Investigating the Prevalence of Low Bone Mass in Children of Southern Iran and Its Associated Factors

PubMed Central

Saki, Forough; Ranjbar Omrani, Gholamhossein; Jeddi, Marjan; Bakhshaieshkaram, Marzie; Dabbaghmanesh, Mohammad Hossein

2017-01-01

Background Improving peak bone mass and bone strength in the first years of life and enhancing it during young adulthood could prevent osteoporosis and fractures in the last years of life. We evaluated the prevalence of low bone mass in the lumbar and femoral neck and its associated factors in southern Iranian children. Methods This is a cross-sectional study on healthy Iranian children aged 9 - 18 years old during 2011 - 2012. Dual energy X-ray absorptiometry (DEXA) was used for measuring bone mineral density (BMD). BMD Z-score ≤ -2 was considered as low. Anthropometric data, physical activity, sun exposure, puberty, and mineral biochemical parameters were assessed. Data were analyzed using SPSS v.15. Results 477 normal children, including 236 (49.5%) girls and 241 (50.5%) boys, aged 13.8 ± 2.7 years were enrolled. Prevalence of low bone mass (LBM) in the femoral and lumbar region was 10.7% and 18.7%, respectively. The prevalence of LBM in femur of girls is twice more than boys. Fat mass index, BMI Z-score, and physical activity were associated with lumbar low bone mass. BMI Z-score and physical activity were associated with femoral low bone mass. Conclusions High prevalence of low bone mineral density in children 9 to 18 years in south of the country is concerned and is needed to plan for prevention and treatment. BMI-Z score, fat mass index, and physical activity were the 3 most important preventive factors in developing low bone mass in children. PMID:29344033

Controlled longitudinal study of bone mass accrual in children and adolescents with cystic fibrosis

PubMed Central

Buntain, H M; Schluter, P J; Bell, S C; Greer, R M; Wong, J C H; Batch, J; Lewindon, P; Wainwright, C E

2006-01-01

Background A study was undertaken to observe the gains in bone mass in children and adolescents with cystic fibrosis (CF) over 24 months and to examine the relationship between areal bone mineral density (aBMD) and associated clinical parameters including physical activity, nutrition, and 25‐hydroxyvitamin D (25OHD). Methods Areal BMD of the total body (TB), lumbar spine (LS), and total femoral neck (FNt) were repeatedly measured in 85 subjects aged 5–18 years with CF and 100 age and sex matched controls over 2 years. At each visit anthropometric variables, nutritional parameters, pubertal status, disease severity, physical activity, dietary calcium, caloric intake, and serum 25OHD were assessed and related to aBMD. Results After adjusting for age, sex, and height Z‐score, gains in LS aBMD in children (5–10 years) and TB and FNt aBMD in adolescents (11–18 years) with CF were significantly less than in controls. Lean tissue mass was significantly associated with TB and LS aBMD gains in children and adolescents and explained a significant proportion of the aBMD deficit observed. Lung function parameters were significantly associated with aBMD gains in adolescents with CF. Conclusions Inadequate bone mass accrual during childhood and adolescence contributes to the low bone mass observed in adults with CF. Accounting for the height discrepancy which is frequently observed in those with CF, in addition to age and sex, is important when assessing low bone mass in children and adolescents with CF. To optimise an individual's potential to acquire maximal bone mass, it is necessary to maximise nutritional status and limit the progression of chronic suppurative lung disease. PMID:16384878

Controlled longitudinal study of bone mass accrual in children and adolescents with cystic fibrosis.

PubMed

Buntain, H M; Schluter, P J; Bell, S C; Greer, R M; Wong, J C H; Batch, J; Lewindon, P; Wainwright, C E

2006-02-01

A study was undertaken to observe the gains in bone mass in children and adolescents with cystic fibrosis (CF) over 24 months and to examine the relationship between areal bone mineral density (aBMD) and associated clinical parameters including physical activity, nutrition, and 25-hydroxyvitamin D (25OHD). Areal BMD of the total body (TB), lumbar spine (LS), and total femoral neck (FNt) were repeatedly measured in 85 subjects aged 5-18 years with CF and 100 age and sex matched controls over 2 years. At each visit anthropometric variables, nutritional parameters, pubertal status, disease severity, physical activity, dietary calcium, caloric intake, and serum 25OHD were assessed and related to aBMD. After adjusting for age, sex, and height Z-score, gains in LS aBMD in children (5-10 years) and TB and FNt aBMD in adolescents (11-18 years) with CF were significantly less than in controls. Lean tissue mass was significantly associated with TB and LS aBMD gains in children and adolescents and explained a significant proportion of the aBMD deficit observed. Lung function parameters were significantly associated with aBMD gains in adolescents with CF. Inadequate bone mass accrual during childhood and adolescence contributes to the low bone mass observed in adults with CF. Accounting for the height discrepancy which is frequently observed in those with CF, in addition to age and sex, is important when assessing low bone mass in children and adolescents with CF. To optimise an individual's potential to acquire maximal bone mass, it is necessary to maximise nutritional status and limit the progression of chronic suppurative lung disease.

Do vegetarians have a normal bone mass?

PubMed

New, Susan A

2004-09-01

Public health strategies targeting the prevention of poor bone health on a population-wide basis are urgently required, with particular emphasis being placed on modifiable factors such as nutrition. The aim of this review was to assess the impact of a vegetarian diet on indices of skeletal integrity to address specifically whether vegetarians have a normal bone mass. Analysis of existing literature, through a combination of observational, clinical and intervention studies were assessed in relation to bone health for the following: lacto-ovo-vegetarian and vegan diets versus omnivorous, predominantly meat diets, consumption of animal versus vegetable protein, and fruit and vegetable consumption. Mechanisms of action for a dietary "component" effect were examined and other potential dietary differences between vegetarians and non-vegetarians were also explored. Key findings included: (i) no differences in bone health indices between lacto-ovo-vegetarians and omnivores; (ii) conflicting data for protein effects on bone with high protein consumption (particularly without supporting calcium/alkali intakes) and low protein intake (particularly with respect to vegan diets) being detrimental to the skeleton; (iii) growing support for a beneficial effect of fruit and vegetable intake on bone, with mechanisms of action currently remaining unclarified. The impact of a "vegetarian" diet on bone health is a hugely complex area since: 1) components of the diet (such as calcium, protein, alkali, vitamin K, phytoestrogens) may be varied; 2) key lifestyle factors which are important to bone (such as physical activity) may be different; 3) the tools available for assessing consumption of food are relatively weak. However, from data available and given the limitations stipulated above, "vegetarians" do certainly appear to have "normal" bone mass. What remains our challenge is to determine what components of a vegetarian diet are of particular benefit to bone, at what levels and under which mechanisms.

[Clinical practice guidelines for evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions. Bone Metabolism Working Group of the Spanish Society of Endocrinology].

PubMed

Reyes García, Rebeca; Jódar Gimeno, Esteban; García Martín, Antonia; Romero Muñoz, Manuel; Gómez Sáez, José Manuel; Luque Fernández, Inés; Varsavsky, Mariela; Guadalix Iglesias, Sonsoles; Cano Rodriguez, Isidoro; Ballesteros Pomar, María Dolores; Vidal Casariego, Alfonso; Rozas Moreno, Pedro; Cortés Berdonces, María; Fernández García, Diego; Calleja Canelas, Amparo; Palma Moya, Mercedes; Martínez Díaz-Guerra, Guillermo; Jimenez Moleón, José J; Muñoz Torres, Manuel

2012-03-01

To provide practical recommendations for evaluation and treatment of osteoporosis associated to endocrine diseases and nutritional conditions. Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology, a methodologist, and a documentalist. Recommendations were formulated according to the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed), using the following terms associated to the name of each condition: AND "osteoporosis", "fractures", "bone mineral density", and "treatment". Papers in English with publication date before 18 October 2011 were included. Current evidence for each disease was reviewed by two group members, and doubts related to the review process or development of recommendations were resolved by the methodologist. Finally, recommendations were discussed in a meeting of the Working Group. The document provides evidence-based practical recommendations for evaluation and management of endocrine and nutritional diseases associated to low bone mass or an increased risk of fracture. For each disease, the associated risk of low bone mass and fragility fractures is given, recommendations for bone mass assessment are provided, and treatment options that have shown to be effective for increasing bone mass and/or to decreasing fragility fractures are listed. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

Influence of muscle strength, physical activity and weight on bone mass in a population-based sample of 1004 elderly women.

PubMed

Gerdhem, P; Ringsberg, K A M; Akesson, K; Obrant, K J

2003-09-01

High physical activity level has been associated with high bone mass and low fracture risk and is therefore recommended to reduce fractures in old age. The aim of this study was to estimate the effect of potentially modifiable variables, such as physical activity, muscle strength, muscle mass and weight, on bone mass in elderly women. The influence of isometric thigh muscle strength, self-estimated activity level, body composition and weight on bone mineral density (dual energy X-ray absorptiometry; DXA) in total body, hip and spine was investigated. Subjects were 1004 women, all 75 years old, taking part in the Malmö Osteoporosis Prospective Risk Assessment (OPRA) study. Physical activity and muscle strength accounted for 1-6% of the variability in bone mass, whereas weight, and its closely associated variables lean mass and fat mass, to a much greater extent explained the bone mass variability. We found current body weight to be the variable with the most substantial influence on the total variability in bone mass (15-32% depending on skeletal site) in a forward stepwise regression model. Our findings suggest that in elderly women, the major fracture-preventive effect of physical activity is unlikely to be mediated through increased bone mass. Retaining or even increasing body weight is likely to be beneficial to the skeleton, but an excess body weight increase may have negative effects on health. Nevertheless, training in elderly women may have advantages by improving balance, co-ordination and mobility and therefore decreasing the risk of fractures.

Vitamin D and nutritional status are related to bone fractures in alcoholics.

PubMed

González-Reimers, Emilio; Alvisa-Negrín, Julio; Santolaria-Fernández, Francisco; Candelaria Martín-González, M; Hernández-Betancor, Iván; Fernández-Rodríguez, Camino M; Viña-Rodríguez, J; González-Díaz, Antonieta

2011-01-01

Bone fractures are common in alcoholics. To analyse which factors (ethanol consumption; liver function impairment; bone densitometry; hormone changes; nutritional status, and disrupted social links and altered eating habits) are related to bone fractures in 90 alcoholic men admitted to our hospitalization unit because of organic problems. Bone homoeostasis-related hormones were measured in patients and age- and sex-matched controls. Whole-body densitometry was performed by a Hologic QDR-2000 (Waltham, MA, USA) densitometer, recording bone mineral density (BMD) and fat and lean mass; nutritional status and liver function were assessed. The presence of prevalent fractures was assessed by anamnesis and chest X-ray film. Forty-nine patients presented at least one fracture. We failed to find differences between patients with and without fractures regarding BMD parameters. Differences regarding fat mass were absent, but lean mass was lower among patients with bone fracture. The presence of fracture was significantly associated with impaired subjective nutritional evaluation (χ² = 5.79, P = 0.016), lower vitamin D levels (Z = 2.98, P = 0.003) and irregular eating habits (χ² = 5.32, P = 0.02). Reduced lean mass and fat mass, and altered eating habits were more prevalent among patients with only rib fractures (n = 36) than in patients with multiple fractures and/or fractures affecting other bones (n = 13). These last were more closely related to decompensated liver disease. Serum vitamin D levels showed a significant relationship with handgrip strength (ρ = 0.26, P = 0.023) and lean mass at different parts of the body, but not with fat mass. By logistic regression analysis, only vitamin D and subjective nutritional evaluation were significantly, independently related with fractures. Prevalent fractures are common among heavy alcoholics. Their presence is related more closely to nutritional status, lean mass and vitamin D levels than to BMD. Lean mass is more reduced, nutritional status is more impaired and there is a trend to more altered eating habits among patients with rib fractures, whereas multiple fractures depend more heavily on advanced liver disease.

Association between fat mass, lean mass, and bone loss: the Dubbo Osteoporosis Epidemiology Study.

PubMed

Yang, S; Center, J R; Eisman, J A; Nguyen, T V

2015-04-01

Lower body fat mass is a risk factor for bone loss at lumbar spine in postmenopausal women, but not in men. Body lean mass and fat mass were not associated with femoral neck bone loss in either gender. Bone density and body mass are closely associated. Whole body lean mass (LM) and fat mass (FM) together account for approximately 95 % of body mass. Bone loss is associated with loss of body mass but which of the components of body mass (FM or LM) is related to bone loss is not well understood. Therefore, in this study, we sought to assess whether baseline FM or LM has predictive value for future relative rate of bone mineral density (BMD) changes (%/year). The present population-based cohort study was part of the ongoing Dubbo Osteoporosis Epidemiology Study (DOES). BMD, FM, and LM were measured with dual energy X-ray absorptiometry (GE-LUNAR Corp, Madison, WI). BMD measurements were taken in approximately every 2 years between 2000 and 2010. We only included the participants with at least two BMD measurements at the femoral neck and lumbar spine. In total, 717 individuals (204 men and 513 women) aged 50 years or older were studied. Rate of bone loss at femoral neck and lumbar spine was faster in women than in men (all P < 0.01). In bivariable regression analysis, each 5 kg greater FM in women was associated with 0.4 %/year (P = 0.003) lower bone loss at lumbar spine. This magnitude of association remained virtually unchanged after adjusting for LM and/or other covariates (P = 0.03). After adjusting for covariates, variation of FM accounted for ∼1.5 % total variation in lumbar spine bone loss. However, there was no significant association between FM and change in femoral neck BMD in either men or women. Lower FM was an independent but modest risk factor for greater bone loss at the lumbar spine in women but not in men. If further studies confirm our findings, FM can help predict lumbar spine bone loss in women.

Body Composition, Nutritional Profile and Muscular Fitness Affect Bone Health in a Sample of Schoolchildren from Colombia: The Fuprecol Study

PubMed Central

Forero-Bogotá, Mónica Adriana; Ojeda-Pardo, Mónica Liliana; García-Hermoso, Antonio; Correa-Bautista, Jorge Enrique; González-Jiménez, Emilio; Schmidt-RíoValle, Jacqueline; Navarro-Pérez, Carmen Flores; Gracia-Marco, Luis; Vlachopoulos, Dimitris; Martínez-Torres, Javier; Ramírez-Vélez, Robinson

2017-01-01

The objective of the present study is to investigate the relationships between body composition, nutritional profile, muscular fitness (MF) and bone health in a sample of children and adolescents from Colombia. Participants included 1118 children and adolescents (54.6% girls). Calcaneal broadband ultrasound attenuation (c-BUA) was obtained as a marker of bone health. Body composition (fat mass and lean mass) was assessed using bioelectrical impedance analysis. Furthermore height, weight, waist circumference and Tanner stage were measured and body mass index (BMI) was calculated. Standing long-jump (SLJ) and isometric handgrip dynamometry were used respectively as indicators of lower and upper body muscular fitness. A muscular index score was also computed by summing up the standardised values of both SLJ and handgrip strength. Dietary intake and degree of adherence to the Mediterranean diet were assessed by a 7-day recall questionnaire for food frequency and the Kidmed questionnaire. Poor bone health was considered using a z-score cut off of ≤−1.5 standard deviation. Once the results were adjusted for age and Tanner stage, the predisposing factors of having a c-BUA z-score ≤−1.5 standard deviation included being underweight or obese, having an unhealthy lean mass, having an unhealthy fat mass, SLJ performance, handgrip performance, and unhealthy muscular index score. In conclusion, body composition (fat mass and lean body mass) and MF both influenced bone health in a sample of children and adolescents from Colombia. Thus promoting strength adaptation and preservation in Colombian youth will help to improve bone health, an important protective factor against osteoporosis in later life. PMID:28165360

Body Composition, Nutritional Profile and Muscular Fitness Affect Bone Health in a Sample of Schoolchildren from Colombia: The Fuprecol Study.

PubMed

Forero-Bogotá, Mónica Adriana; Ojeda-Pardo, Mónica Liliana; García-Hermoso, Antonio; Correa-Bautista, Jorge Enrique; González-Jiménez, Emilio; Schmidt-RíoValle, Jacqueline; Navarro-Pérez, Carmen Flores; Gracia-Marco, Luis; Vlachopoulos, Dimitris; Martínez-Torres, Javier; Ramírez-Vélez, Robinson

2017-02-03

The objective of the present study is to investigate the relationships between body composition, nutritional profile, muscular fitness (MF) and bone health in a sample of children and adolescents from Colombia. Participants included 1118 children and adolescents (54.6% girls). Calcaneal broadband ultrasound attenuation (c-BUA) was obtained as a marker of bone health. Body composition (fat mass and lean mass) was assessed using bioelectrical impedance analysis. Furthermore height, weight, waist circumference and Tanner stage were measured and body mass index (BMI) was calculated. Standing long-jump (SLJ) and isometric handgrip dynamometry were used respectively as indicators of lower and upper body muscular fitness. A muscular index score was also computed by summing up the standardised values of both SLJ and handgrip strength. Dietary intake and degree of adherence to the Mediterranean diet were assessed by a 7-day recall questionnaire for food frequency and the Kidmed questionnaire. Poor bone health was considered using a z -score cut off of ≤-1.5 standard deviation. Once the results were adjusted for age and Tanner stage, the predisposing factors of having a c-BUA z-score ≤-1.5 standard deviation included being underweight or obese, having an unhealthy lean mass, having an unhealthy fat mass, SLJ performance, handgrip performance, and unhealthy muscular index score. In conclusion, body composition (fat mass and lean body mass) and MF both influenced bone health in a sample of children and adolescents from Colombia. Thus promoting strength adaptation and preservation in Colombian youth will help to improve bone health, an important protective factor against osteoporosis in later life.

Coupling multiscale X-ray physics and micromechanics for bone tissue composition and elasticity determination from micro-CT data, by example of femora from OVX and sham rats

NASA Astrophysics Data System (ADS)

Hasslinger, Patricia; Vass, Viktoria; Dejaco, Alexander; Blanchard, Romane; Örlygsson, Gissur; Gargiulo, Paolo; Hellmich, Christian

2016-05-01

Due to its high resolution, micro-CT (Computed Tomograph) scanning is the key to assess bone quality of sham and OVX (ovariectomized) rats. Combination of basic X-ray physics, such as the energy- and chemistry-dependence of attenuation coefficients, with results from ashing tests on rat bones, delivers mineral, organic, and water volume fractions within the voxels. Additional use of a microelastic model for bone provides voxel-specific elastic properties. The new method delivers realistic bone mass densities, and reveals that OVX protocols may indeed induce some bone mass loss, while the average composition of the bone tissue remains largely unaltered.

Using bone densitometry to monitor therapy in treating osteoporosis: pros and cons.

PubMed

Deal, C L

2001-06-01

Measurement of bone density is crucial for evaluating fracture risk. Low bone mass is a powerful predictor of fracture and is necessary to assess the need for treatment. Dual energy x-ray absorptiometry is accurate and precise. Use of bone density for monitoring therapy is an important tool for evaluating response to therapy, but an understanding of the limitations of the procedure are important for the practicing physician. Precision error of the technology and what change in density is clinically significant (least significant change) are important concepts to interpret results and make appropriate treatment decisions. This article reviews the use of bone densitometry as a tool for monitoring treatment in patients with low bone mass.

The evaluation of bone mineral density based on nutritional status, age, and anthropometric parameters in elderly women.

PubMed

Ozeraitiene, Violeta; Būtenaite, Violeta

2006-01-01

To examine the relationship between bone mineral density and nutritional status, age, and anthropometrical data in elderly women. A validated international nutrition-risk-screening questionnaire, the Mini Nutritional Assessment, was used for evaluation of nutrition. The Mini Nutritional Assessment is a clinical tool consisting of four items: anthropometric assessment, global evaluation, dietetic assessment, and subjective assessment. Height and body weight were measured while the participants wore indoor clothes and no shoes; mid-arm and calf circumferences were measured with tape measure. The measurements of skinfold thickness on triceps, waist, and thigh were taken with a caliper. Bone mineral density was measured at distal radius of the nondominant forearm by dual x-ray absorptiometry. Our results indicate that anthropometric parameters (height, weight, body mass index, skinfold thickness) in elderly women with osteoporosis were the smallest. It was determined that more fats and proteins are reserved in the body, the greater the bone mineral density is. The nutritional status and age had a significant influence on bone mineral density. It was determined that women with osteoporosis had a tendency for greater malnutrition risk according to Mini Nutritional Assessment. Women with osteoporosis had worse appetites and suffered from cardiovascular diseases more often. It was determined that the nutritional status of elderly women, assessed by the Mini Nutritional Assessment questionnaire, reflects bone mineral density. It was found that women's age and anthropometric data, reflecting fat reserves in the body (body mass index, skinfold thickness), are significantly related to low bone mineral density.

Sclerostin antibody and interval treadmill training effects in a rodent model of glucocorticoid-induced osteopenia.

PubMed

Achiou, Zahra; Toumi, Hechmi; Touvier, Jérome; Boudenot, Arnaud; Uzbekov, Rustem; Ominsky, Michael S; Pallu, Stéphane; Lespessailles, Eric

2015-12-01

Glucocorticoids have a beneficial anti-inflammatory and immunosuppressive effect, but their use is associated with decreased bone formation, bone mass and bone quality, resulting in an elevated fracture risk. Exercise and sclerostin antibody (Scl-Ab) administration have both been shown to increase bone formation and bone mass, therefore the ability of these treatments to inhibit glucocorticoid-induced osteopenia alone or in combination were assessed in a rodent model. Adult (4 months-old) male Wistar rats were allocated to a control group (C) or one of 4 groups injected subcutaneously with methylprednisolone (5mg/kg/day, 5 days/week). Methylprednisolone treated rats were injected subcutaneously 2 days/week with vehicle (M) or Scl-Ab-VI (M+S: 25mg/kg/day) and were submitted or not to treadmill interval training exercise (1h/day, 5 days/week) for 9 weeks (M+E, M+E+S). Methylprednisolone treatment increased % fat mass and % apoptotic osteocytes, reduced whole body and femoral bone mineral content (BMC), reduced femoral bone mineral density (BMD) and osteocyte lacunae occupancy. This effect was associated with lower trabecular bone volume (BV/TV) at the distal femur. Exercise increased BV/TV, osteocyte lacunae occupancy, while reducing fat mass, the bone resorption marker NTx, and osteocyte apoptosis. Exercise did not affect BMC or cortical microarchitectural parameters. Scl-Ab increased the bone formation marker osteocalcin and prevented the deleterious effects of M on bone mass, further increasing BMC, BMD and BV/TV to levels above the C group. Scl-Ab increased femoral cortical bone parameters at distal part and midshaft. Scl-Ab prevented the decrease in osteocyte lacunae occupancy and the increase in osteocyte apoptosis induced by M. The addition of exercise to Scl-Ab treatment did not result in additional improvements in bone mass or bone strength parameters. These data suggest that although our exercise regimen did prevent some of the bone deleterious effects of glucocorticoid treatment, particularly in trabecular bone volume and osteocyte apoptosis, Scl-Ab treatment resulted in marked improvements in bone mass across the skeleton and in osteocyte viability, resulting in decreased bone fragility. Copyright © 2015 Elsevier Inc. All rights reserved.

Calcium requirements of growing rats based on bone mass, structure, or biomechanical strength are similar.

PubMed

Hunt, Janet R; Hunt, Curtiss D; Zito, Carol Ann; Idso, Joseph P; Johnson, LuAnn K

2008-08-01

Although calcium (Ca) supplementation increases bone density, the increase is small and the effect on bone strength and fracture risk is uncertain. To investigate if bone mass, morphology, and biomechanical properties are affected by deficient to copious dietary Ca concentrations, the long bones (tibia and femur) of growing female Sprague-Dawley rats (8/group) were assessed after 13 wk of consuming 1, 2, 3, 4, 5, 6, or 7 g Ca/kg of a modified AIN-93G diet. Dietary phosphorous (P) and vitamin D remained constant at recommended concentrations. The assessment included mineralization, density, biomechanical properties of breaking by a 3-point flexure test, and morphological properties by microcomputed topography scanning of trabecular bone of the proximal tibia metaphysis. Dietary treatment did not affect food intake, weight gain, renal and muscle Ca concentrations, and bone hydroxyproline. All bone parameters measured were significantly impaired by Ca deficiency in rats fed the diet containing 1 g Ca/kg. Modest impairments occurred with some parameters (bone density, biomechanical bending moment, modulus of elasticity, and stress) in rats fed 2 g Ca/kg, but all parameters stabilized between 2 and 3 g/kg diet, with no differences between 3 and 7 g/kg. The results suggest that a threshold response in bone Ca retention or bone mass at approximately 2.5 g Ca/kg diet is associated with similar threshold responses in bone breaking strength and related biomechanics as well as trabecular structural properties. There was no evidence of a relative P deficiency or of improved or impaired bone strength and structure as Ca intakes increased beyond those needed to maximize bone density.

Radiographic absorptiometry method in measurement of localized alveolar bone density changes.

PubMed

Kuhl, E D; Nummikoski, P V

2000-03-01

The objective of this study was to measure the accuracy and precision of a radiographic absorptiometry method by using an occlusal density reference wedge in quantification of localized alveolar bone density changes. Twenty-two volunteer subjects had baseline and follow-up radiographs taken of mandibular premolar-molar regions with an occlusal density reference wedge in both films and added bone chips in the baseline films. The absolute bone equivalent densities were calculated in the areas that contained bone chips from the baseline and follow-up radiographs. The differences in densities described the masses of the added bone chips that were then compared with the true masses by using regression analysis. The correlation between the estimated and true bone-chip masses ranged from R = 0.82 to 0.94, depending on the background bone density. There was an average 22% overestimation of the mass of the bone chips when they were in low-density background, and up to 69% overestimation when in high-density background. The precision error of the method, which was calculated from duplicate bone density measurements of non-changing areas in both films, was 4.5%. The accuracy of the intraoral radiographic absorptiometry method is low when used for absolute quantification of bone density. However, the precision of the method is good and the correlation is linear, indicating that the method can be used for serial assessment of bone density changes at individual sites.

Dietary long-chain inulin reduces abdominal fat but has no effect on bone density in growing female rats.

PubMed

Jamieson, Jennifer A; Ryz, Natasha R; Taylor, Carla G; Weiler, Hope A

2008-08-01

New strategies to improve Ca absorption and bone health are needed to address the current state of osteoporosis prevention and management. Inulin-type fructans have shown great promise as a dietary intervention strategy, but have not yet been tested in a young female model. Our objective was to investigate the effect of long chain (LC) inulin on bone mineralization and density in growing, female rats, as well as the quality of growth. Weanling Sprague-Dawley rats were assigned to inulin or cellulose treatments for either 4 or 8 weeks. Growth was measured weekly and quality of growth assessed using fat pad weights and dual-energy X-ray absorptiometry (DXA). Whole body (WB) and selected regions were analysed for bone mineral density (BMD) and body composition by DXA. Serum markers of bone turnover were assessed by enzyme-linked immunosorbent assays. Ca and P concentrations were determined in excised femurs by inductively coupled plasma spectrometry. Feeding inulin resulted in 4 % higher femoral weight (adjusted for body weight) and 6 % less feed intake. Inulin did not affect WB or regional BMD, but was associated with a 28 % lower parametrial fat pad mass, 21 % less WB fat mass and 5 % less WB mass. In summary, LC-inulin lowered body fat mass, without consequence to bone density in growing female rats.

Breast-feeding and adherence to infant feeding guidelines do not influence bone mass at age 4 years.

PubMed

Harvey, Nicholas C; Robinson, Sian M; Crozier, Sarah R; Marriott, Lynne D; Gale, Catharine R; Cole, Zoe A; Inskip, Hazel M; Godfrey, Keith M; Cooper, Cyrus

2009-09-01

The impact of variations in current infant feeding practice on bone mineral accrual is not known. We examined the associations between duration of breast-feeding and compliance with infant dietary guidelines and later bone size and density at age 4 years. At total of 599 (318 boys) mother-child pairs were recruited from the Southampton Women's Survey. Duration of breast-feeding was recorded and infant diet was assessed at 6 and 12 months using FFQ. At 6 and 12 months the most important dietary pattern, defined by principal component analysis, was characterised by high consumption of vegetables, fruits and home-prepared foods. As this was consistent with infant feeding recommendations, it was denoted the 'infant guidelines' pattern. At age 4 years, children underwent assessment of whole-body bone size and density using a Hologic Discovery dual-energy X-ray absorptiometry instrument. Correlation methods were used to explore the relationships between infant dietary variables and bone mineral. There was no association between duration of breast-feeding in the first year of life and 4-year bone size or density. 'Infant guidelines' pattern scores at 6 and 12 months were also unrelated to bone mass at age 4 years. We observed wide variations in current infant feeding practice, but these variations were not associated with differences in childhood bone mass at age 4 years.

Physical activity and dark skin tone: protective factors against low bone mass in Mexican men.

PubMed

Vivanco-Muñoz, Nalleli; Jo, Talavera; Gerardo, Huitron-Bravo; Juan, Tamayo; Clark, Patricia

2012-01-01

A cross-sectional study was conducted on 268 Mexican men between the ages of 13 and 80 yr to evaluate the association of clinical factors related with bone mass. Men from high schools, universities, and retirement homes were invited to participate. Body mass index (BMI) was measured, and bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry for L1-L4 and total hip. Factors related to bone mass were assessed by questionnaire and analyzed using a logistic regression model. Demographic factors (age, education, and occupation), clinical data (BMI, skin tone, previous fracture, history of osteoporosis [OP], and history of fractures), and lifestyle variables (diet, physical activity, sun exposure, and smoking) were evaluated. Physical activity (≥ 60 min/5 times a week) reduced the risk for low BMD for age, osteopenia, and OP at the spine and total hip (odds ratio [OR]: 0.276; 95% confidence interval [CI]: 0.099-0.769; p=0.014; and OR: 0.184; 95% CI: 0.04-0.849; p=0.03, respectively). Dark skin tone was a protective factor, decreasing the risk by up to 70%. In this population of healthy Mexican men (aged 13-80 yr), dark skin and physical activity were protective factors against low bone mass. Copyright © 2012 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Artistic versus rhythmic gymnastics: effects on bone and muscle mass in young girls.

PubMed

Vicente-Rodriguez, G; Dorado, C; Ara, I; Perez-Gomez, J; Olmedillas, H; Delgado-Guerra, S; Calbet, J A L

2007-05-01

We compared 35 prepubertal girls, 9 artistic gymnasts and 13 rhythmic gymnasts with 13 nonphysically active controls to study the effect of gymnastics on bone and muscle mass. Lean mass, bone mineral content and areal density were measured by dual energy X-ray absorptiometry, and physical fitness was also assessed. The artistic gymnasts showed a delay in pubertal development compared to the other groups (p<0.05). The artistic gymnasts had a 16 and 17 % higher aerobic power and anaerobic capacity, while the rhythmic group had a 14 % higher anaerobic capacity than the controls, respectively (all p<0.05). The artistic gymnasts had higher lean mass (p<0.05) in the whole body and the extremities than both the rhythmic gymnasts and the controls. Body fat mass was 87.5 and 61.5 % higher in the controls than in the artistic and the rhythmic gymnasts (p<0.05). The upper extremity BMD was higher (p<0.05) in the artistic group compared to the other groups. Lean mass strongly correlated with bone mineral content (r=0.84, p<0.001), and multiple regression analysis showed that total lean mass explained 64 % of the variability in whole body bone mineral content, but only 20 % in whole body bone mineral density. Therefore, recreational artistic gymnastic participation is associated with delayed pubertal development, enhanced physical fitness, muscle mass, and bone density in prepubertal girls, eliciting a higher osteogenic stimulus than rhythmic gymnastic.

The Macular Carotenoids Lutein and Zeaxanthin Are Related to Increased Bone Density in Young Healthy Adults

PubMed Central

Bovier, Emily R.; Hammond, Billy R.

2017-01-01

Lutein (L) and zeaxanthin (Z) status can be quantified by measuring their concentrations both in serum and, non-invasively, in retinal tissue. This has resulted in a unique ability to assess their role in a number of tissues ranging from cardiovascular to central nervous system tissue. Recent reports using animal models have suggested yet another role, a developmental increase in bone mass. To test this, we assessed L and Z status in 63 young healthy adults. LZ status was determined by measuring LZ in serum (using HPLC) and retina tissue (measuring macular pigment optical density, MPOD, using customized heterochromatic flicker photometry). Bone density was measured using dual-energy X-ray absorptiometry (DXA). Although serum LZ was generally not related to bone mass, MPOD was significantly related to bone density in the proximal femur and lumbar spine. In general, our results are consistent with carotenoids, specifically LZ, playing a role in optimal bone health. PMID:28880221

The RSPO3 gene as genetic markers for bone mass assessed by quantitative ultrasound in a population of young adults.

PubMed

Correa-Rodríguez, María; Schmidt Rio-Valle, Jacqueline; Rueda-Medina, Blanca

2018-05-01

Ultrasound bone mass measurement has been postulated as a valuable bone-health assessment tool for primary care. The aim of this study was to analyse the possible relationship between the SPTBN1, RSPO3, CCDC170, DKK1, GPATCH1, and TMEM135 genes, with calcaneal quantitative ultrasound (QUS) in a population of young adults. These genes were first associated with broadband ultrasound attenuation (BUA) in the GEFOS/GENOMOS study. A cross-sectional study was conducted on 575 individuals (mean age 20.41 ± 2.69). Bone mass at the right calcaneus was estimated by QUS. Six single-nucleotide polymorphisms (SNPs) in SPTBN1 (rs11898505), RSPO3 (rs7741021), CCDC170 (rs4869739), DKK1 (rs7902708), TMEM135 (rs597319), and GPATCH1 (rs10416265) were selected as genetic markers based on their previous association with calcaneal QUS. After adjusting for multiple confounding factors, the only significant association with QUS in our population was found for the rs7741021 SNP in the RSPO3 gene (P = 0.006) using the dominant model of inheritance. This suggests the possible implication of the RSPO3 gene in bone mass acquisition during early adulthood. © 2017 John Wiley & Sons Ltd/University College London.

Is Serum Serotonin Involved in the Bone Loss of Young Females with Anorexia Nervosa?

PubMed

Maïmoun, L; Guillaume, S; Lefebvre, P; Philibert, P; Bertet, H; Picot, M-C; Courtet, P; Mariano-Goulart, D; Renard, E; Sultan, C

2016-03-01

Recent experimental data suggest that circulating serotonin interacts with bone metabolism, although this is less clear in humans. This study investigated whether serum serotonin interferes with bone metabolism in young women with anorexia nervosa (AN), a clinical model of energy deprivation. Serum serotonin, markers of bone turnover [osteocalcin (OC), procollagen type I N-terminal propeptide (PINP), type I-C telopeptide breakdown products (CTX)], leptin, soluble leptin receptor (sOB-R), and insulin-like growth factor-1 (IGF-1) and its binding protein (IGFBP-3) were assessed. Whole body, spine, hip, and radius areal bone mineral density BMD (aBMD) were assessed by dual-energy X-ray absorptiometry in 21 patients with AN and 19 age-matched controls. Serum serotonin, leptin, IGF-1, IGFBP-3, OC, PINP, and aBMD at all sites, radius excepted, were significantly reduced in AN whereas CTX and sOB-R were increased compared with controls. Serum serotonin levels were positively correlated with weight, body mass index, whole body fat mass, leptin, and IGF-1, and negatively with CTX for the entire population. Low serum serotonin levels are observed in patients with AN. Although no direct link between low serum serotonin levels and bone mass was identified in these patients, the negative relationship between serotonin and markers of bone resorption found in all population nevertheless suggests the implication of serotonin in bone metabolism. Impact of low serum serotonin on bone in AN warrants further studies. © Georg Thieme Verlag KG Stuttgart · New York.

Does fetal smoke exposure affect childhood bone mass? The Generation R Study.

PubMed

Heppe, D H M; Medina-Gomez, C; Hofman, A; Rivadeneira, F; Jaddoe, V W V

2015-04-01

We assessed the intrauterine influence of maternal smoking on childhood bone mass by comparing parental prenatal and postnatal smoking habits. We observed higher bone mass in children exposed to maternal smoking, explained by higher body weight. Maternal smoking or related lifestyle factors may affect childhood weight gain rather than skeletal growth. Maternal smoking during pregnancy may adversely affect bone health in later life. By comparing the associations of maternal and paternal smoking and of prenatal and postnatal exposure with childhood bone measures, we aimed to explore whether the suggested association could be explained by fetal programming or reflects confounding by familial factors. In 5565 mothers, fathers and children participating in a population-based prospective cohort study, parental smoking habits during pregnancy and current household smoking habits were assessed by postal questionnaires. Total body bone mineral content (BMC), bone area (BA) and bone mineral density (BMD) were measured by dual-energy X-ray absorptiometry (DXA) at the median age of 6.0 years (IQR 0.37). In confounder-adjusted models, maternal smoking during pregnancy was associated with a higher BMC of 11.6 g (95 % confidence interval (CI) 5.6, 17.5), a larger BA of 9.7 cm(2) (95 % CI 3.0, 16.4), a higher BMD of 6.7 g/cm(2) (95 % CI 2.4, 11.0) and a higher BMC of 5.4 g (95 % CI 1.3, 9.6) adjusted for BA of the child. Current weight turned out to mediate these associations. Among mothers who did not smoke, paternal smoking did not show evident associations with childhood bone measures. Also, household smoking practices during childhood were not associated with childhood bone measures. Our results do not support the hypothesis of fetal smoke exposure affecting childhood bone mass via intrauterine mechanisms. Maternal smoking or related lifestyle factors may affect childhood weight gain rather than skeletal growth.

Bone mineral density and metabolic indices in hyperthyroidism.

PubMed

Al-Nuaim, A; El-Desouki, M; Sulimani, R; Mohammadiah, M

1991-09-01

Hyperthyroidism can alter bone metabolism by increasing both bone resorption and formation. The increase in bone resorption predominates, leading to a decrease in bone mass. To assess the effect of hyperthyroidism on bone and mineral metabolism, we measured bone density using single photon absorptiometry in 30 untreated hyperthyroid patients. Patients were categorized into three groups based on sex and alkaline phosphatase levels: 44 sex- and age-matched subjects were used as controls. Bone densities were significanlty lower in all patient groups compared with controls. Alkaline phosphatase was found to be a useful marker for assessing severity of bone disease in hyperthyroid patients as there is significant bone density among patients with higher alkaline phosphatase value. Hyperthyroidism should be considered in the differential diagnosis of unexplained alkaline phophatase activity.

[Effect of high impact movements on body composition, strength and bone mineral density on women over 60 years].

PubMed

Ramírez-Villada, Jhon F; León-Ariza, Henry H; Argüello-Gutiérrez, Yenny P; Porras-Ramírez, Keyla A

2016-01-01

Osteoporosis is characterised by loss of bone mass and deterioration of bone tissue microarchitecture that leads to fragility related to the risk of fractures. The aim of the study is to analyse the effects of a training program based on explosive movements and impact, assessed in a swimming pool, on body composition, explosive strength and bone mineral density in women over 60 years old. A total of 35 healthy physically active women (60±4.19 years) were divided into a training pool group using multi jumps (JG) and a control group (CG). JG trained for 24 weeks, 3 times a week, an hour and a half per session. Body composition testing, explosive strength, and bone mineral density were assessed before and after the program. There were differences in the explosive force (JG vs CG=P<.05 to .001) and the estimated power (JG vs CG=P<.05 to .002) between JG vs CG, with significant increases in JG. There were no significant differences in the percentage of fat and lean mass, bone mineral density lumbar and femoral between groups, although slightly significant increases in bone mineral density lumbar and femoral could be seen in JG after program implementation (JG pre-test vs JG post- test=P<.05). The training program with impact and explosive movements assessed in a pool induces gains in muscle strength and power with slight adaptations in body mass index in women over 60 years. Copyright © 2015 SEGG. Published by Elsevier Espana. All rights reserved.

An update on childhood bone health: mineral accrual, assessment and treatment.

PubMed

Sopher, Aviva B; Fennoy, Ilene; Oberfield, Sharon E

2015-02-01

To update the reader's knowledge about the factors that influence bone mineral accrual and to review the advances in the assessment of bone health and treatment of bone disorders. Maternal vitamin D status influences neonatal calcium levels, bone mineral density (BMD) and bone size. In turn, BMD z-score tends to track in childhood. These factors highlight the importance of bone health as early as fetal life. Dual-energy x-ray absorptiometry is the mainstay of clinical bone health assessment in this population because of the availability of appropriate reference data. Recently, more information has become available about the assessment and treatment of bone disease in chronically ill pediatric patients. Bone health must become a health focus starting prenatally in order to maximize peak bone mass and to prevent osteoporosis-related bone disease in adulthood. Vitamin D, calcium and weight-bearing activity are the factors of key importance throughout childhood in achieving optimal bone health as BMD z-score tracks through childhood and into adulthood. Recent updates of the International Society for Clinical Densitometry focus on the appropriate use of dual-energy x-ray absorptiometry in children of all ages, including children with chronic disease, and on the treatment of pediatric bone disease.

Assessment of bone mineral status in children with Marfan syndrome

USDA-ARS?s Scientific Manuscript database

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder with skeletal involvement. It is caused by mutations in fibrillin1 (FBN1) gene resulting in activation of TGF-ßeta, which developmentally regulates bone mass and matrix properties. There is no consensus regarding bone minerali...

Characterization of microgravity effects on bone structure and strength using fractal analysis

NASA Technical Reports Server (NTRS)

Acharya, Raj S.; Shackelford, Linda

1995-01-01

The effect of micro-gravity on the musculoskeletal system has been well studied. Significant changes in bone and muscle have been shown after long term space flight. Similar changes have been demonstrated due to bed rest. Bone demineralization is particularly profound in weight bearing bones. Much of the current techniques to monitor bone condition use bone mass measurements. However, bone mass measurements are not reliable to distinguish Osteoporotic and Normal subjects. It has been shown that the overlap between normals and osteoporosis is found for all of the bone mass measurement technologies: single and dual photon absorptiometry, quantitative computed tomography and direct measurement of bone area/volume on biopsy as well as radiogrammetry. A similar discordance is noted in the fact that it has not been regularly possible to find the expected correlation between severity of osteoporosis and degree of bone loss. Structural parameters such as trabecular connectivity have been proposed as features for assessing bone conditions. In this report, we use fractal analysis to characterize bone structure. We show that the fractal dimension computed with MRI images and X-Ray images of the patella are the same. Preliminary experimental results show that the fractal dimension computed from MRI images of vertebrae of human subjects before bedrest is higher than during bedrest.

Effects of a short-term whole body vibration intervention on bone mass and structure in elderly people.

PubMed

Gómez-Cabello, Alba; González-Agüero, Alejandro; Morales, Silvia; Ara, Ignacio; Casajús, José A; Vicente-Rodríguez, Germán

2014-03-01

We aimed to clarify whether a short-term whole body vibration training has a beneficial effect on bone mass and structure in elderly men and women. Randomised controlled trial. A total of 49 non-institutionalised elderly (20 men and 29 women) volunteered to participate in the study. Participants who met the inclusion criteria were randomly assigned to one of the study groups (whole body vibration or control). A total of 24 elderly trained squat positioned on a vibration platform 3 times per week for 11 weeks. Bone-related variables were assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Two-way repeated measures one-way analysis of variance (group by time) was used to determine the effects of the intervention on the bone-related variables and also to determinate the changes within group throughout the intervention period. Analysis of covariance was used to test the differences between groups for bone-related variables in pre- and post-training assessments and in the percentage of change between groups. All analysis were carried out including age, height, subtotal lean mass and daily calcium intake as covariates. 11 weeks of whole body vibration training led to no changes in none of the bone mineral content and bone mineral density parameters measured by dual-energy X-ray absorptiometry through the skeleton. At the tibia, total, trabecular and cortical volumetric bone mineral density decreased significantly in the whole body vibration group (all P<0.05). A short-term whole body vibration therapy is not enough to cause any changes on bone mineral content or bone mineral density and it only produces a slight variation on bone structure among elderly people. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Insulin Resistance Is Associated With Smaller Cortical Bone Size in Nondiabetic Men at the Age of Peak Bone Mass.

PubMed

Verroken, Charlotte; Zmierczak, Hans-Georg; Goemaere, Stefan; Kaufman, Jean-Marc; Lapauw, Bruno

2017-06-01

In type 2 diabetes mellitus, fracture risk is increased despite preserved areal bone mineral density. Although this apparent paradox may in part be explained by insulin resistance affecting bone structure and/or material properties, few studies have investigated the association between insulin resistance and bone geometry. We aimed to explore this association in a cohort of nondiabetic men at the age of peak bone mass. Nine hundred ninety-six nondiabetic men aged 25 to 45 years were recruited in a cross-sectional, population-based sibling pair study at a university research center. Insulin resistance was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR), with insulin and glucose measured from fasting serum samples. Bone geometry was assessed using peripheral quantitative computed tomography at the distal radius and the radial and tibial shafts. In age-, height-, and weight-adjusted analyses, HOMA-IR was inversely associated with trabecular area at the distal radius and with cortical area, periosteal and endosteal circumference, and polar strength strain index at the radial and tibial shafts (β ≤ -0.13, P < 0.001). These associations remained essentially unchanged after additional adjustment for dual-energy X-ray absorptiometry-derived body composition, bone turnover markers, muscle size or function measurements, or adiponectin, leptin, insulin-like growth factor 1, or sex steroid levels. In this cohort of nondiabetic men at the age of peak bone mass, insulin resistance is inversely associated with trabecular and cortical bone size. These associations persist after adjustment for body composition, muscle size or function, or sex steroid levels, suggesting an independent effect of insulin resistance on bone geometry. Copyright © 2017 Endocrine Society

Peak bone strength is influenced by calcium intake in growing rats.

PubMed

Viguet-Carrin, S; Hoppler, M; Membrez Scalfo, F; Vuichoud, J; Vigo, M; Offord, E A; Ammann, P

2014-11-01

In this study we investigated the effect of supplementing the diet of the growing male rat with different levels of calcium (from low to higher than recommended intakes at constant Ca/P ratio), on multiple factors (bone mass, strength, size, geometry, material properties, turnover) influencing bone strength during the bone accrual period. Rats, age 28days were supplemented for 4weeks with high Ca (1.2%), adequate Ca (0.5%) or low Ca level (0.2%). Bone metabolism and structural parameters were measured. No changes in body weight or food intake were observed among the groups. As anticipated, compared to the adequate Ca intake, low-Ca intake had a detrimental impact on bone growth (33.63 vs. 33.68mm), bone strength (-19.7% for failure load), bone architecture (-58% for BV/TV) and peak bone mass accrual (-29% for BMD) due to the hormonal disruption implied in Ca metabolism. In contrast, novel, surprising results were observed in that higher than adequate Ca intake resulted in improved peak bone strength (106 vs. 184N/mm for the stiffness and 61 vs. 89N for the failure load) and bone material properties (467 vs. 514mPa for tissue hardness) but these effects were not accompanied by changes in bone mass, size, microarchitecture or bone turnover. Hormonal factors, IGF-I and bone modeling were also evaluated. Compared to the adequate level of Ca, IGF-I level was significantly lower in the low-Ca intake group and significantly higher in the high-Ca intake group. No detrimental effects of high Ca were observed on bone modeling (assessed by histomorphometry and bone markers), at least in this short-term intervention. In conclusion, the decrease in failure load in the low calcium group can be explained by the change in bone geometry and bone mass parameters. Thus, improvements in mechanical properties can be explained by the improved quality of intrinsic bone tissue as shown by nanoindentation. These results suggest that supplemental Ca may be beneficial for the attainment of peak bone strength and that multiple factors linked to bone mass and strength should be taken into account when setting dietary levels of adequate mineral intake to support optimal peak bone mass acquisition. Copyright © 2014 Elsevier Inc. All rights reserved.

Relationship of total body fat mass to weight-bearing bone volumetric density, geometry, and strength in young girls

PubMed Central

Farr, Joshua N.; Chen, Zhao; Lisse, Jeffrey R.; Lohman, Timothy G.; Going, Scott B.

2010-01-01

Understanding the influence of total body fat mass (TBFM) on bone during the peri-pubertal years is critical for the development of future interventions aimed at improving bone strength and reducing fracture risk. Thus, we evaluated the relationship of TBFM to volumetric bone mineral density (vBMD), geometry, and strength at metaphyseal and diaphyseal sites of the femur and tibia of young girls. Data from 396 girls aged 8–13 years from the “Jump-In: Building Better Bones” study were analyzed. Bone parameters were assessed using peripheral quantitative computed tomography (pQCT) at the 4% and 20% distal femur and 4% and 66% distal tibia of the non-dominant leg. Bone parameters at the 4% sites included trabecular vBMD, periosteal circumference, and bone strength index (BSI), while at the 20% femur and 66% tibia, parameters included cortical vBMD, periosteal circumference, and strength-strain index (SSI). Multiple linear regression analyses were used to assess associations between bone parameters and TBFM, controlling for muscle cross-sectional area (MCSA). Regression analyses were then repeated with maturity, bone length, physical activity, and ethnicity as additional covariates. Analysis of covariance (ANCOVA) was used to compare bone parameters among tertiles of TBFM. In regression models with TBFM and MCSA, associations between TBFM and bone parameters at all sites were not significant. TBFM explained very little variance in all bone parameters (0.2–2.3%). In contrast, MCSA was strongly related (p < 0.001) to all bone parameters, except cortical vBMD. The addition of maturity, bone length, physical activity, and ethnicity did not alter the relationship between TBFM and bone parameters. With bone parameters expressed relative to total body mass, ANCOVA showed that all outcomes were significantly (p < 0.001) greater in the lowest compared to the middle and highest tertiles of TBFM. Although TBFM is correlated with femur and tibia vBMD, periosteal circumference, and strength in young girls, this relationship is significantly attenuated after adjustment for MCSA. Nevertheless, girls with higher TBFM relative to body mass have markedly diminished vBMD, geometry, and bone strength at metaphyseal and diaphyseal sites of the femur and tibia. PMID:20060079

Bone Turnover Markers and Lean Mass in Pubescent Boys: Comparison Between Elite Soccer Players and Controls.

PubMed

Nebigh, Ammar; Abed, Mohamed Elfethi; Borji, Rihab; Sahli, Sonia; Sellami, Slaheddine; Tabka, Zouhair; Rebai, Haithem

2017-11-01

The aim of this study was to examine the relationship between bone mass and bone turnover markers with lean mass (LM) in pubescent soccer players. Two groups participated in this study, which included 65 elite young soccer players who trained for 6-8 hours per week and 60 controls. Bone mineral density; bone mineral content in the whole body, lower limbs, lumbar spine, and femoral neck; biochemical markers of osteocalcin; bone-specific alkaline phosphatase; C-telopeptide type I collagen; and total LM were assessed. Young soccer players showed higher bone mineral density and bone mineral content in the whole body and weight-bearing sites (P < .001). Indeed, the total LM correlated with whole-body bone mineral density and bone mineral content (P < .001). There were significant differences within the bone formation markers and osteocalcin (formation)/C-telopeptide type I collagen (resorption) ratio between young soccer players compared with the control group, but no significant difference in C-telopeptide type I collagen was observed between the 2 groups. This study showed a significant positive correlation among bone-specific alkaline phosphatase, osteocalcin, and total LM (r = .29; r = .31; P < .05) only for the young soccer players. Findings of this study highlight the importance of soccer practice for bone mineral parameters and bone turnover markers during the puberty stage.

Rapidly Assessing Changes in Bone Mineral Balance Using Natural Stable Calcium Isotopes

NASA Technical Reports Server (NTRS)

Morgan, J. L. L.; Gordon, G. W.; Romaniello, S. J.; Skulan, J. L.; Smith, S. M.; Anbar, A. D.

2011-01-01

We demonstrate that variations in the Ca isotope ratios in urine rapidly and quantitatively reflect changes in bone mineral balance. This variation occurs because bone formation depletes soft tissue of light Ca isotopes, while bone resorption releases that isotopically light Ca back into soft tissue. In a study of 12 individuals confined to bed rest, a condition known to induce bone resorption, we show that Ca isotope ratios shift in a direction consistent with net bone loss after just 7 days, long before detectible changes in bone density occur. Consistent with this interpretation, the Ca isotope variations track changes observed in N-teleopeptide, a bone resorption biomarker, while bone-specific alkaline phosphatase, a bone formation biomarker, is unchanged. Ca isotopes can in principle be used to quantify net changes in bone mass. Ca isotopes indicate an average loss of 0.62 +/- 0.16 % in bone mass over the course of this 30-day study. The Ca isotope technique should accelerate the pace of discovery of new treatments for bone disease and provide novel insights into the dynamics of bone metabolism.

Behavioral Intervention in Adolescents Improves Bone Mass, Yet Lactose Maldigestion Is a Barrier

PubMed Central

Lee, Yujin; Savaiano, Dennis A.; McCabe, George P.; Pottenger, Francis M.; Welshimer, Kathleen; Weaver, Connie M.; McCabe, Linda D.; Novotny, Rachel; Read, Marsha; Going, Scott; Mason, April; Van Loan, Marta

2018-01-01

Calcium intake during adolescence is important for attainment of peak bone mass. Lactose maldigestion is an autosomal recessive trait, leading to lower calcium intake. The Adequate Calcium Today study aimed to determine if a school-based targeted behavioral intervention over one year could improve calcium intake and bone mass in early adolescent girls. The school-randomized intervention was conducted at middle schools in six states over one school year. A total of 473 girls aged 10–13 years were recruited for outcome assessments. Bone mineral content (BMC) was determined by dual energy X-ray absorptiometry. Dietary calcium intake was assessed with a semi-quantitative food frequency questionnaire. Baseline calcium intake and BMC were not significantly different between groups. After the intervention period, there were no differences in changes in calcium intake and BMC at any site between groups. An unanticipated outcome was a greater increase in spinal BMC among lactose digesters than lactose maldigesters in the intervention schools only (12 months) (6.9 ± 0.3 g vs. 6.0 ± 0.4 g, p = 0.03) and considering the entire study period (18 months) (9.9 ± 0.4 vs. 8.7 ± 0.5 g, p < 0.01). Overall, no significant differences between the intervention and control schools were observed. However, lactose digesters who received the intervention program increased bone mass to a greater extent than lactose maldigesters. PMID:29597337

Lean mass and fat mass have differing associations with bone microarchitecture assessed by high resolution peripheral quantitative computed tomography in men and women from the Hertfordshire Cohort Study.

PubMed

Edwards, Mark H; Ward, Kate A; Ntani, Georgia; Parsons, Camille; Thompson, Jennifer; Sayer, Avan A; Dennison, Elaine M; Cooper, Cyrus

2015-12-01

Understanding the effects of muscle and fat on bone is increasingly important in the optimisation of bone health. We explored relationships between bone microarchitecture and body composition in older men and women from the Hertfordshire Cohort Study. 175 men and 167 women aged 72-81 years were studied. High resolution peripheral quantitative computed tomography (HRpQCT) images (voxel size 82 μm) were acquired from the non-dominant distal radius and tibia with a Scanco XtremeCT scanner. Standard morphological analysis was performed for assessment of macrostructure, densitometry, cortical porosity and trabecular microarchitecture. Body composition was assessed using dual energy X-ray absorptiometry (DXA) (Lunar Prodigy Advanced). Lean mass index (LMI) was calculated as lean mass divided by height squared and fat mass index (FMI) as fat mass divided by height squared. The mean (standard deviation) age in men and women was 76 (3) years. In univariate analyses, tibial cortical area (p<0.01), cortical thickness (p<0.05) and trabecular number (p<0.01) were positively associated with LMI and FMI in both men and women. After mutual adjustment, relationships between cortical area and thickness were only maintained with LMI [tibial cortical area, β (95% confidence interval (CI)): men 6.99 (3.97,10.01), women 3.59 (1.81,5.38)] whereas trabecular number and density were associated with FMI. Interactions by sex were found, including for the relationships of LMI with cortical area and FMI with trabecular area in both the radius and tibia (p<0.05). In conclusion, LMI and FMI appeared to show independent relationships with bone microarchitecture. Further studies are required to confirm the direction of causality and explore the mechanisms underlying these tissue-specific associations. Copyright © 2015 Elsevier Inc. All rights reserved.

Insulin Resistance Negatively Influences the Muscle-Dependent IGF-1-Bone Mass Relationship in Premenarcheal Girls.

PubMed

Kindler, J M; Pollock, N K; Laing, E M; Jenkins, N T; Oshri, A; Isales, C; Hamrick, M; Lewis, R D

2016-01-01

IGF-1 promotes bone growth directly and indirectly through its effects on skeletal muscle. Insulin and IGF-1 share a common cellular signaling process; thus, insulin resistance may influence the IGF-1-muscle-bone relationship. We sought to determine the effect of insulin resistance on the muscle-dependent relationship between IGF-1 and bone mass in premenarcheal girls. This was a cross-sectional study conducted at a university research center involving 147 girls ages 9 to 11 years. Glucose, insulin, and IGF-1 were measured from fasting blood samples. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from glucose and insulin. Fat-free soft tissue (FFST) mass and bone mineral content (BMC) were measured by dual-energy x-ray absorptiometry. Our primary outcome was BMC/height. In our path model, IGF-1 predicted FFST mass (b = 0.018; P = .001), which in turn predicted BMC/height (b = 0.960; P < .001). IGF-1 predicted BMC/height (b = 0.001; P = .002), but not after accounting for the mediator of this relationship, FFST mass. The HOMA-IR by IGF-1 interaction negatively predicted FFST mass (b = -0.044; P = .034). HOMA-IR had a significant and negative effect on the muscle-dependent relationship between IGF-1 and BMC/height (b = -0.151; P = .047). Lean body mass is an important intermediary factor in the IGF-1-bone relationship. For this reason, bone development may be compromised indirectly via suboptimal IGF-1-dependent muscle development in insulin-resistant children.

Effect of age and disease on bone mass in Japanese patients with schizophrenia.

PubMed

Sugawara, Norio; Yasui-Furukori, Norio; Umeda, Takashi; Tsuchimine, Shoko; Fujii, Akira; Sato, Yasushi; Saito, Manabu; Furukori, Hanako; Danjo, Kazuma; Matsuzaka, Masashi; Takahashi, Ippei; Kaneko, Sunao

2012-02-20

There have been a limited number of studies comparing bone mass between patients with schizophrenia and the general population. The aim of this study was to compare the bone mass of schizophrenia patients with that of healthy subjects in Japan. We recruited patients (n = 362), aged 48.8 ± 15.4 (mean ± SD) years who were diagnosed with schizophrenia or schizoaffective disorder based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). Bone mass was measured using quantitative ultrasound densitometry of the calcaneus. The osteosono-assessment index (OSI) was calculated as a function of the speed of sound and the transmission index. For comparative analysis, OSI data from 832 adults who participated in the Iwaki Health Promotion Project 2009 was used as representative of the general community. Mean OSI values among male schizophrenic patients were lower than those in the general population in the case of individuals aged 40 and older. In females, mean OSI values among schizophrenic patients were lower than those in the general community in those aged 60 and older. In an analysis using the general linear model, a significant interaction was observed between subject groups and age in males. Older schizophrenic patients exhibit lower bone mass than that observed in the general population. Our data also demonstrate gender and group differences among schizophrenic patients and controls with regard to changes in bone mass associated with aging. These results indicate that intervention programs designed to delay or prevent decreased bone mass in schizophrenic patients might be tailored according to gender.

Bone mass of female dance students prior to professional dance training: A cross-sectional study

PubMed Central

Amorim, Tânia; Metsios, George S.; Wyon, Matthew; Nevill, Alan M.; Flouris, Andreas D.; Maia, José; Teixeira, Eduardo; Machado, José Carlos; Marques, Franklim; Koutedakis, Yiannis

2017-01-01

Background Professional dancers are at risk of developing low bone mineral density (BMD). However, whether low BMD phenotypes already exist in pre-vocational dance students is relatively unknown. Aim To cross-sectionally assess bone mass parameters in female dance students selected for professional dance training (first year vocational dance students) in relation to aged- and sex-matched controls. Methods 34 female selected for professional dance training (10.9yrs ±0.7) and 30 controls (11.1yrs ±0.5) were examined. Anthropometry, pubertal development (Tanner) and dietary data (3-day food diary) were recorded. BMD and bone mineral content (BMC) at forearm, femur neck (FN) and lumbar spine (LS) were assessed using Dual-Energy X-Ray Absorptiometry. Volumetric densities were estimated by calculating bone mineral apparent density (BMAD). Results Dancers were mainly at Tanner pubertal stage I (vs. stage IV in controls, p<0.001), and demonstrated significantly lower body weight (p<0.001) and height (p<0.01) than controls. Calorie intake was not different between groups, but calcium intake was significantly greater in dancers (p<0.05). Dancers revealed a significantly lower BMC and BMD values at all anatomical sites (p<0.001), and significantly lower BMAD values at the LS and FN (p<0.001). When adjusted for covariates (body weight, height, pubertal development and calcium intake), dance students continued to display a significantly lower BMD and BMAD at the FN (p<0.05; p<0.001) at the forearm (p<0.01). Conclusion Before undergoing professional dance training, first year vocational dance students demonstrated inferior bone mass compared to controls. Longitudinal models are required to assess how bone health-status changes with time throughout professional training. PMID:28678833

Bone mass of female dance students prior to professional dance training: A cross-sectional study.

PubMed

Amorim, Tânia; Metsios, George S; Wyon, Matthew; Nevill, Alan M; Flouris, Andreas D; Maia, José; Teixeira, Eduardo; Machado, José Carlos; Marques, Franklim; Koutedakis, Yiannis

2017-01-01

Professional dancers are at risk of developing low bone mineral density (BMD). However, whether low BMD phenotypes already exist in pre-vocational dance students is relatively unknown. To cross-sectionally assess bone mass parameters in female dance students selected for professional dance training (first year vocational dance students) in relation to aged- and sex-matched controls. 34 female selected for professional dance training (10.9yrs ±0.7) and 30 controls (11.1yrs ±0.5) were examined. Anthropometry, pubertal development (Tanner) and dietary data (3-day food diary) were recorded. BMD and bone mineral content (BMC) at forearm, femur neck (FN) and lumbar spine (LS) were assessed using Dual-Energy X-Ray Absorptiometry. Volumetric densities were estimated by calculating bone mineral apparent density (BMAD). Dancers were mainly at Tanner pubertal stage I (vs. stage IV in controls, p<0.001), and demonstrated significantly lower body weight (p<0.001) and height (p<0.01) than controls. Calorie intake was not different between groups, but calcium intake was significantly greater in dancers (p<0.05). Dancers revealed a significantly lower BMC and BMD values at all anatomical sites (p<0.001), and significantly lower BMAD values at the LS and FN (p<0.001). When adjusted for covariates (body weight, height, pubertal development and calcium intake), dance students continued to display a significantly lower BMD and BMAD at the FN (p<0.05; p<0.001) at the forearm (p<0.01). Before undergoing professional dance training, first year vocational dance students demonstrated inferior bone mass compared to controls. Longitudinal models are required to assess how bone health-status changes with time throughout professional training.

Bone Metabolism in Adolescent Athletes With Amenorrhea, Athletes With Eumenorrhea, and Control Subjects

PubMed Central

Christo, Karla; Prabhakaran, Rajani; Lamparello, Brooke; Cord, Jennalee; Miller, Karen K.; Goldstein, Mark A.; Gupta, Nupur; Herzog, David B.; Klibanski, Anne; Misra, Madhusmita

2011-01-01

OBJECTIVE We hypothesized that, despite increased activity, bone density would be low in athletes with amenorrhea, compared with athletes with eumenorrhea and control subjects, because of associated hypogonadism and would be associated with a decrease in bone formation and increases in bone-resorption markers. METHODS In a cross-sectional study, we examined bone-density measures (spine, hip, and whole body) and body composition by using dual-energy radiograph absorptiometry and assessed fasting levels of insulin-like growth factor I and bone-turnover markers (N-terminal propeptied of type 1 procollagen and N-telopeptide) in 21 athletes with amenorrhea, 18 athletes with eumenorrhea, and 18 control subjects. Subjects were 12 to 18 years of age and of comparable chronologic and bone age. RESULTS Athletes with amenorrhea had lower bone-density z scores at the spine and whole body, compared with athletes with eumenorrhea and control subjects, and lower hip z scores, compared with athletes with eumenorrhea. Lean mass did not differ between groups. However, athletes with amenorrhea had lower BMI z scores than did athletes with eumenorrhea and lower insulin-like growth factor I levels than did control subjects. Levels of both markers of bone turnover were lower in athletes with amenorrhea than in control subjects. BMI z scores, lean mass, insulin-like growth factor I levels, and diagnostic category were important independent predictors of bone mineral density z scores. CONCLUSIONS Although they showed no significant differences in lean mass, compared with athletes with eumenorrhea and control subjects, athletes with amenorrhea had lower bone density at the spine and whole body. Insulin-like growth factor I levels, body-composition parameters, and menstrual status were important predictors of bone density. Follow-up studies are necessary to determine whether amenorrhea in athletes adversely affects the rate of bone mass accrual and therefore peak bone mass. PMID:18519482

Body composition and reproductive function exert unique influences on indices of bone health in exercising women.

PubMed

Mallinson, Rebecca J; Williams, Nancy I; Hill, Brenna R; De Souza, Mary Jane

2013-09-01

Reproductive function, metabolic hormones, and lean mass have been observed to influence bone metabolism and bone mass. It is unclear, however, if reproductive, metabolic and body composition factors play unique roles in the clinical measures of areal bone mineral density (aBMD) and bone geometry in exercising women. This study compares lumbar spine bone mineral apparent density (BMAD) and estimates of femoral neck cross-sectional moment of inertia (CSMI) and cross-sectional area (CSA) between exercising ovulatory (Ov) and amenorrheic (Amen) women. It also explores the respective roles of reproductive function, metabolic status, and body composition on aBMD, lumbar spine BMAD and femoral neck CSMI and CSA, which are surrogate measures of bone strength. Among exercising women aged 18-30 years, body composition, aBMD, and estimates of femoral neck CSMI and CSA were assessed by dual-energy x-ray absorptiometry. Lumbar spine BMAD was calculated from bone mineral content and area. Estrone-1-glucuronide (E1G) and pregnanediol glucuronide were measured in daily urine samples collected for one cycle or monitoring period. Fasting blood samples were collected for measurement of leptin and total triiodothyronine. Ov (n = 37) and Amen (n = 45) women aged 22.3 ± 0.5 years did not differ in body mass, body mass index, and lean mass; however, Ov women had significantly higher percent body fat than Amen women. Lumbar spine aBMD and BMAD were significantly lower in Amen women compared to Ov women (p < 0.001); however, femoral neck CSA and CSMI were not different between groups. E1G cycle mean and age of menarche were the strongest predictors of lumbar spine aBMD and BMAD, together explaining 25.5% and 22.7% of the variance, respectively. Lean mass was the strongest predictor of total hip and femoral neck aBMD as well as femoral neck CSMI and CSA, explaining 8.5-34.8% of the variance. Upon consideration of several potential osteogenic stimuli, reproductive function appears to play a key role in bone mass at a site composed of primarily trabecular bone. However, lean mass is one of the most influential predictors of bone mass and bone geometry at weight-bearing sites, such as the hip. Copyright © 2013 Elsevier Inc. All rights reserved.

No association between LRP5 gene polymorphisms and bone and obesity phenotypes in Chinese male-offspring nuclear families.

PubMed

Yu, Jin-bo; Ke, Yao-hua; He, Jin-wei; Zhang, Hao; Hu, Wei-wei; Hu, Yun-qiu; Li, Miao; Liu, Yu-juan; Gu, Jie-mei; Fu, Wen-zhen; Gao, Gao; Yue, Hua; Xiao, Wen-jin; Zhang, Zhen-lin

2010-11-01

To investigate the effect of low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms on bone and obesity phenotypes in young Chinese men. A total of 1244 subjects from 411 Chinese nuclear families were genotyped by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique at the Q89R, N740N, and A1330V sites in the LRP5 gene. Bone mineral density (BMD) in the lumbar spine and the hip, total fat mass and total lean mass were measured using dual-energy X-ray absorptiometry. The association between LRP5 gene polymorphisms and peak BMD, body mass index (BMI), total fat mass, total lean mass and percentage of fat mass was assessed using a quantitative transmission disequilibrium test (QTDT). No significant within-family associations were found between genotypes or haplotypes of the LRP5 gene and peak BMD, BMI, total fat mass, total lean mass and percentage of fat mass. The 1000 permutations that were subsequently simulated were in agreement with these within-family association results. Our results suggest that common polymorphic variations of the LRP5 gene do not influence peak bone mass acquisition and obesity phenotypes in young Chinese men.

Osteoporosis, Fractures, and Diabetes

PubMed Central

2014-01-01

It is well established that osteoporosis and diabetes are prevalent diseases with significant associated morbidity and mortality. Patients with diabetes mellitus have an increased risk of bone fractures. In type 1 diabetes, the risk is increased by ∼6 times and is due to low bone mass. Despite increased bone mineral density (BMD), in patients with type 2 diabetes the risk is increased (which is about twice the risk in the general population) due to the inferior quality of bone. Bone fragility in type 2 diabetes, which is not reflected by bone mineral density, depends on bone quality deterioration rather than bone mass reduction. Thus, surrogate markers and examination methods are needed to replace the insensitivity of BMD in assessing fracture risks of T2DM patients. One of these methods can be trabecular bone score. The aim of the paper is to present the present state of scientific knowledge about the osteoporosis risk in diabetic patient. The review also discusses the possibility of problematic using the study conclusions in real clinical practice. PMID:25050121

Physical activity during life course and bone mass: a systematic review of methods and findings from cohort studies with young adults

PubMed Central

2013-01-01

Background The purpose of this paper was to review the literature of the cohort studies which evaluated the association between physical activity during the life course and bone mineral content or density in young adults. Methods Prospective cohort studies with bone mineral density or content measured in the whole body, lumbar spine and femoral neck by dual energy x-ray absorptiometry as outcome and physical activity as exposure were searched. Two independent reviewers selected studies retrieved from electronic databases (Medline, Lilacs, Web of Science and Scielo) and reviewed references of all selected full text articles. Downs & Black criterion was used in the quality assessment of these studies. Results Nineteen manuscripts met inclusion criteria. Lumbar spine was the skeletal site most studied (n = 15). Different questionnaires were used for physical activity evaluation. Peak strain score was also used to evaluate physical activity in 5 manuscripts. Lack of statistical power calculation was the main problem found in the quality assessment. Positive associations between physical activity and bone mass were found more in males than in females; in weight bearing anatomical sites (lumbar spine and femoral neck) than in total body and when physical activity measurements were done from adolescence to adulthood – than when evaluated in only one period. Physical activity during growth period was associated with greater bone mass in males. It was not possible to conduct pooled analyses due to the heterogeneity of the studies, considering mainly the different instruments used for physical activity measurements. Conclusions Physical activity seems to be important for bone mass in all periods of life, but especially the growth period should be taking into account due to its important direct effect on bone mass and its influence in physical activity practice in later life. Low participation in peak strain activities may also explain the lower number of associations found in females. PMID:23497066

Unusual Bone Superscan, MIBG Superscan, and 68Ga DOTATATE PET/CT in Metastatic Pheochromocytoma.

PubMed

Tan, Teik Hin; Wong, Teck Huat; Hassan, Siti Zarina Amir; Lee, Boon Nang

2015-11-01

A 17-year-old adolescent boy with biochemically raised 2-hour urinary metanephrine and normetanephrine as well as CT findings of retroperitoneal soft tissue mass and bony metastases was referred for further assessment. Apart from Ga DOTATATE PET/CT evaluation, pretargeted systemic radionuclide therapy assessment with I-MIBG scintigraphy showed unusual phenomenon of MIBG superscan. Postsurgically, restaging Tc-MDP bone scintigraphy showed typical bone superscan features. The MIBG superscan was better delineated on post-I-MIBG therapy images.

Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats

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

Gilmour, Peter S., E-mail: Peter.Gilmour@astrazeneca.com; O'Shea, Patrick J.; Fagura, Malbinder

Wnt activation by inhibiting glycogen synthase kinase 3 (GSK-3) causes bone anabolism in rodents making GSK-3 a potential therapeutic target for osteoporotic and osteolytic metastatic bone disease. To understand the wnt pathway related to human disease translation, the ability of 3 potent inhibitors of GSK-3 (AZD2858, AR79, AZ13282107) to 1) drive osteoblast differentiation and mineralisation using human adipose-derived stem cells (hADSC) in vitro; and 2) stimulate rat bone formation in vivo was investigated. Bone anabolism/resorption was determined using clinically relevant serum biomarkers as indicators of bone turnover and bone formation assessed in femurs by histopathology and pQCT/μCT imaging. GSK-3 inhibitorsmore » caused β-catenin stabilisation in human and rat mesenchymal stem cells, stimulated hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. AZD2858 produced time-dependent changes in serum bone turnover biomarkers and increased bone mass over 28 days exposure in rats. After 7 days, AZD2858, AR79 or AZ13282107 exposure increased the bone formation biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. This biomarker profile was differentiated from anabolic agent PTH{sub 1–34} or the anti-resorptive Alendronate-induced changes. Increased bone formation in cortical and cancellous bone as assessed by femur histopathology supported biomarker changes. 14 day AR79 treatment increased bone mineral density and trabecular thickness, and decreased trabecular number and connectivity assessed by pQCT/μCT. GSK-3 inhibition caused hADSC osteoblastogenesis and mineralisation in vitro. Increased femur bone mass associated with changes in bone turnover biomarkers confirmed in vivo bone formation and indicated uncoupling of bone formation and resorption. - Highlights: • Wnt modulation with 3 novel GSK-3 inhibitors alters bone growth. • Human stem cell osteoblastogenesis and mineralisation produced by GSK-3 inhibition. • In rats, 3 GSK-3 inhibitors produced a unique serum bone turnover biomarker profile. • Enhanced bone formation was seen within 7 to 14 days of compound treatment in rats.« less

Bone formation is not impaired by hibernation (disuse) in black bears Ursus americanus

USGS Publications Warehouse

Donahue, S.W.; Vaughan, M.R.; Demers, L.M.; Donahue, H.J.

2003-01-01

Disuse by bed rest, limb immobilization or space flight causes rapid bone loss by arresting bone formation and accelerating bone resorption. This net bone loss increases the risk of fracture upon remobilization. Bone loss also occurs in hibernating ground squirrels, golden hamsters, and little brown bats by arresting bone formation and accelerating bone resorption. There is some histological evidence to suggest that black bears Ursus americanus do not lose bone mass during hibernation (i.e. disuse). There is also evidence suggesting that muscle mass and strength are preserved in black bears during hibernation. The question of whether bears can prevent bone loss during hibernation has not been conclusively answered. The goal of the current study was to further assess bone metabolism in hibernating black bears. Using the same serum markers of bone remodeling used to evaluate human patients with osteoporosis, we assayed serum from five black bears, collected every 10 days over a 196-day period, for bone resorption and formation markers. Here we show that bone resorption remains elevated over the entire hibernation period compared to the pre-hibernation period, but osteoblastic bone formation is not impaired by hibernation and is rapidly accelerated during remobilization following hibernation.

Body fat and bone mineral content of infants fed breast-milk, cow's-milk formula, or soy formula during the first year of life

USDA-ARS?s Scientific Manuscript database

Our objective was to characterize growth, fat mass (FM), fat free mass (FFM), and bone mineral content (BMC) longitudinally in breast-fed (BF), cow's milk formula-fed (CMF), or soy formula-fed (SF) healthy infants during the first year of life. Infants were assessed at ages 3, 6, 9, and 12 mo. Growt...

[Obesity, fat and bones: friends or foes ?

PubMed

Biver, Emmanuel

2017-04-19

Low fat mass is associated with an increased risk of fracture because of low bone mineral density (BMD) and altered bone micro-architecture. Conversely, overweight and obese patients also have an increased risk of fracture, particularly of the humerus and ankle, despite greater BMD. Visceral abdominal fat, which is the most metabolically active, may be associated with poorer quality of bone tissue properties, as suggested in diabetes. Other factors may contribute to higher fracture risk in overweight patients, notably higher frequency of falls and lower bioavailability of vitamin D stoked in fat. Thus, fat mass and its distribution should be taken into account beyond BMD and classical clinical risk factors in the assessment of fracture risk.

Change in lean body mass is a major determinant of change in areal bone mineral density of the proximal femur: a 12-year observational study.

PubMed

Liu-Ambrose, T; Kravetsky, L; Bailey, D; Sherar, L; Mundt, C; Baxter-Jones, A; Khan, K M; McKay, H A

2006-09-01

Our objective was to assess the contribution of lean body mass (LBM) and fat body mass (FBM) to areal bone mineral density (aBMD) in women during the years surrounding menopause. We used a 12-year observational design. Participants included 75 Caucasian women who were premenopausal, 53 of whom were available for follow-up. There were two measurement periods: baseline and 12-year follow-up. At both measurement periods, bone mineral content and aBMD of the proximal femur, posterior-anterior lumbar spine, and total body was assessed using dual-energy X-ray absorptiometry (DXA). LBM and FBM were derived from the total-body scans. General health, including current menopausal status, hormone replace therapy use, medication use, and physical activity, was assessed by questionnaires. At the end of the study, 44% of the women were postmenopausal. After controlling for baseline aBMD, current menopausal status, and current hormone replacement therapy, we found that change in LBM was independently associated with change in aBMD of the proximal femur (P = 0.001). The cross-sectional analyses also indicated that LBM was a significant determinant of aBMD of all three DXA-scanned sites at both baseline and follow-up. These novel longitudinal data highlight the important contribution of LBM to the maintenance of proximal femur bone mass at a key time in women's life span, the years surrounding menopause.

Alendronate increases skeletal mass of growing rats during unloading by inhibiting resorption of calcified cartilage

NASA Technical Reports Server (NTRS)

Bikle, D. D.; Morey-Holton, E. R.; Doty, S. B.; Currier, P. A.; Tanner, S. J.; Halloran, B. P.

1994-01-01

Loss of bone mass during periods of skeletal unloading remains an important clinical problem. To determine the extent to which resorption contributes to the relative loss of bone during skeletal unloading of the growing rat and to explore potential means of preventing such bone loss, 0.1 mg P/kg alendronate was administered to rats before unloading of the hindquarters. Skeletal unloading markedly reduced the normal increase in tibial mass and calcium content during the 9 day period of observation, primarily by decreasing bone formation, although bone resorption was also modestly stimulated. Alendronate not only prevented the relative loss of skeletal mass during unloading but led to a dramatic increase in calcified tissue in the proximal tibia compared with the vehicle-treated unloaded or normally loaded controls. Bone formation, however, assessed both by tetracycline labeling and by [3H]proline and 45Ca incorporation, was suppressed by alendronate treatment and further decreased by skeletal unloading. Total osteoclast number increased in alendronate-treated animals, but values were similar to those in controls when corrected for the increased bone area. However, the osteoclasts had poorly developed brush borders and appeared not to engage the bone surface when examined at the ultrastructural level. We conclude that alendronate prevents the relative loss of mineralized tissue in growing rats subjected to skeletal unloading, but it does so primarily by inhibiting the resorption of the primary and secondary spongiosa, leading to altered bone modeling in the metaphysis.

Lower bone turnover and relative bone deficits in men with metabolic syndrome: a matter of insulin sensitivity? The European Male Ageing Study.

PubMed

Laurent, M R; Cook, M J; Gielen, E; Ward, K A; Antonio, L; Adams, J E; Decallonne, B; Bartfai, G; Casanueva, F F; Forti, G; Giwercman, A; Huhtaniemi, I T; Kula, K; Lean, M E J; Lee, D M; Pendleton, N; Punab, M; Claessens, F; Wu, F C W; Vanderschueren, D; Pye, S R; O'Neill, T W

2016-11-01

We examined cross-sectional associations of metabolic syndrome and its components with male bone turnover, density and structure. Greater bone mass in men with metabolic syndrome was related to their greater body mass, whereas hyperglycaemia, hypertriglyceridaemia or impaired insulin sensitivity were associated with lower bone turnover and relative bone mass deficits. Metabolic syndrome (MetS) has been associated with lower bone turnover and relative bone mass or strength deficits (i.e. not proportionate to body mass index, BMI), but the relative contributions of MetS components related to insulin sensitivity or obesity to male bone health remain unclear. We determined cross-sectional associations of MetS, its components and insulin sensitivity (by homeostatic model assessment-insulin sensitivity (HOMA-S)) using linear regression models adjusted for age, centre, smoking, alcohol, and BMI. Bone turnover markers and heel broadband ultrasound attenuation (BUA) were measured in 3129 men aged 40-79. Two centres measured total hip, femoral neck, and lumbar spine areal bone mineral density ( a BMD, n = 527) and performed radius peripheral quantitative computed tomography (pQCT, n = 595). MetS was present in 975 men (31.2 %). Men with MetS had lower β C-terminal cross-linked telopeptide (β-CTX), N-terminal propeptide of type I procollagen (PINP) and osteocalcin (P < 0.0001) and higher total hip, femoral neck, and lumbar spine a BMD (P ≤ 0.03). Among MetS components, only hypertriglyceridaemia and hyperglycaemia were independently associated with PINP and β-CTX. Hyperglycaemia was negatively associated with BUA, hypertriglyceridaemia with hip a BMD and radius cross-sectional area (CSA) and stress-strain index. HOMA-S was similarly associated with PINP and β-CTX, BUA, and radius CSA in BMI-adjusted models. Men with MetS have higher a BMD in association with their greater body mass, while their lower bone turnover and relative deficits in heel BUA and radius CSA are mainly related to correlates of insulin sensitivity. Our findings support the hypothesis that underlying metabolic complications may be involved in the bone's failure to adapt to increasing bodily loads in men with MetS.

