic regressions. The diagnostic value of each parameter alone and together was evaluated by odds ratios (OR). The area under curve (AUC) of the receiver operating characteristics (ROC) were assessed in models including BMD, H, and TBS. Women were also classified above and under the lowest tertile of H or TBS according to their BMD status. Women with prevalent fracture were older and had lower TBS, H, LS-BMD, and TH-BMD than women without fracture. Age-adjusted ORs were 1.66, 1.70, and 1.93 for LS, FN, and TH-BMD, respectively. Both TBS and H remained significantly associated with fracture after adjustment for age and TH-BMD: OR 2.07 [1.43; 3.05] and 1.47 [1.04; 2.11], respectively. The addition of texture parameters in the multivariate models didn't show a significant improvement of the ROC-AUC. However, women with normal or osteopenic BMD in the lowest range of TBS or H had significantly more fractures than women above the TBS or the H threshold. We have shown the potential interest of texture parameters such as TBS and H in addition to BMD to discriminate patients with or without osteoporotic fractures. However, their clinical added values should be evaluated relative to other risk factors.

Dietary acid load is associated with lower bone mineral density in men with low intake of dietary calcium.

PubMed

Mangano, Kelsey M; Walsh, Stephen J; Kenny, Anne M; Insogna, Karl L; Kerstetter, Jane E

2014-02-01

High dietary acid load (DAL) may be detrimental to bone mineral density (BMD). The objectives of the study were to: (1) evaluate the cross-sectional relation between DAL and BMD; and (2) determine whether calcium intake modifies this association. Men (n = 1218) and women (n = 907) aged ≥60 years were included from the National Health and Nutrition Examination Survey 2005-2008. Nutrient intake from 2, 24-hour recalls was used to calculate net endogenous acid production (NEAP) and potential renal acid load (PRAL) (mEq/d). PRAL was calculated from dietary calcium (PRALdiet ) and diet + supplemental calcium (PRALtotal ). Tests for linear trend in adjusted mean BMD of the hip and lumbar spine were performed across energy-adjusted NEAP and PRAL quartiles. Modification by calcium intake (dietary or total) above or below 800 mg/d was assessed by interaction terms. Overall, mean age was 69 ± 0.3 years. Among women, there was no association between NEAP and BMD. PRALdiet was positively associated with proximal femur BMD (p trend = 0.04). No associations were observed with PRALtotal at any BMD site (p range, 0.38-0.82). Among men, no significant associations were observed between BMD and NEAP or PRAL. However, an interaction between PRALdiet and calcium intake was observed with proximal femur BMD (p = 0.08). An inverse association between PRALdiet and proximal femur BMD was detected among men with <800 mg/d dietary calcium (p = 0.02); no associations were found among men with ≥800 mg/d (p = 0.98). A significant interaction with PRALtotal was not observed. In conclusion, when supplemental calcium is considered, there is no association between DAL and BMD among adults. Men with low dietary calcium showed an inverse relation with PRAL at the proximal femur; in women no interaction was observed. This study highlights the importance of calcium intake in counteracting the adverse effect of DAL on bone health. Further research should determine the relation between DAL and change in BMD with very low calcium intake. © 2014 American Society for Bone and Mineral Research.

A calibration methodology of QCT BMD for human vertebral body with registered micro-CT images.

PubMed

Dall'Ara, E; Varga, P; Pahr, D; Zysset, P

2011-05-01

The accuracy of QCT-based homogenized finite element (FE) models is strongly related to the accuracy of the prediction of bone volume fraction (BV/TV) from bone mineral density (BMD). The goal of this study was to establish a calibration methodology to relate the BMD computed with QCT with the BV/TV computed with micro-CT (microCT) over a wide range of bone mineral densities and to investigate the effect of region size in which BMD and BV/TV are computed. Six human vertebral bodies were dissected from the spine of six donors and scanned submerged in water with QCT (voxel size: 0.391 x 0.391 x 0.450 mm3) and microCT (isotropic voxel size: 0.018(3) mm3). The microCT images were segmented with a single level threshold. Afterward, QCT-grayscale, microCT-grayscale, and microCT-segmented images were registered. Two isotropic grids of 1.230 mm (small) and 4.920 mm (large) were superimposed on every image, and QCT(BMD) was compared both with microCT(BMD) and microCT(BV/TV) for each grid cell. The ranges of QCT(BMD) for large and small regions were 9-559 mg/cm3 and -90 to 1006 mg/cm3, respectively. QCT(BMD) was found to overestimate microCT(BMD). No significant differences were found between the QCT(BMD)-microCT(BV/TV) regression parameters of the two grid sizes. However, the R2 was higher, and the standard error of the estimate (SEE) was lower for large regions when compared to small regions. For the pooled data, an extrapolated QCTBMD value equal to 1062 mg/ cm3 was found to correspond to 100% microCT(BV/TV). A calibration method was defined to evaluate BV/TV from QCTBMD values for cortical and trabecular bone in vitro. The QCT(BMD-microCT(BV/TV) calibration was found to be dependent on the scanned vertebral section but not on the size of the regions. However, the higher SEE computed for small regions suggests that the deleterious effect of QCT image noise on FE modelling increases with decreasing voxel size.

Long-chain omega-3 polyunsaturated fatty acid dietary intake is positively associated with bone mineral density in normal and osteopenic Spanish women

PubMed Central

Pedrera-Canal, Maria; Aliaga, Ignacio; Leal-Hernandez, Olga; Rico-Martin, Sergio; Canal-Macias, Maria L.

2018-01-01

The regular consumption of long-chain omega-3 polyunsaturated fatty acids (LCO3-PUFAs) results in general health benefits. The intake of LCO3-PUFAs has been reported to contribute to bone metabolism. We aimed to investigate the relationships between dietary intakes of LCO3-PUFAs and bone mineral density (BMD) in Spanish women aged 20–79 years old. A total of 1865 female subjects (20–79 years old) were enrolled, and lumbar (L2, L3, L3 and total spine), hip (femoral neck (FN), femoral trochanter (FT) and Ward’s triangle (WT)) bone mineral density (BMD) were measured by dual energy X-ray absorptiometry (DXA). Dietary intakes of total energy, calcium, vitamin D, alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and n-6 fatty acids (linoleic acid (LA) and arachidonic acid (AA)) were assessed by a self-administered food frequency questionnaire (FFQ). Spearman’s rank correlations between LCO3-PUFAs and BMD were estimated. Partial correlations controlling for age, weight, height, dietary calcium, vitamin D, menopausal status and energy were calculated. A multiple regression analysis was computed to assess significant associations with BMD in this population. After adjustment for potential confounding factors, there were positive correlations between ALA, EPA and DHA intake and BMD. According to the WHO diagnosis criteria for osteoporosis, in this population of normal and osteopenic women, the dietary intake of ALA was also significantly associated with BMD at the hip. In normal women, the dietary intake of DHA was also significantly associated with BMD at the lumbar spine. No significant associations between LCO3-PUFAs and BMD were detected in the lumbar spine of osteopenic or osteoporotic women. The dietary intake of LCO3-PUFAs was positively associated with BMD in Spanish women at both the hips and the lumbar spine. We highlight that the intake of LCO3-PUFAs is not significantly associated with BMD in osteoporotic women; however, the intake of LCO3-PUFAs seems to be positively associated with BMD at both the hips and the lumbar spine in normal and osteopenic women. PMID:29304057

The effect of weight training on bone mineral density and bone turnover in postmenopausal breast cancer survivors with bone loss: a 24-month randomized controlled trial.