Deficiency and Also Transgenic Overexpression of Timp-3 Both Lead to Compromised Bone Mass and Architecture In Vivo

PubMed Central

Hopkinson, Mark; Poulet, Blandine; Pollard, Andrea S.; Shefelbine, Sandra J.; Chang, Yu-Mei; Francis-West, Philippa; Bou-Gharios, George; Pitsillides, Andrew A.

2016-01-01

Tissue inhibitor of metalloproteinases-3 (TIMP-3) regulates extracellular matrix via its inhibition of matrix metalloproteinases and membrane-bound sheddases. Timp-3 is expressed at multiple sites of extensive tissue remodelling. This extends to bone where its role, however, remains largely unresolved. In this study, we have used Micro-CT to assess bone mass and architecture, histological and histochemical evaluation to characterise the skeletal phenotype of Timp-3 KO mice and have complemented this by also examining similar indices in mice harbouring a Timp-3 transgene driven via a Col-2a-driven promoter to specifically target overexpression to chondrocytes. Our data show that Timp-3 deficiency compromises tibial bone mass and structure in both cortical and trabecular compartments, with corresponding increases in osteoclasts. Transgenic overexpression also generates defects in tibial structure predominantly in the cortical bone along the entire shaft without significant increases in osteoclasts. These alterations in cortical mass significantly compromise predicted tibial load-bearing resistance to torsion in both genotypes. Neither Timp-3 KO nor transgenic mouse growth plates are significantly affected. The impact of Timp-3 deficiency and of transgenic overexpression extends to produce modification in craniofacial bones of both endochondral and intramembranous origins. These data indicate that the levels of Timp-3 are crucial in the attainment of functionally-appropriate bone mass and architecture and that this arises from chondrogenic and osteogenic lineages. PMID:27519049

Osteoporosis: Peak Bone Mass in Women

MedlinePlus

... Osteoporosis: Peak Bone Mass in Women Osteoporosis: Peak Bone Mass in Women Bones are the framework for ... that affect peak bone mass. Factors Affecting Peak Bone Mass A variety of genetic and environmental factors ...

Correlates of increased lean muscle mass in women with polycystic ovary syndrome.

PubMed

Carmina, E; Guastella, E; Longo, R A; Rini, G B; Lobo, R A

2009-10-01

Muscle mass plays an important role in determining cardiovascular and metabolic risks in polycystic ovary syndrome (PCOS). In addition, whether lean mass influences carotid intima-media thickness (IMT) in PCOS has not been assessed. Prospective investigation. Ninety-five women with PCOS were age- and weight-matched to 90 ovulatory controls. All women had dual X-ray absorptiometry for lean, fat and bone mass, and bone mass density (BMD). Serum testosterone, sex hormone-binding globulin, insulin, and glucose and carotid IMT were determined. Free androgen index (FAI) and insulin resistance (by QUICKI) were calculated. In PCOS, waist circumference and insulin were higher and QUICKI lower than in controls (P<0.01). Trunk fat mass, % trunk fat, and lean mass were higher in PCOS compared to controls (P<0.01), while total bone mass and BMD were similar. IMT was increased in PCOS (P<0.01) but only 15% of PCOS patients had abnormal (> or = 0.9 mm) values. Lean mass correlated with fat parameters, insulin, QUICKI, and FAI, but not with total testosterone; and after adjustments for insulin and QUICKI, lean mass still correlated with fat mass (P<0.01) but not FAI. Lean mass correlated with IMT (P<0.01), but this was dependent on insulin. However, excluding those patients with abnormal IMT values, IMT correlated with lean mass independently of insulin. Bone mass correlated with lean and fat mass, but not with insulin or androgen. PCOS patients with 'pathological' IMT values had higher % trunk fat, lean mass, and insulin, lower QUICKI, and higher testosterone and FAI compared with those with normal IMT. Lean mass is increased in PCOS, while bone mass is similar to that of matched controls. The major correlates of lean mass are fat mass and insulin but not androgen. Lean mass also correlated with IMT, and although influenced by insulin, small changes in IMT may partially reflect changes in muscle mass, while clearly abnormal values relate to more severe abnormalities of PCOS.

Assessment of Body Composition Using Dual Energy X-Ray Absorptiometry in Patients with Liver Cirrhosis: Comparison with Anthropometry

PubMed Central

Jeong, Seong Han; Lee, Jeong A; Kim, Jin A; Lee, Mun Woo; Chae, Hee Bok; Choi, Won Jun; Shin, Hyoung Shik; Lee, Ki Hyeong; Youn, Sei Jin; Koong, Sung Soo; Park, Seon Mee

1999-01-01

Objectives The aim of this study was to evaluate changes of body composition in cirrhotic patients. Dual energy x-ray absorptiometry (DEXA) and anthropometry were used, and the values obtained were compared. Methods Mid-arm fat and muscle areas were calculated by anthropometry in 66 cirrhotic patients and 94 healthy controls. In 37 of the cirrhotic patients and 39 of the controls, fat mass, lean soft tissue mass and bone mineral contents were measured with DEXA. Results The number of cirrhotic patients with measured values below the fifth percentile of normal controls was 21 (31.8%) by mid-arm fat area, six (9.1%) by mid-arm muscle area, 15 (40.5%) by fat mass and 0 (0%) by lean soft tissue mass. The fat mass in cirrhotic patients was less than in controls, whereas lean soft tissue mass and bone mineral content were not different. Fat depletion was severe in Child-class C patients and with severe ascites. Mid-arm fat area and fat mass showed close correlation (r = 0.85, p<0.01), but mid-arm muscle area and lean soft tissue mass showed poor correlation (r = 0.32, p<0.05). Conclusion Cirrhotic patients showed lower fat component, with preserved lean soft tissue mass and bone mineral content. In clinical practice, the measurement of mid-arm fat area was useful for the assessment of fat mass. PMID:10461427

Role of apparent diffusion coefficients with diffusion-weighted magnetic resonance imaging in differentiating between benign and malignant bone tumors.

PubMed

Wang, Tingting; Wu, Xiangru; Cui, Yanfen; Chu, Caiting; Ren, Gang; Li, Wenhua

2014-11-29

Benign and malignant bone tumors can present similar imaging features. This study aims to evaluate the significance of apparent diffusion coefficients (ADC) in differentiating between benign and malignant bone tumors. A total of 187 patients with 198 bone masses underwent diffusion-weighted (DW) magnetic resonance (MR) imaging. The ADC values in the solid components of the bone masses were assessed. Statistical differences between the mean ADC values in the different tumor types were determined by Student's t-test. Histological analysis showed that 84/198 (42.4%) of the bone masses were benign and 114/198 (57.6%) were malignant. There was a significant difference between the mean ADC values in the benign and malignant bone lesions (P<0.05). However, no significant difference was found in the mean ADC value between non-ossifying fibromas, osteofibrous dysplasia, and malignant bone tumors. When an ADC cutoff value≥1.10×10(-3) mm2/s was applied, malignant bone lesions were excluded with a sensitivity of 89.7%, a specificity of 84.5%, a positive predictive value of 82.6%, and a negative predictive value of 95.3%. The combination of DW imaging with ADC quantification and T2-weighted signal characteristics of the solid components in lesions can facilitate differentiation between benign and malignant bone tumors.

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.

Anthropometric and skeletal phenotype in men with idiopathic osteoporosis and their sons is consistent with deficient estrogen action during maturation.

PubMed

Lapauw, Bruno; Taes, Youri; Goemaere, Stefan; Toye, Kaatje; Zmierczak, Hans-Georg; Kaufman, Jean-Marc

2009-11-01

Pathophysiology of deficient bone mass acquisition in male idiopathic osteoporosis (IO) remains poorly understood. Our objective was to investigate volumetric and geometric parameters of the appendicular skeleton, biochemical markers, and anthropometrics in men with IO. Our cross-sectional study included 107 men diagnosed with idiopathic low bone mass, 23 of their adult sons, and 130 age-matched controls. Body composition and areal bone parameters (dual-energy x-ray absorptiometry) and volumetric and geometric parameters of radius and tibia (peripheral quantitative computed tomography) were assessed. Serum levels of testosterone, estradiol (E(2)), and SHBG, and bone turnover markers were measured using immunoassays. Free hormone fractions were calculated. Men with idiopathic low bone mass had lower weight (-9.6%), truncal height (-3.3%), and upper/lower body segment ratio (-2.7%; all P < 0.001) and presented at the radius and tibia lower trabecular (-19.0 and -23.6%, respectively; both P < 0.001) and cortical volumetric bone mineral density (vBMD) (-2.4 and -1.7%; both P < 0.001) and smaller cortical areas (-9.7 and -13.6%; both P < 0.001) and thicknesses (-13.5 and -14.5%, both P < 0.001) due to larger endosteal circumferences (+11.8 and +7.4%, both P < 0.001) than controls. Furthermore, (free) E(2) was lower and SHBG higher (both P < 0.01). Their sons had lower trabecular vBMD (-10.3%, P = 0.036) and a thinner cortex (-8.3%, P = 0.024) at the radius. Bone mass deficits in men with idiopathic low bone mass involve trabecular and cortical bone, resulting from lower vBMD and smaller cortical bone cross-sectional areas and thicknesses. A similar bone phenotype is present in at least part of their sons. The lower E(2), together with characteristics as lower upper/lower body segment ratio, larger endosteal circumferences and lower vBMD, may indicate an estrogen-related factor in the pathogenesis of male IO.

Effect of ethnicity and sex on the growth of the axial and appendicular skeleton of children living in a developing country.

PubMed

Nyati, Lukhanyo H; Norris, Shane A; Cameron, Noel; Pettifor, John M

2006-05-01

Bones in the axial and appendicular skeletons exhibit heterogeneous growth patterns between different ethnic and sex groups. However, the influence of this differential growth on the expression of bone mineral content is not yet established. The aims of the present study were to investigate: 1) whether there are ethnic and sex differences in axial and appendicular dimensions of South African children; and 2) whether regional segment length is a better predictor of bone mass than stature. Anthropometric measurements of stature, weight, sitting height, and limb lengths were taken on 368 black and white, male and female 9-year-old children. DXA (dual-energy x-ray absorptiometry) scans of the distal ulna, distal radius, and hip and lumbar spine were also obtained. Analyses of covariance were performed to assess differences in limb lengths, adjusted for differences in stature. Multiple regression analyses were used to assess significant predictors of site-specific bone mass. Stature-adjusted means of limb lengths show that black boys have longer legs and humeri but shorter trunks than white boys. In addition, black children have longer forearms than white children, and girls have longer thighs than boys. The regression analysis demonstrated that site-specific bone mass was more strongly associated with regional segment length than stature, but this had little effect on the overall pattern of ethnic and sex differences. In conclusion, there is a differential effect of ethnicity and sex on the growth of the axial and appendicular skeletons, and regional segment length is a better predictor of site-specific bone mass than stature. Copyright 2005 Wiley-Liss, Inc.

The influence of dairy consumption and physical activity on ultrasound bone measurements in Flemish children.

PubMed

De Smet, Stephanie; Michels, Nathalie; Polfliet, Carolien; D'Haese, Sara; Roggen, Inge; De Henauw, Stefaan; Sioen, Isabelle

2015-03-01

The study's aim was to analyse whether children's bone status, assessed by calcaneal ultrasound measurements, is influenced by dairy consumption and objectively measured physical activity (PA). Moreover, the interaction between dairy consumption and PA on bone mass was studied. Participants of this cross-sectional study were 306 Flemish children (6-12 years). Body composition was measured with air displacement plethysmography (BodPod), dairy consumption with a Food Frequency Questionnaire, PA with an accelerometer (only in 234 of the 306 children) and bone mass with quantitative ultrasound, quantifying speed of sound (SOS), broadband ultrasound attenuation (BUA) and Stiffness Index (SI). Regression analyses were used to study the associations between dairy consumption, PA, SOS, BUA and SI. Total dairy consumption and non-cheese dairy consumption were positively associated with SOS and SI, but no significant association could be demonstrated with BUA. In contrast, milk consumption, disregarding other dairy products, had no significant effect on calcaneal bone measurements. PA [vigorous PA, moderate to vigorous physical activity (MVPA) and counts per minute] was positively associated and sedentary time was negatively associated with BUA and SI, but no significant influence on SOS could be detected. Dairy consumption and PA (sedentary time and MVPA) did not show any interaction influencing bone measurements. In conclusion, even at young age, PA and dairy consumption positively influence bone mass. Promoting PA and dairy consumption in young children may, therefore, maximize peak bone mass, an important protective factor against osteoporosis later in life.

[Low bone mineral density in juvenile idiopathic arthritis: Prevalence and related factors].

PubMed

Galindo Zavala, Rocío; Núñez Cuadros, Esmeralda; Martín Pedraz, Laura; Díaz-Cordovés Rego, Gisela; Sierra Salinas, Carlos; Urda Cardona, Antonio

2017-10-01

Height adjustment is currently recommended for Z-score bone mineral density (BMD) assessed by dual energy X-ray absorptiometry. At present there are no studies that evaluate the prevalence of low BMD in paediatric patients with Juvenile Idiopathic Arthritis (JIA) in Spain following current recommendations. To evaluate low BMD in JIA in paediatric patients with JIA in Spain following the latest recommendations, as well as to assess associated factors. Observational cross-sectional study of Spanish JIA patients from 5 to 16 years-old, followed-up in a Paediatric Rheumatology Unit between July 2014 and July 2015. Anthropometric, clinical and treatment data were recorded. Dual energy X-ray absorptiometry, and bone metabolism parameters were collected, and a completed diet and exercise questionnaire was obtained. A total of 92 children participated. The population prevalence estimation of low BMD was less than 5% (95% CI). A significant positive correlation was found in the multiple linear regression analysis between the body mass index percentile (B: 0.021; P<.001) and lean mass index (B: 0.0002; P=.012), and BMD Z-score adjusted for height (Z-SAH). A significant negative correlation was found between fat mass index (B: -0.0001; P=.018) and serum type I collagen N-propeptide (B: -0,0006; P=.036) and Z-SAH. Low BMD prevalence in JIA patients in our population is low. An adequate nutritional status and the prevalence of lean over fat mass seem to promote the acquisition of bone mass. Those JIA patients with lower BMD could be subjected to an increase of bone turnover. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Food Versus Pharmacy: Assessment of Nutritional and Pharmacological Strategies to Improve Bone Health in Energy-Deficient Exercising Women.

PubMed

Southmayd, Emily A; Hellmers, Adelaide C; De Souza, Mary Jane

2017-10-01

The review aims to summarize our current knowledge surrounding treatment strategies aimed at recovery of bone mass in energy-deficient women suffering from the Female Athlete Triad. The independent and interactive contributions of energy status versus estrogen status on bone density, geometry, and strength have recently been reported, highlighting the importance of addressing both energy and estrogen in treatment strategies for bone health. This is supported by reports that have identified energy-related features (low body weight and BMI) and estrogen-related features (late age of menarche, oligo/amenorrhea) to be significant risk factors for low bone mineral density and bone stress injury in female athletes and exercising women. Nutritional therapy is the recommended first line of treatment to recover bone mass in energy-deficient female athletes and exercising women. If nutritional therapy fails after 12 months or if fractures or significant worsening in BMD occurs, pharmacological therapy may be considered in the form of transdermal estradiol with cyclic oral progestin (not COC).

Effect of a program of short bouts of exercise on bone health in adolescents involved in different sports: the PRO-BONE study protocol.

PubMed

Vlachopoulos, Dimitris; Barker, Alan R; Williams, Craig A; Knapp, Karen M; Metcalf, Brad S; Gracia-Marco, Luis

2015-04-11

Osteoporosis is a skeletal disease associated with high morbidity, mortality and increased economic costs. Early prevention during adolescence appears to be one of the most beneficial practices. Exercise is an effective approach for developing bone mass during puberty, but some sports may have a positive or negative impact on bone mass accrual. Plyometric jump training has been suggested as a type of exercise that can augment bone, but its effects on adolescent bone mass have not been rigorously assessed. The aims of the PRO-BONE study are to: 1) longitudinally assess bone health and its metabolism in adolescents engaged in osteogenic (football), non-osteogenic (cycling and swimming) sports and in a control group, and 2) examine the effect of a 9 month plyometric jump training programme on bone related outcomes in the sport groups. This study will recruit 105 males aged 12-14 years who have participated in sport specific training for at least 3 hours per week during the last 3 years in the following sports groups: football (n = 30), cycling (n = 30) and swimming (n = 30). An age-matched control group (n = 15) that does not engage in these sports more than 3 hours per week will also be recruited. Participants will be measured on 5 occasions: 1) at baseline; 2) after 12 months of sport specific training where each sport group will be randomly allocated into two sub-groups: intervention group (sport + plyometric jump training) and sport group (sport only); 3) exactly after the 9 months of intervention; 4) 6 months following the intervention; 5) 12 months following the intervention. Body composition (dual energy X-ray absorptiometry, air displacement plethysmography and bioelectrical impedance), bone stiffness index (ultrasounds), physical activity (accelerometers), diet (24 h recall questionnaire), pubertal maturation (Tanner stage), physical fitness (cardiorespiratory and muscular), bone turnover markers and vitamin D will be measured at each visit. The PRO-BONE study is designed to investigate the impact of osteogenic and non-osteogenic sports on bone development in adolescent males during puberty, and how a plyometric jump training programme is associated with body composition parameters.

Does a novel school-based physical activity model benefit femoral neck bone strength in pre- and early pubertal children?

PubMed

Macdonald, H M; Kontulainen, S A; Petit, M A; Beck, T J; Khan, K M; McKay, H A

2008-10-01

The effects of physical activity on bone strength acquisition during growth are not well understood. In our cluster randomized trial, we found that participation in a novel school-based physical activity program enhanced bone strength acquisition and bone mass accrual by 2-5% at the femoral neck in girls; however, these benefits depended on teacher compliance with intervention delivery. Our intervention also enhanced bone mass accrual by 2-4% at the lumbar spine and total body in boys. We investigated the effects of a novel school-based physical activity program on femoral neck (FN) bone strength and mass in children aged 9-11 yrs. We used hip structure analysis to compare 16-month changes in FN bone strength, geometry and bone mineral content (BMC) between 293 children who participated in Action Schools! BC (AS! BC) and 117 controls. We assessed proximal femur (PF), lumbar spine (LS) and total body (TB) BMC using DXA. We compared change in bone outcomes between groups using linear regression accounting for the random school effect and select covariates. Change in FN strength (section modulus, Z), cross-sectional area (CSA), subperiosteal width and BMC was similar between control and intervention boys, but intervention boys had greater gains in BMC at the LS (+2.7%, p = 0.05) and TB (+1.7%, p = 0.03) than controls. For girls, change in FN-Z tended to be greater (+3.5%, p = 0.1) for intervention girls than controls. The difference in change increased to 5.4% (p = 0.05) in a per-protocol analysis that included girls whose teachers reported 80% compliance. AS! BC benefits bone strength and mass in school-aged children; however, our findings highlight the importance of accounting for teacher compliance in classroom-based physical activity interventions.

Osteoporosis screening is unjustifiably low in older African-American women.

PubMed Central

Wilkins, Consuelo H.; Goldfeder, Jason S.

2004-01-01

BACKGROUND: More than one million Americans suffer osteoporotic fractures yearly, resulting in a marked increase in morbidity and mortality. Despite a decrease in bone mineral density with increasing age in all ethnic groups and both genders, preventative and therapeutics efforts in osteoporosis have been focused on caucasian and Asian women. This study assesses the osteoporosis screening practices and the frequency of low bone density in a primarily African-American population of older women. METHODS: Medical records of 252 women at risk for osteoporosis were reviewed for the diagnosis of osteoporosis, prior osteoporosis screening, prior breast cancer screening, and the use of calcium, vitamin D or estrogen. Subsequently, 128 women were assessed for risk factors for osteoporosis, and their bone mineral density was measured using a peripheral bone densitometer. RESULTS: Osteoporosis screening had been performed in 11.5% of the subjects. Of the women evaluated by peripheral bone densitometry, 44.5% of all women, 40.4% of African-American women, and 53.3% of caucasian women had abnormally low bone density measurements. The frequency of abnormal bone density increased with both increasing age and decreasing body mass index. CONCLUSIONS: Although few women in this population were previously screened for osteoporosis, low bone density occurred in African-American women at substantial rates. Increasing age and low body mass are important risk factors for low bone density in African-American women. Ethnicity should not be used as an exclusion criterion for screening for osteoporosis. PMID:15101666

High-Dietary Alpha-Tocopherol or Mixed Tocotrienols Have No Effect on Bone Mass, Density, or Turnover in Male Rats During Skeletal Maturation.

PubMed

Tennant, Katherine G; Leonard, Scott W; Wong, Carmen P; Iwaniec, Urszula T; Turner, Russell T; Traber, Maret G

2017-07-01

High levels of alpha-tocopherol, the usual vitamin E supplement, are reported to decrease bone mass in rodents; however, the effects of other vitamin E forms on the skeleton are unknown. To test the hypothesis that high intakes of various vitamin E forms or the vitamin E metabolite, carboxyethyl hydroxy chromanol, were detrimental to bone status, Sprague-Dawley rats (n = 6 per group, 11-week males) for 18 weeks consumed semipurified diets that contained adequate alpha-tocopherol, high alpha-tocopherol (500 mg/kg diet), or 50% Tocomin (250 mg mixed tocopherols and tocotrienols/kg diet). Vitamin E status was evaluated by measuring plasma, liver, and bone marrow vitamin E concentrations. Bone density, microarchitecture (cross-sectional volume, cortical volume, marrow volume, cortical thickness, and cancellous bone volume fraction, trabecular number, thickness, and spacing), and cancellous bone formation were assessed in the tibia using dual-energy X-ray absorptiometry, microcomputed tomography, and histomorphometry, respectively. In addition, serum osteocalcin was assessed as a global marker of bone turnover; gene expression in response to treatment was evaluated in the femur using targeted (osteogenesis related) gene profiling. No significant differences were detected between treatment groups for any of the bone endpoints measured. Vitamin E supplementation, either as alpha-tocopherol or mixed tocotrienols, while increasing vitamin E concentrations both in plasma and tissues, had no effect on the skeleton in rats.

[High prevalence of osteoporosis in asymptomatic postmenopausal Mapuche women].

PubMed

Ponce, Lucía; Larenas, Gladys; Riedemann, Pablo

2002-12-01

Genetic and environmental factors are responsible for variations in the frequency of osteoporosis. Prevalence of osteoporosis in Mapuche women (native Chileans) is unknown. To assess the prevalence and risk factors for osteoporosis in Mapuche women. A random sample of 95 asymptomatic postmenopausal Mapuche females, stratified by age, was studied. Women with diseases or medications that could interfere with calcium metabolism were excluded. Spine and femoral neck bone mass density was determined using a Lunar DPX Alpha densitometer. Seventeen percent of women had normal bone mineral density in both spine and femoral neck. In the spine, 25.3% had a normal bone mineral density, 17.9% had osteopenia and 56.8% had osteoporosis. In the femoral neck, 34.7% had a normal bone mineral density, 57.9% had osteopenia, and 7.4% had osteoporosis. There was a positive correlation between bone mineral density and body mass index. Women with more than one hour per day of physical activity, had a significantly lower proportion of osteopenia or osteoporosis. No association between bone mineral density and parity or calcium intake, was observed. There is a high prevalence of osteopenia and osteoporosis among Mapuche women. Osteoporosis was associated with low body mass index.

Comparison study on the feasibility of photoacoustic power spectrum analysis in osteoporosis detection

NASA Astrophysics Data System (ADS)

He, Weizhen; Zhu, Yunhao; Feng, Ting; Wang, Huaideng; Yuan, Jie; Xu, Guan; Wang, Xueding; Carson, Paul

2017-03-01

Osteoporosis is a progressive bone disease which is characterized by a decrease in the bone mass and deterioration in bone micro-architecture. In theory, photoacoustic (PA) imaging analysis has potential to obtain the characteristics of the bone effectively. Previous study demonstrated that photoacoustic spectral analysis (PASA) method with the qualified parameter slope could provide an objective assessment of bone microstructure and deterioration. In this study, we tried to compare PASA method with the traditional quantitative ultrasound (QUS) method in osteoporosis assessment. Numerical simulations of both PA and ultrasound (US) signal are performed on computerized tomographic (CT) images of trabecular bone with different bone mineral densities (BMDs). Ex vivo experiments were conducted on porcine femur bone model of different BMDs. We compared the quantified parameter slope and the broadband ultrasound attenuation (BUA) coefficient from the PASA and QUS among different bone models, respectively. Both the simulation and ex vivo experiment results show that bone with low BMD has a higher slope value and lower BUA value. Our result demonstrated that the PASA method has the same efficacy with QUS in bone assessment, considering PA is a non-ionizing, non-invasive technique, PASA method holds potential for clinical diagnosis in osteoporosis and other bone diseases.

Evidence of a link between resting energy expenditure and bone remodelling, glucose homeostasis and adipokine variations in adolescent girls with anorexia nervosa.

PubMed

Maïmoun, L; Guillaume, S; Lefebvre, P; Philibert, P; Bertet, H; Picot, M-C; Gaspari, L; Paris, F; Seneque, M; Dupuys, A-M; Courtet, P; Thomas, E; Mariano-Goulart, D; Bringer, J; Renard, E; Sultan, C

2016-01-01

Low bone mass is a consequence of anorexia nervosa (AN). This study assessed the effects of energy deficiency on various bone and hormonal parameters. The interrelationships between energy deficiency and bone remodelling, glucose homeostasis and adipokines underscore the importance of preventing energy deficiency to limit demineralisation and hormonal alterations in AN patients. Low areal bone mineral density (aBMD) is a well-known consequence of AN. However, the impact of reduced energy expenditure on bone metabolism is unknown. This study assessed the effects of energy deficiency on bone remodelling and its potential interactions with glucose homeostasis and adipose tissue-derived hormones in AN, a clinical model for reduced energy expenditure. Fifty women with AN and 50 age-matched controls (mean age 18.1 ± 2.7 and 18.0 ± 2.1 years, respectively) were enrolled. aBMD was determined with DXA. Resting energy expenditure (REEm), a marker of energy status, was indirectly assessed by calorimetry. Bone turnover markers, undercarboxylated osteocalcin (ucOC), parameters of glucose homeostasis, adipokines and growth factors were concomitantly evaluated. AN patients presented low aBMD at all bone sites. REEm, bone formation markers, ucOC, glucose, insulin, HOMA-IR, leptin and IGF-1 were significantly reduced, whereas the bone resorption marker, leptin receptor (sOB-R) and adiponectin were elevated in AN compared with CON. In AN patients, REEm was positively correlated with weight, BMI, whole body (WB) fat mass, WB fat-free soft tissue, markers of bone formation, glucose, insulin, HOMA-IR, leptin and IGF-1 and negatively correlated with the bone resorption marker and sOB-R. Biological parameters, aBMD excepted, appeared more affected by the weight variation in the last 6 months than by the disease duration. The strong interrelationships between REEm and bone remodelling, glucose homeostasis and adipokines underscore the importance of preventing energy deficiency to limit short- and long-term bone demineralisation and hormonal alterations in AN patients.

A quantification strategy for missing bone mass in case of osteolytic bone lesions

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

Fränzle, Andrea, E-mail: a.fraenzle@dkfz.de; Giske, Kristina; Bretschi, Maren

Purpose: Most of the patients who died of breast cancer have developed bone metastases. To understand the pathogenesis of bone metastases and to analyze treatment response of different bone remodeling therapies, preclinical animal models are examined. In breast cancer, bone metastases are often bone destructive. To assess treatment response of bone remodeling therapies, the volumes of these lesions have to be determined during the therapy process. The manual delineation of missing structures, especially if large parts are missing, is very time-consuming and not reproducible. Reproducibility is highly important to have comparable results during the therapy process. Therefore, a computerized approachmore » is needed. Also for the preclinical research, a reproducible measurement of the lesions is essential. Here, the authors present an automated segmentation method for the measurement of missing bone mass in a preclinical rat model with bone metastases in the hind leg bones based on 3D CT scans. Methods: The affected bone structure is compared to a healthy model. Since in this preclinical rat trial the metastasis only occurs on the right hind legs, which is assured by using vessel clips, the authors use the left body side as a healthy model. The left femur is segmented with a statistical shape model which is initialised using the automatically segmented medullary cavity. The left tibia and fibula are segmented using volume growing starting at the tibia medullary cavity and stopping at the femur boundary. Masked images of both segmentations are mirrored along the median plane and transferred manually to the position of the affected bone by rigid registration. Affected bone and healthy model are compared based on their gray values. If the gray value of a voxel indicates bone mass in the healthy model and no bone in the affected bone, this voxel is considered to be osteolytic. Results: The lesion segmentations complete the missing bone structures in a reasonable way. The mean ratiov{sub r}/v{sub m} of the reconstructed bone volume v{sub r} and the healthy model bone volume v{sub m} is 1.07, which indicates a good reconstruction of the modified bone. Conclusions: The qualitative and quantitative comparison of manual and semi-automated segmentation results have shown that comparing a modified bone structure with a healthy model can be used to identify and measure missing bone mass in a reproducible way.« less

Strontium Ranelate Reduces the Fracture Incidence in a Growing Mouse Model of Osteogenesis Imperfecta.

PubMed

Shi, Changgui; Hu, Bo; Guo, Lei; Cao, Peng; Tian, Ye; Ma, Jun; Chen, Yuanyuan; Wu, Huiqiao; Hu, Jinquan; Deng, Lianfu; Zhang, Ying; Yuan, Wen

2016-05-01

Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by brittle bones with increased fracture risk. Although current treatment options to improve bone strength in OI focus on antiresorptive bisphosphonates, controlled clinical trials suggest they have an equivocal effect on reducing fracture risk. Strontium ranelate (SrR) is a promising therapy with a dual mode of action that is capable of simultaneously maintaining bone formation and reducing bone resorption, and may be beneficial for the treatment of OI. In this study, SrR therapy was investigated to assess its effects on fracture frequency and bone mass and strength in an animal model of OI, the oim/oim mouse. Three-week-old oim/oim and wt/wt mice were treated with either SrR or vehicle (Veh) for 11 weeks. After treatment, the average number of fractures sustained by SrR-treated oim/oim mice was significantly reduced compared to Veh-treated oim/oim mice. Micro-computed tomographic (μCT) analyses of femurs showed that both trabecular and cortical bone mass were significantly improved with SrR treatment in both genotypes. SrR significantly inhibited bone resorption, whereas bone formation indices were maintained. Biomechanical testing revealed improved bone structural properties in both oim/oim and wild-type (wt/wt) mice under the treatment, whereas no significant effects on bone brittleness and material quality were observed. In conclusion, SrR was able to effectively reduce fractures in oim/oim mice by improving bone mass and strength and thus represents a potential therapy for the treatment of pediatric OI. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research.

Higher premenarcheal bone mass in elite gymnasts is maintained into young adulthood after long-term retirement from sport: a 14-year follow-up.

PubMed

Erlandson, Marta C; Kontulainen, Saija A; Chilibeck, Phil D; Arnold, Cathy M; Faulkner, Robert A; Baxter-Jones, Adam D G

2012-01-01

Sports that impact-load the skeleton during childhood and adolescence increase determinants of bone strength such as bone mineral content and density; however, it is unclear if this benefit is maintained after retirement from the sport. The purpose of this study was to assess whether the previously reported higher bone mass in a group of premenarcheal gymnasts was still apparent 10 years after the cessation of participation and withdrawal of the gymnastics loading stimulus. In 1995, 30 gymnasts 8 to 15 years of age were measured and compared with 30 age-matched nongymnasts. Twenty-five former gymnasts and 22 nongymnasts were measured again 14 years later (2009 to 2010). Gymnasts had been retired from gymnastics training and competition for an average of 10 years. Total body (TB), lumbar spine (LS), and femoral neck (FN) bone mineral content (BMC) was assessed at both measurement occasions by dual-energy X-ray absorptiometry (DXA). Multivariate analysis of covariance (MANCOVA) was used to compare former gymnasts' and nongymnasts' BMC while controlling for differences in body size and maturation (covariates: age, height, weight, and years from menarche [1995] or age at menarche [2009 to 2010]). Premenarcheal gymnasts (measured in 1995) had significantly greater size-adjusted TB, LS, and FN BMC (p < 0.05) (15%, 17%, and 12%, respectively) than nongymnasts. Ten years after retirement, gymnasts had maintained similar size-adjusted TB, LS, and FN BMC differences (p < 0.05) (13%, 19%, and 13%, respectively) when compared with nongymnasts. Bone mass benefits in premenarcheal gymnasts were still apparent even after long-term (10 years) removal of the gymnastics loading stimulus. Copyright © 2012 American Society for Bone and Mineral Research.

Reduced bone mass and preserved marrow adipose tissue in patients with inflammatory bowel diseases in long-term remission.

PubMed

Bastos, C M; Araújo, I M; Nogueira-Barbosa, M H; Salmon, C E G; de Paula, F J A; Troncon, L E A

2017-07-01

Bone marrow adipose tissue has not been studied in patients with inactive inflammatory bowel disease. We found that these patients have preserved marrow adiposity even with low bone mass. Factors involved in bone loss in active disease may have long-lasting effects but do not seem to affect bone marrow adiposity. Reduced bone mass is known to occur at varying prevalence in patients with inflammatory bowel diseases (IBD) because of inflammation, malnutrition, and steroid therapy. Osteoporosis may develop in these patients as the result of an imbalanced relationship between osteoblasts and adipocytes in bone marrow. This study aimed to evaluate for the first time bone mass and bone marrow adipose tissue (BMAT) in a particular subgroup of IBD patients characterized by long-term, steroid-free remission. Patients with Crohn's disease (CD; N = 21) and ulcerative colitis (UC; N = 15) and controls (C; N = 65) underwent dual X-ray energy absorptiometry and nuclear magnetic resonance spectroscopy of the L3 lumbar vertebra for BMAT assessment. Both the CD and UC subgroups showed significantly higher proportions of patients than controls with Z-score ≤-2.0 at L1-L4 (C 1.54%; CD 19.05%; UC 20%; p = 0.02), but not at other sites. The proportions of CD patients with a T-score ˂-1.0 at the femoral neck (C 18.46%; CD 47.62%; p = 0.02) and total hip (C 16.92%; CD 42.86%; p = 0.03) were significantly higher than among controls. There were no statistically significant differences between IBD patients and controls regarding BMAT at L3 (C 28.62 ± 8.15%; CD 29.81 ± 6.90%; UC 27.35 ± 9.80%; p = 0.67). IBD patients in long-term, steroid-free remission may have a low bone mass in spite of preserved BMAT. These findings confirm the heterogeneity of bone disorders in IBD and may indicate that factors involved in bone loss in active disease may have long-lasting effects on these patients.

Bone density in the obese child - clinical considerations and diagnostic challenges

PubMed Central

Kelley, Jennifer; Crabtree, Nicola; Zemel, Babette S.

2017-01-01

The prevalence of obesity in children has reached epidemic proportions. Concern about bone health in obese children, in part, derives from the potentially increased fracture risk associated with obesity. Additional risk factors that affect bone mineral accretion, may also contribute to obesity, such as low physical activity and nutritional factors. Consequences of obesity, such as inflammation, insulin resistance and non-alcoholic fatty liver disease, may also affect bone mineral acquisition, especially during the adolescent years when rapid increases in bone contribute to attaining peak bone mass. Further, numerous pediatric health conditions are associated with excess adiposity, altered body composition or endocrine disturbances that can affect bone accretion. Thus, there is a multitude of reasons for considering clinical assessment of bone health in an obese child. Multiple diagnostic challenges affect the measurement of bone density and its interpretation. These include greater precision error, difficulty in positioning, and the effects of increased lean and fat tissue on bone health outcomes. Future research is required to address these issues to improve bone health assessment in obese children. PMID:28105511

[Effects of sexual maturation on body composition, dermatoglyphics, somatotype and basic physical qualities of adolescents].

PubMed

Linhares, Renato Vidal; Matta, Marcelo de Oliveira; Lima, Jorge R P; Dantas, Paulo M Silva; Costa, Mônica Barros; Fernandes Filho, José

2009-02-01

Describe the characteristics of body composition, somatotype, basic physical qualities, dermatoglyphics and bone age regarding sexual maturation stages of boys. A transversal study was carried out in 136 boys, between 10 and 14 years of age. Clinical assessment, physical examination and radiography of wrists and hands to calculate bone age were performed. A tendency of increasing total body mass, stature, body mass index, body bone diameters and muscle circumferences and basic physical qualities was found with the advancing of puberty. No differences were found in dermatoglyphics and somatotype between different stages of puberty maturation. Due to the changes in important parameters of physical training that occur during puberty, it can be concluded that the selection of children and adolescents for sport training and competitions should be based not only on chronological age but also, and mainly on sexual maturation, for better physical assessment and appropriate training for this population.

MRI differentiation of low-grade from high-grade appendicular chondrosarcoma.

PubMed

Douis, Hassan; Singh, Leanne; Saifuddin, Asif

2014-01-01

To identify magnetic resonance imaging (MRI) features which differentiate low-grade chondral lesions (atypical cartilaginous tumours/grade 1 chondrosarcoma) from high-grade chondrosarcomas (grade 2, grade 3 and dedifferentiated chondrosarcoma) of the major long bones. We identified all patients treated for central atypical cartilaginous tumours and central chondrosarcoma of major long bones (humerus, femur, tibia) over a 13-year period. The MRI studies were assessed for the following features: bone marrow oedema, soft tissue oedema, bone expansion, cortical thickening, cortical destruction, active periostitis, soft tissue mass and tumour length. The MRI-features were compared with the histopathological tumour grading using univariate, multivariate logistic regression and receiver operating characteristic curve (ROC) analyses. One hundred and seventy-nine tumours were included in this retrospective study. There were 28 atypical cartilaginous tumours, 79 grade 1 chondrosarcomas, 36 grade 2 chondrosarcomas, 13 grade 3 chondrosarcomas and 23 dedifferentiated chondrosarcomas. Multivariate analysis demonstrated that bone expansion (P = 0.001), active periostitis (P = 0.001), soft tissue mass (P < 0.001) and tumour length (P < 0.001) were statistically significant differentiating factors between low-grade and high-grade chondral lesions with an area under the ROC curve of 0.956. On MRI, bone expansion, active periostitis, soft tissue mass and tumour length can reliably differentiate high-grade chondrosarcomas from low-grade chondral lesions of the major long bones. • Accurate differentiation of low-grade from high-grade chondrosarcomas is essential before surgery • MRI can reliably differentiate high-grade from low-grade chondrosarcomas of long bone • Differentiating features are bone expansion, periostitis, soft tissue mass and tumour length • Presence of these four MRI features demonstrated a diagnostic accuracy (AUC) of 95.6 % • The findings may result in more accurate diagnosis before definitive surgery.

Comparison of muscle/lean mass measurement methods: correlation with functional and biochemical testing.

PubMed

Buehring, B; Siglinsky, E; Krueger, D; Evans, W; Hellerstein, M; Yamada, Y; Binkley, N

2018-03-01

DXA-measured lean mass is often used to assess muscle mass but has limitations. Thus, we compared DXA lean mass with two novel methods-bioelectric impedance spectroscopy and creatine (methyl-d3) dilution. The examined methodologies did not measure lean mass similarly and the correlation with muscle biomarkers/function varied. Muscle function tests predict adverse health outcomes better than lean mass measurement. This may reflect limitations of current mass measurement methods. Newer approaches, e.g., bioelectric impedance spectroscopy (BIS) and creatine (methyl-d3) dilution (D3-C), may more accurately assess muscle mass. We hypothesized that BIS and D3-C measured muscle mass would better correlate with function and bone/muscle biomarkers than DXA measured lean mass. Evaluations of muscle/lean mass, function, and serum biomarkers were obtained in older community-dwelling adults. Mass was assessed by DXA, BIS, and orally administered D3-C. Grip strength, timed up and go, and jump power were examined. Potential muscle/bone serum biomarkers were measured. Mass measurements were compared with functional and serum data using regression analyses; differences between techniques were determined by paired t tests. Mean (SD) age of the 112 (89F/23M) participants was 80.6 (6.0) years. The lean/muscle mass assessments were correlated (.57-.88) but differed (p < 0.0001) from one another with DXA total body less head being highest at 37.8 (7.3) kg, D3-C muscle mass at 21.1 (4.6) kg, and BIS total body intracellular water at 17.4 (3.5) kg. All mass assessment methods correlated with grip strength and jump power (R = 0.35-0.63, p < 0.0002), but not with gait speed or repeat chair rise. Lean mass measures were unrelated to the serum biomarkers measured. These three methodologies do not similarly measure muscle/lean mass and should not be viewed as being equivalent. Functional tests assessing maximal muscle strength/power (grip strength and jump power) correlated with all mass measures whereas gait speed was not. None of the selected serum measures correlated with mass. Efforts to optimize muscle mass assessment and identify their relationships with health outcomes are needed.

Osteoporosis and gait and balance disturbances in older sarcopenic obese New Zealanders.

PubMed

Waters, D L; Hale, L; Grant, A M; Herbison, P; Goulding, A

2010-02-01

Bone, muscle, and fat may affect gait and balance in older adults. Osteoporosis was prevalent in low muscle mass participants and related to gait and balance deficits. Low muscle combined with high fat mass had more functional deficits and poorer bone health, which has implications for falls risk and fractures. Decreasing bone density and muscle mass and increasing fat mass may act synergistically to affect gait and balance in older adults. One hundred eighty-three older adults (age 72.7 +/- 6 years, range 56-93; body mass index 28.2 +/- 4.9, range 16.6-46.0) were recruited from a New Zealand falls prevention intervention trial. Total and appendicular skeletal muscle mass (ASM), percent fat, and bone mineralization were assessed by dual energy X-ray absorptiometry and used to characterize normal lean (NL, n = 51), sarcopenic (SS, n = 18), sarcopenic obese (SO, n = 29), and obese (OO, n = 85) phenotypes. Functional performance was assessed using timed up and go, chair stand, single leg stand, and step test. Regression models were adjusted for age, sex, medications, and physical activity. Femoral neck osteoporosis was present in 22% SS, 17% SO, 12% NL, and 7% OO. Femoral neck osteoporosis with low ASM predicted poor chair stand performance (beta -3.3, standard error 1.6, p = 0.04). SO scored lowest on the chair stand (p = 0.03) and step test (p = 0.03). Higher ASM predicted faster timed up and go performance (p = 0.001). Osteoporosis was prevalent in low ASM groups (SS and SO) and related to gait and balance deficits, particularly in the SO. This has implications for falls risk, fractures, and interventions.

The peak bone mass concept: is it still relevant?

PubMed

Schönau, Eckhard

2004-08-01

The peak bone mass concept implies that optimal skeletal development during childhood and adolescence will prevent fractures in late adulthood. This concept is based on the observation that areal bone density increases with growth during childhood, is highest around 20 years of age and declines thereafter. However, it is now clear that strong bones in the youngster do not necessarily lead to a fracture-free old age. In the recent bone densitometric literature, the terms bone mass and bone density are typically used synonymously. In physics, density has been defined as the mass of a body divided by its volume. In clinical practice and science, "bone density" usually has a different meaning-the degree to which a radiation beam is attenuated by a bone, as judged from a two-dimensional projection image (areal bone density). The attenuation of a radiation beam does not only depend on physical density, but also on bone size. A small bone therefore has a lower areal bone density than a larger bone, even if the physical density is the same. Consequently, a low areal bone density value can simply reflect the small size of an otherwise normal bone. At present, bone mass analysis is very useful for epidemiological studies on factors that may have an impact on bone development. There is an ongoing discussion about whether the World Health Organization (WHO) definition of osteoporosis is over-simplistic and requires upgrading to include indices representing the distribution of bone and mineral (bone strength indices). The following suggestions and recommendations outline a new concept: bone mass should not be related to age. There is now more and more evidence that bone mass should be related to bone size or muscle function. Thus analyzed, there is no such entity as a "peak bone mass". Many studies are currently under way to evaluate whether these novel approaches increase sensitivity and specificity of fracture prediction in an individual. Furthermore, the focus of many bone researchers is shifting away from bone mass to bone geometry or bone strength. Bone mass is one surrogate marker of bone strength. Widely available techniques for measurement of bone mass, such as dual-energy X-ray absorptiometry, radiogrammetry, and computed tomography, can also be used to measure variables of bone geometry such as cortical thickness, cortical area, and moment of inertia.

Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption, and increases bone formation markers in hypogonadal men--a clinical research center study.

PubMed

Wang, C; Eyre, D R; Clark, R; Kleinberg, D; Newman, C; Iranmanesh, A; Veldhuis, J; Dudley, R E; Berman, N; Davidson, T; Barstow, T J; Sinow, R; Alexander, G; Swerdloff, R S

1996-10-01

To study the effects of androgen replacement therapy on muscle mass and strength and bone turnover markers in hypogonadal men, we administered sublingual testosterone (T) cyclodextrin (SLT; 5 mg, three times daily) to 67 hypogonadal men (baseline serum T, < 8.4 nmol/L) recruited from 4 centers in the U.S.: Torrance (n = 34), Durham (n = 12), New York (n = 9), and Salem (n = 12). Subjects who had received prior T therapy were withdrawn from injections for at least 6 weeks and from oral therapy for 4 weeks. Body composition, muscle strength, and serum and urinary bone turnover markers were measured before and after 6 months of SLT. We have shown previously that this regimen for 60 days will maintain adequate serum T levels and restore sexual function. Total body (P = 0.0104) and lean body mass (P = 0.007) increased with SLT treatment in the 34 subjects in whom body composition was assessed. There was no significant change in total body fat or percent fat. The increase in lean body mass was mainly in the legs; the right leg lean mass increased from 8.9 +/- 0.3 kg at 0 months to 9.2 +/- 0.3 kg at 6 months (P = 0.0008). This increase in leg lean mass was associated with increased leg muscle strength, assessed by leg press (0 months, 139.0 +/- 4.0 kg; 6 months, 147.7 +/- 4.2 kg; P = 0.0038). SLT replacement in hypogonadal men led to small, but significant, decreases in serum Ca (P = 0.0029) and the urinary calcium/creatinine ratio (P = 0.0066), which were associated with increases in serum PTH (P = 0.0001). At baseline, the urinary type I collagen-cross linked N-telopeptides/creatinine ratio [75.6 +/- 7.9 nmol bone collagen equivalents (BCE/mmol] was twice the normal adult male mean (41.0 +/- 3.6 nmol BCE/mmol) and was significantly decreased in response to SLT treatment at 6 months (68.2 +/- 7.7 nmol BCE/mmol; P = 0.0304) without significant changes in urinary creatinine. Serum skeletal alkaline phosphatase did not change. In addition, SLT replacement caused significant increases in serum osteocalcin (P = 0.0001) and type I procollagen (P = 0.0012). Bone mineral density did not change during the 6 months of SLT treatment. We conclude that SLT replacement therapy resulted in increases in lean muscle mass and muscle strength. Like estrogen replacement in hypogonadal postmenopausal females, androgen replacement therapy led to decreased bone resorption and urinary calcium excretion. Moreover, androgen replacement therapy may have the additional benefit of increasing bone formation. A longer term study for several years duration would be necessary to demonstrate whether these changes in bone turnover marker levels will result in increased bone mineral density decreased fracture risks, and reduced frailty in hypogonadal men.

Rodent bone densitometer on the International Space Station: Instrument design and performance

NASA Astrophysics Data System (ADS)

Vellinger, John C.; Barton, Kenneth; Faget, Paul; Todd, Paul; Boland, Eugene

2016-07-01

The study of bone loss dynamics, mechanisms and countermeasures has been a publicly stated purpose of biomedical research aboard the International Space Station. Rodent research has always played a major role in terrestrial laboratories studying bone loss. The "gold standard" for assessing bone loss in human patients has been dual-energy x-ray absorptiometry (DEXA). DEXA is also widely applied to the study of bone loss in laboratory animals, so this technology has been added to the ISS inventory of analytical tools in the form of the ISS Bone Densitometer (BD) designed, constructed, tested and integrated by Techshot, Inc. (Greenville, Indiana, USA). The BD is a re-packaged COTS device known as PIXImus (GE-Lunar, USA), which was installed on ISS in November 2014 after launching on SpaceX-4. To facilitate operations in microgravity and to meet spaceflight facility and safety requirements the commercial x-ray source, control electronics and imaging system were modified and packaged by Techshot into a drawer that fits into a single EXPRESS Locker replacement. A space-rated "Exam Box" is also supplied for containment of the anesthetized subject during transfer into the BD and during exposure. The commercial software package controls four paired-energy exposures, 80 and 35 kV, and applies DEXA algorithms to the fluorescence images and displays bone mineral density (BMD), bone mineral content, lean mass, fat mass, total mass and per cent fat. The BD is therefore also a means for measuring mass and body composition making it a versatile tool for many types of rodent studies on orbit. The BD has been operated multiple times on orbit, and its performance has not differed significantly from its performance on the ground. It has been shown to measure body mass with a precision of +/- 0.1 g and on-orbit accuracy of -0.3 g. It is expected to detect BMD losses of approximately 2%. The image data are stored in a manner that allows post-test data analysis especially including the identification of a region of interest (ROI) by the investigator who wishes to assess BMD changes in femur only or spine only, for example. This research was supported by the Center for Advancement of Science in Space (CASIS) and NASA Contract NNJ13GA01C.

Nutritional Status Assessment (SMO 016E)

NASA Technical Reports Server (NTRS)

Smith, S. M.; Heer, M. A.; Zwart, S. R.

2014-01-01

The Nutritional Status Assessment Supplemental Medical Objective was initiated to expand nominal clinical nutrition testing of ISS astronauts, and to gain a better understanding of the time course of changes in nutritional status during flight. The primary activity of this effort was collecting blood and urine samples during flight for analysis after return to Earth. Samples were subjected to a battery of tests. The resulting data provide a comprehensive survey of how nutritional status and related systems are affected by 4-6 months of space flight. Analysis of these data has yielded many findings to date, including: Vision. Documented evidence that biochemical markers involved in one-carbon metabolism were altered in crewmembers who experienced vision-related issues during and after flight (1). Iron, Oxidative Stress, and Bone. In-flight data document a clear association of increased iron stores, markers of oxidative damage to DNA, and bone loss (2). Exercise. Documented that well-nourished crewmembers performing heavy resistance exercise returned from ISS with bone mineral densities unchanged from preflight (3). Furthermore, the response of bone to space flight and exercise countermeasures was the same in men and women (4). Body Mass. Crewmembers lose 2-5% of their body mass in the first month of flight, and maintain the lower body mass during flight (5). Additionally, the two devices to measure body mass on orbit, the SLAMMD and BMMD, provide similar results (5). Cytokines. Findings indicated that a pattern of persistent physiological adaptations occurs during space flight that includes shifts in immune and hormonal regulation (6). Fish/Bone. Documented a relationship between fish intake and bone loss in astronauts (that is, those who ate more fish lost less bone) (7). Vitamin K. Documented that in generally well-fed and otherwise healthy individuals, vitamin K status and bone vitamin K-dependent proteins are unaffected by space flight (and bed rest) (8). Testosterone. Documented that blood concentrations of testosterone were unchanged during flight, but a transient decline occurred after landing (9). Calcium. Nutrition SMO data contributed to the ISS Program by helping understand how and why the Urine Processor Assembly clogged with calcium sulfate precipitate (10). Sample Processing. Ground-based analytical testing results have also been published (11).

Differences of bone mineral mass, volumetric bone mineral density, geometrical and structural parameters and derived strength of the tibia between premenopausal and postmenopausal women of different age groups: a peripheral Quantitative Computed Tomography (pQCT) study

PubMed Central

Stathopoulos, K.D.; Zoubos, A.B.; Papaioannou, N.A.; Mastrokalos, D.; Galanos, A.; Papagelopoulos, P.J.; Skarantavos, G.

2016-01-01

Menopause constitutes a significant cause of bone loss, and it is currently debated whether bone mass is preserved or begins to decline substantially before that time in women. We used pQCT of the tibia to estimate differences of bone mineral mass, bone geometry and derived strength between premenopausal and postmenopausal Caucasian women of different age-groups per decade of age (20-79y). For each individual, we assessed total, trabecular and cortical bone mineral content (BMC, mg) and volumetric bone mineral density (BMD, mg/cm3); total and cortical cross-sectional areas (CSA, mm2); periosteal circumference (PERI_C, mm); endosteal circumference (ENDO_C, mm); mean cortical thickness (CRT_THK, mm); and Stress-Strain Index (SSI). Comparisons were made both between premenopausal (N=84) and postmenopausal (N=231) women as distinct groups, and among women of the different age-groups. Our results indicated that premenopausal women had significantly higher trabecular and cortical BMC and vBMD, with higher cortical CSA, CRT_THK and SSI than postmenopausal women. Moreover, significant differences of trabecular but not cortical BMC, vBMD or SSI were found between women of the younger (<48y) age-groups. PERI_C, ENDO_C displayed lower values in the 20-29y group and higher values in the 70-79y group, denoting significant differences of bone geometry with aging. PMID:27282455

Longitudinal relationships between whole body and central adiposity on weight-bearing bone geometry, density, and bone strength: a pQCT study in young girls

PubMed Central

Farr, Joshua N.; Laudermilk, Monica J.; Lee, Vinson R.; Blew, Robert M.; Stump, Craig; Houtkooper, Linda; Lohman, Timothy G.; Going, Scott B.

2015-01-01

Summary Longitudinal relationships between adiposity (total body and central) and bone development were assessed in young girls. Total body and android fat masses were positively associated with bone strength and density parameters of the femur and tibia. These results suggest adiposity may have site-specific stimulating effects on the developing bone. Introduction Childhood obesity may impair bone development, but the relationships between adiposity and bone remain unclear. Failure to account for fat pattern may explain the conflicting results. Purpose Longitudinal associations of total body fat mass (TBFM) and android fat mass (AFM) with 2-year changes in weight-bearing bone parameters were examined in 260 girls aged 8–13 years at baseline. Peripheral quantitative computed tomography was used to measure bone strength index (BSI, square milligrams per quartic millimeter), strength–strain index (SSI, cubic millimeters), and volumetric bone mineral density (vBMD, milligrams per cubic centimeter) at distal metaphyseal and diaphyseal regions of the femur and tibia. TBFM and AFM were assessed by dual-energy x-ray absorptiometry. Results Baseline TBFM and AFM were positively associated with the change in femur BSI (r =0.20, r =0.17, respectively) and femur trabecular vBMD (r =0.19, r =0.19, respectively). Similarly, positive associations were found between TBFM and change in tibia BSI and SSI (r =0.16, r =0.15, respectively), and femur total and trabecular vBMD (r =0.12, r =0.14, respectively). Analysis of covariance showed that girls in the middle thirds of AFM had significantly lower femur trabecular vBMD and significantly higher tibia cortical vBMD than girls in the highest thirds of AFM. All results were significant at p <0.05. Conclusions Whereas baseline levels of TBFM and AFM are positive predictors of bone strength and density at the femur and tibia, higher levels of AFM above a certain level may impair cortical vBMD growth at weight-bearing sites. Future studies in obese children will be needed to test this possibility. NIH/NICHD #HD-050775. PMID:24113839

Markers of Bone Health, Bone-Specific Physical Activities, Nutritional Intake, and Quality of Life of Professional Jockeys in Hong Kong.

PubMed

Poon, Eric Tsz-Chun; O'Reilly, John; Sheridan, Sinead; Cai, Michelle Mingjing; Wong, Stephen Heung-Sang

2018-04-28

Weight-making practices, regularly engaged in by horse racing jockeys, have been suggested to impair both physiological and mental health. This study aimed to assess bone health markers, nutritional intake, bone-specific physical activity (PA) habits, and quality of life of professional jockeys in Hong Kong (n = 14), with gender-, age-, and body mass index-matched controls (n = 14). Anthropometric measurements, serum hormonal biomarkers, bone mineral density, bone-specific PA habits, nutritional intake, and quality of life were assessed in all participants. The jockey group displayed significantly lower bone mineral density at both calcanei than the control group (left: 0.50 ± 0.06 vs. 0.63 ± 0.07 g/cm 2 ; right: 0.51 ± 0.07 vs. 0.64 ± 0.10 g/cm 2 , both ps < .01). Thirteen of the 14 jockeys (93%) showed either osteopenia or osteoporosis in at least one of their calcanei. No significant difference in bone mineral density was detected for either forearm between the groups. The current bone-specific PA questionnaire score was lower in the jockey group than the control group (5.61 ± 1.82 vs. 8.27 ± 2.91, p < .05). Daily energy intake was lower in the jockeys than the controls (1,360 ± 515 vs. 1,985 ± 1,046 kcal/day, p < .01). No significant group difference was found for micronutrient intake assessed by the bone-specific food frequency questionnaire, blood hormonal markers, and quality of life scores. Our results revealed suboptimal bone conditions at calcanei and insufficient energy intake and bone-loading PAs among professional jockeys in Hong Kong compared with healthy age-, gender-, and body mass index-matched controls. Further research is warranted to examine the effect of improved bone-loading PAs and nutritional habits on the musculoskeletal health of professional jockeys.

Measurement of Bone: Diagnosis of SCI-Induced Osteoporosis and Fracture Risk Prediction

PubMed Central

Morse, Leslie R.

2015-01-01

Background: Spinal cord injury (SCI) is associated with a rapid loss of bone mass, resulting in severe osteoporosis and a 5- to 23-fold increase in fracture risk. Despite the seriousness of fractures in SCI, there are multiple barriers to osteoporosis diagnosis and wide variations in treatment practices for SCI-induced osteoporosis. Methods: We review the biological and structural changes that are known to occur in bone after SCI in the context of promoting future research to prevent or reduce risk of fracture in this population. We also review the most commonly used methods for assessing bone after SCI and discuss the strengths, limitations, and clinical applications of each method. Conclusions: Although dual-energy x-ray absorptiometry assessments of bone mineral density may be used clinically to detect changes in bone after SCI, 3-dimensional methods such as quantitative CT analysis are recommended for research applications and are explained in detail. PMID:26689691

Measurement of Bone: Diagnosis of SCI-Induced Osteoporosis and Fracture Risk Prediction.

PubMed

Troy, Karen L; Morse, Leslie R

2015-01-01

Spinal cord injury (SCI) is associated with a rapid loss of bone mass, resulting in severe osteoporosis and a 5- to 23-fold increase in fracture risk. Despite the seriousness of fractures in SCI, there are multiple barriers to osteoporosis diagnosis and wide variations in treatment practices for SCI-induced osteoporosis. We review the biological and structural changes that are known to occur in bone after SCI in the context of promoting future research to prevent or reduce risk of fracture in this population. We also review the most commonly used methods for assessing bone after SCI and discuss the strengths, limitations, and clinical applications of each method. Although dual-energy x-ray absorptiometry assessments of bone mineral density may be used clinically to detect changes in bone after SCI, 3-dimensional methods such as quantitative CT analysis are recommended for research applications and are explained in detail.

Body weight change since menopause and percentage body fat mass are predictors of subsequent bone mineral density change of the proximal femur in women aged 75 years and older: results of a 5 year prospective study.

PubMed

Blain, H; Carrière, I; Favier, F; Jeandel, C; Papoz, L

2004-07-01

Few studies have evaluated risk factors for bone loss in elderly women. We examined risk factors associated with a 5-year longitudinal change in bone mineral density (BMD) at the hip in healthy women aged 75 years and older. The BMD of 276 women from the French EPIDOS (Epidémiologie des Osteoporoses) study was assessed in Montpellier from 1992 to 1993 and again from 1997 to 1998. BMD was measured at the femoral neck, trochanter, and Ward's area using the same Lunar densitometer. We examined the relationship between clinical and behavioral factors at baseline and their variations during follow-up, with percentage BMD change adjusted for baseline BMD. Depending on the femur subregion studied, a significant decrease in BMD (exceeding the least significant difference, i.e., > 2.8 CV) was observed in 36.2% to 51.1% of women. Multivariate analysis showed that both postmenopausal weight change before baseline and baseline percentage of fat mass were positively correlated with BMD change at the Ward's triangle and the trochanter. Yearly absolute and relative weight changes over the follow-up period were significantly associated with change of trochanter and femoral neck BMD. Our results show that maintenance of body weight throughout the postmenopause period and body fat mass play protective roles against bone loss at the proximal femur in women aged 75 years and older and suggest the value in including assessment of weight change throughout postmenopause and percentage body fat mass in screening programs for elderly women who are at higher risk of accelerated bone loss.

Physical activity benefits bone density and bone-related hormones in adult men with cervical spinal cord injury.

PubMed

Chain, Amina; Koury, Josely C; Bezerra, Flávia Fioruci

2012-09-01

Severe bone loss is a recognized complication of chronic spinal cord injury (SCI). Physical exercise contributes to bone health; however, its influence on bone mass of cervical SCI individuals has not been investigated. The aim of this study was to investigate the influence of physical activity on bone mass, bone metabolism, and vitamin D status in quadriplegics. Total, lumbar spine (L1-L4), femur and radius bone mineral density (BMD) were assessed in active (n = 15) and sedentary (n = 10) quadriplegic men by dual energy X-ray absorptiometry. Concentrations of 25-hydroxyvitamin D [25(OH)D], PTH, IGF1, osteocalcin and NTx were measured in serum. After adjustments for duration of injury, total body mass, and habitual calcium intake, bone indices were similar between groups, except for L1-L4 BMD Z score that was higher in the sedentary group (P < 0.05). Hours of physical exercise per week correlated positively with 25(OH)D (r = 0.59; P < 0.05) and negatively with PTH (r = -0.50; P < 0.05). Femur BMD was negatively associated with the number of months elapsed between the injury and the onset of physical activity (r = -0.60; P < 0.05). Moreover, in the active subjects, both L1-L4 BMD Z score (r = 0.72; P < 0.01) and radius BMD (r = 0.59; P < 0.05) were positively associated with calcium intake. In this cross-sectional study, both the onset of physical activity after injury and the number of hours dedicated to exercise were able to influence bone density and bone-related hormones in quadriplegic men. Our results also suggest a positive combined effect of exercise and calcium intake on bone health of quadriplegic individuals.

How does bone quality differ between healthy-weight and overweight adolescents and young adults?

PubMed

Hoy, Christa L; Macdonald, Heather M; McKay, Heather A

2013-04-01

Overweight youth have greater bone mass than their healthy-weight peers but sustain more fractures. However, it is unclear whether and how excess body fat influences bone quality in youth. We determined whether overweight status correlated with three-dimensional aspects of bone quality influencing bone strength in adolescent and young adult females and males. We categorized males (n=103; mean age, 17 years) and females (n=85; mean age, 18 years) into healthy-weight and overweight groups. We measured lean mass (LM) and fat mass (FM) with dual-energy x-ray absorptiometry (DXA). We used high-resolution peripheral quantitative CT to assess the distal radius (7% site) and distal tibia (8% site). Bone quality measures included total bone mineral density (Tt.BMD), total area (Tt.Ar), trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), separation (Tb.Sp), and thickness (Tb.Th). We used multiple regression to compare bone quality between healthy-weight and overweight adolescents adjusting for age, ethnicity, limb length, LM, and FM. Overweight males had higher (10%-21%) Tt.BMD, BV/TV, and Tb.N and lower Tb.Sp at the tibia and lower Tt.Ar at the radius than healthy-weight males. No differences were observed between overweight and healthy-weight females. LM attenuated the differences in bone quality between groups in males while FM negatively predicted Tt.BMD, BV/TV, Tb.N, and Tb.Th. Our data suggest overweight males have enhanced bone quality compared with healthy-weight males; however, when group differences are interpreted in the context of the mechanostat theory, it appears bone quality of overweight adolescents adapts to LM and not to greater FM.

Bodybuilders' body composition: effect of nandrolone decanoate.

PubMed

van Marken Lichtenbelt, Wouter D; Hartgens, Fred; Vollaard, Niels B J; Ebbing, Spike; Kuipers, Harm

2004-03-01

The use of androgenic-anabolic steroids (AAS) among bodybuilders to increase muscle mass is widespread. Nandrolone decanoate (ND) is one of the most popular misused AAS, although the effects on body composition are equivocal. Therefore, the purpose of this study was to determine the effect of ND on body composition in male bodybuilders, with special reference to muscle mass alterations. Using a randomized "double-blind" "placebo-controlled" design, 16 experienced male bodybuilders (age: 19-44 yr) either received ND (200 mg.wk(-1), intramuscularly) or placebo for 8 wk. Body composition was assessed using the four-component model, combining results from underwater weighing, dual-energy x-ray absorptiometry (DXA), and deuterium dilution. Total bone mineral content and density were measured using DXA. Water compartments (extracellular water [ECW] and intracellular water [ICW]) were determined using deuterium dilution and bromide dilution. ND administration resulted in significant increments of body mass (+2.2 kg), fat-free mass (FFM: +2.6 kg), and total body water (+1.4 kg). No significant changes in fat mass, percentage fat, ECW, ICW, ECW/ICW ratio, hydration of the FFM, and on bone mineral measurements were observed. The results show that the administration of 200 mg.wk(-1) of ND (intramuscularly) for 8 wk significantly increased body mass and FFM, whereas fat mass, bone mineral content, bone mineral density, and the hydration of the FFM remained unaffected. These data indicate that the changes can be attributed to an increase of muscle mass.

Growth and development of male "little" mice assessed with Parks' theory of feeding and growth.

PubMed

Puche, Rodolfo C; Alloatti, Rosa; Chapo, Gustavo

2002-01-01

This work was designed to characterize the appetite kinetics and growth of male C57BL/6J (lit) mice. Those variables were assessed with Parks' function of ad libitum feeding and growth. Heterozygous mice (lit/+) attained their mature weight at 12-15 weeks of age, peak growth rate (3.5 g/week) at 5 weeks and displayed the normal decay of food conversion efficiency as a function of age. The homozygous genotype has a chronic defect in the synthesis and secretion of growth hormone (GH). Homozygous mice could not be assessed with Park's function. From the 4th to the 15th week of age, body weight increased linearly and exhibited constant food conversion efficiency. Food intake of both genotypes was commensurate with their body weights. Lit/lit mice became progressively obese. At 40 weeks of age, body fat of lit/lit mice was fivefold that of lit/+ and their body weight was similar to their heterozygous controls. The chronic deficiency of growth hormone produced a lower bone mass (compared to heterozygous controls). Bone mass of both genotypes attained maturity at 12-15 weeks with a maximum growth rate at 5 weeks. Body weight and bone mass grow harmoniously in lit/+ but not in lit/lit mice.

Relationship of obesity with osteoporosis

PubMed Central

Zhao, Lan-Juan; Liu, Yong-Jun; Liu, Peng-Yuan; Hamilton, James; Recker, Robert R.; Deng, Hong-Wen

2007-01-01

Context The relationship between obesity and osteoporosis has been widely studied, and epidemiological evidence shows that obesity is correlated with increased bone mass. Previous analyses, however, did not control for the mechanical loading effects of total body weight on bone mass and may have generated a confounded or even biased relationship between obesity and osteoporosis. Objective To re-evaluate the relationship between obesity and osteoporosis by accounting for the mechanical loading effects of total body weight on bone mass. Methods We measured whole body fat mass, lean mass, percentage fat mass (PFM), body mass index (BMI), and bone mass in two large samples of different ethnicity: 1,988 unrelated Chinese subjects and 4,489 Caucasian subjects from 512 pedigrees. We first evaluated the Pearson correlations among different phenotypes. We then dissected the phenotypic correlations into genetic and environmental components, with bone mass unadjusted, or adjusted, for body weight. This allowed us to compare the results with and without controlling for mechanical loading effects of body weight on bone mass. Results In both Chinese and Caucasians, when the mechanical loading effect of body weight on bone mass was adjusted for, the phenotypic correlation (including its genetic and environmental components) between fat mass (or PFM) and bone mass was negative. Further multivariate analyses in subjects stratified by body weight confirmed the inverse relationship between bone mass and fat mass, after mechanical loading effects due to total body weight was controlled. Conclusions Increasing fat mass may not have a beneficial effect on bone mass. PMID:17299077

Effects of whole-body vibration exercise on bone mineral content and density in thermally injured children.

PubMed

Edionwe, Joel; Hess, Cameron; Fernandez-Rio, Javier; Herndon, David N; Andersen, Clark R; Klein, Gordon L; Suman, Oscar E; Amonette, William E

2016-05-01

Loss of bone mass, muscle mass, and strength leads to significant disability in severely burned children. We assessed the effects of exercise combined with whole-body vibration (WBV) on bone mass, lean mass (LM), and muscle strength in children recovering from burns. Nineteen burned children (≥30% total body surface area [TBSA] burns) were randomly assigned to a 6-week exercise regimen either alone (EX; n=10) or in combination with a 6-week WBV training regimen (EX+WBV; n=9). WBV was performed concurrent to the exercise regimen for 5days/week on a vibrating platform. Dual-energy X-ray absorptiometry quantified bone mineral content (BMC), bone mineral density (BMD), and LM; knee extension strength was assessed using isokinetic dynamometry before and after training. Alpha was set at p<0.05. Both groups were similar in age, height, weight, TBSA burned, and length of hospitalization. Whole-body LM increased in the EX group (p=0.041) and trended toward an increase in the EX+WBV group (p=0.055). On the other hand, there were decreases in leg BMC for both groups (EX, p=0.011; EX+WBV, p=0.047), and in leg BMD for only the EX group (EX, p<0.001; EX+WBV, p=0.26). Truncal BMC decreased in only the EX group (EX, p=0.009; EX+WBV, p=0.61), while BMD decreased in both groups (EX, p<0.001; EX+WBV group, p<0.001). Leg strength increased over time in the EX group (p<0.001) and the EX+WBV group (p<0.001; between-group p=0.31). Exercise in combination with WBV may help attenuate regional bone loss in children recovering from burns. Studies are needed to determine the optimal magnitude, frequency, and duration of the vibration protocol, with attention to minimizing any potential interference with wound healing and graft closure. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

Effects of Whole-Body Vibration Exercise on Bone Mineral Content and Density in Thermally Injured Children

PubMed Central

Edionwe, Joel; Hess, Cameron; Fernandez-Rio, Javier; Herndon, David N.; Andersen, Clark R.; Klein, Gordon L.; Suman, Oscar E.; Amonette, William E.

2015-01-01

Background Loss of bone mass, muscle mass, and strength leads to significant disability in severely burned children. We assessed the effects of exercise combined with whole-body vibration (WBV) on bone mass, lean mass (LM), and muscle strength in children recovering from burns. Methods Nineteen burned children (≥30% total body surface area [TBSA] burns) were randomly assigned to a 6-week exercise regimen either alone (EX; n = 10) or in combination with a 6-week WBV training regimen (EX+WBV; n = 9). WBV was performed concurrent to the exercise regimen for 5 days/week on a vibrating platform. Dual-energy X-ray absorptiometry quantified bone mineral content (BMC), bone mineral density (BMD) and LM; knee extension strength was assessed using isokinetic dynamometry before and after training. Alpha was set at p < 0.05. Results Both groups were similar in age, height, weight, TBSA burned, and length of hospitalization. Whole-body LM increased in the EX group (p = 0.041) and trended toward an increase in the EX+WBV group (p = 0.055). On the other hand, there were decreases in leg BMC for both groups (EX, p = 0.011; EX+WBV, p = 0.047), and in leg BMD for only the EX group (EX, p < 0.001; EX+WBV, p = 0.26). Truncal BMC decreased in only the EX group (EX, p = 0.009; EX+WBV, p = 0.61), while BMD decreased in both groups (EX, p < 0.001; EX+WBV group, p < 0.001). Leg strength increased over time in the EX group (p < 0.001) and the EX+WBV group (p < 0.001; between-group P = 0.31). Conclusions Exercise in combination with WBV may help attenuate regional bone loss in children recovering from burns. Studies are needed to determine the optimal magnitude, frequency, and duration of the vibration protocol, with attention to minimizing any potential interference with wound healing and graft closure. PMID:26796240

Bone health in HIV-infected children and adolescents.

PubMed

Eckard, Allison R; Mora, Stefano

2016-05-01

Chronic HIV infection and exposure to antiretroviral therapy compromises bone health in children and adolescents, potentially impacting their long-term quality of life. Thus, the purpose of this article is to review the most recent literature on this topic in HIV-infected children and adolescents. Recent studies continue to demonstrate bone abnormalities in HIV-infected children and adolescents, whether HIV is acquired perinatally or during adolescence. Researchers have employed new modalities, both high tech and those that can be utilized in resource-limited settings, to better assess bone health. New data suggest that this population may also be experiencing an increase incidence of fractures, and they may not acquire the same peak bone mass as their HIV-uninfected counterparts. Reassuringly, however, in-utero tenofovir exposure does not appear to have a significant impact on bone health in HIV-exposed, uninfected infants. HIV-infected children and adolescents are exposed to HIV and antiretroviral therapy for many decades starting early in life and during the most critical time for skeletal growth and bone mass accrual. Recent findings underscore the need for further research on bone in this population. Longitudinal studies are especially needed to evaluate long-term risk of osteoporosis and fracture.

Expanding the Description of Spaceflight Effects beyond Bone Mineral Density [BMD]: Trabecular Bone Score [TBS] in ISS Astronauts

NASA Technical Reports Server (NTRS)

Sibonga, J. D.; Spector, E. R.; King, L. J.; Evans, H. J.; Smith, S. A.

2014-01-01

Dual-energy x-ray absorptiometry [DXA] is the widely-applied bone densitometry method used to diagnose osteoporosis in a terrestrial population known to be at risk for age-related bone loss. This medical test, which measures areal bone mineral density [aBMD] of clinically-relevant skeletal sites (e.g., hip and spine), helps the clinician to identify which persons, among postmenopausal women and men older than 50 years, are at high risk for low trauma or fragility fractures and might require an intervention. The most recognized osteoporotic fragility fracture is the vertebral compression fracture which can lead to kyphosis or hunched backs typically seen in the elderly. DXA measurement of BMD however is recognized to be insufficient as a sole index for assessing fracture risk. DXA's limitation may be related to its inability to monitor changes in structural parameters, such as trabecular vs. cortical bone volumes, bone geometry or trabecular microarchitecture. Hence, in order to understand risks to human health and performance due to space exposure, NASA needs to expand its measurements of bone to include other contributors to skeletal integrity. To this aim, the Bone and Mineral Lab conducted a pilot study for a novel measurement of bone microarchitecture that can be obtained by retrospective analysis of DXA scans. Trabecular Bone Score (TBS) assesses changes to trabecular microarchitecture by measuring the grey color "texture" information extracted from DXA images of the lumbar spine. An analysis of TBS in 51 ISS astronauts was conducted to assess if TBS could detect 1) an effect of spaceflight and 2) a response to countermeasures independent of DXA BMD. In addition, changes in trunk body lean tissue mass and in trunk body fat tissue mass were also evaluated to explore an association between body composition, as impacted by ARED exercise, and bone microarchitecture. The pilot analysis of 51 astronaut scans of the lumbar spine suggests that, following an ISS mission, DXA BMD and TBS are detecting different effects of ARED exercise and of ARED + Bisphosphonate on the lumbar spine of astronauts. There is emerging evidence associating reduced TBS with terrestrial metabolic bone disorders where a TBS <1.200 is associated with "degraded" while > 1.350 is associated with "normal." However, it is not possible to conclude how the spaceflight-induced changes in TBS increase risk for vertebral fractures in the astronaut or if changes in body composition of the trunk region could be an indirect method of assessing exercise effect on bone microarchitecture. More importantly, this pilot analysis demonstrates a new, minimal risk approach for monitoring changes to vertebral bone microarchitecture. This method could help assess the combined skeletal effects of spaceflight with the effects of aging in the astronaut after return to Earth.

Relation of adrenal-derived steroids with bone maturation, mineral density and geometry in healthy prepubertal and early pubertal boys.

PubMed

Vandewalle, S; Taes, Y; Fiers, T; Toye, K; Van Caenegem, E; Kaufman, J-M; De Schepper, J

2014-12-01

Little is known about the effects of adrenal steroids on skeletal maturation and bone mass acquisition in healthy prepubertal boys. To study whether adrenal-derived steroids within the physiological range are associated with skeletal maturation, areal and volumetric bone mineral density (aBMD and vBMD) and bone geometry in healthy prepubertal and early pubertal boys. 98 healthy prepubertal and early pubertal boys (aged 6-14 y) were studied cross-sectionally. Androstenedione (A) and estrone (E1) were determined by liquid chromatography tandem mass spectrometry and DHEAS was determined by immunoassay. Whole body and lumbar spine aBMD and bone area were determined by dual-energy X-ray absorptiometry. Trabecular (distal site) and cortical (proximal site) vBMD and bone geometry were assessed at the non-dominant forearm and leg using peripheral QCT. Skeletal age was determined by X-ray of the left hand. Adrenal-derived steroids (DHEAS, A and E1) are positively associated with bone age in prepubertal and early pubertal children, independently of age. There are no associations between the adrenal-derived steroids and the studied parameters of bone size (lumbar spine and whole body bone area, trabecular or cortical area at the radius or tibia, periosteal circumference and cortical thickness at the radius or tibia) or BMD (aBMD or vBMD). In healthy prepubertal and early pubertal boys, serum adrenal-derived steroid levels, are associated with skeletal maturation, independently of age, but not with bone size or (v)BMD. Our data suggest that adrenal derived steroids are not implicated in the accretion of bone mass before puberty in boys. Copyright © 2014 Elsevier Inc. All rights reserved.

An Investigation Into the Differences in Bone Density and Body Composition Measurements Between 2 GE Lunar Densitometers and Their Comparison to a 4-Component Model.

PubMed

Watson, Laura P E; Venables, Michelle C; Murgatroyd, Peter R

We describe a study to assess the precision of the GE Lunar iDXA and the agreement between the iDXA and GE Lunar Prodigy densitometers for the measurement of regional- and total-body bone and body composition in normal to obese healthy adults. We compare the whole-body fat mass by dual-energy X-ray absorptiometry (DXA) to measurements by a 4-component (4-C) model. Sixty-nine participants, aged 37 ± 12 yr, with a body mass index of 26.2 ± 5.1 kg/cm 2 , were measured once on the Prodigy and twice on the iDXA. The 4-C model estimated fat mass from body mass, total body water by deuterium dilution, body volume by air displacement plethysmography, and bone mass by DXA. Agreements between measurements made on the 2 instruments and by the 4-C model were analyzed by Bland-Altman and linear regression analyses. Where appropriate, translational cross-calibration equations were derived. Differences between DXA software versions were investigated. iDXA precision was less than 2% of the measured value for all regional- and whole-body bone and body composition measurements with the exception of arm fat mass (2.28%). We found significant differences between iDXA and Prodigy (p < 0.05) whole-body and regional bone, fat mass (FM), and lean mass, with the exception of hip bone mass, area and density, and spine area. Compared to iDXA, Prodigy overestimated FM and underestimated lean mass. However, compared to 4-C, iDXA showed a smaller bias and narrower limits of agreement than Prodigy. No significant differences between software versions in FM estimations existed. Our results demonstrate excellent iDXA precision. However, significant differences exist between the 2 GE Lunar instruments, Prodigy and iDXA measurement values. A divergence from the reference 4-C observations remains in FM estimations made by DXA even following the recent advances in technology. Further studies are particularly warranted in individuals with large FM contents. Copyright © 2017. Published by Elsevier Inc.

Whole Body Vibration Training is Osteogenic at the Spine in College-Age Men and Women.

PubMed

Ligouri, Gianna C; Shoepe, Todd C; Almstedt, Hawley C

2012-03-01

Osteoporosis is a chronic skeletal disease characterized by low bone mass which is currently challenging the American health care system. Maximizing peak bone mass early in life is a cost-effective method for preventing osteoporosis. Whole body vibration (WBV) is a novel exercise method with the potential to increase bone mass, therefore optimizing peak bone and decreasing the risk for osteoporotic fracture. The aim of this investigation was to evaluate changes in bone mineral density at the hip, spine, and whole body in college-age men and women who underwent a WBV training protocol. Active men (n=6) and women (n=4), ages 18-22 participated in the WBV training; while an additional 14 volunteers (1 male, 13 female) served as controls. All participants completed baseline and follow-up questionnaires to assess health history, physical activity, dietary intake, and menstrual history. The WBV training program, using a Vibraflex 550, incorporated squats, stiff-leg dead lifts, stationary lunges, push-up holds, bent-over rows, and jumps performed on the platform, and occurred 3 times a week, for 12 weeks. Dual energy x-ray absorptiometry (Hologic Explorer, Waltham, MA, USA) was used to assess bone mineral density (BMD, g/cm(2)). A two-tailed, t-test identified significantly different changes in BMD between the WBV and control groups at the lateral spine (average change of 0.022 vs. -0.015 g/cm(2)). The WBV group experienced a 2.7% and 1.0% increase in BMD in the lateral spine and posterior-anterior spine while the control group decreased 1.9% and 0.9%, respectively. Results indicate that 12 weeks of WBV training was osteogenic at the spine in college-age men and women.

Body mass index and bone loss among postmenopausal women: the 10-year follow-up of the OSTPRE cohort.

PubMed

Saarelainen, Jarmo; Kiviniemi, Vesa; Kröger, Heikki; Tuppurainen, Marjo; Niskanen, Leo; Jurvelin, Jukka; Honkanen, Risto

2012-03-01

Obesity protects against osteoporosis, but the magnitude of this association has been difficult to assess from cross-sectional or short term studies. We examined the time course of bone loss as a function of body mass index (BMI) in early and late postmenopausal women. Our study population (n = 300) was a random sample of the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) Study, Finland. We excluded women without complete BMD results, premenopausal women during the second bone densitometry and women who had used hormone replacement therapy, bisphosphonates or calcitonin. BMI along with femoral neck and spinal bone mineral density (BMD) were assessed three times by dual-energy X-ray absorptiometry during a mean follow-up of 10.5 years (SD 0.5). The mean baseline age was 53.6 years (SD 2.8), time since menopause 2.9 years (SD 4.3) and BMI 27.3 kg/m(2) (SD 4.4). The data was analyzed by linear mixed models. Thus, we were able to approximate the bone loss up to 20 postmenopausal years. To illustrate, a woman with a baseline BMI of 20 kg/m(2) became osteopenic 2 (spine) and 4 (femoral neck) years after menopause, while obesity (BMI of 30 kg/m(2)) delayed the incidence of osteopenia by 5 (spine) and 9 (femoral neck) years, respectively. The delay was due to high baseline BMD of the obese, while bone loss rate was similar for both lean and obese subjects. This lean versus obese difference may also be partly due to altered X-ray attenuation due to fat mass.

[Effect of milk product with soy isoflavones on quality of life and bone metabolism in postmenopausal Spanish women: randomized trial].

PubMed

García-Martín, Antonia; Quesada Charneco, Miguel; Alvárez Guisado, Alejandro; Jiménez Moleón, José Juan; Fonollá Joya, Juristo; Muñoz-Torres, Manuel

2012-02-04

To analyze the effects of nutritional intervention with a milk product enriched with soy isoflavones on quality of life and bone metabolism in postmenopausal Spanish women. We performed a double-blind controlled randomized trial in ninety-nine postmenopausal women. Group S women (n=48) were randomized to consume milk product enriched with soy isoflavone (50 mg/day) while group C (n=51) consumed product control for 12 months. Parameters of quality of life (Cervantes scale), markers of bone metabolism and bone mass estimated by ultrasound of the calcaneus (QUS) were evaluated. Overall, there was an improvement in the domains menopause (P=.015) and vasomotor symptoms (P<.001). S group emphasized the assessment of vasomotor symptoms (P=.001) and differed positively from group C in health (P=.019), sex (P=.021) and partner (P=.002). Serum levels TRAP (P<.001) and OPG (P=.007) decreased and concentrations of 25-OH-vitamin D increased (P<.001) without differences between groups. In the assessment of QUS, there was an increase in estimated bone mineral density in group S (P=.040), whereas in group C there were no significant differences. Daily consumption of these milk products increases levels of 25-OH-vitamin D and decreases bone metabolism markers. Additional supplementation with soy isoflavones seems to improve quality of life and bone mass in Spanish postmenopausal women. Copyright © 2010 Elsevier España, S.L. All rights reserved.

A protocol for pressurized liquid extraction and processing methods to isolate modern and ancient bone cholesterol for compound-specific stable isotope analysis.

PubMed

Laffey, Ann O; Krigbaum, John; Zimmerman, Andrew R

2017-02-15

Bone lipid compound-specific isotope analysis (CSIA) and bone collagen and apatite stable isotope ratio analysis are important sources of ecological and paleodietary information. Pressurized liquid extraction (PLE) is quicker and utilizes less solvent than traditional methods of lipid extraction such as soxhlet and ultrasonication. This study facilitates dietary analysis by optimizing and testing a standardized methodology for PLE of bone cholesterol. Modern and archaeological bones were extracted by PLE using varied temperatures, solvent solutions, and sample weights. The efficiency of PLE was assessed via quantification of cholesterol yields. Stable isotopic ratio integrity was evaluated by comparing isotopic signatures (δ 13 C and δ 18 O values) of cholesterol derived from whole bone, bone collagen and bone apatite. Gas chromatography/mass spectrometry (GC/MS) and gas chromatography isotope ratio mass spectrometry (GC/IRMS) were conducted on purified collagen and lipid extracts to assess isotopic responses to PLE. Lipid yield was optimized at two PLE extraction cycles of 75 °C using dichloromethane/methanol (2:1 v/v) as a solvent with 0.25-0.75 g bone sample. Following lipid extraction, saponification combined with the derivatization of the neutral fraction using trimethylsilylation yielded nearly twice the cholesterol of non-saponified or non-derivatized samples. It was also found that lipids extracted from purified bone collagen and apatite could be used for cholesterol CSIA. There was no difference in the bulk δ 13 C values of collagen extracted from bone with or without lipid. However, there was a significant depletion in 18 O of bone apatite due to lipid presence or processing. These results should assist sample selection and provide an effective, alternative extraction method for bone cholesterol that may be used for isotopic and paleodietary analysis. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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.

Odanacatib, effects of 16-month treatment and discontinuation of therapy on bone mass, turnover and strength in the ovariectomized rabbit model of osteopenia.

PubMed

Duong, Le T; Crawford, Randy; Scott, Kevin; Winkelmann, Christopher T; Wu, Gouxin; Szczerba, Pete; Gentile, Michael A

2016-12-01

Odanacatib (ODN) a selective and reversible cathepsin K inhibitor, inhibits bone resorption, increases bone mass and reduces fracture risk in women with osteoporosis. A 16-month (~7-remodeling cycles) study was carried out in treatment mode to assess the effects of ODN versus ALN on bone mass, remodeling status and biomechanical properties of lumbar vertebrae (LV) and femur in ovariectomized (OVX) rabbits. This study also evaluated the impact of discontinuing ODN on these parameters. Rabbits at 7.5months post-OVX were dosed for 16-months with ODN (7.5μM·h 0-24 , in food) or ALN (0.2mg/kg/wk, s.c.) and compared to vehicle-treated OVX- (OVX+Veh) or Sham-operated animals. After 8months, treatment was discontinued in half of the ODN group. ODN treatment increased in vivo LV aBMD and trabecular (Tb) vBMD until reaching plateau at month 12 by 16% and 23% vs. baseline, respectively, comparable levels to that in Sham and significantly above OVX+Veh. LV BMD was also higher in ALN that plateaued around month 8 to levels below that in ODN or Sham. ODN treatment resulted in higher BMD, structure and improved biomechanical strength of LV and central femur (CF) to levels similar to Sham. ALN generally showed less robust efficacy compared to ODN. Neither ODN nor ALN influenced material properties at these bone sites following ODN or ALN treatment for 7 remodeling cycles in rabbits. ODN and ALN persistently reduced the bone resorption marker urinary helical peptide over study duration. While ALN reduced the bone formation marker BSAP, ODN treatment did not affect this marker. ODN also preserved histomorphometry-based bone formation indices in LV trabecular, CF endocortical and intracortical surfaces, at the levels of OVX+Veh. Discontinuation of ODN returned bone mass, structure and strength parameters to the comparable respective levels in OVX+Veh. Together, these data demonstrate efficacy and bone safety profile of ODN and suggests the potential long-term benefits of this agent over ALN with respect to accrued bone mass without long-term effects on bone formation. Copyright © 2016 Elsevier Inc. All rights reserved.

Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years.

PubMed

Kindler, Joseph M; Pollock, Norman K; Laing, Emma M; Oshri, Assaf; Jenkins, Nathan T; Isales, Carlos M; Hamrick, Mark W; Ding, Ke-Hong; Hausman, Dorothy B; McCabe, George P; Martin, Berdine R; Hill Gallant, Kathleen M; Warden, Stuart J; Weaver, Connie M; Peacock, Munro; Lewis, Richard D

2017-07-01

IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p < 0.001). HOMA-IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF-I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA-IR (p Interaction  < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF-I and Ct.Ar via FFST in the total cohort (β Indirect Effect  = 0.321, p < 0.001). However, this relationship was moderated in the children with high (β Indirect Effect  = 0.200, p < 0.001) versus normal (β Indirect Effect  = 0.408, p < 0.001) HOMA-IR. These data implicate insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Genetic selection to increase bone strength affects prevalence of keel bone damage and egg parameters in commercially housed laying hens.

PubMed

Stratmann, A; Fröhlich, E K F; Gebhardt-Henrich, S G; Harlander-Matauschek, A; Würbel, H; Toscano, M J

2016-05-01

The prevalence of keel bone damage as well as external egg parameters of 2 pure lines divergently selected for high (H) and low (L) bone strength were investigated in 2 aviary systems under commercial conditions. A standard LSL hybrid was used as a reference group. Birds were kept mixed per genetic line (77 hens of the H and L line and 201 or 206 hens of the LSL line, respectively, per pen) in 8 pens of 2 aviary systems differing in design. Keel bone status and body mass of 20 focal hens per line and pen were assessed at 17, 18, 23, 30, 36, 43, 52, and 63 wk of age. External egg parameters (i.e., egg mass, eggshell breaking strength, thickness, and mass) were measured using 10 eggs per line at both 38 and 57 wk of age. Body parameters (i.e. tarsus and third primary wing feather length to calculate index of wing loading) were recorded at 38 wk of age and mortality per genetic line throughout the laying cycle. Bone mineral density (BMD) of 15 keel bones per genetic line was measured after slaughter to confirm assignment of the experimental lines. We found a greater BMD in the H compared with the L and LSL lines. Fewer keel bone fractures and deviations, a poorer external egg quality, as well as a lower index of wing loading were found in the H compared with the L line. Mortality was lower and production parameters (e.g., laying performance) were higher in the LSL line compared with the 2 experimental lines. Aviary design affected prevalence of keel bone damage, body mass, and mortality. We conclude that selection of specific bone traits associated with bone strength as well as the related differences in body morphology (i.e., lower index of wing loading) have potential to reduce keel bone damage in commercial settings. Also, the housing environment (i.e., aviary design) may have additive effects. © 2016 Poultry Science Association Inc.

Gender-specific increase of bone mass by CART peptide treatment is ovary-dependent.

PubMed

Gerrits, Han; Bakker, Nicole Ec; van de Ven-de Laat, Cindy Jm; Bourgondien, Freek Gm; Peddemors, Carolien; Litjens, Ralph Hgm; Kok, Han J; Vogel, Gerard Mt; Krajnc-Franken, Magda Am; Gossen, Jan A

2011-12-01

Cocaine- and amphetamine-regulated transcript (CART) has emerged as a neurotransmitter and hormone that has been implicated in many processes including food intake, maintenance of body weight, and reward, but also in the regulation of bone mass. CART-deficient mice are characterized by an osteoporotic phenotype, whereas female transgenic mice overexpressing CART display an increase in bone mass. Here we describe experiments that show that peripheral subcutaneous sustained release of different CART peptide isoforms for a period up to 60 days increased bone mass by 80% in intact mice. CART peptides increased trabecular bone mass, but not cortical bone mass, and the increase was caused by reduced osteoclast activity in combination with normal osteoblast activity. The observed effect on bone was gender-specific, because male mice did not respond to treatment with CART peptides. In addition, male transgenic CART overexpressing mice did not display increased bone mass. Ovariectomy (OVX) completely abolished the increase of bone mass by CART peptides, both in CART peptide-treated wild-type mice and in CART transgenic mice. The effect of CART peptide treatment on trabecular bone was not mediated by 17β-estradiol (E(2)) because supplementation of OVX mice with E(2) could not rescue the effect of CART peptides on bone. Together, these results indicate that sustained release of CART peptides increases bone mass in a gender-specific way via a yet unknown mechanism that requires the presence of the ovary. Copyright © 2011 American Society for Bone and Mineral Research.

Changes in bone density and bone markers in rhythmic gymnasts and ballet dancers: implications for puberty and leptin levels.

PubMed

Muñoz, María Teresa; de la Piedra, Concepción; Barrios, Vicente; Garrido, Guadalupe; Argente, Jesús

2004-10-01

Our aim was to compare physical activity and biochemical markers with bone mineral acquisition in rhythmic gymnasts and ballet dancers. Weight, height, body mass index, nutritional intake, bone age and menstrual histories were analyzed in nine rhythmic gymnasts, twelve ballet dancers and fourteen controls. Bone mineral density (BMD) was assessed by X-ray absorptiometry at the lumbar spine, hip and radius. Bone alkaline phosphatase (bAP) and amino-terminal propeptide of procollagen I (PNIP) in serum and urinary alpha-isomer of the carboxy-terminal telopeptide of collagen I (alpha-CTX) were measured. Bone age was delayed 2 years and mean age at menarche was 15+/-0.9 years in rhythmic gymnasts and 13.7+/-1 years in ballet dancers, compared with 12.5+/-1 years in controls. Trocanteric and femoral neck BMD was significantly higher in rhythmic gymnasts compared with ballet dancers and controls. Right forearm (non-loaded zone) BMD was significantly decreased in rhythmic gymnasts and ballet dancers compared with controls. All subjects had normal bAP and PNIP levels, but the alpha-CTX/creatinine (Cr) ratio was increased in rhythmic gymnasts (P<0.001) with an inverse correlation between right forearm BMD and the alpha-CTX/Cr ratio (r=-0.74, P<0.001). Serum leptin levels were decreased in rhythmic gymnasts and ballet dancers. Rhythmic gymnasts had a positive correlation between right forearm BMD and leptin levels (r=0.85, P<0.001). Decreased bone mass in rhythmic gymnasts could be partially explained by an increase in bone resorption. Serum leptin levels could be implicated in the pubertal delay and be a good marker of bone mass in these subjects.

[Bone turnover in children and adolescents with diabetes mellitus type 1].

PubMed

Pater, Agnieszka; Odrowąż-Sypniewska, Grażyna

2013-01-01

Biochemical bone turnover markers are fragments of protein structural elements of the bone created during the synthesis or degradation and enzymes specific for bone cells, released into the circulation during the metabolic activity of osteoblasts and osteoclasts. Bone turnover markers are used as indicators to evaluate the activity of modeling and remodeling processes. They are the result of the activity of all remodeling processes taking place at the moment in the whole skeleton. The assay allows quick assessment of the rate of bone formation and resorption processes. Among many complications in children with type 1 diabetes increased bone turnover leading to a reduction in bone mass may increase the risk of osteopenia or osteoporosis in adulthood. The aim of this manuscript is to review recent papers about bone turnover in children and adolescents with diabetes mellitus type 1.

Changes in body composition and bone of female collegiate soccer players through the competitive season and off-season.

PubMed

Minett, M M; Binkley, T B; Weidauer, L A; Specker, B L

2017-03-01

To assess body composition and bone changes pre- to post-season (pre-post) and post- to off-season (post-off) in female soccer athletes (SC). Outcomes were assessed using DXA and pQCT in 23 SC and 17 controls at three times throughout season. SC, non-starters in particular, lost lean mass pre-post (-0.9±0.2 kg, p<0.01; not different from controls, p=0.2) and gained fat mass post-off (1.4±0.3 kg, p<0.01; differed from controls, p=0.01). Baseline femoral neck and hip aBMD were higher in SC than controls (both,p<0.04), but increased in controls more than SC in pre-post and decreased post-off. SC cortical bone mineral content (BMC), cortical area and periosteal circumference increased pre-post (all, p<0.01; differed from controls, p<0.05) and trabecular vBMD decreased post-off (-3.0±1.3 mg/cm 3 ; p=0.02; not different from controls, p=0.4). Both SC and controls increased cortical BMC, cortical area, and thickness post-off (all, p<0.01). Soccer players lost lean mass over the competitive season that was not recovered during off-season. Bone size increased pre- to post-season. Female soccer athletes experience body composition and bone geometry changes that differ depending on the time of season and on athlete's playing status. Evaluations of athletes at key times across the training season are necessary to understand changes that occur.

Changes in body composition and bone of female collegiate soccer players through the competitive season and off-season

PubMed Central

Minett, M.M.; Binkley, T.B.; Weidauer, L.A.; Specker, B.L.

2017-01-01

Objectives: To assess body composition and bone changes pre- to post-season (pre-post) and post- to off-season (post-off) in female soccer athletes (SC). Methods: Outcomes were assessed using DXA and pQCT in 23 SC and 17 controls at three times throughout season. Results: SC, non-starters in particular, lost lean mass pre-post (-0.9±0.2 kg, p<0.01; not different from controls, p=0.2) and gained fat mass post-off (1.4±0.3 kg, p<0.01; differed from controls, p=0.01). Baseline femoral neck and hip aBMD were higher in SC than controls (both, p<0.04), but increased in controls more than SC in pre-post and decreased post-off. SC cortical bone mineral content (BMC), cortical area and periosteal circumference increased pre-post (all, p<0.01; differed from controls, p<0.05) and trabecular vBMD decreased post-off (-3.0±1.3 mg/cm3; p=0.02; not different from controls, p=0.4). Both SC and controls increased cortical BMC, cortical area, and thickness post-off (all, p<0.01). Conclusion: Soccer players lost lean mass over the competitive season that was not recovered during off-season. Bone size increased pre- to post-season. Female soccer athletes experience body composition and bone geometry changes that differ depending on the time of season and on athlete’s playing status. Evaluations of athletes at key times across the training season are necessary to understand changes that occur. PMID:28250243

The relationship between objectively assessed physical activity and bone health in older adults differs by sex and is mediated by lean mass.

PubMed

McMillan, L B; Aitken, D; Ebeling, P; Jones, G; Scott, D

2018-03-12

Relationships between objectively assessed free-living physical activity (PA) and changes in bone health over time are poorly understood in older adults. This study suggests these relationships are sex-specific and that body composition may influence the mechanical loading benefits of PA. To investigate associations of objectively assessed PA and bone health in community-dwelling older adults. This secondary analysis of a subset of the Tasmanian Older Adult Cohort study included participants with PA assessed utilising ActiGraph GT1M accelerometers over 7 days (N = 209 participants, 53% female; mean ± SD age 64.5 ± 7.2 years). Steps/day and PA intensity were estimated via established thresholds. Bone mineral content (BMC) was acquired at the total hip, lumbar spine, legs and whole body by DXA at baseline and approximately 2.2 years later. Relationships between PA and BMC were assessed by multivariable linear regression analyses adjusted for age, smoking status, height and total lean mass. Men with above-median total hip BMC completed significantly less steps per day, but there was no significant difference in PA intensity compared with those with below-median BMC. There were no significant differences in PA in women stratified by median BMC. In women, steps/day were positively associated with leg BMC (B = 0.178; P = 0.017), and sedentary behaviour was negatively associated with leg BMC (- 0.165; 0.016) at baseline. After adjustment for confounders including lean mass and height, higher sedentary behaviour at baseline was associated with declines in femoral neck BMC (- 0.286; 0.011) but also with increases in pelvic BMC (0.246; 0.030) in men and increases in total hip BMC (0.215; 0.032) in women, over 2.2 years. No other significant longitudinal associations were observed after adjustment for body composition. Associations of accelerometer-determined sedentary behaviour and PA with bone health in older adults differ by sex and anatomical site and are mediated by body composition.

Biomarkers for osteoporosis management: utility in diagnosis, fracture risk prediction and therapy monitoring.

PubMed

Garnero, Patrick

2008-01-01

Osteoporosis is a systemic disease characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in an increased risk of fracture. While the level of bone mass can be estimated by measuring bone mineral density (BMD) using dual X-ray absorptiometry (DXA), its measurement does not capture all the risk factors for fracture. Quantitative changes in skeletal turnover can be assessed easily and non-invasively by the measurement of serum and urinary biochemical markers; the most sensitive markers include serum osteocalcin, bone specific alkaline phosphatase, the N-terminal propeptide of type I collagen for bone formation, and the crosslinked C- (CTX) and N- (NTX) telopeptides of type I collagen for bone resorption. Advances in our knowledge of bone matrix biochemistry, most notably of post-translational modifications in type I collagen, are likely to lead to the development of new biochemical markers that reflect changes in the material property of bone, an important determinant of bone strength. Among those, the measurement of the urinary ratio of native (alpha) to isomerized (beta) CTX - an index of bone matrix maturation - has been shown to be predictive of fracture risk independently of BMD and bone turnover. In postmenopausal osteoporosis, levels of bone resorption markers above the upper limit of the premenopausal range are associated with an increased risk of hip, vertebral, and nonvertebral fracture, independent of BMD. Therefore, the combined use of BMD measurement and biochemical markers is helpful in risk assessment, especially in those women who are not identified as at risk by BMD measurement alone. Levels of bone markers decrease rapidly with antiresorptive therapies, and the levels reached after 3-6 months of therapy have been shown to be more strongly associated with fracture outcome than changes in BMD. Preliminary studies indicate that monitoring changes of bone formation markers could also be useful to monitor anabolic therapies, including intermittent parathyroid hormone administration and, possibly, to improve adherence to treatment. Thus, repeated measurements of bone markers during therapy may help improve the management of osteoporosis in patients.

Genetic Factors in Determining Bone Mass

PubMed Central

Smith, David M.; Nance, Walter E.; Kang, Ke Won; Christian, Joe C.; Johnston, C. Conrad

1973-01-01

This investigation was undertaken to evaluate possible genetic determinants of bone mass with the premise that inheritance of bone mass could be of etiologic importance in osteoporosis. Bone mass and width measurements were made with the photon absorption technique on the right radius of 71 juvenile and 80 adult twin paris. The variance of intrapair differences of bone mass in monozygotic (MZ) juvenile twins was 0.0013 g2/cm2 compared to 0.0052 g2/cm2 in the dizygotic (DZ) twins. For the adult twins the variance of intrapair differences in bone mass was 0.0069 for MZ and 0.0137 for DZ twins. Similar results were obtained for bone width. The significantly larger variation in intrapair differences in DZ twins indicates that these traits have significant genetic determinants. These intrapair differences were found to increase with age, suggesting that genetic-environmental interaction also contributes to the observed variation in bone mass. These data provide evidence that bone mass does have significant genetic factors, which alone or in conjunction with environmental factors may predispose persons to the development of osteoporosis. PMID:4795916

Greater fruit intake was associated with better bone mineral status among Chinese elderly men and women: results of Hong Kong Mr. Os and Ms. Os studies.

PubMed

Liu, Zhao-min; Leung, Jason; Wong, Samuel Yeung-shan; Wong, Carmen Ka Man; Chan, Ruth; Woo, Jean

2015-04-01

Although studies in white populations have reported the beneficial effects of intakes of fruit and vegetables (F&V) on bone mass, limited data are available in Asians, especially among the elderly population. We examined the association of F&V intakes and bone mineral status in Chinese elderly adults and explored the potential mechanisms. The study was a population-based cross-sectional study among 4000 Hong Kong Chinese men and women aged 65 years and older. Habitual F&V intakes were ascertained from a validated food frequency questionnaire. Bone mineral measurements of the whole body, hip, lumber spine, and femoral neck were made by dual-energy X-ray absorptiometry. Information on demographic, health, and lifestyles factors was obtained by standardized questionnaire. Relations between F&V intakes and bone mass at various sites were assessed by regression models. Whole-body and femoral neck bone mineral density and content were significantly and positively associated with fruit intake in both men and women, even when adjustment for a range of potential confounders was made. A daily increase of 100 g/kcal total fruit intake was associated with 4.5% and 6.4% increase of BMD at whole body, and 3.9% and 4.8% increase at the femoral neck in men and women, respectively. No significant association was found between vegetable intake and bone mass. The adjustment for vitamin C intake, but not dietary acid load, attenuated the association between fruit intake and bone mass. Greater fruit intake was independently associated with better bone mineral status among Chinese elderly men and women. The association is probably modified by dietary vitamin C. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

High-fat Diet Decreases Cancellous Bone Mass But Has No Effect on Cortical Bone Mass in the Tibia in Mice

USDA-ARS?s Scientific Manuscript database

Introduction: Body mass has a positive effect on bone mineral density and the strength. Whether mass derived from an obesity condition is beneficial to bone has not been established; neither have the mechanism by which obesity affects bone metabolism. The aim of this study was to examine the effects...

Ward's area location, physical activity, and body composition in 8- and 9-year-old boys and girls.

PubMed

Cardadeiro, Graça; Baptista, Fátima; Zymbal, Vera; Rodrigues, Luís A; Sardinha, Luís B

2010-11-01

Bone strength is the result of its material composition and structural design, particularly bone mass distribution. The purpose of this study was to analyze femoral neck bone mass distribution by Ward's area location and its relationship with physical activity (PA) and body composition in children 8 and 9 years of age. The proximal femur shape was defined by geometric morphometric analysis in 88 participants (48 boys and 40 girls). Using dual-energy X-ray absorptiometry (DXA) images, 18 landmarks were digitized to define the proximal femur shape and to identify Ward's area position. Body weight, lean and fat mass, and bone mineral were assessed by DXA, PA by accelerometry, and bone age by the Tanner-Whitehouse III method. Warps analysis with Thin-Plate Spline software showed that the first axis explained 63% of proximal femur shape variation in boys and 58% in girls. Most of this variation was associated with differences in Ward's area location, from the central zone to the superior aspect of the femoral neck in both genders. Regression analysis demonstrated that body composition explained 4% to 7% of the proximal femur shape variation in girls. In boys, body composition variables explained a similar amount of variance, but moderate plus vigorous PA (MVPA) also accounted for 6% of proximal femur shape variation. In conclusion, proximal femur shape variation in children ages 8 and 9 was due mainly to differences in Ward's area position determined, in part, by body composition in both genders and by MVPA in boys. These variables were positively associated with a central Ward's area and thus with a more balanced femoral neck bone mass distribution. © 2010 American Society for Bone and Mineral Research.

"Bounce at the Bell": a novel program of short bouts of exercise improves proximal femur bone mass in early pubertal children

PubMed Central

McKay, H; MacLean, L; Petit, M; MacKelvie-O'Brien, K; Janssen, P; Beck, T; Khan, K

2005-01-01

Objectives: To examine the effects of a simple and inexpensive physical activity intervention on change in bone mass and structure in school aged children. Methods: Fifty one children (n = 23 boys and 28 girls; mean age 10.1 years) participated in "Bounce at the Bell" which consisted of 10 counter-movement jumps 3x per day (total ∼3 min/day). Controls were 71 matched children who followed usual school practice. We assessed dietary calcium, physical activity, physical performance, and anthropometry in September and after 8 months of intervention (June). We measured bone mineral content (BMC) and bone area at the lumbar spine, total body, and proximal femur. Proximal femur scans were also analysed for bone geometry and structural strength using the hip structural analysis program. Lean and fat mass (g) were also calculated. Results: Groups were similar at baseline and did not differ in weight, height, total body, lumbar spine, proximal femur, or femoral neck BMC. Control children had a greater increase in adjusted total body BMC (1.4%). Intervention children gained significantly more BMC at the total proximal femur (2%) and the intertrochanteric region (27%). Change in bone structural parameters did not differ between groups. Conclusions: This novel, easily implemented exercise program, took only a few minutes each day and enhanced bone mass at the weight bearing proximal femur in early pubertal children. A large, randomised study of boys and girls should be undertaken powered to test the effectiveness of Bounce at the Bell in children at different stages of maturity, and in boys and girls independently. PMID:16046335

Reloading partly recovers bone mineral density and mechanical properties in hind limb unloaded rats

NASA Astrophysics Data System (ADS)

Zhao, Fan; Li, Dijie; Arfat, Yasir; Chen, Zhihao; Liu, Zonglin; Lin, Yu; Ding, Chong; Sun, Yulong; Hu, Lifang; Shang, Peng; Qian, Airong

2014-12-01

Skeletal unloading results in decreased bone formation and bone mass. During long-term space flight, the decreased bone mass is impossible to fully recover. Therefore, it is necessary to develop the effective countermeasures to prevent spaceflight-induced bone loss. Hindlimb Unloading (HLU) simulates effects of weightlessness and is utilized extensively to examine the response of musculoskeletal systems to certain aspects of space flight. The purpose of this study is to investigate the effects of a 4-week HLU in rats and subsequent reloading on the bone mineral density (BMD) and mechanical properties of load-bearing bones. After HLU for 4 weeks, the rats were then subjected to reloading for 1 week, 2 weeks and 3 weeks, and then the BMD of the femur, tibia and lumbar spine in rats were assessed by dual energy X-ray absorptiometry (DXA) every week. The mechanical properties of the femur were determined by three-point bending test. Dry bone and bone ash of femur were obtained through Oven-Drying method and were weighed respectively. Serum alkaline phosphatase (ALP) and serum calcium were examined through ELISA and Atomic Absorption Spectrometry. The results showed that 4 weeks of HLU significantly decreased body weight of rats and reloading for 1 week, 2 weeks or 3 weeks did not recover the weight loss induced by HLU. However, after 2 weeks of reloading, BMD of femur and tibia of HLU rats partly recovered (+10.4%, +2.3%). After 3 weeks of reloading, the reduction of BMD, energy absorption, bone mass and mechanical properties of bone induced by HLU recovered to some extent. The changes in serum ALP and serum calcium induced by HLU were also recovered after reloading. Our results indicate that a short period of reloading could not completely recover bone after a period of unloading, thus some interventions such as mechanical vibration or pharmaceuticals are necessary to help bone recovery.

Correlation between broiler lameness and anatomical measurements of bone using radiographical projections with assessments of consistency across and within radiographs.

PubMed

Toscano, M J; Nasr, M A F; Hothersall, B

2013-09-01

Lameness represents a major welfare and production issue in the poultry industry with a recent survey estimating 27% of birds lame and 3% unable to walk by 40 d of age. A variety of factors may induce lameness and are typically grouped into 2 broad classes on the basis of being infectious or skeletal in nature with the latter accounting for the majority of cases. The current work sought to build upon a large body of literature assessing the anatomical properties of bone in lame birds. Our specific objectives sought to identify relationships between relevant anatomical properties of the tibia and metatarsus using digital quantification from radiographs of legs and a measure of walking difficulty. Resulting output was statistically analyzed to assess 1) observer reliability for consistency in placing the leg during the radiograph procedure and quantification of the various measures within a radiograph, 2) the relationship between the various measurements of anatomical bone properties and sex, bird mass, and gait score, and 3) the relationship between each measurement and leg symmetry. Our anatomical bone measures were found to be reliable (intra-rater and test-retest reliabilities < 0.75) within radiograph for all measures and 8 of the 10 measures across radiographs. Several measures of bone properties in the tibia correlated to difficulty walking as measured by gait score (P < 0.05), indicating greater angulations with increasing lameness. Of the measures that manifested a gait score × bird mass interaction, heavier birds appeared to exhibit less angulation with increasing difficulty walking with lighter birds the opposite. These interactions suggest possibilities for influencing effects of activity or feed intake on bone mineralization with the bone angulation observed. Our efforts agree with that of others and indicate that angulation of the tibia may be related to lameness, though subsequent efforts involving comprehensive measures of bird activity, growth rates, and internal bone structure will be needed if the validity of the measures are to be accepted.

Adiposity and TV viewing are related to less bone accrual in young children.

PubMed

Wosje, Karen S; Khoury, Philip R; Claytor, Randal P; Copeland, Kristen A; Kalkwarf, Heidi J; Daniels, Stephen R

2009-01-01

To examine the relation between baseline fat mass and gain in bone area and bone mass in preschoolers studied prospectively for 4 years, with a focus on the role of physical activity and TV viewing. Children were part of a longitudinal study in which measures of fat, lean and bone mass, height, weight, activity, and diet were taken every 4 months from ages 3 to 7 years. Activity was measured by accelerometer and TV viewing by parent checklist. We included 214 children with total body dual energy x-ray absorptiometry (Hologic 4500A) scans at ages 3.5 and 7 years. Higher baseline fat mass was associated with smaller increases in bone area and bone mass over the next 3.5 years (P < .001). More TV viewing was related to smaller gains in bone area and bone mass accounting for race, sex, and height. Activity by accelerometer was not associated with bone gains. Adiposity and TV viewing are related to less bone accrual in preschoolers.

A soluble bone morphogenetic protein type IA receptor increases bone mass and bone strength

PubMed Central

Baud’huin, Marc; Solban, Nicolas; Cornwall-Brady, Milton; Sako, Dianne; Kawamoto, Yoshimi; Liharska, Katia; Lath, Darren; Bouxsein, Mary L.; Underwood, Kathryn W.; Ucran, Jeffrey; Kumar, Ravindra; Pobre, Eileen; Grinberg, Asya; Seehra, Jasbir; Canalis, Ernesto; Pearsall, R. Scott; Croucher, Peter I.

2012-01-01

Diseases such as osteoporosis are associated with reduced bone mass. Therapies to prevent bone loss exist, but there are few that stimulate bone formation and restore bone mass. Bone morphogenetic proteins (BMPs) are members of the TGFβ superfamily, which act as pleiotropic regulators of skeletal organogenesis and bone homeostasis. Ablation of the BMPR1A receptor in osteoblasts increases bone mass, suggesting that inhibition of BMPR1A signaling may have therapeutic benefit. The aim of this study was to determine the skeletal effects of systemic administration of a soluble BMPR1A fusion protein (mBMPR1A–mFc) in vivo. mBMPR1A–mFc was shown to bind BMP2/4 specifically and with high affinity and prevent downstream signaling. mBMPR1A–mFc treatment of immature and mature mice increased bone mineral density, cortical thickness, trabecular bone volume, thickness and number, and decreased trabecular separation. The increase in bone mass was due to an early increase in osteoblast number and bone formation rate, mediated by a suppression of Dickkopf-1 expression. This was followed by a decrease in osteoclast number and eroded surface, which was associated with a decrease in receptor activator of NF-κB ligand (RANKL) production, an increase in osteoprotegerin expression, and a decrease in serum tartrate-resistant acid phosphatase (TRAP5b) concentration. mBMPR1A treatment also increased bone mass and strength in mice with bone loss due to estrogen deficiency. In conclusion, mBMPR1A–mFc stimulates osteoblastic bone formation and decreases bone resorption, which leads to an increase in bone mass, and offers a promising unique alternative for the treatment of bone-related disorders. PMID:22761317

A longitudinal analysis of sex differences in bone mineral accrual in healthy 8-19-year-old boys and girls.

PubMed

Baxter-Jones, A D G; Mirwald, R L; McKay, H A; Bailey, D A

2003-01-01

Although early in life there is little discernible difference in bone mass between boys and girls, at puberty sex differences are observed. It is uncertain if these differences represent differences in bone mass or just differences in anthropometric dimensions. The study aimed to identify whether sex independently affects bone mineral content (BMC) accrual in growing boys and girls. Three sites are investigated: total body (TB), femoral neck (FN) and lumbar spine (LS). 85 boys and 67 girls were assessed annually for seven consecutive years. BMC was assessed by dual energy X-ray absorptiometry (DXA). Biological age was defined as years from age at peak height velocity (PHV). Data were analysed using a hierarchical (random effects) modelling approach. When biological age, body size and body composition were controlled, boys had statistically significantly higher TB and FN BMC at all maturity levels (p < 0.05). No independent sex differences were found at the LS (p > 0.05). Although a statistical significant sex effect is observed, it is less than the error of the measurement, and thus sex difference are debatable. In general, sex difference are explained by anthropometric difference.

Risk factors for decreased bone mineral density in inflammatory bowel disease: A cross-sectional study.

PubMed

Wada, Yasuyo; Hisamatsu, Tadakazu; Naganuma, Makoto; Matsuoka, Katsuyoshi; Okamoto, Susumu; Inoue, Nagamu; Yajima, Tomoharu; Kouyama, Keisuke; Iwao, Yasushi; Ogata, Haruhiko; Hibi, Toshifumi; Abe, Takayuki; Kanai, Takanori

2015-12-01

Although inflammatory bowel disease (IBD) patients are at risk for metabolic bone disease, studies analyzing this correlation have identified various risk factors, including disease phenotype, age, sex and steroid therapy. Furthermore, few studies have assessed risk factors for bone loss in Japanese IBD patients. This study analyzed risk factors for metabolic bone disease in Japanese IBD patients. This cross-sectional study assessed 388 patients with IBD aged 20-50 years, including 232 with ulcerative colitis (UC) and 156 with Crohn's disease (CD). Bone mineral density of the femoral neck, total femur and lumbar spine was quantified by dual-energy X-ray absorptiometry. The blood concentrations of bone metabolism markers were measured. History of smoking and bone fracture, and nutritional intake were assessed using questionnaires. Of the 388 patients with IBD, 78 (20.1%; UC, 17.2%; CD, 24.4%) had osteopenia and 17 (4.4%; UC, 3.4%; CD, 5.8%) had osteoporosis, as assessed by T-score. Bone mineral density of the lumbar vertebrae was lower in males than in females. Multivariate regression analysis showed that risk factors for bone loss in UC patients were male sex, low body mass index (BMI), high steroid dose and disease location. Risk factors for bone loss in CD patients were male sex and low BMI. Among Japanese patients with IBD, male sex and low BMI were associated with increased risk for metabolic bone disease. In addition, Steroid therapy shouldn't be indiscriminate in UC patients. These findings may help identify patients at particularly high risk of metabolic bone disease and may help implement appropriate therapies in a timely manner and improve long-term quality of life. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Beneficial impact of aerobic exercises on bone mineral density in obese premenopausal women under caloric restriction.

PubMed

Hosny, Iman Abbas; Elghawabi, Hamed Samir; Younan, Wael Bahat Fahmy; Sabbour, Adly Aly; Gobrial, Mona Abdel Messih

2012-04-01

The aim of this study was to assess the impact of caloric restriction diet versus caloric restriction diet combined with aerobic exercises on bone mineral density (BMD) in obese premenopausal women. Forty premenopausal obese women were classified randomly into two groups equal in number. The first group (group A) received caloric restriction diet, while the second (group B) received caloric restriction diet combined with a program of aerobic exercises, over 3 months. The variables measured in this study included age, weight, height, body mass index, fat weight, lean mass, fat percent, basal metabolic rate, and BMD. The comparison between group A and group B showed significantly higher post-treatment lean mass, basal metabolic rate, and BMD in weight-bearing bones (L2-L4 lumbar spine and total hip) in group B compared to group A. In contrast to the BMD of the weight-bearing bones, the BMD of the radius showed significant decrease between the pre- and post-treatment results in groups A and B with no significant differences between the two groups. A greater improvement in the BMD of weight-bearing bones was observed in obese premenopausal women undergoing caloric restriction combined with exercise than in those not undergoing exercise. Anaerobic exercises incorporated into weight loss programs help offset the adverse effects of dietary restriction on bone.

The gut microbiota regulates bone mass in mice

PubMed Central

Sjögren, Klara; Engdahl, Cecilia; Henning, Petra; Lerner, Ulf H; Tremaroli, Valentina; Lagerquist, Marie K; Bäckhed, Fredrik; Ohlsson, Claes

2012-01-01

The gut microbiota modulates host metabolism and development of immune status. Here we show that the gut microbiota is also a major regulator of bone mass in mice. Germ-free (GF) mice exhibit increased bone mass associated with reduced number of osteoclasts per bone surface compared with conventionally raised (CONV-R) mice. Colonization of GF mice with a normal gut microbiota normalizes bone mass. Furthermore, GF mice have decreased frequency of CD4+ T cells and CD11b+/GR 1 osteoclast precursor cells in bone marrow, which could be normalized by colonization. GF mice exhibited reduced expression of inflammatory cytokines in bone and bone marrow compared with CONV-R mice. In summary, the gut microbiota regulates bone mass in mice, and we provide evidence for a mechanism involving altered immune status in bone and thereby affected osteoclast-mediated bone resorption. Further studies are required to evaluate the gut microbiota as a novel therapeutic target for osteoporosis. © 2012 American Society for Bone and Mineral Research. PMID:22407806

Bone mass density estimation: Archimede’s principle versus automatic X-ray histogram and edge detection technique in ovariectomized rats treated with germinated brown rice bioactives

PubMed Central

Muhammad, Sani Ismaila; Maznah, Ismail; Mahmud, Rozi Binti; Esmaile, Maher Faik; Zuki, Abu Bakar Zakaria

2013-01-01

Background Bone mass density is an important parameter used in the estimation of the severity and depth of lesions in osteoporosis. Estimation of bone density using existing methods in experimental models has its advantages as well as drawbacks. Materials and methods In this study, the X-ray histogram edge detection technique was used to estimate the bone mass density in ovariectomized rats treated orally with germinated brown rice (GBR) bioactives, and the results were compared with estimated results obtained using Archimede’s principle. New bone cell proliferation was assessed by histology and immunohistochemical reaction using polyclonal nuclear antigen. Additionally, serum alkaline phosphatase activity, serum and bone calcium and zinc concentrations were detected using a chemistry analyzer and atomic absorption spectroscopy. Rats were divided into groups of six as follows: sham (nonovariectomized, nontreated); ovariectomized, nontreated; and ovariectomized and treated with estrogen, or Remifemin®, GBR-phenolics, acylated steryl glucosides, gamma oryzanol, and gamma amino-butyric acid extracted from GBR at different doses. Results Our results indicate a significant increase in alkaline phosphatase activity, serum and bone calcium, and zinc and ash content in the treated groups compared with the ovariectomized nontreated group (P < 0.05). Bone density increased significantly (P < 0.05) in groups treated with estrogen, GBR, Remifemin®, and gamma oryzanol compared to the ovariectomized nontreated group. Histological sections revealed more osteoblasts in the treated groups when compared with the untreated groups. A polyclonal nuclear antigen reaction showing proliferating new cells was observed in groups treated with estrogen, Remifemin®, GBR, acylated steryl glucosides, and gamma oryzanol. There was a good correlation between bone mass densities estimated using Archimede’s principle and the edge detection technique between the treated groups (r2 = 0.737, P = 0.004). Conclusion Our study shows that GBR bioactives increase bone density, which might be via the activation of zinc formation and increased calcium content, and that X-ray edge detection technique is effective in the measurement of bone density and can be employed effectively in this respect. PMID:24187491

The Association of Fat and Lean Tissue With Whole Body and Spine Bone Mineral Density Is Modified by HIV Status and Sex in Children and Youth.

PubMed

Jacobson, Denise L; Lindsey, Jane C; Coull, Brent A; Mulligan, Kathleen; Bhagwat, Priya; Aldrovandi, Grace M

2018-01-01

HIV-infected (HIV-pos) male children/youth showed lower bone mineral density at sexual maturity than HIV-uninfected (HIV-neg) females. It is not known whether complications of HIV disease, including abnormal body fat distribution, contribute to lower bone accrual in male HIV-pos adolescents. In a cross-sectional study, we evaluated the relationship between body composition (fat and lean mass) and bone mass in HIV-pos and HIV-neg children/youth and determined if it is modified by HIV status and sex. We used generalized estimating equations to simultaneously model the effect of fat/lean mass on multiple bone outcomes, including total body bone mineral density and bone mineral content and spine bone mineral density. We evaluated effect modification by HIV and sex. The analysis cohort consisted of 143 HIV-neg and 236 HIV-pos, of whom 55% were black non-Hispanic and 53% were male. Ages ranged from 7 to < 25 years. Half of the children/youth were at Tanner stage 1 and 20% at Tanner 5. Fat mass was more strongly positively correlated with bone mass in HIV-neg than HIV-pos children/youth and these relationships were more evident for total body bone than spine outcomes. Within HIV strata, fat mass and bone were more correlated in female than male children/youth. The relationship between lean mass and bone varied by sex, but not by HIV status. HIV disease diminishes the positive relationship of greater fat mass on bone mass in children/youth. Disruptions in body fat distribution, which are common in HIV disease, may have an impact on bone accretion during pubertal development.

Morphometric analysis - Cone beam computed tomography to predict bone quality and quantity.

PubMed

Hohlweg-Majert, B; Metzger, M C; Kummer, T; Schulze, D

2011-07-01

Modified quantitative computed tomography is a method used to predict bone quality and quantify the bone mass of the jaw. The aim of this study was to determine whether bone quantity or quality was detected by cone beam computed tomography (CBCT) combined with image analysis. MATERIALS AND PROCEDURES: Different measurements recorded on two phantoms (Siemens phantom, Comac phantom) were evaluated on images taken with the Somatom VolumeZoom (Siemens Medical Solutions, Erlangen, Germany) and the NewTom 9000 (NIM s.r.l., Verona, Italy) in order to calculate a calibration curve. The spatial relationships of six sample cylinders and the repositioning from four pig skull halves relative to adjacent defined anatomical structures were assessed by means of three-dimensional visualization software. The calibration curves for computer tomography (CT) and cone beam computer tomography (CBCT) using the Siemens phantom showed linear correlation in both modalities between the Hounsfield Units (HU) and bone morphology. A correction factor for CBCT was calculated. Exact information about the micromorphology of the bone cylinders was only available using of micro computer tomography. Cone-beam computer tomography is a suitable choice for analysing bone mass, but, it does not give any information about bone quality. 2010 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Bone Tissue Collagen Maturity and Mineral Content Increase With Sustained Hyperglycemia in the KK-Ay Murine Model of Type 2 Diabetes.

PubMed

Hunt, Heather B; Pearl, Jared C; Diaz, David R; King, Karen B; Donnelly, Eve

2018-05-01

Type 2 diabetes mellitus (T2DM) increases fracture risk for a given bone mineral density (BMD), which suggests that T2DM changes bone tissue properties independently of bone mass. In this study, we assessed the effects of hyperglycemia on bone tissue compositional properties, enzymatic collagen crosslinks, and advanced glycation end-products (AGEs) in the KK-Ay murine model of T2DM using Fourier transform infrared (FTIR) imaging and high-performance liquid chromatography (HPLC). Compared to KK-aa littermate controls (n = 8), proximal femoral bone tissue of KK-Ay mice (n = 14) exhibited increased collagen maturity, increased mineral content, and less heterogeneous mineral properties. AGE accumulation assessed by the concentration of pentosidine, as well as the concentrations of the nonenzymatic crosslinks hydroxylysylpyridinoline (HP) and lysyl pyridinoline (LP), did not differ in the proximal femurs of KK-Ay mice compared to controls. The observed differences in tissue-level compositional properties in the KK-Ay mice are consistent with bone that is older and echo observations of reduced remodeling in T2DM. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Building better bones in childhood: a randomized controlled study to test the efficacy of a dietary intervention program to increase calcium intake.

PubMed

Weber, D R; Stark, L J; Ittenbach, R F; Stallings, V A; Zemel, B S

2017-06-01

Many children do not consume the recommended daily allowance of calcium. Inadequate calcium intake in childhood may limit bone accrual. The objective of this study was to determine if a behavioral modification and nutritional education (BM-NE) intervention improved dietary calcium intake and bone accrual in children. 139 (86 female) healthy children, 7-10 years of age, were enrolled in this randomized controlled trial conducted over 36 months. Participants randomized to the BM-NE intervention attended five sessions over a 6-week period designed to increase calcium intake to 1500 mg/day. Participants randomized to the usual care (UC) group received a single nutritional counseling session. The Calcium Counts Food Frequency Questionnaire was used to assess calcium intake; dual energy X-ray absorptiometry was used to assess areal bone mineral density (aBMD) and bone mineral content (BMC). Longitudinal mixed effects models were used to assess for an effect of the intervention on calcium intake, BMC and aBMD. BM-NE participants had greater increases in calcium intake that persisted for 12 months following the intervention compared with UC. The intervention had no effect on BMC or aBMD accrual. Secondary analyses found a negative association between calcium intake and adiposity such that greater calcium intake was associated with lesser gains in body mass index and fat mass index. A family-centered BM-NE intervention program in healthy children was successful in increasing calcium intake for up to 12 months but had no effect on bone accrual. A beneficial relationship between calcium intake and adiposity was observed and warrants future study.

Positive effects of vegetable and fruit consumption and calcium intake on bone mineral accrual in boys during growth from childhood to adolescence: the University of Saskatchewan Pediatric Bone Mineral Accrual Study.

PubMed

Vatanparast, Hassanali; Baxter-Jones, Adam; Faulkner, Robert A; Bailey, Donald A; Whiting, Susan J

2005-09-01

Nutrition is an important modifiable factor in the development of bone mass during adolescence. Recent studies of children and adolescents examined the effects of foods such as milk products and fruit and vegetables on bone growth; however, few studies included both boys and girls. The purpose was to ascertain the role of consumption of milk products and vegetables and fruit in the accrual of total-body bone mineral content (TBBMC) in boys and girls from childhood to late adolescence. Seven-year longitudinal data were obtained from 85 boys and 67 girls aged 8-20 y. Biological maturity was defined by the number of years from the age at peak height velocity. Dietary intake was assessed by serial 24-h recalls. Anthropometric measurements and physical activity were assessed every 6 mo. TBBMC assessed with dual-energy X-ray absorptiometry in the fall of each year was the indicator of bone mass. Most boys (87.8%) met Canadian recommendations for milk product intake. Few subjects (<30%) consumed vegetables and fruit in recommended amounts. Using a multilevel modeling statistical approach containing important biological and environmental factors, we found that vegetable and fruit intakes, calcium intake, and physical activity were significant independent environmental predictors of TBBMC in boys but not in girls. In addition to adequate dietary calcium intake, appropriate intakes of vegetables and fruit have a beneficial effect on TBBMC in boys aged 8-20 y. Underreporting of dietary intake by girls may explain why this effect was not apparent in girls.

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.

Predictive value of low BMD for 1-year fracture outcomes is similar for postmenopausal women ages 50-64 and 65 and Older: results from the National Osteoporosis Risk Assessment (NORA).

PubMed

Siris, Ethel S; Brenneman, Susan K; Miller, Paul D; Barrett-Connor, Elizabeth; Chen, Ya-Ting; Sherwood, Louis M; Abbott, Thomas A

2004-08-01

The relationship of low bone mass and fracture in younger postmenopausal women has not been extensively studied. In a large cohort of postmenopausal women > or =50 years of age, we found the relationship of BMD measured at peripheral sites and subsequent 1-year fracture risk to be similar between women <65 and those > or =65 years of age. Low bone mass and fractures are prevalent in older postmenopausal women. However, the frequency of low bone mass and fracture in younger postmenopausal women has not been studied extensively. There are very limited data regarding the association between BMD measurements and fractures in postmenopausal women who are between the ages of 50 and 64. In the National Osteoporosis Risk Assessment (NORA) we studied the frequency of low bone mass and its association with fracture in women 50-64 years of age in comparison with women > or =65 of age. NORA enrolled 200,160 postmenopausal women > or =50 years of age who had no prior diagnosis of osteoporosis. Baseline BMD was measured at the heel, forearm, or finger. A 1-year follow-up survey requesting incident fractures since baseline was completed by 163,935 women, 87,594 (53%) of whom were 50-64 years of age. The association between BMD and fracture was assessed using logistic regression, adjusted for important covariates. Thirty-one percent of women 50-64 years of age had low bone mass (T scores < or = -1.0) compared to 62% of women > or =65 years of age. During the first year of follow-up, 2440 women reported fractures of wrist/forearm, rib, spine, or hip, including 440 hip fractures. Nine hundred four women 50-64 years of age reported fractures, including 86 hip fractures, accounting for 37% of fractures and 20% of hip fractures reported in the entire NORA cohort. Relative risk for osteoporotic fracture was 1.5 for each SD decrease in BMD for both the younger and older groups of women. Low BMD in younger postmenopausal women 50-64 years of age showed a 1-year relative risk of fracture similar to that found in women > or =65 years of age.

Posttranslational heterogeneity of bone alkaline phosphatase in metabolic bone disease.

PubMed

Langlois, M R; Delanghe, J R; Kaufman, J M; De Buyzere, M L; Van Hoecke, M J; Leroux-Roels, G G

1994-09-01

Bone alkaline phosphatase is a marker of osteoblast activity. In order to study the posttranscriptional modification (glycosylation) of bone alkaline phosphatase in bone disease, we investigated the relationship between mass and catalytic activity of bone alkaline phosphatase in patients with osteoporosis and hyperthyroidism. Serum bone alkaline phosphatase activity was measured after lectin precipitation using the Iso-ALP test kit. Mass concentration of bone alkaline phosphatase was determined with an immunoradiometric assay (Tandem-R Ostase). In general, serum bone alkaline phosphatase mass and activity concentration correlated well. The activity : mass ratio of bone alkaline phosphatase was low in hyperthyroidism. Activation energy of the reaction catalysed by bone alkaline phosphatase was high in osteoporosis and in hyperthyroidism. Experiments with neuraminidase digestion further demonstrated that the thermodynamic heterogeneity of bone alkaline phosphatase can be explained by a different glycosylation of the enzyme.

Depressive symptoms, body composition and bone mass in young adults: a prospective cohort study.

PubMed

Zhu, K; Allen, K; Mountain, J; Lye, S; Pennell, C; Walsh, J P

2017-04-01

An association between depression and obesity is well recognised, but longitudinal studies of depressive symptoms in adolescents as a predictor of body composition are lacking. We examined depressive symptoms at age 14, 17 and 20 years as predictors of lean, fat and bone mass at age 20 years in a birth cohort. In 1161 participants (569 females) in the Western Australia Pregnancy Cohort (Raine) Study, depressive symptoms were assessed using the Beck Depression Inventory for Youth at age 14 and 17 years, and the Depression, Anxiety and Stress Scale 21 at age 20 years. Participants were further classified into two trajectories using latent class analysis: no/transient and persistent/recurrent depression. At age 20 years, lean body mass (LBM), fat body mass (FBM) and total body bone mass were measured by dual-energy X-ray absorptiometry. In females, accounting for age and lifestyle factors, depression scores at age 14 and 20 years were positively associated with body weight, body mass index (BMI), FBM and % FBM (r=0.110-0.184, P<0.05) but negatively correlated with % LBM (r=-0.120, P<0.05) at age 20 years. Females in the persistent/recurrent depression trajectory (n=99) had significantly higher body weight (+5.1 kg), BMI (+1.8 kg m -2 ), FBM (+3.9 kg) and % FBM (+2.2%) and significantly lower % LBM (-2.2%) at age 20 years than those with no/transient depression (n=470; all P<0.05). In males, depression scores at age 17 and 20 years were negatively associated with LBM but not weight or BMI, and depression trajectory was not a predictor of body composition at age 20 years. Depression scores and trajectories did not predict bone mass in either males or females. Depressive symptoms and persistent/recurrent depression in adolescence are predictors of greater adiposity at age 20 years in females, but not males, but do not predict bone mass in either gender.

Development and validation of the ORACLE score to predict risk of osteoporosis.

PubMed

Richy, Florent; Deceulaer, Fréderic; Ethgen, Olivier; Bruyère, Olivier; Reginster, Jean-Yves

2004-11-01

To develop and validate a composite index, the Osteoporosis Risk Assessment by Composite Linear Estimate (ORACLE), that includes risk factors and ultrasonometric outcomes to screen for osteoporosis. Two cohorts of postmenopausal women aged 45 years and older participated in the development (n = 407) and the validation (n = 202) of ORACLE. Their bone mineral density was determined by dual energy x-ray absorptiometry and quantitative ultrasonometry (QUS), and their historical and clinical risk factors were assessed (January to June 2003). Logistic regression analysis was used to select significant predictors of bone mineral density, whereas receiver operating characteristic (ROC) analysis was used to assess the discriminatory performance of ORACLE. The final logistic regression model retained 4 biometric or historical variables and 1 ultrasonometric outcome. The ROC areas under the curves (AUCs) for ORACLE were 84% for the prediction of osteoporosis and 78% for low bone mass. A sensitivity of 90% corresponded to a specificity of 50% for identification of women at risk of developing osteoporosis. The corresponding positive and negative predictive values were 86% and 54%, respectively, in the development cohort. In the validation cohort, the AUCs for identification of osteoporosis and low bone mass were 81% and 76% for ORACLE, 69% and 64% for QUS T score, 71% and 68% for QUS ultrasonometric bone profile index, and 76% and 75% for Osteoporosis Self-assessment Tool, respectively. ORACLE had the best discriminatory performance in identifying osteoporosis compared with the other approaches (P < .05). ORACLE exhibited the highest discriminatory properties compared with ultrasonography alone or other previously validated risk indices. It may be helpful to enhance the predictive value of QUS.

A 5-year cohort study of the effects of high protein intake on lean mass and BMC in elderly postmenopausal women.

PubMed

Meng, Xingqiong; Zhu, Kun; Devine, Amanda; Kerr, Deborah A; Binns, Colin W; Prince, Richard L

2009-11-01

Long-term effects of high dietary protein intake on muscle and bone structure in the elderly are not clear. The aim of this study was to investigate the relationship between baseline protein intake and lean mass and BMC 5 yr later in a cohort of elderly postmenopausal women. A total of 862 community-dwelling women 75 +/- 3 yr of age provided baseline data including nutrient intake assessed by a food frequency questionnaire. At 5 yr, upper arm muscle area (UAMA) and body composition using DXA were measured. Baseline protein intake was 81 +/- 28 g/d (1.2 +/- 0.4 g/kg/d), contributing 19 +/- 3% of total energy intake. There were positive correlations between baseline protein intake and whole body and appendicular bone-free lean mass and BMC (r = 0.14-0.18, p < 0.001) and UAMA (r = 0.08, p < 0.05). Compared with those in the lowest tertile of protein intake (<66 g/d), women in the top tertile (>87 g/d) had 5.4-6.0% higher whole body and appendicular lean mass and UAMA and 5.3-6.0% higher whole body and appendicular BMC. These effects remained after adjusting for potential confounders. However, the effect on BMC disappeared after further adjustment for lean mass. This study shows that high protein intake is associated with long-term beneficial effects on muscle mass and size and bone mass in elderly women. The protein effect on bone may be partly mediated by its effects on muscle.

Smad4 is required to inhibit osteoclastogenesis and maintain bone mass.

PubMed

Morita, Mayu; Yoshida, Shigeyuki; Iwasaki, Ryotaro; Yasui, Tetsuro; Sato, Yuiko; Kobayashi, Tami; Watanabe, Ryuichi; Oike, Takatsugu; Miyamoto, Kana; Takami, Masamichi; Ozato, Keiko; Deng, Chu-Xia; Aburatani, Hiroyuki; Tanaka, Sakae; Yoshimura, Akihiko; Toyama, Yoshiaki; Matsumoto, Morio; Nakamura, Masaya; Kawana, Hiromasa; Nakagawa, Taneaki; Miyamoto, Takeshi

2016-10-12

Bone homeostasis is maintained as a delicate balance between bone-resorption and bone-formation, which are coupled to maintain appropriate bone mass. A critical question is how bone-resorption is terminated to allow bone-formation to occur. Here, we show that TGFβs inhibit osteoclastogenesis and maintain bone-mass through Smad4 activity in osteoclasts. We found that latent-TGFβ1 was activated by osteoclasts to inhibit osteoclastogenesis. Osteoclast-specific Smad4 conditional knockout mice (Smad4-cKO) exhibited significantly reduced bone-mass and elevated osteoclast formation relative to controls. TGFβ1-activation induced expression of Irf8 and Bcl6, both of which encode factors inhibiting osteoclastogenesis, by blocking their negative regulator, Prdm1, in osteoclasts in a Smad4-dependent manner. Reduced bone-mass and accelerated osteoclastogenesis seen in Smad4-cKO were abrogated by Prdm1 deletion. Administration of latent-TGFβ1-Fc to wild-type mice antagonized LPS-induced bone destruction in a model of activated osteoclast-mediated bone destruction. Thus, latent-TGFβ1-Fc could serve as a promising new therapeutic agent in bone diseases marked by excessive resorption.

42 CFR 410.31 - Bone mass measurement: Conditions for coverage and frequency standards.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 2 2011-10-01 2011-10-01 false Bone mass measurement: Conditions for coverage and... Medical and Other Health Services § 410.31 Bone mass measurement: Conditions for coverage and frequency... applies: Bone mass measurement means a radiologic, radioisotopic, or other procedure that meets the...

42 CFR 410.31 - Bone mass measurement: Conditions for coverage and frequency standards.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 2 2012-10-01 2012-10-01 false Bone mass measurement: Conditions for coverage and... Medical and Other Health Services § 410.31 Bone mass measurement: Conditions for coverage and frequency... applies: Bone mass measurement means a radiologic, radioisotopic, or other procedure that meets the...

42 CFR 410.31 - Bone mass measurement: Conditions for coverage and frequency standards.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 2 2014-10-01 2014-10-01 false Bone mass measurement: Conditions for coverage and... Medical and Other Health Services § 410.31 Bone mass measurement: Conditions for coverage and frequency... applies: Bone mass measurement means a radiologic, radioisotopic, or other procedure that meets the...

42 CFR 410.31 - Bone mass measurement: Conditions for coverage and frequency standards.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Bone mass measurement: Conditions for coverage and... Medical and Other Health Services § 410.31 Bone mass measurement: Conditions for coverage and frequency... applies: Bone mass measurement means a radiologic, radioisotopic, or other procedure that meets the...

42 CFR 410.31 - Bone mass measurement: Conditions for coverage and frequency standards.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 2 2013-10-01 2013-10-01 false Bone mass measurement: Conditions for coverage and... Medical and Other Health Services § 410.31 Bone mass measurement: Conditions for coverage and frequency... applies: Bone mass measurement means a radiologic, radioisotopic, or other procedure that meets the...

Five-class height-weight model for systematization of seventeen-year-old recruits' anthropometric data.

PubMed

Lintsi, Mart; Kaarma, Helje

2003-12-01

An anthropometric study of 552 Tartu city and Tartu county recruits aged 17 years was carried out. Height and weight, 33 anthropometric measurements and 12 skinfolds were measured. Body fat percentage was assessed by Omron BF 300 hand-held segmental body fat analyzer. From anthropometric measurements bone mass was derived by the Drink-water et al. (1986) equation, and total skeletal muscle mass by the Lee et al. (2000) equation. The data were systematized into five height-weight SD-classes. There were 3 classes with harmony between height and weight class: 1--small (small height and small weight), 2--medium (medium height and medium weight), 3--large (large height and large weight), 4--weight class dominating (pyknomorphic) and 5--height class dominating (leptomorphic). It was revealed that in classes 1, 2 and 3 the height and weight increase corresponded to the increase in all heights, breadths and depths, circumferences, skinfolds, body fat, muscle and bone mass. In class 4 circumferences, skinfolds, body fat and muscle mass were bigger. In class 5 all heights and the relative bone mass were bigger. The present investigation confirms the hypothesis that the five height-weight class system is applicable to seventeen-year-old recruits.

Association of adiposity indices with bone density and bone turnover in the Chinese population.

PubMed

Wang, J; Yan, D; Hou, X; Chen, P; Sun, Q; Bao, Y; Hu, C; Zhang, Z; Jia, W

2017-09-01

Associations of adiposity indices with bone mineral density (BMD) and bone turnover markers were evaluated in Chinese participants. Body mass index, fat mass, and lean mass are positively related to BMD in both genders. Subcutaneous fat area was proved to be negatively associated with BMD and positively correlated with osteocalcin in postmenopausal females. Obesity is highly associated with osteoporosis, but the effect of adipose tissue on bone is contradictory. Our study aimed to assess the associations of adiposity indices with bone mineral density (BMD) and bone turnover markers (BTMs) in the Chinese population. Our study recruited 5215 participants from the Shanghai area, evaluated related anthropometric and biochemical traits in all participants, tested serum BTMs, calculated fat distribution using magnetic resonance imaging (MRI) images and image analysis software, and tested BMD with dual-energy X-ray absorptiometry. When controlled for age, all adiposity indices were positively correlated with BMD of all sites for both genders. As for the stepwise regression analysis, body mass index (BMI), fat mass, and lean mass were protective for BMD in both genders. However, subcutaneous fat area (SFA) was detrimental for BMD of the L1-4 and femoral neck (β ± SE -0.0742 ± 0.0174; p = 2.11E-05; β ± SE -0.0612 ± 0.0147; p = 3.07E-05). Adiposity indices showed a negative correlation with BTMs adjusting for age, especially with osteocalcin. In the stepwise regression analysis, fat mass was negatively correlated with osteocalcin (β ± SE -8.8712 ± 1.4902; p = 4.17E-09) and lean mass showed a negative correlation with N-terminal procollagen of type I collagen (PINP) for males (β ± SE -0.3169 ± 0.0917; p = 0.0006). In females, BMI and visceral fat area (VFA) were all negatively associated with osteocalcin (β ± SE -0.4423 ± 0.0663; p = 2.85E-11; β ± SE -7.1982 ± 1.1094; p = 9.95E-11), while SFA showed a positive correlation with osteocalcin (β ± SE: 5.5993 ± 1.1753; p = 1.98E-06). BMI, fat mass, and lean mass are proved to be beneficial for BMD in both males and postmenopausal females. SFA is negatively associated with BMD and positively correlated with osteocalcin in postmenopausal females.

High fat diet promotes achievement of peak bone mass in young rats.

PubMed

Malvi, Parmanand; Piprode, Vikrant; Chaube, Balkrishna; Pote, Satish T; Mittal, Monika; Chattopadhyay, Naibedya; Wani, Mohan R; Bhat, Manoj Kumar

2014-12-05

The relationship between obesity and bone is complex. Epidemiological studies demonstrate positive as well as negative correlation between obesity and bone health. In the present study, we investigated the impact of high fat diet-induced obesity on peak bone mass. After 9 months of feeding young rats with high fat diet, we observed obesity phenotype in rats with increased body weight, fat mass, serum triglycerides and cholesterol. There were significant increases in serum total alkaline phosphatase, bone mineral density and bone mineral content. By micro-computed tomography (μ-CT), we observed a trend of better trabecular bones with respect to their microarchitecture and geometry. This indicated that high fat diet helps in achieving peak bone mass and microstructure at younger age. We subsequently shifted rats from high fat diet to normal diet for 6 months and evaluated bone/obesity parameters. It was observed that after shifting rats from high fat diet to normal diet, fat mass, serum triglycerides and cholesterol were significantly decreased. Interestingly, the gain in bone mineral density, bone mineral content and trabecular bone parameters by HFD was retained even after body weight and obesity were normalized. These results suggest that fat rich diet during growth could accelerate achievement of peak bone mass that is sustainable even after withdrawal of high fat diet.

Factors associated with appendicular bone mass in older women. The Study of Osteoporotic Fractures Research Group.

PubMed

Bauer, D C; Browner, W S; Cauley, J A; Orwoll, E S; Scott, J C; Black, D M; Tao, J L; Cummings, S R

1993-05-01

To determine the factors associated with appendicular bone mass in older women. Cross-sectional analysis of baseline data collected for a multicenter, prospective study of osteoporotic fractures. Four clinical centers in Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela valley, Pennsylvania. A total of 9704 ambulatory, nonblack women, ages 65 years or older, recruited from population-based listings. Demographic and historical information and anthropometric measurements were obtained from a baseline questionnaire, interview, and examination. Single-photon absorptiometry scans were obtained at three sites: the distal radius, midradius, and calcaneus. Multivariate associations with bone mass were first examined in a randomly selected half of the cohort (training group) and were then tested on the other half of the cohort (validation group). In order of decreasing strength of association, estrogen use, non-insulin-dependent diabetes, thiazide use, increased weight, greater muscle strength, later age at menopause, and greater height were independently associated with higher bone mass. Gastric surgery, age, history of maternal fracture, smoking, and caffeine intake were associated with lower bone mass (all P < 0.05). For example, we found that 2 or more years of estrogen use was associated with a 7.2% increase in distal radius bone mass, whereas gastrectomy was associated with an 8.2% decrease in bone mass. The associations between bone mass and dietary calcium intake and rheumatoid arthritis were inconsistent. Alcohol use, physical activity, use of calcium supplements, pregnancy, breast-feeding, parental nationality, and hair color were among the many variables not associated with bone mass. Multivariate models accounted for 20% to 35% of the total variance of bone mass. A large number of factors influence the bone mass of elderly women; however, age, weight, muscle strength, and estrogen use are the most important factors.

Musculoskeletal phenotype through the life course: the role of nutrition.

PubMed

Ward, Kate

2012-02-01

This review considers the definition of a healthy bone phenotype through the life course and the modulating effects of muscle function and nutrition. In particular, it will emphasise that optimal bone strength (and how that is regulated) is more important than simple measures of bone mass. The forces imposed on bone by muscle loading are the primary determinants of musculoskeletal health. Any factor that changes muscle loading on the bone, or the response of bone to loading results in alterations of bone strength. Advances in technology have enhanced the understanding of a healthy bone phenotype in different skeletal compartments. Multiple components of muscle strength can also be quantified. The critical evaluation of emerging technologies for assessment of bone and muscle phenotype is vital. Populations with low and moderate/high daily Ca intakes and/or different vitamin D status illustrate the importance of nutrition in determining musculoskeletal phenotype. Changes in mass and architecture maintain strength despite low Ca intake or vitamin D status. There is a complex interaction between body fat and bone which, in addition to protein intake, is emerging as a key area of research. Muscle and bone should be considered as an integrative unit; the role of body fat requires definition. There remains a lack of longitudinal evidence to understand how nutrition and lifestyle define musculoskeletal health. In conclusion, a life-course approach is required to understand the definition of healthy skeletal phenotype in different populations and at different stages of life.

Adiposity and TV viewing are related to less bone accrual in young children

PubMed Central

Wosje, Karen S.; Khoury, Philip R.; Claytor, Randal P.; Copeland, Kristen A.; Kalkwarf, Heidi J.; Daniels, Stephen R.

2008-01-01

Objective To examine the relation between baseline fat mass and gain in bone area and bone mass in preschoolers studied prospectively for 4 y, with a focus on the role of physical activity and TV viewing. Study design Children were part of a longitudinal study in which measures of fat, lean and bone mass, height, weight, activity, and diet were taken every 4 months from ages 3 to 7 y. Activity was measured by accelerometer, and TV viewing by parent checklist. We included 214 children with total body dual energy x-ray absorptiometry (Hologic 4500A) scans at ages 3.5 and 7 y. Results Higher baseline fat mass was associated with smaller increases in bone area and bone mass over the next 3.5 y (p<0.001). More TV viewing was related to smaller gains in bone area and bone mass accounting for race, sex, and height. Activity by accelerometer was not associated with bone gains. Conclusions Adiposity and TV viewing are related to less bone accrual in preschoolers. PMID:18692201

BONE MASS BY QUANTITATIVE ULTRASOUND OF FINGER PHALANGES IN YOUNG KARATE PRACTITIONERS

PubMed Central

Barbeta, Camila Justino de Oliveira; Gonçalves, Ezequiel Moreira; Ribeiro, Keila Donassolo Santos; Ribeiro, Roberto; Roman, Everton Paulo; Guerra-Júnior, Gil

2017-01-01

ABSTRACT Objective: To evaluate bone mass by quantitative ultrasound of the phalanges in young karate practitioners compared to a control group. Methods: Sample composed of 162 karate practitioners (52 females) and 326 healthy controls (110 females) aged 6 to 16 years old, in Western Paraná (Southern Brazil). Weight, height, BMI, amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) were evaluated. BMI, AD-SoS and BTT values were converted to Z scores. Mann-Whitney, chi-square or Fisher Exact tests and multiple linear regression were applied, with significance level set at p≤0.05. Results: Both genders showed higher values of BTT as Z scores when compared to control group. Females from the control group had higher AD-SoS values (m/s and Z score) compared to female karate practitioners. When relative and absolute frequencies were assessed according to BTT Z score in both groups, male karate practitioners’ bone mass was shown to be adequate more frequently. In female practitioners, age and weight were independent predictors of AD-SoS (R2=0.42) and BTT (R2=0.45), respectively. Among male karate practitioners, age was related to 26% of AD-SoS variances and height was responsible for 36% of BTT variances. Conclusions: Children and adolescents who practice karate were shown to have more bone mass in comparison to the control group, regardless of gender. BTT was more sensitive for this evaluation. PMID:28977128

Female Mice Lacking Estrogen Receptor-α in Hypothalamic Proopiomelanocortin (POMC) Neurons Display Enhanced Estrogenic Response on Cortical Bone Mass.

PubMed

Farman, H H; Windahl, S H; Westberg, L; Isaksson, H; Egecioglu, E; Schele, E; Ryberg, H; Jansson, J O; Tuukkanen, J; Koskela, A; Xie, S K; Hahner, L; Zehr, J; Clegg, D J; Lagerquist, M K; Ohlsson, C

2016-08-01

Estrogens are important regulators of bone mass and their effects are mainly mediated via estrogen receptor (ER)α. Central ERα exerts an inhibitory role on bone mass. ERα is highly expressed in the arcuate (ARC) and the ventromedial (VMN) nuclei in the hypothalamus. To test whether ERα in proopiomelanocortin (POMC) neurons, located in ARC, is involved in the regulation of bone mass, we used mice lacking ERα expression specifically in POMC neurons (POMC-ERα(-/-)). Female POMC-ERα(-/-) and control mice were ovariectomized (OVX) and treated with vehicle or estradiol (0.5 μg/d) for 6 weeks. As expected, estradiol treatment increased the cortical bone thickness in femur, the cortical bone mechanical strength in tibia and the trabecular bone volume fraction in both femur and vertebrae in OVX control mice. Importantly, the estrogenic responses were substantially increased in OVX POMC-ERα(-/-) mice compared with the estrogenic responses in OVX control mice for cortical bone thickness (+126 ± 34%, P < .01) and mechanical strength (+193 ± 38%, P < .01). To test whether ERα in VMN is involved in the regulation of bone mass, ERα was silenced using an adeno-associated viral vector. Silencing of ERα in hypothalamic VMN resulted in unchanged bone mass. In conclusion, mice lacking ERα in POMC neurons display enhanced estrogenic response on cortical bone mass and mechanical strength. We propose that the balance between inhibitory effects of central ERα activity in hypothalamic POMC neurons in ARC and stimulatory peripheral ERα-mediated effects in bone determines cortical bone mass in female mice.

Genetic effects on bone mass and turnover-relevance to black/white differences.

PubMed

Parfitt, A M

1997-08-01

The mass of a bone is given by its volume and its apparent density--mass per unit external volume. Most measurements of so-called density are of mass incompletely normalized by some index of bone size. Genes control about 60% to 75% of the variance of peak bone mass/density and a much smaller proportion of the variance in rate of loss. Genetic influence on bone mass/density are mediated in large part by body size, bone size, and muscle mass. Most of the fifty-fold increase in bone mass from birth to maturity is due to bone growth, which is linked to muscle growth and bodily growth. Three-D apparent bone density in the vertebrae increases about 15% during the pubertal growth spurt. The genetic potential for bone accumulation can be frustrated by insufficient calcium intake, disruption of the calendar of puberty and inadequate physical activity. The growing skeleton is much more responsive than the mature skeleton to the osteotrophic effect of exercise, which is mediated by the detection of deviations from a target value for strain, and orchestration of cellular responses that restore the target value, processes collectively termed the mechanostat. Production of metaphyseal cancellous bone and growth in length are both linked to endochondral ossification, which is driven by growth plate cartilage cell proliferation. Production of diaphyseal cortical bone and growth in width are both linked to periosteal apposition, which is driven by osteoblast precursor proliferation. During adolescence trabeculae and cortices become thicker by net endosteal apposition, which increases apparent density. Two lines of evidence support a genetic basis for black/white differences in bone mass. First, the magnitude (10% to 40%) is incommensurate with known nongenetic factors. Second, the difference is already evident in the fetus and increases progressively during growth, especially in adolescence; the difference in peak bone mass persists throughout life. The genetic determination of bone mass is mediated by two classes of gene. The first regulates growth of the body, including muscles and bones, under the control of a master gene or set of genes whose products function as the sizostat. The second regulates the increase in apparent bone density in response to load bearing, under the control of a master gene or set of genes whose products function as the mechanostat.

High fat diet promotes achievement of peak bone mass in young rats

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

Malvi, Parmanand; Piprode, Vikrant; Chaube, Balkrishna

Highlights: • High fat diet helps in achieving peak bone mass at younger age. • Shifting from high fat to normal diet normalizes obese parameters. • Bone parameters are sustained even after withdrawal of high fat diet. - Abstract: The relationship between obesity and bone is complex. Epidemiological studies demonstrate positive as well as negative correlation between obesity and bone health. In the present study, we investigated the impact of high fat diet-induced obesity on peak bone mass. After 9 months of feeding young rats with high fat diet, we observed obesity phenotype in rats with increased body weight, fatmore » mass, serum triglycerides and cholesterol. There were significant increases in serum total alkaline phosphatase, bone mineral density and bone mineral content. By micro-computed tomography (μ-CT), we observed a trend of better trabecular bones with respect to their microarchitecture and geometry. This indicated that high fat diet helps in achieving peak bone mass and microstructure at younger age. We subsequently shifted rats from high fat diet to normal diet for 6 months and evaluated bone/obesity parameters. It was observed that after shifting rats from high fat diet to normal diet, fat mass, serum triglycerides and cholesterol were significantly decreased. Interestingly, the gain in bone mineral density, bone mineral content and trabecular bone parameters by HFD was retained even after body weight and obesity were normalized. These results suggest that fat rich diet during growth could accelerate achievement of peak bone mass that is sustainable even after withdrawal of high fat diet.« less

Site-specific, adult bone benefits attributed to loading during youth: A preliminary longitudinal analysis.

PubMed

Scerpella, Tamara A; Bernardoni, Brittney; Wang, Sijian; Rathouz, Paul J; Li, Quefeng; Dowthwaite, Jodi N

2016-04-01

We examined site-specific bone development in relation to childhood and adolescent artistic gymnastics exposure, comparing up to 10years of prospectively acquired longitudinal data in 44 subjects, including 31 non-gymnasts (NON) and 13 gymnasts (GYM) who participated in gymnastics from pre-menarche to ≥1.9years post-menarche. Subjects underwent annual regional and whole-body DXA scans; indices of bone geometry and strength were calculated. Anthropometrics, physical activity, and maturity were assessed annually, coincident with DXA scans. Non-linear mixed effect models centered growth in bone outcomes at menarche and adjusted for menarcheal age, height, and non-bone fat-free mass to evaluate GYM-NON differences. A POST-QUIT variable assessed the withdrawal effect of quitting gymnastics. Curves for bone area, mass (BMC), and strength indices were higher in GYM than NON at both distal radius metaphysis and diaphysis (p<0.0001). At the femoral neck, greater GYM BMC (p<0.01), narrower GYM endosteal diameter (p<0.02), and similar periosteal width (p=0.09) yielded GYM advantages in narrow neck cortical thickness and buckling ratio (both p<0.001; lower BR indicates lower fracture risk). Lumbar spine and sub-head BMC were greater in GYM than NON (p<0.036). Following gymnastics cessation, GYM slopes increased for distal radius diaphysis parameters (p≤0.01) and for narrow neck BR (p=0.02). At the distal radius metaphysis, GYM BMC and compressive strength slopes decreased, as did slopes for lumbar spine BMC, femoral neck BMC, and narrow neck cortical thickness (p<0.02). In conclusion, advantages in bone mass, geometry, and strength at multiple skeletal sites were noted across growth and into young adulthood in girls who participated in gymnastics loading to at least 1.9years post-menarche. Following gymnastics cessation, advantages at cortical bone sites improved or stabilized, while advantages at corticocancellous sites stabilized or diminished. Additional longitudinal observation is necessary to determine whether residual loading benefits enhance lifelong skeletal strength. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of Associated Carpal Bone Fractures in Distal Radial Fractures

PubMed Central

Heo, Youn Moo; Kim, Sang Bum; Yi, Jin Woong; Park, Cheol Yong; Yoon, Jeong Yong; Kim, Doo Hyun

2013-01-01

Background The purpose of this study was to investigate the frequency and distribution of associated carpal bone fractures (CBFs) in distal radial fractures (DRFs). Methods Three hundred and thirteen patients who underwent surgical treatment for DRFs between March 2007 and January 2010 were reviewed retrospectively. In this study, 223 patients who had preoperative computed tomography (CT) were included. We investigated the frequency and distribution of associated CBFs on CT scans. The relationship between the frequency of associated CBFs and patient factors such as age, gender, body mass index, and the mechanism of injury was assessed. Results CBFs were complicated in 46 of 223 DRFs (20.9%). The distribution of CBFs was 23 cases in the triquetrum, 16 in the lunate, 12 in the scaphoid, five in the hamate, and four in the pisiform. Among the 46 cases, a fracture of one carpal bone occurred in 36 cases, two in seven cases, three in two cases, and four in one case. In 10 of the 46 cases, associated CBFs occurred in more than two carpal bones. No significant differences were observed for age, sex, body mass index, or the mechanism of injury between patients with DRFs and CBFs and those without CBFs. Conclusions Because CBFs that mainly occur in the proximal carpal row are complicated in DRFs at a relatively high frequency, assessment of carpal bones using CT scans is beneficial. PMID:23730472

The longitudinal effects of physical activity and dietary calcium on bone mass accrual across stages of pubertal development.

PubMed

Lappe, Joan M; Watson, Patrice; Gilsanz, Vicente; Hangartner, Thomas; Kalkwarf, Heidi J; Oberfield, Sharon; Shepherd, John; Winer, Karen K; Zemel, Babette

2015-01-01

Childhood and adolescence are critical periods of bone mineral content (BMC) accrual that may have long-term consequences for osteoporosis in adulthood. Adequate dietary calcium intake and weight-bearing physical activity are important for maximizing BMC accrual. However, the relative effects of physical activity and dietary calcium on BMC accrual throughout the continuum of pubertal development in childhood remains unclear. The purpose of this study was to determine the effects of self-reported dietary calcium intake and weight-bearing physical activity on bone mass accrual across the five stages of pubertal development in a large, diverse cohort of US children and adolescents. The Bone Mineral Density in Childhood study was a mixed longitudinal study with 7393 observations on 1743 subjects. Annually, we measured BMC by dual-energy X-ray absorptiometry (DXA), physical activity and calcium intake by questionnaire, and pubertal development (Tanner stage) by examination for up to 7 years. Mixed-effects regression models were used to assess physical activity and calcium intake effects on BMC accrual at each Tanner stage. We found that self-reported weight-bearing physical activity contributed to significantly greater BMC accrual in both sexes and racial subgroups (black and nonblack). In nonblack males, the magnitude of the activity effect on total body BMC accrual varied among Tanner stages after adjustment for calcium intake; the greatest difference between high- and low-activity boys was in Tanner stage 3. Calcium intake had a significant effect on bone accrual only in nonblack girls. This effect was not significantly different among Tanner stages. Our findings do not support differential effects of physical activity or calcium intake on bone mass accrual according to maturational stage. The study demonstrated significant longitudinal effects of weight-bearing physical activity on bone mass accrual through all stages of pubertal development. © 2014 American Society for Bone and Mineral Research.