PubMed

Waltman, N L; Twiss, J J; Ott, C D; Gross, G J; Lindsey, A M; Moore, T E; Berg, K; Kupzyk, K

2010-08-01

This study examined whether 24 months of weight training exercises enhanced the effectiveness of risedronate, calcium, and vitamin D in maintaining or improving bone mineral density (BMD) in 223 postmenopausal breast cancer survivors. Subjects who were > or =50% adherent to exercise had no improvement in BMD but were less likely to lose BMD. This study examined whether (1) postmenopausal breast cancer survivors (BCS) with bone loss taking 24 months of risedronate, calcium, and vitamin D had increased bone mineral density (BMD) at the total hip, femoral neck, L1-L4 spine, total radius and 33% radius, and decreased bone turnover; (2) subjects who also participated in strength/weight training (ST) exercises had greater increases in BMD and greater decreases in bone turnover; and (3) subjects who also exercised were more likely to preserve (at least maintain) BMD. Postmenopausal BCS (223) were randomly assigned to exercise plus medication or medication only groups. Both groups received 24 months of 1,200 mg of calcium and 400 IU of vitamin D daily and 35 mg of risedronate weekly, and the exercise group additionally had ST exercises twice weekly. After 24 months, women who took medications without exercising had significant improvements in BMD at the total hip (+1.81%) and spine (+2.85%) and significant decreases in Alkphase B (-8.7%) and serum NTx (-16.7%). Women who also exercised had additional increases in BMD at the femoral neck (+0.29%), total hip (+0.34%), spine (+0.23%), total radius (+0.30%), and additional decreases in Alkphase B (-2.4%) and Serum NTx (-6.5%). Additional changes in BMD and bone turnover with exercise were not significant. Subjects who were > or =50% adherent to exercise were less likely to lose BMD at the total hip (chi-square [1] = 4.66, p = 0.03) and femoral neck (chi-square [1] = 4.63, p = 0.03). Strength/weight training exercises may prevent loss of BMD in postmenopausal BCS at risk for bone loss.

Volumetric bone mineral density (vBMD), bone structure, and structural geometry among rural South Indian, US Caucasian, and Afro-Caribbean older men.

PubMed

Jammy, Guru Rajesh; Boudreau, Robert M; Singh, Tushar; Sharma, Pawan Kumar; Ensrud, Kristine; Zmuda, Joseph M; Reddy, P S; Newman, Anne B; Cauley, Jane A

2018-05-22

Peripheral quantitative computed tomography (pQCT) provides biomechanical estimates of bone strength. Rural South Indian men have reduced biomechanical indices of bone strength compared to US Caucasian and Afro-Caribbean men. This suggests an underlying higher risk of osteoporotic fractures and greater future fracture burden among the rural South Indian men. Geographical and racial comparisons of bone mineral density (BMD) have largely focused on DXA measures of areal BMD. In contrast, peripheral quantitative computed tomography (pQCT) measures volumetric BMD (vBMD), bone structural geometry and provides estimates of biomechanical strength. To further understand potential geographical and racial differences in skeletal health, we compared pQCT measures among US Caucasian, Afro-Caribbean, and rural South Indian men. We studied men aged ≥ 60 years enrolled in the Mobility and Independent Living among Elders Study (MILES) in rural south India (N = 245), Osteoporotic Fractures in Men Study (MrOS) in the US (N = 1148), and the Tobago Bone Health Study (N = 828). The BMI (kg/m 2 ) of rural South Indian men (21.6) was significantly lower compared to the US Caucasians (28) and Afro-Caribbean men (26.9). Adjusting for age, height, body weight, and grip strength; rural South Indian men compared to US Caucasians had significantly lower trabecular vBMD [- 1.3 to - 1.5 standard deviation (SD)], cortical thickness [- 0.8 to - 1.2 SD]; significantly higher endosteal circumference [0.5 to 0.8 SD]; but similar cortical vBMD. Afro-Caribbean men compared to US Caucasians had similar trabecular vBMD but significantly higher cortical vBMD [0.9 to 1.2 SD], SSIp [0.2 to 1.4 SD], and tibial endosteal circumference [1 SD], CONCLUSIONS: In comparison to US Caucasians, rural South Indian men have reduced bone strength (lower trabecular vBMD) and Afro-Caribbean men have greater bone strength (higher cortical vBMD). These results suggest an underlying higher risk of osteoporotic fractures and greater future fracture burden among rural South Indian men.

Quantitative trait loci on chromosomes 2p, 4p, and 13q influence bone mineral density of the forearm and hip in Mexican Americans.

PubMed

Kammerer, Candace M; Schneider, Jennifer L; Cole, Shelley A; Hixson, James E; Samollow, Paul B; O'Connell, Jeffrey R; Perez, Reina; Dyer, Thomas D; Almasy, Laura; Blangero, John; Bauer, Richard L; Mitchell, Braxton D

2003-12-01

We performed a genome scan using BMD data of the forearm and hip on 664 individuals in 29 Mexican-American families. We obtained evidence for QTL on chromosome 4p, affecting forearm BMD overall, and on chromosomes 2p and 13q, affecting hip BMD in men. The San Antonio Family Osteoporosis Study (SAFOS) was designed to identify genes and environmental factors that influence bone mineral density (BMD) using data from large Mexican-American families. We performed a genome-wide linkage analysis using 416 highly polymorphic microsatellite markers spaced approximately 9.5 cM apart to locate and identify quantitative trait loci (QTL) that affect BMD of the forearm and hip. Multipoint variance components linkage analyses were done using data on all 664 subjects, as well as two subgroups of 259 men and 261 premenopausal women, from 29 families for which genotypic and phenotypic data were available. We obtained significant evidence for a QTL affecting forearm (radius midpoint) BMD in men and women combined on chromosome 4p near D4S2639 (maximum LOD = 4.33, genomic p = 0.006) and suggestive evidence for a QTL on chromosome 12q near locus D12S2070 (maximum conditional LOD = 2.35). We found suggestive evidence for a QTL influencing trochanter BMD on chromosome 6 (maximum LOD = 2.27), but no evidence for QTL affecting the femoral neck in men and women combined. In men, we obtained evidence for QTL affecting neck and trochanter BMD on chromosomes 2p near D2S1780 (maximum LOD = 3.98, genomic p = 0.013) and 13q near D13S788 (maximum LOD = 3.46, genomic p = 0.039), respectively. We found no evidence for QTL affecting forearm or hip BMD in premenopausal women. These results provide strong evidence that a QTL on chromosome 4p affects radius BMD in Mexican-American men and women, as well as evidence that QTL on chromosomes 2p and 13q affect hip BMD in men. Our results are consistent with some reports in humans and mice. J Bone Miner Res 2003;18:2245-2252

Breastfeeding as the sole source of milk for 6 months and adolescent bone mineral density.