Prevalence of low bone mass among adolescents with nontransfusion-dependent hemoglobin E/β-thalassemia and its relationship with anemia severity.

PubMed

Nakavachara, Pairunyar; Petchkul, Jaturat; Jeerawongpanich, Krittha; Kiattisakthavee, Pornpimol; Manpayak, Teerarat; Netsakulnee, Parichat; Chaichanwattanakul, Katharee; Pooliam, Julaporn; Srichairatanakool, Somdet; Viprakasit, Vip

2018-01-01

Low bone mass is common among adolescents with transfusion-dependent β-thalassemia despite adequate transfusion and iron chelation. However, there are few reports regarding bone mineral density (BMD) among adolescents with nontransfusion-dependent thalassemia (NTDT). Indeed, only BMD data in patients with nontransfusion-dependent (NTD) β-thalassemia intermedia have been reported. No previous study has investigated BMD among adolescents with NTD hemoglobin (Hb) E/β-thalassemia. To determine the prevalence of low bone mass among adolescents with NTD Hb E/β-thalassemia and factors relating to low bone mass. We investigated BMD of lumbar spine (L2-L4; BMDLS) and total body (BMDTB), as measured by dual-energy X-ray absorptiometry, in 22 adolescents (aged 13.2-20 years) with NTD Hb E/β-thalassemia. Low bone mass was found to be 18.2% and 22.7% at the lumbar spine (BMDLS Z-score adjusted for bone age and height age) and 13.6% and 9.1% at the total body (BMDTB Z-score adjusted for bone age and height age). Patients with mean Hb level <8 g/dl were more likely to have low bone mass (BMDLS and BMDTB Z-scores adjusted for bone age) compared to those with Hb level ≥ 8 g/dl. Mean Hb level correlated with BMDLS and BMDTB Z-scores adjusted for bone age. We demonstrated that a low Hb level was associated with low bone mass among adolescents with NTD Hb E/β-thalassemia. A significant proportion of low bone mass among these patients highlights the importance of appropriate management, including red cell transfusion, vitamin D and calcium supplementation for improved long-term bone health. © 2017 Wiley Periodicals, Inc.

Regulation of bone mass through pineal-derived melatonin-MT2 receptor pathway.

PubMed

Sharan, Kunal; Lewis, Kirsty; Furukawa, Takahisa; Yadav, Vijay K

2017-09-01

Tryptophan, an essential amino acid through a series of enzymatic reactions gives rise to various metabolites, viz. serotonin and melatonin, that regulate distinct biological functions. We show here that tryptophan metabolism in the pineal gland favors bone mass accrual through production of melatonin, a pineal-derived neurohormone. Pineal gland-specific deletion of Tph1, the enzyme that catalyzes the first step in the melatonin biosynthesis lead to a decrease in melatonin levels and a low bone mass due to an isolated decrease in bone formation while bone resorption parameters remained unaffected. Skeletal analysis of the mice deficient in MT1 or MT2 melatonin receptors showed a low bone mass in MT2-/- mice while MT1-/- mice had a normal bone mass compared to the WT mice. This low bone mass in the MT2-/- mice was due to an isolated decrease in osteoblast numbers and bone formation. In vitro assays of the osteoblast cultures derived from the MT1-/- and MT2-/- mice showed a cell intrinsic defect in the proliferation, differentiation and mineralization abilities of MT2-/- osteoblasts compared to WT counterparts, and the mutant cells did not respond to melatonin addition. Finally, we demonstrate that daily oral administration of melatonin can increase bone accrual during growth and can cure ovariectomy-induced structural and functional degeneration of bone by specifically increasing bone formation. By identifying pineal-derived melatonin as a regulator of bone mass through MT2 receptors, this study expands the role played by tryptophan derivatives in the regulation of bone mass and underscores its therapeutic relevance in postmenopausal osteoporosis. © 2017 The Authors. Journal of Pineal Research Published by John Wiley & Sons Ltd.

Modified Creatinine Index and the Risk of Bone Fracture in Patients Undergoing Hemodialysis: The Q-Cohort Study.

PubMed

Yamada, Shunsuke; Taniguchi, Masatomo; Tokumoto, Masanori; Yoshitomi, Ryota; Yoshida, Hisako; Tatsumoto, Narihito; Hirakata, Hideki; Fujimi, Satoru; Kitazono, Takanari; Tsuruya, Kazuhiko

2017-08-01

Hemodialysis patients are at increased risk for bone fracture and sarcopenia. There is close interplay between skeletal muscle and bone. However, it is still unclear whether lower skeletal muscle mass increases the risk for bone fracture. Cross-sectional study and prospective longitudinal cohort study. An independent cohort of 78 hemodialysis patients in the cross-sectional study and 3,030 prevalent patients undergoing maintenance hemodialysis prospectively followed up for 4 years. Skeletal muscle mass measured by bioelectrical impedance analysis (BIA) and modified creatinine index, an estimate of skeletal muscle mass based on age, sex, Kt/V for urea, and serum creatinine level. Bone fracture at any site. In the cross-sectional study, modified creatinine index was significantly correlated with skeletal muscle mass measured by BIA. During a median follow-up of 3.9 years, 140 patients had bone fracture. When patients were divided into sex-specific quartiles based on modified creatinine index, risk for bone fracture estimated by a Fine-Gray proportional subdistribution hazards model with all-cause death as a competing risk was significantly higher in the lower modified creatinine index quartiles (Q1 and Q2) compared to the highest modified creatinine index quartile (Q4) as the reference value in both sexes (multivariable-adjusted HRs for men were 7.81 [95% CI, 2.63-23.26], 5.48 [95% CI, 2.08-14.40], 2.24 [95% CI, 0.72-7.00], and 1.00 [P for trend < 0.001], and for women were 4.44 [95% CI, 1.50-13.11], 2.33 [95% CI, 0.86-6.31], 1.96 [95% CI, 0.82-4.65], and 1.00 [P for trend = 0.007] for Q1, Q2, Q3, and Q4, respectively). One-time assessment of modified creatinine index; no data for residual kidney function and fracture sites and causes. Modified creatinine index was correlated with skeletal muscle mass measured by BIA. Lower modified creatinine index was associated with increased risk for bone fracture in male and female hemodialysis patients. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Bone Metabolism in Anorexia Nervosa

PubMed Central

Fazeli, Pouneh K.; Klibanski, Anne

2014-01-01

Anorexia nervosa (AN), a psychiatric disorder predominantly affecting young women, is characterized by self-imposed chronic nutritional deprivation and distorted body image. AN is associated with a number of medical co-morbidities including low bone mass. The low bone mass in AN is due to an uncoupling of bone formation and bone resorption, which is the result of hormonal adaptations aimed at decreasing energy expenditure during periods of low energy intake. Importantly, the low bone mass in AN is associated with a significant risk of fractures and therefore treatments to prevent bone loss are critical. In this review, we discuss the hormonal determinants of low bone mass in AN and treatments that have been investigated in this population. PMID:24419863

Increasing Bone Mass and Bone Strength in Individuals with Chronic Spinal Cord Injury: Maximizing Response to Therapy

DTIC Science & Technology

2017-10-01

Award Number: W81XWH-16-1-0763 TITLE: Increasing Bone Mass and Bone Strength in Individuals with Chronic Spinal Cord Injury: Maximizing Response...TYPE Annual 3. DATES COVERED (From - To) 30 Sep 2016-29 Sep 2017 5a. CONTRACT NUMBER Increasing Bone Mass and Bone Strength in Individuals with...DISTRIBUTION / AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Rapid bone loss is a universal

Body composition and bone mineral density of national football league players.

PubMed

Dengel, Donald R; Bosch, Tyler A; Burruss, T Pepper; Fielding, Kurt A; Engel, Bryan E; Weir, Nate L; Weston, Todd D

2014-01-01

The purpose of the present study was to examine the body composition of National Football League (NFL) players before the start of the regular season. Four hundred eleven NFL players were measured for height, weight and lean, fat, and bone mass using dual-energy x-ray absorptiometry (DXA). Subjects were categorized by their offensive or defensive position for comparison. On average, positions that mirror each other (i.e., offensive lineman [OL] vs. defensive lineman [DL]) have very similar body composition. Although OL had more fat mass than DL, they were similar in total and upper and lower lean mass. Linebackers (LB) and running backs (RB) were similar for all measures of fat and lean mass. Tight ends were unique in that they were similar to RB and LB on measures of fat mass; however, they had greater lean mass than both RB and LB and upper-body lean mass that was similar to OL. Quarterbacks and punters/kickers were similar in fat and lean masses. All positions had normal levels of bone mineral density. The DXA allowed us to measure differences in lean mass between arms and legs for symmetry assessments. Although most individuals had similar totals of lean mass in each leg and or arms, there were outliers who may be at risk for injury. The data presented demonstrate not only differences in total body composition, but also show regional body composition differences that may provide positional templates.

Diversity of activity participation determines bone mineral content in the lower limbs of pre-pubertal children with developmental coordination disorder.

PubMed

Fong, S S M; Vackova, D; Choi, A W M; Cheng, Y T Y; Yam, T T T; Guo, X

2018-04-01

This study examined the relationships between activity participation and bone mineralization in children with developmental coordination disorder. Limited participation in physical, recreational, social, and skill-based and self-improvement activities contributed to lower bone mineral content. For improved bone health, these children should participate in a variety of activities, not only physical activities. Limited activity participation in children with developmental coordination disorder (DCD) may have a negative impact on bone mineral accrual. The objectives of this study were to compare bone mineralization and activity participation patterns of pre-pubertal children with DCD and those with typical development, and to determine the association between activity participation patterns and bone mineralization in children with DCD. Fifty-two children with DCD (mean age = 7.51 years) and 61 children with typical development (mean age = 7.22 years) participated in the study. Appendicular and total body (less head) bone mineral content (BMC) and bone mineral density (BMD) were evaluated by a whole-body dual-energy X-ray absorptiometry scan. Activity participation patterns were assessed using the Children's Assessment of Participation and Enjoyment (CAPE) questionnaire. Children with DCD had lower appendicular and total body BMCs and BMDs than children with typical development overall (p < 0.05). They also had lower CAPE total activity and physical activity diversity scores (p < 0.05). After accounting for the effects of age, sex, height, lean mass, and fat mass, the total activity diversity score remained independently associated with leg BMC in children with DCD, explaining 5.1% of the variance (p = 0.030). However, the physical activity diversity score was no longer associated with leg BMC (p = 0.090). Diversity of activity participation and bone mineralization were lower in pre-pubertal children with DCD. Decreased total activity participation diversity was a contributing factor to lower BMC in the legs of children with DCD.

Stimulation of liver IGF-1 expression promotes peak bone mass achievement in growing rats: a study with pomegranate seed oil.

PubMed

Bachagol, Deepa; Joseph, Gilbert Stanley; Ellur, Govindraj; Patel, Kalpana; Aruna, Pamisetty; Mittal, Monika; China, Shyamsundar Pal; Singh, Ravendra Pratap; Sharan, Kunal

2018-02-01

Peak bone mass (PBM) achieved at adulthood is a strong determinant of future onset of osteoporosis, and maximizing it is one of the strategies to combat the disease. Recently, pomegranate seed oil (PSO) has been shown to have bone-sparing effect in ovariectomized mice. However, its effect on growing skeleton and its molecular mechanism remain unclear. In the present study, we evaluated the effect of PSO on PBM in growing rats and associated mechanism of action. PSO was given at various doses to 21-day-old growing rats for 90 days by oral gavage. The changes in bone parameters were assessed by micro-computed tomography and histology. Enzyme-linked immunosorbent assay was performed to analyze the levels of serum insulin-like growth factor type 1 (IGF-1). Western blotting from bone and liver tissues was done. Chromatin immunoprecipitation assay was performed to study the histone acetylation levels at IGF-1 gene. The results of the study show that PSO treatment significantly increases bone length, bone formation rate, biomechanical parameters, bone mineral density and bone microarchitecture along with enhancing muscle and brown fat mass. This effect was due to the increased serum levels of IGF-1 and stimulation of its signaling in the bones. Studies focusing on acetylation of histones in the liver, the major site of IGF-1 synthesis, showed enrichment of acetylated H3K9 and H3K14 at IGF-1 gene promoter and body. Further, the increased acetylation at H3K9 and H3K14 was associated with a reduced HDAC1 protein level. Together, our data suggest that PSO promotes the PBM achievement via increased IGF-1 expression in liver and IGF-1 signaling in bone. Copyright © 2017 Elsevier Inc. All rights reserved.

A myostatin and activin decoy receptor enhances bone formation in mice.

PubMed

Bialek, P; Parkington, J; Li, X; Gavin, D; Wallace, C; Zhang, J; Root, A; Yan, G; Warner, L; Seeherman, H J; Yaworsky, P J

2014-03-01

Myostatin is a member of the bone morphogenetic protein/transforming growth factor-β (BMP/TGFβ) super-family of secreted differentiation factors. Myostatin is a negative regulator of muscle mass as shown by increased muscle mass in myostatin deficient mice. Interestingly, these mice also exhibit increased bone mass suggesting that myostatin may also play a role in regulating bone mass. To investigate the role of myostatin in bone, young adult mice were administered with either a myostatin neutralizing antibody (Mstn-mAb), a soluble myostatin decoy receptor (ActRIIB-Fc) or vehicle. While both myostatin inhibitors increased muscle mass, only ActRIIB-Fc increased bone mass. Bone volume fraction (BV/TV), as determined by microCT, was increased by 132% and 27% in the distal femur and lumbar vertebrae, respectively. Histological evaluation demonstrated that increased BV/TV in both locations was attributed to increased trabecular thickness, trabecular number and bone formation rate. Increased BV/TV resulted in enhanced vertebral maximum compressive force compared to untreated animals. The fact that ActRIIB-Fc, but not Mstn-mAb, increased bone volume suggested that this soluble decoy receptor may be binding a ligand other than myostatin, that plays a role in regulating bone mass. This was confirmed by the significant increase in BV/TV in myostatin deficient mice treated with ActRIIB-Fc. Of the other known ActRIIB-Fc ligands, BMP3 has been identified as a negative regulator of bone mass. However, BMP3 deficient mice treated with ActRIIB-Fc showed similar increases in BV/TV as wild type (WT) littermates treated with ActRIIB-Fc. This result suggests that BMP3 neutralization is not the mechanism responsible for increased bone mass. The results of this study demonstrate that ActRIIB-Fc increases both muscle and bone mass in mice. Therefore, a therapeutic that has this dual activity represents a potential approach for the treatment of frailty. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Physical performance in relation to body composition and bone mineral density in healthy, overweight, and obese postmenopausal women.

PubMed

Shin, Hyehyung; Liu, Pei-Yang; Panton, Lynn B; Ilich, Jasminka Z

2014-01-01

Diminished physical performance can be detrimental among the older adults, causing falls and subsequent fractures, loss of independence, and increased morbidity and mortality rates. Therefore, it is important to maintain functional ability from the early onset of aging. The purpose of this study was to investigate the relationship between physical performance measures and body composition (bone, fat, and lean mass) in healthy, overweight and obese, early postmenopausal white women. A total of 97 participants aged 56.0 (4.4) years (mean (SD)) with body mass index of 31.0 (4.6) kg/m(2) were included. Weight and height were recorded and 3 days of dietary records and physical activity were collected. Dual-energy x-ray absorptiometry measurements for body composition and bone mineral density were performed. Fasting blood samples were used for serum 25-hydroxy vitamin D (25OHD) analysis. Measures of physical performance included handgrip strength, 8-meter walking speed, one-leg-stance time, 8-foot Timed Get-Up-and-Go Test, and chair sit-to-stand test. Results showed that higher lean mass was related to better physical performance on items assessing body strength, including handgrip (r ranged from 0.22 to 0.25, P < .05) while higher body fat was related to the poorer physical performance in each of the assessed measures. Bone mineral density of the forearm was positively related to the handgrip strength (r = 0.207, P < .05). In regression analyses (controlled for age, weight, height, serum 25OHD status, calcium intake, physical activity, and smoking), fat mass of the lower extremities was inversely related to walking speed, one-leg-stance time, and Get-Up-and-Go measures, all crucial for mobility (r(2) = 0.13-0.23, P < .05). Overall, higher fat and lower lean mass was related to poorer physical performance, while forearm bone mineral density was related to the handgrip strength only. Further investigation may be beneficial for a better understanding of how body composition may prevent decline in physical performance among overweight/obese, mid-age, and older women.

Skeletal Phenotype of Transgenic Mice Expressing the Beta1 Integrin Cytoplasmic Tail In Osteoblasts

NASA Technical Reports Server (NTRS)

Globus, R. K.; vanderMeulen, M. C. H.; Damsky, D.; Kim, J.-B.; Amblard, D.; Amblard, D.; Nishimura, Y.; Almeida, E.; Iwaniec, U. T.; Wronski, T. J.;

Body adiposity and bone parameters of male rats from mothers fed diet containing flaxseed flour during lactation.

PubMed

da Costa, C A S; da Silva, P C A; Ribeiro, D C; Pereira, A D D; Santos, A D S D; Maia, L D A; Ruffoni, L D G; de Santana, F C; de Abreu, M D C; Boueri, B F D C; Pessanha, C R; Nonaka, K O; Mancini-Filho, J; do Nascimento-Saba, C C A; Boaventura, G T

2015-12-07

Obesity and osteoporosis may have their origins in early postnatal life. This study was designed to evaluate whether flaxseed flour use during lactation period bears effect on body adiposity and skeletal structure of male rat pups at weaning. At birth, male Wistar rats were randomly assigned to control and experimental (FF) groups, whose dams were treated with control or flaxseed flour diet, respectively, during lactation. At 21 days of age, pups were weaned to assess body mass, length and composition by dual-energy X-ray absorptiometry. The animals were then sacrificed to carry out analysis of serum profile, intra-abdominal adipocyte morphology and femur characteristics. Differences were considered significant when P<0.05. The FF group displayed the following characteristics (P<0.05): higher body mass, length, bone mineral content, bone area and concentrations of osteoprotegerin, osteocalcin and high-density lipoprotein cholesterol; higher levels of stearic, α-linolenic, eicosapentaenoic and docosapentaenoic acids and lower levels of arachidonic acid and cholesterol; smaller adipocyte area; and higher mass, epiphysis distance, diaphysis width, maximal load, break load, resilience and stiffness of femur. Flaxseed flour intake during lactation period promoted adipocyte hypertrophy down-regulation and contributed to pup bone quality at weaning.

Maternal Dietary Supplementation with Oligofructose-Enriched Inulin in Gestating/Lactating Rats Preserves Maternal Bone and Improves Bone Microarchitecture in Their Offspring

PubMed Central

Diaz-Castro, Javier; López-Aliaga, Inmaculada; Rueda, Ricardo

2016-01-01

Nutrition during pregnancy and lactation could exert a key role not only on maternal bone, but also could influence the skeletal development of the offspring. This study was performed in rats to assess the relationship between maternal dietary intake of prebiotic oligofructose-enriched inulin and its role in bone turnover during gestation and lactation, as well as its effect on offspring peak bone mass/architecture during early adulthood. Rat dams were fed either with standard rodent diet (CC group), calcium-fortified diet (Ca group), or prebiotic oligofructose-enriched inulin supplemented diet (Pre group), during the second half of gestation and lactation. Bone mineral density (BMD) and content (BMC), as well as micro-structure of dams and offspring at different stages were analysed. Dams in the Pre group had significantly higher trabecular thickness (Tb.Th), trabecular bone volume fraction (BV/TV) and smaller specific bone surface (BS/BV) of the tibia in comparison with CC dams. The Pre group offspring during early adulthood had an increase of the lumbar vertebra BMD when compared with offspring of CC and Ca groups. The Pre group offspring also showed significant increase versus CC in cancellous and cortical structural parameters of the lumbar vertebra 4 such as Tb.Th, cortical BMD and decreased BS/BV. The results indicate that oligofructose-enriched inulin supplementation can be considered as a plausible nutritional option for protecting against maternal bone loss during gestation and lactation preventing bone fragility and for optimizing peak bone mass and architecture of the offspring in order to increase bone strength. PMID:27115490

Effect of bone chip orientation on quantitative estimates of changes in bone mass using digital subtraction radiography.

PubMed

Mol, André; Dunn, Stanley M

2003-06-01

To assess the effect of the orientation of arbitrarily shaped bone chips on the correlation between radiographic estimates of bone loss and true mineral loss using digital subtraction radiography. Twenty arbitrarily shaped bone chips (dry weight 1-10 mg) were placed individually on the superior lingual aspect of the interdental alveolar bone of a dry dentate hemi-mandible. After acquiring the first baseline image, each chip was rotated 90 degrees and a second radiograph was captured. Follow-up images were created without the bone chips and after rotating the mandible 0, 1, 2, 4, and 6 degrees around a vertical axis. Aluminum step tablet intensities were used to normalize image intensities for each image pair. Follow-up images were registered and geometrically standardized using projective standardization. Bone chips were dry ashed and analyzed for calcium content using atomic absorption. No significant difference was found between the radiographic estimates of bone loss from the different bone chip orientations (Wilcoxon: P > 0.05). The correlation between the two series of estimates for all rotations was 0.93 (Spearman: P < 0.05). Linear regression analysis indicated that both correlates did not differ appreciably ( and ). It is concluded that the spatial orientation of arbitrarily shaped bone chips does not have a significant impact on quantitative estimates of changes in bone mass in digital subtraction radiography. These results were obtained in the presence of irreversible projection errors of up to six degrees and after application of projective standardization for image reconstruction and image registration.

Osteoporosis in patients on long-term home parenteral nutrition: a longitudinal study.

PubMed

Cohen-Solal, M; Baudoin, C; Joly, F; Vahedi, K; D'Aoust, L; De Vernejoul, M C; Messing, B

2003-11-01

The prevalence of osteoporosis was investigated in 88 patients with intestinal failure (IF). Osteoporosis was found in 67%, dependent of body mass index and age when IF occurred. In 56 patients on HPN, followed prospectively, changes in bone density were dependent on the duration of HPN; older patients had a higher increase. It has been suggested that low bone mass and negative bone balance may occur in adult patients receiving home parenteral nutrition (HPN). The aim of this study was to assess prospectively the prevalence of osteoporosis in intestinal failure (IF) patients and the changes in bone mineral density in those on long-term HPN and to analyze the factors that may influence the occurrence and evolution of osteoporosis. Bone mineral density was measured at the lumbar spine and femoral neck in 88 IF patients. At the first bone mineral density determination (baseline), the prevalence of osteoporosis was 67% in this population (median age, 52 years). Ten percent of the patients with osteoporosis experienced fragility fractures. Osteoporosis was independent of age and gender but occurred earlier in patients who had received corticosteroids. At baseline, the lumbar Z-score was positively correlated mainly to body mass index and age when IF occurred; these two parameters explained 34% of the Z-score. Repeated measurements were performed in 56 patients during long-term HPN (mean duration, 5.5 +/- 1.2 years). The changes in Z-score at the lumbar spine were dependent on the age when IF occurred and on the duration of HPN, with a synergistic effect between them. The older the patients, the higher the increase in Z-score during HPN. HPN had no deleterious effect on cortical bone and actually improved trabecular bone in patients whose intestinal disease started after the age of 21 years.

Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton

PubMed Central

Rianon, Nahid; Rajagopal, Abbhirami; Munivez, Elda; Bertin, Terry; Dawson, Brian; Chen, Yuqing; Jiang, Ming-Ming; Lee, Brendan; Yang, Tao; Bae, Yangjin

2015-01-01

Angiotensin receptor blockers (ARBs) are a group of anti-hypertensive drugs that are widely used to treat pediatric hypertension. Recent application of ARBs to treat diseases such as Marfan syndrome or Alport syndrome has shown positive outcomes in animal and human studies, suggesting a broader therapeutic potential for this class of drugs. Multiple studies have reported a benefit of ARBs on adult bone homeostasis; however, its effect on the growing skeleton in children is unknown. We investigated the effect of Losartan, an ARB, in regulating bone mass and cartilage during development in mice. Wild type mice were treated with Losartan from birth until 6 weeks of age, after which bones were collected for microCT and histomorphometric analyses. Losartan increased trabecular bone volume vs. tissue volume (a 98% increase) and cortical thickness (a 9% increase) in 6-weeks old wild type mice. The bone changes were attributed to decreased osteoclastogenesis as demonstrated by reduced osteoclast number per bone surface in vivo and suppressed osteoclast differentiation in vitro. At the molecular level, Angiotensin II-induced ERK1/2 phosphorylation in RAW cells was attenuated by Losartan. Similarly, RANKL-induced ERK1/2 phosphorylation was suppressed by Losartan, suggesting a convergence of RANKL and angiotensin signaling at the level of ERK1/2 regulation. To assess the effect of Losartan on cartilage development, we examined the cartilage phenotype of wild type mice treated with Losartan in utero from conception to 1 day of age. Growth plates of these mice showed an elongated hypertrophic chondrocyte zone and increased Col10a1 expression level, with minimal changes in chondrocyte proliferation. Altogether, inhibition of the angiotensin pathway by Losartan increases bone mass and accelerates chondrocyte hypertrophy in growth plate during skeletal development. PMID:25779879

Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton.

PubMed

Chen, Shan; Grover, Monica; Sibai, Tarek; Black, Jennifer; Rianon, Nahid; Rajagopal, Abbhirami; Munivez, Elda; Bertin, Terry; Dawson, Brian; Chen, Yuqing; Jiang, Ming-Ming; Lee, Brendan; Yang, Tao; Bae, Yangjin

2015-05-01

Angiotensin receptor blockers (ARBs) are a group of anti-hypertensive drugs that are widely used to treat pediatric hypertension. Recent application of ARBs to treat diseases such as Marfan syndrome or Alport syndrome has shown positive outcomes in animal and human studies, suggesting a broader therapeutic potential for this class of drugs. Multiple studies have reported a benefit of ARBs on adult bone homeostasis; however, its effect on the growing skeleton in children is unknown. We investigated the effect of Losartan, an ARB, in regulating bone mass and cartilage during development in mice. Wild type mice were treated with Losartan from birth until 6 weeks of age, after which bones were collected for microCT and histomorphometric analyses. Losartan increased trabecular bone volume vs. tissue volume (a 98% increase) and cortical thickness (a 9% increase) in 6-weeks old wild type mice. The bone changes were attributed to decreased osteoclastogenesis as demonstrated by reduced osteoclast number per bone surface in vivo and suppressed osteoclast differentiation in vitro. At the molecular level, Angiotensin II-induced ERK1/2 phosphorylation in RAW cells was attenuated by Losartan. Similarly, RANKL-induced ERK1/2 phosphorylation was suppressed by Losartan, suggesting a convergence of RANKL and angiotensin signaling at the level of ERK1/2 regulation. To assess the effect of Losartan on cartilage development, we examined the cartilage phenotype of wild type mice treated with Losartan in utero from conception to 1 day of age. Growth plates of these mice showed an elongated hypertrophic chondrocyte zone and increased Col10a1 expression level, with minimal changes in chondrocyte proliferation. Altogether, inhibition of the angiotensin pathway by Losartan increases bone mass and accelerates chondrocyte hypertrophy in growth plate during skeletal development. Copyright © 2015 Elsevier Inc. All rights reserved.

Appendicular and whole body lean mass outcomes are associated with finite element analysis-derived bone strength at the distal radius and tibia in adults aged 40years and older.

PubMed

Gibbs, Jenna C; Giangregorio, Lora M; Wong, Andy K O; Josse, Robert G; Cheung, Angela M

2017-10-01

The purpose of this cross-sectional study was to determine how appendicular lean mass index (ALMI), and whole body lean (LMI) and fat mass indices (FMI) associate with estimated bone strength outcomes at the distal radius and tibia in adults aged 40 years and older. Dual energy X-ray absorptiometry (DXA) scans were performed to determine body composition, including whole body lean and fat mass, and appendicular lean mass. ALMI (appendicular lean mass/height 2 ), LMI (lean tissue mass/height 2 ) and FMI (fat mass/height 2 ) were calculated. High-resolution peripheral quantitative computed tomography (HRpQCT) scans were performed to assess bone structural properties at the distal radius and tibia. Using finite element analysis, failure load (N), stiffness (N/mm), ultimate stress (MPa), and cortical-to-trabecular load ratio were estimated from HRpQCT scans. The associations between body composition (ALMI, LMI, FMI) and estimated bone strength were examined using bivariate and multivariable linear regression analyses adjusting for age, sex, and other confounding variables. In 197 participants (127 women; mean±SD, age: 69.5±10.3y, body mass index: 27.95±4.95kg/m 2 , ALMI: 7.31±1.31kg/m 2 ), ALMI and LMI were significantly associated with failure load at the distal radius and tibia (explained 39%-48% of the variance) and remained significant after adjusting for confounding variables and multiple testing (R 2 =0.586-0.645, p<0.001). ALMI, LMI, and FMI did not have significant associations with ultimate stress in our multivariable models. FMI was significantly associated with cortical-to-trabecular load ratio at the distal radius and tibia (explained 6%-12% of the variance) and remained significant after adjusting for confounders and multiple testing (R 2 =0.208-0.243, p<0.001). FMI was no longer significantly associated with failure load after adjusting for confounders. These findings suggest that ALMI and LMI are important determinants of estimated bone strength, particularly failure load, at the distal radius and tibia, and may contribute to preservation of bone strength in middle-to-late adulthood. Copyright © 2017 Elsevier Inc. All rights reserved.

Changes in bone mineral density in response to 24 weeks of resistance training in college-age men and women.

PubMed

Almstedt, Hawley C; Canepa, Jacqueline A; Ramirez, David A; Shoepe, Todd C

2011-04-01

Osteoporosis is a chronic disease of major public health concern. Characterized by low bone mass and increasing risk for fracture, osteoporosis occurs to a greater extent in women. Resistance training is a mode of exercise that can be used to build peak bone mass during youth, thereby preventing osteoporosis later in life. Our aim was to evaluate the effectiveness of a resistance training protocol designed to apply loads to the hip and spine in men and women. We recruited recreationally active men (n = 12) and women (n = 12), ages of 18-23. An additional 10 participants (5 men, 5 women) served as controls. Volunteers completed questionnaires to assess health history, physical activity, dietary intake, and menstrual history. The training program was performed for 24 weeks, on 3 nonconsecutive days per week, including exercises for the upper, lower, and core musculature, marked by an undulating periodization varying between 67 and 95% of 1 repetition maximum (1RM) on the multijoint exercises of bench press, squats, and deadlifts. Dual energy X-ray absorptiometry (Hologic Explorer, Waltham, MA, USA) was used to assess bone mineral density (BMD, g · cm(-2)). A 2-tailed analysis of covariance, controlling for body mass index, revealed that in comparison to women, men had significantly greater increases in BMD at the lateral spine and femoral neck. Male exercisers were found to increase BMD by 2.7-7.7%, whereas percent change in women ranged from -0.8 to 1.5%, depending on the bone site. Both male and female controls demonstrated about 1% change at any bone site. Results indicate that 24 weeks of resistance training, including squat and deadlift exercises, is effective in increasing BMD in young healthy men. Similar benefits were not derived by women who followed the same protocol.

The Clinical and Biochemical Predictors of Bone Mass in Preterm Infants.

PubMed

Czech-Kowalska, Justyna; Czekuc-Kryskiewicz, Edyta; Pludowski, Pawel; Zaniuk, Katarzyna; Jaworski, Maciej; Łuba, Anna; Grzybowska, Karolina; Piłat, Krystyna; Dobrzanska, Anna

2016-01-01

Metabolic bone disease of prematurity still occurs in preterm infants, although a significant improvement in neonatal care has been observed in recent decades. Dual-energy X-ray absorptiometry (DXA) is the precise technique for assessing bone mineral content (BMC) in preterm infants, but is not widely available. To investigate the clinical and biochemical parameters, including bone metabolism markers as potential predictors of BMC, in preterm infants up to 3 months corrected age (CA). Ca-P homeostasis, iPTH, 25-hydroxyvitamin D, osteocalcin, N-terminal propeptide, cross-linked C-telopeptide and amino-terminal pro C-type natriuretic peptide and the DXA scans were prospectively performed in 184 preterm infants (≤ 34 weeks' gestation) between term age and 3 mo CA. Lower bone mass was defined as BMC below or equal to respective median value for the whole study group, rounded to the nearest whole number. The appropriate quality DXA scans were available for 160 infants (87%) examined at term and for 130 (71%) tested at 3 mo CA. Higher iPTH level was the only independent predictor of lower BMC at term, whereas lower BMC at 3 mo CA was associated both with lower urinary phosphate excretion and higher serum osteocalcin level. ROC analysis showed that iPTH >43.6 pg/mL provided 40% sensitivity and 88% specificity in identification of preterm infants with lower BMC at term. In turn, urinary phosphate excretion (TRP>97% or UP/Cr ≤0.74 mg/mg) and serum osteocalcin >172 ng/mL provided 40% sensitivity and 93% specificity in identification of infants with decreased BMC at 3 mo CA. Serum iPTH might to be a simple predictor of reduced BMC in preterm infants at term age, but urinary phosphate excretion and serum osteocalcin might predict reduced BMC at 3 mo CA. These results represent a promising diagnostic tool based on simple, widely available biochemical measurements for bone mass assessment in preterm infants.

The effect of whole-body vibration therapy on bone metabolism, motor function, and anthropometric parameters in women with postmenopausal osteoporosis.

PubMed

Luo, Xiaotian; Zhang, Jifeng; Zhang, Chi; He, Chengqi; Wang, Pu

2017-11-01

To review the research literature on the effectiveness of whole-body vibration (WBV) therapy in women with postmenopausal osteoporosis. A systematic review was conducted by two independent reviewers. Mean differences (MDs), standardized mean differences (SMDs), and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed with the I 2 test. The Cochrane risk of bias tool was used to assess the methodological quality of the selected studies. Nine randomized controlled trials involving 625 patients met the inclusion criteria. No significant improvement was found in bone mineral density (BMD) (SMD = -0.06, 95%CI= -0.22-0.11, p = 0.50); bone turnover markers (MD = -0.25, 95%CI= -0.54-0.03, p = 0.08); anthropometric parameters, including muscle mass, fat mass, body mass index (BMI), and weight (SMD = 0.02, 95%CI= -0.16-0.21, p = 0.81); or maximal isotonic knee extensor strength (SMD = 0.16, 95%CI= -0.63-0.95, p = 0.69). However, maximal isometric knee extensor strength improved (SMD = 0.71, 95%CI = 0.34-1.08, p = 0.0002). WBV is beneficial for enhancing maximal isometric knee extensor strength, but it has no overall treatment effect on BMD, bone turnover markers, anthropometric parameters, or maximal isotonic knee extensor strength in women with postmenopausal osteoporosis. Implication of rehabilitation Osteoporosis is the leading underlying cause of fractures in postmenopausal women, whole body vibration (WBV) has received much attention as a potential intervention for the management of osteoporosis in recent years. Whole body vibration is beneficial for enhancing maximal isometric knee extensor strength in women with postmenopausal osteoporosis. Whole body vibration has no overall treatment effect on bone mineral density, bone turnover markers, anthropometric parameters and maximal isotonic knee extensor strength in women with postmenopausal osteoporosis.

Using Natural Stable Calcium Isotopes to Rapidly Assess Changes in Bone Mineral Balance Using a Bed Rest Model to Induce Bone Loss

NASA Technical Reports Server (NTRS)

Morgan, J. L. L.; Skulan, J. L.; Gordon, G. E.; Smith, Scott M.; Romaniello, S. J.; Anbar, A. D.

2012-01-01

Metabolic bone diseases like osteoporosis result from the disruption of normal bone mineral balance (BMB) resulting in bone loss. During spaceflight astronauts lose substantial bone. Bed rest provides an analog to simulate some of the effects of spaceflight; including bone and calcium loss and provides the opportunity to evaluate new methods to monitor BMB in healthy individuals undergoing environmentally induced-bone loss. Previous research showed that natural variations in the Ca isotope ratio occur because bone formation depletes soft tissue of light Ca isotopes while bone resorption releases that isotopically light Ca back into soft tissue (Skulan et al, 2007). Using a bed rest model, we demonstrate that the Ca isotope ratio of urine shifts in a direction consistent with bone loss after just 7 days of bed rest, long before detectable changes in bone mineral density (BMD) occur. The Ca isotope variations tracks changes observed in urinary N-teleopeptide, a bone resorption biomarker. Bone specific alkaline phosphatase, a bone formation biomarker, is unchanged. The established relationship between Ca isotopes and BMB can be used to quantitatively translate the changes in the Ca isotope ratio to changes in BMD using a simple mathematical model. This model predicts that subjects lost 0.25 0.07% ( SD) of their bone mass from day 7 to day 30 of bed rest. Given the rapid signal observed using Ca isotope measurements and the potential to quantitatively assess bone loss; this technique is well suited to study the short-term dynamics of bone metabolism.

Assessment of the Breakaway Torque at the Posterior Pelvic Ring in Human Cadavers.

PubMed

Bastian, Johannes Dominik; Bergmann, Mathias; Schwyn, Ronald; Keel, Marius Johann Baptist; Benneker, Lorin Michael

2015-01-01

To enhance the diminished screw purchase in cancellous, osteoporotic bone following the fixation of posterior pelvic ring injuries by iliosacral screws an increased bone-implant contact area using modificated screws, techniques or bone cement may become necessary. The aim of the study was to identify sites within the pathway of iliosacral screws requiring modifications of the local bone or the design of instrumentations placed at this site. The breakaway torque was measured mechanically at the iliosacral joint ("ISJ"), the sacral lateral mass ("SLM") and the center of the S1 ("CS1"), at a superior and an inferior site under fluoroscopic control on five human cadaveric specimens (3 female; mean age 87 years, range: 76-99) using the DensiProbe™Spine device. The measured median (range) breakaway torque was 0.63 Nm (0.31-2.52) at the "iliosacral joint", 0.14 Nm (0.05-1.22) at the "sacral lateral mass", 0.57 Nm (0.05-1.42) at the "S1 center." The "sacral lateral mass" breakaway torque was lower than compared to that at the "iliosacral joint" (p < .001) or "S1 center" (p < .001). The median (range) breakaway torque measured at all superior measurement points was 0.52 Nm (0.10-2.52), and 0.48 Nm (0.05-1.18) at all inferior sites. The observed difference was statistically significant (p < .05). The lateral mass of the sacrum provides the lowest bone quality for implant anchorage. Iliosacral screws should be placed as superior as safely possible, should bridge the iliosacral joint and may allow for cement application at the lateral mass of the sacrum through perforations.

Factors that influence bone mass of healthy children and adolescents measured by quantitative ultrasound at the hand phalanges: a systematic review☆

PubMed Central

Krahenbühl, Tathyane; Gonçalves, Ezequiel Moreira; Costa, Eduardo Tavares; Barros, Antonio de Azevedo

2014-01-01

Objective: To analyze the main factors that influence bone mass in children and teenagers assessed by quantitative ultrasound (QUS) of the phalanges. Data source: A systematic literature review was performed according to the PRISMA method with searches in databases Pubmed/Medline, SciELO and Bireme for the period 2001-2012, in English and Portuguese languages, using the keywords: children, teenagers, adolescent, ultrasound finger phalanges, quantitative ultrasound of phalanges, phalangeal quantitative ultrasound. Data synthesis: 21 articles were included. Girls had, in QUS, Amplitude Dependent Speed of Sound (AD-SoS) values higher than boys during pubertal development. The values of the parameters of QUS of the phalanges and dual-energy X-ray Absorptiometry (DXA) increased with the increase of the maturational stage. Anthropometric variables such as age, weight, height, body mass index (BMI), lean mass showed positive correlations with the values of QUS of the phalanges. Physical activity has also been shown to be positively associated with increased bone mass. Factors such as ethnicity, genetics, caloric intake and socioeconomic profile have not yet shown a conclusive relationship and need a larger number of studies. Conclusions: QUS of the phalanges is a method used to evaluate the progressive acquisition of bone mass during growth and maturation of individuals in school phase, by monitoring changes that occur with increasing age and pubertal stage. There were mainly positive influences variables of sex, maturity, height, weight and BMI, with similar data when compared to the gold standard method, the DXA. PMID:25479860

Quantification of Cyclic Ground Reaction Force Histories During Daily Activity in Humans

NASA Technical Reports Server (NTRS)

Breit, G. A.; Whalen, R. T.; Wade, Charles E. (Technical Monitor)

1994-01-01

Theoretical models and experimental studies of bone remodeling suggest that bone density and structure are influenced by local cyclic skeletal tissue stress and strain histories. Estimation of long-term loading histories in humans is usually achieved by assessment of physical activity level by questionnaires, logbooks, and pedometers, since the majority of lower limb cyclic loading occurs during walking and running. These methods provide some indication of the mechanical loading history, but fail to consider the true magnitude of the lower limb skeletal forces generated by various daily activities. These techniques cannot account for individual gait characteristics, gait speed, and unpredictable high loading events that may influence bone mass significantly. We have developed portable instrumentation to measure and record the vertical component of the ground reaction force (GRFz) during normal daily activity. This equipment allows long-term quantitative monitoring of musculoskeletal loads, which in conjunction with bone mineral density assessments, promises to elucidate the relationship between skeletal stresses and bone remodeling.

Adherence to the gluten-free diet can achieve the therapeutic goals in almost all patients with coeliac disease: A 5-year longitudinal study from diagnosis.

PubMed

Newnham, Evan D; Shepherd, Susan J; Strauss, Boyd J; Hosking, Patrick; Gibson, Peter R

2016-02-01

Key aims of treatment of coeliac disease are to heal the intestinal mucosa and correct nutritional abnormalities. We aim to determine prospectively the degree of success and time course of achieving those goals with a gluten-free diet. Ninety-nine patients were enrolled at diagnosis and taught the diet. The first 52 were reassessed at 1 year and 46 at 5 years, 25 being assessed at the three time points regarding dietary compliance (dietitian-assessed), coeliac serology, bone mineral density and body composition analysis by dual energy X-ray absorptiometry, and intestinal histology. Mean age (range) was 40 (18-71) years and 48 (76%) were female. Dietary compliance was very good to excellent in all but one. Tissue transglutaminase IgA was persistently elevated in 44% at 1 year and 30% at 5 years and were poorly predictive of mucosal disease. Rates of mucosal remission (Marsh 0) and response (Marsh 0/1) were 37% and 54%, and 50% and 85% at 1 and 5 years, respectively. Fat mass increased significantly over the first year in those with normal/reduced body mass index. Lean body mass indices more slowly improved irrespective of status at diagnosis with significant improvement at 5 years. Bone mass increased only in those with osteopenia or osteoporosis, mostly in year 1. Dietary compliance is associated with a high chance of healing the intestinal lesion and correction of specific body compositional abnormalities. The time course differed with body fat improving within 1 year, and correction of the mucosal lesion and improvement in lean mass and bone mass taking longer. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Bone health in cerebral palsy and introduction of a novel therapy

PubMed Central

Scheinberg, Morton Aaron; Golmia, Ricardo Prado; Sallum, Adriana Maluf Elias; Pippa, Maria Guadalupe Barbosa; Cortada, Aline Pinheiros dos Santos; da Silva, Telma Gomes

2015-01-01

ABSTRACT Objective To assess the bone health status of children with cerebral palsy and the therapeutic effect of denosumab in a subgroup of children with cerebral palsy and decreased bone mass. Methods Children with cerebral palsy were evaluated according to their motor disability score (classification system gross motor functions III to V), bone density and bone turnover markers. Dual X-ray energy absorption was used to measure the lumbar spine, and total body, except the head. Thereafter a group of children with cerebral palsy and osteoporosis was treated with denosumab, a fully human monoclonal antibody. Bone turnover markers were measured before and three months after treatment. Results Reduction in bone mineral density was observed, particularly in children with greater impairment evaluated by the motor score. Decreased bone turnover markers were found in a selected group of children three months after exposure to denosumab. Conclusion Bone loss was present in children with significant impairment of motor function, as well as decreased serum levels of bone resorption markers with new forms. PMID:26761553

Single- and dual-photon absorptiometry in osteoporosis and osteomalacia

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

Wahner, H.W.

Single- and dual-photon absorptiometric methods have been used in the past to identify populations at risk for bone loss, to define the osteoporotic syndrome in terms of bone mass, and to evaluate treatment regimens to prevent bone loss. Technical improvements have made these procedures available for the nontraumatic measurement of bone mineral in the management of the individual patient suspected of having osteoporosis or other bone loss. This requires a different approach to data interpretation because decisions have to be made on the basis of a single measurement. Osteoporosis and osteomalacia cannot be distinguished by bone mineral measurements because bothmore » are characterized by a decrease in content of bone mineral. Bone mineral measurements can be used to assess the risk of fracture and, with it, the severity of bone loss. This allows treatment decisions to be made. Repeated measurements made under well-defined conditions allow estimation of long-term rate of bone loss and monitoring of treatment effect. 38 references.« less

Mice Drawer System

NASA Technical Reports Server (NTRS)

Cancedda, Ranieri

2008-01-01

The Mice Drawer System (MDS) is an Italian Space Agency (ASI) facility which is able to support mice onboard the International Space Station during long-duration exploration missions (from 100 to 150-days) by living space, food, water, ventilation and lighting. Mice can be accommodated either individually (maximum 6) or in groups (4 pairs). MDS is integrated in the Space Shuttle middeck during transportation (uploading and downloading) to the ISS and in an EXPRESS Rack in Destiny, the US Laboratory during experiment execution. Osteoporosis is a debilitating disease that afflicts millions of people worldwide. One of the physiological changes experienced by astronauts during space flight is the accelerated loss of bone mass due to the lack of gravitational loading on the skeleton. This bone loss experienced by astronauts is similar to osteoporosis in the elderly population. MDS will help investigate the effects of unloading on transgenic (foreign gene that has been inserted into its genome to exhibit a particular trait) mice with the Osteoblast Stimulating Factor-1, OSF-1, a growth and differentiation factor, and to study the genetic mechanisms underlying the bone mass pathophysiology. MDS will test the hypothesis that mice with an increased bone density are likely to be more protected from osteoporosis, when the increased bone mass is a direct effect of a gene involved in skeletogenesis (skeleton formation). Osteoporosis is a debilitating disease that afflicts millions worldwide. One of the physiological changes experienced by astronauts during space flight is the accelerated loss of bone mass due to the lack of gravitational loading on the skeleton, a loss that is similar to osteoporosis in the elderly population on Earth. Osteoblast Stimulating Factor-1 (OSF-1), also known as pleiotrophin (PTN) or Heparin-Binding Growth- Associated Molecule (HB-GAM) belongs to a family of secreted heparin binding proteins..OSF-1 is an extracellular matrix-associated growth and differentiation factor that is normally expressed in cartilage; it can stimulate the proliferation and differentiation of human osteoprogenitor cells (cell that differentiate into an osteoblast) in vitro. The Mice Drawer System will study the effects of microgravity on transgenic mouse bones in order to identify genetic mechanisms playing a role in the reduction of the bone mass observed in humans and animals as a consequence of long-duration (greater than 100 days) microgravity exposure. Onboard the ISS, MDS is relatively self-sufficient; a crewmember will check the health status of the rodents on a daily basis, by assessing them through the viewing window. Water levels will be assessed by the crew daily and refilled as needed. Replacement of the food bars and replacement of the waste filters will be conducted inflight by crewmembers every 20-days.

Early-onset type 2 diabetes impairs skeletal acquisition in the male TALLYHO/JngJ mouse.

PubMed

Devlin, M J; Van Vliet, M; Motyl, K; Karim, L; Brooks, D J; Louis, L; Conlon, C; Rosen, C J; Bouxsein, M L

2014-10-01

Type 2 diabetes (T2D) incidence in adolescents is rising and may interfere with peak bone mass acquisition. We tested the effects of early-onset T2D on bone mass, microarchitecture, and strength in the TALLYHO/JngJ mouse, which develops T2D by 8 weeks of age. We assessed metabolism and skeletal acquisition in male TALLYHO/JngJ and SWR/J controls (n = 8-10/group) from 4 weeks to 8 and 17 weeks of age. Tallyho mice were obese; had an approximately 2-fold higher leptin and percentage body fat; and had lower bone mineral density vs SWR at all time points (P < .03 for all). Tallyho had severe deficits in distal femur trabecular bone volume fraction (-54%), trabecular number (-27%), and connectivity density (-82%) (P < .01 for all). Bone formation was higher in Tallyho mice at 8 weeks but lower by 17 weeks of age vs SWR despite similar numbers of osteoblasts. Bone marrow adiposity was 7- to 50-fold higher in Tallyho vs SWR. In vitro, primary bone marrow stromal cell differentiation into osteoblast and adipocyte lineages was similar in SWR and Tallyho, suggesting skeletal deficits were not due to intrinsic defects in Tallyho bone-forming cells. These data suggest the Tallyho mouse might be a useful model to study the skeletal effects of adolescent T2D.

High Serum Retinol as a Relevant Contributor to Low Bone Mineral Density in Postmenopausal Osteoporotic Women.

PubMed

Navarro-Valverde, Cristina; Caballero-Villarraso, Javier; Mata-Granados, José M; Casado-Díaz, Antonio; Sosa-Henríquez, Manuel; Malouf-Sierra, Jorge; Nogués-Solán, Xavier; Rodríguez-Mañas, Leocadio; Cortés-Gil, Xavier; Delgadillo-Duarte, Joaquín; Quesada-Gómez, José Manuel

2018-06-01

There is controversial information about the impact of vitamin A on bone. Some epidemiological studies show that excessive intake of vitamin A, or an excess of serum vitamin A, has related with adverse impact on bone mass; however, other studies did not find these links, and some authors have proposed that this vitamin might promote a better bone health. The present work aims to contribute to clarify the real role of vitamin A in bone tissue. For this purpose, a cross-sectional study of 154 osteoporotic non-treated postmenopausal women (> 65 years old) was carried out. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. We assessed concentrations of serum retinol, osteocalcin, parathyroid hormone, alkaline phosphatase, calcium, and phosphorus. We also studied demographic and anthropometric parameters. Spearman's correlations between retinol levels and other variables found negative correlations with BMD in both lumbar spine (R = - 0.162, P < 0.01) and femoral neck (R = - 0.182, P < 0.01), as well as alkaline phosphatase (R = - 0.110; P < 0.05) and phosphorus (R = - 0.110; P < 0.05). A positive correlation between retinol and fertile window was observed (R = 0.158; P < 0.01). After multivariable adjustment, we still found a negative correlation between serum retinol and BMD, both at the lumbar spine (R = - 0.210; P < 0.01) and at the femoral neck (R = - 0.324, P < 0.001). It is concluded that elevated serum-retinol levels are associated with an increased risk of low bone mass and thus with osteoporotic fractures. Therefore, osteoporosis-risk assessment should include quantification of serum metabolite of vitamin A.

High-Dose α-Tocopherol Supplementation Does Not Induce Bone Loss in Normal Rats

PubMed Central

Kasai, Shunji; Ito, Akemi; Shindo, Kaori; Toyoshi, Tohru; Bando, Masahiro

2015-01-01

Oxidative stress affects bone turnover. Preventative effects of antioxidants such as vitamin E on reduced bone mineral density and fractures associated with aging, osteoporosis, and smoking have been examined in animals and humans. The effects of vitamin E (α-tocopherol; αT) on bone health have yielded conflicting and inconclusive results from animal studies. In this study, to determine the bone effects of αT, we investigated the in vivo effects of αT on the bone mineral density, bone mass, bone microstructure, bone resorption, and osteogenesis through peripheral quantitative computed tomography (pQCT) measurements, micro-computed tomography (micro-CT) analyses, and bone histomorphometry of lumbar vertebrae and femurs in normal female Wistar rats fed diets containing αT in different quantities (0, 30, 120, or 600 mg/kg diet) for 8 weeks. To validate our hypotheses regarding bone changes, we examined ovariectomized rats as an osteoporosis model and control sham-operated rats in parallel. As expected, ovariectomized rats had reduced bone mineral density in lumbar vertebrae and the distal metaphyses of their femurs, reduced bone mass and deteriorated microstructure of cancellous bones in the vertebral body and distal femur metaphyses, and reduced bone mass due to resorption-dominant enhanced bone turnover in secondary cancellous bones in these sites. In comparison, αT administered to normal rats, even at the highest dose, did not induce reduced bone mineral density of lumbar vertebrae and femurs or a reduced bone mass or fragile microstructure of cancellous bones of the vertebral body and distal femur metaphyses. Instead, αT-fed rats showed a tendency for an osteogenesis-dominant bone mass increase in secondary cancellous bones in the vertebral body, in which active bone remodeling occurs. Thus, αT consumption may have beneficial effects on bone health. PMID:26147575

Strontium enhances osseointegration of calcium phosphate cement: a histomorphometric pilot study in ovariectomized rats.

PubMed

Baier, Martin; Staudt, Patric; Klein, Roman; Sommer, Ulrike; Wenz, Robert; Grafe, Ingo; Meeder, Peter Jürgen; Nawroth, Peter P; Kasperk, Christian

2013-06-07

Calcium phosphate cements are used frequently in orthopedic and dental surgeries. Strontium-containing drugs serve as systemic osteoblast-activating medication in various clinical settings promoting mechanical stability of the osteoporotic bone. Strontium-containing calcium phosphate cement (SPC) and calcium phosphate cement (CPC) were compared regarding their local and systemic effects on bone tissue in a standard animal model for osteoporotic bone. A bone defect was created in the distal femoral metaphysis of 60 ovariectomized Sprague-Dawley rats. CPC and SPC were used to fill the defects in 30 rats in each group. Local effects were assessed by histomorphometry at the implant site. Systemic effects were assessed by bone mineral density (BMD) measurements at the contralateral femur and the spine. Faster osseointegration and more new bone formation were found for SPC as compared to CPC implant sites. SPC implants exhibited more cracks than CPC implants, allowing more bone formation within the implant. Contralateral femur BMD and spine BMD did not differ significantly between the groups. The addition of strontium to calcium phosphate stimulates bone formation in and around the implant. Systemic release of strontium from the SPC implants did not lead to sufficiently high serum strontium levels to induce significant systemic effects on bone mass in this rat model.

Body composition, adipokines, bone mineral density and bone remodeling markers in relation to IGF-1 levels in adults with Prader-Willi syndrome.

PubMed

van Nieuwpoort, I Caroline; Twisk, Jos W R; Curfs, Leopold M G; Lips, Paul; Drent, Madeleine L

2018-01-01

In patients with Prader-Willi syndrome (PWS) body composition is abnormal and alterations in appetite regulating factors, bone mineral density and insulin-like growth factor-1 (IGF-1) levels have been described. Studies in PWS adults are limited. In this study, we investigated body composition, appetite regulating peptides, bone mineral density and markers of bone remodeling in an adult PWS population. Furthermore, we investigated the association between these different parameters and IGF-1 levels because of the described similarities with growth hormone deficient patients. In this cross-sectional observational cohort study in a university hospital setting we studied fifteen adult PWS patients. Anthropometric and metabolic parameters, IGF-1 levels, bone mineral density and bone metabolism were evaluated. The homeostasis model assessment of insulin resistance (HOMA2-IR) was calculated. Fourteen healthy siblings served as a control group for part of the measurements. In the adult PWS patients, height, fat free mass, IGF-1 and bone mineral content were significantly lower when compared to controls; body mass index (BMI), waist, waist-to-hip ratio and fat mass were higher. There was a high prevalence of osteopenia and osteoporosis in the PWS patients. Also, appetite regulating peptides and bone remodelling markers were aberrant when compared to reference values. Measurements of body composition were significantly correlated to appetite regulating peptides and high-sensitive C-reactive protein (hs-CRP), furthermore HOMA was correlated to BMI and adipokines. In adults with Prader-Willi syndrome alterations in body composition, adipokines, hs-CRP and bone mineral density were demonstrated but these were not associated with IGF-1 levels. Further investigations are warranted to gain more insight into the exact pathophysiology and the role of these alterations in the metabolic and cardiovascular complications seen in PWS, so these complications can be prevented or treated as early as possible.

Dietary patterns associated with fat and bone mass in young children123

PubMed Central

Khoury, Philip R; Claytor, Randal P; Copeland, Kristen A; Hornung, Richard W; Daniels, Stephen R; Kalkwarf, Heidi J

2010-01-01

Background: Obesity and osteoporosis have origins in childhood, and both are affected by dietary intake and physical activity. However, there is little information on what constitutes a diet that simultaneously promotes low fat mass and high bone mass accrual early in life. Objective: Our objective was to identify dietary patterns related to fat and bone mass in children during the age period of 3.8–7.8 y. Design: A total of 325 children contributed data from 13 visits over 4 separate study years (age ranges: 3.8–4.8, >4.8–5.8, >5.8–6.8, and >6.8–7.8 y). We performed reduced-rank regression to identify dietary patterns related to fat mass and bone mass measured by dual-energy X-ray absorptiometry for each study year. Covariables included race, sex, height, weight, energy intake, calcium intake, physical activity measured by accelerometry, and time spent viewing television and playing outdoors. Results: A dietary pattern characterized by a high intake of dark-green and deep-yellow vegetables was related to low fat mass and high bone mass; high processed-meat intake was related to high bone mass; and high fried-food intake was related to high fat mass. Dietary pattern scores remained related to fat mass and bone mass after all covariables were controlled for (P < 0.001–0.03). Conclusion: Beginning at preschool age, diets rich in dark-green and deep-yellow vegetables and low in fried foods may lead to healthy fat and bone mass accrual in young children. PMID:20519562

Changes in osteocyte density correspond with changes in osteoblast and osteoclast activity in an osteoporotic sheep model.

PubMed

Zarrinkalam, M R; Mulaibrahimovic, A; Atkins, G J; Moore, R J

2012-04-01

Histomorphometric assessment of trabecular bone in osteoporotic sheep showed that bone volume, osteoid surface area, bone formation rate, and osteocyte density were reduced. In contrast, eroded surface area and empty lacunae density were increased. Changes in osteocyte density correlated with changes in osteoblast and osteoclast activity. Osteocytes contribute to the regulation of the activity of osteoclasts and osteoblasts that together control bone mass. Osteocytes therefore likely play a role in the loss of bone mass associated with osteoporosis. The purpose of this study was to investigate the relationships between osteocyte lacunar density and other bone histomorphometric parameters in the iliac crest (IC) and lumbar spine (LS) of osteoporotic sheep. Osteoporosis was induced in ten mature ewes by an established protocol involving a combination of ovariectomy, dexamethasone injection, and low calcium diet for 6 months. Five ewes were used as controls. Post-mortem IC and LS biopsies were collected and processed for further histomorphometric assessment. Bone volume, osteoid surface, and bone formation rate in the IC and LS of osteoporotic sheep were reduced compared to those of the controls. In contrast, eroded surface area was increased in osteoporotic sheep. In the osteoporotic group, osteocyte density was reduced in the LS region and to a greater extent in the IC region. The empty osteocyte lacunae were increased 1.7-fold in LS and 2.1-fold in IC in the osteoporotic group. The osteocyte density correlated positively with markers of osteoblast activity and negatively with those of osteoclast activity. Depletion of osteocytes and an increase in the empty lacunae could be important factors contributing to bone loss in this model since they may adversely affect intercellular communication between osteoblasts and osteoclasts. The regional differences in histology suggest that there may be different pathological mechanisms operating at different anatomical sites.

The Relationship of Fat Distribution and Insulin Resistance with Lumbar Spine Bone Mass in Women

PubMed Central

de Paula, Francisco J. A.; de Araújo, Iana M.; Carvalho, Adriana L.; Elias, Jorge; Salmon, Carlos E. G.; Nogueira-Barbosa, Marcello H.

2015-01-01

Bone marrow harbors a significant amount of body adipose tissue (BMAT). While BMAT might be a source of energy for bone modeling and remodeling, its increment can also represent impairment of osteoblast differentiation. The relationship between BMAT, bone mass and insulin sensitivity is only partially understood and seems to depend on the circumstances. The present study was designed to assess the association of BMAT with bone mineral density in the lumbar spine as well as with visceral adipose tissue, intrahepatic lipids, HOMA-IR, and serum levels of insulin and glucose. This cross-sectional clinical investigation included 31 non-diabetic women, but 11 had a pre-diabetes status. Dual X-ray energy absorptiometry was used to measure bone mineral density and magnetic resonance imaging was used to assess fat deposition in BMAT, visceral adipose tissue and liver. Our results suggest that in non-diabetic, there is an inverse relationship between bone mineral density in lumbar spine and BMAT and a trend persists after adjustment for weight, age, BMI and height. While there is a positive association between visceral adipose tissue and intrahepatic lipids with serum insulin levels, there is no association between BMAT and serum levels of insulin. Conversely, a positive relationship was observed between BMAT and serum glucose levels, whereas this association was not observed with other fat deposits. These relationships did not apply after adjustment for body weight, BMI, height and age. The present study shows that in a group of predominantly non-obese women the association between insulin resistance and BMAT is not an early event, as occurs with visceral adipose tissue and intrahepatic lipids. On the other hand, BMAT has a negative relationship with bone mineral density. Taken together, the results support the view that bone has a complex and non-linear relationship with energy metabolism. PMID:26067489

The Relationship of Fat Distribution and Insulin Resistance with Lumbar Spine Bone Mass in Women.

PubMed

de Paula, Francisco J A; de Araújo, Iana M; Carvalho, Adriana L; Elias, Jorge; Salmon, Carlos E G; Nogueira-Barbosa, Marcello H

2015-01-01

Bone marrow harbors a significant amount of body adipose tissue (BMAT). While BMAT might be a source of energy for bone modeling and remodeling, its increment can also represent impairment of osteoblast differentiation. The relationship between BMAT, bone mass and insulin sensitivity is only partially understood and seems to depend on the circumstances. The present study was designed to assess the association of BMAT with bone mineral density in the lumbar spine as well as with visceral adipose tissue, intrahepatic lipids, HOMA-IR, and serum levels of insulin and glucose. This cross-sectional clinical investigation included 31 non-diabetic women, but 11 had a pre-diabetes status. Dual X-ray energy absorptiometry was used to measure bone mineral density and magnetic resonance imaging was used to assess fat deposition in BMAT, visceral adipose tissue and liver. Our results suggest that in non-diabetic, there is an inverse relationship between bone mineral density in lumbar spine and BMAT and a trend persists after adjustment for weight, age, BMI and height. While there is a positive association between visceral adipose tissue and intrahepatic lipids with serum insulin levels, there is no association between BMAT and serum levels of insulin. Conversely, a positive relationship was observed between BMAT and serum glucose levels, whereas this association was not observed with other fat deposits. These relationships did not apply after adjustment for body weight, BMI, height and age. The present study shows that in a group of predominantly non-obese women the association between insulin resistance and BMAT is not an early event, as occurs with visceral adipose tissue and intrahepatic lipids. On the other hand, BMAT has a negative relationship with bone mineral density. Taken together, the results support the view that bone has a complex and non-linear relationship with energy metabolism.

In healthy elderly postmenopausal women variations in BMD and BMC at various skeletal sites are associated with differences in weight and lean body mass rather than by variations in habitual physical activity, strength or VO2max.

PubMed

Schöffl, I; Kemmler, W; Kladny, B; Vonstengel, S; Kalender, W A; Engelke, K

2008-01-01

The objective of this study was an integrated cross-sectional investigation for answering the question whether differences in bone mineral density in elderly postmenopausal women are associated with differences in habitual physical activity and unspecific exercise levels. Two hundred and ninety nine elderly women (69-/+3 years), without diseases or medication affecting bone metabolism were investigated. The influence of weight, body composition and physical activity on BMD was measured at multiple sites using different techniques (DXA, QCT, and QUS). Physical activity and exercise level were assessed by questionnaire, maximum strength of the legs and aerobic capacity. Variations in physical activity or habitual exercise had no effect on bone. The only significant univariate relation between strength/VO(2)max and BMD/BMC that remained after adjusting for confounding variables was between arm BMD (DXA) and hand-grip strength. The most important variable for explaining BMD was weight and for cortical BMC of the femur (QCT) lean body mass. Weight and lean body mass emerge as predominant predictors of BMD in normal elderly women, whereas the isolated effect of habitual physical activity, unspecific exercise participation, and muscle strength on bone parameters is negligible. Thus, an increase in the amount of habitual physical activity will probably have no beneficial impact on bone.

The effect of a short-term delay of puberty on trabecular bone mass and structure in female rats: A texture-based and histomorphometric analysis.

PubMed Central

Yingling, Vanessa R; Xiang, Yongqing; Raphan, Theodore; Schaffler, Mitchell; Koser, Karen; Malique, Rumena

2007-01-01

Accrual of bone mass and strength during development is imperative in order to reduce the risk of fracture later in life. Although delayed pubertal onset is associated with an increased incidence of stress fracture, evidence supports the concept of “catch up” growth. It remains unclear if deficits in bone mass associated with delayed puberty have long term effects on trabecular bone structure and strength. The purpose of this study was to use texture-based analysis and histomorphometry to investigate the effect of a delay in puberty on trabecular bone mass and structure immediately post-puberty and at maturity in female rats. Forty-eight female Sprague Dawley rats (25 days) were randomly assigned to one of four groups; 1) short-term control (C-ST), 2) long-term control (C-LT), 3) short-term GnRH antagonist (G-ST) and 4) long-term GnRH antagonist (G-LT). Injections of either saline or gonadotropin-releasing hormone antagonist (GnRH-a) (100 μg/day) (Cetrotide™, Serono, Inc) were given intraperitoneally for 18 days (day 35–42) to both ST and LT. The ST groups were sacrificed after the last injection (day 43) and the LT groups at 6 months of age. Pubertal and gonadal development was retarded by the GnRA antagonist injections as indicated by a delay in vaginal opening, lower ovarian and uterine weights and suppressed estradiol levels in the short-term experimental animals (G-ST). Delayed puberty caused a transient reduction in trabecular bone area as assessed by histomorphometry. Specifically, the significant deficit in bone area resulted from a decreased number of trabecula and an increase in trabecular separation. Texture analysis, a new method to assess bone density and structural anisotropy, correlated well with the standard histomorphometry and measured significant deficits in the density measure (MDensity) in the G-ST group that remained at maturity (6 months). The texture energy deficit in the G-ST group was primarily in the 0° orientation (−13.2 %), which measures the longitudinal trabeculae in the proximal tibia. However, the deficit in the G-LT group was in the 45° and 135° orientations. These results suggest that any “catch-up” growth following the cessation of the GnRH-antagonist injection protocol may be directed in trabeculae oriented perpendicular to 0° at the expense of trabeculae in other orientations. PMID:16979963

Early diet and peak bone mass: 20 year follow-up of a randomized trial of early diet in infants born preterm.

PubMed

Fewtrell, Mary S; Williams, Jane E; Singhal, Atul; Murgatroyd, Peter R; Fuller, Nigel; Lucas, Alan

2009-07-01

Preterm infants are at risk of metabolic bone disease due to inadequate mineral intake with unknown consequences for later bone health. To test the hypotheses that (1) early diet programs peak bone mass and bone turnover; (2) human milk has a beneficial effect on these outcomes; (3) preterm subjects have reduced peak bone mass compared to population reference data. 20 year follow-up of 202 subjects (43% male; 24% of survivors) who were born preterm and randomized to: (i) preterm formula versus banked breast milk or (ii) preterm versus term formula; as sole diet or supplement to maternal milk. Outcome measures were (i) anthropometry; (ii) hip, lumbar spine (LS) and whole body (WB) bone mineral content (BMC) and bone area (BA) measured using DXA; (iii) bone turnover markers. Infant dietary randomization group did not influence peak bone mass or turnover. The proportion of human milk in the diet was significantly positively associated with WBBA and BMC. Subjects receiving >90% human milk had significantly higher WBBA (by 3.5%, p=0.01) and BMC (by 4.8%, p=0.03) than those receiving <10%. Compared to population data, subjects had significantly lower height SDS (-0.41 (SD 1.05)), higher BMI SDS (0.31 (1.33)) and lower LSBMD SDS (-0.29 (1.16)); height and bone mass deficits were greatest in those born SGA with birthweight <1250 g (height SDS -0.81 (0.95), LSBMD SDS -0.61 (1.3)). Infant dietary randomization group did not affect peak bone mass or turnover suggesting the observed reduced final height and LS bone mass, most marked in growth restricted subjects with the lowest birthweight, may not be related to sub-optimal early nutrition. The higher WB bone mass associated with human milk intake, despite its low nutrient content, may reflect non-nutritive factors in breast milk. These findings may have implications for later osteoporosis risk and require further investigation.

[Analysis of elderly outpatients in relation to nutritional status, sarcopenia, renal function, and bone density].

PubMed

Salmaso, Franciany Viana; Vigário, Patrícia dos Santos; Mendonça, Laura Maria Carvalho de; Madeira, Miguel; Vieira Netto, Leonardo; Guimarães, Marcela Rodrigues Moreira; Farias, Maria Lucia Fleiuss de

2014-04-01

To evaluate relationships between nutritional status, sarcopenia and osteoporosis in older women. We studied 44 women, 67-94 years, by mini-nutritional assessment (MAN), glomerular filtration corr. 1.73 m(2), body mass index (BMI), arm circumference and calf (CP and CB), bone mineral density and body composition, DXA (fat mass MG; lean MM). We gauge sarcopenia: IMM MM = MSS + MIS/height(2). We used the Pearson correlation coefficient, p < 0.05 as significant. MNA and IMM were positively correlated with BMI, CP, CB and MG. Age influenced negatively FG corr., BMI, FM, IMM and CP. Fourteen had a history of osteoporotic fractures. The lowest T-score was directly related to MAN and MG. CONCLUSIONS The aging caused the decline of FG, fat mass and muscle; the calf circumference, and brachial reflected nutritional status and body composition; and major influences on BMD were nutritional status and fat mass.

Differential Effects of Dietary Fat Content and Protein Source on Bone Phenotype and Fatty Acid Oxidation in Female C57Bl/6 Mice

PubMed Central

Sawin, Emily A.; Stroup, Bridget M.; Murali, Sangita G.; O’Neill, Lucas M.; Ntambi, James M.

2016-01-01

Background Glycomacropeptide (GMP) is a 64-amino acid glycophosphopeptide released from κ-casein during cheesemaking that promotes satiety, reduces body fat, increases bone mass and infers prebiotic and anti-inflammatory effects. The impact of adiposity and gender on bone health is unclear. Objective To determine how feeding female mice diets providing 60% Fat Kcal (high-fat) or 13% Fat Kcal (control) with either GMP or casein as the protein source impacts: body composition, ex vivo fatty acid oxidation, bone (femoral) biomechanical performance, and the relationship between body composition and bone. Methods Weanling female C57Bl/6 mice were fed high-fat (60% Fat Kcal) or control diets (13% Fat Kcal) with GMP or casein from 3 to 32 weeks of age with assessment of body weight and food intake. Body composition was assessed by dual-energy X-ray absorptiometry (DXA). Fatty acid oxidation was measured in liver, muscle, and fat tissues using 14C-palmitate. Plasma concentrations of hormones and cytokines were determined. Bone biomechanical performance was assessed by the 3-point bending test. Results Female mice fed high-fat diets showed increased fatty acid oxidation capacity in both gastrocnemius muscle and brown adipose tissue compared to mice fed the control diets with a lower fat content. Despite increased fat mass in mice fed the high-fat diets, there was little evidence of glucose impairment or inflammation. Mice fed the high-fat diets had significantly greater total body bone mineral density (BMD), femoral BMD, and femoral cross-sectional area than mice fed the control diets. Femora of mice fed the high-fat diets had increased yield load and maximum load before fracture, consistent with greater bone strength, but reduced post-yield displacement or ductility, consistent with bone brittleness. Female mice fed a high-fat GMP diet displayed increased fat oxidation capacity in subcutaneous fat relative to mice fed the high-fat casein diet. Regardless of dietary fat content, GMP increased total body bone mineral content and femur length. The prebiotic properties of GMP may mediate the beneficial effects of GMP on bone. Conclusions Female mice adapt to high-fat feeding by increasing oxidative capacity in muscle tissue and to a lesser extent brown adipose tissue. High-fat feeding in female mice leads to development of a bone phenotype where femora show increased BMD and are stronger, yet more brittle. The increased brittleness of bone was associated with increased body fat content due to high-fat feeding. In summary, high-fat feeding in female mice increases mineralization of bone, but negatively impacts bone quality resulting in brittle bones. PMID:27695036

Effect of chronic undernutrition on body mass and mechanical bone quality under normoxic and altitude hypoxic conditions.

PubMed

Lezon, Christian; Bozzini, Clarisa; Agûero Romero, Alan; Pinto, Patricia; Champin, Graciela; Alippi, Rosa M; Boyer, Patricia; Bozzini, Carlos E

2016-05-01

Both undernutrition and hypoxia exert a negative influence on both growth pattern and bone mechanical properties in developing rats. The present study explored the effects of chronic food restriction on both variables in growing rats exposed to simulated high-altitude hypoxia. Male rats (n 80) aged 28 d were divided into normoxic (Nx) and hypoxic (Hx) groups. Hx rats were exposed to hypobaric air (380 mmHg) in decompression chambers. At T0, Nx and Hx rats were subdivided into four equal subgroups: normoxic control and hypoxic controls, and normoxic growth-restricted and hypoxic growth-restricted received 80 % of the amount of food consumed freely by their respective controls for a 4-week period. Half of these animals were studied at the end of this period (T4). The remaining rats in each group continued under the same environmental conditions, but food was offered ad libitum to explore the type of catch-up growth during 8 weeks. Structural bone properties (strength and stiffness) were evaluated in the right femur midshaft by the mechanical three-point bending test; geometric properties (length, cross-sectional area, cortical mass, bending cross-sectional moment of inertia) and intrinsic properties of the bone tissue (elastic modulus) were measured or derived from appropriate equations. Bone mineralisation was assessed by ash measurement of the left femur. These data indicate that the growth-retarded effects of diminished food intake, induced either by food restriction or hypoxia-related inhibition of appetite, generated the formation of corresponding smaller bones in which subnormal structural and geometric properties were observed. However, they seemed to be appropriate to the body mass of the animals and suggest, therefore, that the bones were not osteopenic. When food restriction was imposed in Hx rats, the combined effects of both variables were additive, inducing a further reduction of bone mass and bone load-carrying capacity. In all cases, the mechanical properties of the mineralised tissue were unaffected. This and the capacity of the treated bones to undergone complete catch-up growth with full restoration of the biomechanical properties suggest that undernutrition, under either Nx or Hx conditions, does not affect bone behaviour because it remains appropriate to its mechanical functions.

Effects of whole-body vibration training on physical function, bone and muscle mass in adolescents and young adults with cerebral palsy.

PubMed

Gusso, Silmara; Munns, Craig F; Colle, Patrícia; Derraik, José G B; Biggs, Janene B; Cutfield, Wayne S; Hofman, Paul L

2016-03-03

We performed a clinical trial on the effects of whole-body vibration training (WBVT) on muscle function and bone health of adolescents and young adults with cerebral palsy. Forty participants (11.3-20.8 years) with mild to moderate cerebral palsy (GMFCS II-III) underwent 20-week WBVT on a vibration plate for 9 minutes/day 4 times/week at 20 Hz (without controls). Assessments included 6-minute walk test, whole-body DXA, lower leg pQCT scans, and muscle function (force plate). Twenty weeks of WBVT were associated with increased lean mass in the total body (+770 g; p = 0.0003), trunk (+410 g; p = 0.004), and lower limbs (+240 g; p = 0.012). Bone mineral content increased in total body (+48 g; p = 0.0001), lumbar spine (+2.7 g; p = 0.0003), and lower limbs (+13 g; p < 0.0001). Similarly, bone mineral density increased in total body (+0.008 g/cm(2); p = 0.013), lumbar spine (+0.014 g/cm(2); p = 0.003), and lower limbs (+0.023 g/cm(2); p < 0.0001). Participants reduced the time taken to perform the chair test, and improved the distance walked in the 6-minute walk test by 11% and 35% for those with GMFCS II and III, respectively. WBVT was associated with increases in muscle mass and bone mass and density, and improved mobility of adolescents and young adults with cerebral palsy.

Gracility of the modern Homo sapiens skeleton is the result of decreased biomechanical loading.

PubMed

Ryan, Timothy M; Shaw, Colin N

2015-01-13

The postcranial skeleton of modern Homo sapiens is relatively gracile compared with other hominoids and earlier hominins. This gracility predisposes contemporary humans to osteoporosis and increased fracture risk. Explanations for this gracility include reduced levels of physical activity, the dissipation of load through enlarged joint surfaces, and selection for systemic physiological characteristics that differentiate modern humans from other primates. This study considered the skeletal remains of four behaviorally diverse recent human populations and a large sample of extant primates to assess variation in trabecular bone structure in the human hip joint. Proximal femur trabecular bone structure was quantified from microCT data for 229 individuals from 31 extant primate taxa and 59 individuals from four distinct archaeological human populations representing sedentary agriculturalists and mobile foragers. Analyses of mass-corrected trabecular bone variables reveal that the forager populations had significantly higher bone volume fraction, thicker trabeculae, and consequently lower relative bone surface area compared with the two agriculturalist groups. There were no significant differences between the agriculturalist and forager populations for trabecular spacing, number, or degree of anisotropy. These results reveal a correspondence between human behavior and bone structure in the proximal femur, indicating that more highly mobile human populations have trabecular bone structure similar to what would be expected for wild nonhuman primates of the same body mass. These results strongly emphasize the importance of physical activity and exercise for bone health and the attenuation of age-related bone loss.

Primary pericranial Ewing's sarcoma on the temporal bone: A case report.

PubMed

Kawano, Hiroto; Nitta, Naoki; Ishida, Mitsuaki; Fukami, Tadateru; Nozaki, Kazuhiko

2016-01-01

Primary Ewing's sarcoma originating in the pericranium is an extremely rare disease entity. A 9-year-old female patient was admitted to our department due to a left temporal subcutaneous mass. The mass was localized under the left temporal muscle and attached to the surface of the temporal bone. Head computed tomography revealed a mass with bony spicule formation on the temporal bone, however, it did not show bone destruction or intracranial invasion. F-18 fluorodeoxyglucose positron emission tomography showed no lesions other than the mass on the temporal bone. Magnetic resonance imaging showed that the mass was located between the temporal bone and the pericranium. The mass was completely resected with the underlying temporal bone and the overlying deep layer of temporal muscle, and was diagnosed as primary Ewing's sarcoma. Because the tumor was located in the subpericranium, we created a new classification, "pericranial Ewing's sarcoma," and diagnosed the present tumor as pericranial Ewing's sarcoma. We herein present an extremely rare case of primary pericranial Ewing's sarcoma that developed on the temporal bone.

The recent prevalence of Osteoporosis and low bone mass in the United States based on bone mineral density at the Femoral Neck or Lumbar Spine

USDA-ARS?s Scientific Manuscript database

The goal of our study was to estimate the prevalence of osteoporosis and low bone mass based on bone mineral density (BMD) at the femoral neck and the lumbar spine in adults 50 years and older in the United States (US). We applied prevalence estimates of osteoporosis or low bone mass at the femoral ...

Characterization of bone microstructure using photoacoustic spectrum analysis

NASA Astrophysics Data System (ADS)

Feng, Ting; Kozloff, Kenneth M.; Xu, Guan; Du, Sidan; Yuan, Jie; Deng, Cheri X.; Wang, Xueding

2015-03-01

Osteoporosis is a progressive bone disease that is characterized by a decrease in bone mass and deterioration in microarchitecture. This study investigates the feasibility of characterizing bone microstructure by analyzing the frequency spectrum of the photoacoustic signals from the bone. Modeling and numerical simulation of photoacoustic signals and their frequency-domain analysis were performed on trabecular bones with different mineral densities. The resulting quasilinear photoacoustic spectra were fit by linear regression, from which spectral parameter slope can be quantified. The modeling demonstrates that, at an optical wavelength of 685 nm, bone specimens with lower mineral densities have higher slope. Preliminary experiment on osteoporosis rat tibia bones with different mineral contents has also been conducted. The finding from the experiment has a good agreement with the modeling, both demonstrating that the frequency-domain analysis of photoacoustic signals can provide objective assessment of bone microstructure and deterioration. Considering that photoacoustic measurement is non-ionizing, non-invasive, and has sufficient penetration in both calcified and noncalcified tissues, this new technology holds unique potential for clinical translation.

Guiding bone formation in a critical-sized defect and assessments.