PubMed

Blanco, E; Burrows, R; Reyes, M; Lozoff, B; Gahagan, S; Albala, C

2017-10-01

Little is known regarding the relationship between early life factors and bone mineral density (BMD). We found a positive association between breastfeeding for at least 6 months, without formula supplementation, and whole body adolescent BMD z-score. The aim of the study is to assess the role of breastfeeding BF on adolescent bone mineral density (BMD) in a cohort prospectively followed since infancy. We studied 679 participants from an infancy iron deficiency anemia preventive trial in Santiago, Chile, followed to adolescence. Breast and bottle feeding were ascertained weekly from 4 to 12 months. At 16 years, whole body BMD was assessed by DEXA. Using linear regression, we evaluated associations between BF duration and BF as the sole source of milk and adolescent BMD z-score, adjusting for possible infancy, adolescent, and background confounders. Mean birth weight and length were 3.5 (0.3) kg and 50.7 (1.6) cm. For at least 6 months, BF was the sole source of milk for 26.3% and with supplementation for 36.7%. For 37%, BF was provided for less than 6 months. Mean 16-year BMD z-score was 0.25 (1.0). Covariates included male sex, birth length, and gestational age. BF as the sole source of milk ≥6 months, compared to BF < 6 months, was associated with higher adolescent BMD z-score adjusting for covariates (β = 0.29, p < 0.05). Mixed BF was not significantly related to adolescent BMD z-score (β = 0.06, p = 0.47). For every 30 days of BF as the sole source of milk, adolescent BMD z-score increased by 0.03 (p = 0.01). BF without formula supplementation for at least 6 months was associated with higher adolescent BMD z-score and a suggestive trend in the same direction for BMD suggests that exclusivity and duration of BF may play a role in adolescent bone health.

Bone mineral content and density of the lumbar spine of infants and toddlers: influence of age, sex, race, growth, and human milk feeding.

PubMed

Kalkwarf, Heidi J; Zemel, Babette S; Yolton, Kimberly; Heubi, James E

2013-01-01

Little is known about factors that affect bone mass and density of infants and toddlers and the means to assess their bone health owing to challenges in studying this population. The objectives of this study were to describe age, sex, race, growth, and human milk feeding effects on bone mineral content (BMC) and areal density (aBMD) of the lumbar spine, and determine precision of BMC and aBMD measurements. We conducted a cross-sectional study of 307 healthy participants (63 black), ages 1 to 36 months. BMC and aBMD of the lumbar spine were measured by dual-energy X-ray absorptiometry. Duplicate scans were obtained on 76 participants for precision determination. Age-specific Z-scores for aBMD, weight, and length (BMDZ, WAZ, LAZ) were calculated. Information on human milk feeding duration was ascertained by questionnaire. Between ages 1 and 36 months, lumbar spine BMC increased about fivefold and aBMD increased twofold (p < 0.0001). BMC was greater (5.8%) in males than in females (p = 0.001), but there was no difference in aBMD (p = 0.37). There was no difference in BMC or aBMD between whites and blacks (p ≥ 0.16). WAZ and LAZ were positively associated with BMDZ (r = 0.34 and 0.24, p < 0.001). Duration of human milk feeding was negatively associated with BMDZ in infants <12 months of age (r = -0.42, p < 0.001). Precision of BMC and aBMD measurements was good, 2.20% and 1.84%, respectively. Dramatic increases in BMC and aBMD of the lumbar spine occur in the first 36 months of life. We provide age-specific values for aBMD of healthy infants and toddlers that can be used to evaluate bone deficits. Future studies are needed to identify the age when sex and race differences in aBMD occur, and how best to account for delayed or accelerated growth in the context of bone health assessment of infants and toddlers. Copyright © 2013 American Society for Bone and Mineral Research.

Dietary patterns and longitudinal change in hip bone mineral density among older men.

PubMed

Rogers, T S; Harrison, S; Judd, S; Orwoll, E S; Marshall, L M; Shannon, J; Langsetmo, L; Lane, N E; Shikany, J M

2018-05-01

Studying dietary patterns is often more informative than individual nutrients or foods. We found that a Prudent dietary pattern (rich in vegetables and fish) was associated with reduced loss of total hip BMD in older men. A Prudent dietary pattern may be a potential lifestyle strategy for minimizing bone loss. This study aimed to identify baseline dietary patterns using factor analysis in a cohort of older men and to evaluate whether the dietary patterns were associated with bone mineral density change (%ΔBMD) at the total hip and femoral neck over time. Participants (n = 4379; mean age 72.9 ± 5.5 years) were from the Osteoporotic Fractures in Men (MrOS) prospective cohort study and had dietary data collected at baseline (March 2000-April 2002) and BMD measured at baseline and Visit 2 (March 2005-May 2006). Dietary intake was assessed with a brief Block food frequency questionnaire (FFQ); factor analysis was used to derive dietary patterns. BMD was measured by dual-energy x-ray absorptiometry (DXA); %ΔBMD was calculated from baseline to Visit 2. We used generalized linear regression to estimate least square (LS) means of %ΔBMD in quartiles of the dietary pattern scores adjusted for potential confounding factors. Two major dietary patterns were derived: Prudent (abundant in vegetables, salad, and non-fried fish) and Western (rich in hamburger, fries, processed meats, cheese, and sweets/desserts). There was an inverse association between adherence to the Prudent pattern and total hip %ΔBMD (p-trend = 0.028 after adjusting for age and clinical site; p-trend = 0.033 after further adjustment for smoking, calcium supplement use, diabetes, hypertension, and total energy intake). No other consistent associations between dietary patterns and %ΔBMD were observed. Greater adherence to a Prudent dietary pattern may attenuate total hip BMD loss (%ΔBMD) in older men.

No impact of disease and its treatment on bone mineral density in survivors of childhood acute lymphoblastic leukemia.