PubMed

Jannetty, Joseph; Kolb, Eric; Boxberger, John; Deslauriers, Richard; Ganey, Timothy

2010-11-01

Development of alternatives to autologous bone has been served by many hypotheses and developments. Favorable properties of synthetic materials used currently in bone grafting support tissue differentiation without shielding capacity for integrated modeling. Ideally, new materials provide tissue compatibility and minimize patient morbidity and are attractive because of potential for in situ delivery, isothermal polymerization, porous structure, and nontoxic chemistry. For application in cranial bone, ability for materials to be laid adjacent to brain and offer postsurgical protection without neural risk is a critical asset. Kryptonite Bone Cement (KBC) meets the property criteria for cranial bone repair with regard to adhesive, conductive, and biologic transparency and US Food and Drug Administration approval for cranial bone void repair. To better delineate the morphology effective in cranial bone repair, a comparison was made between KBC and BoneSource, another material approved for the same indication. After Institutional Animal Care and Use Committee approval, the study assessed 24 rabbits, each with 2 separate cranial implants, to evaluate integration and absorption of the biomaterial at defined time points of 12, 18, 24, and 36 weeks. The 36-week assessment demonstrated near-complete resorption/integration of the BoneSource graft material. Bone was present within the biomaterial as well as independent of contact. The KBC was similarly integrated throughout the mass of the material, and new bone was in contact with the grafting material and also seen as separate islands of new bone. The bone demonstrated lamellar bone architecture with clear trabecular morphology. At higher magnification, the bone architecture can be clearly delineated, and comparison between the graft fillers is not obvious relative to the bone that has formed. Despite microscopic similarities, the most striking difference was maintenance of scaffold anatomy during bone regeneration. Kryptonite Bone Cement meets the criteria described in the introduction; properties of biologic transparency, osteoconductivity, and ergonomic utility offer other potential uses in bone repair. Key tenets of bone tissue regeneration observed in this analysis included adequate cell differentiation and tissue support. Bone that formed demonstrated lamellar rather than woven bone to suggest response to loading strain rather than merely biochemical precipitation. Over the 36-week study, the graft showed progressive bioabsorbable potential with calibrated replacement.

Oxytocin and bone

PubMed Central

Sun, Li; Zaidi, Mone; Zallone, Alberta

2014-01-01

One of the most meaningful results recently achieved in bone research has been to reveal that the pituitary hormones have profound effect on bone, so that the pituitary-bone axis has become one of the major topics in skeletal physiology. Here, we discuss the relevant evidence about the posterior pituitary hormone oxytocin (OT), previously thought to exclusively regulate parturition and breastfeeding, which has recently been established to directly regulate bone mass. Both osteoblasts and osteoclasts express OT receptors (OTR), whose stimulation enhances bone mass. Consistent with this, mice deficient in OT or OTR display profoundly impaired bone formation. In contrast, bone resorption remains unaffected in OT deficiency because, even while OT stimulates the genesis of osteoclasts, it inhibits their resorptive function. Furthermore, in addition to its origin from the pituitary, OT is also produced by bone marrow osteoblasts acting as paracrine-autocrine regulator of bone formation modulated by estrogens. In turn, the power of estrogen to increase bone mass is OTR-dependent. Therefore, OTR−/− mice injected with 17β-estradiol do not show any effects on bone formation parameters, while the same treatment increases bone mass in wild-type mice. These findings together provide evidence for an anabolic action of OT in regulating bone mass and suggest that bone marrow OT may enhance the bone-forming action of estrogen through an autocrine circuit. This established new physiological role for OT in the maintenance of skeletal integrity further suggests the potential use of this hormone for the treatment of osteoporosis. PMID:25209411

Calcium Intake, Major Dietary Sources and Bone Health Indicators in Iranian Primary School Children.

PubMed

Omidvar, Nasrin; Neyestani, Tirang-Reza; Hajifaraji, Majid; Eshraghian, Mohammad-Reza; Rezazadeh, Arezoo; Armin, Saloumeh; Haidari, Homa; Zowghi, Telma

2015-02-01

Adequate calcium intake may have a crucial role with regards to prevention of many chronic diseases, including hypertension, hypercholesterolemia, different types of cancer, obesity and osteoporosis. In children, sufficient calcium intake is especially important to support the accelerated growth spurt during the preteen and teenage years and to increase bone mineral mass to lay the foundation for older age. This study aimed to assess daily calcium intake in school-age children to ensure whether they fulfill the FGP dairy serving recommendations, the recommended levels of daily calcium intake and to assess the relationship between dietary calcium intake and major bone health indicators. A total of 501 Iranian school-age children were randomly selected. Calcium intake was assessed using a semi-quantitative food frequency questionnaire. Bone health indicators were also assessed. Dairy products contributed to 69.3% of the total calcium intake of the children. Daily adequate intake of calcium was achieved by 17.8% of children. Only 29.8% met the Food guide pyramid recommendations for dairy intake. Dietary calcium intake was not significantly correlated with serum calcium and other selected biochemical indicators of bone health. The need for planning appropriate nutrition strategies for overcoming inadequate calcium intake in school age children in the city of Tehran is inevitable.

A retrospective analysis of longitudinal changes in bone mineral content in cystic fibrosis.

PubMed

Chirita-Emandi, Adela; Shepherd, Sheila; Kyriakou, Andreas; McNeilly, Jane D; Dryden, Carol; Corrigan, Donna; Devenny, Anne; Ahmed, Syed Faisal

2017-08-28

We aimed to describe the longitudinal changes in bone mineral content and influencing factors, in children with cystic fibrosis (CF). One hundred children (50 females) had dual X-ray absorptiometry (DXA) performed. Of these, 48 and 24 children had two to three scans, respectively over 10 years of follow-up. DXA data were expressed as lumbar spine bone mineral content standard deviation score (LSBMCSDS) adjusted for age, gender, ethnicity and bone area. Markers of disease, anthropometry and bone biochemistry were collected retrospectively. Baseline LSBMCSDS was >0.5 SDS in 13% children, between -0.5; 0.5 SDS, in 50% and ≤-0.5 in the remainder. Seventy-eight percent of the children who had baseline LSBMCSDS >-0.5, and 35% of the children with poor baseline (LSBMCSDS<-0.5), showed decreasing values in subsequent assessments. However, mean LS BMC SDS did not show a significant decline in subsequent assessments (-0.51; -0.64; -0.56; p=0.178). Lower forced expiratory volume in 1 s percent (FEV1%) low body mass index standard deviation scores (BMI SDS) and vitamin D were associated with reduction in BMC. Bone mineral content as assessed by DXA is sub-optimal and decreases with time in most children with CF and this study has highlighted parameters that can be addressed to improve bone health.

Association of Stimulant Medication Use With Bone Mass in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder.

PubMed

Feuer, Alexis J; Thai, Ashley; Demmer, Ryan T; Vogiatzi, Maria

2016-12-05

Murine studies reveal that sympathetic nervous system activation leads to decreased bone mass. Stimulant medications used to treat attention-deficit/hyperactivity disorder (ADHD) increase sympathetic tone and may affect bone remodeling. Because bone mass accrual is completed by young adulthood, assessing stimulant effects on bone density in growing children is of critical importance. To investigate associations between stimulant use and bone mass in children and adolescents. This cross-sectional analysis used data collected from January 1, 2005, to December 31, 2010, from the National Health and Nutrition Examination Survey (NHANES) database. NHANES is a series of cross-sectional, nationally representative health and nutrition surveys of the US population. All children, adolescents, and young adults aged 8 to 20 years with dual-energy x-ray absorptiometry (DXA), anthropometric, demographic, and prescription medication use data were eligible for participation. Of the 6489 respondents included in the multivariable linear regression analysis, 159 were stimulant users and 6330 were nonusers. Data were analyzed from October 8, 2015, to December 31, 2016. Stimulant use, determined by questionnaires administered via interview. The association between stimulant use and total femur, femoral neck, and lumbar spine bone mineral content (BMC) and bone mineral density (BMD) was assessed using DXA. Study participants included 6489 NHANES participants with a mean (SD) age of 13.6 (3.6) years. Stimulant use was associated with lower bone mass after adjustment for covariates. Mean lumbar spine BMC was significantly lower in stimulant users vs nonusers (12.76 g; 95% CI, 12.28-13.27 g vs 13.38 g; 95% CI, 13.26-13.51 g; P = .02), as was mean lumbar spine BMD (0.90 g/cm2; 95% CI, 0.87-0.94 g/cm2 vs 0.94 g/cm2; 95% CI, 0.94-0.94 g/cm2; P = .03) and mean femoral neck BMC (4.34 g; 95% CI, 4.13-4.57 g vs 4.59 g; 95% CI, 4.56-4.62 g; P = .03). Mean BMD of the femoral neck (0.88 g/cm2; 95% CI, 0.84-0.91 g/cm2 vs 0.91 g/cm2; 95% CI, 0.90-0.91 g/cm2; P = .08) and total femur (0.94 g/cm2; 95% CI, 0.90-0.99 g/cm2 vs 0.99 g/cm2; 95% CI, 0.98-0.99 g/cm2; P = .05) were also lower in stimulant users vs nonusers. Participants treated with stimulants for 3 months or longer had significantly lower lumbar spine BMD (0.89 g/cm2; 95% CI, 0.85-0.93 g/cm2 vs 0.94 g/cm2; 95% CI, 0.94-0.94 g/cm2; P = .02) and BMC (12.71 g; 95% CI, 12.14-13.32 g vs 13.38 g; 95% CI, 13.25-13.51 g; P = .03) and femoral neck BMD (0.87 g/cm2; 95% CI, 0.74-0.83 g/cm2 vs 0.91 g/cm2; 95% CI, 0.83-0.84 g/cm2; P = .048) than nonusers. Children and adolescents reporting stimulant use had lower DXA measurements of the lumbar spine and femur compared with nonusers. These findings support the need for future prospective studies to examine the effects of stimulant use on bone mass in children.

Effects of a moderately high-protein diet and interval aerobic training combined with strength-endurance exercise on markers of bone metabolism, microarchitecture and turnover in obese Zucker rats.

PubMed

Nebot, Elena; Aparicio, Virginia A; Coll-Risco, Irene; Camiletti-Moirón, Daniel; Schneider, Johannes; Kapravelou, Garyfallia; Heimel, Patrick; Martínez, Rosario; Andrade, Ana; Slezak, Paul; Redl, Heinz; Porres, Jesús M; López-Jurado, María; Pietschmann, Peter; Aranda, Pilar

2016-11-01

Weight loss is a public health concern in obesity-related diseases such as metabolic syndrome, and the protein level of the diets seem to be crucial for the development and maintenance of bone. The nature of exercise and whether exercise in combination with moderately high-protein dietary interventions could protect against potential bone mass deficits remains unclear. To investigate the effects of a moderately high-protein diet and interval aerobic training combined with strength-endurance exercise (IASE) protocol on bone status, and to assess potential interaction effects (i.e. diet*IASE). Male Zucker fatty rats were randomized distributed into 4 groups (n=8): normoprotein+sedentary; normoprotein+exercise; moderately high-protein+sedentary, and moderately high-protein+exercise. Training groups conducted an IASE program, 5days/week for 2months. Markers of bone metabolism were measured in plasma. Parameters of bone mass and 3D outcomes for trabecular and cortical bone microarchitecture were assessed by micro-computed tomography. Femur length, plasma osteocalcin, sclerostin, osteoprotegerin, receptor activator of nuclear factor kappa-B ligand, insulin, leptin, PTH, uric acid and urinary phosphorus levels were lower in the moderately high-protein compared to the normoprotein groups (all, p<0.05), whereas plasma alkaline phosphatase, aspartate aminotransferase, alanine transaminase, and urinary uric acid concentrations, and cortical total volume (TV) and bone volume (BV) were higher in the moderately high-protein (all, p<0.01). Final body weight and alkaline phosphatase levels were lower in the exercise compared to the sedentary (both, p<0.05), whereas femur length and weight, aminoterminal propeptides of type I procollagen and C-terminal telopeptides of type I collagen concentrations, and cortical TV and BV were higher in the exercise compared to the sedentary groups (all, p<0.05). The combination of interventions may be effective to enhance trabecular bone microarchitecture and BMD, and has a partial impact on cortical bone in obese rats. Nevertheless, they do not induce any alteration on the bone turnover markers. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Bisphosphonates for prevention of postmenopausal osteoporosis.

PubMed

Ravn, Pernille

2002-02-01

Our studies showed that 5 mg alendronate per day was the lowest, most effective dose that persistently prevented bone loss in recently postmenopausal women with normal bone mass. The effect on bone mass and biochemical markers was found comparable to that of commonly recommended regimens of postmenopausal HRT, and 5 mg alendronate per day is suggested as a new option for prevention of postmenopausal osteoporosis. HRT must, however, still be considered the first choice for this indication because of additional beneficial effects on other organ systems. The effect of alendronate was unaffected by bone or fat mass status, but increased with increasing postmenopausal age. The implications were that alendronate stabilized bone mass to a comparable extent in women at particular risk of osteoporosis because of thin body habitus or low bone mass and in healthy postmenopausal women with normal bone mass. Calcium supplementation was insufficient to prevent bone loss and did not add an effect on bone metabolism when combined with alendronate treatment in recently postmenopausal women. The gastrointestinal risk and adverse event profile of 5 mg alendronate per day was comparable to that of placebo, and this dose of alendronate appeared safe for long-term use. Bone loss resumed at a normal postmenopausal rate promptly after withdrawal of alendronate in early postmenopausal women consistent with a substantial underlying natural bone loss during early menopause. Oral ibandronate increased bone mass at all skeletal regions in elderly postmenopausal women with low bone mass, and 2.5 mg ibandronate per day was the lowest dose with this effect. The results are indicative of ibandronate as an option for secondary prevention of postmenopausal osteoporosis, but longer-term phase III trials should be performed before ibandronate can be recommended for this indication. The study showed that 2.5 mg ibandronate per day was efficient for prevention of bone loss and increment in bone mass in a population of women at particular risk of osteoporosis because of low bone mass. There were no differences between 2.5 mg ibandronate per day and placebo in terms of side effects, including complaints from the gastrointestinal tract, and ibandronate appeared safe for longer-term use in this dosing. Bone loss resumed at a normal postmenopausal rate when treatment was withdrawn. The response in bone mass and biochemical markers indicated that 2.5 mg ibandronate per day is equivalent to 10 mg alendronate per day in postmenopausal women. Our studies of two recently developed biochemical markers, urine CTX and serum total OC, showed that bone turnover was lowest in the premenopausal period, where these biochemical markers furthermore revealed a negative association with bone mass. It indicated that increased bone turnover contributes to a small premenopausal bone loss and resulting lowered bone mass. In consistence, a small premenopausal bone loss was observed in some regions of the hip. The biochemical markers increased at the time of menopause, consistent with initiation of the postmenopausal bone loss, and became gradually more negatively associated with bone mass as time past the menopause increased. The biochemical markers were furthermore higher in postmenopausal women with low bone mass, consistent with the characterization of postmenopausal osteoporosis as a condition with increased bone turnover. Our results consistently indicated a central role of increased bone turnover for development of low bone mass and osteoporosis. It is, however, also important to stress that the associations between biochemical markers and bone mass were too weak to allow for a valid individual estimation of bone mass based on biochemical markers. In contrast, the biochemical markers were shown as valid tools for monitoring and prediction of treatment effect of bisphosphonates. CTX, NTX, and total OC revealed the best performance characteristics in this respect. Six months after start of treatment, the level of suppression of these biochemical markers of bone resorption and formation accurately reflected the size of the 1-2 year response in bone mass in groups of women treated with bisphosphonate. This was a clear advance over bone densitometry, which has a precision error in the area of the anticipated yearly bone mass response during bisphosphonate therapy. The relationship was consistent during treatment with alendronate or ibandronate and in younger or elderly postmenopausal women. In individual patients, cut-off values of an about 40% decrease in urine CTX or NTX and an about 20% decrease in total OC validly predicted long-term prevention of bone loss. The sensitivity of prediction was high, but the specificity low. This implicated that the biochemical markers could be used as an exact method to detect "responders" to therapy, whereas "non-responders" to bisphosphonate treatment should be detected with bone densitometry in patients who do not reveal a decrease below the cut-off value in the biochemical marker during treatment. However, before such approach can be generally recommended the cut-off values of the biochemical markers should be validated in future clinical trials of bisphosphonate. Postmenopausal osteoporosis develops slowly over many years and mainly becomes a significant individual and socio-economic health problem 1-3 decades after the menopause. Prevention of postmenopausal osteoporosis by bisphosphonates is therefore likely to imply a treatment regimen of at least a decade, as presently recommended for HRT (Consensus Development Statement 1997). However, future cost-effectiveness studies should reveal when bisphosphonate treatment should ideally be initiated. Our studies showed that the bisphosphonates were effective over the range from general recommendation (recently postmenopausal women with normal bone mass) to a reservation for women at particular risk of osteoporosis (elderly women, thin women, or women with osteopenia). Presently available biochemical markers could be used for groupwise and individual monitoring and prediction of treatment response. Most presently available biochemical markers, however, have the drawback of a low specificity. Recent studies of CTX measured in serum are promising, and indicate that this new biochemical marker might have overcome these drawbacks due to a pronounced response to treatment and a low long-term biological variation (Christgau et al. 1998b, Rosen et al. 1998, and 2000).

[Relationship between weight, body composition and bone mass in peritoneal dialysis].

PubMed

Negri, A L; Barone, R; Bogado, C E; Zanchetta, J R

2005-01-01

Patients in chronic dialysis show a decrease in total bone mass. The factors that determine this decrease are not well known. In normal populations weight and its compartments are important determinants of bone mass. We studied total bone mineral content (TBMC), a measure of bone mass, and body composition using DEXA densitometry in 65 patients (45 females and 20 males) who had been in peritoneal dialysis for a mean of 40.3 +/- 23.2 months. Forty-eight patients (73.8%) had been previously in hemodialysis. The mean total time in dialysis for these patients was 76.8 months. As a group patients showed a very significant positive correlation between TBMC and weight, height, and lean body mass. A negative correlation was found between TBMC with the time in dialysis and iPTH. In men we found significant simple positive correlations between TBMC and weight, height and lean body mass. In women we found simple positive correlations of TBMC with weight, height and lean body mass and a negative correlation with iPTH. In the multiple regression analysis, lean body mass was the only body composition parameter that had a significantly positive correlation with TBMC in men; in women only height correlated positively with TBMC and iPTH continued to correlate negatively with bone mass. When we considered pre and postmenopausal women separately, bone mass was correlated positively with height and lean body mass and negatively with iPTH in postmenopausal women and only with height in pre-menopausal females. We conclude that the lean body mass compartment. is the most important component of weight that determines TBMC in peritoneal dialysis patients particularly in males and postmenopausal women. In postmenopausal women, secondary hyperparathyroidism seems to be particularly detrimental on bone mass.

Effects of deletion of ER-alpha in osteoblast-lineage cells on bone mass and adaptation to mechanical loading differs in female and male mice

PubMed Central

Melville, Katherine M.; Kelly, Natalie H.; Surita, Gina; Buchalter, Daniel B.; Schimenti, John C.; Main, Russell P.; Ross, F. Patrick; van der Meulen, Marjolein C. H.

2015-01-01

Estrogen receptor alpha (ERα) has been implicated in bone’s response to mechanical loading in both males and females. ERα in osteoblast lineage cells is important for determining bone mass, but results depend on animal sex and the cellular stage at which ERα is deleted. We demonstrated previously that when ERα is deleted from mature osteoblasts and osteocytes in mixed background female mice, bone mass and strength are decreased. However, few studies exist examining the skeletal response to loading in bone cell-specific ERαKO mice. Therefore, we crossed ERα floxed (ERαfl/fl) and osteocalcin-Cre (OC-Cre) mice to generate animals lacking ERα in mature osteoblasts and osteocytes (pOC-ERαKO) and littermate controls (LC). At 10 weeks of age the left tibia was loaded in vivo for two weeks. We analyzed bone mass through microCT, bone formation rate by dynamic histomorphometry, bone strength from mechanical testing, and osteoblast and osteoclast activity by serum chemistry and immunohistochemistry. ERα in mature osteoblasts differentially regulated bone mass in males and females. Compared to LC, female pOC-ERαKO mice had decreased cortical and cancellous bone mass, while male pOC-ERαKO mice had equal or greater bone mass than LC. Bone mass results correlated with decreased compressive strength in pOC-ERαKO female L5 vertebrae, and with increased maximum moment in pOC-ERαKO male femora. Female pOC-ERαKO mice responded more to mechanical loading, while the response of pOC-ERαKO male animals was similar to their littermate controls. PMID:25707500

Orexin Regulates Bone Remodeling via a Dominant Positive Central Action and a Subordinate Negative Peripheral Action

PubMed Central

Wei, Wei; Motoike, Toshiyuki; Krzeszinski, Jing Y.; Jin, Zixue; Xie, Xian-Jin; Dechow, Paul C.; Yanagisawa, Masashi; Wan, Yihong

2014-01-01

SUMMARY Orexin neuropeptides promote arousal, appetite, reward, and energy expenditure. However, whether orexin affects bone mass accrual is unknown. Here we show that orexin functions centrally through orexin receptor 2 (OX2R) in the brain to enhance bone formation. OX2R-null mice exhibit low-bone-mass owing to elevated circulating leptin; whereas central administration of an OX2R-selective agonist augments bone mass. Conversely, orexin also functions peripherally through orexin receptor 1 (OX1R) in the bone to suppress bone formation. OX1R-null mice exhibit high-bone-mass owing to a mesenchymal stem cell differentiation shift from adipocyte to osteoblast that results from higher osseous ghrelin expression. The central action is dominant over the peripheral action because bone mass is reduced in orexin-null and OX1R2R-double-null mice but enhanced in orexin over-expressing transgenic mice. These findings reveal orexin as a critical rheostat of skeletal homeostasis that exerts a yin-yang dual regulation, and highlight orexin as a therapeutic target for osteoporosis. PMID:24794976

Effect of transforming growth factor beta (TGF-β) receptor I kinase inhibitor on prostate cancer bone growth.

PubMed

Wan, Xinhai; Li, Zhi-Gang; Yingling, Jonathan M; Yang, Jun; Starbuck, Michael W; Ravoori, Murali K; Kundra, Vikas; Vazquez, Elba; Navone, Nora M

2012-03-01

Transforming growth factor beta 1 (TGF-β1) has been implicated in the pathogenesis of prostate cancer (PCa) bone metastasis. In this study, we tested the antitumor efficacy of a selective TGF-β receptor I kinase inhibitor, LY2109761, in preclinical models. The effect of LY2109761 on the growth of MDA PCa 2b and PC-3 human PCa cells and primary mouse osteoblasts (PMOs) was assessed in vitro by measuring radiolabeled thymidine incorporation into DNA. In vivo, the right femurs of male SCID mice were injected with PCa cells. We monitored the tumor burden in control- and LY2109761-treated mice with MRI analysis and the PCa-induced bone response with X-ray and micro-CT analyses. Histologic changes in bone were studied by performing bone histomorphometric evaluations. PCa cells and PMOs expressed TGF-β receptor I. TGF-β1 induced pathway activation (as assessed by induced expression of p-Smad2) and inhibited cell growth in PC-3 cells and PMOs but not in MDA PCa 2b cells. LY2109761 had no effect on PCa cells but induced PMO proliferation in vitro. As expected, LY2109761 reversed the TGF-β1-induced pathway activation and growth inhibition in PC-3 cells and PMOs. In vivo, LY2109761 treatment for 6weeks resulted in increased volume in normal bone and increased osteoblast and osteoclast parameters. In addition, LY2109761 treatment significantly inhibited the growth of MDA PCa 2b and PC-3 in the bone of SCID mice (p<0.05); moreover, it resulted in significantly less bone loss and change in osteoclast-associated parameters in the PC-3 tumor-bearing bones than in the untreated mice. In summary, we report for the first time that targeting TGF-β receptors with LY2109761 can control PCa bone growth while increasing the mass of normal bone. This increased bone mass in nontumorous bone may be a desirable side effect of LY2109761 treatment for men with osteopenia or osteoporosis secondary to androgen-ablation therapy, reinforcing the benefit of effectively controlling PCa growth in bone. Thus, targeting TGF-β receptor I is a valuable intervention in men with advanced PCa. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of transforming growth factor beta (TGF-β) receptor I kinase inhibitor on prostate cancer bone growth

PubMed Central

Wan, Xinhai; Li, Zhi-Gang; Yingling, Jonathan M.; Yang, Jun; Starbuck, Michael W.; Ravoori, Murali K.; Kundra, Vikas; Vazquez, Elba; Navone, Nora M.

2012-01-01

Transforming growth factor beta 1 (TGF-β1) has been implicated in the pathogenesis of prostate cancer (PCa) bone metastasis. In this study, we tested the antitumor efficacy of a selective TGF-β receptor I kinase inhibitor, LY2109761, in preclinical models. The effect of LY2109761 on the growth of MDA PCa 2b and PC-3 human PCa cells and primary mouse osteoblasts (PMOs) was assessed in vitro by measuring radiolabeled thymidine incorporation into DNA. In vivo, the right femurs of male SCID mice were injected with PCa cells. We monitored the tumor burden in control- and LY2109761-treated mice with MRI analysis and the PCa-induced bone response with x-ray and micro-CT analyses. Histologic changes in bone were studied by performing bone histomorphometric evaluations. PCa cells and PMOs expressed TGF-β receptor I. TGF-β1 induced pathway activation (as assessed by induced expression of p-Smad2) and inhibited cell growth in PC-3 cells and PMOs but not in MDA PCa 2b cells. LY2109761 had no effect on PCa cells but induced PMO proliferation in vitro. As expected, LY2109761 reversed the TGF-β1–induced pathway activation and growth inhibition in PC-3 cells and PMOs. In vivo, LY2109761 treatment for 6 weeks resulted in increased volume in normal bone and increased osteoblast and osteoclast parameters. In addition, LY2109761 treatment significantly inhibited the growth of MDA PCa 2b and PC-3 in the bone of SCID mice (p < 0.05); moreover, it resulted in significantly less bone loss and change in osteoclast-associated parameters in the PC-3 tumor–bearing bones than in the untreated mice. In summary, we report for the first time that targeting TGF-β receptors with LY2109761 can control PCa bone growth while increasing the mass of normal bone. This increased bone mass in nontumorous bone may be a desirable side effect of LY2109761 treatment for men with osteopenia or osteoporosis secondary to androgen-ablation therapy, reinforcing the benefit of effectively controlling PCa growth in bone. Thus, targeting TGF-β receptor I is a valuable intervention in men with advanced PCa. PMID:22173053

Body Mass, Training, Menses, and Bone in Adolescent Runners: A 3-y Follow-Up

USDA-ARS?s Scientific Manuscript database

Abstract: Endurance runners with low bone mass during adolescence may be at risk of developing a low peak bone mineral density (BMD) as a young adult. However, it is possible that they mature late and undergo delayed bone mass accumulation. PURPOSE: We evaluated 40 adolescent runners (age 15.9 ± 0....

Invited review of a workshop: anabolic hormones in bone: basic research and therapeutic potential.

PubMed

Margolis, R N; Canalis, E; Partridge, N C

1996-03-01

Age-, postmenopause-, and disease-related conditions that result in low bone mass represent important public health issues. Maintenance of bone mass is a balance between bone resorption and formation and is influenced by diet, body composition, activity level, and the interactions between and among a large number of hormones, growth factors, and cytokines. Recent research has emphasized establishing a more complete understanding of the hormonal regulation of bone and developing anabolic agents with therapeutic potential for the treatment of low bone mass. The NIDDK at the NIH recently sponsored a Workshop, entitled Anabolic Hormones in Bone: Basic Research and Therapeutic Potential, that attempted to define the current state of the art knowledge of hormones, growth factors, and cytokines that affect bone mass, with particular emphasis on those that could potentially have a role as anabolic agents in bone. This review presents a condensed proceedings of that workshop along with a summary of the optimal requisites for the development of anabolic agents with therapeutic potential in bone.

Common endocrine control of body weight, reproduction, and bone mass

NASA Technical Reports Server (NTRS)

Takeda, Shu; Elefteriou, Florent; Karsenty, Gerard

2003-01-01

Bone mass is maintained constant between puberty and menopause by the balance between osteoblast and osteoclast activity. The existence of a hormonal control of osteoblast activity has been speculated for years by analogy to osteoclast biology. Through the search for such humoral signal(s) regulating bone formation, leptin has been identified as a strong inhibitor of bone formation. Furthermore, intracerebroventricular infusion of leptin has shown that the effect of this adipocyte-derived hormone on bone is mediated via a brain relay. Subsequent studies have led to the identification of hypothalamic groups of neurons involved in leptin's antiosteogenic function. In addition, those neurons or neuronal pathways are distinct from neurons responsible for the regulation of energy metabolism. Finally, the peripheral mediator of leptin's antiosteogenic function has been identified as the sympathetic nervous system. Sympathomimetics administered to mice decreased bone formation and bone mass. Conversely, beta-blockers increased bone formation and bone mass and blunted the bone loss induced by ovariectomy.

Increased Leg Bone Mineral Density and Content During the Initial Years of College Sport.

PubMed

Scerpella, John J; Buehring, Bjoern; Hetzel, Scott J; Heiderscheit, Bryan C

2018-04-01

Scerpella, JJ, Buehring, B, Hetzel, SJ, and Heiderscheit, BC. Increased leg bone mineral density and content during the initial years of college sport. J Strength Cond Res 32(4): 1123-1130, 2018-Bone mineral density (BMD) and bone mineral content (BMC) data are useful parameters for evaluating how training practices promote bone health. We used dual-energy X-ray absorptiometry (DXA) to longitudinally assess sport-specific growth in leg and total body BMD/BMC over the initial 2 years of collegiate training. Eighty-five Division 1 collegiate basketball, hockey, and soccer athletes (50 males and 35 females; age 19.0 [0.8] years) underwent annual DXA scans. Leg and total body BMD/BMC were compared within and across two 1-year intervals (periods 1 and 2) using repeated-measures analysis of variance, adjusting for age, sex, race, and sport. Leg BMD, leg BMC, and total body BMC all increased over period 1 (0.05 g·cm [p = 0.001], 0.07 kg [p = 0.002], and 0.19 kg [p < 0.001] respectively). Changes in period 2 compared with period 1 were smaller for leg BMD (p = 0.001), leg BMC (p < 0.001), leg fat mass (p = 0.028), and total BMC (p = 0.005). Leg lean mass increased more during period 2 than period 1 (p = 0.018). Sports participation was the only significant predictor of change in leg BMD. Significant increases in both leg BMD and BMC were demonstrated over both 2-year periods, with greater gains during period 1. These gains highlight the importance of attentive training procedures, capitalizing on attendant physical benefits of increased BMD/BMC. Additional research in young adults, evaluating bone mass acquisition, will optimize performance and decrease risk of bone stress injury among collegiate athletes.

Calcium and vitamin D supplementation through fortified dairy products counterbalances seasonal variations of bone metabolism indices: the Postmenopausal Health Study.

PubMed

Tenta, Roxane; Moschonis, George; Koutsilieris, Michael; Manios, Yannis

2011-08-01

To assess the effectiveness of a dietary intervention combined with fortified dairy products on bone metabolism and bone mass indices in postmenopausal women. Forty postmenopausal women (55-65 years old) were equally randomized into a dietary group (DG), receiving daily and for 30 months, 1,200 mg of calcium and 7.5 μg of vitamin D(3) for the first 12 months that increased to 22.5 μg for the remaining 18 months of intervention through fortified dairy products; and a control group (CG). Differences in the changes of bone metabolism and bone mass indices were examined with repeated measures ANOVA. A significant increase was observed for PTH levels only in the CG during the first six winter months of intervention (p = 0.049). After 30 months of intervention, during winter, serum 25(OH)D significantly decreased in the CG while remained in the same high levels as in the summer period in the DG. Serum RANKL levels decreased significantly in the DG compared with the increase in the CG during the 30-month intervention period (p = 0.005). Serum CTx decreased significantly in the DG after six (-0.08; -0.12 to -0.03) and 12 (-0.03; -0.08 to -0.02) months of intervention. Finally, the DG had more favorable changes in total body BMD than the CG (p < 0.001). Increasing dietary intake of calcium and vitamin D in osteopenic postmenopausal women appears to be effective in producing favorable changes in several bone metabolism and bone mass indices and in counterbalancing seasonal variations in hormonal and biochemical molecules.

Effect of high dietary sodium on bone turnover markers and urinary calcium excretion in Korean postmenopausal women with low bone mass.

PubMed

Park, S M; Joung, J Y; Cho, Y Y; Sohn, S Y; Hur, K Y; Kim, J H; Kim, S W; Chung, J H; Lee, M K; Min, Y-K

2015-03-01

High salt intake is a well-recognized risk factor of osteoporosis for its modulating effect on calcium metabolism. To understand the effect of dietary sodium on bone turnover, we evaluated the association between urinary sodium excretion and bone turnover markers in Korean postmenopausal women with low bone mass. A retrospective review of medical records at a single institution identified 537 postmenopausal women who were first diagnosed with osteopenia or osteoporosis between 2008 and 2013. Subjects were stratified by low (<2 g/day, n=77), moderate (2-4.4 g/day, n=354) and high (⩾4.4 g/day, n=106) sodium excretion. A 24-h urine was collected to estimate sodium, calcium and creatinine. Bone turnover markers and calciotropic hormones were measured in serum. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry. Sodium intake was positively associated with urinary sodium excretion (P=0.006, r=0.29). Bone turnover markers were significantly higher in the moderate-to-high urinary sodium excretion group (⩾2 g/day) than in the low urinary sodium excretion group (<2 g/day); CTX-I (C-telopeptides of type I collagen) was 21.3% higher (P=0.001) and osteocalcin (OC) was 15.7% higher (P=0.004). Calciotropic hormones and BMD were not significantly different across the sodium excretion groups. High urinary sodium excretion (⩾2 g/day) increased bone turnover markers in Korean postmenopausal women, suggesting that excessive sodium intake might accelerate bone turnover.

Accumulation of carboxymethyl-lysine (CML) in human cortical bone.

PubMed

Thomas, Corinne J; Cleland, Timothy P; Sroga, Grazyna E; Vashishth, Deepak

2018-05-01

Advanced glycation end-products (AGEs) are a category of post translational modification associated with the degradation of the structural properties of multiple different types of tissues. Typically, AGEs are the result of a series of post-translational modification reactions between sugars and proteins through a process known as non-enzymatic glycation (NEG). Increases in the rate of NEG of bone tissue are associated with type 2 diabetes and skeletal fragility. Current methods of assessing NEG and its impact on bone fracture risk involve measurement of pentosidine or total fluorescent AGEs (fAGEs). However, pentosidine represents only a small fraction of possible fAGEs present in bone, and neither pentosidine nor total fAGE measurement accounts for non-fluorescent AGEs, which are known to form in significant amounts in skin and other collagenous tissues. Carboxymethyl-lysine (CML) is a non-fluorescent AGE that is often measured and has been shown to accumulate in tissues such as skin, heart, arteries, and intervertebral disks, but is currently not assessed in bone. Here we show the localization of CML to collagen I using mass spectrometry for the first time in human bone. We then present a new method using demineralization followed by heating and trypsin digestion to measure CML content in human bone and demonstrate that CML in bone is 40-100 times greater than pentosidine (the current most commonly used marker of AGEs in bone). We then establish the viability of CML as a measurable AGE in bone by showing that levels of CML, obtained from bone using this technique, increase with age (p<0.05) and are correlated with previously reported measures of bone toughness. Thus, CML is a viable non-fluorescent AGE target to assess AGE accumulation and fragility in bone. The method developed here to extract and measure CML from human bone could facilitate the development of a new diagnostic assay to evaluate fracture risk and potentially lead to new therapeutic approaches to address bone fragility. Copyright © 2018 Elsevier Inc. All rights reserved.

Maximal voluntary isokinetic knee flexion torque is associated with femoral shaft bone strength indices in knee replacement patients.

PubMed

Rantalainen, T; Valtonen, A; Sipilä, S; Pöyhönen, T; Heinonen, A

2012-03-01

It is currently unknown whether knee replacement-associated bone loss is modified by rehabilitation programs. Thus, a sample of 45 (18 men and 25 women) persons with unilateral knee replacement were recruited; age 66 years (sd 6), height 169 cm (sd 8), body mass 83 kg (sd 15), time since operation 10 months (sd 4) to explore the associations between maximal torque/power in knee extension/flexion and femoral mid-shaft bone traits (Cortical cross-sectional area (CoA, mm(2)), cortical volumetric bone mineral density (CoD, mg/mm(3)) and bone bending strength index (SSI, mm(3))). Bone traits were calculated from a single computed tomography slice from the femoral mid-shaft. Pain in the operated knee was assessed with the WOMAC questionnaire. Stepwise regression models were built for the operated leg bone traits, with knee extension and flexion torque and power, age, height, body mass, pain score and time since operation as independent variables. CoA was 2.3% (P=0.015), CoD 1.2% (P<0.001) and SSI 1.6% (P=0.235) lower in the operated compared to non-operated leg. The overall proportions of the variation explained by the regression models were 50%, 29% and 55% for CoA, CoD and SSI, respectively. Body mass explained 12% of Coa, 11% of CoD and 11% of SSI (P≤0.003). Maximal knee flexion torque explained 38% of Coa, 7% of CoD and 44% of SSI (p≤0.047). For CoD time since operation also became a significant predictor (11%, P=0.045). Knee flexion torque of the operated leg was positively associated with bone strength in the operated leg. Thus, successful rehabilitation may diminish bone loss in the operated leg. Copyright © 2011 Elsevier B.V. All rights reserved.

Insights into relationships between body mass, composition and bone: findings in elite rugby players.

PubMed

Hind, Karen; Gannon, Lisa; Brightmore, Amy; Beck, Belinda

2015-01-01

Recent reports indicate that bone strength is not proportional to body weight in obese populations. Elite rugby players have a similar body mass index (BMI) to obese individuals but differ markedly with low body fat, high lean mass, and frequent skeletal exposure to loading through weight-bearing exercise. The purpose of this study was to determine relationships between body weight, composition, and bone strength in male rugby players characterized by high BMI and high lean mass. Fifty-two elite male rugby players and 32 nonathletic, age-matched controls differing in BMI (30.2 ± 3.2 vs 24.1 ± 2.1 kg/m²; p = 0.02) received 1 total body and one total hip dual-energy X-ray absorptiometry scan. Hip structural analysis of the proximal femur was used to determine bone mineral density (BMD) and cross-sectional bone geometry. Multiple linear regression was computed to identify independent variables associated with total hip and femoral neck BMD and hip structural analysis-derived bone geometry parameters. Analysis of covariance was used to explore differences between groups. Further comparisons between groups were performed after normalizing parameters to body weight and to lean mass. There was a trend for a positive fat-bone relationship in rugby players, and a negative relationship in controls, although neither reached statistical significance. Correlations with lean mass were stronger for bone geometry (r(2): 0.408-0.520) than for BMD (r(2): 0.267-0.293). Relative to body weight, BMD was 6.7% lower in rugby players than controls (p < 0.05). Rugby players were heavier than controls, with greater lean mass and BMD (p < 0.01). Relative to lean mass, BMD was 10%-14.3% lower in rugby players (p < 0.001). All bone geometry measures except cross-sectional area were proportional to body weight and lean mass. To conclude, BMD in elite rugby players was reduced in proportion to body weight and lean mass. However, their superior bone geometry suggests that overall bone strength may be adequate for loading demands. Fat-bone interactions in athletes engaged in high-impact sports require further exploration. Copyright © 2015. Published by Elsevier Inc.

Predicting bone mineral acquisition during puberty: data from a 3-year follow-up study in Hamamatsu, Japan.

PubMed

Kouda, Katsuyasu; Ohara, Kumiko; Nakamura, Harunobu; Fujita, Yuki; Iki, Masayuki

2017-03-01

Although most adult bone mass is acquired before adolescence, only a few studies have assessed bone turnover markers in children. Thus, the utility of bone markers to evaluate and predict bone mineral accrual in children is unclear. The present study assessed the association between serum bone markers at 11 years of age and subsequent changes in bone gain. Information on bone minerals and bone markers at baseline and at the 3-year follow-up were obtained from 121 children who registered as fifth-grade students in 2010, in Hamamatsu, Japan. Whole-body bone mineral content (WBBMC) and whole-body bone mineral density (WBBMD) were measured using dual-energy X-ray absorptiometry. Boys showed significant (P < 0.05) positive relationships between intact osteocalcin at baseline and WBBMC at follow-up (β = 0.24), between tartrate-resistant acid phosphatase isoenzyme 5b (TRAP5b) and WBBMC (β = 0.34), and between TRAP5b and WBBMD (β = 0.34), after adjusting for potential confounding factors. In girls, adjusted means of 3-year gain in both WBBMC and WBBMD significantly increased from the lowest to highest quartiles of type 1 collagen cross-linked C-terminal telopeptide. In boys, adjusted means of 3-year gain in both WBBMC and WBBMD significantly increased from the lowest to highest quartiles of TRAP5b. Children with a high concentration of bone turnover markers tended to exhibit substantial accrual of bone minerals. These results suggest that serum levels of circulating biomarkers at age 11 predict subsequent bone mineral accrual.

Diagnostic value of MRI signs in differentiating Ewing sarcoma from osteomyelitis.

PubMed

Kasalak, Ömer; Overbosch, Jelle; Adams, Hugo Ja; Dammann, Amelie; Dierckx, Rudi Ajo; Jutte, Paul C; Kwee, Thomas C

2018-01-01

Background The value of magnetic resonance imaging (MRI) signs in differentiating Ewing sarcoma from osteomyelitis has not be thoroughly investigated. Purpose To investigate the value of various MRI signs in differentiating Ewing sarcoma from osteomyelitis. Material and Methods Forty-one patients who underwent MRI because of a bone lesion of unknown nature with a differential diagnosis that included both Ewing sarcoma and osteomyelitis were included. Two observers assessed several MRI signs, including the transition zone of the bone lesion, the presence of a soft-tissue mass, intramedullary and extramedullary fat globules, and the penumbra sign. Results Diagnostic accuracies for discriminating Ewing sarcoma from osteomyelitis were 82.4% and 79.4% for the presence of a soft-tissue mass, and 64.7% and 58.8% for a sharp transition zone of the bone lesion, for readers 1 and 2 respectively. Inter-observer agreement with regard to the presence of a soft-tissue mass and the transition zone of the bone lesion were moderate (κ = 0.470) and fair (κ = 0.307), respectively. Areas under the receiver operating characteristic curve of the diameter of the soft-tissue mass (if present) were 0.829 and 0.833, for readers 1 and 2 respectively. Mean inter-observer difference in soft-tissue mass diameter measurement ± limits of agreement was 35.0 ± 75.0 mm. Diagnostic accuracies of all other MRI signs were all < 50%. Conclusion Presence and size of a soft-tissue mass, and sharpness of the transition zone, are useful MRI signs to differentiate Ewing sarcoma from osteomyelitis, but inter-observer agreement is relatively low. Other MRI signs are of no value in this setting.

Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice.

PubMed

Oestreich, A K; Carleton, S M; Yao, X; Gentry, B A; Raw, C E; Brown, M; Pfeiffer, F M; Wang, Y; Phillips, C L

2016-01-01

Mice with osteogenesis imperfecta (+/oim), a disorder of bone fragility, were bred to mice with muscle over growth to test whether increasing muscle mass genetically would improve bone quality and strength. The results demonstrate that femora from mice carrying both mutations have greater mechanical integrity than their +/oim littermates. Osteogenesis imperfecta is a heritable connective tissue disorder due primarily to mutations in the type I collagen genes resulting in skeletal deformity and fragility. Currently, there is no cure, and therapeutic strategies encompass the use of antiresorptive pharmaceuticals and surgical bracing, with limited success and significant potential for adverse effects. Bone, a mechanosensing organ, can respond to high mechanical loads by increasing new bone formation and altering bone geometry to withstand increased forces. Skeletal muscle is a major source of physiological loading on bone, and bone strength is proportional to muscle mass. To test the hypothesis that congenic increases in muscle mass in the osteogenesis imperfecta murine model mouse (oim) will improve their compromised bone quality and strength, heterozygous (+/oim) mice were bred to mice deficient in myostatin (+/mstn), a negative regulator of muscle growth. The resulting adult offspring were evaluated for hindlimb muscle mass, and bone microarchitecture, physiochemistry, and biomechanical integrity. +/oim mice deficient in myostatin (+/mstn +/oim) were generated and demonstrated that myostatin deficiency increased body weight, muscle mass, and biomechanical strength in +/mstn +/oim mice as compared to +/oim mice. Additionally, myostatin deficiency altered the physiochemical properties of the +/oim bone but did not alter bone remodeling. Myostatin deficiency partially improved the reduced femoral bone biomechanical strength of adult +/oim mice by increasing muscle mass with concomitant improvements in bone microarchitecture and physiochemical properties.

Associations of components of sarcopenic obesity with bone health and balance in older adults.

PubMed

Scott, David; Shore-Lorenti, Catherine; McMillan, Lachlan; Mesinovic, Jakub; Clark, Ross A; Hayes, Alan; Sanders, Kerrie M; Duque, Gustavo; Ebeling, Peter R

To determine characteristics of sarcopenic obesity that are independently associated with bone health and balance in older adults. Cross-sectional study of 168 community-dwelling older adults (mean age 67.7 ± 8.4 years; 55% women). Appendicular lean mass (ALM), whole-body areal BMD (aBMD) and body fat percentage were assessed by dual-energy X-ray absorptiometry. Peripheral quantitative computed tomography assessed muscle density and cortical volumetric BMD (vBMD), area, thickness, and strength-strain index (SSI) at 66% tibial length. Hand grip strength (dynamometry) and balance path length (computerised posturography) were assessed. Obesity was defined as high body fat percentage. Greater lower-leg muscle density was associated with lower balance path length in men (r = -0.36; P < .01) and women (r = -0.40; P = < .01). Obese participants by body fat percentage did not differ to non-obese on bone indices, although a trend towards lower cortical vBMD was observed in obese compared with non-obese men (1041.4 ± 39.8 vs 1058.8 ± 36.1 mg/cm 3 ; P = .051). In multivariable models, ALM was positively associated with all bone parameters in obese women, and with whole-body aBMD, proximal tibial cortical area and SSI in non-obese women, and both non-obese and obese men (all P < .05). Lower-leg muscle density was also positively associated with cortical vBMD (B = 2.91; 95% CI 0.02, 5.80) and area (2.70; 0.06, 5.33) in obese women. Amongst components of sarcopenic obesity, higher ALM is a consistent independent predictor of better bone health. Low muscle density may also compromise bone health and balance. Interventions which improve muscle mass and composition may lower fracture risk in sarcopenic obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

Synchrotron Ultraviolet Microspectroscopy on Rat Cortical Bone: Involvement of Tyrosine and Tryptophan in the Osteocyte and Its Environment

PubMed Central

Pallu, Stéphane; Rochefort, Gael Y.; Jaffre, Christelle; Refregiers, Matthieu; Maurel, Delphine B.; Benaitreau, Delphine; Lespessailles, Eric; Jamme, Frédéric; Chappard, Christine; Benhamou, Claude-Laurent

2012-01-01

Alcohol induced osteoporosis is characterized by a bone mass decrease and microarchitecture alterations. Having observed an excess in osteocyte apoptosis, we aimed to assess the bone tissue biochemistry, particularly in the osteocyte and its environment. For this purpose, we used a model of alcohol induced osteoporosis in rats. Bone sections of cortical bone were investigated using synchrotron UV-microspectrofluorescence at subcellular resolution. We show that bone present three fluorescence peaks at 305, 333 and 385 nm, respectively corresponding to tyrosine, tryptophan and collagen. We have determined that tyrosine/collagen and tryptophan/collagen ratios were higher in the strong alcohol consumption group. Tryptophan is related to the serotonin metabolism involved in bone formation, while tyrosine is involved in the activity of tyrosine kinases and phosphatases in osteocytes. Our experiment represents the first combined synchrotron UV microspectroscopy analysis of bone tissue with a quantitative biochemical characterization in the osteocyte and surrounding matrix performed separately. PMID:22937127

Bone mineralization in childhood and adolescence.

PubMed

Bachrach, L K

1993-08-01

Prevention of osteoporosis depends on establishing adequate peak bone mass in the first two decades of life. Achievement of this goal requires an understanding of factors that promote skeletal health. Genetic factors are important determinants of adult bone mass, but nonheritable variables, including body mass, calcium nutriture, sex steroids, and activity can strongly influence whether maximal bone mineral is achieved. Acquisition of bone mineral continues throughout childhood and adolescence, reaching a lifetime maximum in early adulthood. Adolescence is a particularly critical time for bone mineral accretion as more than half of the bone calcium is normally laid down during the teen years. Chronic illness, malnutrition, or endocrine deficiencies at this age may result in profound deficits in bone mass, which may not be fully reversible. These risk factors contribute to the osteopenia associated with anorexia nervosa, exercise-induced amenorrhea, delayed puberty, Turner's syndrome, and growth hormone deficiency.

Effect of swimming on bone metabolism in adolescents.

PubMed

Derman, Orhan; Cinemre, Alphan; Kanbur, Nuray; Doğan, Muhsin; Kiliç, Mustafa; Karaduman, Erdem

2008-01-01

Physical activity has been shown to have a positive effect on bone metabolism among adolescents. The objective of this study was to determine the effect of swimming on bone metabolism during adolescence. Swimming, as a non-weight-bearing sport, has been considered to be insignificant in the maintenance of bone mass. We studied whether swimming is associated with a higher peak bone mass. Forty swimmers (males aged 10-17 years and females aged 9-16 years) were studied. The control group consisted of the same number of adolescents aged between 10-16 years who did not swim; distribution of male and female gender was similar in the non-swimming control group compared to the swimming group. Adolescents were matched for age, gender and pubertal stages based on Tanner staging. All subjects underwent combined measurement of bone mineral metabolism by dual-energy X-ray absorptiometry of total body calcium content, and specific biochemical markers of turnover including osteocalcin, calcium, phosphorus and alkaline phosphatase. Bone age (determined by Greulich and Pyle's Radiographic Atlas of Skeletal Development of the Hand and Wrist), weight, height, ideal body weight, ideal body weight ratio, body mass index, Tanner classification (rated by examiner), diet, history of tobacco and alcohol exposure, exercise, socioeconomic status and history of chronic illness and medications were recorded to evaluate potential mediators that would affect bone metabolism. Tanner staging was used to assess puberty, and diet was evaluated based on reported consumption of milk, yogurt and cheese and cola/caffeine beverage consumption daily. There was significant difference in bone mineral content between adolescent male swimmers and the control group males. Consumption of cola beverages were significantly higher among the control group compared with the swimmer group. Ideal body weight ratio was significantly high among the female control group compared with female swimmers. Milk consumption was significantly higher for both male and female swimmer groups, whereas yogurt consumption was only significantly higher in the male swimmer group compared with control group. These results indicate that a highly active nonimpact sport such as swimming may lead to increased bone mineral content only for male swimmers. However, dietary behaviors may be more important than swimming on bone metabolism among adolescents.

Is Bone Tissue Really Affected by Swimming? A Systematic Review

PubMed Central

Gómez-Bruton, Alejandro; Gónzalez-Agüero, Alejandro; Gómez-Cabello, Alba; Casajús, José A.; Vicente-Rodríguez, Germán

2013-01-01

Background Swimming, a sport practiced in hypogravity, has sometimes been associated with decreased bone mass. Aim This systematic review aims to summarize and update present knowledge about the effects of swimming on bone mass, structure and metabolism in order to ascertain the effects of this sport on bone tissue. Methods A literature search was conducted up to April 2013. A total of 64 studies focusing on swimmers bone mass, structure and metabolism met the inclusion criteria and were included in the review. Results It has been generally observed that swimmers present lower bone mineral density than athletes who practise high impact sports and similar values when compared to sedentary controls. However, swimmers have a higher bone turnover than controls resulting in a different structure which in turn results in higher resistance to fracture indexes. Nevertheless, swimming may become highly beneficial regarding bone mass in later stages of life. Conclusion Swimming does not seem to negatively affect bone mass, although it may not be one of the best sports to be practised in order to increase this parameter, due to the hypogravity and lack of impact characteristic of this sport. Most of the studies included in this review showed similar bone mineral density values in swimmers and sedentary controls. However, swimmers present a higher bone turnover than sedentary controls that may result in a stronger structure and consequently in a stronger bone. PMID:23950908

Targeted disruption of BMP signaling through type IA receptor (BMPR1A) in osteocyte suppresses SOST and RANKL, leading to dramatic increase in bone mass, bone mineral density and mechanical strength.

PubMed

Kamiya, Nobuhiro; Shuxian, Lin; Yamaguchi, Ryosuke; Phipps, Matthew; Aruwajoye, Olumide; Adapala, Naga Suresh; Yuan, Hui; Kim, Harry K W; Feng, Jian Q

2016-10-01

Recent studies suggest a critical role of osteocytes in controlling skeletal development and bone remodeling although the molecular mechanism is largely unknown. This study investigated BMP signaling in osteocytes by disrupting Bmpr1a under the Dmp1-promoter. The conditional knockout (cKO) mice displayed a striking osteosclerotic phenotype with increased trabecular bone volume, thickness, number, and mineral density as assessed by X-ray and micro-CT. The bone histomorphometry, H&E, and TRAP staining revealed a dramatic increase in trabecular and cortical bone masses but a sharp reduction in osteoclast number. Moreover, there was an increase in BrdU positive osteocytes (2-5-fold) and osteoid volume (~4-fold) but a decrease in the bone formation rate (~85%) in the cKO bones, indicating a defective mineralization. The SEM analysis revealed poorly formed osteocytes: a sharp increase in cell numbers, a great reduction in cell dendrites, and a remarkable change in the cell distribution pattern. Molecular studies demonstrated a significant decrease in the Sost mRNA levels in bone (>95%), and the SOST protein levels in serum (~85%) and bone matrices. There was a significant increase in the β-catenin (>3-fold) mRNA levels as well as its target genes Tcf1 (>6-fold) and Tcf3 (~2-fold) in the cKO bones. We also showed a significant decrease in the RANKL levels of serum proteins (~65%) and bone mRNA (~57%), and a significant increase in the Opg mRNA levels (>20-fold) together with a significant reduction in the Rankl/Opg ratio (>95%), which are responsible for a sharp reduction in the cKO osteoclasts. The values of mechanical strength were higher in cKO femora (i.e. max force, displacement, and work failure). These results suggest that loss of BMP signaling specifically in osteocytes dramatically increases bone mass presumably through simultaneous inhibition of RANKL and SOST, leading to osteoclast inhibition and Wnt activation together. Finally, a working hypothesis is proposed to explain how BMPR1A controls bone remodeling by inhibiting cell proliferation and stimulating differentiation. It is reported that RANKL and SOST are abundantly expressed by osteocytes. Thus, BMP signaling through BMPR1A plays important roles in osteocytes. Copyright © 2016 Elsevier Inc. All rights reserved.

Muscle and bone follow similar temporal patterns of recovery from muscle-induced disuse due to botulinum toxin injection.

PubMed

Manske, Sarah L; Boyd, Steven K; Zernicke, Ronald F

2010-01-01

If muscle force is a primary source for triggering bone adaptation, with disuse and reloading, bone changes should follow muscle changes. We examined the timing and magnitude of changes in muscle cross-sectional area (MCSA) and bone architecture in response to muscle inactivity following botulinum toxin (BTX) injection. We hypothesized that MCSA would return to baseline levels sooner than bone properties following BTX injection. Female BALB mice (15 weeks old) were injected with 20 muL of BTX (1 U/100 g body mass, n=18) or saline (SAL, n=18) into the posterior calf musculature of one limb. The contralateral limb (CON) served as an internal control. MCSA and bone properties were assessed at baseline, 2, 4, 8, 12, and 16 weeks post-injection using in vivo micro-CT at the tibia proximal metaphysis (bone only) and diaphysis. Muscles were dissected and weighed after sacrifice. Significant GroupxLegxTime interactions indicated that the maximal decrease in MCSA (56%), proximal metaphyseal BV/TV (38%) and proximal diaphyseal Ct.Ar (7%) occurred 4 weeks after injection. There was no delay prior to bone recovery as both muscle and bone properties began to recover after this time, but MCSA and BV/TV remained 15% and 20% lower, respectively, in the BTX-injected leg than the BTX-CON leg 16 weeks post-injection. Gastrocnemius mass (primarily fast-twitch) was 14% lower in the BTX-injected leg than the SAL-injected leg, while soleus mass (primarily slow-twitch) was 15% greater in the BTX group than the SAL group. Our finding that muscle size and bone began to recover at similar times after BTX injection was unexpected. This suggested that partial weight-bearing and/or return of slow-twitch muscle activity in the BTX leg may have been sufficient to stimulate bone recovery. Alternatively, muscle function may have recovered sooner than MCSA. Our results indicated that muscle cross-sectional area, while important, may not be the primary factor associated with bone loss and recovery when muscle atrophy is induced through BTX injection. To understand the nature of the interaction between muscle and bone, future work should focus on the functional recovery of individual muscles in relation to bone. Copyright (c) 2009 Elsevier Inc. All rights reserved.

The Assessment of Bone Regulatory Pathways, Bone Turnover, and Bone Mineral Density in Vegetarian and Omnivorous Children

PubMed Central

Ambroszkiewicz, Jadwiga; Chełchowska, Magdalena; Szamotulska, Katarzyna; Rowicka, Grażyna; Klemarczyk, Witold; Strucińska, Małgorzata

2018-01-01

Vegetarian diets contain many beneficial properties as well as carry a risk of inadequate intakes of several nutrients important to bone health. The aim of the study was to evaluate serum levels of bone metabolism markers and to analyze the relationships between biochemical bone markers and anthropometric parameters in children on vegetarian and omnivorous diets. The study included 70 prepubertal children on a lacto-ovo-vegetarian diet and 60 omnivorous children. Body composition, bone mineral content (BMC), and bone mineral density (BMD) were assessed by dual-energy X-ray absorptiometry. Biochemical markers—bone alkaline phosphatase (BALP), C-terminal telopeptide of type I collagen (CTX-I), osteoprotegerin (OPG), nuclear factor κB ligand (RANKL), sclerostin, and Dickkopf-related protein 1 (Dkk-1)—were measured using immunoenzymatic assays. In vegetarians, we observed a significantly higher level of BALP (p = 0.002) and CTX-I (p = 0.027), and slightly lower spine BMC (p = 0.067) and BMD (p = 0.060) than in omnivores. Concentrations of OPG, RANKL, sclerostin, and Dkk-1 were comparable in both groups of children. We found that CTX-I was positively correlated with BMC, total BMD, and lumbar spine BMD in vegetarians, but not in omnivores. A well-planned vegetarian diet with proper dairy and egg intake does not lead to significantly lower bone mass; however, children following a lacto-ovo-vegetarian diet had a higher rate of bone turnover and subtle changes in bone regulatory markers. CTX-I might be an important marker for the protection of vegetarians from bone abnormalities. PMID:29414859

The Assessment of Bone Regulatory Pathways, Bone Turnover, and Bone Mineral Density in Vegetarian and Omnivorous Children.

PubMed

Ambroszkiewicz, Jadwiga; Chełchowska, Magdalena; Szamotulska, Katarzyna; Rowicka, Grażyna; Klemarczyk, Witold; Strucińska, Małgorzata; Gajewska, Joanna

2018-02-07

Vegetarian diets contain many beneficial properties as well as carry a risk of inadequate intakes of several nutrients important to bone health. The aim of the study was to evaluate serum levels of bone metabolism markers and to analyze the relationships between biochemical bone markers and anthropometric parameters in children on vegetarian and omnivorous diets. The study included 70 prepubertal children on a lacto-ovo-vegetarian diet and 60 omnivorous children. Body composition, bone mineral content (BMC), and bone mineral density (BMD) were assessed by dual-energy X-ray absorptiometry. Biochemical markers-bone alkaline phosphatase (BALP), C-terminal telopeptide of type I collagen (CTX-I), osteoprotegerin (OPG), nuclear factor κB ligand (RANKL), sclerostin, and Dickkopf-related protein 1 (Dkk-1)-were measured using immunoenzymatic assays. In vegetarians, we observed a significantly higher level of BALP ( p = 0.002) and CTX-I ( p = 0.027), and slightly lower spine BMC ( p = 0.067) and BMD ( p = 0.060) than in omnivores. Concentrations of OPG, RANKL, sclerostin, and Dkk-1 were comparable in both groups of children. We found that CTX-I was positively correlated with BMC, total BMD, and lumbar spine BMD in vegetarians, but not in omnivores. A well-planned vegetarian diet with proper dairy and egg intake does not lead to significantly lower bone mass; however, children following a lacto-ovo-vegetarian diet had a higher rate of bone turnover and subtle changes in bone regulatory markers. CTX-I might be an important marker for the protection of vegetarians from bone abnormalities.

Effects of vitamin K2 on cortical and cancellous bone mass, cortical osteocyte and lacunar system, and porosity in sciatic neurectomized rats.

PubMed

Iwamoto, Jun; Matsumoto, Hideo; Takeda, Tsuyoshi; Sato, Yoshihiro; Yeh, James K

2010-09-01

The purpose of the present study was to examine the effects of vitamin K2 on cortical and cancellous bone mass, cortical osteocyte and lacunar system, and porosity in sciatic neurectomized rats. Thirty-four female Sprague-Dawley retired breeder rats were randomized into three groups: age-matched control, sciatic neurectomy (NX), and NX + vitamin K2 administration (menatetrenone, 30 mg/kg/day p.o., three times a week). At the end of the 8-week experiment, bone histomorphometric analysis was performed on cortical and cancellous bone of the tibial diaphysis and proximal metaphysis, respectively, and osteocyte lacunar system and porosity were evaluated on cortical bone of the tibial diaphysis. NX decreased cortical and cancellous bone mass compared with age-matched controls as a result of increased endocortical and trabecular bone erosion and decreased trabecular mineral apposition rate (MAR). Vitamin K2 ameliorated the NX-induced increase in bone erosion, prevented the NX-induced decrease in MAR, and increased bone formation rate (BFR/bone surface) in cancellous bone, resulting in an attenuation of NX-induced cancellous bone loss. However, vitamin K2 did not significantly influence cortical bone mass. NX also decreased osteocyte density and lacunar occupancy and increased porosity in cortical bone compared with age-matched controls. Vitamin K2 ameliorated the NX-induced decrease in lacunar occupancy by viable osteocytes and the NX-induced increase in porosity. The present study showed the efficacy of vitamin K2 for cancellous bone mass and cortical lacunar occupancy by viable osteocytes and porosity in sciatic NX rats.

Physical activity in the prevention and amelioration of osteoporosis in women : interaction of mechanical, hormonal and dietary factors.

PubMed

Borer, Katarina T

2005-01-01

Osteoporosis is a serious health problem that diminishes quality of life and levies a financial burden on those who fear and experience bone fractures. Physical activity as a way to prevent osteoporosis is based on evidence that it can regulate bone maintenance and stimulate bone formation including the accumulation of mineral, in addition to strengthening muscles, improving balance, and thus reducing the overall risk of falls and fractures. Currently, our understanding of how to use exercise effectively in the prevention of osteoporosis is incomplete. It is uncertain whether exercise will help accumulate more overall peak bone mass during childhood, adolescence and young adulthood. Also, the consistent effectiveness of exercise to increase bone mass, or at least arrest the loss of bone mass after menopause, is also in question. Within this framework, section 1 introduces mechanical characteristics of bones to assist the reader in understanding their responses to physical activity. Section 2 reviews hormonal, nutritional and mechanical factors necessary for the growth of bones in length, width and mineral content that produce peak bone mass in the course of childhood and adolescence using a large sample of healthy Caucasian girls and female adolescents for reference. Effectiveness of exercise is evaluated throughout using absolute changes in bone with the underlying assumption that useful exercise should produce changes that approximate or exceed the absolute magnitude of bone parameters in a healthy reference population. Physical activity increases growth in width and mineral content of bones in girls and adolescent females, particularly when it is initiated before puberty, carried out in volumes and at intensities seen in athletes, and accompanied by adequate caloric and calcium intakes. Similar increases are seen in young women following the termination of statural growth in response to athletic training, but not to more limited levels of physical activity characteristic of longitudinal training studies. After 9-12 months of regular exercise, young adult women often show very small benefits to bone health, possibly because of large subject attrition rates, inadequate exercise intensity, duration or frequency, or because at this stage of life accumulation of bone mass may be at its natural peak. The important influence of hormones as well as dietary and specific nutrient abundance on bone growth and health are emphasised, and premature bone loss associated with dietary restriction and estradiol withdrawal in exercise-induced amenorrhoea is described. In section 3, the same assessment is applied to the effects of physical activity in postmenopausal women. Studies of postmenopausal women are presented from the perspective of limitations of the capacity of the skeleton to adapt to mechanical stress of exercise due to altered hormonal status and inadequate intake of specific nutrients. After menopause, effectiveness of exercise to increase bone mineral depends heavily on adequate availability of dietary calcium. Relatively infrequent evidence that physical activity prevents bone loss or increases bone mineral after menopause may be a consequence of inadequate calcium availability or low intensity of exercise in training studies. Several studies with postmenopausal women show modest increases in bone mineral toward the norm seen in a healthy population in response to high-intensity training. Physical activities continue to stimulate increases in bone diameter throughout the lifespan. These exercise-stimulated increases in bone diameter diminish the risk of fractures by mechanically counteracting the thinning of bones and increases in bone porosity. Seven principles of bone adaptation to mechanical stress are reviewed in section 4 to suggest how exercise by human subjects could be made more effective. They posit that exercise should: (i) be dynamic, not static; (ii) exceed a threshold intensity; (iii) exceed a threshold strain frequency; (iv) be relatively brief but intermittent; (v) impose an unusual loading pattern on the bones; (vi) be supported by unlimited nutrient energy; and (vii) include adequate calcium and cholecalciferol (vitamin D3) availability.

Impaired rib bone mass and quality in end-stage cystic fibrosis patients.

PubMed

Mailhot, Geneviève; Dion, Natalie; Farlay, Delphine; Rizzo, Sébastien; Bureau, Nathalie J; Jomphe, Valérie; Sankhe, Safiétou; Boivin, Georges; Lands, Larry C; Ferraro, Pasquale; Ste-Marie, Louis-Georges

2017-05-01

Advancements in research and clinical care have considerably extended the life expectancy of cystic fibrosis (CF) patients. However, with this extended survival come comorbidities. One of the leading co-morbidities is CF-related bone disease (CFBD), which progresses with disease severity and places patients at high risk for fractures, particularly of the ribs and vertebrae. Evidence that CF patients with vertebral fractures had higher bone mineral density (BMD) than the nonfracture group led us to postulate that bone quality is impaired in these patients. We therefore examined rib specimens resected at the time of lung transplant in CF patients to measure parameters of bone quantity and quality. In this exploratory study, we analysed 19 end-stage CF and 13 control rib specimens resected from otherwise healthy lung donors. BMD, bone microarchitecture, static parameters of bone formation and resorption and microcrack density of rib specimens were quantified by imaging, histomorphometric and histological methods. Variables reflecting the mineralization of ribs were assessed by digitized microradiography. The degree of bone mineralization (g/cm 3 ) and the heterogeneity index of the mineralization (g/cm 3 ) were calculated for trabecular and cortical bone. Compared to controls, CF ribs exhibited lower areal and trabecular volumetric BMD, decreased trabecular thickness and osteoid parameters, and increased microcrack density, that was particularly pronounced in specimens from patients with CF-related diabetes. Static parameters of bone resorption were similar in both groups. Degree of mineralization of total bone, but not heterogeneity index, was increased in CF specimens. The combination of reduced bone mass, altered microarchitecture, imbalanced bone remodeling (maintained bone resorption but decreased formation), increased microdamage and a small increase of the degree of mineralization, may lead to decreased bone strength, which, when coupled with chronic coughing and chest physical therapy, may provide an explanation for the increased incidence of rib fractures previously reported in this population. Copyright © 2017 Elsevier Inc. All rights reserved.

High fat diet attenuates hyperglycemia, body composition changes, and bone loss in male streptozotocin-induced type 1 diabetic mice.

PubMed

Carvalho, Adriana Lelis; DeMambro, Victoria E; Guntur, Anyonya R; Le, Phuong; Nagano, Kenichi; Baron, Roland; de Paula, Francisco José Albuquerque; Motyl, Katherine J

2018-02-01

There is a growing and alarming prevalence of obesity and the metabolic syndrome in type I diabetic patients (T1DM), particularly in adolescence. In general, low bone mass, higher fracture risk, and increased marrow adipose tissue (MAT) are features of diabetic osteopathy in insulin-deficient subjects. On the other hand, type 2 diabetes (T2DM) is associated with normal or high bone mass, a greater risk of peripheral fractures, and no change in MAT. Therefore, we sought to determine the effect of weight gain on bone turnover in insulin-deficient mice. We evaluated the impact of a 6-week high-fat (HFD) rich in medium chain fatty acids or low-fat diet (LFD) on bone mass and MAT in a streptozotocin (STZ)-induced model using male C57BL/6J mice at 8 weeks of age. Dietary intervention was initiated after diabetes confirmation. At the endpoint, lower non-fasting glucose levels were observed in diabetic mice fed with high fat diet compared to diabetic mice fed the low fat diet (STZ-LFD). Compared to euglycemic controls, the STZ-LFD had marked polydipsia and polyphagia, as well as reduced lean mass, fat mass, and bone parameters. Interestingly, STZ-HFD mice had higher bone mass, namely less cortical bone loss and more trabecular bone than STZ-LFD. Thus, we found that a HFD, rich in medium chain fatty acids, protects against bone loss in a T1DM mouse model. Whether this may also translate to T1DM patients who are overweight or obese in respect to maintenance of bone mass remains to be determined through longitudinal studies. © 2017 Wiley Periodicals, Inc.

Bone and Skeletal Muscle: Key Players in Mechanotransduction and Potential Overlapping Mechanisms

PubMed Central

Goodman, Craig A.; Hornberger, Troy A.; Robling, Alexander G.

2015-01-01

The development and maintenance of skeletal muscle and bone mass is critical for movement, health and issues associated with the quality of life. Skeletal muscle and bone mass are regulated by a variety of factors that include changes in mechanical loading. Moreover, bone mass is, in large part, regulated by muscle-derived mechanical forces and thus by changes in muscle mass/strength. A thorough understanding of the cellular mechanism(s) responsible for mechanotransduction in bone and skeletal muscle is essential for the development of effective exercise and pharmaceutical strategies aimed at increasing, and/or preventing the loss of, mass in these tissues. Thus, in this review we will attempt to summarize the current evidence for the major molecular mechanisms involved in mechanotransduction in skeletal muscle and bone. By examining the differences and similarities in mechanotransduction between these two tissues, it is hoped that this review will stimulate new insights and ideas for future research and promote collaboration between bone and muscle biologists. PMID:26453495

Bone mass and lifestyle related factors: a comparative study between Japanese and Inner Mongolian young premenopausal women.

PubMed

Zhang, M; Shimmura, T; Bi, L F; Nagase, H; Nishino, H; Kajita, E; Eto, M; Wang, H B; Su, X L; Chang, H; Aratani, T; Kagamimori, S

2004-07-01

The purpose of this study was to evaluate the ethnic difference in bone mass between Japanese and Inner Mongolian young premenopausal women and to assess the contribution of lifestyle related and anthropometric factors to bone mass. We studied 33 Japanese and 44 Inner Mongolian healthy young women, aged 20-34 years, in urban area. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness index (SI) were measured at the calcaneus using quantitative ultrasound (QUS) analysis. Age at menarche, regularity of menstruation and lifestyle related factors were estimated by a self-reported questionnaire. There were no differences between the two groups in age, height, weight, BMI, regularity of menstruation, frequency of meat intake, frequency of yellow-green vegetable intake and exercise habit. Japanese women had significantly lower age at menarche and higher proportion of milk consumption habit at junior high school, senior school and present. Before adjustment, Japanese women had significantly higher SOS and SI than Inner Mongolian women. However, after adjustment for age at menarche and milk consumption habit at junior high school, both of which were significantly different between groups, no group-differences remained in either SOS or SI. These results suggest that the differences in age at menarche and milk consumption habit at junior high school, which relate to hormonal and nutritional status during puberty, may account for the differences in bone mass between Japanese and Inner Mongolian young women.

Marrow Fat Quality Differences by Sex in Healthy Adults.

PubMed

Maciel, Jamilly G; de Araújo, Iana M; Carvalho, Adriana L; Simão, Marcelo N; Bastos, Clara M; Troncon, Luiz E A; Salmon, Carlos E G; de Paula, Francisco J A; Nogueira-Barbosa, Marcello H

Several studies have demonstrated the relationship between bone marrow adiposity (BMAT) and bone mass. 1 H magnetic resonance spectroscopy is a noninvasive technique able to assess both BMAT quantity and quality. The aim of our study was to perform quantitative and qualitative analyses of BMAT and to investigate its association with bone mineral density (BMD) in healthy nonobese volunteers. Fifty-one healthy volunteers, 21 men and 30 women, underwent 1.5 T 1 H magnetic resonance spectroscopy of the lumbar spine. BMD was determined by dual-energy X-ray absorptiometry of the lumbar spine. Correlation analysis was performed to evaluate association among lipids fractions, BMD, and age. The female and male volunteers had similar body mass index and BMD (p > 0.05). Our data demonstrated an inverse correlation of BMD and BMAT with age, with a stronger correlation of saturated lipids (r = 0.701; p < 0.0001) compared with unsaturated lipids (UL) (r = 0.278; p = 0.004). Importantly, female subjects had the highest amount of UL (confidence interval: 0.685%-1.722%; p < 0.001). Our study reports that men and women with similar BMD and body mass index have striking differences in bone marrow lipids composition, namely women have higher UL than men. In addition, we believe that our study brings new insights to the complex network involving BMAT and other factors that influence bone integrity. Copyright © 2016 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Effects of whole-body vibration training on physical function, bone and muscle mass in adolescents and young adults with cerebral palsy

PubMed Central

Gusso, Silmara; Munns, Craig F; Colle, Patrícia; Derraik, José G B; Biggs, Janene B; Cutfield, Wayne S; Hofman, Paul L

2016-01-01

We performed a clinical trial on the effects of whole-body vibration training (WBVT) on muscle function and bone health of adolescents and young adults with cerebral palsy. Forty participants (11.3–20.8 years) with mild to moderate cerebral palsy (GMFCS II–III) underwent 20-week WBVT on a vibration plate for 9 minutes/day 4 times/week at 20 Hz (without controls). Assessments included 6-minute walk test, whole-body DXA, lower leg pQCT scans, and muscle function (force plate). Twenty weeks of WBVT were associated with increased lean mass in the total body (+770 g; p = 0.0003), trunk (+410 g; p = 0.004), and lower limbs (+240 g; p = 0.012). Bone mineral content increased in total body (+48 g; p = 0.0001), lumbar spine (+2.7 g; p = 0.0003), and lower limbs (+13 g; p < 0.0001). Similarly, bone mineral density increased in total body (+0.008 g/cm2; p = 0.013), lumbar spine (+0.014 g/cm2; p = 0.003), and lower limbs (+0.023 g/cm2; p < 0.0001). Participants reduced the time taken to perform the chair test, and improved the distance walked in the 6-minute walk test by 11% and 35% for those with GMFCS II and III, respectively. WBVT was associated with increases in muscle mass and bone mass and density, and improved mobility of adolescents and young adults with cerebral palsy. PMID:26936535

Association between site-specific bone mineral density and glucose homeostasis and anthropometric traits in healthy men and women.

PubMed

Kim, Se-Min; Cui, Jinrui; Rhyu, Jane; Guo, Xiuqing; Chen, Yii-Der I; Hsueh, Willa A; Rotter, Jerome I; Goodarzi, Mark O

2018-06-01

Patients with type 2 diabetes mellitus have an increased risk of fracture despite normal or increased bone mineral density (BMD). Studies on the relationship of glucose homeostasis with BMD phenotypes have been inconclusive because distinguishing the roles of insulin resistance and hyperglycaemia in bone remodelling is challenging. In this study, we sought to define the relationship of site-specific BMD with glucose homeostasis traits and anthropometric traits. In a cross-sectional study, we examined 787 subjects from the Mexican-American Coronary Artery Disease (MACAD) cohort who had undergone euglycaemic-hyperinsulinaemic clamps, oral glucose tolerance testing and dual X-ray absorptiometry. Glucose homeostasis traits included insulinogenic index (IGI30), insulin sensitivity (M value), insulin clearance (MCRI), fasting insulin, fasting glucose and 2-hour glucose. Univariate and multivariate analyses were performed to assess the association of glucose homeostasis and anthropometric traits with site-specific BMD. Two-hour glucose was negatively associated with arm BMD in women, which remained significant in multivariate analysis (β = -.15, P = .0015). Positive correlations between fasting insulin and BMD at weight-bearing sites, including pelvis (β = .22, P < .0001) and legs (β = .17, P = .001) in women and pelvis (β = .33, P < .0001) in men, lost significance after multivariate adjustment. Lean mass exhibited strong independent positive associations with BMD at multiple sites in both sexes. Our findings suggest that (i) anabolic effects of insulin might work via mechanical loading from lean mass; (ii) a direct negative effect of increasing glucose might be more prominent at cortical-bone-rich sites in women; and (iii) lean mass is a strong positive predictor of bone mass. © 2018 John Wiley & Sons Ltd.

Relationship between markers of body fat and calcaneal bone stiffness differs between preschool and primary school children: results from the IDEFICS baseline survey.

PubMed

Sioen, Isabelle; Mouratidou, Theodora; Herrmann, Diana; De Henauw, Stefaan; Kaufman, Jean-Marc; Molnár, Dénes; Moreno, Luis A; Marild, Staffan; Barba, Gianvincenzo; Siani, Alfonso; Gianfagna, Francesco; Tornaritis, Michael; Veidebaum, Toomas; Ahrens, Wolfgang

2012-10-01

The aim of this study was to investigate the relationship between markers of body fat and bone status assessed as calcaneal bone stiffness in a large sample of European healthy pre- and primary school children. Participants were 7,447 children from the IDEFICS study (spread over eight different European countries), age 6.1 ± 1.8 years (range 2.1-9.9), 50.5 % boys. Anthropometric measurements (weight, height, bioelectrical impedance, waist and hip circumference, and tricipital and subscapular skinfold thickness) as well as quantitative ultrasonographic measurements to determine calcaneal stiffness index (SI) were performed. Partial correlation analysis, linear regression analysis, and ANCOVA were stratified by sex and age group: preschool boys (n = 1,699) and girls (n = 1,599) and primary school boys (n = 2,062) and girls (n = 2,087). In the overall study population, the average calcaneal SI was equal to 80.2 ± 14.0, ranging 42.4-153. The results showed that preschool children with higher body fat had lower calcaneal SI (significant correlation coefficients between -0.05 and -0.20), while primary school children with higher body fat had higher calcaneal SI (significant correlation coefficients between 0.05 and 0.13). After adjusting for fat-free mass, both preschool and primary school children showed an inverse relationship between body fat and calcaneal stiffness. To conclude, body fat is negatively associated with calcaneal bone stiffness in children after adjustment for fat-free mass. Fat-free mass may confound the association in primary school children but not in preschool children. Muscle mass may therefore be an important determinant of bone stiffness.

Bone mineral density in anorexia nervosa: Only weight and menses recovery?

PubMed

Jáuregui-Lobera, Ignacio; Bolaños-Ríos, Patricia; Sabaté, Juan

2016-11-01

The study objectives were to analyze the presence of reduced bone mass in a sample of patients with anorexia nervosa (AN) and amenorrhea, to assess Bone Mineral Density (BMD) recovery after having a normal weight is reached and regular menses are resumed, and to predict BMD after a treatment period considering different variables (baseline BMD, baseline and final body mass index (BMI), treatment duration). 35 patients with AN (mean age 20.57±5.77) were studied at treatment start (T 0 ) and after they had recovered their normal weight and regular menses (T 1 ) in order to measure their BMD using quantitative computed tomography (QCT) of the lumbar spine (L2-L4). At T 0 , 2.86% of patients had normal BMD, while a reduced bone mass consistent with osteopenia or with osteoporosis was found in 22.86% and 74.28% of patients respectively. At T 1 , the percentages were 20%, 20%, and 60% respectively. No significant differences were seen in L2-L3 and mean BMD (L2-L4). A significant difference was however found for L4 (p<0.05). A positive relationship was seen between final body mass index (BMI) and final BMD in patients with T 0 -T 1 >11 months, but not when the time period was ≤11 months. This follow-up study of changes not only in BMD but also in BMI and recovery of menses has clinical relevance from the viewpoint of the day-by-day treatment process. Use of QCT makes the study more relevant because this is a more advanced technique that allows for differentiating trabecular and cortical bone. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Risk of low bone mineral density and low body mass index in patients with non-celiac wheat-sensitivity: a prospective observation study.

PubMed

Carroccio, Antonio; Soresi, Maurizio; D'Alcamo, Alberto; Sciumè, Carmelo; Iacono, Giuseppe; Geraci, Girolamo; Brusca, Ignazio; Seidita, Aurelio; Adragna, Floriana; Carta, Miriam; Mansueto, Pasquale

2014-11-28

Non-celiac gluten sensitivity (NCGS) or 'wheat sensitivity' (NCWS) is included in the spectrum of gluten-related disorders. No data are available on the prevalence of low bone mass density (BMD) in NCWS. Our study aims to evaluate the prevalence of low BMD in NCWS patients and search for correlations with other clinical characteristics. This prospective observation study included 75 NCWS patients (63 women; median age 36 years) with irritable bowel syndrome (IBS)-like symptoms, 65 IBS and 50 celiac controls. Patients were recruited at two Internal Medicine Departments. Elimination diet and double-blind placebo controlled (DBPC) wheat challenge proved the NCWS diagnosis. All subjects underwent BMD assessment by Dual Energy X-Ray Absorptiometry (DXA), duodenal histology, HLA DQ typing, body mass index (BMI) evaluation and assessment for daily calcium intake. DBPC cow's milk proteins challenge showed that 30 of the 75 NCWS patients suffered from multiple food sensitivity. Osteopenia and osteoporosis frequency increased from IBS to NCWS and to celiac disease (CD) (P <0.0001). Thirty-five NCWS patients (46.6%) showed osteopenia or osteoporosis. Low BMD was related to low BMI and multiple food sensitivity. Values of daily dietary calcium intake in NCWS patients were significantly lower than in IBS controls. An elevated frequency of bone mass loss in NCWS patients was found; this was related to low BMI and was more frequent in patients with NCWS associated with other food sensitivity. A low daily intake of dietary calcium was observed in patients with NCWS.