PubMed

Jain, Silky; Jain, Sandeep; Kapoor, Gauri; Virmani, Anju; Bajpai, Ram

2017-04-01

Acute lymphoblastic leukemia (ALL) and its treatment are often implicated in adversely affecting bone health. Conflicting reports in the literature and a paucity of studies from the developing world prompted us to study bone mineral density (BMD) in childhood ALL survivors. BMD lumbar spine (LS) and whole body (WB) were evaluated, using dual energy x-ray absorptiometry in 65 pediatric ALL survivors who had been off-therapy for at least 2 years. The control group constituted of 50 age- and sex-matched healthy siblings. Kernel density plots were used to compare BMD among cases and controls. The disease-, treatment-, hormone- and lifestyle-related factors likely to modulate BMD were analyzed using the Mann-Whitney U test and Student's t-test. At a median of 4.3 years (range, 2-14.8 years) since cessation of therapy, height-adjusted (HA) mean BMD Z-scores of LS (-0.67 ± 1.11, -0.607 ± 1.05, P = 0.759) and WB (-0.842 ± 0.92, -0.513 ± 0.97, P = 0.627) were comparable among the cases and controls. Disease, treatment (chemotherapy, cranial radiotherapy) and endocrine factors did not predict low BMD. However, survivors with calcium intake <800 mg/day (WB, P = 0.018) and hypovitaminosis D (≤25 nmol/L) had lower BMD values (HA-WB, P = 0.046) than the controls. A significant proportion of survivors were overweight or obese and had higher BMD Z-scores (HA-LS, P = 0.003; HA-WB, P = 0.028). BMD Z-scores were similar among ALL survivors and controls. It was reassuring that there was no detrimental impact of the disease or its treatment on BMD. Future studies are required to determine the best possible ways to target the modifiable risk factors (diet, vitamin D) to optimize bone health. © 2016 Wiley Periodicals, Inc.

Associations between body mass index, lean and fat body mass and bone mineral density in middle-aged Australians: The Busselton Healthy Ageing Study.

PubMed

Zhu, Kun; Hunter, Michael; James, Alan; Lim, Ee Mun; Walsh, John P

2015-05-01

Low BMI is a risk factor for osteoporosis, but it is not clear if relationships between BMI, lean mass (LM), fat mass (FM) and BMD are consistent across different levels of BMI. We studied 1929 Caucasian participants (1014 females) aged 45-66years in the Busselton Healthy Ageing Study in Western Australia. Body composition and BMD of total body, lumbar spine, total hip and femoral neck were measured using DXA. From generalized additive models, the positive relationships between BMI and BMD were weaker at high BMI, particularly at the spine and in males. In the entire cohort, adjusting for relevant covariates, LM and FM were significant predictors of all BMD measures in both genders. In men, analysis by tertiles of BMI showed that LM and FM (in kg) were positively associated with BMD (in mg/cm(2)) in tertile 1 except for LM and spine BMD (LM β: 5.18-6.80, FM β: 3.38-9.24, all P<0.05), but not in the middle or upper tertiles (LM β: -3.12-3.07, FM β: -4.75-1.82, P>0.05). In women, LM was positively associated with BMD in each tertile of BMI, except for spine BMD in the upper tertile, with regression coefficients lower in the upper tertile (β: 5.16-9.95, 5.76-9.56 and 2.80-5.78, respectively, all P<0.05). FM was positively associated with total body, spine and total hip BMD in women in BMI tertile 1 (β: 2.86-6.68, P<0.05); these associations were weaker or absent in the middle and upper tertiles. In conclusion, in middle-aged adults the positive relationships between lean or fat mass with BMD among those with higher BMI are absent in males and weaker in females. Copyright © 2015 Elsevier Inc. All rights reserved.

Relationships of muscle strength and bone mineral density in ambulatory children with cerebral palsy.

PubMed

Chen, C-L; Lin, K-C; Wu, C-Y; Ke, J-Y; Wang, C-J; Chen, C-Y

2012-02-01

This work explores the relationships of muscle strength and areal bone mineral density (aBMD) in ambulatory children with cerebral palsy (CP). The knee extensor strength, but not motor function, was related to aBMD. Thus, muscle strength, especially antigravity muscle strength, was more associated with aBMD in these children than motor function. Muscle strength is related to bone density in normal children. However, no studies have examined these relationships in ambulatory children with CP. This work explores the relationships of muscle strength and aBMD in ambulatory children with CP. Forty-eight ambulatory children with spastic CP, aged 5-15 years, were classified into two groups based on Gross Motor Function Classification System levels: I (n = 28) and II (n = 20). Another 31 normal development (ND) children were recruited as the comparison group for the aBMD. Children with CP underwent assessments of growth, lumbar and distal femur aBMD, Gross Motor Function Measure-66 (GMFM-66), and muscle strength of knee extensor and flexor by isokinetic dynamometer. The distal femur aBMD, but not lumbar aBMD, was lower in children with CP than in ND children (p < 0.05). Children with level I had greater knee flexor strength and GMFM-66 scores than those with level II (p < 0.001). However, the knee extensor strength and distal femur and lumbar aBMD did not differ between two groups. Regression analysis revealed the weight and knee extensor strength, but not GMFM-66 scores, were related positively to the distal femur and lumbar aBMD (adjusted r (2) = 0.56-0.65, p < 0.001). These results suggest the muscle strength, especially antigravity muscle strength, were more associated with the bone density of ambulatory children with CP than motor function. The data may allow clinicians for early identifying the ambulatory CP children of potential low bone density.

Positive association between mammographic breast density and bone mineral density in the Postmenopausal Estrogen/Progestin Interventions Study

PubMed Central

Crandall, Carolyn; Palla, Shana; Reboussin, Beth A; Ursin, Giske; Greendale, Gail A

2005-01-01

Introduction Mammographic breast density is a strong independent risk factor for breast cancer. We hypothesized that demonstration of an association between mammographic breast density and bone mineral density (BMD) would suggest a unifying underlying mechanism influencing both breast density and BMD. Methods In a cross-sectional analysis of baseline data from the Postmenopausal Estrogen/Progestin Interventions Study (PEPI), participants were aged 45 to 64 years and were at least 1 year postmenopausal. Mammographic breast density (percentage of the breast composed of dense tissue), the outcome, was assessed with a computer-assisted percentage-density method. BMD, the primary predictor, was measured with dual-energy X-ray absorptiometry. Women quitting menopausal hormone therapy to join PEPI were designated recent hormone users. Results The mean age of the 594 women was 56 years. The average time since menopause was 5.6 years. After adjustment for age, body mass index, and cigarette smoking, in women who were not recent hormone users before trial enrollment (n = 415), mammographic density was positively associated with total hip (P = 0.04) and lumbar (P = 0.08) BMD. Mammographic density of recent hormone users (n = 171) was not significantly related to either total hip (P = 0.51) or lumbar (P = 0.44) BMD. In participants who were not recent hormone users, mammographic density was 4% greater in the highest quartile of total hip BMD than in the lowest. In participants who were not recent hormone users, mammographic density was 5% greater in the highest quartile of lumbar spine BMD than in the lowest. Conclusion Mammographic density and BMD are positively associated in women who have not recently used postmenopausal hormones. A unifying biological mechanism may link mammographic density and BMD. Recent exogenous postmenopausal hormone use may obscure the association between mammographic density and BMD by having a persistent effect on breast tissue. PMID:16280044

Bone Mineral Density Changes Among Women Initiating Proton Pump Inhibitors or H2 Receptor Antagonists: A SWAN Cohort Study

PubMed Central

Solomon, Daniel H; Diem, Susan J; Ruppert, Kristine; Juan Lian, Yin; Liu, Chih-Chin; Wohlfart, Alyssa; Greendale, Gail A; Finkelstein, Joel S