Functional integration of skeletal traits: an intraskeletal assessment of bone size, mineralization, and volume covariance.

PubMed

Schlecht, Stephen H; Jepsen, Karl J

2013-09-01

Understanding the functional integration of skeletal traits and how they naturally vary within and across populations will benefit assessments of functional adaptation directed towards interpreting bone stiffness in contemporary and past humans. Moreover, investigating how these traits intraskeletally vary will guide us closer towards predicting fragility from a single skeletal site. Using an osteological collection of 115 young adult male and female African-Americans, we assessed the functional relationship between bone robustness (i.e. total area/length), cortical tissue mineral density (Ct.TMD), and cortical area (Ct.Ar) for the upper and lower limbs. All long bones demonstrated significant trait covariance (p < 0.005) independent of body size, with slender bones having 25-50% less Ct.Ar and 5-8% higher Ct.TMD compared to robust bones. Robustness statistically explained 10.2-28% of Ct.TMD and 26.6-64.6% of Ct.Ar within male and female skeletal elements. This covariance is systemic throughout the skeleton, with either the slender or robust phenotype consistently represented within all long bones for each individual. These findings suggest that each person attains a unique trait set by adulthood that is both predictable by robustness and partially independent of environmental influences. The variation in these functionally integrated traits allows for the maximization of tissue stiffness and minimization of mass so that regardless of which phenotype is present, a given bone is reasonably stiff and strong, and sufficiently adapted to perform routine, habitual loading activities. Covariation intrinsic to functional adaptation suggests that whole bone stiffness depends upon particular sets of traits acquired during growth, presumably through differing levels of cellular activity, resulting in differing tissue morphology and composition. The outcomes of this intraskeletal examination of robustness and its correlates may have significant value in our progression towards improved clinical assessments of bone strength and fragility. Copyright © 2013 Elsevier Inc. All rights reserved.

Trabecular bone adaptation to low-magnitude high-frequency loading in microgravity.

PubMed

Torcasio, Antonia; Jähn, Katharina; Van Guyse, Maarten; Spaepen, Pieter; Tami, Andrea E; Vander Sloten, Jos; Stoddart, Martin J; van Lenthe, G Harry

2014-01-01

Exposure to microgravity causes loss of lower body bone mass in some astronauts. Low-magnitude high-frequency loading can stimulate bone formation on earth. Here we hypothesized that low-magnitude high-frequency loading will also stimulate bone formation under microgravity conditions. Two groups of six bovine cancellous bone explants were cultured at microgravity on a Russian Foton-M3 spacecraft and were either loaded dynamically using a sinusoidal curve or experienced only a static load. Comparable reference groups were investigated at normal gravity. Bone structure was assessed by histology, and mechanical competence was quantified using μCT and FE modelling; bone remodelling was assessed by fluorescent labelling and secreted bone turnover markers. Statistical analyses on morphometric parameters and apparent stiffness did not reveal significant differences between the treatment groups. The release of bone formation marker from the groups cultured at normal gravity increased significantly from the first to the second week of the experiment by 90.4% and 82.5% in response to static and dynamic loading, respectively. Bone resorption markers decreased significantly for the groups cultured at microgravity by 7.5% and 8.0% in response to static and dynamic loading, respectively. We found low strain magnitudes to drive bone turnover when applied at high frequency, and this to be valid at normal as well as at microgravity. In conclusion, we found the effect of mechanical loading on trabecular bone to be regulated mainly by an increase of bone formation at normal gravity and by a decrease in bone resorption at microgravity. Additional studies with extended experimental time and increased samples number appear necessary for a further understanding of the anabolic potential of dynamic loading on bone quality and mechanical competence.

Regulatory mechanism of food factors in bone metabolism and prevention of osteoporosis.

PubMed

Yamaguchi, Masayoshi

2006-11-01

Aging induces a decrease in bone mass, and osteoporosis with its accompanying decrease in bone mass is widely recognized as a major public health problem. Bone loss with increasing age may be due to decreased bone formation and increased bone resorption. Pharmacologic and nutritional factors may prevent bone loss with aging, although chemical compounds in food and plants which act on bone metabolism are poorly understood. We have found that isoflavones (including genistein and daidzein), which are contained in soybeans, have a stimulatory effect on osteoblastic bone formation and an inhibitory effect on osteoclastic bone resorption, thereby increasing bone mass. Menaquinone-7, an analogue of vitamin K(2) which is abundant in fermented soybeans, has been demonstrated to stimulate osteoblastic bone formation and to inhibit osteoclastic bone resorption. Of various carotenoids, beta-cryptoxanthin, which is abundant in Satsuma mandarin (Citrus unchiu MARC), has a stimulatory effect on osteoblastic bone formation and an inhibitory effect on osteoclastic bone resorption. The supplementation of these factors has a preventive effect on bone loss induced by ovariectomy in rats, which are an animal model of osteoporosis, and their intake has been shown to have a stimulatory effect on bone mass in humans. Factors with an anabolic effect on bone metabolism were found in extracts obtained from wasabi leafstalk (Wasabi japonica MATSUM), the marine alga Sargassum horneri, and bee pollen Cistus ladaniferus. Phytocomponent p-hydroxycinnamic acid was also found to have an anabolic effect on bone metabolism. Food chemical factors thus play a role in bone health and may be important in the prevention of bone loss with increasing age.

Calcium- and Phosphorus-Supplemented Diet Increases Bone Mass after Short-Term Exercise and Increases Bone Mass and Structural Strength after Long-Term Exercise in Adult Mice

PubMed Central

Friedman, Michael A.; Bailey, Alyssa M.; Rondon, Matthew J.; McNerny, Erin M.; Sahar, Nadder D.; Kohn, David H.

2016-01-01

Exercise has long-lasting benefits to bone health that may help prevent fractures by increasing bone mass, bone strength, and tissue quality. Long-term exercise of 6–12 weeks in rodents increases bone mass and bone strength. However, in growing mice, a short-term exercise program of 3 weeks can limit increases in bone mass and structural strength, compared to non-exercised controls. Short-term exercise can, however, increase tissue strength, suggesting that exercise may create competition for minerals that favors initially improving tissue-level properties over structural-level properties. It was therefore hypothesized that adding calcium and phosphorus supplements to the diet may prevent decreases in bone mass and structural strength during a short-term exercise program, while leading to greater bone mass and structural strength than exercise alone after a long-term exercise program. A short-term exercise experiment was done for 3 weeks, and a long-term exercise experiment was done for 8 weeks. For each experiment, male 16-week old C57BL/6 mice were assigned to 4 weight-matched groups–exercise and non-exercise groups fed a control or mineral-supplemented diet. Exercise consisted of treadmill running at 12 m/min, 30 min/day for 7 days/week. After 3 weeks, exercised mice fed the supplemented diet had significantly increased tibial tissue mineral content (TMC) and cross-sectional area over exercised mice fed the control diet. After 8 weeks, tibial TMC, cross-sectional area, yield force, and ultimate force were greater from the combined treatments than from either exercise or supplemented diet alone. Serum markers of bone formation (PINP) and resorption (CTX) were both decreased by exercise on day 2. In exercised mice, day 2 PINP was significantly positively correlated with day 2 serum Ca, a correlation that was weaker and negative in non-exercised mice. Increasing dietary mineral consumption during an exercise program increases bone mass after 3 weeks and increases structural strength after 8 weeks, making bones best able to resist fracture. PMID:27008546

Bioimpedance analysis vs. DEXA as a screening tool for osteosarcopenia in lean, overweight and obese Caucasian postmenopausal females.

PubMed

Peppa, Melpomeni; Stefanaki, Charikleia; Papaefstathiou, Athanasios; Boschiero, Dario; Dimitriadis, George; Chrousos, George P

2017-04-01

We aimed at evaluating the efficiency of a newly developed, advanced Bioimpedance Analysis (BIA-ACC®) device as a screening tool for determining the degree of obesity and osteosarcopenia in postmenopausal women with normal or decreased bone density determined by Dual-Energy X-Ray absorptiometry (DEXA) in a representative sample of Greek postmenopausal women. This is a single-gate cross-sectional study of body composition measured by BIA-ACC® and DEXA. Postmenopausal females with BMI ranging from 18.5 to 40 kg/m2 were subjected to two consecutive measurements of DEXA and BIA-ACC® within 5-10 minutes of each other. We used Pearson's co-efficient to examine linear correlations, the intraclass correlation co-efficient (ICC) to test reliability, Bland-Atman plots to assess bias and Deming regressions to establish the agreement in parameters measured by BIA-ACC® and DEXA. Last, we used ANOVA, with Bonferroni correction and Dunnett T3 post hoc tests, for assessing the differences between quantitative and Pearson's x2 between qualitative variables. Our sample consisted of 84 overweight/obese postmenopausal women, aged 39-83 years, of whom 22 had normal bone density, 38 had osteopenia and 24 had osteoporosis based on DEXA measurements, using quota sampling. ICCs and Deming regressions showed strong agreement between BIA-ACC® and DEXA and demonstrated minimal proportional differences of no apparent clinical significance. Bland-Altman plots indicated minimal biases. Fat, skeletal and bone mass measured by BIA-ACC® and DEXA were increased in the non-osteopenic/non-osteoporotic women compared with those of the osteopenic and osteoporotic groups. BIA-ACC® is a rapid, bloodless and useful screening tool for determining body composition adiposity and presence of osteo-sarcopenic features in postmenopausal women. Women with osteopenia and osteoporosis evaluated by DEXA had decreased fat, skeletal and bone mass compared with normal bone density women, suggesting concordance in the change of these three organ masses in postmenopausal women.

Association of insulin resistance with near peak bone mass in the femur and lumbar spine of Korean adults aged 25-35: The Korean National Health and Nutrition Examination Survey 2008-2010

PubMed Central

Choo, Min Soo; Choi, Se Rin; Han, Jun Hyun; Lee, Seong Ho

2017-01-01

Objective This study aimed to evaluate the relationship between insulin resistance and the bone mineral density (BMD) of femur and lumbar spine in Korean adults who are expected to exhibit near peak bone mass. Methods Data from the Korean National Health and Nutrition Examination Survey 2008–2010 were analyzed. A total of 2,750 participants aged 25−35 years were included. Insulin resistance was assessed using a homeostatic model assessment of insulin resistance (HOMA-IR) and serum fasting insulin. Results In a multivariate linear regression analysis, the HOMA-IR was significantly inversely associated with the BMD of the total hip (TH, β = −0.052, P = 0.002), femoral neck (FN, β = −0.072, P<0.001), femoral trochanter (FTr, β = −0.055, P = 0.003), femoral intertrochanter (FITr, β = −0.041, P = 0.015), and lumbar spine (LS, β = −0.063, P = 0.001) among all study subjects after adjustment for gender, age, height, weight, whole body fat mass percentage, systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, vitamin D, smoking, alcohol intake, physical activity, education level, and household income in both genders as well as labor, the use of oral contraceptives, and age at menarche in females. The serum fasting insulin was significantly inversely associated with the BMD of the TH (β = −0.055, P = 0.001), FN (β = −0.072, P<0.001), FTr (β = −0.055, P = 0.003), FITr (β = −0.045, P = 0.009), and LS (β = −0.064, P = 0.001) among all subjects in a multivariate linear regression analysis. Conclusion Our results suggest that insulin resistance may be independently and inversely associated with the near peak bone mass of the femur and lumbar spine. PMID:28704413

Long-term anabolic effects of prostaglandin-E2 on tibial diaphyseal bone in male rats

NASA Technical Reports Server (NTRS)

Jee, Webster S. S.; Ke, Hua Zhu; Li, Xiao Jian

1991-01-01

The effects of long-term prostaglandin E2 (PGE2) on tibial diaphyseal bone were studied in 7-month-old male Sprague-Dawley rats given daily subcutaneous injections of 0, 1, 3 and 6 mg PGE2/kg/day for 60, 120 and 180 days. The tibial shaft was measured by single photon absorptiometry and dynamic histomorphometric analyses were performed on double-fluorescent labeled undecalcified tibial diaphyseal bone samples. Exogenous PGE2 administration produced the following transient changes in a dose-response manner between zero and 60 days: (1) increased bone width and mineral density; (2) increased total tissue and total bone areas; (3) decreased marrow area; (4) increased periosteal and corticoendosteal lamellar bone formation; (5) activated corticoendosteal lamellar and woven trabecular bone formation; and (6) activated intracortical bone remodeling. A new steady-state of increased tibial diaphyseal bone mass and elevated bone activities were observed from day 60 onward. The elevated bone mass level attained after 60 days of PGE2 treatment was maintained at 120 and 180 days. These observations indicate that the powerful anabolic effects of PGE2 will increase both periosteal and corticoendosteal bone mass and sustain the transient increase in bone mass with continuous daily administration of PGE2.

Growth, body composition, and bone density following pediatric liver transplantation.

PubMed

Sheikh, Amin; Cundy, Tim; Evans, Helen Maria

2018-04-24

Patients transplanted for cholestatic liver disease are often significantly fat-soluble vitamin deficient and malnourished pretransplant, with significant corticosteroid exposure post-transplant, with increasing evidence of obesity and metabolic syndrome post-LT. Our study aimed to assess growth, body composition, and BMD in patients post-pediatric LT. Body composition and bone densitometry scans were performed on 21 patients. Pre- and post-transplant anthropometric data were analyzed. Bone health was assessed using serum ALP, calcium, phosphate, and procollagen-1-N-peptide levels. Median ages at transplant and at this assessment were 2.7 and 10.6 years, respectively. Physiological markers of bone health, median z-scores for total body, and lumbar spine aBMD were normal. Bone area was normal for height and BMAD at L3 was normal for age, indicating, respectively, normal cortical and trabecular bone accrual. Median z-scores for weight, height, and BMI were 0.6, -0.9, 1.8 and 0.6, 0.1, 0.8 pre- and post-transplant, respectively. Total body fat percentages measured on 21 body composition scans revealed 2 underweight, 7 normal, 6 overweight, and 6 obese. Bone mass is preserved following pediatric LT with good catch-up height. About 52% of patients were either overweight/obese post-transplant, potentially placing them at an increased risk of metabolic syndrome and its sequelae in later life. BMI alone is a poor indicator of nutritional status post-transplant. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Relationship between oxidative stress and bone mass in obesity and effects of berry supplementation on bone remodeling in obese male mice: an exploratory study.

PubMed

Lee, Sang Gil; Kim, Bohkyung; Soung, Do Yu; Vance, Terrence; Lee, Jong Suk; Lee, Ji-Young; Koo, Sung I; Kim, Dae-Ok; Drissi, Hicham; Chun, Ock K

2015-04-01

Berry consumption can prevent bone loss. However, the effects of different berries with distinct anthocyanin composition have not been thoroughly examined. The present study compared the effects of blueberry, blackberry, and black currant on bone health using a mouse model of diet-induced obesity. To investigate the effect of different berry supplements against a high-fat (HF) diet in vivo, 40 HF diet-induced obese (DIO) C57BL mice were assigned into four groups and fed a HF diet (35% w/w) with or without berry supplementation for 12 weeks (n=10). We measured adipose tissue mass (epididymal and retroperitoneal), plasma antioxidant, bone-related biomarkers, femur bone mineral density (BMD), and bone mineral content (proximal and distal). Adipose masses were negatively correlated with proximal BMD, but positively associated with plasma superoxide dismutase (SOD) concentrations (P<.001). Berry supplementation did not change the plasma ferric reducing antioxidant power, SOD, and insulin-like growth factor-1. However, the black currant group exhibited greater plasma alkaline phosphatase compared with the control group (P<.05). BMD in the distal epiphysis was significantly different between the blueberry and blackberry group (P<.05). However, berry supplementation did not affect bone mass compared with control. The present study demonstrates a negative relationship between fat mass and bone mass. In addition, our findings suggest that the anthocyanin composition of berries will affect bone turnover, warranting further research to investigate the underlying mechanisms.

Constitutional bone impairment in Noonan syndrome.

PubMed

Baldassarre, Giuseppina; Mussa, Alessandro; Carli, Diana; Molinatto, Cristina; Ferrero, Giovanni Battista

2017-03-01

Noonan syndrome (NS) is an autosomal dominant trait characterized by genotypic and phenotypic variability. It belongs to the Ras/MAPK pathway disorders collectively named Rasopathies or neurocardiofaciocutaneous syndromes. Phenotype is characterized by short stature, congenital heart defects, facial dysmorphisms, skeletal and ectodermal anomalies, cryptorchidism, mild to moderate developmental delay/learning disability, and tumor predisposition. Short stature and skeletal dysmorphisms are almost constant and several studies hypothesized a role for the RAS pathway in regulating bone metabolism. In this study, we investigated the bone quality assessed by phalangeal quantitative ultrasound (QUS) and the metabolic bone profiling in a group of patients with NS, to determine whether low bone mineralization is primary or secondary to NS characteristics. Thirty-five patients were enrolled, including 20 males (55.6%) and 15 females (44.5%) aged 1.0-17.8 years (mean 6.4 ± 4.5, median 4.9 years). Each patients was submitted to clinical examination, estimation of the bone age, laboratory assays, and QUS assessment. Twenty-five percent of the cohort shows reduced QUS values for their age based on bone transmission time. Bone measurement were adjusted for multiple factors frequently observed in NS patients, such as growth retardation, delayed bone age, retarded puberty, and reduced body mass index, potentially affecting bone quality or its appraisal. In spite of the correction attempts, QUS measurement indicates that bone impairment persists in nearly 15% of the cohort studied. Our results indicate that bone impairment in NS is likely primary and not secondary to any of the phenotypic traits of NS, nor consistent with metabolic disturbances. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Assessment of bone in Ehlers Danlos syndrome by ultrasound and densitometry.

PubMed

Dolan, A L; Arden, N K; Grahame, R; Spector, T D

1998-10-01

Ehlers Danlos syndrome (EDS) is an inherited disorder of connective tissue characterised by hyperextensible skin, joint laxity, and easy bruising. There are phenotypic similarities with osteogenesis imperfecta, but in EDS a tendency to fracture or altered bone mass has not previously been considered to be a cardinal feature. This case-control design study investigates whether 23 patients with EDS had differences in fracture rates, bone mass, and calcaneal ultrasound parameters compared with age and sex matched controls. 23 cases of EDS (mean (SD) age 38.5 (15.5)) were compared with 23 controls (mean age 37.8 (14.5)). A significant reduction in bone density measured by dual energy x ray absorptiometry was found at the neck of femur by 0.9 SD, p = 0.05, and lumbar spine by 0.74 SD, p = 0.02. At the calcaneum, broad band ultrasound attenuation and speed of sound were significantly reduced compared with controls by 0.95 SD (p = 0.004) and 0.49 SD (p = 0.004) for broad band ultrasound attenuation and speed of sound respectively. Broad band ultrasound attenuation and speed of sound remained significantly reduced after adjusting for bone mineral density (BMD). After adjusting for functional status (HAQ), age and sex, hypermobility was inversely correlated with broad band ultrasound attenuation and SOS, but not BMD at hip or spine. Previous fracture was 10 times more common in EDS (p < 0.001), with 86.9% of patients reporting a total of 47 low impact fractures, compared with 8.7% of controls. This study has identified a tendency of EDS patients to fracture, have low bone mass and abnormal bone structure. The aetiology is likely to be multifactorial, with an inherited structural element, accentuated by immobility or reduced exercise. This is one of the first clinical studies to suggest ultrasound can detect structural differences in bone, independent of dual energy x ray absorptiometry.

Relationship between body mass, lean mass, fat mass, and limb bone cross-sectional geometry: Implications for estimating body mass and physique from the skeleton.

PubMed

Pomeroy, Emma; Macintosh, Alison; Wells, Jonathan C K; Cole, Tim J; Stock, Jay T

2018-05-01

Estimating body mass from skeletal dimensions is widely practiced, but methods for estimating its components (lean and fat mass) are poorly developed. The ability to estimate these characteristics would offer new insights into the evolution of body composition and its variation relative to past and present health. This study investigates the potential of long bone cross-sectional properties as predictors of body, lean, and fat mass. Humerus, femur and tibia midshaft cross-sectional properties were measured by peripheral quantitative computed tomography in sample of young adult women (n = 105) characterized by a range of activity levels. Body composition was estimated from bioimpedance analysis. Lean mass correlated most strongly with both upper and lower limb bone properties (r values up to 0.74), while fat mass showed weak correlations (r ≤ 0.29). Estimation equations generated from tibial midshaft properties indicated that lean mass could be estimated relatively reliably, with some improvement using logged data and including bone length in the models (minimum standard error of estimate = 8.9%). Body mass prediction was less reliable and fat mass only poorly predicted (standard errors of estimate ≥11.9% and >33%, respectively). Lean mass can be predicted more reliably than body mass from limb bone cross-sectional properties. The results highlight the potential for studying evolutionary trends in lean mass from skeletal remains, and have implications for understanding the relationship between bone morphology and body mass or composition. © 2018 The Authors. American Journal of Physical Anthropology Published by Wiley Periodicals, Inc.

Strategies for skeletal health in the elderly.

PubMed

Eastell, Richard; Lambert, Helen

2002-05-01

Osteoporosis is a common disease in the elderly, and the fractures that result from this disorder affect 40 % of women and 14 % of men over the age of 50 years. The risk of fracture relates to bone mineral density and the risk of falling, among other factors. Low bone mineral density in the elderly can result from either low peak bone mass or accelerated bone loss, or a combination of the two. Nutritional factors play a role in both the attainment of peak bone mass and in the rate of age-related bone loss. The main determinants of peak bone mass are genetic factors, early-life nutrition, diet and exercise. Of the nutritional factors Ca, and particularly milk, are the most important contributors to peak bone mass. Some of these factors may interact; for example, a low dietary Ca in addition to an unfavourable vitamin D receptor gene polymorphism may result in low peak bone mass. The age-related changes in bone mass may also have a genetic basis, but deficiency of oestrogen is a major contributor. In addition, undernutrition is common in the elderly, and lack of dietary protein contributes both to impaired bone mineral conservation and increased propensity to fall. There is a decreased ability of the intestine to adapt to a low-Ca diet with increasing age. Other dietary factors include vitamin K, Zn and fruit and vegetables. Adequate nutritional status, particularly of Ca and vitamin D, is essential for the successful pharmaceutical treatment of osteoporosis. Thus, strategies for enhancing skeletal health in the elderly must begin in early childhood, and continue throughout life.

Calcium Intake, Major Dietary Sources and Bone Health Indicators in Iranian Primary School Children

PubMed Central

Omidvar, Nasrin; Neyestani, Tirang-Reza; Hajifaraji, Majid; Eshraghian, Mohammad-Reza; Rezazadeh, Arezoo; Armin, Saloumeh; Haidari, Homa; Zowghi, Telma

2015-01-01

Background: Adequate calcium intake may have a crucial role with regards to prevention of many chronic diseases, including hypertension, hypercholesterolemia, different types of cancer, obesity and osteoporosis. In children, sufficient calcium intake is especially important to support the accelerated growth spurt during the preteen and teenage years and to increase bone mineral mass to lay the foundation for older age. Objectives: This study aimed to assess daily calcium intake in school-age children to ensure whether they fulfill the FGP dairy serving recommendations, the recommended levels of daily calcium intake and to assess the relationship between dietary calcium intake and major bone health indicators. Patients and Methods: A total of 501 Iranian school-age children were randomly selected. Calcium intake was assessed using a semi-quantitative food frequency questionnaire. Bone health indicators were also assessed. Results: Dairy products contributed to 69.3% of the total calcium intake of the children. Daily adequate intake of calcium was achieved by 17.8% of children. Only 29.8% met the Food guide pyramid recommendations for dairy intake. Dietary calcium intake was not significantly correlated with serum calcium and other selected biochemical indicators of bone health. Conclusions: The need for planning appropriate nutrition strategies for overcoming inadequate calcium intake in school age children in the city of Tehran is inevitable. PMID:26199684

Increased activity of osteocyte autophagy in ovariectomized rats and its correlation with oxidative stress status and bone loss

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

Yang, Yuehua, E-mail: yuesjtu@126.com; Zheng, Xinfeng, E-mail: zxf272@126.com; Li, Bo, E-mail: libo@126.com

Highlights: • Examine autophagy level in the proximal tibia of ovariectomized rats. • Investigate whether autophagy level is associated with bone loss. • Investigate whether autophagy level is associated with oxidative stress status. - Abstract: Objectives: The objectives of the present study were to investigate ovariectomy on autophagy level in the bone and to examine whether autophagy level is associated with bone loss and oxidative stress status. Methods: 36 female Sprague–Dawley rats were randomly divided into sham-operated (Sham), and ovariectomized (OVX) rats treated either with vehicle or 17-β-estradiol. At the end of the six-week treatment, bone mineral density (BMD) andmore » bone micro-architecture in proximal tibias were assessed by micro-CT. Serum 17β-estradiol (E2) level were measured. Total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity in proximal tibia was also determined. The osteocyte autophagy in proximal tibias was detected respectively by Transmission Electron Microscopy (TEM), immunofluorescent histochemistry (IH), realtime-PCR and Western blot. In addition, the spearman correlation between bone mass, oxidative stress status, serum E2 and autophagy were analyzed. Results: Ovariectomy increased Atg5, LC3, and Beclin1 mRNA and proteins expressions while decreased p62 expression. Ovariectomy also declined the activities of T-AOC, CAT, and SOD. Treatment with E2 prevented the reduction in bone mass as well as restored the autophagy level. Furthermore, LC3-II expression was inversely correlated with T-AOC, CAT, and SOD activities. A significant inverse correlation between LC3-II expression and BV/TV, Tb.N, BMD in proximal tibias was found. Conclusions: Ovariectomy induced oxidative stress, autophagy and bone loss. Autophagy of osteocyte was inversely correlated with oxidative stress status and bone loss.« less

Mitogen‐inducible gene‐6 partly mediates the inhibitory effects of prenatal dexamethasone exposure on endochondral ossification in long bones of fetal rats

PubMed Central

Shang‐Guan, Yangfan; Ma, Jing; Hu, Hang; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin

2016-01-01

Abstract Background and Purpose Prenatal exposure to dexamethasone slows down fetal linear growth and bone mineralization but the regulatory mechanism remains unknown. Here we assessed how dexamethasone regulates bone development in the fetus. Experimental Approach Dexamethasone (1 mg·kg−1·day−1) was injected subcutaneously every morning in pregnant rats from gestational day (GD)9 to GD20. Fetal femurs and tibias were harvested at GD20 for histological and gene expression analysis. Femurs of 12‐week‐old female offspring were harvested for microCT (μCT) measurement. Primary chondrocytes were treated with dexamethasone (10, 50, 250 and 1000 nM). Key Results Prenatal dexamethasone exposure resulted in accumulation of hypertrophic chondrocytes and delayed formation of the primary ossification centre in fetal long bone. The retardation was accompanied by reduced maturation of hypertrophic chondrocytes, decreased osteoclast number and down‐regulated expression of osteocalcin and bone sialoprotein in long bone. In addition, the mitogen‐inducible gene‐6 (Mig6) and osteoprotegerin (OPG) expression were stimulated, and the receptor activator of NF‐κB ligand (RANKL) expression was repressed. Moreover, dexamethasone activated OPG and repressed RANKL expression in both primary chondrocytes and primary osteoblasts, and the knockdown of Mig6 abolished the effect of dexamethasone on OPG expression. Further, μCT measurement showed loss of bone mass in femur of 12‐week‐old offspring with prenatal dexamethasone exposure. Conclusions and Implications Prenatal dexamethasone exposure delays endochondral ossification by suppressing chondrocyte maturation and osteoclast differentiation, which may be partly mediated by Mig6 activation in bone. Bone development retardation in the fetus may be associated with reduced bone mass in later life. PMID:27128203

Evaluation of methylation status of the eNOS promoter at birth in relation to childhood bone mineral content

PubMed Central

Harvey, Nicholas C.; Lillycrop, Karen A.; Garratt, Emma; Sheppard, Allan; McLean, Cameron; Burdge, Graham; Slater-Jefferies, Jo; Rodford, Joanne; Crozier, Sarah; Inskip, Hazel; Emerald, Bright Starling; Gale, Catharine R; Hanson, Mark; Gluckman, Peter; Godfrey, Keith; Cooper, Cyrus

2013-01-01

Aim Our previous work has shown associations between childhood adiposity and perinatal methylation status of several genes in umbilical cord tissue, including endothelial nitric oxide synthase (eNOS). There is increasing evidence that eNOS is important in bone metabolism; we therefore related the methylation status of the eNOS gene promoter in stored umbilical cord to childhood bone size and density in a group of 9-year old children. Methods We used Sequenom MassARRAY to assess the methylation status of 2 CpGs in the eNOS promoter, identified from our previous study, in stored umbilical cords of 66 children who formed part of a Southampton birth cohort and who had measurements of bone size and density at age 9 years (Lunar DPXL DXA instrument). Results Percentage methylation varied greatly between subjects. For one of the two CpGs, eNOS chr7:150315553+, after taking account of age and sex there was a strong positive association between methylation status and the child’s whole body bone area (r=0.28,p=0.02), bone mineral content (r=0.34,p=0.005) and areal bone mineral density (r=0.34,p=0.005) at age 9 years. These associations were independent of previously documented maternal determinants of offspring bone mass. Conclusions Our findings suggest an association between methylation status at birth of a specific CpG within the eNOS promoter and bone mineral content in childhood. This supports a role for eNOS in bone growth and metabolism and implies that its contribution may at least in part occur during early skeletal development. PMID:22159788

Maternal Active Mastication during Prenatal Stress Ameliorates Prenatal Stress-Induced Lower Bone Mass in Adult Mouse Offspring

PubMed Central

Azuma, Kagaku; Ogura, Minori; Kondo, Hiroko; Suzuki, Ayumi; Hayashi, Sakurako; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-ya

2017-01-01

Chronic psychological stress is a risk factor for osteoporosis. Maternal active mastication during prenatal stress attenuates stress response. The aim of this study is to test the hypothesis that maternal active mastication influences the effect of prenatal stress on bone mass and bone microstructure in adult offspring. Pregnant ddY mice were randomly divided into control, stress, and stress/chewing groups. Mice in the stress and stress/chewing groups were placed in a ventilated restraint tube for 45 minutes, 3 times a day, and was initiated on day 12 of gestation and continued until delivery. Mice in the stress/chewing group were allowed to chew a wooden stick during the restraint stress period. The bone response of 5-month-old male offspring was evaluated using quantitative micro-CT, bone histomorphometry, and biochemical markers. Prenatal stress resulted in significant decrease of trabecular bone mass in both vertebra and distal femur of the offspring. Maternal active mastication during prenatal stress attenuated the reduced bone formation and increased bone resorption, improved the lower trabecular bone volume and bone microstructural deterioration induced by prenatal stress in the offspring. These findings indicate that maternal active mastication during prenatal stress can ameliorate prenatal stress-induced lower bone mass of the vertebra and femur in adult offspring. Active mastication during prenatal stress in dams could be an effective coping strategy to prevent lower bone mass in their offspring. PMID:28553167

Maternal Active Mastication during Prenatal Stress Ameliorates Prenatal Stress-Induced Lower Bone Mass in Adult Mouse Offspring.

PubMed

Azuma, Kagaku; Ogura, Minori; Kondo, Hiroko; Suzuki, Ayumi; Hayashi, Sakurako; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

2017-01-01

Chronic psychological stress is a risk factor for osteoporosis. Maternal active mastication during prenatal stress attenuates stress response. The aim of this study is to test the hypothesis that maternal active mastication influences the effect of prenatal stress on bone mass and bone microstructure in adult offspring. Pregnant ddY mice were randomly divided into control, stress, and stress/chewing groups. Mice in the stress and stress/chewing groups were placed in a ventilated restraint tube for 45 minutes, 3 times a day, and was initiated on day 12 of gestation and continued until delivery. Mice in the stress/chewing group were allowed to chew a wooden stick during the restraint stress period. The bone response of 5-month-old male offspring was evaluated using quantitative micro-CT, bone histomorphometry, and biochemical markers. Prenatal stress resulted in significant decrease of trabecular bone mass in both vertebra and distal femur of the offspring. Maternal active mastication during prenatal stress attenuated the reduced bone formation and increased bone resorption, improved the lower trabecular bone volume and bone microstructural deterioration induced by prenatal stress in the offspring. These findings indicate that maternal active mastication during prenatal stress can ameliorate prenatal stress-induced lower bone mass of the vertebra and femur in adult offspring. Active mastication during prenatal stress in dams could be an effective coping strategy to prevent lower bone mass in their offspring.

Bone health status and lipid profile among post-menopausal malay women in Cheras, Kuala Lumpur.

PubMed

Hasnah, H; Amin, I; Suzana, S

2012-08-01

A cross-sectional study was conducted to determine bone health status and nutrient intakes among post-menopausal women residing in low cost houses in Cheras, Kuala Lumpur. A total of 125 subjects aged 60 +/- 4 years who had attained menopause at age 50 +/- 5 years participated in this study. Subjects' weight and height were measured and calculated for body mass index (BMI). They were also assessed for bone health status using the Quantitative Ultrasound (QUS). Nutrient intake was assessed using a dietary history Questionnaire. Fasting serum lipid and blood pressure measurements were also taken. The majority of the subjects were overweight and obese (80%) based on BMI status. Calcaneal measurements using the QUS indicated that while 57% or the subjects had normal bone mineral density, 37% were osteopenic and 6% osteoporotic. Calcium intake of the subjects was 505 +/- 263 mg /day, which is only 50% of the Malaysian Recommended Nutrient Intake for calcium (1000 mg/d). About 74% of the subjects were hypercholesterolemic and 58% were hypertriglyceridemic. Two-thirds reported that they were taking medication for hypertension, diabetes mellitus and heart disease. The results showed low health and nutritional status among post-menopausal women living in low-cost flats in Kuala Lumpur. They have low bone mass which may be due to their predominantly non-milk based diets which places them at high risk of hip fractures. Apart from milk, other food sources of calcium, including soya bean products such as 'tempeh' and healthy ways of cooking should be recommended to older people.

Olive Oil and Vitamin D Synergistically Prevent Bone Loss in Mice

PubMed Central

Tagliaferri, Camille; Davicco, Marie-Jeanne; Lebecque, Patrice; Georgé, Stéphane; Amiot, Marie-Jo; Mercier, Sylvie; Dhaussy, Amélie; Huertas, Alain; Walrand, Stéphane; Wittrant, Yohann; Coxam, Véronique

2014-01-01

As the Mediterranean diet (and particularly olive oil) has been associated with bone health, we investigated the impact of extra virgin oil as a source of polyphenols on bone metabolism. In that purpose sham-operated (SH) or ovariectomized (OVX) mice were subjected to refined or virgin olive oil. Two supplementary OVX groups were given either refined or virgin olive oil fortified with vitamin D3, to assess the possible synergistic effects with another liposoluble nutrient. After 30 days of exposure, bone mineral density and gene expression were evaluated. Consistent with previous data, ovariectomy was associated with increased bone turnover and led to impaired bone mass and micro-architecture. The expression of oxidative stress markers were enhanced as well. Virgin olive oil fortified with vitamin D3 prevented such changes in terms of both bone remodeling and bone mineral density. The expression of inflammation and oxidative stress mRNA was also lower in this group. Overall, our data suggest a protective impact of virgin olive oil as a source of polyphenols in addition to vitamin D3 on bone metabolism through improvement of oxidative stress and inflammation. PMID:25551374

Clinical Imaging of Bone Microarchitecture with HR-pQCT

PubMed Central

Nishiyama, Kyle K.; Shane, Elizabeth

2014-01-01

Osteoporosis, a disease characterized by loss of bone mass and structural deterioration, is currently diagnosed by dual-energy x-ray absorptiometry (DXA). However, DXA does not provide information about bone microstructure, which is a key determinant of bone strength. Recent advances in imaging permit the assessment of bone microstructure in vivo using high-resolution peripheral quantitative computed tomography (HR-pQCT). From these data, novel image processing techniques can be applied to characterize bone quality and strength. To date, most HR-pQCT studies are cross-sectional comparing subjects with and without fracture. These studies have shown that HR-pQCT is capable of discriminating fracture status independent of DXA. Recent longitudinal studies present new challenges in terms of analyzing the same region of interest and multisite calibrations. Careful application of analysis techniques and educated clinical interpretation of HR-pQCT results have improved our understanding of various bone-related diseases and will no doubt continue to do so in the future. PMID:23504496

Changes in bone structure of Corriedale sheep with inherited rickets: a peripheral quantitative computed tomography assessment.

PubMed

Dittmer, Keren E; Firth, Elwyn C; Thompson, Keith G; Marshall, Jonathan C; Blair, Hugh T

2011-03-01

An inherited skeletal disease with gross and microscopic features of rickets has been diagnosed in Corriedale sheep in New Zealand. The aim of this study was to quantify the changes present in tibia from sheep with inherited rickets using peripheral quantitative computed tomography. In affected sheep, scans in the proximal tibia, where metaphysis becomes diaphysis, showed significantly greater trabecular bone mineral content (BMC) and bone mineral density (BMD). The sheep with inherited rickets had significantly greater BMC and bone area in the mid-diaphysis of the proximal tibia compared to control sheep. However, BMD in the mid-diaphysis was significantly less in affected sheep than in controls, due to the greater cortical area and lower voxel density values in affected sheep. From this it was concluded that the increased strain on under-mineralised bone in sheep with inherited rickets led to increased bone mass in an attempt to improve bone strength. Copyright © 2010 Elsevier Ltd. All rights reserved.

Sex steroids, bone mass, and bone loss. A prospective study of pre-, peri-, and postmenopausal women.

PubMed

Slemenda, C; Longcope, C; Peacock, M; Hui, S; Johnston, C C

1996-01-01

Although bone loss around the time of menopause is driven by estrogen deficiency, the roles of estrogens and androgens in the preservation of skeletal mass at other stages of life are less well understood. To address this issue we studied 231 women between the ages of 32 and 77 with multiple measurements of sex steroids and bone mass over a period of 2-8 yr. In all women bone mass was negatively associated with concentrations of sex-hormone binding globulin, and positively associated with weight. Bone loss occurred from all skeletal sites in peri- and postmenopausal women, but premenopausal women lost bone only from the hip (-0.3%/yr) and had positive rates of change in the radius and spine. Bone loss was significantly associated with lower androgen concentrations in premenopausal women, and with lower estrogens and androgens in peri- and postmenopausal women. Sex steroids are important for the maintenance of skeletal integrity before menopause, and for as long as 20-25 yr afterwards.

Proandrogenic and Antiandrogenic Progestins in Transgender Youth: Differential Effects on Body Composition and Bone Metabolism.

PubMed

Tack, Lloyd J W; Craen, Margarita; Lapauw, Bruno; Goemaere, Stefan; Toye, Kaatje; Kaufman, Jean-Marc; Vandewalle, Sara; T'Sjoen, Guy; Zmierczak, Hans-Georg; Cools, Martine

2018-06-01

Progestins can be used to attenuate endogenous hormonal effects in late-pubertal transgender (trans) adolescents (Tanner stage B4/5 and G4/5). Currently, no data are available on the effects of progestins on the development of bone mass or body composition in trans youth. To study prospectively the evolution of body composition and bone mass in late-pubertal trans adolescents using the proandrogenic or antiandrogenic progestins lynestrenol (L) and cyproterone acetate (CA), respectively. Forty-four trans boys (Tanner B4/5) and 21 trans girls (Tanner G4/5) were treated with L or CA for 11.6 (4 to 40) and 10.6 (5 to 31) months, respectively. Anthropometry, grip strength, body composition, and bone mass, size, and density were determined by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography before the start of progestin and before addition of cross-sex hormones. Using L, lean mass [+3.2 kg (8.6%)] and grip strength [+3 kg (10.6%)] significantly increased, which coincided with a more masculine body shape in trans boys. Trans girls showed loss of lean mass [-2.2 kg (4.7%)], gain of fat mass [+1.5 kg (9.4%)], and decreased grip strength Z scores. CA limited normal bone expansion and impeded pubertal bone mass accrual, mostly at the lumbar spine [Z score: -0.765 to -1.145 (P = 0.002)]. L did not affect physiological bone development. Proandrogenic and antiandrogenic progestins induce body composition changes in line with the desired appearance within 1 year of treatment. Bone health, especially at the lumbar spine, is of concern in trans girls, as bone mass accrual is severely affected by androgen suppressive therapy.

[Toward an anthropometric diagnosis of osteopenia and a biochemical diagnosis of osteoporoses].

PubMed

Cointry, Gustavo R; Capozza, Ricardo F; Ferretti, Jose L; Frost, Harold M

2003-01-01

The current (metabolic) conception of bone-weakening diseases regards bone strength as determined by a systemically-controlled "mineralized mass" which grows until it reaches a peak and then is lost at individually-specific rates. This concept disregards bone biomechanics. Skeletons are structures, it reaches of which depends on the stiffness and the spatial distribution rather than the volume of the calcified material. Rather than allowing a systemic regulation of their "mass" as a way to optimize their strength, bones autocontrol their stiffness by orienting bone formation and destruction as locally determined by the directional sensing, by osteocytes, of the strains caused by mechanical usage (gravity, muscle contractions). Bone mass and strength are just side products of that control. Endocrine-metabolic systems modulate non-directionally the work of bone cells as required for achieving a mineral equilibrium, despite the biomechanical controls, and can determine osteopenias and osteoporoses. Osteoporoses are not "intense osteopenias" (as per the current WHO's conception) but "osteopenic bone fragilities" (as recently stated by the NIH). The diagnosis of osteopenia is an anthropometric problem that can be solved densitometrically; but that of bone fragility is a biomechanical matter that requires evaluation of bone material's stiffness and distribution by other means ("resistometry"). For therapeutic purposes, osteopenias and osteoporoses should be also evaluated according to the relationship between bone mass or strength and muscle mass or strength in order to distinguish between "mechanical" (disuse) and "metabolic" etiologies (intrinsic bone lesion, or systemic disequilibrium), in which the bone/muscle proportionality tends to remain normal or to deteriorate, respectively.

Quantifying Bone–relevant Activity and its Relation to Bone Strength in Girls

PubMed Central

Farr, Joshua N.; Lee, Vinson R.; Blew, Robert M.; Lohman, Timothy G.; Going, Scott B.

2011-01-01

Physical activity (PA) is critical for maximizing bone development during growth. However, there is no consensus on how well existing PA measurement tools predict bone strength. PURPOSE Compare four methods of quantifying physical activity (PA) (pedometer, 3-day physical activity recall (3DPAR), bone-specific physical activity questionnaire (BPAQ), and past year physical activity questionnaire (PYPAQ)), in young girls and evaluate their ability to predict indices of bone strength. METHODS 329 girls aged 8–13 years completed a pedometer assessment, the 3DPAR, the BPAQ, and a modified PYPAQ. Peripheral quantitative computed tomography (pQCT) was used to assess bone strength index (BSI) at metaphyseal (4% distal femur and tibia) sites and strength-strain index (SSI) at diaphyseal (femur = 20%, tibia = 66%) sites of the non-dominant leg. Correlations and hierarchical multiple regression were used to assess relationships among PA measures and indices of bone strength. RESULTS After adjustment for maturity, correlations between PA measures and indices of bone strength were positive, although low (r = 0.01–0.20). Regression models that included covariates (maturity, body mass, leg length, and ethnicity) and PA variables showed that PYPAQ score was significantly (P < 0.05) associated with BSI and SSI at all sites and explained more variance in BSI and SSI than any other PA measure. Pedometer steps were significantly (P < 0.05) associated with metaphyseal femur and tibia BSI and 3DPAR score was significantly (P < 0.05) associated with metaphyseal femur BSI. BPAQ score was not significantly (P > 0.05) associated with BSI or SSI at any sites. CONCLUSION A modified PYPAQ that accounts for the duration, frequency, and load of PA predicted indices of bone strength better than other PA measures. PMID:20631644

The role of lean body mass and physical activity in bone health in children.

PubMed

Baptista, Fátima; Barrigas, Carlos; Vieira, Filomena; Santa-Clara, Helena; Homens, Pedro Mil; Fragoso, Isabel; Teixeira, Pedro J; Sardinha, Luís B

2012-01-01

In the context of physical education curricula, markers of physical fitness (e.g., aerobic capacity, muscular strength, flexibility, and body mass index or body fat) are usually evaluated in reference to health standards. Despite their possible mediating role in the relationship between weight-bearing or muscle forces and features of bone tissue, these attributes of fitness may not be the most relevant to predict skeletal health. It is therefore important to analyze the relative contribution of these factors to the variability in bone tissue of different parts of the skeleton, and to analyze it by gender, as sensitivity to mechanical loading can diverge for boys and girls. We compared the effects of habitual physical activity (PA) and lean mass, as surrogates of weight-bearing and muscle forces, and of physical fitness (aerobic and muscle capacity of lower and upper limbs) on bone mineral content (BMC) and size of total body, lumbar spine, femoral neck, and 1/3 radius in 53 girls and 64 boys from 7.9 to 9.7 years of age. After controlling for bone age, body mass, body height, and calcium intake, lean mass was the most important predictor of bone size and/or mineral in both genders (p < 0.05), while habitual weight-bearing PA positively influenced BMC in boys (p < 0.05). The effect of muscle in bone was not determined by PA and fitness score did not explain bone variability. Femoral neck was the bone site more closely associated with mechanical loading factors; boys with a PA > 608 counts/min/day (~105 min/day of moderate and vigorous intensity) showed 13-20% more BMC than those with less physical activity, and girls with a lean mass >19 kg showed 12-19% more BMC than those with less lean mass. These findings suggest that lean mass was the most important predictor of bone size and/or mineralization in both genders, while habitual weight-bearing PA appears to positively impact on bone mineral in prepubertal boys and that both lean mass and PA need to be considered in physical education curricula and other health-enhancing programs.

Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases.

PubMed

Ke, Hua Zhu; Richards, William G; Li, Xiaodong; Ominsky, Michael S

2012-10-01

The processes of bone growth, modeling, and remodeling determine the structure, mass, and biomechanical properties of the skeleton. Dysregulated bone resorption or bone formation may lead to metabolic bone diseases. The Wnt pathway plays an important role in bone formation and regeneration, and expression of two Wnt pathway inhibitors, sclerostin and Dickkopf-1 (DKK1), appears to be associated with changes in bone mass. Inactivation of sclerostin leads to substantially increased bone mass in humans and in genetically manipulated animals. Studies in various animal models of bone disease have shown that inhibition of sclerostin using a monoclonal antibody (Scl-Ab) increases bone formation, density, and strength. Additional studies show that Scl-Ab improves bone healing in models of bone repair. Inhibition of DKK1 by monoclonal antibody (DKK1-Ab) stimulates bone formation in younger animals and to a lesser extent in adult animals and enhances fracture healing. Thus, sclerostin and DKK1 are emerging as the leading new targets for anabolic therapies to treat bone diseases such as osteoporosis and for bone repair. Clinical trials are ongoing to evaluate the effects of Scl-Ab and DKK1-Ab in humans for the treatment of bone loss and for bone repair.

Cortisol Secretory Parameters in Young Exercisers in Relation to LH Secretion and Bone Parameters

PubMed Central

Ackerman, Kathryn E.; Patel, Kamal T.; Guereca, Gabriela; Pierce, Lisa; Herzog, David B.; Misra, Madhusmita

2012-01-01

Objective Amenorrhoea and low bone density are common in excessive exercisers, yet endocrine factors that differentiate adolescent amenorrhoeic exercisers (AE) from eumenorrhoeic exercisers (EE) are unclear. We have previously reported that high ghrelin and low leptin predict lower LH secretion in AE. Leptin and ghrelin impact cortisol secretion, and hypercortisolaemia can inhibit LH pulsatility. We hypothesized that higher cortisol secretion in young endurance weight-bearing AE compared with EE and non-exercisers predicts lower LH secretion, lower levels of a bone formation marker and higher levels of a bone resorption marker. Design Cross-sectional Subjects We studied 21 AE, 18 EE and 20 non-exercisers 14–21 years (BMI 10th–90th%iles). Measurements Subjects underwent frequent sampling (11 p.m. to 7 a.m.) to assess cortisol, ghrelin, leptin and LH secretory dynamics. Fasting levels of a bone formation (P1NP) and bone resorption (CTX) marker were measured. Results BMI did not differ among groups. Cortisol pulse amplitude, mass, half-life and area under the curve (AUC) were highest in AE (p=0.04, 0.007, 0.04 and 0.003) and were associated inversely with fat mass (r=−0.29, −0.28 and −0.35, p=0.03, 0.04 and 0.007). We observed inverse associations between cortisol and LH AUC (r= −0.36, p=0.008), which persisted after controlling for fat mass, leptin and ghrelin AUC. Cortisol correlated positively with CTX in EE and inversely with P1NP in non-exercisers. Conclusions Higher cortisol secretion in AE compared with EE and non-exercisers is associated with lower LH secretion. Effects of leptin and ghrelin on LH secretion may be mediated by increased cortisol. PMID:22671919

Association between low lean mass and low bone mineral density in 653 women with hip fracture: does the definition of low lean mass matter?

PubMed

Di Monaco, Marco; Castiglioni, Carlotta; Di Monaco, Roberto; Tappero, Rosa

2017-12-01

Loss of both muscle and bone mass results in fragility fractures with increased risk of disability, poor quality of life, and death. Our aim was to assess the association between low appendicular lean mass (aLM) defined according to different criteria and low bone mineral density (BMD) in hip-fracture women. Six hundred fifty-three women admitted to our rehabilitation hospital underwent dual energy X-ray absorptiometry 19.1 ± 4.1 (mean ± SD) days after hip-fracture occurrence. Low aLM was identified according to either Baumgartner's definition (aLM/height 2 less than two standard deviations below the mean of the young reference group) or FNIH criteria: aLM <15.02 kg, or aLM adjusted for body mass index (BMI) <0.512. Low BMD was diagnosed with a T-score <-2.5 at the unfractured femoral neck. Using Baumgartner's definition, the association between low aLM/height 2 and low BMD was significant: χ 2 (1, n = 653) = 8.52 (p = 0.004), but it was erased by adjustments for age and fat mass. Using the FNIH definition the association between low aLM and low BMD was significant: χ 2 (1, n = 653) = 42.5 (p < 0.001), and it was confirmed after adjustment for age and fat mass (p < 0.001). With the FNIH definition based on aLM/BMI ratio the association between low aLM/BMI ratio and low BMD was nonsignificant: χ 2 (1, n = 653) = 0.003 (p = 0.957). The association between low aLM and low BMD in women with hip fracture dramatically depends on the adopted definition of low aLM. FNIH threshold for aLM (<15.02 kg) emerges as a useful tool to capture women with damage of the muscle-bone unit.

Are levels of bone turnover related to lower bone mass of adolescents previously fed a macrobiotic diet?

PubMed

Parsons, T J; van Dusseldorp, M; Seibel, M J; van Staveren, W A

2001-01-01

Dutch adolescents who consumed a macrobiotic (vegan-type) diet in early life, demonstrate a lower relative bone mass than their omnivorous counterparts. We investigated whether subjects from the macrobiotic group showed signs of catching up with controls in terms of relative bone mass, reflected by higher levels of serum osteocalcin and alkaline phosphatase and lower levels of urinary cross-links. Group differences in calciotropic hormones and mineral excretion were also investigated. Bone measurements, blood, and urine samples were obtained from 69 macrobiotic (34 girls, 35 boys) and 99 control (57 girls, 42 boys) subjects, aged 9-15. Bone turnover markers and 1,25(OH)2D reached maximal levels at pubertal stages 3-4, and decreased thereafter. After adjusting for puberty, age, and lean body mass, no group differences were found in markers of bone turnover, 1,25(OH)2D, PTH, or calcium excretion, but phosphate excretion was 23% lower in macrobiotic girls. After adjustment for puberty, 1,25(OH)2D was positively related to osteocalcin. In summary, we found no evidence for group differences in bone turnover, or catch up in relative bone mass, which might be due to the fact that 60% of subjects were still in early stages of puberty.

Osseous outgrowth on the buccal maxilla associated with piezosurgery-assisted en-masse retraction: A case series.

PubMed

Tunçer, Nilüfer İrem; Arman-Özçırpıcı, Ayça; Oduncuoğlu, Bahar Füsun; Kantarcı, Alpdoğan

2018-01-01

Piezoelectric surgery is a novel surgical approach used in orthodontic treatment for rapid tooth movement. This paper presents a case series wherein osseous outgrowths were observed in response to piezosurgery-assisted en-masse retraction. Sixteen patients requiring upper premolar extractions were treated with miniscrew-supported en-masse retraction and received minimally invasive decortication via piezosurgery. Computed tomography (CT) of the maxillary anterior region was performed to investigate the nature of the outgrowths. In 8 of the 16 patients, hemispheric or disc-shaped osseous outgrowths were observed on the sites where piezosurgery was performed during retraction. CT images revealed that these outgrowths were alveolar bone. This case series presents a previously unreported osseous response to piezosurgery-assisted tooth movement during orthodontic treatment. The response is mostly transient and is observed in 50% of the treated patients, suggesting a bone turnover that can be assessed clinically and radiographically.

Osseous outgrowth on the buccal maxilla associated with piezosurgery-assisted en-masse retraction: A case series

PubMed Central

Arman-Özçırpıcı, Ayça; Oduncuoğlu, Bahar Füsun; Kantarcı, Alpdoğan

2018-01-01

Piezoelectric surgery is a novel surgical approach used in orthodontic treatment for rapid tooth movement. This paper presents a case series wherein osseous outgrowths were observed in response to piezosurgery-assisted en-masse retraction. Sixteen patients requiring upper premolar extractions were treated with miniscrew-supported en-masse retraction and received minimally invasive decortication via piezosurgery. Computed tomography (CT) of the maxillary anterior region was performed to investigate the nature of the outgrowths. In 8 of the 16 patients, hemispheric or disc-shaped osseous outgrowths were observed on the sites where piezosurgery was performed during retraction. CT images revealed that these outgrowths were alveolar bone. This case series presents a previously unreported osseous response to piezosurgery-assisted tooth movement during orthodontic treatment. The response is mostly transient and is observed in 50% of the treated patients, suggesting a bone turnover that can be assessed clinically and radiographically. PMID:29291189

N-cadherin Regulation of Bone Growth and Homeostasis is Osteolineage Stage-Specific

PubMed Central

Fontana, Francesca; Hickman-Brecks, Cynthia L.; Salazar, Valerie S.; Revollo, Leila; Abou-Ezzi, Grazia; Grimston, Susan K.; Jeong, Sung Yeop; Watkins, Marcus; Fortunato, Manuela; Alippe, Yael; Link, Daniel C.; Mbalaviele, Gabriel; Civitelli, Roberto

2017-01-01

N-cadherin inhibits osteogenic cell differentiation and canonical Wnt/β-catenin signaling in vitro. However, in vivo both conditional Cdh2 ablation and overexpression in osteoblasts lead to low bone mass. We tested the hypothesis that N-cadherin has different effects on osteolineage cells depending upon their differentiation stage. Embryonic conditional osteolineage Cdh2 deletion in mice results in defective growth, low bone mass and reduced osteoprogenitor number. These abnormalities are prevented by delaying Cdh2 ablation until 1 month of age, thus targeting only committed and mature osteoblasts, suggesting they are the consequence of N-cadherin deficiency in osteoprogenitors. Indeed, diaphyseal trabecularization actually increases when Cdh2 is ablated postnatally. The sclerostin-insensitive Lrp5A214V mutant, associated with high bone mass, does not rescue the growth defect, but it overrides the low bone mass of embryonically Cdh2 deleted mice, suggesting N-cadherin interacts with Wnt signaling to control bone mass. Finally, bone accrual and β-catenin accumulation after administration of an anti-Dkk1 antibody are enhanced in N-cadherin deficient mice. Thus, while lack of N-cadherin in embryonic and perinatal age is detrimental to bone growth and bone accrual, in adult mice loss of N-cadherin in osteolineage cells favors bone formation. Hence, N-cadherin inhibition may widen the therapeutic window of osteoanabolic agents. PMID:28240364

Greater association of peak neuromuscular performance with cortical bone geometry, bone mass and bone strength than bone density: A study in 417 older women.

PubMed

Belavý, Daniel L; Armbrecht, Gabriele; Blenk, Tilo; Bock, Oliver; Börst, Hendrikje; Kocakaya, Emine; Luhn, Franziska; Rantalainen, Timo; Rawer, Rainer; Tomasius, Frederike; Willnecker, Johannes; Felsenberg, Dieter

2016-02-01

We evaluated which aspects of neuromuscular performance are associated with bone mass, density, strength and geometry. 417 women aged 60-94years were examined. Countermovement jump, sit-to-stand test, grip strength, forearm and calf muscle cross-sectional area, areal bone mineral content and density (aBMC and aBMD) at the hip and lumbar spine via dual X-ray absorptiometry, and measures of volumetric vBMC and vBMD, bone geometry and section modulus at 4% and 66% of radius length and 4%, 38% and 66% of tibia length via peripheral quantitative computed tomography were performed. The first principal component of the neuromuscular variables was calculated to generate a summary neuromuscular variable. Percentage of total variance in bone parameters explained by the neuromuscular parameters was calculated. Step-wise regression was also performed. At all pQCT bone sites (radius, ulna, tibia, fibula), a greater percentage of total variance in measures of bone mass, cortical geometry and/or bone strength was explained by peak neuromuscular performance than for vBMD. Sit-to-stand performance did not relate strongly to bone parameters. No obvious differential in the explanatory power of neuromuscular performance was seen for DXA aBMC versus aBMD. In step-wise regression, bone mass, cortical morphology, and/or strength remained significant in relation to the first principal component of the neuromuscular variables. In no case was vBMD positively related to neuromuscular performance in the final step-wise regression models. Peak neuromuscular performance has a stronger relationship with leg and forearm bone mass and cortical geometry as well as proximal forearm section modulus than with vBMD. Copyright © 2015 Elsevier Inc. All rights reserved.

Impact of skeletal maturation on bone metabolism biomarkers and bone mineral density in healthy Brazilian male adolescents.

PubMed

Silva, Carla C; Goldberg, Tamara B L; Nga, Hong S; Kurokawa, Cilmery S; Capela, Renata C; Teixeira, Altamir S; Dalmas, José C

2011-01-01

To evaluate the behavior of biomarkers of bone formation and resorption in healthy male Brazilian adolescents according to their biological maturation. Eighty-seven volunteers were divided into age groups according to bone age (BA): 10-12 years (n = 25), 13-15 years (n = 36), and 16-18 years (n = 26). Weight (kg), height (m), body mass index (kg/m(2)), calcium intake from 3 days assessed by 24-h food recall (mg/day), pubertal event evaluation by Tanner criteria, and serum biomarker levels (osteocalcin [OC] [ng/mL], bone alkaline phosphatase [BAP] [U/L], and serum carboxyterminal telopeptide [S-CTx] [ng/mL]) were recorded and correlated to bone mineral density (BMD) (g/cm(2)) measured by dual energy X-ray absorptiometry of the lumbar spine, proximal femur, and whole body. Biomarkers showed similar behaviors, presenting higher median values in the 13-15 year group (BAP = 154.71 U/L, OC = 43.0 ng/mL, S-CTx = 2.09 ng/mL; p < 0.01) and when adolescents were in the pubertal stage G4. Median biomarker values decreased with advancing BA and sexual maturation. Biomarker values showed parallelism with peak height velocity, and, interestingly, bone formation biomarkers indicated significant negative correlation with BMD in the different evaluated locations, i.e., higher BMD values correlated with lower bone biomarker values. This is the first study of healthy Brazilian adolescents with rigid and careful inclusion and exclusion criteria to assess the correlation of bone markers and BMD with biological maturation indicators. Our results can help understand bone turnover and monitor bone metabolism.

Physical activity for prevention of osteoporosis in patients with severe haemophilia on long-term prophylaxis.

PubMed

Khawaji, M; Astermark, J; Akesson, K; Berntorp, E

2010-05-01

Physical activity has been considered as an important factor for bone density and as a factor facilitating prevention of osteoporosis. Bone density has been reported to be reduced in haemophilia. To examine the relation between different aspects of physical activity and bone mineral density (BMD) in patients with severe haemophilia on long-term prophylaxis. The study group consisted of 38 patients with severe haemophilia (mean age 30.5 years). All patients received long-term prophylaxis to prevent bleeding. The bone density (BMD g cm(-2)) of the total body, lumbar spine, total hip, femoral neck and trochanter was measured by dual energy X-ray absorptiometry. Physical activity was assessed using the self-report Modifiable Activity Questionnaire, an instrument which collects information about leisure and occupational activities for the prior 12 months. There was only significant correlation between duration and intensity of vigorous physical activity and bone density at lumber spine L1-L4; for duration (r = 0.429 and P = 0.020) and for intensity (r = 0.430 and P = 0.019); whereas no significant correlation between all aspects of physical activity and bone density at any other measured sites. With adequate long-term prophylaxis, adult patients with haemophilia are maintaining bone mass, whereas the level of physical activity in terms of intensity and duration play a minor role. These results may support the proposition that the responsiveness to mechanical strain is probably more important for bone mass development in children and during adolescence than in adults and underscores the importance of early onset prophylaxis.

Exercise and bone mass in adults.

PubMed

Guadalupe-Grau, Amelia; Fuentes, Teresa; Guerra, Borja; Calbet, Jose A L

2009-01-01

There is a substantial body of evidence indicating that exercise prior to the pubertal growth spurt stimulates bone growth and skeletal muscle hypertrophy to a greater degree than observed during growth in non-physically active children. Bone mass can be increased by some exercise programmes in adults and the elderly, and attenuate the losses in bone mass associated with aging. This review provides an overview of cross-sectional and longitudinal studies performed to date involving training and bone measurements. Cross-sectional studies show in general that exercise modalities requiring high forces and/or generating high impacts have the greatest osteogenic potential. Several training methods have been used to improve bone mineral density (BMD) and content in prospective studies. Not all exercise modalities have shown positive effects on bone mass. For example, unloaded exercise such as swimming has no impact on bone mass, while walking or running has limited positive effects. It is not clear which training method is superior for bone stimulation in adults, although scientific evidence points to a combination of high-impact (i.e. jumping) and weight-lifting exercises. Exercise involving high impacts, even a relatively small amount, appears to be the most efficient for enhancing bone mass, except in postmenopausal women. Several types of resistance exercise have been tested also with positive results, especially when the intensity of the exercise is high and the speed of movement elevated. A handful of other studies have reported little or no effect on bone density. However, these results may be partially attributable to the study design, intensity and duration of the exercise protocol, and the bone density measurement techniques used. Studies performed in older adults show only mild increases, maintenance or just attenuation of BMD losses in postmenopausal women, but net changes in BMD relative to control subjects who are losing bone mass are beneficial in decreasing fracture risk. Older men have been less studied than women, and although it seems that men may respond better than their female counterparts, the experimental evidence for a dimorphism based on sex in the osteogenic response to exercise in the elderly is weak. A randomized longitudinal study of the effects of exercise on bone mass in elderly men and women is still lacking. It remains to be determined if elderly females need a different exercise protocol compared with men of similar age. Impact and resistance exercise should be advocated for the prevention of osteoporosis. For those with osteoporosis, weight-bearing exercise in general, and resistance exercise in particular, as tolerated, along with exercise targeted to improve balance, mobility and posture, should be recommended to reduce the likelihood of falling and its associated morbidity and mortality. Additional randomized controlled trials are needed to determine the most efficient training loads depending on age, sex, current bone mass and training history for improvement of bone mass.

N-acetylcysteine supplementation decreases osteoclast differentiation and increases bone mass in mice fed a high-fat diet

USDA-ARS?s Scientific Manuscript database

Studies have demonstrated that obesity induced by high-fat diets increases bone resorption, decreases trabecular bone mass, and reduces bone strength in various animal models. This study investigated whether N-acetylcysteine (NAC), an antioxidant and a glutathione precursor, alters glutathione statu...

Better Bones Buddies: An Osteoporosis Prevention Program

ERIC Educational Resources Information Center

Schrader, Susan L.; Blue, Rebecca; Horner, Arlene

2005-01-01

Although osteoporosis typically surfaces in later life, peak bone mass attained before age 20 is a key factor in its prevention. However, most American children's diets lack sufficient calcium during the critical growth periods of preadolescence and adolescence to achieve peak bone mass. "Better Bones (BB) Buddies" is an educational…

Bone Mass Measurement: What the Numbers Mean

MedlinePlus

... or more osteoporotic fractures. Low Bone Mass Versus Osteoporosis The information provided by a BMD test can ... 15-7877-E Last Reviewed 2015-06 NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 ...

CT and MRI of superficial solid tumors

PubMed Central

Zhang, Jingfeng; Li, Yanyuan; Zhao, Yilei

2018-01-01

Superficial solid masses are common conditions in clinical practice, however, some of which can be easily diagnosed and others would be difficult. Although imaging of superficial masses is not always characteristic, it would be helpful to give a definitive diagnosis or narrow a differential diagnosis. Crossing-section imaging can depicture the masses directly, find some pathognomonic signs and demonstrate their relationship with adjacent structures, which can provide decision support for clinician’s reference. Computed tomography (CT) can be used to detect calcifications and bone erosion which could not be seen on radiographs. Magnetic resonance imaging (MRI) is the preferred way for evaluating soft tissue lesions and provides information on hemorrhage, necrosis, edema, cystic and myxoid degeneration, and fibrosis. Other advantages of MRI are its superior soft tissue resolution and any profile imaging, which can aid the assessment of extension and adjacent infiltration. Positron emission tomography (PET)/CT and PET/MRI have been increasingly used in bone and soft tissue sarcomas and provides advantages in the initial tumor staging, tumor grading, therapy assessment, and recurrence detection. Therefore, imaging examination can play an important role in treatment decision making for superficial solid tumors. Here we review the important conditions presenting as superficial mass and show the imaging of typical cases diagnosed in our hospital. PMID:29675364

Control of bone and fat mass by oxytocin.

PubMed

Amri, Ez-Zoubir; Pisani, Didier F

2016-11-01

Osteoporosis and overweight/obesity constitute major worldwide public health burdens. Aging is associated with a decrease in hormonal secretion, lean mass and bone mass, and an increase in fat accumulation. It is established that both obesity and osteoporosis are affected by genetic and environmental factors, bone remodeling and adiposity are both regulated through the hypothalamus and sympathetic nervous system. Oxytocin (OT), belongs to the pituitary hormone family and regulates the function of peripheral target organs, its circulating levels decreased with age. Nowadays, it is well established that OT plays an important role in the control of bone and fat mass and their metabolism. Of note, OT and oxytocin receptor knock out mice develop bone defects and late-onset obesity. Thus OT emerges as a promising molecule in the treatment of osteoporosis and obesity as well as associated metabolic disorders such as type 2 diabetes and cardiovascular diseases. In this review, we will discuss findings regarding the OT effects on bone and fat mass.

[Pregnancy and lactation are not risk factors for osteoporosis or fractures].

PubMed

Karlsson, Magnus K; Ahlborg, Henrik G; Karlsson, Caroline

Observational and case control studies infer that a pregnancy and a period of lactation are followed by loss in bone mass of up to 5%. The reason for this loss is virtually impossible to conclude as so many factors known to influence the bone mass undergo changes during a pregnancy and lactation. The increased calcium demand, changed nutritional habits, reduced smoking and alcohol consumption seen in many women during these periods, the changes in body weight and fat content, the changed level of physical activity and the changed levels of hormones with potential to influence the bone metabolism could all influence the bone mass. Most studies also report that the deficit in "bone mass" normalises after weaning. Multiple pregnancies and long total duration of lactation can not be regarded as risk factors for osteoporosis and fragility fractures as most reports indicate that women with multiple pregnancies have similar or higher bone mass and similar or lower fracture incidence than their peers with no children.

Hypochlorhydria-induced calcium malabsorption does not affect fracture healing but increases post-traumatic bone loss in the intact skeleton.

PubMed

Haffner-Luntzer, Melanie; Heilmann, Aline; Heidler, Verena; Liedert, Astrid; Schinke, Thorsten; Amling, Michael; Yorgan, Timur Alexander; Vom Scheidt, Annika; Ignatius, Anita

2016-11-01

Efficient calcium absorption is essential for skeletal health. Patients with impaired gastric acidification display low bone mass and increased fracture risk because calcium absorption is dependent on gastric pH. We investigated fracture healing and post-traumatic bone turnover in mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells. Cckbr-/- mice display hypochlorhydria, calcium malabsorption, and osteopenia. Cckbr-/- and wildtype (WT) mice received a femur osteotomy and were fed either a standard or calcium-enriched diet. Healed and intact bones were assessed by biomechanical testing, histomorphometry, micro-computed tomography, and quantitative backscattering. Parathyroid hormone (PTH) serum levels were determined by enzyme-linked immunosorbent assay. Fracture healing was unaffected in Cckbr-/- mice. However, Cckbr-/- mice displayed increased calcium mobilization from the intact skeleton during bone healing, confirmed by significantly elevated PTH levels and osteoclast numbers compared to WT mice. Calcium supplementation significantly reduced secondary hyperparathyroidism and bone resorption in the intact skeleton in both genotypes, but more efficiently in WT mice. Furthermore, calcium administration improved bone healing in WT mice, indicated by significantly increased mechanical properties and bone mineral density of the fracture callus, whereas it had no significant effect in Cckbr-/- mice. Therefore, under conditions of hypochlorhydria-induced calcium malabsorption, calcium, which is essential for callus mineralization, appears to be increasingly mobilized from the intact skeleton in favor of fracture healing. Calcium supplementation during fracture healing prevented systemic calcium mobilization, thereby maintaining bone mass and improving fracture healing in healthy individuals whereas the effect was limited by gastric hypochlorhydria. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1914-1921, 2016. © 2016 The Authors. Journal of Orthopaedic Research Published by by Wiley Periodicals, Inc.

Childhood fractures are associated with decreased bone mass gain during puberty: an early marker of persistent bone fragility?

PubMed

Ferrari, Serge L; Chevalley, Thierry; Bonjour, Jean-Philippe; Rizzoli, René

2006-04-01

Whether peak bone mass is low among children with fractures remains uncertain. In a cohort of 125 girls followed over 8.5 years, 42 subjects reported 58 fractures. Among those, BMC gain at multiple sites and vertebral bone size at pubertal maturity were significantly decreased. Hence, childhood fractures may be markers of low peak bone mass acquisition and persistent skeletal fragility. Fractures in childhood may result from a deficit in bone mass accrual during rapid longitudinal growth. Whether low bone mass persists beyond this period however remains unknown. BMC at the spine, radius, hip, and femur diaphysis was prospectively measured over 8.5 years in 125 girls using DXA. Differences in bone mass and size between girls with and without fractures were analyzed using nonparametric tests. The contribution of genetic factors was evaluated by mother-daughter correlations and that of calcium intake by Cox proportional hazard models. Fifty-eight fractures occurred in 42 among 125 girls (cumulative incidence, 46.4%), one-half of all fractures affecting the forearm and wrist. Girls with and without fractures had similar age, height, weight. and calcium intake at all time-points. Before and during early puberty, BMC and width of the radius diaphysis was lower in the fracture compared with no-fracture group (p < 0.05), whereas aBMD and BMAD were similar in the two groups. At pubertal maturity (Tanner's stage 5, mean age +/- SD, 16.4 +/- 0.5 years), BMC at the ultradistal radius (UD Rad.), femur trochanter, and lumbar spine (LS), and LS projected bone area were all significantly lower in girls with fractures. Throughout puberty, BMC gain at these sites was also decreased in the fracture group (LS, -8.0%, p = 0.015; UD Rad., -12.0%, p = 0.004; trochanter, -8.4%, p = 0.05 versus no fractures). BMC was highly correlated between prepuberty and pubertal maturity (R = 0.54-0.81) and between mature daughters and their mothers (R = 0.32-0.46). Calcium intake was not related to fracture risk. Girls with fractures have decreased bone mass gain in the axial and appendicular skeleton and reduced vertebral bone size when reaching pubertal maturity. Taken together with the evidence of tracking and heritability for BMC, these observations indicate that childhood fractures may be markers for low peak bone mass and persistent bone fragility.

Analysis of imaging characteristics of primary malignant bone tumors in children

PubMed Central

Sun, Yingwei; Liu, Xueyong; Pan, Shinong; Deng, Chunbo; Li, Xiaohan; Guo, Qiyong

2017-01-01

The present study aimed to investigate the imaging characteristics of primary malignant bone tumors in children. The imaging results of 34 children with primary malignant bone tumors confirmed by histopathological diagnosis between March 2008 and January 2014 were retrospectively analyzed. In total, 25 patients had osteosarcoma, with radiography and computed tomography (CT) showing osteolytic bone destruction or/and osteoblastic bone sclerosis, an aggressive periosteal reaction, a soft-tissue mass and cancerous bone. The tumors appeared as mixed magnetic resonance imaging (MRI) signals that were inhomogeneously enhanced. A total of 5 patients presented with Ewing sarcoma, with radiography and CT showing invasive bone destruction and a soft-tissue mass. Of the 5 cases, 2 showed a laminar periosteal reaction. The tumors were shown to have mixed low signal on T1-weighted images (T1WI) and high signal on T2-weighted images (T2WI); 1 case showed marked inhomogeneous enhancement. Another 3 patients exhibited chondrosarcoma. Of these cases, 1 was adjacent to the cortex of the proximal tibia, and presented with local cortical bone destruction and a soft-tissue mass containing scattered punctate and amorphous calcifications. MRI revealed mixed low T1 signal and high T2 signals. Another case was located in the medullary cavity of the distal femur, with radiography revealing a localized periosteal reaction. The tumor appeared with mixed MRI signals, and with involvement of the epiphysis and epiphyseal plates. Radiography and CT of the third case showed bone destruction in the right pubic ramus, with patchy punctate, cambered calcifications in the soft-tissue mass. MRI of the soft-tissue mass revealed isointensity on T1WI and heterogeneous hyperintensity on T2WI. Ossifications and the septum appeared as low T1WI and T2WI. Of the 34 patients, 1 patient presented with lymphoma involving the T12, L1 and L2 vertebrae. CT showed vertebral bone destruction, a soft-tissue mass and a compression fracture of L1. MRI showed a soft-tissue mass with low T1 signal and high T2 signal and marked inhomogeneous enhancement. Overall, osteosarcoma was the most common primary malignant bone tumor, followed by Ewing sarcoma, chondrosarcoma and lymphoma. Osteoblastic or osteolytic bone destruction, an invasive periosteal reaction, soft-tissue masses, a tumor matrix and inhomogeneous enhancement were important imaging features of malignant bone tumors. PMID:29113210

The Beneficial Effects of Group-Based Exercises on Fall Risk Profile and Physical Activity Persist One-Year Post-Intervention in Older Women with Low Bone Mass: Follow-up After Withdrawal of Exercise

PubMed Central

Liu-Ambrose, Teresa YL; Khan, Karim M; Eng, Janice J; Gillies, Graham L; Lord, Stephen R; McKay, Heather A

2012-01-01

OBJECTIVE To determine whether exercise-induced reductions in fall risk are maintained in older women one year following the cessation of three types of interventions – resistance training, agility training, and general stretching. DESIGN One-year observational study. PARTICIPANTS 98 women aged 75–85 years with low bone mass. MEASUREMENTS Primary outcome measure was fall risk as measured by the Physiological Profile Assessment tool. Secondary outcome measures were current physical activity level as assessed by the Physical Activity Scale for the Elderly and formal exercise participation as assessed by interview. RESULTS At the end of the follow-up, the fall risk among former participants of all three exercise programs was maintained (i.e., still reduced) from trial completion. Mean fall risk value at the end of follow-up was 43.3% reduced compared with the mean baseline value among former participants of the Resistance Training group, 40.1% reduced in the Agility Training group, and 37.4% reduced in the general Stretching group. Physical activity levels were also maintained from trial completion. Specifically, there was a 3.8% increase in physical activity from baseline for the Resistance Training group, a 29.2% increase for the Agility Training group, and 37.7% increase for the general Stretching group. CONCLUSION After three types of group-based exercise programs, benefits are sustained for at least 12 months without further formal exercise intervention. Thus, these six-month exercise interventions appeared to act as a catalyst for increasing physical activity with resultant reductions in fall risk profile that were maintained for at least 18 months among older women with low bone mass. PMID:16181178

Osteoporosis: Modern Paradigms for Last Century's Bones.

PubMed

Kruger, Marlena C; Wolber, Frances M

2016-06-17

The skeleton is a metabolically active organ undergoing continuously remodelling. With ageing and menopause the balance shifts to increased resorption, leading to a reduction in bone mineral density and disruption of bone microarchitecture. Bone mass accretion and bone metabolism are influenced by systemic hormones as well as genetic and lifestyle factors. The classic paradigm has described osteoporosis as being a "brittle bone" disease that occurs in post-menopausal, thin, Caucasian women with low calcium intakes and/or vitamin D insufficiency. However, a study of black women in Africa demonstrated that higher proportions of body fat did not protect bone health. Isoflavone interventions in Asian postmenopausal women have produced inconsistent bone health benefits, due in part to population heterogeneity in enteric bacterial metabolism of daidzein. A comparison of women and men in several Asian countries identified significant differences between countries in the rate of bone health decline, and a high incidence rate of osteoporosis in both sexes. These studies have revealed significant differences in genetic phenotypes, debunking long-held beliefs and leading to new paradigms in study design. Current studies are now being specifically designed to assess genotype differences between Caucasian, Asian, African, and other phenotypes, and exploring alternative methodology to measure bone architecture.

Low bone mineral mass is associated with decreased bone formation and diet in girls with Rett syndrome.

PubMed

Motil, Kathleen J; Barrish, Judy O; Neul, Jeffrey L; Glaze, Daniel G

2014-09-01

The aim of the present study was to characterize biomarkers of bone turnover and their relation with bone mineral mass in a cross-sectional cohort of girls with Rett syndrome (RTT) and to examine the role of dietary, biochemical, hormonal, and inflammatory factors on bone mineral mass and bone biomarkers in this disorder. Total body bone mineral content (BMC) and bone mineral density (BMD) were determined by dual-energy x-ray absorptiometry. Dietary nutrient intakes were determined from 3-day food records. Biomarkers of bone turnover, bone metabolites, vitamin D metabolites, hormones, and inflammatory markers were measured by standard clinical laboratory methods. Serum osteocalcin, bone alkaline phosphatase, and C-telopeptide showed significant inverse relations with age in the RTT cohort. Mean osteocalcin concentrations were significantly lower and mean bone alkaline phosphatase concentrations were significantly higher for individual age groups in the RTT cohort than mean values for their respective age ranges in the reference population. Significant inverse associations were identified between urinary calcium losses, expressed as calcium:creatinine ratios, and total body BMC and BMD z scores. Dietary protein, calcium, and phosphorus intakes, expressed as a proportion of Dietary Reference Intakes for age and sex, showed significant positive associations with total body BMD z scores. The present study suggests decreased bone formation instead of increased bone resorption may explain in part the deficits in bone mineral mass in RTT and that attention to the adequacy of dietary protein, calcium, and phosphorus intakes may offer an opportunity to improve bone health in RTT.

Lifetime physical activity and calcium intake related to bone density in young women.

PubMed

Wallace, Lorraine Silver; Ballard, Joyce E

2002-05-01

Osteoporosis is a significant public health problem associated with increased mortality and morbidity. Our aim in this cross-sectional study was to investigate the relationship between lifetime physical activity and calcium intake and bone mineral density (BMD) and BMC (bone mineral content) in 42 regularly menstruating Caucasian women (age 21.26+/-1.91 years, BMI 23.83+/-5.85). BMD and BMC at the lumbar spine (L2-L4), hip (femoral neck, trochanter, total), and total body were assessed by dual energy x-ray absorptiometry (DXA). Lifetime history of physical activity and calcium intake was obtained by a structured interview using valid and reliable instruments. Measures of both lifetime physical activity and calcium intake were highly correlated. In stepwise multiple regression analyses, lean mass was the most important and consistent factor for predicting BMD and BMC at all skeletal sites (attributable r2 = 28.8%-78.7%). Lifetime physical activity contributed to 3.0% of the variation in total body BMD, and life-time weight-bearing physical activity explained 15.1% of variance in lumbar spine BMC. Current calcium intake predicted 6% of the variance in BMD at the femoral neck and trochanter. We found lean mass to be a powerful predictor of BMD and BMC in young women. Because lean mass can be modified to some extent by physical activity, public health efforts must be directed at increasing physical activity throughout the lifespan. Furthermore, our results suggest that adequate calcium intake may help to enhance bone mass, thus decreasing the risk of osteoporotic fracture later in life.

Bone mineral density in children with acute leukemia and its associated factors in Iran: a case-control study.