2015-01-01

Proton pump inhibitors (PPIs) have been associated with diminished bone mineral density (BMD) and an increased risk of fracture; however, prior studies have not yielded consistent results, and many have suboptimal ascertainment of both PPI use and BMD. We used data from the Study of Women’s Health Across the Nation (SWAN), a multicenter, multi-ethnic, community-based longitudinal cohort study of women across the menopause transition to examine the association between annualized BMD changes and new use of PPIs. We compared changes in BMD in new PPI users with changes in BMD in new users of histamine 2 receptor antagonists (H2RAs) and with changes in BMD in subjects who did not use either class of medications. Mixed linear regression models included recognized risk factors for osteoporosis, including demographics, menopausal transition stage, body mass index (BMI), lifestyle factors, as well as comorbidities and concomitant medications. To provide further evidence for the validity of our analytic approach, we also examined the effects of hormone-replacement therapy (HT), a class of medications that should reduce bone loss, on changes in BMD as an internal positive control group. We identified 207 new users of PPIs, 185 new users of H2RAs, and 1,676 non-users. Study subjects had a mean age of 50 years and were followed for a median of 9.9 years. Adjusted models found no difference in the annualized BMD change at the lumbar spine, femoral neck, or total hip in PPI users compared with H2RA users or non-users. These results were robust to sensitivity analyses. BMD increased as expected in HT users, supporting the validity of our study design. These longitudinal analyses plus similar prior studies argue against an association between PPI use and BMD loss. PMID:25156141

Changes in bone mineral density may predict the risk of fracture differently in older adults according to fall history.

PubMed

Berry, Sarah D; McLean, Robert R; Hannan, Marian T; Cupples, L Adrienne; Kiel, Douglas P

2014-12-01

To determine whether the association between change in bone mass density (BMD) over 4 years and risk of hip and nonvertebral fracture differs according to an individual's history of falls. Population-based cohort study. Framingham, Massachusetts. Individuals with two measures of BMD at the femoral neck (mean age 78.8; 310 male, 492 female). Cox proportional hazards models were used to estimate hazard ratios (HRs) for the association between percentage change in BMD (per sex-specific standard deviation) and risk of incident hip and nonvertebral fracture. Models were stratified based on history of falls (≥1 falls in the past year) and recurrent falls (≥2 falls) ascertained at the time of the second BMD test. Interactions were tested by including the term "fall history * change in BMD" in the models. Mean change in BMD was -0.6%/year; 27.8% of participants reported falls, and 10.8% reported recurrent falls. Seventy-six incident hip and 175 incident nonvertebral fractures occurred over a median follow-up of 9.0 years. There was no difference in the association between change in BMD and hip fracture according to history of falls (P for interaction = .57). The HR associated with change in BMD and nonvertebral fracture was 1.31 (95% confidence interval (CI) = 1.10-1.56) in participants without a history of falls and 0.95 (95% CI 0.70-1.28) in those with a fall (interaction P = .07). Results for recurrent fallers were similar. The effect of BMD loss on risk of nonvertebral fracture may be greater in persons without a history of falls. It is possible that change in BMD contributes less to fracture risk when a strong risk factor for fracture, such as falls, is present. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

Replication of Caucasian loci associated with bone mineral density in Koreans.

PubMed

Kim, Y A; Choi, H J; Lee, J Y; Han, B G; Shin, C S; Cho, N H

2013-10-01

Most bone mineral density (BMD) loci were reported in Caucasian genome-wide association studies (GWAS). This study investigated the association between 59 known BMD loci (+200 suggestive SNPs) and DXA-derived BMD in East Asian population with respect to sex and site specificity. We also identified four novel BMD candidate loci from the suggestive SNPs. Most GWAS have reported BMD-related variations in Caucasian populations. This study investigates whether the BMD loci discovered in Caucasian GWAS are also associated with BMD in East Asian ethnic samples. A total of 2,729 unrelated Korean individuals from a population-based cohort were analyzed. We selected 747 single-nucleotide polymorphisms (SNPs). These markers included 547 SNPs from 59 loci with genome-wide significance (GWS, p value less than 5 × 10(-8)) levels and 200 suggestive SNPs that showed weaker BMD association with p value less than 5 × 10(-5). After quality control, 535 GWS SNPs and 182 suggestive SNPs were included in the replication analysis. Of the 535 GWS SNPs, 276 from 25 loci were replicated (p < 0.05) in the Korean population with 51.6 % replication rate. Of the 182 suggestive variants, 16 were replicated (p < 0.05, 8.8 % of replication rate), and five reached a significant combined p value (less than 7.0 × 10(-5), 0.05/717 SNPs, corrected for multiple testing). Two markers (rs11711157, rs3732477) are for the same signal near the gene CPN2 (carboxypeptidase N, polypeptide 2). The other variants, rs6436440 and rs2291296, were located in the genes AP1S3 (adaptor-related protein complex 1, sigma 3 subunit) and RARB (retinoic acid receptor, beta). Our results illustrate ethnic differences in BMD susceptibility genes and underscore the need for further genetic studies in each ethnic group. We were also able to replicate some SNPs with suggestive associations. These SNPs may be BMD-related genetic markers and should be further investigated.

Characteristics of bone turnover in the long bone metaphysis fractured patients with normal or low Bone Mineral Density (BMD).

PubMed

Wölfl, Christoph; Schweppenhäuser, Daniela; Gühring, Thorsten; Takur, Caner; Höner, Bernd; Kneser, Ulrich; Grützner, Paul Alfred; Kolios, Leila

2014-01-01

The incidence of osteoporotic fractures increases as our population ages. Until now, the exact biochemical processes that occur during the healing of metaphyseal fractures remain unclear. Diagnostic instruments that allow a dynamic insight into the fracture healing process are as yet unavailable. In the present matched pair analysis, we study the time course of the osteoanabolic markers bone specific alkaline phosphatase (BAP) and transforming growth factor β1 (TGFβ1), as well as the osteocatabolic markers crosslinked C-telopeptide of type-I-collagen (β-CTX) and serum band 5 tartrate-resistant acid phosphatase (TRAP5b), during the healing of fractures that have a low level of bone mineral density (BMD) compared with fractures that have a normal BMD. Between March 2007 and February 2009, 30 patients aged older than 50 years who suffered a metaphyseal fracture were included in our study. BMDs were verified by dual energy Xray absorptiometry (DXEA) scans. The levels of BTMs were examined over an 8-week period. Osteoanabolic BAP levels in those with low levels of BMD were significantly different from the BAP levels in those with normal BMD. BAP levels in the former group increased constantly, whereas the latter group showed an initial strong decrease in BAP followed by slowly rising values. Osteocatabolic β-CTX increased in the bone of the normal BMD group constantly, whereas these levels decreased significantly in the bone of the group with low BMD from the first week. TRAP5b was significantly reduced in the low level BMD group. With this work, we conduct first insights into the molecular biology of the fracture healing process in patients with low levels of BMD that explains the mechanism of its fracture healing. The results may be one reason for the reduced healing qualities in bones with low BMD.

Replication of associations between LRP5 and ESRRA variants and bone density in premenopausal women.

PubMed

Giroux, S; Elfassihi, L; Cole, D E C; Rousseau, F

2008-12-01

Replication is a critical step to validate positive genetic associations. In this study, we tested two previously reported positive associations. The low density lipoprotein receptor-related protein 5 (LRP5) Val667Met and lumbar spine bone density are replicated. This result is in line with results from large consortiums such as Genomos. However, the estrogen-related receptor alpha (ESRRA) repeat in the promoter is not replicated although the polymorphism studied was functional and could have been a causative variant. We sought to validate associations previously reported between LRP5 V667M polymorphism and lumbar spine (LS, p = 0.013) and femoral neck (FN, p = 0.0002) bone mineral density (BMD), and between ESRRA 23 base pair repeat polymorphism and LS BMD (p = 0.0036) in a sample of premenopausal Caucasian women using an independent sample. For the replication sample, we recruited 673 premenopausal women from the Toronto metropolitan area. All women were Caucasian and had BMD measured. LRP5 V667M was genotyped by allele-specific PCR and ESRRA repeats by sizing of PCR products on agarose gels. We reproduced the same association as we reported previously between LRP5 V667M and LS BMD (p = 0.015) but not with FN BMD (p = 0.254). The combined data from the two populations indicate an effect size of 0.28SD for LS BMD (p = 0.00048) and an effect size of 0.26 SD for FN BMD (p = 0.00037). In contrast, the association we reported earlier between ESRRA repeats and LS BMD was not replicated in the sample from Toronto (p = 0.645). The association between LRP5 V667M and LS BMD is confirmed but not that between ESRRA repeats and LS BMD. This result indicates that it is imperative to validate any positive association in an independent sample.

A frequent regulatory variant of the estrogen-related receptor alpha gene associated with BMD in French-Canadian premenopausal women.

PubMed

Laflamme, Nathalie; Giroux, Sylvie; Loredo-Osti, J Concepción; Elfassihi, Latifa; Dodin, Sylvie; Blanchet, Claudine; Morgan, Kenneth; Giguère, Vincent; Rousseau, François

2005-06-01

Genes are important BMD determinants. We studied the association of an ESRRA gene functional variant with BMD in 1335 premenopausal women. The ESRRA genotype was an independent predictor of L2-L4 BMD, with an effect similar to smoking and equivalent to a 10-kg difference in weight. Several genetic polymorphisms have been associated with osteoporosis or osteoporosis fractures, but no functional effect has been shown for most of these gene variants. Because functional studies have implicated estrogen-related receptor alpha (ESRRA) in bone metabolism, we evaluated whether a recently described regulatory variant of the ESRRA gene is associated with lumbar and hip BMD as measured by DXA and with heel bone parameters as measured by quantitative ultrasound (QUS). Heel bone parameters were measured by right calcaneal QUS in 1335 healthy French-Canadian premenopausal women, and one-half of these women also had their BMD evaluated at two sites: femoral neck and lumbar spine (L2-L4) by DXA. All bone measures were tested separately for association with the ESRRA genotype by analysis of covariance. The significance of the ESRRA contribution to the model was also assessed by two different permutation tests. A statistically significant association between ESRRA genotype and lumbar spine BMD was observed: women carrying the long ESRRA genotype had a 3.9% (0.045 g/cm2) higher lumbar spine BMD than those carrying the short ESRRA genotype (p = 0.004), independently of other risk factors measured. This effect of ESRRA genotype is similar to the effect of smoking and equivalent to a 10-kg difference in weight. This association was confirmed by permutation tests (p = 0.004). The same trend was observed for femoral neck BMD (2.6%, p = 0.07). However, no association was observed between ESRRA and QUS heel bone measures. These results support the genetic influence of this ESRRA regulatory variant on BMD.

Prevalence of low bone mineral density in female dancers.

PubMed

Amorim, Tânia; Wyon, Matthew; Maia, José; Machado, José Carlos; Marques, Franklim; Metsios, George S; Flouris, Andreas D; Koutedakis, Yiannis

2015-02-01

While some authors report that dancers have reduced bone mineral density (BMD) and increased risk of osteoporosis, others have stressed the positive effects of dance training on developing healthy BMD. Given the existing controversy, the aim of this systematic review was to examine the best evidence-based information available in relation to female dancers. Four databases (Web of Science, PubMed, EBSCO, Scopus) and two dance science journals (Journal of Dance Medicine and Science and Medical Problems of Performing Artists) were searched for relevant material using the keywords "dance", "ballet", "BMD", "bone density", "osteoporosis" and "female athlete triad syndrome". A total of 257 abstracts were screened using selected inclusion (studies involving bone measurements in dancers) and exclusion (editorials, opinion papers, chapters in books, narrative reviews and non-English language papers) criteria according to PRISMA guidelines. Following the above screening, a total of 108 abstracts were identified as potentially relevant. After the exclusion of conference proceedings, review papers, studies focusing only in male dancers and studies in which dancers' information were combined with other athletes, the eligible papers were subsequently assessed using the GRADE system and grouped according to: (1) prevalence of low BMD and associated factors, (2) incidence of low BMD and risk factors, (3) prevention/treatment of low BMD in dancers, and (4) other studies. Of the 257 abstracts that were initially screened, only 35 studies were finally considered. Only one of these 35 was of high quality, while the remaining 34 were of relatively low quality. Seven studies reported prevalence of low BMD and associated factors, 10 reported associated factors with no prevalence data, while one reported prevalence with no associated factors data. One study cited risk factors, while another one elaborated on the treatment of low BMD in dancers. The remaining 15 studies were classified as "other studies". It remains unclear whether low BMD is prevalent in female dancers. The present review highlights the need for high-quality BMD research in this area.

Calcium and Dairy Products Consumption and Association with Total Hip Bone Mineral Density in Women from Kosovo

PubMed Central

Bahtiri, Elton; Islami, Hilmi; Hoxha, Rexhep; Bytyqi, Hasime Qorraj-; Sermaxhaj, Faton; Halimi, Enis

2014-01-01

Background and objective: There is paucity of evidence in southeastern Europe and Kosovo regarding dairy products consumption and association with bone mineral density (BMD). Therefore, the objective of present study was to assess calcium intake and dairy products consumption and to investigate relationship with total hip BMD in a Kosovo women sample. Methods: This cross-sectional study included a sample of 185 women divided into respective groups according to total hip BMD. All the study participants completed a food frequency questionnaire and underwent dual-energy X-ray absorptiometry (DEXA) to estimate BMD. Nonparametric tests were performed to compare characteristics of the groups. Results: The average dietary calcium intake was 818.41 mg/day. Only 16.75% of the subjects met calcium recommended dietary reference intakes (DRIs). There were no significant differences between low BMD group and normal BMD group regarding average dietary calcium intake, but it was significantly higher in BMDT3 subgroup than in BMDT2 and BMDT1 subgroups. Conclusions: The results of this study demonstrate significant relationship of daily dietary calcium intake with upper BMD tertile. Further initiatives are warranted from this study to highlight the importance of nutrition education. PMID:25568548

Diet, physical activity, and bone density in soldiers before and after deployment.