PubMed

Bordbar, Mohammad Reza; Haghpanah, Sezaneh; Dabbaghmanesh, Mohammad Hossein; Omrani, Gholamhossein Ranjbar; Saki, Forough

2016-12-01

Acute leukemia is the most common malignancy in children. We showed that low bone mass is prevalent among children with leukemia, especially in femur. Serum calcium, exercise, chemotherapy protocol, and radiotherapy are the main contributing factors. We suggest that early diagnosis and treatment of this problem could improve bone health in them. Acute leukemia is the most common malignancy in children and has been reported to be associated with low bone mass. Due to lack of sufficient data about the bone mineral density of children with leukemia in the Middle East, and inconsistencies between possible associated factors contributing to decreasing bone density in these children, we aimed to conduct a case-control study in Iran. This case-control study was conducted on 60 children with acute leukemia and 60 age- and sex-matched healthy controls. Anthropometric data, sun exposure, puberty, physical activity, and mineral biochemical parameters were assessed. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXA). Data analysis was done by SPSS software v. 21. Serum calcium was higher in the control group (P = 0.012) while serum phosphorous, alkaline phosphatase, and serum 25(OH)D 3 were higher in children with leukemia with P values of 0.04, 0.002, and 0.036, respectively. Sun exposure and physical activity were more in healthy controls (P values <0.001 and 0.003, respectively). Prevalence of vitamin D deficiency in case and control groups was 57.8 and 79.4 %, respectively. This prevalence was higher in healthy controls (P value = 0.007). Both lumbar and femoral neck bone mineral apparent density (BMAD) were higher in the control group (P value <0.001). Serum calcium, physical activity, and radiotherapy were the most relevant factors associated with lumbar BMAD. Femoral neck BMAD was associated with chemotherapy protocol. Low bone mass for chronological age is prevalent among children with leukemia, especially in the femoral neck. Serum calcium, physical activity, chemotherapy protocol, and radiotherapy are the main contributing factors.

Effects of Romosozumab Compared With Teriparatide on Bone Density and Mass at the Spine and Hip in Postmenopausal Women With Low Bone Mass.

PubMed

Genant, Harry K; Engelke, Klaus; Bolognese, Michael A; Mautalen, Carlos; Brown, Jacques P; Recknor, Chris; Goemaere, Stefan; Fuerst, Thomas; Yang, Yu-Ching; Grauer, Andreas; Libanati, Cesar

2017-01-01

Romosozumab, a monoclonal antibody that binds sclerostin, has a dual effect on bone by increasing bone formation and reducing bone resorption, and thus has favorable effects in both aspects of bone volume regulation. In a phase 2 study, romosozumab increased areal BMD at the lumbar spine and total hip as measured by DXA compared with placebo, alendronate, and teriparatide in postmenopausal women with low bone mass. In additional analyses from this international, randomized study, we now describe the effect of romosozumab on lumbar spine and hip volumetric BMD (vBMD) and BMC at month 12 as assessed by QCT in the subset of participants receiving placebo, s.c. teriparatide (20 µg once daily), and s.c. romosozumab (210 mg once monthly). QCT measurements were performed at the lumbar spine (mean of L 1 and L 2 entire vertebral bodies, excluding posterior processes) and hip. One year of treatment with romosozumab significantly increased integral vBMD and BMC at the lumbar spine and total hip from baseline, and compared with placebo and teriparatide (all p < 0.05). Trabecular vertebral vBMD improved significantly and similarly from baseline (p < 0.05) with both romosozumab (18.3%) and teriparatide (20.1%), whereas cortical vertebral vBMD gains were larger with romosozumab compared with teriparatide (13.7% versus 5.7%, p < 0.0001). Trabecular hip vBMD gains were significantly larger with romosozumab than with teriparatide (10.8% versus 4.2%, p = 0.01), but were similar for cortical vBMD (1.1% versus -0.9%, p = 0.12). Cortical BMC gains were larger with romosozumab compared with teriparatide at both the spine (23.3% versus 10.9%, p < 0.0001) and hip (3.4% versus 0.0%, p = 0.03). These improvements are expected to result in strength gains and support the continued clinical investigation of romosozumab as a potential therapy to rapidly reduce fracture risk in ongoing phase 3 studies. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Relationship of Fibroblast Growth Factor 23 (FGF-23) Serum Levels With Low Bone Mass in Postmenopausal Women.

PubMed

Shen, Jun; Fu, Shiping; Song, Yuan

2017-12-01

The aim of this study was to determine the relationship between serum fibroblast growth factor-23 (FGF-23) level and bone mass in postmenopausal women. A total of 60 premenopausal, 60 early postmenopausal, and 60 late postmenopausal women were investigated by the measurement of bone mineral densities (BMDs) at lumbar spine and proximal femur by DXA, together with serum concentrations of Ca, P, 25 (OH) D 3 , OC, iPTH, CTX-I, PINP, and FGF-23. The levels of FGF-23 and PINP in early postmenopausal group were significantly higher than that in the premenopausal or the late postmenopausal groups, their changing patterns were different form 25(OH)D 3, iPTH, IGF, CTX-I, and OC. According to the AUCs in the ROC analysis, we found that serum FGF-23 level was associated with the highest validity as compared to the other bone metabolism factors. Further study indicated the significant negative relationships between serum FGF-23 level and lumbar spine/proximal femur BMDs in postmenopausal women. After detection of the sensitivity and specificity of serum FGF- 23 for the low bone mass at different T-score (SD) lumbar spine/proximal femur BMDs, we found that serum FGF-23 level may be a reliable marker for low bone mass in postmenopausal women. The performance of FGF-23 in the differential diagnosis low bone mass from healthy participants indicated that FGF-23 has the capacity to differentiate the women with low bone mass from the normal ones. Our study indicated that serum FGF-23 level could be served as the utility in the early detection of women with low bone mass. J. Cell. Biochem. 118: 4454-4459, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Miniature X-Ray Bone Densitometer

NASA Technical Reports Server (NTRS)

Charles, Harry K., Jr.

1999-01-01

The purpose of the Dual Energy X-ray Absorptiometry (DEXA) project is to design, build, and test an advanced X-ray absorptiometry scanner capable of being used to monitor the deleterious effects of weightlessness on the human musculoskeletal system during prolonged spaceflight. The instrument is based on the principles of dual energy x-ray absorptiometry and is designed not only to measure bone, muscle, and fat masses but also to generate structural information about these tissues so that the effects on mechanical integrity may be assessed using biomechanical principles. A skeletal strength assessment could be particularly important for an astronaut embarking on a remote planet where the consequences of a fragility fracture may be catastrophic. The scanner will employ multiple projection images about the long axis of the scanned subject to provide geometric properties in three dimensions, suitable for a three-dimensional structural analysis of the scanned region. The instrument will employ advanced fabrication techniques to minimize volume and mass (100 kg current target with a long-term goal of 60 kg) of the scanner as appropriate for the space environment, while maintaining the required mechanical stability for high precision measurement. The unit will have the precision required to detect changes in bone mass and geometry as small as 1% and changes in muscle mass as small as 5%. As the system evolves, advanced electronic fabrication technologies such as chip-on-board and multichip modules will be combined with commercial (off-the-shelf) parts to produce a reliable, integrated system which not only minimizes size and weight, but, because of its simplicity, is also cost effective to build and maintain. Additionally, the system is being designed to minimize power consumption. Methods of heat dissipation and mechanical stowage (for the unit when not in use) are being optimized for the space environment.

Calcineurin/NFAT signaling in osteoblasts regulates bone mass.

PubMed

Winslow, Monte M; Pan, Minggui; Starbuck, Michael; Gallo, Elena M; Deng, Lei; Karsenty, Gerard; Crabtree, Gerald R

2006-06-01

Development and repair of the vertebrate skeleton requires the precise coordination of bone-forming osteoblasts and bone-resorbing osteoclasts. In diseases such as osteoporosis, bone resorption dominates over bone formation, suggesting a failure to harmonize osteoclast and osteoblast function. Here, we show that mice expressing a constitutively nuclear NFATc1 variant (NFATc1(nuc)) in osteoblasts develop high bone mass. NFATc1(nuc) mice have massive osteoblast overgrowth, enhanced osteoblast proliferation, and coordinated changes in the expression of Wnt signaling components. In contrast, viable NFATc1-deficient mice have defects in skull bone formation in addition to impaired osteoclast development. NFATc1(nuc) mice have increased osteoclastogenesis despite normal levels of RANKL and OPG, indicating that an additional NFAT-regulated mechanism influences osteoclastogenesis in vivo. Calcineurin/NFATc signaling in osteoblasts controls the expression of chemoattractants that attract monocytic osteoclast precursors, thereby coupling bone formation and bone resorption. Our results indicate that NFATc1 regulates bone mass by functioning in both osteoblasts and osteoclasts.

Leptin regulates bone formation via the sympathetic nervous system

NASA Technical Reports Server (NTRS)

Takeda, Shu; Elefteriou, Florent; Levasseur, Regis; Liu, Xiuyun; Zhao, Liping; Parker, Keith L.; Armstrong, Dawna; Ducy, Patricia; Karsenty, Gerard

2002-01-01

We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.

Functions of vasopressin and oxytocin in bone mass regulation

PubMed Central

Sun, Li; Tamma, Roberto; Yuen, Tony; Colaianni, Graziana; Ji, Yaoting; Cuscito, Concetta; Bailey, Jack; Dhawan, Samarth; Lu, Ping; Calvano, Cosima D.; Zhu, Ling-Ling; Zambonin, Carlo G.; Di Benedetto, Adriana; Stachnik, Agnes; Liu, Peng; Grano, Maria; Colucci, Silvia; Davies, Terry F.; New, Maria I.; Zallone, Alberta; Zaidi, Mone

2016-01-01

Prior studies show that oxytocin (Oxt) and vasopressin (Avp) have opposing actions on the skeleton exerted through high-affinity G protein-coupled receptors. We explored whether Avp and Oxtr can share their receptors in the regulation of bone formation by osteoblasts. We show that the Avp receptor 1α (Avpr1α) and the Oxt receptor (Oxtr) have opposing effects on bone mass: Oxtr−/− mice have osteopenia, and Avpr1α−/− mice display a high bone mass phenotype. More notably, this high bone mass phenotype is reversed by the deletion of Oxtr in Oxtr−/−:Avpr1α−/− double-mutant mice. However, although Oxtr is not indispensable for Avp action in inhibiting osteoblastogenesis and gene expression, Avp-stimulated gene expression is inhibited when the Oxtr is deleted in Avpr1α−/− cells. In contrast, Oxt does not interact with Avprs in vivo in a model of lactation-induced bone loss in which Oxt levels are high. Immunofluorescence microscopy of isolated nucleoplasts and Western blotting and MALDI-TOF of nuclear extracts show that Avp triggers Avpr1α localization to the nucleus. Finally, a specific Avpr2 inhibitor, tolvaptan, does not affect bone formation or bone mass, suggesting that Avpr2, which primarily functions in the kidney, does not have a significant role in bone remodeling. PMID:26699482

ABCD: Anthropometry, Body Composition, and Crohn Disease.

PubMed

Brookes, Denise S K; Briody, Julie N; Davies, Peter S W; Hill, Rebecca J

2016-07-01

Young individuals with Crohn disease (CD) are at risk of poor bone mineral density (BMD) and reduced lean tissue mass (LTM). The importance of LTM for maintaining skeletal health, in both incident and established CD, is evidenced. We used dual-energy x-ray absorptiometry assessment to identify areal BMD and LTM in individuals with CD. In 57 patients with CD (15F; 12.99-14.16 years) anthropometric, disease activity, bone age assessment, and total body dual-energy x-ray absorptiometry measurements were acquired. A 4-step algorithm was used to assess simultaneous bone and body composition data: areal BMD and height z scores, and LTM for height and bone mineral content (BMC) for LTM z scores were calculated. Low z score cut-off values were defined as ≤1 standard deviations below the population means. The CD cohort showed: low areal BMD z scores (P = 0.00); and low LTM for height (P = 0.00) according to defined cut-off values. BMC appeared to be adapting for the lower amount of LTM. Correcting for bone age eliminated the low areal BMD z scores. As expected, LTM for height and BMC for LTM z scores remained unchanged. We present a useful clinical algorithm to show significant LTM for height deficits, regardless of chronological or bone age, in this CD cohort. BMC seemed to adapt to the reduced LTM, indicating clinically "normal" areal BMD for age when considered for height. The ongoing deficits in LTM may, however, create chronic long-term consequences for bone health. Improving LTM should be a focus of clinical treatment in individuals with CD.

In vivo assessment of forearm bone mass and ulnar bending stiffness in healthy men

NASA Technical Reports Server (NTRS)

Myburgh, K. H.; Zhou, L. J.; Steele, C. R.; Arnaud, S.; Marcus, R.

1992-01-01

The cross-sectional bending stiffness EI of the ulna was measured in vivo by mechanical resistance tissue analysis (MRTA) in 90 men aged 19-89 years. MRTA measures the impedance response of low-frequency vibrations to determine EI, which is a reflection of elastic modulus E and moment of inertia I for the whole ulna. EI was compared to conventional estimates of bone mineral content (BMC), bone width (BW), and BMC/BW, which were all measured by single-photon absorptiometry. Results obtained from the nondominant ulna indicate that BW increases (r = 0.27, p = 0.01) and ulnar BMC/BW decreases (r = -0.31, p < or = 0.005) with age. Neither BMC nor EI declined with age. The single best predictor of EI was BW (r2 = 0.47, p = 0.0001), and further small but significant contributions were made by BMC (r2 = 0.53, p = 0.0001) and grip strength (r2 = 0.55, p = 0.0001). These results suggest that the resistance of older men to forearm fracture is related to age-associated changes in the moment of inertia achieved by redistributing bone mineral farther from the bending axis. We conclude that the in vivo assessment of bone geometry offers important insights to the comprehensive evaluation of bone strength.

Spontaneous recovery of bone mass after cure of endogenous hypercortisolism.

PubMed

Randazzo, Maria Elena; Grossrubatscher, Erika; Dalino Ciaramella, Paolo; Vanzulli, Angelo; Loli, Paola

2012-06-01

Patients with Cushing's syndrome (CS) develop osteopenia-osteoporosis. The present study evaluates the recovery of bone mass within 2 years after remission of hypercortisolism and in long term follow up, an issue rarely addressed. Twenty patients (6M, 14F, 3 post-menopausal, 15-64 years old), 15 with Cushing's disease, 2 with ectopic ACTH syndrome, 3 with ACTH-independent CS were studied. BMD, T and Z scores at lumbar spine and proximal femur were assessed by dual-energy X-ray absorptiometry before and 7-33 months after treatment of hypercortisolism. Five patients were treated with bisphosphonates. Four patients had hypogonadism and 4 GH-deficiency. At baseline all patients showed osteopenia/osteoporosis and the spine appeared more damaged than the femur; femur BMD was positively related with body mass index (BMI). No correlations were observed between spine and femur bone parameters and duration of disease or severity of hypercortisolism. Bone parameters did not differ in patients with or without GH or other pituitary deficiencies. After cure of hypercortisolism a significant improvement in spine BMD, Z and T scores and in femur Z and T scores was observed with normalization in 3 patients; there was no significant difference in percent improvement between femur and spine. The increase in bone parameters at spine and femur was independent from values at baseline. The percent increase in spine T and Z scores was positively related with time elapsed since cure. Bisphosphonates did not influence the recovery of bone mineralization. In long term follow up, after a median period of 7 years a further improvement in bone density was observed in 100% of patients at spine and in 9/11 at femur, although 8/11 patients still had femoral and/or vertebral T score in the range of osteopenia/osteoporosis. Spontaneous improvement of osteoporosis after cure of hypercortisolism occurs both at spine and femur, is independent from basal conditions and not affected by bisphosphonates. The improvement at spine depends on time since cure.

Effect of resistance training with vibration and compression on the formation of muscle and bone.

PubMed

Zinner, Christoph; Baessler, Bettina; Weiss, Kilian; Ruf, Jasmine; Michels, Guido; Holmberg, Hans-Christer; Sperlich, Billy

2017-12-01

In this study we investigated the effects of resistance training with vibration in combination with leg compression to restrict blood flow on strength, muscle oxygenation, muscle mass, and bone formation. Twelve participants were tested before and after 12 weeks of resistance training with application of vibration (VIBRA; 1-2 mm, 30 Hz) to both legs and compression (∼35 mm Hg, VIBRA+COMP) to only 1 leg. VIBRA+COMP and VIBRA improved 1 repetition maximum (1-RM), increased the number of repetitions preceding muscle exhaustion, enhanced cortical bone mass, and lowered the mass and fat fraction in the thigh, with no changes in total muscle mass. The mass of cancellous bone decreased to a similar extent after VIBRA and VIBRA+COMP. Resistance training with VIBRA+COMP and VIBRA improved 1-RM, increased the number of repetitions preceding muscular exhaustion, and enhanced formation of cortical bone, with no alteration of muscle mass. Muscle Nerve 56: 1137-1142, 2017. © 2017 Wiley Periodicals, Inc.

Metabolic and clinical assessment of efficacy of cryoablation therapy on skeletal masses by 18F-FDG positron emission tomography/computed tomography (PET/CT) and visual analogue scale (VAS): initial experience.

PubMed

Masala, Salvatore; Schillaci, Orazio; Bartolucci, Alberto D; Calabria, Ferdinando; Mammucari, Matteo; Simonetti, Giovanni

2011-02-01

Various therapy modalities have been proposed as standard treatments in management of bone metastases. Radiation therapy remains the standard of care for patients with localized bone pain, but up to 30% of them do not experience notable pain relief. Percutaneous cryoablation is a minimally invasive technique that induces necrosis by alternately freezing and thawing a target tissue. This technique is successfully used to treat a variety of malignant and benign diseases in different sites. (18)F-FDG positron emission tomography/computed tomography ((18)F-FDG PET/CT) is a single technique of imaging that provides in a "single step" both morphological and metabolic features of neoplastic lesions of the bone. The aim of this study was to evaluate the efficacy of the cryosurgical technique on secondary musculoskeletal masses according to semi-quantitative PET analysis and clinical-test evaluation with the visual analogue scale (VAS). We enrolled 20 patients with painful bone lesions (score pain that exceeded 4 on the VAS) that were non-responsive to treatment; one lesion per patient was treated. All patients underwent a PET-CT evaluation before and 8 weeks after cryotherapy; maximum standardized uptake value (SUV(max)) was measured before and after treatment for metabolic assessment of response to therapy. After treatment, 18 patients (90%) showed considerable reduction in SUV(max) value (>50%) suggestive of response to treatment; only 2 patients did not show meaningful reduction in metabolic activity. Our preliminary study demonstrates that quantitative analysis provided by PET correlates with response to cryoablation therapy as assessed by CT data and clinical VAS evaluation.

Analysis of the independent power of age-related, anthropometric and mechanical factors as determinants of the structure of radius and tibia in normal adults. A pQCT study.

PubMed

Reina, P; Cointry, G R; Nocciolino, L; Feldman, S; Ferretti, J L; Rittweger, J; Capozza, R F

2015-03-01

To compare the independent influence of mechanical and non-mechanical factors on bone features, multiple regression analyses were performed between pQCT indicators of radius and tibia bone mass, mineralization, design and strength as determined variables, and age or time since menopause (TMP), body mass, bone length and regional muscles' areas as selected determinant factors, in Caucasian, physically active, untrained healthy men and pre- and post-menopausal women. In men and pre-menopausal women, the strongest influences were exerted by muscle area on radial features and by both muscle area and bone length on the tibia. Only for women, was body mass a significant factor for tibia traits. In men and pre-menopausal women, mass/design/strength indicators depended more strongly on the selected determinants than the cortical vBMD did (p<0.01-0.001 vs n.s.), regardless of age. However, TMP was an additional factor for both bones (p<0.01-0.001). The selected mechanical factors (muscle size, bone lengths) were more relevant than age/TMP or body weight to the development of allometrically-related bone properties (mass/design/strength), yet not to bone tissue 'quality' (cortical vBMD), suggesting a determinant, rather than determined role for cortical stiffness. While the mechanical impacts of muscles and bone levers on bone structure were comparable in men and pre-menopausal women, TMP exerted a stronger impact than allometric or mechanical factors on bone properties, including cortical vBMD.

Deletion of FoxO1, 3, and 4 in Osteoblast Progenitors Attenuates the Loss of Cancellous Bone Mass in a Mouse Model of Type 1 Diabetes

PubMed Central

Iyer, Srividhya; Han, Li; Ambrogini, Elena; Yavropoulou, Maria; Fowlkes, John; Manolagas, Stavros C; Almeida, Maria

2017-01-01

Type 1 diabetes is associated with osteopenia and increased fragility fractures, attributed to reduced bone formation. However, the molecular mechanisms mediating these effects remain unknown. Insulin promotes osteoblast formation and inhibits the activity of the FoxO transcription factors. FoxOs, on the other hand, inhibit osteoprogenitor proliferation and bone formation. Here, we investigated whether FoxOs play a role in the low bone mass associated with type 1 diabetes, using mice lacking FoxO1, 3, and 4 in osteoprogenitor cells (FoxO1,3,4ΔOsx1-Cre). Streptozotocin-induced diabetes caused a reduction in bone mass and strength in FoxO-intact mice. In contrast, cancellous bone was unaffected in diabetic FoxO1,3,4ΔOsx1-Cre mice. The low bone mass in the FoxO-intact diabetic mice was associated with decreased osteoblast number and bone formation, as well as decreased expression of the anti-osteoclastogenic cytokine osteoprotegerin (OPG) and increased osteoclast number. FoxO deficiency did not alter the effects of diabetes on bone formation; however, it did prevent the decrease in OPG and the increase in osteoclast number. Addition of high glucose to osteoblastic cell cultures decreased OPG mRNA, indicating that hyperglycemia in and of itself contributes to diabetic bone loss. Taken together, these results suggest that FoxOs exacerbate the loss of cancellous bone mass associated with type 1 diabetes and that inactivation of FoxOs might ameliorate the adverse effects of insulin deficiency. PMID:27491024

Low Bone Mineral Mass Is Associated with Decreased Bone Formation and Diet in Females with Rett Syndrome

PubMed Central

Motil, Kathleen J.; Barrish, Judy O.; Neul, Jeffrey L.; Glaze, Daniel G.

2014-01-01

Objective To characterize biomarkers of bone turnover and their relation with bone mineral mass in a cross-sectional cohort of females with Rett syndrome (RTT) and to examine the role of dietary, biochemical, hormonal, and inflammatory factors on bone mineral mass and bone biomarkers in this disorder. Methods Total body bone mineral content (BMC) and density (BMD) were determined by dual-energy x-ray absorptiometry. Dietary nutrient intakes were determined from 3-day food records. Biomarkers of bone turnover, bone metabolites, vitamin D metabolites, hormones, and inflammatory markers were measured by standard clinical laboratory methods. Results Serum osteocalcin, bone alkaline phosphatase, and C-telopeptide showed significant inverse relations with age in the RTT cohort. Mean osteocalcin concentrations were significantly lower and mean bone alkaline phosphatase concentrations were significantly higher for individual age groups in the RTT cohort than mean values for their respective age ranges in the reference population. Significant inverse associations were identified between urinary calcium losses, expressed as calcium:creatinine ratios, and total body BMC and BMD z-scores. Dietary protein, calcium, and phosphorus intakes, expressed as a proportion of Dietary Reference Intakes for age and gender, showed significant positive associations with total body BMD z-scores. Conclusion This study suggests decreased bone formation rather than increased bone resorption may explain in part the deficits in bone mineral mass in RTT and that attention to the adequacy of dietary protein, calcium and phosphorus intakes may offer an opportunity to improve bone health in RTT. PMID:25144778

Osteoporosis: Are we measuring what we intend to measure? In search of the ideal bone strength study

NASA Astrophysics Data System (ADS)

de Riese, Cornelia

2006-02-01

In 1991 the World Health Organization (WHO) defined osteoporosis as a "loss of bone mass and micro architectural deterioration of the skeleton leading to increased risk of fracture." 1,2 Since microarchitecture can not be measured directly, a panel of the WHO recommended that the diagnosis be made according to a quantifiable surrogate marker, calcium mineral, in bone. Subsequently in 1994, the definition focused on the actual bone "density," giving densitometric technology a central place in establishing the diagnosis of osteoporosis. 3,4 But soon it became obvious that there was only limited correlation between bone mineral density (BMD) and actual occurrence of fractures and that decreases in bone mass account for only about 50% of the deterioration of bone strength with aging. In other words only about 60% of bone strength is related to BMD. 5 Recent developments in bone research have shown that bone mineral density in itself is not sufficient to accurately predict fracture risk. Bone is composed of inorganic calcium apatite crystals that mineralize an organic type I collagen matrix. The degree of mineralization, the properties of the collagen matrix, crystal size, trabecular orientation, special distribution of the different components and many more factors are all impacting bone strength. 6-14 Human cadaver studies have confirmed the correlation between bone density and bone. 26 strength. 5,15-20 Changes in cancellous bone morphology appear to lead to a disproportionate decrease in bone strength. 21-26 When postmenopausal women are stratified by age, obvious differences between BMD and actual fracture risk are observed. 24 Felsenberg eloquently summarizes what he calls the "Bone Quality Framework." In great detail he talks about the geometry and micro- architecture of bone and how the different components are related to functional stability. 27 Are our current testing modalities appropriately addressing these structural factors? Are we keeping in mind that in screening for osteoporosis the key variable is fragility, not bone density itself? All currently FDA approved and commercially available equipments for the evaluation of bone status claim that they - at least indirectly - assess the biological fracture risk. This review summarizes an extensive current literature research covering FDA approved as well as experimental devices for the evaluation of bone. The pros and cons of the different techniques are discussed in the context of diagnostic accuracies and practical implications.

The Effects of Hypergravity and Adrenalectomy on Bone Mineral Content, Urine Calcium and Body Mass in Rats

NASA Technical Reports Server (NTRS)

Lau, A.; Ramirez, J.; Melson, E.; Moran, M.; Baer, L.; Arnaud, S.; Wade, C.; Girten, B.; Dalton, Bonnie (Technical Monitor)

2001-01-01

The effects of 14 days of increased gravitational load, and the absence of adrenal stress hormones on total body bone mineral content (BMC) were examined in male Sprague-Dawley rats. Centrifugation at 2 Gs (2G) was used to increase the gravitational load, and bilateral adrenalectomy (ADX) was used to eliminate the production of adrenal stress hormones. Stationary groups at 1 G (1G) and sham operated (SHAM) animals served as controls. Thirty rats (n=6 or 8) made up the four experimental groups (1G SHAM, 1G ADX, 2G SHAM and 2G ADX). BMC was assessed by dual energy x-ray absorptiometry (DXA) which was performed to determine the total body bone mineral content, and also through bone ashing of the left femur and the left humerus. Activity was determined through biotelemetry, also body mass and food intake were measured. Multi-factorial analysis of variance (MANCOVA) and Newman Keuls post hoc tests were used to analyze significant effects (p is less than 0.05) for the primary variables. Results from both DXA and the ashed femur indicated that BMC decreased significantly with increased G for both the SHAM and ADX groups. The BMC determined by DXA for the 1G ADX group was also significantly lower than the 1G SHAM group, however the 2G SHAM and 2G ADX groups were not significantly different. However, the bone ashing results showed the femur differed significantly only between the rates of centrifugation and not between the ADX and SHAM. The humerus showed no significant difference between any of the groups. There was a significant decrease in body mass with increased G and there was no ADX effect on body mass. When DXA BMC was normalized for body mass changes, there were no significant group differences. However, with bone ashing, the femur BMC/BW still showed significant difference between rates of centrifugation, with the 2G group being lower. Activity level decreased with body mass, and food intake data showed there was significant hypophagia during the first few days of centrifugation. Urine calcium was measured and was found decrease at the start of centrifugation for the 2G groups and rise to a level higher than that of the stationary groups. Finally, the correlation between BW and BMC was determined to be highly correlated (r = .71). These results suggest that the decrease in total body BMC seen with hypergravity may be based to a large extent on the differences in body mass induced by the 2G load.

Bone density and the lightweight skeletons of birds.

PubMed

Dumont, Elizabeth R

2010-07-22

The skeletons of birds are universally described as lightweight as a result of selection for minimizing the energy required for flight. From a functional perspective, the weight (mass) of an animal relative to its lift-generating surfaces is a key determinant of the metabolic cost of flight. The evolution of birds has been characterized by many weight-saving adaptations that are reflected in bone shape, many of which strengthen and stiffen the skeleton. Although largely unstudied in birds, the material properties of bone tissue can also contribute to bone strength and stiffness. In this study, I calculated the density of the cranium, humerus and femur in passerine birds, rodents and bats by measuring bone mass and volume using helium displacement. I found that, on average, these bones are densest in birds, followed closely by bats. As bone density increases, so do bone stiffness and strength. Both of these optimization criteria are used in the design of strong and stiff, but lightweight, manmade airframes. By analogy, increased bone density in birds and bats may reflect adaptations for maximizing bone strength and stiffness while minimizing bone mass and volume. These data suggest that both bone shape and the material properties of bone tissue have played important roles in the evolution of flight. They also reconcile the conundrum of how bird skeletons can appear to be thin and delicate, yet contribute just as much to total body mass as do the skeletons of terrestrial mammals.

Bone mineral density, muscle strength and physical activity. A population-based study of 332 subjects aged 15-42 years.

PubMed

Düppe, H; Gärdsell, P; Johnell, O; Nilsson, B E; Ringsberg, K

1997-04-01

The aim of this population-based study was to find out whether differences in levels of physical activity have an influence on bone mass quantity and whether quadriceps muscle strength is a reliable determinant of bone mass. Included were 175 men and 157 women, aged 15-42 years. Bone mineral density (BMD) was measured at various sites by dual X-ray absorptiometry (DXA) and single photon absorptiometry (SPA). Muscle strength was assessed using an isokinetic muscle force meter. A questionnaire was used to estimate the level of physical activity. We found a positive correlation between physical activity and BMD for boys at the distal forearm and for girls at the trochanter (age group 15-16 years). Active men (age group 21-42 years) had up to 9% higher BMD levels at the hip than those who were less active. Quadriceps muscle torque was not an independent predictor of BMD. Our data suggest that a higher level of physical activity-within the limits of a "normal life style"-may have a positive effect on BMD in the proximal femur of young adults, which in turn may lessen the subsequent risk of fracture.

Are there effects of age, gender, height, and body fat on the functional muscle-bone unit in children and adults?

PubMed

Duran, I; Martakis, K; Hamacher, S; Stark, C; Semler, O; Schoenau, E

2018-05-01

The aim was to describe the effect of age, gender, height, different stages of human life, and body fat on the functional muscle-bone unit. All these factors had a significant effect on the functional muscle-bone unit and should be addressed when assessing functional muscle-bone unit in children and adults. For the clinical evaluation of the functional muscle-bone unit, it was proposed to evaluate the adaptation of the bone to the acting forces. A frequently used parameter for this is the total body less head bone mineral content (TBLH-BMC) determined by dual-energy X-ray absorptiometry (DXA) in relation to the lean body mass (LBM by DXA). LBM correlates highly with muscle mass. Therefore, LBM is a surrogate parameter for the muscular forces acting in everyday life. The aim of the study was to describe the effect of age and gender on the TBLH-BMC for LBM and to evaluate the impact of other factors, such as height, different stages of human life, and of body fat. As part of the National Health and Nutrition Examination Survey (NHANES) study, between the years 1999-2006 whole-body DXA scans on randomly selected Americans from 8 years of age were carried out. From all eligible DXA scans (1999-2004), three major US ethnic groups were evaluated (non-Hispanic Whites, non-Hispanic Blacks, and Mexican Americans) for further statistical analysis. For the statistical analysis, the DXA scans of 8190 non-Hispanic White children and adults (3903 female), of 4931 non-Hispanic Black children and adults (2250 female) and 5421 of Mexican-American children and adults (2424 female) were eligible. Age, gender, body height, and especially body fat had a significant effect on the functional muscle-bone unit. When assessing TBLH-BMC for LBM in children and adults, the effects of age, gender, body fat, and body height should be addressed. These effects were analyzed for the first time in such a large cohort.

Hypericum perforatum L. treatment restored bone mass changes in swimming stressed rats.

PubMed

Seferos, Nikos; Petrokokkinos, Loukas; Kotsiou, Antonia; Rallis, George; Tesseromatis, Christine

2016-01-01

Stress, via corticosteroids release, influences bone mass density. Hypericum perforatum (Hp) a traditional remedy possess antidepressive activity (serotonin reuptake inhibitor) and wound healing properties. Hp preparation contains mainly hypericin, hyperforin, hyperoside and flavonoids exerting oestrogen-mimetic effect. Cold swimming represents an experimental model of stress associating mental strain and corporal exhaustion. This study investigates the Hp effect on femur and mandible bone mass changes in rats under cold forced swimming procedure. 30 male Wistar rats were randomized into three groups. Group A was treated with Methanolic extract of Hp (Jarsin®) via gastroesophageal catheter, and was submitted to cold swimming stress for 10 min/daily. Group B was submitted to cold stress, since group C served as control. Experiment duration was 10 days. Haematocrite and serum free fatty acids (FFA) were estimated. Furthermore volume and specific weight of each bone as well as bone mass density via dual energy X-Ray absorptiometry (DEXA) were measured. Statistic analysis by t-test. Hp treatment restores the stress injuries. Adrenals and bone mass density regain their normal values. Injuries occurring by forced swimming stress in the rats are significantly improved by Hp treatment. Estrogen-like effects of Hp flavonoids eventually may act favorable in bone remodeling.

Targeting the LRP5 pathway improves bone properties in a mouse model of osteogenesis imperfecta.

PubMed

Jacobsen, Christina M; Barber, Lauren A; Ayturk, Ugur M; Roberts, Heather J; Deal, Lauren E; Schwartz, Marissa A; Weis, MaryAnn; Eyre, David; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

2014-10-01

The cell surface receptor low-density lipoprotein receptor-related protein 5 (LRP5) is a key regulator of bone mass and bone strength. Heterozygous missense mutations in LRP5 cause autosomal dominant high bone mass (HBM) in humans by reducing binding to LRP5 by endogenous inhibitors, such as sclerostin (SOST). Mice heterozygous for a knockin allele (Lrp5(p.A214V) ) that is orthologous to a human HBM-causing mutation have increased bone mass and strength. Osteogenesis imperfecta (OI) is a skeletal fragility disorder predominantly caused by mutations that affect type I collagen. We tested whether the LRP5 pathway can be used to improve bone properties in animal models of OI. First, we mated Lrp5(+/p.A214V) mice to Col1a2(+/p.G610C) mice, which model human type IV OI. We found that Col1a2(+/p.G610C) ;Lrp5(+/p.A214V) offspring had significantly increased bone mass and strength compared to Col1a2(+/p.G610C) ;Lrp5(+/+) littermates. The improved bone properties were not a result of altered mRNA expression of type I collagen or its chaperones, nor were they due to changes in mutant type I collagen secretion. Second, we treated Col1a2(+/p.G610C) mice with a monoclonal antibody that inhibits sclerostin activity (Scl-Ab). We found that antibody-treated mice had significantly increased bone mass and strength compared to vehicle-treated littermates. These findings indicate increasing bone formation, even without altering bone collagen composition, may benefit patients with OI. © 2014 American Society for Bone and Mineral Research.

Protocol for a randomized controlled trial to compare bone-loading exercises with risedronate for preventing bone loss in osteopenic postmenopausal women.

PubMed

Bilek, Laura D; Waltman, Nancy L; Lappe, Joan M; Kupzyk, Kevin A; Mack, Lynn R; Cullen, Diane M; Berg, Kris; Langel, Meghan; Meisinger, Melissa; Portelli-Trinidad, Ashlee; Lang, Molly

2016-08-30

In the United States, over 34 million American post-menopausal women have low bone mass (osteopenia) which increases their risk of osteoporosis and fractures. Calcium, vitamin D and exercise are recommended for prevention of osteoporosis, and bisphosphonates (BPs) are prescribed in women with osteoporosis. BPs may also be prescribed for women with low bone mass, but are more controversial due to the potential for adverse effects with long-term use. A bone loading exercise program (high-impact weight bearing and resistance training) promotes bone strength by preserving bone mineral density (BMD), improving bone structure, and by promoting bone formation at sites of mechanical stress. The sample for this study will be 309 women with low bone mass who are within 5 years post-menopause. Subjects are stratified by exercise history (≥2 high intensity exercise sessions per week; < 2 sessions per week) and randomized to a control or one of two treatment groups: 1) calcium + vitamin D (CaD) alone (Control); 2) a BP plus CaD (Risedronate); or 3) a bone loading exercise program plus CaD (Exercise). After 12 months of treatment, changes in bone structure, BMD, and bone turnover will be compared in the 3 groups. Primary outcomes for the study are bone structure measures (Bone Strength Index [BSI] at the tibia and Hip Structural Analysis [HSA] scores). Secondary outcomes are BMD at the hip and spine and serum biomarkers of bone formation (alkaline phosphase, AlkphaseB) and resorption (Serum N-terminal telopeptide, NTx). Our central hypothesis is that improvements in bone strength will be greater in subjects randomized to the Exercise group compared to subjects in either Control or Risedronate groups. Our research aims to decrease the risk of osteoporotic fractures by improving bone strength in women with low bone mass (pre-osteoporotic) during their first 5 years' post-menopause, a time of rapid and significant bone loss. Results of this study could be used in developing a clinical management pathway for women with low bone mass at their peak period of bone loss that would involve lifestyle modifications such as exercises prior to medications such as BPs. Clinicaltrials.gov NCT02186600 . Initial registration: 7/7/2014.

Parallels between Nutrition and Physical Activity: Research Questions in Development of Peak Bone Mass

ERIC Educational Resources Information Center

Weaver, Connie M.

2015-01-01

Lifestyle choices are attributed to 40% to 60% of adult peak bone mass. The National Osteoporosis Foundation (NOF) sought to update its 2000 consensus statement on peak bone mass and partnered with the American Society for Nutrition, which, in turn, charged a 9-member writing committee with using a systematic review approach to update the previous…

A myostatin inhibitor (propeptide-Fc) increases muscle mass and muscle fiber size in aged mice but does not increase bone density or bone strength.

PubMed

Arounleut, Phonepasong; Bialek, Peter; Liang, Li-Fang; Upadhyay, Sunil; Fulzele, Sadanand; Johnson, Maribeth; Elsalanty, Mohammed; Isales, Carlos M; Hamrick, Mark W

2013-09-01

Loss of muscle and bone mass with age are significant contributors to falls and fractures among the elderly. Myostatin deficiency is associated with increased muscle mass in mice, dogs, cows, sheep and humans, and mice lacking myostatin have been observed to show increased bone density in the limb, spine, and jaw. Transgenic overexpression of myostatin propeptide, which binds to and inhibits the active myostatin ligand, also increases muscle mass and bone density in mice. We therefore sought to test the hypothesis that in vivo inhibition of myostatin using an injectable myostatin propeptide (GDF8 propeptide-Fc) would increase both muscle mass and bone density in aged (24 mo) mice. Male mice were injected weekly (20 mg/kg body weight) with recombinant myostatin propeptide-Fc (PRO) or vehicle (VEH; saline) for four weeks. There was no difference in body weight between the two groups at the end of the treatment period, but PRO treatment significantly increased mass of the tibialis anterior muscle (+ 7%) and increased muscle fiber diameter of the extensor digitorum longus (+ 16%) and soleus (+ 6%) muscles compared to VEH treatment. Bone volume relative to total volume (BV/TV) of the femur calculated by microCT did not differ significantly between PRO- and VEH-treated mice, and ultimate force (Fu), stiffness (S), toughness (U) measured from three-point bending tests also did not differ significantly between groups. Histomorphometric assays also revealed no differences in bone formation or resorption in response to PRO treatment. These data suggest that while developmental perturbation of myostatin signaling through either gene knockout or transgenic inhibition may alter both muscle and bone mass in mice, pharmacological inhibition of myostatin in aged mice has a more pronounced effect on skeletal muscle than on bone. © 2013. Published by Elsevier Inc. All rights reserved.

Impact of hemodialysis on dual X-ray absorptiometry, bioelectrical impedance measurements, and anthropometry.

PubMed

Abrahamsen, B; Hansen, T B; Høgsberg, I M; Pedersen, F B; Beck-Nielsen, H

1996-01-01

Dual X-ray absorptiometry (DXA) performs noninvasive assessment of bone and soft tissue with high precision. However, soft tissue algorithms assume that 73.2% of the lean body mass is water, a potential source of error in fluid retention. We evaluated DXA (model QDR-2000; Hologic Inc, Waltham, MA), bioelectrical impedance analysis (BIA), and simple anthropometry in 19 patients (9 women and 10 men, mean age 46 y) before and after hemodialysis, removing 0.9-4.3 L (x: 2.8L) of ultrafiltrate. The reduction in fat-free mass (FFM) measured by DXA was highly correlated with the ultrafiltrate, as determined by the reduction in gravimetric weight (r = 0.975, P < 0.0001; SEE: 233 g), whereas BIA was considerably less accurate in assessing FFM reductions (r = 0.66, P < 0.01; SEE: 757 g). Lumbar bone mineral density (BMD) was unaffected by dialysis, as were whole-body fat and BMD. Whole-body bone mineral content, however, was estimated to be 0.6% lower after dialysis. None of the simple anthropometric measurements correlated significantly with the reduction in FFM. In an unmodified clinical setting, DXA appears to be superior to other simple noninvasive methods for determining body composition, particularly when the emphasis is on repeated measurements.

Optimizing Bone Health in Duchenne Muscular Dystrophy.

PubMed

Buckner, Jason L; Bowden, Sasigarn A; Mahan, John D

2015-01-01

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive muscle weakness, with eventual loss of ambulation and premature death. The approved therapy with corticosteroids improves muscle strength, prolongs ambulation, and maintains pulmonary function. However, the osteoporotic impact of chronic corticosteroid use further impairs the underlying reduced bone mass seen in DMD, leading to increased fragility fractures of long bones and vertebrae. These serious sequelae adversely affect quality of life and can impact survival. The current clinical issues relating to bone health and bone health screening methods in DMD are presented in this review. Diagnostic studies, including biochemical markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry (DXA), as well as spinal imaging using densitometric lateral spinal imaging, and treatment to optimize bone health in patients with DMD are discussed. Treatment with bisphosphonates offers a method to increase bone mass in these children; oral and intravenous bisphosphonates have been used successfully although treatment is typically reserved for children with fractures and/or bone pain with low bone mass by DXA.

21 CFR 101.72 - Health claims: calcium, vitamin D, and osteoporosis.

Code of Federal Regulations, 2012 CFR

2012-04-01

... bone mass, which has been identified as one of many risk factors in the development of osteoporosis. Peak bone mass is the total quantity of bone present at maturity, and experts believe that it has the greatest bearing on whether a person will be at risk of developing osteoporosis and related bone fractures...

21 CFR 101.72 - Health claims: calcium, vitamin D, and osteoporosis.

Code of Federal Regulations, 2010 CFR

2010-04-01

... bone mass, which has been identified as one of many risk factors in the development of osteoporosis. Peak bone mass is the total quantity of bone present at maturity, and experts believe that it has the greatest bearing on whether a person will be at risk of developing osteoporosis and related bone fractures...

21 CFR 101.72 - Health claims: calcium, vitamin D, and osteoporosis.

Code of Federal Regulations, 2011 CFR

2011-04-01

... bone mass, which has been identified as one of many risk factors in the development of osteoporosis. Peak bone mass is the total quantity of bone present at maturity, and experts believe that it has the greatest bearing on whether a person will be at risk of developing osteoporosis and related bone fractures...

21 CFR 101.72 - Health claims: calcium, vitamin D, and osteoporosis.

Code of Federal Regulations, 2014 CFR

2014-04-01

... bone mass, which has been identified as one of many risk factors in the development of osteoporosis. Peak bone mass is the total quantity of bone present at maturity, and experts believe that it has the greatest bearing on whether a person will be at risk of developing osteoporosis and related bone fractures...

21 CFR 101.72 - Health claims: calcium, vitamin D, and osteoporosis.

Code of Federal Regulations, 2013 CFR

2013-04-01

... bone mass, which has been identified as one of many risk factors in the development of osteoporosis. Peak bone mass is the total quantity of bone present at maturity, and experts believe that it has the greatest bearing on whether a person will be at risk of developing osteoporosis and related bone fractures...

The Rho-GEF Kalirin regulates bone mass and the function of osteoblasts and osteoclasts

PubMed Central

Huang, Su; Eleniste, Pierre P.; Wayakanon, Kornchanok; Mandela, Prashant; Eipper, Betty A.; Mains, Richard E.; Allen, Matthew R.; Bruzzaniti, Angela

2014-01-01

Bone homeostasis is maintained by the balance between bone resorption by osteoclasts and bone formation by osteoblasts. Dysregulation in the activity of the bone cells can lead to osteoporosis, a disease characterized by low bone mass and an increase in bone fragility and risk of fracture. Kalirin is a novel GTP-exchange factor protein that has been shown to play a role in cytoskeletal remodeling and dendritic spine formation in neurons. We examined Kalirin expression in skeletal tissue and found that it was expressed in osteoclasts and osteoblasts. Furthermore, micro-CT analyses of the distal femur of global Kalirin knockout (Kal-KO) mice revealed significantly reduced trabecular and cortical bone parameters in Kal-KO mice, compared to WT mice, with significantly reduced bone mass in 8, 14 and 36 week-old female Kal-KO mice. Male mice also exhibited a decrease in bone parameters but not to the level seen in female mice. Histomorphometric analyses also revealed decreased bone formation rate in 14 week-old female Kal-KO mice, as well as decreased osteoblast number/bone surface and increased osteoclast surface/bone surface. Consistent with our in vivo findings, the bone resorbing activity and differentiation of Kal-KO osteoclasts was increased in vitro. Although alkaline phosphatase activity by Kal-KO osteoblasts was increased in vitro, Kal-KO osteoblasts showed decreased mineralizing activity, as well as decreased secretion of OPG, which was inversely correlated with ERK activity. Taken together, our findings suggest that deletion of Kalirin directly affects osteoclast and osteoblast activity, leading to decreased OPG secretion by osteoblasts which is likely to alter the RANKL/OPG ratio and promote osteoclastogenesis. Therefore, Kalirin may play a role in paracrine and/or endocrine signaling events that control skeletal bone remodeling and the maintenance of bone mass. PMID:24380811

Osteoporosis: Modern Paradigms for Last Century’s Bones †

PubMed Central

Kruger, Marlena C.; Wolber, Frances M.

2016-01-01

The skeleton is a metabolically active organ undergoing continuously remodelling. With ageing and menopause the balance shifts to increased resorption, leading to a reduction in bone mineral density and disruption of bone microarchitecture. Bone mass accretion and bone metabolism are influenced by systemic hormones as well as genetic and lifestyle factors. The classic paradigm has described osteoporosis as being a “brittle bone” disease that occurs in post-menopausal, thin, Caucasian women with low calcium intakes and/or vitamin D insufficiency. However, a study of black women in Africa demonstrated that higher proportions of body fat did not protect bone health. Isoflavone interventions in Asian postmenopausal women have produced inconsistent bone health benefits, due in part to population heterogeneity in enteric bacterial metabolism of daidzein. A comparison of women and men in several Asian countries identified significant differences between countries in the rate of bone health decline, and a high incidence rate of osteoporosis in both sexes. These studies have revealed significant differences in genetic phenotypes, debunking long-held beliefs and leading to new paradigms in study design. Current studies are now being specifically designed to assess genotype differences between Caucasian, Asian, African, and other phenotypes, and exploring alternative methodology to measure bone architecture. PMID:27322315

Lower Trabecular Volumetric BMD at Metaphyseal Regions of Weight-Bearing Bones is Associated With Prior Fracture in Young Girls

PubMed Central

Farr, Joshua N; Tomás, Rita; Chen, Zhao; Lisse, Jeffrey R; Lohman, Timothy G; Going, Scott B

2011-01-01

Understanding the etiology of skeletal fragility during growth is critical for the development of treatments and prevention strategies aimed at reducing the burden of childhood fractures. Thus we evaluated the relationship between prior fracture and bone parameters in young girls. Data from 465 girls aged 8 to 13 years from the Jump-In: Building Better Bones study were analyzed. Bone parameters were assessed at metaphyseal and diaphyseal sites of the nondominant femur and tibia using peripheral quantitative computed tomography (pQCT). Dual-energy X-ray absorptiometry (DXA) was used to assess femur, tibia, lumbar spine, and total body less head bone mineral content. Binary logistic regression was used to evaluate the relationship between prior fracture and bone parameters, controlling for maturity, body mass, leg length, ethnicity, and physical activity. Associations between prior fracture and all DXA and pQCT bone parameters at diaphyseal sites were nonsignificant. In contrast, lower trabecular volumetric BMD (vBMD) at distal metaphyseal sites of the femur and tibia was significantly associated with prior fracture. After adjustment for covariates, every SD decrease in trabecular vBMD at metaphyseal sites of the distal femur and tibia was associated with 1.4 (1.1–1.9) and 1.3 (1.0–1.7) times higher fracture prevalence, respectively. Prior fracture was not associated with metaphyseal bone size (ie, periosteal circumference). In conclusion, fractures in girls are associated with lower trabecular vBMD, but not bone size, at metaphyseal sites of the femur and tibia. Lower trabecular vBMD at metaphyseal sites of long bones may be an early marker of skeletal fragility in girls. © 2011 American Society for Bone and Mineral Research. PMID:20721933

Lower trabecular volumetric BMD at metaphyseal regions of weight-bearing bones is associated with prior fracture in young girls.

PubMed

Farr, Joshua N; Tomás, Rita; Chen, Zhao; Lisse, Jeffrey R; Lohman, Timothy G; Going, Scott B

2011-02-01

Understanding the etiology of skeletal fragility during growth is critical for the development of treatments and prevention strategies aimed at reducing the burden of childhood fractures. Thus we evaluated the relationship between prior fracture and bone parameters in young girls. Data from 465 girls aged 8 to 13 years from the Jump-In: Building Better Bones study were analyzed. Bone parameters were assessed at metaphyseal and diaphyseal sites of the nondominant femur and tibia using peripheral quantitative computed tomography (pQCT). Dual-energy X-ray absorptiometry (DXA) was used to assess femur, tibia, lumbar spine, and total body less head bone mineral content. Binary logistic regression was used to evaluate the relationship between prior fracture and bone parameters, controlling for maturity, body mass, leg length, ethnicity, and physical activity. Associations between prior fracture and all DXA and pQCT bone parameters at diaphyseal sites were nonsignificant. In contrast, lower trabecular volumetric BMD (vBMD) at distal metaphyseal sites of the femur and tibia was significantly associated with prior fracture. After adjustment for covariates, every SD decrease in trabecular vBMD at metaphyseal sites of the distal femur and tibia was associated with 1.4 (1.1-1.9) and 1.3 (1.0-1.7) times higher fracture prevalence, respectively. Prior fracture was not associated with metaphyseal bone size (ie, periosteal circumference). In conclusion, fractures in girls are associated with lower trabecular vBMD, but not bone size, at metaphyseal sites of the femur and tibia. Lower trabecular vBMD at metaphyseal sites of long bones may be an early marker of skeletal fragility in girls. Copyright © 2011 American Society for Bone and Mineral Research.

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.

Scaling of human body composition to stature: new insights into body mass index.

PubMed

Heymsfield, Steven B; Gallagher, Dympna; Mayer, Laurel; Beetsch, Joel; Pietrobelli, Angelo

2007-07-01

Although Quetelet first reported in 1835 that adult weight scales to the square of stature, limited or no information is available on how anatomical body compartments, including adipose tissue (AT), scale to height. We examined the critical underlying assumptions of adiposity-body mass index (BMI) relations and extended these analyses to major anatomical compartments: skeletal muscle (SM), bone, residual mass, weight (AT+SM+bone), AT-free mass, and organs (liver, brain). This was a cross-sectional analysis of 2 body-composition databases: one including magnetic resonance imaging and dual-energy X-ray absorptiometry (DXA) estimates of evaluated components in adults (total n=411; organs=76) and the other a larger DXA database (n=1346) that included related estimates of fat, fat-free mass, and bone mineral mass. Weight, primary lean components (SM, residual mass, AT-free mass, and fat-free mass), and liver scaled to height with powers of approximately 2 (all P<0.001); bone and bone mineral mass scaled to height with powers >2 (2.31-2.48), and the fraction of weight as bone mineral mass was significantly (P<0.001) correlated with height in women. AT scaled weakly to height with powers of approximately 2, and adiposity was independent of height. Brain mass scaled to height with a power of 0.83 (P=0.04) in men and nonsignificantly in women; the fraction of weight as brain was inversely related to height in women (P=0.002). These observations suggest that short and tall subjects with equivalent BMIs have similar but not identical body composition, provide new insights into earlier BMI-related observations and thus establish a foundation for height-normalized indexes, and create an analytic framework for future studies.

Scaling of human body composition to stature: new insights into body mass index 123

PubMed Central

Heymsfield, Steven B; Gallagher, Dympna; Mayer, Laurel; Beetsch, Joel; Pietrobelli, Angelo

2009-01-01

Background Although Quetelet first reported in 1835 that adult weight scales to the square of stature, limited or no information is available on how anatomical body compartments, including adipose tissue (AT), scale to height. Objective We examined the critical underlying assumptions of adiposity–body mass index (BMI) relations and extended these analyses to major anatomical compartments: skeletal muscle (SM), bone, residual mass, weight (AT+SM+bone), AT-free mass, and organs (liver, brain). Design This was a cross-sectional analysis of 2 body-composition databases: one including magnetic resonance imaging and dual-energy X-ray absorptiometry (DXA) estimates of evaluated components in adults (total n = 411; organs = 76) and the other a larger DXA database (n = 1346) that included related estimates of fat, fat-free mass, and bone mineral mass. Results Weight, primary lean components (SM, residual mass, AT-free mass, and fat-free mass), and liver scaled to height with powers of ≈2 (all P < 0.001); bone and bone mineral mass scaled to height with powers > 2 (2.31–2.48), and the fraction of weight as bone mineral mass was significantly (P < 0.001) correlated with height in women. AT scaled weakly to height with powers of ≈2, and adiposity was independent of height. Brain mass scaled to height with a power of 0.83 (P = 0.04) in men and nonsignificantly in women; the fraction of weight as brain was inversely related to height in women (P = 0.002). Conclusions These observations suggest that short and tall subjects with equivalent BMIs have similar but not identical body composition, provide new insights into earlier BMI-related observations and thus establish a foundation for height-normalized indexes, and create an analytic framework for future studies. PMID:17616766

Assessing mineral metabolism in children using stable isotopes

USDA-ARS?s Scientific Manuscript database

Mineral metabolism may be altered in children with acute or chronic illnesses. The effects may be short term, such as hypomagnesemia associated with chemotherapy, or long-term, such as loss of bone mineral mass after steroid use. Understanding the causes, consequences, and potential therapies for mi...

Effect of Teriparatide, Vibration and the Combination on Bone Mass and Bone Architecture in Chronic Spinal Cord Injury

DTIC Science & Technology

2014-10-01

Cord Injury PRINCIPAL INVESTIGATOR: Thomas J. Schnitzer, M.D., Ph.D. CONTRACTING ORGANIZATION : Northwestern University, Evanston, IL 60208 REPORT...Bone Architechture in Chronic Spinal Cord Injury Effect of Teriparatide, Vibration and the Combination on Bone Mass and Bone Architechture in Chronic...PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Northwestern University, 633 Clark St., Evanston,IL 60208-0001 AND ADDRESS(ES) 8. PERFORMING ORGANIZATION

Whole-body vibration improves fracture healing and bone quality in rats with ovariectomy-induced osteoporosis.

PubMed

Butezloff, Mariana Maloste; Zamarioli, Ariane; Leoni, Graziela Bianchi; Sousa-Neto, Manoel Damião; Volpon, Jose Batista

2015-11-01

To investigate the effect of vibration therapy on the bone callus of fractured femurs and the bone quality of intact femurs in ovariectomized rats. Fifty-six rats aged seven weeks were divided into four groups: control with femoral fracture (CON, n=14), ovariectomized with femoral fracture (OVX, n=14), control with femoral fracture plus vibration therapy (CON+VT, n=14), and ovariectomized with femoral fracture plus vibration therapy (OVX+VT, n=14). Three months after ovariectomy or sham surgery, a complete fracture was produced at the femoral mid-diaphysis and stabilized with a 1-mm-diameter intramedullary Kirschner wire. X-rays confirmed the fracture alignment and fixation. Three days later, the VT groups underwent vibration therapy (1 mm, 60 Hz for 20 minutes, three times per week for 14 or 28 days). The bone and callus quality were assessed by densitometry, three-dimensional microstructure, and mechanical test. Ovariectomized rats exhibited a substantial loss of bone mass and severe impairment in bone microarchitecture, both in the non-fractured femur and the bone callus. Whole-body vibration therapy exerted an important role in ameliorating the bone and fracture callus parameters in the osteoporotic bone. Vibration therapy improved bone quality and the quality of the fracture bone callus in ovariectomized rats.

In vivo cyclic compression causes cartilage degeneration and subchondral bone changes in mouse tibiae.

PubMed

Ko, Frank C; Dragomir, Cecilia; Plumb, Darren A; Goldring, Steven R; Wright, Timothy M; Goldring, Mary B; van der Meulen, Marjolein C H

2013-06-01

Alterations in the mechanical loading environment in joints may have both beneficial and detrimental effects on articular cartilage and subchondral bone, and may subsequently influence the development of osteoarthritis (OA). Using an in vivo tibial loading model, the aim of this study was to investigate the adaptive responses of cartilage and bone to mechanical loading and to assess the influence of load level and duration. Cyclic compression at peak loads of 4.5N and 9.0N was applied to the left tibial knee joint of adult (26-week-old) C57BL/6 male mice for 1, 2, and 6 weeks. Only 9.0N loading was utilized in young (10-week-old) mice. Changes in articular cartilage and subchondral bone were analyzed by histology and micro-computed tomography. Mechanical loading promoted cartilage damage in both age groups of mice, and the severity of joint damage increased with longer duration of loading. Metaphyseal bone mass increased with loading in young mice, but not in adult mice, whereas epiphyseal cancellous bone mass decreased with loading in both young and adult mice. In both age groups, articular cartilage thickness decreased, and subchondral cortical bone thickness increased in the posterior tibial plateau. Mice in both age groups developed periarticular osteophytes at the tibial plateau in response to the 9.0N load, but no osteophyte formation occurred in adult mice subjected to 4.5N peak loading. This noninvasive loading model permits dissection of temporal and topographic changes in cartilage and bone and will enable investigation of the efficacy of treatment interventions targeting joint biomechanics or biologic events that promote OA onset and progression. Copyright © 2013 by the American College of Rheumatology.

In vivo cyclic compression causes cartilage degeneration and subchondral bone changes in mouse tibiae

PubMed Central

Ko, Frank C.; Dragomir, Cecilia; Plumb, Darren A.; Goldring, Steven R.; Wright, Timothy M.; Goldring, Mary B.; van der Meulen, Marjolein C.H.

2013-01-01

Objectives Alterations in the mechanical loading environment in joints may have both beneficial and detrimental effects on articular cartilage and subchondral bone and subsequently influence the development of osteoarthritis (OA). We used an in vivo tibial loading model to investigate the adaptive responses of cartilage and bone to mechanical loading and to assess the influence of load level and duration. Methods We applied cyclic compression of 4.5 and 9.0N peak loads to the left tibia via the knee joint of adult (26-week-old) C57Bl/6 male mice for 1, 2, and 6 weeks. Only 9.0N loading was utilized in young (10-week-old) mice. The changes in articular cartilage and subchondral bone were analyzed by histology and microcomputed tomography. Results Loading promoted cartilage damage in both age groups, with increased damage severity dependent upon the duration of loading. Metaphyseal bone mass increased in the young mice, but not in the adult mice, whereas epiphyseal cancellous bone mass decreased with loading in both young and adult mice. Articular cartilage thickness decreased, and subchondral cortical bone thickness increased in the posterior tibial plateau in both age groups. Both age groups developed periarticular osteophytes at the tibial plateau in response to the 9.0N load, but no osteophyte formation occurred in adult mice subjected to 4.5N peak loading. Conclusion This non-invasive loading model permits dissection of temporal and topographical changes in cartilage and bone and will enable investigation of the efficacy of treatment interventions targeting joint biomechanics or biological events that promote OA onset and progression. PMID:23436303

Use of ossein-hydroxyapatite complex in the prevention of bone loss: a review.

PubMed

Castelo-Branco, C; Dávila Guardia, J

2015-02-01

The ossein-hydroxyapatite complex (OHC) is a microcrystalline form of calcium which provides a number of additional minerals (magnesium, phosphorus, potassium, zinc), and proteins (osteocalcin, type I collagen, type I insulin growth factor I and II, transforming growth factor beta) associated with bone metabolism. The objective of this review is to examine the role of OHC in preventing bone loss in different conditions. A review of clinical trials assessing the relationship between OHC and bone loss was made using the following data sources: Medline (from 1966 to December 2013), the Cochrane Controlled Clinical Trials Register, Embase (up to December 2013), contact with companies marketing the supplements studied, and reference lists. Different randomized, clinical trials and meta-analysis suggest that OHC is more effective than calcium supplements in maintaining bone mass in postmenopausal women and in different conditions related to bone loss. In addition, OHC improves pain symptoms and accelerates fracture consolidation in patients with osteopenia or osteoporosis. The ossein-hydroxyapatite complex is significantly more effective in preventing bone loss than calcium carbonate.

Two single nucleotide polymorphisms in the CYP17 and COMT Genes--relation to bone mass and longitudinal bone changes in postmenopausal women with or without hormone replacement therapy. The Danish Osteoporosis Prevention Study.

PubMed

Tofteng, C L; Abrahamsen, B; Jensen, J E B; Petersen, S; Teilmann, J; Kindmark, A; Vestergaard, P; Gram, J; Langdahl, B L; Mosekilde, L

2004-08-01

Sex steroids are important physiologic regulators of bone mass, and genes regulating sex steroid production and metabolism are obvious as candidate genes for osteoporosis susceptibility. We present data from a study of 1795 recent postmenopausal women, assigned to either hormone replacement therapy (HRT) or no treatment and followed for 5 years. The association between bone mass measurements and two single nucleotide polymorphisms, a T (A1) to C (A2) transition in the 5'-UTR of the cytochrome P450c17alpha (CYP17) gene and a G (Val) to A (Met) transition in exon 4 of the catechol- O-methyltransferase (COMT) gene, was evaluated. Association with CYP17 genotype was modified by body mass index (BMI). In lean women, individuals homozygous for the CYP17 A2 allele were 1 cm shorter and had lower baseline BMD (bone mineral density), BMC, and CSA (cross sectional area) in the spine and femoral neck than did other women (BMD spine A2A2: 0.975 g/cm2 versus 1.011 g/cm2 in A1A1 + A1A2, P = 0.002). Conversely, an adverse association with A2A2 and bone loss over 5 years seemed present only in overweight women, but differences were small. Response to HRT was not dependent on CYP17 genotype. COMT genotype was not associated with bone mass at baseline, bone loss in untreated women, or response to HRT. In conclusion, the A2 allele of the CYP17 T(27)-C polymorphism is associated with reduced bone mass and bone size in lean perimenopausal women, whereas high BMI protects against this negative association. The COMT G(1947)-A polymorphism is not associated with bone parameters in this study.

Primary sacral hydatid cyst. A case report.

PubMed

Joshi, Nayana; Hernandez-Martinez, Alejandro; Seijas-Vazquez, Roberto

2007-10-01

This case report highlights an unusual osseous spinal presentation of a well described disease, hydatidosis. A 59-year-old woman presented with increasing back pain and bilateral radiculopathy. Examination disclosed symptoms of spinal stenosis and urinary incontinence. Radiographs showed an expansive lytic lesion affecting the pelvic bones with destruction of the bone cortex. Laboratory analyses were performed and the patient underwent CT and MRI studies. Serology for Echinococcus was positive. When assessing sciatica, low back pain or lower limb weakness the pelvic cavity should be examined for hidden disease that might explain the neurological symptoms. Hydatid disease of bone should be considered in the differential diagnosis of any bone mass discovered in the human body. Diagnosis was delayed in this case because the pelvic cavity was not studied when radiculopathy symptoms started and there was no coexisting visceral involvement.

Polymethoxy flavonoids, nobiletin and tangeretin, prevent lipopolysaccharide-induced inflammatory bone loss in an experimental model for periodontitis.

PubMed

Tominari, Tsukasa; Hirata, Michiko; Matsumoto, Chiho; Inada, Masaki; Miyaura, Chisato

2012-01-01

Nobiletin, a polymethoxy flavonoid (PMF), inhibits systemic bone resorption and maintains bone mass in estrogen-deficient ovariectomized mice. This study examined the anti-inflammatory effects of PMFs, nobiletin, and tangeretin on lipopolysaccharide (LPS)-induced bone resorption. Nobiletin and tangeretin suppressed LPS-induced osteoclast formation and bone resorption and suppressed the receptor activator of NFκB ligand-induced osteoclastogenesis in RAW264.7 macrophages. Nobiletin clearly restored the alveolar bone mass in a mouse experimental model for periodontitis by inhibiting LPS-induced bone resorption. PMFs may therefore provide a new therapeutic approach for periodontal bone loss.

Intercomparison of techniques for the non-invasive measurement of bone mass

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

Cohn, S.H.

1981-01-01

A variety of methods are presently available for the non-invasive measurement of bone mass of both normal individuals and patients with metabolic disorders. Chief among these methods are radiographic techniques such as radiogrammetry, photon absorptiometry, computer tomography, Compton scattering and neutron activation analysis. In this review, the salient features of the bone measurement techniques are discussed along with their accuracy and precision. The advantages and disadvantages of the various techniques for measuring bone mass are summarized. Where possible, intercomparisons are made of the various techniques.

Intrinsic material properties of cortical bone.

PubMed

Lopez Franco, Gloria E; Blank, Robert D; Akhter, Mohammed P

2011-01-01

The G171V mutation (high bone mass, HBM) is autosomal dominant and is responsible for high bone mass in humans. Transgenic HBM mice in which the human LRP5 G171V gene is inserted also show a similar phenotype with greater bone mass and biomechanical performance than wild-type mice, as determined by whole bone testing. Whole bone mechanics, however, depend jointly on bone mass, architecture, and intrinsic bone tissue mechanical properties. To determine whether the HBM mutation affects tissue-level biomechanical performance, we performed nano-indentation testing of unembedded cortical bone from HBM mice and their nontransgenic (NTG) littermates. Femora from 17-week-old mice (female, 8 mice/genotype) were subjected to nano-indentation using a Triboscope (Hysitron, Minneapolis, MN, USA). For each femoral specimen, approximately 10 indentations were made on the midshaft anterior surface with a target force of either 3 or 9 mN at a constant loading rate of 400 mN/s. The load-displacement data from each test were used to calculate indentation modulus and hardness for bone tissue. The intrinsic material property that reflected the bone modulus was greater (48%) in the HBM as compared to the NTG mice. Our results of intrinsic properties are consistent with the published structural and material properties of the midshaft femur in HBM and NTG mice. The greater intrinsic modulus in HBM reflects greater bone mineral content as compared to NTG (wild-type, WT) mice. This study suggests that the greater intrinsic property of cortical bone is derived from the greater bone mineral content and BMD, resulting in greater bone strength in HBM as compared to NTG (WT) mice.

DLX3 regulates bone mass by targeting genes supporting osteoblast differentiation and mineral homeostasis in vivo

PubMed Central

Isaac, J; Erthal, J; Gordon, J; Duverger, O; Sun, H-W; Lichtler, A C; Stein, G S; Lian, J B; Morasso, M I

2014-01-01

Human mutations and in vitro studies indicate that DLX3 has a crucial function in bone development, however, the in vivo role of DLX3 in endochondral ossification has not been established. Here, we identify DLX3 as a central attenuator of adult bone mass in the appendicular skeleton. Dynamic bone formation, histologic and micro-computed tomography analyses demonstrate that in vivo DLX3 conditional loss of function in mesenchymal cells (Prx1-Cre) and osteoblasts (OCN-Cre) results in increased bone mass accrual observed as early as 2 weeks that remains elevated throughout the lifespan owing to increased osteoblast activity and increased expression of bone matrix genes. Dlx3OCN-conditional knockout mice have more trabeculae that extend deeper in the medullary cavity and thicker cortical bone with an increased mineral apposition rate, decreased bone mineral density and increased cortical porosity. Trabecular TRAP staining and site-specific Q-PCR demonstrated that osteoclastic resorption remained normal on trabecular bone, whereas cortical bone exhibited altered osteoclast patterning on the periosteal surface associated with high Opg/Rankl ratios. Using RNA sequencing and chromatin immunoprecipitation-Seq analyses, we demonstrate that DLX3 regulates transcription factors crucial for bone formation such as Dlx5, Dlx6, Runx2 and Sp7 as well as genes important to mineral deposition (Ibsp, Enpp1, Mepe) and bone turnover (Opg). Furthermore, with the removal of DLX3, we observe increased occupancy of DLX5, as well as increased and earlier occupancy of RUNX2 on the bone-specific osteocalcin promoter. Together, these findings provide novel insight into mechanisms by which DLX3 attenuates bone mass accrual to support bone homeostasis by osteogenic gene pathway regulation. PMID:24948010

Preservation of volumetric bone density and geometry in trans women during cross-sex hormonal therapy: a prospective observational study.

PubMed

Van Caenegem, E; Wierckx, K; Taes, Y; Schreiner, T; Vandewalle, S; Toye, K; Kaufman, J-M; T'Sjoen, G

2015-01-01

Although trans women before the start of hormonal therapy have a less bone and muscle mass compared with control men, their bone mass and geometry are preserved during the first 2 years of hormonal therapy, despite of substantial muscle loss, illustrating the major role of estrogen in the male skeleton. The aim of this study is to examine the evolution of areal and volumetric bone density, geometry, and turnover in trans women undergoing sex steroid changes, during the first 2 years of hormonal therapy. In a prospective observational study, we examined 49 trans women (male-to-female) before and after 1 and 2 years of cross-sex hormonal therapy (CSH) in comparison with 49 age-matched control men measuring grip strength (hand dynamometer), areal bone mineral density (aBMD), and total body fat and lean mass using dual X-ray absorptiometry (DXA), bone geometry and volumetric bone mineral density, regional fat, and muscle area at the forearm and calf using peripheral quantitative computed tomography. Standardized treatment regimens were used with oral estradiol valerate, 4 mg daily (or transdermal 17-β estradiol 100 μg/24 h for patients >45 years old), both combined with oral cyproterone acetate 50 mg daily. Prior to CSH, trans women had lower aBMD at all measured sites (all p < 0.001), smaller cortical bone size (all p < 0.05), and lower muscle mass and strength and lean body mass (all p < 0.05) compared with control men. During CSH, muscle mass and strength decreased and all measures of fat mass increased (all p < 0.001). The aBMD increased at the femoral neck, radius, lumbar spine, and total body; cortical and trabecular bone remained stable and bone turnover markers decreased (all p < 0.05). Although trans women, before CSH, have a lower aBMD and cortical bone size compared with control men, their skeletal status is well preserved during CSH treatment, despite of substantial muscle loss.

Biological Regulation of Bone Quality

PubMed Central

Alliston, Tamara

2014-01-01

The ability of bone to resist fracture is determined by the combination of bone mass and bone quality. Like bone mass, bone quality is carefully regulated. Of the many aspects of bone quality, this review focuses on biological mechanisms that control the material quality of the bone extracellular matrix (ECM). Bone ECM quality depends upon ECM composition and organization. Proteins and signaling pathways that affect the mineral or organic constituents of bone ECM impact bone ECM material properties, such as elastic modulus and hardness. These properties are also sensitive to pathways that regulate bone remodeling by osteoblasts, osteoclasts, and osteocytes. Several extracellular proteins, signaling pathways, intracellular effectors, and transcription regulatory networks have been implicated in the control of bone ECM quality. A molecular understanding of these mechanisms will elucidate the biological control of bone quality and suggest new targets for the development of therapies to prevent bone fragility. PMID:24894149

Targeting the LRP5 pathway improves bone properties in a mouse model of Osteogenesis Imperfecta

PubMed Central

Jacobsen, Christina M.; Barber, Lauren A.; Ayturk, Ugur M.; Roberts, Heather J.; Deal, Lauren E.; Schwartz, Marissa A.; Weis, MaryAnn; Eyre, David; Zurakowski, David; Robling, Alexander G.; Warman, Matthew L.

2014-01-01

The cell surface receptor low-density lipoprotein receptor-related protein 5 (LRP5) is a key regulator of bone mass and bone strength. Heterozygous missense mutations in LRP5 cause autosomal dominant high bone mass (HBM) in humans by reducing binding to LRP5 by endogenous inhibitors, such as sclerostin (SOST). Mice heterozygous for a knockin allele (Lrp5p.A214V) that is orthologous to a human HBM-causing mutation have increased bone mass and strength. Osteogenesis Imperfecta (OI) is a skeletal fragility disorder predominantly caused by mutations that affect type I collagen. We tested whether the LRP5 pathway can be used to improve bone properties in animal models of OI. First, we mated Lrp5+/p.A214V mice to Col1a2+/p.G610C mice, which model human type IV OI. We found that Col1a2+/p.G610C;Lrp5+/p.A214V offspring had significantly increased bone mass and strength compared to Col1a2+/p.G610C;Lrp5+/+ littermates. The improved bone properties were not due to altered mRNA expression of type I collagen or its chaperones, nor were they due to changes in mutant type I collagen secretion. Second, we treated Col1a2+/p.G610C mice with a monoclonal antibody that inhibits sclerostin activity (Scl-Ab). We found that antibody treated mice had significantly increased bone mass and strength compared to vehicle treated littermates. These findings indicate increasing bone formation, even without altering bone collagen composition, may benefit patients with OI. PMID:24677211

[Role of physical activity in the prevention of osteoporosis].

PubMed

Siegrist, Monika

2008-07-01

In recent years, osteoporosis has become a leading cause of morbidity and mortality in elderly women. Research has demonstrated that the prevention of osteoporosis and osteoporosis-related fractures may best be achieved by initiating sound health behaviors early in life and continuing them throughout life. Evidence suggests that osteoporosis is easier to prevent than to treat. In fact, healthy early life practices, including the adequate consumption of most nutrients, calcium in particular, and regular physical activity, contribute to greater bone mineral mass and optimal peak bone mass. Bone is living tissue that responds to exercise by becoming stronger. Two types of exercises are important for building and maintaining bone mass and density: Weight-bearing exercises, in which bones and muscles work against gravity and resistance training that use muscular strength to improve muscle mass and strengthen bone. Exercise can also improve gait, balance, coordination, proprioception, reaction time, and muscle strength, even in very old and frail elderly people. Overall, the evidence strongly suggests that regular physical activity, especially started in childhood and adolescence, is a cheap and safe way of both improving bone strength and reducing the risk to fall.

Bone mineral density before and after OLT: long-term follow-up and predictive factors.

PubMed

Guichelaar, Maureen M J; Kendall, Rebecca; Malinchoc, Michael; Hay, J Eileen

2006-09-01

Fracturing after liver transplantation (OLT) occurs due to the combination of preexisting low bone mineral density (BMD) and early posttransplant bone loss, the risk factors for which are poorly defined. The prevalence and predictive factors for hepatic osteopenia and osteoporosis, posttransplant bone loss, and subsequent bone gain were studied by the long-term posttransplant follow-up of 360 consecutive adult patients with end-stage primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Only 20% of patients with advanced PBC or PSC have normal bone mass. Risk factors for low spinal BMD are low body mass index, older age, postmenopausal status, muscle wasting, high alkaline phosphatase and low serum albumin. A high rate of spinal bone loss occurred in the first 4 posttransplant months (annual rate of 16%) especially in those with younger age, PSC, higher pretransplant bone density, no inflammatory bowel disease, shorter duration of liver disease, current smoking, and ongoing cholestasis at 4 months. Factors favoring spinal bone gain from 4 to 24 months after transplantation were lower baseline and/or 4-month bone density, premenopausal status, lower cumulative glucocorticoids, no ongoing cholestasis, and higher levels of vitamin D and parathyroid hormone. Bone mass therefore improves most in patients with lowest pretransplant BMD who undergo successful transplantation with normal hepatic function and improved gonadal and nutritional status. Patients transplanted most recently have improved bone mass before OLT, and although bone loss still occurs early after OLT, these patients also have a greater recovery in BMD over the years following OLT.

Unloading-induced bone loss was suppressed in gold-thioglucose treated mice.

PubMed

Hino, K; Nifuji, A; Morinobu, M; Tsuji, K; Ezura, Y; Nakashima, K; Yamamoto, H; Noda, M

2006-10-15

Loss of mechanical stress causes bone loss. However, the mechanisms underlying the unloading-induced bone loss are largely unknown. Here, we examined the effects of gold-thioglucose (GTG) treatment, which destroys ventromedial hypothalamus (VMH), on unloading-induced bone loss. Unloading reduced bone volume in control (saline-treated) mice. Treatment with GTG-reduced bone mass and in these GTG-treated mice, unloading-induced reduction in bone mass levels was not observed. Unloading reduced the levels of bone formation rate (BFR) and mineral apposition rate (MAR). GTG treatment also reduced these parameters and under this condition, unloading did not further reduce the levels of BFR and MAR. Unloading increased the levels of osteoclast number (Oc.N/BS) and osteoclast surface (Oc.S/BS). GTG treatment did not alter the basal levels of these bone resorption parameters. In contrast to control, GTG treatment suppressed unloading-induced increase in the levels of Oc.N/BS and Oc.S/BS. Unloading reduced the levels of mRNA expression of the genes encoding osteocalcin, type I collagen and Cbfa1 in bone. In contrast, GTG treatment suppressed such unloading-induced reduction of mRNA expression. Unloading also enhanced the levels of fat mass in bone marrow and mRNA expression of the genes encoding PPARgamma2, C/EBPalpha, and C/EBPbeta in bone. In GTG-treated mice, unloading did not increase fat mass and the levels of fat-related mRNA expression. These results indicated that GTG treatment suppressed unloading-induced alteration in bone loss. 2006 Wiley-Liss, Inc.

Physiological Notch Signaling Maintains Bone Homeostasis via RBPjk and Hey Upstream of NFATc1

PubMed Central

Tu, Xiaolin; Chen, Jianquan; Lim, Joohyun; Karner, Courtney M.; Lee, Seung-Yon; Heisig, Julia; Wiese, Cornelia; Surendran, Kameswaran; Kopan, Raphael; Gessler, Manfred; Long, Fanxin

2012-01-01

Notch signaling between neighboring cells controls many cell fate decisions in metazoans both during embryogenesis and in postnatal life. Previously, we uncovered a critical role for physiological Notch signaling in suppressing osteoblast differentiation in vivo. However, the contribution of individual Notch receptors and the downstream signaling mechanism have not been elucidated. Here we report that removal of Notch2, but not Notch1, from the embryonic limb mesenchyme markedly increased trabecular bone mass in adolescent mice. Deletion of the transcription factor RBPjk, a mediator of all canonical Notch signaling, in the mesenchymal progenitors but not the more mature osteoblast-lineage cells, caused a dramatic high-bone-mass phenotype characterized by increased osteoblast numbers, diminished bone marrow mesenchymal progenitor pool, and rapid age-dependent bone loss. Moreover, mice deficient in Hey1 and HeyL, two target genes of Notch-RBPjk signaling, exhibited high bone mass. Interestingly, Hey1 bound to and suppressed the NFATc1 promoter, and RBPjk deletion increased NFATc1 expression in bone. Finally, pharmacological inhibition of NFAT alleviated the high-bone-mass phenotype caused by RBPjk deletion. Thus, Notch-RBPjk signaling functions in part through Hey1-mediated inhibition of NFATc1 to suppress osteoblastogenesis, contributing to bone homeostasis in vivo. PMID:22457635

Epidemiology, etiology, and diagnosis of osteoporosis.

PubMed

Lane, Nancy E

2006-02-01

Osteoporosis, a major public health problem, is becoming increasingly prevalent with the aging of the world population. Osteoporosis is a skeletal disorder characterized by compromised bone strength, which predisposes the individual to an increased risk of fractures of the hip, spine, and other skeletal sites. The clinical consequences and economic burden of this disease call for measures to assess individuals who are at high risk to allow for appropriate intervention. Many risk factors are associated with osteoporotic fracture, including low peak bone mass, hormonal factors, the use of certain drugs (eg, glucocorticoids), cigarette smoking, low physical activity, low intake of calcium and vitamin D, race, small body size, and a personal or a family history of fracture. All of these factors should be taken into account when assessing the risk of fracture and determining whether further treatment is required. Because osteoporotic fracture risk is higher in older women than in older men, all postmenopausal women should be evaluated for signs of osteoporosis during routine physical examinations. Radiologic laboratory assessments of bone mineral density generally should be reserved for patients at highest risk, including all women over the age of 65, younger postmenopausal women with risk factors, and all postmenopausal women with a history of fractures. The evaluation of biochemical markers of bone turnover has been useful in clinical research. However, the predictive factor of these measurements is not defined clearly, and these findings should not be used as a replacement for bone density testing. Together, clinical assessment of osteoporotic risk factors and objective measures of bone mineral density can help to identify patients who will benefit from intervention and, thus, can potentially reduce the morbidity and mortality associated with osteoporosis-associated fractures in this population.