PubMed

Carlson, Ashley R; Smith, Martha A; McCarthy, Mary S

2013-01-01

To investigate diet, physical activity, and bone mineral density (BMD) in combat service support Soldiers before and after deployment, and to determine if any components of diet or physical activity impacted BMD. Fifty-three Soldiers participated in the study. The BMD of the femoral neck and lumbar spine were measured using dual-energy x-ray absorptiometry. Diet was assessed using the Block Food Frequency Questionnaire. Physical activity was assessed using the Baecke Habitual Physical Activity Questionnaire. The BMD of the spine (0.79%; P=.03) increased significantly during deployment. Reported physical activity at work (-10.76%; P=.01) decreased and vitamin K intake increased (37.21%; P=.01). Soldiers did not meet the dietary reference intake for vitamin D and exceeded the dietary reference intakes for all other nutrients. No significant relationships were observed between change in diet or physical activity and change in BMD. Due to the small sample size, we could not determine if deployment impacted BMD, diet, or physical activity in combat service support Soldiers. Future research should focus on investigating the association between lower levels of physical activity, inadequate diet, and decreased BMD in larger military populations.

Bone mineral density in elite junior Olympic weightlifters.

PubMed

Conroy, B P; Kraemer, W J; Maresh, C M; Fleck, S J; Stone, M H; Fry, A C; Miller, P D; Dalsky, G P

1993-10-01

The purpose of this study was to examine the relationship of bone mineral density (BMD) to muscular strength in highly trained young male athletes in order to gain insights concerning the influence of heavy resistance training on BMD. Twenty-five elite junior weightlifters (age, 17.4 +/- 1.4 yr) and 11 age-matched controls (16.9 +/- 1.1 yr) volunteered for this investigation. Measurements of BMD (g.cm-2) utilizing dual energy x-ray absorptiometry were obtained for the lumbar spine (L2-4) and the proximal femur (neck; trochanter, Ward's triangle). The BMD values for the junior lifters were found to be significantly greater at all sites for the junior weightlifters compared with their age-matched control group. The BMD values of the spine and femoral neck of the junior weightlifters when compared with adult reference data (i.e., 20-39 yr old men) were found to be significantly greater. Both simple and multiple regression analyses demonstrated significant relationships of BMD with strength accounting for 30-65% of the variance. These data suggest that in elite junior weightlifters, muscle strength, highly specific to the sport of weightlifting, has a major influence on BMD due to the influence of the chronic overloads experienced in training.

Benchmark Dose Analysis from Multiple Datasets: The Cumulative Risk Assessment for the N-Methyl Carbamate Pesticides

EPA Science Inventory

The US EPA’s N-Methyl Carbamate (NMC) Cumulative Risk assessment was based on the effect on acetylcholine esterase (AChE) activity of exposure to 10 NMC pesticides through dietary, drinking water, and residential exposures, assuming the effects of joint exposure to NMCs is dose-...

Concordance of transcriptional and apical benchmark dose levels for conazole-ind uced liver effects in mice

EPA Science Inventory

The ability to anchor chemical class-based gene expression changes to phenotypic lesions and to describe these changes as a function of dose and time can inform mode of action and improve quantitative risk assessment. Previous research identified a 330-gene cluster commonly resp...

Issues in the Design and Interpretation of Chronic Toxicity and Carcinogenicity Studies in Rodents: Approaches to Dose Selection

EPA Science Inventory

For more than three decades chronic studies in rodents have been the benchmark for assessing the potential long-term toxicity, and particularly the carcinogenicity, of chemicals. With doses typically administered for about 2 years (18 months to lifetime), the rodent bioassay has ...

Mouse Models for Bone Research to Assess Military Stress Fracture Risk

DTIC Science & Technology

2005-04-01

analyses. DEXA scanning by PIXImus: The PIXImus densitometer (GE-Lunar, Madison , WI) was used to assess whole body areal (a)BMD and body composition...between sexes in 18 of the 28 strains. Sex differences for whole body BMD (aBMD) and BcD of the lumbar spine are not congruent, consequently predicting...cannot be used to predict aBMD, either whole body or at the lumbar spine, or body cornposition compartments. It is important to note that in this

SU-E-I-32: Benchmarking Head CT Doses: A Pooled Vs. Protocol Specific Analysis of Radiation Doses in Adult Head CT Examinations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujii, K; UCLA School of Medicine, Los Angeles, CA; Bostani, M

Purpose: The aim of this study was to collect CT dose index data from adult head exams to establish benchmarks based on either: (a) values pooled from all head exams or (b) values for specific protocols. One part of this was to investigate differences in scan frequency and CT dose index data for inpatients versus outpatients. Methods: We collected CT dose index data (CTDIvol) from adult head CT examinations performed at our medical facilities from Jan 1st to Dec 31th, 2014. Four of these scanners were used for inpatients, the other five were used for outpatients. All scanners used Tubemore » Current Modulation. We used X-ray dose management software to mine dose index data and evaluate CTDIvol for 15807 inpatients and 4263 outpatients undergoing Routine Brain, Sinus, Facial/Mandible, Temporal Bone, CTA Brain and CTA Brain-Neck protocols, and combined across all protocols. Results: For inpatients, Routine Brain series represented 84% of total scans performed. For outpatients, Sinus scans represented the largest fraction (36%). The CTDIvol (mean ± SD) across all head protocols was 39 ± 30 mGy (min-max: 3.3–540 mGy). The CTDIvol for Routine Brain was 51 ± 6.2 mGy (min-max: 36–84 mGy). The values for Sinus were 24 ± 3.2 mGy (min-max: 13–44 mGy) and for Facial/Mandible were 22 ± 4.3 mGy (min-max: 14–46 mGy). The mean CTDIvol for inpatients and outpatients was similar across protocols with one exception (CTA Brain-Neck). Conclusion: There is substantial dose variation when results from all protocols are pooled together; this is primarily a function of the differences in technical factors of the protocols themselves. When protocols are analyzed separately, there is much less variability. While analyzing pooled data affords some utility, reviewing protocols segregated by clinical indication provides greater opportunity for optimization and establishing useful benchmarks.« less

Peripheral DXA measurement around ankle joint to diagnose osteoporosis as assessed by central DXA measurement.

PubMed

Sung, Ki Hyuk; Choi, Young; Cho, Gyeong Hee; Chung, Chin Youb; Park, Moon Seok; Lee, Kyoung Min

2018-02-05

This study evaluated the correlation between central and peripheral bone mineral density (BMD) of the ankle joint, using dual-energy X-ray absorptiometry (DXA). We also investigated whether peripheral ankle BMD could be used to identify individuals who were diagnosed with osteoporosis, using central DXA. We recruited 134 volunteers aged 20-90 years who agreed to participate in this study. Central BMD of the lumbar spine and left femur, and peripheral BMD of the medial malleolus, distal tibia, lateral malleolus, and talus were measured with DXA. Among the peripheral sites of the ankle, the highest and lowest BMD were observed in the talus and lateral malleolus, respectively. All peripheral DXA measurements of the ankle joint were significantly correlated with central DXA measurements. There was a good correlation (r: 0.656-0.725) between peripheral and central BMD for the older age group (> 50 years), but fair-to-good correlation (r: 0.263-0.654) for the younger age group (< 50 years). The cut-off values for peripheral BMD of the ankle joint between osteoporosis and non-osteoporosis were 0.548 g/cm 2 (sensitivity, 89.0%; specificity, 69.0%) for the medial malleolus, 0.626 g/cm 2 (sensitivity, 83.3%; specificity, 82.8%) for the distal tibia, 0.47 g/cm 2 (sensitivity, 100.0%; specificity, 65.5%) for the lateral malleolus, and 0.973 g/cm 2 (sensitivity, 72.2%; specificity, 83.6%) for the talus (p < 0.001). This study showed good correlation between peripheral BMD around ankle joint and central BMD for older age group. Further study is required to use the ankle DXA as a valid clinical tool for the diagnosis of osteoporosis and fracture risk assessment.

Increased migration of uncemented acetabular cups in female total hip arthroplasty patients with low systemic bone mineral density. A 2-year RSA and 8-year radiographic follow-up study of 34 patients.

PubMed

Finnilä, Sami; Moritz, Niko; SvedströM, Erkki; Alm, Jessica J; Aro, Hannu T

2016-02-01

Low bone mineral density (BMD) may jeopardize the initial component stability and delay osseointegration of uncemented acetabular cups in total hip arthroplasty (THA). We measured the migration of uncemented cups in women with low or normal BMD. We used radiostereometric analysis (RSA) to measure the migration of hydroxyapatite-coated titanium alloy cups with alumina-on-alumina bearings in THA of 34 female patients with a median age of 64 (41-78) years. 10 patients had normal BMD and 24 patients had low systemic BMD (T-score ≤ -1) based on dual-energy X-ray absorptiometry (DXA). Cup migration was followed with RSA for 2 years. Radiographic follow-up was done at a median of 8 (2-10) years. Patients with normal BMD did not show a statistically significant cup migration after the settling period of 3 months, while patients with low BMD had a continuous proximal migration between 3 and 12 months (p = 0.03). These differences in cup migration persisted at 24 months. Based on the perceived risk of cup revision, 14 of the 24 cases were "at risk" (proximal translation of 0.2 to 1.0 mm) in the low-BMD group and 2 of the 10 cases were "at risk" in the normal-BMD group (odds ratio (OR) = 8.0, 95% CI: 1.3-48). The radiographic follow-up showed no radiolucent lines or osteolysis. 2 cups have been revised for fractures of the ceramic bearings, but none for loosening. Low BMD contributed to cup migration beyond the settling period of 3 months, but the migrating cups appeared to osseointegrate eventually.

Bone mineral density, muscle strength, and recreational exercise in men

NASA Technical Reports Server (NTRS)

Snow-Harter, C.; Whalen, R.; Myburgh, K.; Arnaud, S.; Marcus, R.

1992-01-01

Muscle strength has been shown to predict bone mineral density (BMD) in women. We examined this relationship in 50 healthy men who ranged in age from 28 to 51 years (average 38.3 years). BMD of the lumbar spine, proximal femur, whole body, and tibia were measured by dual-energy x-ray absorptiometry (Hologic QDR 1000W). Dynamic strength using one repetition maximum was assessed for the biceps, quadriceps, and back extensors and for the hip abductors, adductors, and flexors. Isometric grip strength was measured by dynamometry. Daily walking mileage was assessed by 9 week stepmeter records and kinematic analysis of video filming. Subjects were designated as exercisers and nonexercisers. Exercisers participated in recreational exercise at least two times each week. The results demonstrated that BMD at all sites correlated with back and biceps strength (p < 0.01 to p = 0.0001). Body weight correlated with tibia and whole-body BMD (p < 0.001); age negatively correlated with Ward's triangle BMD (p < 0.01). In stepwise multiple regressions, back strength was the only independent predictor of spine and femoral neck density (R2 = 0.27). Further, back strength was the most robust predictor of BMD at the trochanter, Ward's triangle, whole body, and tibia, although biceps strength, age, body weight, and leg strength contributed significantly to BMD at these skeletal sites, accounting for 35-52% of the variance in BMD. Exercisers and nonexercisers were similar for walking (3.97 versus 3.94 miles/day), age (37.8 versus 38.5) years, and weight (80.0 versus 77.7 kg). However, BMD and muscle strength were significantly greater in exercises than in nonexercisers.(ABSTRACT TRUNCATED AT 250 WORDS).

Low bone mineral density and associated risk factors in HIV-infected patients

PubMed Central

Chiţu-Tișu, Cristina-Emilia; Barbu, Ecaterina-Constanţa; Lazăr, Mihai; Ion, Daniela Adriana; Bădărău, Ioana Anca

2016-01-01

Background Aging of persons with human immunodeficiency virus (HIV) resulted in high rates of osteopenia and osteoporosis. Multiple cohort studies have reported an increased prevalence of bone demineralization among HIV-infected individuals. The aim of this study was to evaluate bone mineral density (BMD) and risk factors for osteopenia/osteoporosis among HIV-positive patients attending the National Institute for Infectious Diseases “Prof.Dr. Matei Balș”, Bucharest, Romania. Methods We performed a cross-sectional study that enrolled 60 patients with HIV. The association between BMD and lifestyle habits (smoking), body mass index (BMI), nadir cluster of differentiation 4 (CD4) cell count, current CD4 cell count, HIV viral load and history of combination antiretroviral therapy (cART) were investigated. The BMD was measured at the lumbar spine, hips and total body using dual-energy X-ray absorptiometry (DEXA). Results In the present study, DEXA evaluation showed an overall prevalence of osteoporosis of 16.66% (ten patients) and a prevalence of osteopenia of 48.33% (29 patients). In men, low BMI and cigarette smoking showed significant association with the diagnosis of lumbar spine demineralization (p=0.034 and p=0.041, respectively). Duration of exposure to cART classes in relation to BMD was also evaluated. The use of non-nucleoside reverse-transcriptase inhibitors (NNRTIs) was associated with low lumbar spine BMD in all patients (p=0.015). Reduced BMD was significantly associated with protease inhibitors (PIs)-containing treatment (p=0.043) in women. Conclusion At lumbar spine DEXA, male gender was statistically associated with reduced BMD. At the left hip Ward’s area, decreased BMD T scores were significantly associated with aging. The reduced BMD was higher in patients receiving PI- or NNRTI-containing regimens. PMID:27482514