Trabecular bone in the calcaneus of runners

PubMed Central

Holt, Brigitte; Troy, Karen; Hamill, Joseph

2017-01-01

Trabecular bone of the human calcaneus is subjected to extreme repetitive forces during endurance running and should adapt in response to this strain. To assess possible bone functional adaptation in the posterior region of the calcaneus, we recruited forefoot-striking runners (n = 6), rearfoot-striking runners (n = 6), and non-runners (n = 6), all males aged 20–41 for this institutionally approved study. Foot strike pattern was confirmed for each runner using a motion capture system. We obtained high resolution peripheral computed tomography scans of the posterior calcaneus for both runners and non-runners. No statistically significant differences were found between runners and nonrunners or forefoot strikers and rearfoot strikers. Mean trabecular thickness and mineral density were greatest in forefoot runners with strong effect sizes (<0.80). Trabecular thickness was positively correlated with weekly running distance (r2 = 0.417, p<0.05) and years running (r2 = 0.339, p<0.05) and negatively correlated with age at onset of running (r2 = 0.515, p<0.01) Trabecular thickness, mineral density and bone volume ratio of nonrunners were highly correlated with body mass (r2 = 0.824, p<0.05) and nonrunners were significantly heavier than runners (p<0.05). Adjusting for body mass revealed significantly thicker trabeculae in the posterior calcaneus of forefoot strikers, likely an artifact of greater running volume and earlier onset of running in this subgroup; thus, individuals with the greatest summative loading stimulus had, after body mass adjustment, the thickest trabeculae. Further study with larger sample sizes is necessary to elucidate the role of footstrike on calcaneal trabecular structure. To our knowledge, intraspecific body mass correlations with measures of trabecular robusticity have not been reported elsewhere. We hypothesize that early adoption of running and years of sustained moderate volume running stimulate bone modeling in trabeculae of the posterior calcaneus. PMID:29141022

Trabecular bone in the calcaneus of runners.

PubMed

Best, Andrew; Holt, Brigitte; Troy, Karen; Hamill, Joseph

2017-01-01

Trabecular bone of the human calcaneus is subjected to extreme repetitive forces during endurance running and should adapt in response to this strain. To assess possible bone functional adaptation in the posterior region of the calcaneus, we recruited forefoot-striking runners (n = 6), rearfoot-striking runners (n = 6), and non-runners (n = 6), all males aged 20-41 for this institutionally approved study. Foot strike pattern was confirmed for each runner using a motion capture system. We obtained high resolution peripheral computed tomography scans of the posterior calcaneus for both runners and non-runners. No statistically significant differences were found between runners and nonrunners or forefoot strikers and rearfoot strikers. Mean trabecular thickness and mineral density were greatest in forefoot runners with strong effect sizes (<0.80). Trabecular thickness was positively correlated with weekly running distance (r2 = 0.417, p<0.05) and years running (r2 = 0.339, p<0.05) and negatively correlated with age at onset of running (r2 = 0.515, p<0.01) Trabecular thickness, mineral density and bone volume ratio of nonrunners were highly correlated with body mass (r2 = 0.824, p<0.05) and nonrunners were significantly heavier than runners (p<0.05). Adjusting for body mass revealed significantly thicker trabeculae in the posterior calcaneus of forefoot strikers, likely an artifact of greater running volume and earlier onset of running in this subgroup; thus, individuals with the greatest summative loading stimulus had, after body mass adjustment, the thickest trabeculae. Further study with larger sample sizes is necessary to elucidate the role of footstrike on calcaneal trabecular structure. To our knowledge, intraspecific body mass correlations with measures of trabecular robusticity have not been reported elsewhere. We hypothesize that early adoption of running and years of sustained moderate volume running stimulate bone modeling in trabeculae of the posterior calcaneus.

Androgens in Women with Anorexia Nervosa and Normal-Weight Women with Hypothalamic Amenorrhea

PubMed Central

Miller, K. K.; Lawson, E. A.; Mathur, V.; Wexler, T. L.; Meenaghan, E.; Misra, M.; Herzog, D. B.; Klibanski, A.

2011-01-01

Context Anorexia nervosa and normal-weight hypothalamic amenorrhea are characterized by hypogonadism and hypercortisolemia. However, it is not known whether these endocrine abnormalities result in reductions in adrenal and/or ovarian androgens or androgen precursors in such women, nor is it known whether relative androgen deficiency contributes to abnormalities in bone density and body composition in this population. Objective Our objective was to determine whether endogenous androgen and dehydroepiandrosterone sulfate (DHEAS) levels: 1) are reduced in women with anorexia nervosa and normal-weight hypothalamic amenorrhea, 2) are reduced further by oral contraceptives in women with anorexia nervosa, and 3) are predictors of weight, body composition, or bone density in such women. Design and Setting We conducted a cross-sectional study at a general clinical research center. Study Participants A total of 217 women were studied: 137 women with anorexia nervosa not receiving oral contraceptives, 32 women with anorexia nervosa receiving oral contraceptives, 21 normal-weight women with hypothalamic amenorrhea, and 27 healthy eumenorrheic controls. Main Outcome Measures Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed. Results Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. More marked reductions in both free testosterone and DHEAS were observed in women with anorexia nervosa receiving oral contraceptives. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Lower free testosterone, total testosterone, and DHEAS levels predicted lower bone density at most skeletal sites measured, and free testosterone was positively associated with fat-free mass. Conclusions Androgen levels are low, appear to be even further reduced by oral contraceptive use, and are predictors of bone density and fat-free mass in women with anorexia nervosa. Interventional studies are needed to confirm these findings and determine whether oral contraceptive use, mediated by reductions in endogenous androgen levels, is deleterious to skeletal health in such women. PMID:17284620

Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea.

PubMed

Miller, K K; Lawson, E A; Mathur, V; Wexler, T L; Meenaghan, E; Misra, M; Herzog, D B; Klibanski, A

2007-04-01

Anorexia nervosa and normal-weight hypothalamic amenorrhea are characterized by hypogonadism and hypercortisolemia. However, it is not known whether these endocrine abnormalities result in reductions in adrenal and/ or ovarian androgens or androgen precursors in such women, nor is it known whether relative androgen deficiency contributes to abnormalities in bone density and body composition in this population. Our objective was to determine whether endogenous androgen and dehydroepiandrosterone sulfate (DHEAS) levels: 1) are reduced in women with anorexia nervosa and normal-weight hypothalamic amenorrhea, 2) are reduced further by oral contraceptives in women with anorexia nervosa, and 3) are predictors of weight, body composition, or bone density in such women. We conducted a cross-sectional study at a general clinical research center. A total of 217 women were studied: 137 women with anorexia nervosa not receiving oral contraceptives, 32 women with anorexia nervosa receiving oral contraceptives, 21 normal-weight women with hypothalamic amenorrhea, and 27 healthy eumenorrheic controls. Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed. Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. More marked reductions in both free testosterone and DHEAS were observed in women with anorexia nervosa receiving oral contraceptives. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Lower free testosterone, total testosterone, and DHEAS levels predicted lower bone density at most skeletal sites measured, and free testosterone was positively associated with fat-free mass. Androgen levels are low, appear to be even further reduced by oral contraceptive use, and are predictors of bone density and fat-free mass in women with anorexia nervosa. Interventional studies are needed to confirm these findings and determine whether oral contraceptive use, mediated by reductions in endogenous androgen levels, is deleterious to skeletal health in such women.

Differences in Femoral Geometry and Structure Due to Immobilization

NASA Technical Reports Server (NTRS)

Kiratli, Beatrice Jenny; Yamada, M.; Smith, A.; Marcus, R. M.; Arnaud, S.; vanderMeulen, M. C. H.; Hargens, Alan R. (Technical Monitor)

1996-01-01

Reduction in bone mass of the lower extremity is well documented in individuals with paralysis resulting from spinal cord injury (SCI). The consequent osteopenia leads to elevated fracture risk with fractures occurring more commonly in the femoral shaft and supracondylar regions than the hip. A model has recently been described to estimate geometry and structure of the femoral midshaft from whole body scans by dual X-ray absorptiometry (DXA). Increases in femoral geometric and structural properties during growth were primarily related to mechanical loading as reflected by body mass. In this study, we investigate the relationship between body mass and femoral geometry and structure in adults with normal habitual mechanical loading patterns and those with severely reduced loading. The subjects were 78 ambulatory men (aged 20-72 yrs) and 113 men with complete paralysis from SCI of more than 4 years duration (aged 21 73 yrs). Subregional analysis was performed on DXA whole body scans to obtain bone mineral content (BMC, g), cortical thickness (cm), crosssectional moment of inertia (CSMI, cm4), and section modulus (cm3) of the femoral midshaft. All measured bone variables were significantly lower in SCI compared with ambulatory subjects: -29% (BMC), -33% (cortical thickness), -23% (CSMI), and -22% (section modulus) while body mass was not significantly different. However, the associations between body mass and bone properties were notably different; r2 values were higher for ambulatory than SCI subjects in regressions of body mass on BMC (0.48 vs 0.20), CSMI (0.59 vs 0.32), and section modulus (0.59 vs 0.31). No association was seen between body mass and cortical thickness for either group. The greatest difference between groups is in the femoral cortex, consistent with reduced bone mass via endosteal expansion. The relatively lesser difference in geometric and structural properties implies that there is less effect on mechanical integrity than would be expected from bone mass results alone. The reduced association in SCI subjects between body mass and bone properties is not unexpected. Although mean body mass differs little between ambulatory and SCI individuals, the association between body mass and in vivo skeletal loading is no longer present, as mechanical influences are removed except for transfer activities. The residual association is probably attributable to the strength of this influence during growth. These results highlight the importance of examining geometry and structure in conjunction with bone mass.

Central and peripheral fat body mass have a protective effect on osteopenia or osteoporosis in adults and elderly?

PubMed

Freitas, P M S S; Garcia Rosa, M L; Gomes, A M; Wahrlich, V; Di Luca, D G; da Cruz Filho, R A; da Silva Correia, D M; Faria, C A; Yokoo, E M

2016-04-01

This cross-sectional study involves randomly selected men aged 50 to 99 years and postmenopausal women. Either central fat mass or peripheral fat mass were associated to osteoporosis or osteopenia independently from fat-free body mass and other confounding factors. Obesity and osteoporosis are public health problems that probably share common pathophysiological mechanisms. The question if body fat mass, central or peripheral, is protective or harmful for osteoporosis or osteopenia is not completely resolved. This study aims to investigate the association between osteoporosis or osteopenia, and fat body mass (central and peripheral) independently from fat-free body mass, in men aged 50 to 99 years old and postmenopausal women randomly selected in the community. This is a cross-sectional investigation with a random sample of registered population in Niterói Family Doctor Program (FDP), State of Rio de Janeiro, Brazil. Bone mineral density (BMD) and fat-free mass were assessed by dual X-ray absorptiometry (DXA). There was statistically significant bivariate association between bone loss with gender, age, skin color, alcohol consumption at risk dose, use of thiazide, fat-free body mass, and fat body mass (central and peripheral). In the multiple analysis of fat-free body mass, central and peripheral fat body mass showed an independent and protective effect on the presence of osteoporosis or osteopenia (p value <0.001). Since both obesity and osteoporosis are public health problems worldwide, strategies aimed at preventing both conditions should be encouraged during aging.

Effects of physical exercise on bone mass, balance skill and aerobic capacity in women and men with low bone mineral density, after one year of training--a prospective study.

PubMed

Kronhed, A C; Möller, M

1998-10-01

Vadstena is a small community in the county of Ostergötland, Sweden, where a project began in 1989 to prevent osteoporosis and to lower the expected incidence of osteoporotic fractures. Persons aged 40-70 years who had a low bone mineral density (BMD) value at screening of the distal radius by single-photon absorptiometry (SPA) were invited to participate in a training study during one year. The definition of low BMD was a densitometry value below -1 SD (standard deviation) from a sex- and age-specific reference value (z-score). Fifteen persons wanted to exercise in a group and 15 persons wanted to become a control group. All participants answered a questionnaire about lifestyle, occupation, diseases, medication and heredity. Clinical tests were made regarding mobility of the joints and muscles, balance and physical fitness. BMD for the hip and the lumbar spine were assessed by dual-energy X-ray absorptiometry (DXA) before and after the investigation period. The training programme was carried out for 60 min twice a week during one year and had the intention to improve bone mass, muscle strength and flexibility, balance skill and aerobic capacity. After the training period there was a significant increase in BMD at the greater trochanter (P < 0.01), in balance skill (standing on one leg with closed eyes and "ski step"-test) (P < 0.05) and in oxygen uptake capacity (P < 0.05) in the exercise group. In the control group, there was a significant increase in BMD at the lumbar spine (P < 0.05). However, these results should be judged with caution because several participants were over the age of 60, and at that age degenerative changes in the lumbar spine may increase to a greater or lesser extent. Regular weight-bearing exercises during one year seem to influence BMD at the greater trochanter in a training group comprising both women and men. However, our study was small in number and further training studies are needed to assess the effect of weight-bearing training on bone mass in different sex- and age-specific groups.

Micro-architectural changes in cancellous bone differ in female and male C57BL/6 mice with high-fat diet-induced low bone mineral density.

PubMed

Gautam, Jyoti; Choudhary, Dharmendra; Khedgikar, Vikram; Kushwaha, Priyanka; Singh, Ravi Shankar; Singh, Divya; Tiwari, Swasti; Trivedi, Ritu

2014-05-28

The relationship between fat and bone mass at distinct trabecular and cortical skeletal compartments in a high-fat diet (HFD) model was studied. For this, C57BL/6 mice were assigned to four groups of eight animals each. Two groups, each of males and females, received a standard chow diet while the remaining other two groups received the HFD for a period of 10 weeks. Male mice on the HFD were heavier and gained more weight (15·8 %; P<  0·05) v. those on the control diet or when compared with the female rats fed the HFD. We observed an increased lipid profile in both males and females, with significantly higher lipid levels (about 20-25 %; P< 0·01) in males. However, glucose intolerance was more pronounced in females than males on the HFD (about 30 %; P< 0·05). The micro-architectural assessment of bones showed that compared with female mice on the HFD, male mice on the HFD showed more deterioration at the trabecular region. This was corroborated by plasma osteocalcin and carboxy-terminal collagen crosslinks (CTx) levels confirming greater loss in males (about 20 %; P< 0·01). In both sexes cortical bone parameters and strength remained unchanged after 10 weeks of HFD treatment. The direct effect of the HFD on bone at the messenger RNA level in progenitor cells isolated from femoral bone marrow was a significantly increased expression of adipogenic marker genes v. osteogenic genes. Overall, the present data indicate that obesity induced by a HFD aggravates bone loss in the cancellous bone compartment, with a greater loss in males than females, although 10 weeks of HFD treatment did not alter cortical bone mass and strength in both males and females.

Invited review: Dairy intake and bone health: a viewpoint from the state of the art.

PubMed

Caroli, A; Poli, A; Ricotta, D; Banfi, G; Cocchi, D

2011-11-01

The aim of this review was to focus on the complex relationships between milk and dairy products intake and bone health, with particular emphasis on osteoporosis. The literature was extensively examined to provide an objective overview of the most significant achievements on the subject. Osteoporosis can be defined as a disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. Although the major determinants of peak bone mass and strength are genetic, major factors during childhood and adolescence may affect the ability to achieve peak bone mass. These include nutrition, particularly calcium and protein intake, physical activity, endocrine status, as well as exposure to a wide variety of risk factors. The role of calcium intake in determining bone mineral mass is well recognized to be the most critical nutritional factor to achieve optimal peak bone mass. The greatest amount of dietary calcium is obtained from milk and dairy foods, which also provide the human diet with vitamin D (particularly for products fortified with vitamin D), potassium, and other macro- and micronutrients. Although studies supporting the beneficial effects of milk or calcium on bone health are predominant in the literature, perplexity or discordance on this subject was expressed by some authors. Discordant data, mainly on the risk of fractures, provided limited proof of the unfavorable effect of dairy intake. More often, discordant works indicate no effect of dairy consumption on bone safety. Some considerations can be drawn from this viewpoint. Milk and dairy products are an optimal source of calcium as well as of other limiting nutrients (e.g., potassium and magnesium), with important effects on bone health. Bioactive components occurring in milk and dairy products may play an essential role on bone metabolism, as shown by in vivo and in vitro studies on colostrum acidic proteins and milk basic proteins. Calcium intake positively affects bone mass and is crucial in childhood and youth for correct bone development. In elderly people, calcium intake as well as vitamin D availability should be carefully checked. As a general conclusion, calcium is essential for bone health, although it will not prevent bone loss due to other factors; in this context, milk and dairy foods are bioavailable, relatively inexpensive sources of calcium for the human diet. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Diet in midpuberty and sedentary activity in prepuberty predict peak bone mass.

PubMed

Wang, May-Choo; Crawford, Patricia B; Hudes, Mark; Van Loan, Marta; Siemering, Kirstin; Bachrach, Laura K

2003-02-01

An average daily calcium intake of 1300 mg is recommended for North American adolescents aged 9-18 y. However, questions remain about these recommendations. We assessed whether there is a stage of puberty when dietary calcium is more strongly related to peak bone mass, as indicated by young adult bone mass (YABM); whether dietary calcium intake > 1000 mg/d in adolescence is associated with higher YABM; and whether race affects any of these associations between dietary calcium and YABM. Secondarily, we evaluated relations between sedentariness and YABM. In a retrospective cohort study, we recruited 693 black and white women aged 21-24 y who had participated in the 10-y National Heart, Lung, and Blood Institute Growth and Health Study and measured YABM with the use of dual-energy X-ray absorptiometry. Dietary calcium and sedentary activity data, gathered through 3-d food records and self-reports of television-video viewing at 8 annual examinations, were averaged over 3 pubertal stages. Complete data were available from 161 black and 180 white females. Multiple regression, controlling for race, weight, and height, was applied to assess diet and activity relations with YABM. Dietary calcium was most strongly associated with YABM in midpuberty. Calcium intake > 1000 mg/d was associated with higher YABM, but this association was not significant at all skeletal sites. Race did not affect the observed relations between calcium and YABM. Sedentary activity in prepuberty was inversely associated with YABM. Interventions should focus on ensuring adequate calcium intake in midpuberty and on minimizing sedentariness in prepuberty.

Rapidly Growing Brtl/+ Mouse Model of Osteogenesis Imperfecta Improves Bone Mass and Strength with Sclerostin Antibody Treatment

PubMed Central

Sinder, Benjamin P.; Salemi, Joseph D.; Ominsky, Michael S.; Caird, Michelle S.; Marini, Joan C.; Kozloff, Kenneth M.

2014-01-01

Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk that presents most severely in children. Anti-resorptive bisphosphonates are frequently used to treat pediatric OI and controlled clinical trials have shown bisphosphonate therapy improves vertebral outcomes but has little benefit on long bone fracture rate. New treatments which increase bone mass throughout the pediatric OI skeleton would be beneficial. Sclerostin antibody (Scl-Ab) is a potential candidate anabolic therapy for pediatric OI and functions by stimulating osteoblastic bone formation via the canonical wnt signaling pathway. To explore the effect of Scl-Ab on the rapidly growing OI skeleton, we treated rapidly growing 3 week old Brtl/+ mice, harboring a typical heterozygous OI-causing Gly->Cys substitution on col1a1, for 5 weeks with Scl-Ab. Scl-Ab had anabolic effects in Brtl/+ and led to new cortical bone formation and increased cortical bone mass. This anabolic action resulted in improved mechanical strength to WT Veh levels without altering the underlying brittle nature of the material. While Scl-Ab was anabolic in trabecular bone of the distal femur in both genotypes, the effect was less strong in these rapidly growing Brtl/+ mice compared to WT. In conclusion, Scl-Ab was able to stimulate bone formation in a rapidly growing Brtl/+ murine model of OI, and represents a potential new therapy to improve bone mass and reduce fracture risk in pediatric OI. PMID:25445450

Fat Mass Is Positively Associated with Estimated Hip Bone Strength among Chinese Men Aged 50 Years and above with Low Levels of Lean Mass.

PubMed

Han, Guiyuan; Chen, Yu-Ming; Huang, Hua; Chen, Zhanyong; Jing, Lipeng; Xiao, Su-Mei

2017-04-24

This study investigated the relationships of fat mass (FM) and lean mass (LM) with estimated hip bone strength in Chinese men aged 50-80 years (median value: 62.0 years). A cross-sectional study including 889 men was conducted in Guangzhou, China. Body composition and hip bone parameters were generated by dual-energy X-ray absorptiometry (DXA). The relationships of the LM index (LMI) and the FM index (FMI) with bone phenotypes were detected by generalised additive models and multiple linear regression. The associations between the FMI and the bone variables in LMI tertiles were further analysed. The FMI possessed a linear relationship with greater estimated hip bone strength after adjustment for the potential confounders ( p < 0.05). Linear relationships were also observed for the LMI with most bone phenotypes, except for the cross-sectional area ( p < 0.05). The contribution of the LMI (4.0%-12.8%) was greater than that of the FMI (2.0%-5.7%). The associations between the FMI and bone phenotypes became weaker after controlling for LMI. Further analyses showed that estimated bone strength ascended with FMI in the lowest LMI tertile ( p < 0.05), but not in the subgroups with a higher LMI. This study suggested that LM played a critical role in bone health in middle-aged and elderly Chinese men, and that the maintenance of adequate FM could help to promote bone acquisition in relatively thin men.

Outcomes of bone density measurements in coeliac disease.

PubMed

Bolland, Mark J; Grey, Andrew; Rowbotham, David S

2016-01-29

Some guidelines recommend that patients with newly diagnosed coeliac disease undergo bone density scanning. We assessed the bone density results in a cohort of patients with coeliac disease. We searched bone density reports over two 5-year periods in all patients from Auckland District Health Board (2008-12) and in patients under 65 years from Counties Manukau District Health Board (2009-13) for the term 'coeliac.' Reports for 137 adults listed coeliac disease as an indication for bone densitometry. The average age was 47 years, body mass index (BMI) 25 kg/m(2), and 77% were female. The median time between coeliac disease diagnosis and bone densitometry was 261 days. The average bone density Z-score was slightly lower than expected (Z-score -0.3 to 0.4) at the lumbar spine, total hip and femoral neck, but 88-93% of Z-scores at each site lay within the normal range. Low bone density was strongly related to BMI: the proportions with Z-score <-2 for BMI <20, 20-25, 25-30, and >30 kg/m(2) were 28%, 15%, 6% and 0% respectively. Average bone density was normal, suggesting that bone density measurement is not indicated routinely in coeliac disease, but could be considered on a case-by-case basis for individuals with strong risk factors for fracture.

Relationships among diet, physical activity, and dual plane dual-energy X-ray absorptiometry bone outcomes in pre-pubertalgirls.

PubMed

Ren, Jie; Brann, Lynn S; Bruening, Kay S; Scerpella, Tamara A; Dowthwaite, Jodi N

2017-12-01

In pre-pubertal girls, nutrient intakes and non-aquatic organized activity were evaluated as factors in vertebral body bone mass, structure, and strength. Activity, vitamin B 12 , and dietary fiber predicted bone outcomes most consistently. Exercise and vitamin B 12 appear beneficial, whereas high fiber intake appears to be adverse for vertebral body development. Childhood development sets the baseline for adult fracture risk. Most studies evaluate development using postero-anterior (PA) dual-energy X-ray absorptiometry (DXA) areal bone mineral density, bone mineral content, and bone mineral apparent density. In a prior analysis, we demonstrated that PA DXA reflects posterior element properties, rather than vertebral body fracture sites, such that loading is associated with subtle differences in vertebral body geometry, not 3D density. The current analysis is restricted to pre-pubertal girls, for a focused exploration of key nutrient intakes and physical activity as factors in dual plane indices of vertebral body geometry, density, and strength. This cross-sectional analysis used paired PA and supine lateral (LAT) lumbar spine DXA scans to assess "3D" vertebral body bone mineral apparent density (PALATBMAD), "3D" index of structural strength in axial compression (PALATIBS), and fracture risk index (PALATFRI). Diet data were collected using the Youth/Adolescent Questionnaire (YAQ, 1995); organized physical activity was recorded via calendar-based form. Pearson correlations and backward stepwise multiple linear regression analyzed associations among key nutrients, physical activity, and bone outcomes. After accounting for activity and key covariates, fiber, unsupplemented vitamin B 12 , zinc, carbohydrate, vitamin C, unsupplemented magnesium, and unsupplemented calcium intake explained significant variance for one or more bone outcomes (p < 0.05). After adjustment for influential key nutrients and covariates, activity exposure was associated with postero-anterior (PA) areal bone mineral density, PA bone mineral content, PA width, lateral (LAT) BMC, "3D" bone cross-sectional area (coronal plane), "3D" PALATIBS, and PALATFRI benefits (p < 0.05). Physical activity, fiber intake, and unsupplemented B 12 intake appear to influence vertebral body bone mass, density, geometry, and strength in well-nourished pre-pubertal girls; high fiber intakes may adversely affect childhood vertebral body growth.

Effects of Eggshell Calcium Supplementation on Bone Mass in Postmenopausal Vietnamese Women.

PubMed

Sakai, Seigo; Hien, Vu Thi Thu; Tuyen, Le Danh; Duc, Ha Anh; Masuda, Yasunobu; Yamamoto, Shigeru

2017-01-01

Bone mass decreases along with aging, especially for women after menopause because of lower estrogen secretion together with low calcium intake. This study was conducted to study the effect of eggshell calcium supplementation on bone mass in 54 postmenopausal Vietnamese women living in a farming area about 60 km from Hanoi, Vietnam. Sets of 3 subjects matched by age, bone mass, BMI and calcium intake were divided randomly into 3 groups with 18 subjects in each group. The eggshell calcium group was administered 300 mg/d calcium from eggshell, the calcium carbonate group 300 mg/d calcium from calcium carbonate and the placebo group received no calcium supplementation. Bone mass (Speed of Sound (SOS)) was measured at the beginning (the baseline), the middle (6th month) and the end of the study (12th month) by the single blind method. SOS of the eggshell group increased significantly at 12 mo (p<0.05) and was significantly higher than that of the placebo and calcium carbonate groups at 12 mo (p<0.05). The SOS of the calcium carbonate group tended to be higher than that of the placebo group but without a significant difference (p>0.05). In conclusion, eggshell calcium was more effective in increasing bone mass than calcium carbonate in postmenopausal Vietnamese women.

Osteophagia provide giraffes with phosphorus and calcium?

PubMed

Bredin, I P; Skinner, J D; Mitchell, G

2008-03-01

The daily requirement for calcium and phosphorus by giraffes to sustain the growth and maintenance of their skeletons is large. The source of sufficient calcium is browse. The source of necessary phosphorus is obscure, but it could be osteophagia, a frequently observed behaviour in giraffes. We have assessed whether bone ingested as a result of osteophagia can be digested in the rumen. Bone samples from cancellous (cervical vertebrae) and dense bones (metacarpal shaft) were immersed in the rumens of five sheep, for a period of up to 30 days, and the effect compared to immersion in distilled water and in artificial saliva for 30 days. Distilled water had no effect on the bones. Dense bone samples were softened by exposure to the saliva and rumen fluid, but did not lose either calcium or phosphorus. In saliva and rumen fluid the cancellous bone samples also softened, and their mass and volume decreased as a result of exposure to saliva, but in neither fluid did they lose significant amounts of calcium and phosphorus. We conclude that although saliva and rumen fluid can soften ingested bones, there is an insignificant digestion of bones in the rumen.

Bone formation: roles of genistein and daidzein

USDA-ARS?s Scientific Manuscript database

Bone remodeling consists of a balance between bone formation by osteoblasts and bone resorption by osteoclasts. Osteoporosis is the result of increased bone resorption and decreased bone formation causing a decreased bone mass density, loss of bone microarchitecture, and an increased risk of fractu...

Physical activity, but not sedentary time, influences bone strength in late adolescence.

PubMed

Tan, Vina Ps; Macdonald, Heather M; Gabel, Leigh; McKay, Heather A

2018-03-20

Physical activity is essential for optimal bone strength accrual, but we know little about interactions between physical activity, sedentary time, and bone outcomes in older adolescents. Physical activity (by accelerometer and self-report) positively predicted bone strength and the distal and midshaft tibia in 15-year-old boys and girls. Lean body mass mediated the relationship between physical activity and bone strength in adolescents. To examine the influence of physical activity (PA) and sedentary time on bone strength, structure, and density in older adolescents. We used peripheral quantitative computed tomography to estimate bone strength at the distal tibia (8% site; bone strength index, BSI) and tibial midshaft (50% site; polar strength strain index, SSI p ) in adolescent boys (n = 86; 15.3 ± 0.4 years) and girls (n = 106; 15.3 ± 0.4 years). Using accelerometers (GT1M, Actigraph), we measured moderate-to-vigorous PA (MVPA Accel ), vigorous PA (VPA Accel ), and sedentary time in addition to self-reported MVPA (MVPA PAQ-A ) and impact PA (ImpactPA PAQ-A ). We examined relations between PA and sedentary time and bone outcomes, adjusting for ethnicity, maturity, tibial length, and total body lean mass. At the distal tibia, MVPA Accel and VPA Accel positively predicted BSI (explained 6-7% of the variance, p < 0.05). After adjusting for lean mass, only VPA Accel explained residual variance in BSI. At the tibial midshaft, MVPA Accel , but not VPA Accel , positively predicted SSI p (explained 3% of the variance, p = 0.01). Lean mass attenuated this association. MVPA PAQ-A and ImpactPA PAQ-A also positively predicted BSI and SSI p (explained 2-4% of the variance, p < 0.05), but only ImpactPA PAQ-A explained residual variance in BSI after accounting for lean mass. Sedentary time did not independently predict bone strength at either site. Greater tibial bone strength in active adolescents is mediated, in part, by lean mass. Despite spending most of their day in sedentary pursuits, adolescents' bone strength was not negatively influenced by sedentary time.

Reduced bone mass and muscle strength in male 5α-reductase type 1 inactivated mice.

PubMed

Windahl, Sara H; Andersson, Niklas; Börjesson, Anna E; Swanson, Charlotte; Svensson, Johan; Movérare-Skrtic, Sofia; Sjögren, Klara; Shao, Ruijin; Lagerquist, Marie K; Ohlsson, Claes

2011-01-01

Androgens are important regulators of bone mass but the relative importance of testosterone (T) versus dihydrotestosterone (DHT) for the activation of the androgen receptor (AR) in bone is unknown. 5α-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5α-reductase (type 1 and type 2), encoded by separate genes (Srd5a1 and Srd5a2). 5α-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5α-reductase type 1 is highly expressed in liver and moderately expressed in several other tissues including bone. The aim of the present study was to investigate the role of 5α-reductase type 1 for bone mass using Srd5a1⁻/⁻ mice. Four-month-old male Srd5a1⁻/⁻ mice had reduced trabecular bone mineral density (-36%, p<0.05) and cortical bone mineral content (-15%, p<0.05) but unchanged serum androgen levels compared with wild type (WT) mice. The cortical bone dimensions were reduced in the male Srd5a1⁻/⁻ mice as a result of a reduced cortical periosteal circumference compared with WT mice. T treatment increased the cortical periosteal circumference (p<0.05) in orchidectomized WT mice but not in orchidectomized Srd5a1⁻/⁻ mice. Male Srd5a1⁻/⁻ mice demonstrated a reduced forelimb muscle grip strength compared with WT mice (p<0.05). Female Srd5a1⁻/⁻ mice had slightly increased cortical bone mass associated with elevated circulating levels of androgens. In conclusion, 5α-reductase type 1 inactivated male mice have reduced bone mass and forelimb muscle grip strength and we propose that these effects are due to lack of 5α-reductase type 1 expression in bone and muscle. In contrast, the increased cortical bone mass in female Srd5a1⁻/⁻ mice, is an indirect effect mediated by elevated circulating androgen levels.

Reduced Bone Mass and Muscle Strength in Male 5α-Reductase Type 1 Inactivated Mice

PubMed Central

Windahl, Sara H.; Andersson, Niklas; Börjesson, Anna E.; Swanson, Charlotte; Svensson, Johan; Movérare-Skrtic, Sofia; Sjögren, Klara; Shao, Ruijin; Lagerquist, Marie K.; Ohlsson, Claes

2011-01-01

Androgens are important regulators of bone mass but the relative importance of testosterone (T) versus dihydrotestosterone (DHT) for the activation of the androgen receptor (AR) in bone is unknown. 5α-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5α-reductase (type 1 and type 2), encoded by separate genes (Srd5a1 and Srd5a2). 5α-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5α-reductase type 1 is highly expressed in liver and moderately expressed in several other tissues including bone. The aim of the present study was to investigate the role of 5α-reductase type 1 for bone mass using Srd5a1−/− mice. Four-month-old male Srd5a1 −/− mice had reduced trabecular bone mineral density (−36%, p<0.05) and cortical bone mineral content (−15%, p<0.05) but unchanged serum androgen levels compared with wild type (WT) mice. The cortical bone dimensions were reduced in the male Srd5a1 −/− mice as a result of a reduced cortical periosteal circumference compared with WT mice. T treatment increased the cortical periosteal circumference (p<0.05) in orchidectomized WT mice but not in orchidectomized Srd5a1 −/− mice. Male Srd5a1 −/− mice demonstrated a reduced forelimb muscle grip strength compared with WT mice (p<0.05). Female Srd5a1 −/− mice had slightly increased cortical bone mass associated with elevated circulating levels of androgens. In conclusion, 5α-reductase type 1 inactivated male mice have reduced bone mass and forelimb muscle grip strength and we propose that these effects are due to lack of 5α-reductase type 1 expression in bone and muscle. In contrast, the increased cortical bone mass in female Srd5a1 −/− mice, is an indirect effect mediated by elevated circulating androgen levels. PMID:21731732

Effect of dexamethasone on mandibular bone biomechanics in rats during the growth phase as assessed by bending test and peripheral quantitative computerized tomography.

PubMed

Bozzini, Clarisa; Champin, Graciela; Alippi, Rosa M; Bozzini, Carlos E

2015-04-01

Long-term glucocorticoid administration to growing rats induces osteopenia and alterations in the biomechanical behavior of the bone. This study was performed to estimate the effects of dexamethasone (DTX), a synthetic steroid with predominant glucocorticoid activity, on the biomechanical properties of the mandible of rats during the growth phase, as assessed by bending test and peripheral quantitative computed tomographic (pQCT) analysis. The data obtained by the two methods will provide more precise information when analyzed together than separately. Female rats aged 23 d (n=7) received 500μg.kg-1 per day of DXT for 4 weeks. At the end of the treatment period, their body weight and body length were 51.3% and 20.6% lower, respectively, than controls. Hemimandible weight and area (an index of mandibular size) were 27.3% and 9.7% lower, respectively. The right hemimandible of each animal was subjected to a mechanical 3-point bending test. Significant weakening of the bone, as shown by a correlative impairment of strength and stiffness, was observed in experimental rats. Bone density and cross-sectional area were measured by pQCT. Cross-sectional, cortical and trabecular areas were reduced by 20% to 30% in the DTX group, as were other cortical parameters, including the bone density, mineral content and cross-sectional moment of inertia. The "bone strength index" (BSI, the product of the pQCT-assessed xCSMI and vCtBMD) was 56% lower in treated rats, which compares well with the 54% and 52% reduction observed in mandibular strength and stiffness determined through the bending test. Data suggest that the corticosteroid exerts a combined, negative action on bone geometry (mass and architecture) and volumetric bone mineral density of cortical bone, which would express independent effects on both cellular (material quality) and tissue (cross-sectional design) levels of biological organization of the skeleton in the species.

Bone Mass in Boys with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Calarge, Chadi A.; Schlechte, Janet A.

2017-01-01

To examine bone mass in children and adolescents with autism spectrum disorders (ASD). Risperidone-treated 5 to 17 year-old males underwent anthropometric and bone measurements, using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Multivariable linear regression analysis models examined whether skeletal outcomes…

Growth hormone and bone health.

PubMed

Bex, Marie; Bouillon, Roger

2003-01-01

Growth hormone (GH) and insulin-like growth factor-I have major effects on growth plate chondrocytes and all bone cells. Untreated childhood-onset GH deficiency (GHD) markedly impairs linear growth as well as three-dimensional bone size. Adult peak bone mass is therefore about 50% that of adults with normal height. This is mainly an effect on bone volume, whereas true bone mineral density (BMD; g/cm(3)) is virtually normal, as demonstrated in a large cohort of untreated Russian adults with childhood-onset GHD. The prevalence of fractures in these untreated childhood-onset GHD adults was, however, markedly and significantly increased in comparison with normal Russian adults. This clearly indicates that bone mass and bone size matter more than true bone density. Adequate treatment with GH can largely correct bone size and in several studies also bone mass, but it usually requires more than 5 years of continuous treatment. Adult-onset GHD decreases bone turnover and results in a mild deficit, generally between -0.5 and -1.0 z-score, in bone mineral content and BMD of the lumbar spine, radius and femoral neck. Cross-sectional surveys and the KIMS data suggest an increased incidence of fractures. GH replacement therapy increases bone turnover. The three controlled studies with follow-up periods of 18 and 24 months demonstrated a modest increase in BMD of the lumbar spine and femoral neck in male adults with adult-onset GHD, whereas no significant changes in BMD were observed in women. GHD, whether childhood- or adult-onset, impairs bone mass and strength. Appropriate substitution therapy can largely correct these deficiencies if given over a prolonged period. GH therapy for other bone disorders not associated with primary GHD needs further study but may well be beneficial because of its positive effects on the bone remodelling cycle. Copyright 2003 S. Karger AG, Basel

Can physical activity improve peak bone mass?

PubMed

Specker, Bonny; Minett, Maggie

2013-09-01

The pediatric origin of osteoporosis has led many investigators to focus on determining factors that influence bone gain during growth and methods for optimizing this gain. Bone responds to bone loading activities by increasing mass or size. Overall, pediatric studies have found a positive effect of bone loading on bone size and accrual, but the types of loads necessary for a bone response have only recently been investigated in human studies. Findings indicate that responses vary by sex, maturational status, and are site-specific. Estrogen status, body composition, and nutritional status also may influence the bone response to loading. Despite the complex interrelationships among these various factors, it is prudent to conclude that increased physical activity throughout life is likely to optimize bone health.

'Sink or swim': an evaluation of the clinical characteristics of individuals with high bone mass.

PubMed

Gregson, C L; Steel, S A; O'Rourke, K P; Allan, K; Ayuk, J; Bhalla, A; Clunie, G; Crabtree, N; Fogelman, I; Goodby, A; Langman, C M; Linton, S; Marriott, E; McCloskey, E; Moss, K E; Palferman, T; Panthakalam, S; Poole, K E S; Stone, M D; Turton, J; Wallis, D; Warburton, S; Wass, J; Duncan, E L; Brown, M A; Davey-Smith, G; Tobias, J H

2012-02-01

High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI). HBM cases may harbour an underlying genetic disorder. High bone mineral density is a sporadic incidental finding on routine DXA scanning of apparently asymptomatic individuals. Such individuals may have an underlying skeletal dysplasia, as seen in LRP5 mutations. We aimed to characterize unexplained HBM and determine the potential for an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained HBM (defined as L1 Z-score ≥ +3.2 plus total hip Z-score ≥ +1.2, or total hip Z-score ≥ +3.2) were recruited from 15 UK centres, by screening 335,115 DXA scans. Unexplained HBM affected 0.181% of DXA scans. Next 236 relatives were recruited of whom 94 (41%) had HBM (defined as L1 Z-score + total hip Z-score ≥ +3.2). Fifty-eight spouses were also recruited together with the unaffected relatives as controls. Phenotypes of cases and controls, obtained from clinical assessment, were compared using random-effects linear and logistic regression models, clustered by family, adjusted for confounders, including age and sex. Individuals with unexplained HBM had an excess of sinking when swimming (7.11 [3.65, 13.84], p < 0.001; adjusted odds ratio with 95% confidence interval shown), mandible enlargement (4.16 [2.34, 7.39], p < 0.001), extra bone at tendon/ligament insertions (2.07 [1.13, 3.78], p = 0.018) and broad frame (3.55 [2.12, 5.95], p < 0.001). HBM cases also had a larger shoe size (mean difference 0.4 [0.1, 0.7] UK sizes, p = 0.009) and increased BMI (mean difference 2.2 [1.3, 3.1] kg/m(2), p < 0.001). Individuals with unexplained HBM have an excess of clinical characteristics associated with skeletal dysplasia and their relatives are commonly affected, suggesting many may harbour an underlying genetic disorder affecting bone mass.

High protein consumption in trained women: bad to the bone?

PubMed

Antonio, Jose; Ellerbroek, Anya; Evans, Cassandra; Silver, Tobin; Peacock, Corey A

2018-01-01

It has been posited that the consumption of extra protein (> 0.8 g/kg/d) may be deleterious to bone mineral content. However, there is no direct evidence to show that consuming a high-protein diet results in a demineralization of the skeleton. Thus, the primary endpoint of this randomized controlled trial was to determine if a high-protein diet affected various parameters of whole body and lumbar bone mineral content in exercise-trained women. Twenty-four women volunteered for this 6-month investigation ( n  = 12 control, n = 12 high-protein). The control group was instructed to consume their habitual diet; however, the high-protein group was instructed to consume ≥2.2 g of protein per kilogram body weight daily (g/kg/d). Body composition was assessed via dual-energy x-ray absorptiometry (DXA). Subjects were instructed to keep a food diary via the mobile app MyFitnessPal ® . Exercise or activity level was not controlled. Subjects were asked to maintain their current levels of exercise. During the 6-month treatment period, there was a significant difference in protein intake between the control and high-protein groups (mean±SD; control: 1.5±0.3, high-protein: 2.8±1.1 g/kg/d); however, there were no differences in the consumption total calories, carbohydrate or fat. Whole body bone mineral density did not change in the control (pre: 1.22±0.08, post: 1.22±0.09 g/cm 2 ) or high-protein group (pre: 1.25±0.11, post: 1.24±0.10 g/cm 2 ). Similarly, lumbar bone mineral density did not change in the control (pre: 1.08±0.16, post: 1.05±0.13 g/cm 2 ) or high-protein group (pre: 1.07±0.11, post: 1.08±0.12 g/cm 2 ). In addition, there were no changes in whole body or lumbar T-Scores in either group. Furthermore, there were no changes in fat mass or lean body mass. Despite an 87% higher protein intake (high-protein versus control), 6 months of a high-protein diet had no effect on whole body bone mineral density, lumbar bone mineral density, T-scores, lean body mass or fat mass.

Lean Body Mass and Bone Health in Urban Adolescents From Northern India.

PubMed

Marwaha, Raman K; Garg, M K; Bhadra, Kuntal; Mahalle, Namita; Mithal, Ambrish; Tandon, Nikhil

2017-03-15

To prepare percentile charts of lean body mass (LBM) among Indian urban children and adolescents; and to evaluate gender differences in LBM, and its relation with pubertal status. Secondary data analysis. School in city of Delhi, India. 1403 apparently healthy children and adolescents (826 boys) with mean (SD) age 13.2 (2.7) years. Lean body mass assessed by dual energy absorptiometry. Total and regional lean mass were greater in older age groups in both sexes. LBM showed rising trends up to the age of 18 years in boys, whereas it plateaued after the age of 15 years in girls. The age-associated increase in LBM was significantly higher in boys (130%) compared to girls (83%) (P<0.001). Total and regional lean mass increased with progression of pubertal staging in both genders. During pubertal development, LBM almost doubled (100% increase) from stage-2 to stage-5 in boys, as opposed to a 73% rise in girls (P<0.001). Total and regional lean mass and Appendicular skeletal muscle mass index (ASMI) was positively correlated with age, body mass index (BMI), serum 25(OH)D, total fat mass, and bone mineral content (BMC). Relation between LBM and BMC remained significant even after adjusting for age, fat mass and various biochemical parameters. Total and regional LBM rise with age and pubertal maturation in both genders, but more so in boys when compared to girls. LBM has direct bearing on BMC even after adjusting for age, fat mass and biochemical parameters.

Gymnastics participation is associated with skeletal benefits in the distal forearm: a 6-month study using peripheral Quantitative Computed Tomography.

PubMed

Burt, L A; Ducher, G; Naughton, G A; Courteix, D; Greene, D A

2013-12-01

Musculoskeletal development of the upper limbs during exposure to weight-bearing loading is under-researched during early pubescent growth. The purpose was to assess the changes in upper body musculoskeletal strength in young girls following 6 months of non-elite gymnastics participation. Eighty-four girls, 6-12 years were divided into groups based on gymnastics participation: high-training (HGYM, 6-16 hr/wk), low-training (LGYM, 1-5 hr/wk), and non-gymnasts (NONGYM). Volumetric BMD, bone geometry, estimated bone strength and muscle size were assessed at the non-dominant forearm (4% and 66% radius and ulna) with pQCT. DXA assessed aBMD and body composition. Tests for explosive power, muscle strength, and endurance were also performed. Interaction effects were observed in all variables at the 4% radius. At the 66% ulna, HGYM and LGYM had greater bone mass, size and bone strength than NONGYM, furthermore a dose-response relationship was observed at this location. Body composition was better for HGYM than LGYM and NONGYM, however muscle function was better for HGYM and LGYM than NONGYM. The greatest changes were obtained with more than one gymnastics class per week. Separating gymnastics participation-related changes from those associated with normal growth and development remains difficult, particularly at the 4% radius.

Rowing performance, body composition, and bone mineral density outcomes in college-level rowers after a season of concurrent training.

PubMed

Young, Kaelin C; Kendall, Kristina L; Patterson, Kaitlyn M; Pandya, Priyanka D; Fairman, Ciaran M; Smith, Samuel W

2014-11-01

To assess changes in body composition, lumbar-spine bone mineral density (BMD), and rowing performance in college-level rowers over a competition season. Eleven Division I college rowers (mean ± SD 21.4 ± 3.7 y) completed 6 testing sessions throughout the course of their competition season. Testing included measurements of fat mass, bone-free lean mass (BFLM), body fat (%BF), lumbar-spine BMD, and 2000-m time-trial performance. After preseason testing, rowers participated in a periodized training program, with the addition of resistance training to the traditional aerobic-training program. Significant (P < .05) improvements in %BF, total mass, and BFLM were observed at midseason and postseason compared with preseason. Neither lumbar-spine BMD nor BMC significantly changed over the competitive season (P > .05). Finally, rowing performance (as measured by 2000-m time and average watts achieved) significantly improved at midseason and postseason compared with preseason. Our results highlight the efficacy of a seasonal concurrent training program serving to improve body composition and rowing performance, as measured by 2000-m times and average watts, among college-level rowers. Our findings offer practical applications for coaches and athletes looking to design a concurrent strength and aerobic training program to improve rowing performance across a season.

Higher glucocorticoid secretion in the physiological range is associated with lower bone strength at the proximal radius in healthy children: importance of protein intake adjustment.

PubMed

Shi, Lijie; Sánchez-Guijo, Alberto; Hartmann, Michaela F; Schönau, Eckhard; Esche, Jonas; Wudy, Stefan A; Remer, Thomas

2015-02-01

Whether higher production of glucocorticoids (GCs) within the physiological range may already be affecting bone status in healthy children is unknown. Because dietary protein intake affects both bone and GCs, we examined the association of urinary measures of glucocorticoid status and cortical bone in healthy non-obese children, after particularly controlling for protein intake. Proximal forearm bone parameters were measured by peripheral quantitative computed tomography (pQCT). Subjects studied (n = 175, 87 males, aged 6 to 18 years) had two 24-hour urine samples collected: the first sample at 1 year before bone measurement, and the second sample at the time of bone measurement. Major urinary GC metabolites were measured by mass spectrometry and summed to assess daily adrenal GC secretion (∑C21). Urinary free cortisol (UFF) and cortisone (UFE) were summed to assess potentially bioactive free GCs (UFF + UFE). After controlling for several covariates and especially urinary nitrogen (the biomarker of protein intake) cortisol secretion ∑C21 was inversely associated with all analyzed pQCT measures of bone quality. ∑C21 also predicted a higher endosteal and lower periosteal circumference, explaining both a smaller cortical area and (together with lower BMD) a lower strength-strain-index (SSI). UFF + UFE, UFE itself, and a urinary metabolite-estimate of 11beta-hydroxysteroid dehydrogenase type1 (11beta-HSD1) activity showed corresponding reciprocal associations (p < 0.05) with BMD and bone mineral content, but not with SSI and bone geometry variables. In conclusion, higher GC levels, even within the physiological range, appear to exert negative influences on bone modeling and remodeling already during growth. Our physiological data also suggest a relevant role of cortisone as the direct source for intracrine-generated cortisol by bone cell 11beta-HSD1. © 2014 American Society for Bone and Mineral Research.

Prevalence of Poor Bone Quality in Women Undergoing Spinal Fusion Using Biomechanical-CT Analysis.

PubMed

Burch, Shane; Feldstein, Michael; Hoffmann, Paul F; Keaveny, Tony M

2016-02-01

Retrospective, cross-sectional analysis of vertebral bone quality in spine-fusion patients at a single medical center. To characterize the prevalence of osteoporosis and fragile bone strength in a spine-fusion population of women with an age range of 50 years to 70 years. Fragile bone strength is defined as the level of vertebral strength below which a patient is at as high a risk of future vertebral fracture as a patient having bone density-defined osteoporosis. Poor bone quality--defined here as the presence of either osteoporosis or fragile bone strength--is a risk factor for spine-fusion patients that often goes undetected but can now be assessed preoperatively by additional postprocessing of computed tomography (CT) scans originally ordered for perioperative clinical assessment. Utilizing such perioperative CT scans for a cohort of 98 women (age range: 51-70 yr) about to undergo spine fusion, we retrospectively used a phantomless calibration technique and biomechanical-CT postprocessing analysis to measure vertebral trabecular bone mineral density (BMD) (in mg/cm³) and by nonlinear finite element analysis, vertebral compressive strength (in Newtons, N) in the L1 or L2 vertebra. Preestablished validated threshold values were used to define the presence of osteoporosis (trabecular BMD of 80 mg/cm³ or lower) and fragile bone strength (vertebral strength of 4500 N or lower). Fourteen percent of the women tested positive for osteoporosis, 27% tested positive for fragile bone strength, and 29% were classified as having poor bone quality (either osteoporosis or fragile bone strength). Over this narrow age range, neither BMD nor vertebral strength were significantly correlated with age, weight, height, or body mass index (P values 0.14-0.97 for BMD; 0.13-0.51 for strength). Poor bone quality appears to be common in women between ages 50 years and 70 years undergoing spinal fusion surgery. 3.

Suppression of Autophagy in Osteocytes Mimics Skeletal Aging*

PubMed Central

Onal, Melda; Piemontese, Marilina; Xiong, Jinhu; Wang, Yiying; Han, Li; Ye, Shiqiao; Komatsu, Masaaki; Selig, Martin; Weinstein, Robert S.; Zhao, Haibo; Jilka, Robert L.; Almeida, Maria; Manolagas, Stavros C.; O'Brien, Charles A.

2013-01-01

Bone mass declines with age but the mechanisms responsible remain unclear. Here we demonstrate that deletion of a conditional allele for Atg7, a gene essential for autophagy, from osteocytes caused low bone mass in 6-month-old male and female mice. Cancellous bone volume and cortical thickness were decreased, and cortical porosity increased, in conditional knock-out mice compared with control littermates. These changes were associated with low osteoclast number, osteoblast number, bone formation rate, and wall width in the cancellous bone of conditional knock-out mice. In addition, oxidative stress was higher in the bones of conditional knock-out mice as measured by reactive oxygen species levels in the bone marrow and by p66shc phosphorylation in L6 vertebra. Each of these changes has been previously demonstrated in the bones of old versus young adult mice. Thus, these results demonstrate that suppression of autophagy in osteocytes mimics, in many aspects, the impact of aging on the skeleton and suggest that a decline in autophagy with age may contribute to the low bone mass associated with aging. PMID:23645674

Osteoporosis prevention, diagnosis, and therapy.

PubMed

The objective of this NIH Consensus Statement is to inform the biomedical research and clinical practice communities of the results of the NIH Consensus Development Conference on Osteoporosis Prevention, Diagnosis, and Therapy. The statement provides state-of-the-art information and presents the conclusions and recommendations of the consensus panel regarding these issues. In addition, the statement identifies those areas of study that deserve further investigation. The target audience of clinicians for this statement includes, but is not limited to, family practitioners, internists, gerontologists, orthopaedic surgeons, rheumatologists, obstetricians and gynecologists, and preventive medicine specialisits. A nonfederal, nonadvocate, 13-member panel representing the fields of internal medicine, family and community medicine, endocrinology, epidemiology, orthopaedic surgery, gerontology, rheumatology, obstetrics and gynecology, preventive medicine, and cell biology. In addition, 32 experts from these same fields presented data to the panel and a conference audience of approximately 700. The literature was searched using MEDLINE and an extensive bibliography of references was provided to the panel. Experts prepared abstracts for their conference presentations with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement, which was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately following its release at the conference and was updated with the panel's final revisions. Osteoporosis occurs in all populations and at all ages. Though more prevalent in white postmenopausal females, it often goes unrecognized in other populations. Osteoporosis is a devastating disorder with significant physical, psychosocial, and financial consequences. The risks for osteoporosis, as reflected by low bone density, and the risks for fracture overlap but are not identical. More attention should be paid to skeletal health in persons with conditions known to be associated with secondary osteoporosis. Clinical risk factors have an important, but as yet poorly validated, role in determining who should have BMD measurement, in assessing risk of fracture, and in determining who should be treated. Adequate calcium and vitamin D intake are crucial to develop optimal peak bone mass and to preserve bone mass throughout life. Supplementation of these two components in bioavailable forms may be necessary in individuals who do not achieve recommended intake from dietary sources. Gonadal steroids are important determinants of peak and lifetime bone mass in men, women, and children. Regular exercise, especially resistance and high-impact activities, contributes to development of high peak bone mass and may reduce the risk of falls in older individuals. Assessment of bone mass, identification of fracture risk, and determination of who should be treated are the optimal goals when evaluating patients for osteoporosis. Fracture prevention is the primary goal in the treatment of patients with osteoporosis. Several treatments have been shown to reduce the risk of osteoporotic fractures. These include therapies that enhance bone mass and reduce risk or consequences of falls. Adults with vertebral, rib, hip, or distal forearm fractures should be evaluated for the presence of osteoporosis and given appropriate therapy.

Factors affecting bone mineral mass loss after lower-limb fractures in a pediatric population.

PubMed

Ceroni, Dimitri; Martin, Xavier; Kherad, Omar; Salvo, Davide; Dubois-Ferrière, Victor

2015-06-01

The purpose of this study was to assess the effects of the durations of cast immobilization and non-weight-bearing periods, and decreases in vigorous physical activity (VPA) on bone mineral parameters in a pediatric population treated for a lower-limb fracture. Fifty children and teenagers who had undergone a cast-mediated immobilization for a leg or ankle fracture were prospectively recruited. The durations of cast immobilization and non-weight-bearing periods were recorded for each participant. Dual-energy x-ray absorptiometry scans were performed at the time of fracture treatment (baseline) and at cast removal. Physical activity during cast immobilization was assessed using accelerometers. A strong negative correlation was found between the total duration of cast immobilization and decreases in both calcaneal bone mineral density (BMD) (r=-0.497) and total lower-limb bone mineral content (BMC) (r=-0.405). A strong negative correlation was also noted between the durations of the non-weight-bearing periods and alterations in calcaneal BMD (r=-0.420). No apparent correlations were found between lower BMD and BMC and decreased VPA. Bone mineral loss was correlated to the total duration of cast immobilization for all measurement sites on the affected leg, whereas it was only correlated to the durations of non-weight-bearing periods for calcaneal BMD and total lower-limb BMC. However, no correlations were noted between bone mineral loss and decreased VPA.

Bone mass in Indian children--relationships to maternal nutritional status and diet during pregnancy: the Pune Maternal Nutrition Study.

PubMed

Ganpule, A; Yajnik, C S; Fall, C H D; Rao, S; Fisher, D J; Kanade, A; Cooper, C; Naik, S; Joshi, N; Lubree, H; Deshpande, V; Joglekar, C

2006-08-01

Bone mass is influenced by genetic and environmental factors. Recent studies have highlighted associations between maternal nutritional status during pregnancy and bone mass in the offspring. We hypothesized that maternal calcium intakes and circulating micronutrients during pregnancy are related to bone mass in Indian children. DESIGN/SETTING/PARTICIPANTS/MAIN OUTCOME MEASURES: Nutritional status was measured at 18 and 28 wk gestation in 797 pregnant rural Indian women. Measurements included anthropometry, dietary intakes (24-h recall and food frequency questionnaire), physical workload (questionnaire), and circulating micronutrients (red cell folate and plasma ferritin, vitamin B12, and vitamin C). Six years postnatally, total body and total spine bone mineral content and bone mineral density (BMD) were measured using dual-energy x-ray absorptiometry (DXA) in the children (n = 698 of 762 live births) and both parents. Both parents' DXA measurements were positively correlated with the equivalent measurements in the children (P < 0.001 for all). The strength of these correlations was similar for fathers and mothers. Children of mothers who had a higher frequency of intake of calcium-rich foods during pregnancy (milk, milk products, pulses, non-vegetarian foods, green leafy vegetables, fruit) had higher total and spine bone mineral content and BMD, and children of mothers with higher folate status at 28 wk gestation had higher total and spine BMD, independent of parental size and DXA measurements. Modifiable maternal nutritional factors may influence bone health in the offspring. Fathers play a role in determining their child's bone mass, possibly through genetic mechanisms or through shared environment.

Skeletal dosimetry models for alpha-particles for use in molecular radiotherapy

NASA Astrophysics Data System (ADS)

Watchman, Christopher J.

Molecular radiotherapy is a cancer treatment methodology whereby a radionuclide is combined with a biologically active molecule to preferentially target cancer cells. Alpha-particle emitting radionuclides show significant potential for use in molecular radiotherapy due to the short range of the alpha-particles in tissue and their high rates of energy deposition. Current radiation dosimetry models used to assess alpha emitter dose in the skeleton were developed originally for occupational applications. In medical dosimetry, individual variability in uptake, translocation and other biological factors can result in poor correlation of clinical outcome with marrow dose estimates determined using existing skeletal models. Methods presented in this work were developed in response to the need for dosimetry models which account for these biological and patient-specific factors. Dosimetry models are presented for trabecular bone alpha particle dosimetry as well as a model for cortical bone dosimetry. These radiation transport models are the 3D chord-based infinite spongiosa transport model (3D-CBIST) and the chord-based infinite cortical transport model (CBICT), respectively. Absorbed fraction data for several skeletal tissues for several subjects are presented. Each modeling strategy accounts for biological parameters, such as bone marrow cellularity, not previously incorporated into alpha-particle skeletal dosimetry models used in radiation protection. Using these data a study investigating the variability in alpha-particle absorbed fractions in the human skeleton is also presented. Data is also offered relating skeletal tissue masses in individual bone sites for a range of ages. These data are necessary for dose calculations and have previously only been available as whole body tissue masses. A revised 3D-CBIST model is also presented which allows for changes in endosteum thickness to account for revised target cell location of tissues involved in the radiological induction of bone cancer. In addition, new data are presented on the location of bone-marrow stem cells within the marrow cavities of trabecular bone of the pelvis. All results presented in this work may be applied to occupational exposures, but their greatest utility lies in dose assessments for alpha-emitters in molecular radiotherapy.

The associations of exposure to combined hormonal contraceptive use on bone mineral content and areal bone mineral density accrual from adolescence to young adulthood: A longitudinal study.

PubMed

Jackowski, Stefan A; Baxter-Jones, Adam D G; McLardy, Ashlee J; Pierson, Roger A; Rodgers, Carol D

2016-12-01

The association of long term combined hormone based contraceptives (CHC) use on bone mineral content (BMC) and areal bone mineral density (aBMD) development remains controversial, as it appears that the relationship may be age-dependent. The purpose of this study was to investigate the long-term associations of CHC exposure on the accrual of bone parameters from adolescence into young-adulthood. 110 women (67 exposed to CHC) were drawn from the Pediatric Bone Mineral Accrual Study (PBMAS). Serial measures of total body (TB), lumbar spine (LS) and femoral neck (FN) BMC and aBMD were assessed by DXA (a total of 950 scans) and aligned by biological age (BA, years from peak height velocity [PHV]). Multilevel random effects models were constructed to assess the time dependent associations between annual CHC exposure and the development of bone parameters. After BA, height, lean tissue mass, fat mass, calcium and vitamin D intake, and physical activity were controlled, it was observed that those individuals exposed to CHC 6-years post PHV developed significantly less (-0.00986 ± 0.00422 g/cm 2 ) TB aBMD than their non CHC exposed peers. Additionally, there were significant BA by CHC exposure interactions, where CHC exposure 6-years or more post PHV resulted in developing less TB BMC (-4.94 ± 2.41 g), LS BMC (-0.29 ± 0.11 g) and LS aBMD (-0.00307 ± 0.00109 g/cm 2 ). One year after the attainment of PHV, CHC users were predicted to have 1.2% more TB BMC, 3.8% more LS BMC and 1.7% more LS aBMD than non-users. At 9-years post PHV the predicted differences showed that CHC users had 0.9% less TB BMC and 2.7% less LS BMC and 1.6% less LS BMD than those not exposed to CHC. CHC may not hinder the development of BMC or aBMD during adolescence; however, exposure 6-years or more after PHV may be detrimental.

The beneficial effects of aerobic and concurrent training on metabolic profile and body composition after detraining: a 1-year follow-up in postmenopausal women.

PubMed

Rossi, F E; Diniz, T A; Neves, L M; Fortaleza, A C S; Gerosa-Neto, J; Inoue, D S; Buonani, C; Cholewa, J M; Lira, F S; Freitas, I F

2017-05-01

Aerobic and concurrent training (CT, aerobic and strength training) improves body composition and metabolic profile; however, it is not known whether these positive outcomes acquired after aerobic or CT are maintained long term (⩾6 months) after program interruption in postmenopausal women. This study investigated the changes in total and appendicular body composition, bone mineral density and metabolic profile following 16 weeks of aerobic or CT, and through 6 months and 1 year of detraining in postmenopausal women. In total, 60 postmenopausal women were divided into the following groups: aerobic (AT), aerobic plus strength training (CT) and control group (CG), and 31 participants were assessed for the 1 year follow-up. Body composition and bone mineral density were evaluated by dual-energy X-ray absorptiometry (DXA), and total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triacylglycerol, glucose, insulin, leptin, adiponectin and plasminogen activator inhibitor-1 (PAI-1) were assessed. There were main effects of time for arm fat mass, arm lean mass and trunk lean mass (P<0.05). There was a statistical difference between AT and CG for leg fat mass and percentage of fat (P<0.05). After 6 months of detraining, leg lean mass decreased in relation to post-intervention, and there was a statistically significant interaction for total and appendicular lean mass (P<0.05). There were differences between CT and CG in glucose and between AT and CG in glucose and triacylglycerol (P<0.05). A duration of 16 weeks of aerobic or CT improved total and appendicular body composition and metabolic profile but after 6 months of detraining, leg lean mass returned to the values obtained pre-training in CT.

Drinking water fluoridation and bone.

PubMed

Allolio, B; Lehmann, R

1999-01-01

Drinking water fluoridation has an established role in the prevention of dental caries, but may also positively or negatively affect bone. In bone fluoride is incorporated into hydroxylapatite to form the less soluble fluoroapatite. In higher concentrations fluoride stimulates osteoblast activity leading to an increase in cancellous bone mass. As optimal drinking water fluoridation (1 mg/l) is widely used, it is of great interest, whether long-term exposition to artificial water fluoridation has any impact on bone strength, bone mass, and -- most importantly -- fracture rate. Animal studies suggest a biphasic pattern of the effect of drinking water fluoridation on bone strength with a peak strength at a bone fluoride content of 1200 ppm followed by a decline at higher concentrations eventually leading to impaired bone quality. These changes are not paralleled by changes in bone mass suggesting that fluoride concentrations remain below the threshold level required for activation of osteoblast activity. Accordingly, in most epidemiological studies in humans bone mass was not altered by optimal drinking water fluoridation. In contrast, studies on the effect on hip fracture rate gave conflicting results ranging from an increased fracture incidence to no effect, and to a decreased fracture rate. As only ecological studies have been performed, they may be biased by unknown confounding factors -- the so-called ecological fallacy. However, the combined results of these studies indicate that any increase or decrease in fracture rate is likely to be small. It has been calculated that appropriately designed cohort studies to solve the problem require a sample size of >400,000 subjects. Such studies will not be performed in the foreseeable future. Future investigations in humans should, therefore, concentrate on the effect of long-term drinking water fluoridation on bone fluoride content and bone strength.

Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

NASA Technical Reports Server (NTRS)

Halloran, B. P.; Bikle, D. D.; Harris, J.; Autry, C. P.; Currier, P. A.; Tanner, S.; Patterson-Buckendahl, P.; Morey-Holton, E.

1995-01-01

Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p < 0.002) of GH on periosteal bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.

Preservation and promotion of bone formation in the mandible as a response to a novel calcium-phosphate based biomaterial in mineral deficiency induced low bone mass male versus female rats

PubMed Central

Srinivasan, Kritika; Naula, Diana P.; Mijares, Dindo Q.; Janal, Malvin N.; LeGeros, Raquel Z.; Zhang, Yu

2016-01-01

Calcium and other trace mineral supplements have previously demonstrated to safely improve bone quality. We hypothesize that our novel calcium-phosphate based biomaterial (SBM) preserves and promotes mandibular bone formation in male and female rats on mineral deficient diet (MD). Sixty Sprague-Dawley rats were randomly assigned to receive one of three diets (n = 10): basic diet (BD), MD or mineral deficient diet with 2% SBM. Rats were sacrificed after 6 months. Micro-Computed Tomography (μCT) was used to evaluate bone volume and 3D-microarchitecture while microradiography (Faxitron) was used to measure bone mineral density from different sections of the mandible. Results showed that bone quality varied with region, gender and diet. MD reduced bone mineral density (BMD) and volume and increased porosity. SBM preserved BMD and bone mineral content (BMC) in the alveolar bone and condyle in both genders. In the alveolar crest and mandibular body, while preserving more bone in males, SBM also significantly supplemented female bone. Results indicate that mineral deficiency leads to low bone mass in skeletally immature rats, comparatively more in males. Furthermore, SBM administered as a dietary supplement was effective in preventing mandibular bone loss in all subjects. This study suggests that the SBM preparation has potential use in minimizing low peak bone mass induced by mineral deficiency and related bone loss irrespective of gender. PMID:26914814

Anorexia Nervosa and Bone

PubMed Central

Misra, Madhusmita; Klibanski, Anne

2014-01-01

Anorexia nervosa (AN) is a condition of severe low weight that is associated with low bone mass, impaired bone structure and reduced bone strength, all of which contribute to increased fracture risk., Adolescents with AN have decreased rates of bone accrual compared with normal-weight controls, raising addition concerns of suboptimal peak bone mass and future bone health in this age group. Changes in lean mass and compartmental fat depots, hormonal alterations secondary to nutritional factors contribute to impaired bone metabolism in AN. The best strategy to improve bone density is to regain weight and menstrual function. Oral estrogen-progesterone combinations are not effective in increasing bone density in adults or adolescents with AN, and transdermal testosterone replacement is not effective in increasing bone density in adult women with AN. However, physiologic estrogen replacement as transdermal estradiol with cyclic progesterone does increase bone accrual rates in adolescents with AN to approximate that in normal-weight controls, leading to a maintenance of bone density Z-scores. A recent study has shown that risedronate increases bone density at the spine and hip in adult women with AN. However, bisphosphonates should be used with great caution in women of reproductive age given their long half-life and potential for teratogenicity, and should be considered only in patients with low bone density and clinically significant fractures when non-pharmacological therapies for weight gain are ineffective. Further studies are necessary to determine the best therapeutic strategies for low bone density in AN. PMID:24898127

The Rho-GEF Kalirin regulates bone mass and the function of osteoblasts and osteoclasts.

PubMed

Huang, Su; Eleniste, Pierre P; Wayakanon, Kornchanok; Mandela, Prashant; Eipper, Betty A; Mains, Richard E; Allen, Matthew R; Bruzzaniti, Angela

2014-03-01

Bone homeostasis is maintained by the balance between bone resorption by osteoclasts and bone formation by osteoblasts. Dysregulation in the activity of the bone cells can lead to osteoporosis, a disease characterized by low bone mass and an increase in bone fragility and risk of fracture. Kalirin is a novel GTP-exchange factor protein that has been shown to play a role in cytoskeletal remodeling and dendritic spine formation in neurons. We examined Kalirin expression in skeletal tissue and found that it was expressed in osteoclasts and osteoblasts. Furthermore, micro-CT analyses of the distal femur of global Kalirin knockout (Kal-KO) mice revealed significantly reduced trabecular and cortical bone parameters in Kal-KO mice, compared to WT mice, with significantly reduced bone mass in 8, 14 and 36week-old female Kal-KO mice. Male mice also exhibited a decrease in bone parameters but not to the level seen in female mice. Histomorphometric analyses also revealed decreased bone formation rate in 14week-old female Kal-KO mice, as well as decreased osteoblast number/bone surface and increased osteoclast surface/bone surface. Consistent with our in vivo findings, the bone resorbing activity and differentiation of Kal-KO osteoclasts was increased in vitro. Although alkaline phosphatase activity by Kal-KO osteoblasts was increased in vitro, Kal-KO osteoblasts showed decreased mineralizing activity, as well as decreased secretion of OPG, which was inversely correlated with ERK activity. Taken together, our findings suggest that deletion of Kalirin directly affects osteoclast and osteoblast activity, leading to decreased OPG secretion by osteoblasts which is likely to alter the RANKL/OPG ratio and promote osteoclastogenesis. Therefore, Kalirin may play a role in paracrine and/or endocrine signaling events that control skeletal bone remodeling and the maintenance of bone mass. Copyright © 2013 Elsevier Inc. All rights reserved.

Early life vitamin D depletion alters the postnatal response to skeletal loading in growing and mature bone

PubMed Central

Buckley, Harriet; Owen, Robert; Marin, Ana Campos; Lu, Yongtau; Eyles, Darryl; Lacroix, Damien; Reilly, Gwendolen C.; Skerry, Tim M.; Bishop, Nick J.

2018-01-01

There is increasing evidence of persistent effects of early life vitamin D exposure on later skeletal health; linking low levels in early life to smaller bone size in childhood as well as increased fracture risk later in adulthood, independently of later vitamin D status. A major determinant of bone mass acquisition across all ages is mechanical loading. We tested the hypothesis in an animal model system that early life vitamin D depletion results in abrogation of the response to mechanical loading, with consequent reduction in bone size, mass and strength during both childhood and adulthood. A murine model was created in which pregnant dams were either vitamin D deficient or replete, and their offspring moved to a vitamin D replete diet at weaning. Tibias of the offspring were mechanically loaded and bone structure, extrinsic strength and growth measured both during growth and after skeletal maturity. Offspring of vitamin D deplete mice demonstrated lower bone mass in the non loaded limb and reduced bone mass accrual in response to loading in both the growing skeleton and after skeletal maturity. Early life vitamin D depletion led to reduced bone strength and altered bone biomechanical properties. These findings suggest early life vitamin D status may, in part, determine the propensity to osteoporosis and fracture that blights later life in many individuals. PMID:29370213

Natural Ca Isotope Composition of Urine as a Rapid Measure of Bone Mineral Balance

NASA Astrophysics Data System (ADS)

Skulan, J.; Gordon, G. W.; Morgan, J.; Romaniello, S. J.; Smith, S. M.; Anbar, A. D.

2011-12-01

Naturally occurring stable Ca isotope variations in urine are emerging as a powerful tool to detect changes in bone mineral balance. Bone formation depletes soft tissue of light Ca isotopes while bone resorption releases isotopically light Ca into soft tissue. Previously published work found that variations in Ca isotope composition could be detected at 4 weeks of bed rest in a 90-day bed rest study (data collected at 4, 8 and 12 weeks). A new 30-day bed rest study involved 12 patients on a controlled diet, monitored for 7 days prior to bed rest and 7 days post bed rest. Samples of urine, blood and food were collected throughout the study. Four times daily blood samples and per void urine samples were collected to monitor diurnal or high frequency variations. An improved chemical purification protocol, followed by measurement using multiple collector inductively coupled plasma mass spectrometry (MC-ICP-MS) allowed accurate and precise determinations of mass-dependent Ca isotope variations in these biological samples to better than ±0.2% (δ44/42Ca) on <25 μg of Ca. Results from this new study show that Ca isotope ratios shift in a direction consistent with net bone loss after just 7 days, long before detectible changes in bone density by X-ray measurements occur. Consistent with this interpretation, the Ca isotope variations track changes observed in N-teleopeptide, a bone resorption biomarker. Bone-specific alkaline phosphatase, a bone formation biomarker, is unchanged over this period. Ca isotopes can in principle be used to quantify net changes in bone mass. Using a mass-balance model, our results indicate an average loss of 0.62 ± 0.16 % in bone mass over the course of this 30-day study. This is consistent with the rate of bone loss in longer-term studies as seen by X-ray measurements. This Ca isotope technique should accelerate the pace of discovery of new treatments for bone disease and provide novel insights into the dynamics of bone metabolism.

Treatment with soluble activin type IIB-receptor improves bone mass and strength in a mouse model of Duchenne muscular dystrophy.

PubMed

Puolakkainen, Tero; Ma, Hongqian; Kainulainen, Heikki; Pasternack, Arja; Rantalainen, Timo; Ritvos, Olli; Heikinheimo, Kristiina; Hulmi, Juha J; Kiviranta, Riku

2017-01-19

Inhibition of activin/myostatin pathway has emerged as a novel approach to increase muscle mass and bone strength. Duchenne muscular dystrophy (DMD) is a neuromuscular disorder that leads to progressive muscle degeneration and also high incidence of fractures. The aim of our study was to test whether inhibition of activin receptor IIB ligands with or without exercise could improve bone strength in the mdx mouse model for DMD. Thirty-two mdx mice were divided to running and non-running groups and to receive either PBS control or soluble activin type IIB-receptor (ActRIIB-Fc) once weekly for 7 weeks. Treatment of mdx mice with ActRIIB-Fc resulted in significantly increased body and muscle weights in both sedentary and exercising mice. Femoral μCT analysis showed increased bone volume and trabecular number (BV/TV +80%, Tb.N +70%, P < 0.05) in both ActRIIB-Fc treated groups. Running also resulted in increased bone volume and trabecular number in PBS-treated mice. However, there was no significant difference in trabecular bone structure or volumetric bone mineral density between the ActRIIB-Fc and ActRIIB-Fc-R indicating that running did not further improve bone structure in ActRIIB-Fc-treated mice. ActRIIB-Fc increased bone mass also in vertebrae (BV/TV +20%, Tb.N +30%, P < 0.05) but the effects were more modest. The number of osteoclasts was decreased in histological analysis and the expression of several osteoblast marker genes was increased in ActRIIB-Fc treated mice suggesting decreased bone resorption and increased bone formation in these mice. Increased bone mass in femurs translated into enhanced bone strength in biomechanical testing as the maximum force and stiffness were significantly elevated in ActRIIB-Fc-treated mice. Our results indicate that treatment of mdx mice with the soluble ActRIIB-Fc results in a robust increase in bone mass, without any additive effect by voluntary running. Thus ActRIIB-Fc could be an attractive option in the treatment of musculoskeletal disorders.

Sost deficiency does not alter bone's lacunar or vascular porosity in mice

NASA Astrophysics Data System (ADS)

Mosey, Henry; Núñez, Juan A.; Goring, Alice; Clarkin, Claire E.; Staines, Katherine A.; Lee, Peter D.; Pitsillides, Andrew A.; Javaheri, Behzad

2017-09-01

SCLEROSTIN (Sost) is expressed predominantly in osteocytes acting as a negative regulator of bone formation. In humans, mutations in the SOST gene lead to skeletal overgrowth and increased bone mineral density, suggesting that SCLEROSTIN is a key regulator of bone mass. The function of SCLEROSTIN as an inhibitor of bone formation is further supported by Sost knockout (KO) mice which display a high bone mass with elevated bone formation. Previous studies have indicated that Sost exerts its effect on bone formation through Wnt-mediated regulation of osteoblast differentiation, proliferation and activity. Recent in vitro studies have also suggested that SCLEROSTIN regulates angiogenesis and osteoblast-to-osteocyte transition. Despite this wealth of knowledge of the mechanisms responsible for SCLEROSTIN action, no previous studies have examined whether SCLEROSTIN regulates osteocyte and vascular configuration in cortices of mouse tibia. Herein, we image tibiae from Sost KO mice and their wild-type (WT) counterparts with high resolution CT to examine whether lack of SCLEROSTIN influences the morphometric properties of lacunae and vascular canal porosity relating to osteocytes and vessels within cortical bone. Male Sost KO and WT mice (n = 6 /group) were sacrificed at 12 weeks of age. Fixed tibiae were analysed using microCT to examine cortical bone mass and architecture. Then, samples were imaged by using benchtop and synchrotron nanoCT at the tibiofibular junction. Our data, consistent with previous studies show that, Sost deficiency leads to significant enhancement of bone mass by cortical thickening and bigger cross-sectional area and we find that this occurs without modifications of tibial ellipticity, a measure of bone shape. In addition, our data show that there are no significant differences in any lacunar or vascular morphometric or geometric parameters between Sost KO mouse tibia and WT counterparts. We therefore conclude that the significant increases in bone mass induced by Sost deficiency are not accompanied by any significant modification in the density, organisation or shape of osteocyte lacunae or vascular content within the cortical bone. These data may imply that SCLEROSTIN does not modify the frequency of osteocytogenic recruitment of osteoblasts to initiate terminal osteocytic differentiation in mice.

The role of estrogen and androgen receptors in bone health and disease

PubMed Central

2014-01-01

Mouse models with cell-specific deletion of the estrogen receptor (ER) α, the androgen receptor (AR) or the receptor activator of nuclear factor κB ligand (RANKL), as well as cascade-selective estrogenic compounds have provided novel insights into the function and signalling of ERα and AR. The studies reveal that the effects of estrogens on trabecular versus cortical bone mass are mediated by direct effects on osteoclasts and osteoblasts, respectively. The protection of cortical bone mass by estrogens is mediated via ERα, using a non-nucleus-initiated mechanism. By contrast, the AR of mature osteoblasts is indispensable for the maintenance of trabecular bone mass in male mammals, but not required for the anabolic effects of androgens on cortical bone. Most unexpectedly, and independently of estrogens, ERα in osteoblast progenitors stimulates Wnt signalling and periosteal bone accrual in response to mechanical strain. RANKL expression in B lymphocytes, but not T lymphocytes, contributes to the loss of trabecular bone caused by estrogen deficiency. In this Review, we summarize this evidence and discuss its implications for understanding the regulation of trabecular and cortical bone mass; the integration of hormonal and mechanical signals; the relative importance of estrogens versus androgens in the male skeleton; and, finally, the pathogenesis and treatment of osteoporosis. PMID:24042328

DYSAPOPTOSIS OF OSTEOBLASTS AND OSTEOCYTES INCREASES CANCELLOUS BONE FORMATION BUT EXAGGERATES BONE POROSITY WITH AGE

PubMed Central

Jilka, Robert L.; O’Brien, Charles A.; Roberson, Paula K.; Bonewald, Lynda F.; Weinstein, Robert S.; Manolagas, Stavros C.

2013-01-01

Skeletal aging is accompanied by decreased cancellous bone mass and increased formation of pores within cortical bone. The latter accounts for a large portion of the increase in non-vertebral fractures after age 65 in humans. We selectively deleted Bak and Bax, two genes essential for apoptosis, in two types of terminally differentiated bone cells: the short-lived osteoblasts that elaborate the bone matrix, and the long-lived osteocytes that are immured within the mineralized matrix and choreograph the regeneration of bone. Attenuation of apoptosis in osteoblasts increased their working lifespan and thereby cancellous bone mass in the femur. In long-lived osteocytes, however, it caused dysfunction with advancing age and greatly magnified intracortical femoral porosity associated with increased production of receptor activator of nuclear factor-κB ligand and vascular endothelial growth factor. Increasing bone mass by artificial prolongation of the inherent lifespan of short-lived osteoblasts, while exaggerating the adverse effects of aging on long-lived osteocytes, highlights the seminal role of cell age in bone homeostasis. In addition, our findings suggest that distress signals produced by old and/or dysfunctional osteocytes are the culprits of the increased intracortical porosity in old age. PMID:23761243

Correlation between bone mineral density and serum trace elements in response to supervised aerobic training in older adults.

PubMed

Alghadir, Ahmad H; Gabr, Sami A; Al-Eisa, Einas S; Alghadir, Muaz H

2016-01-01

Life style and physical activity play a pivotal role in prevention and treatment of osteoporosis. The mechanism for better bone metabolism and improvement of physical disorders is not clear yet. Trace minerals such as Ca, Mn, Cu, and Zn are essential precursors for most vital biological process, especially those of bone health. The main target of this study was evaluating the effective role of supervised aerobic exercise for 1 hour/day, 3 days/week for 12 weeks in the functions of trace elements in bone health through measuring bone mineral density (BMD), osteoporosis (T-score), bone markers, and trace element concentrations in healthy subjects aged 30-60 years with age average of 41.2±4.9. A total of 100 healthy subjects (47 males, 53 females; age range 30-60 years) were recruited for this study. Based on dual-energy x-ray absorptiometry (DEXA) scan analysis, the participants were classified into three groups: normal (n=30), osteopenic (n=40), and osteoporotic (n=30). Following, 12 weeks of moderate aerobic exercise, bone-specific alkaline phosphatase (BAP), BMD, T-score, and trace elements such as Ca, Mn, Cu, and Zn were assessed at baseline and post-intervention. Significant improvement in serum BAP level, T-score, and BMD were observed in all participants following 12 weeks of moderate exercise. Participants with osteopenia and osteoporosis showed significant increase in serum Ca and Mn, along with decrease in serum Cu and Zn levels following 12 weeks of aerobic training. In control group, the improvements in serum trace elements and body mass index were significantly linked with the enhancement in the levels of BAP, BMD hip, and BMD spine. These results supported the preventive effects of moderate exercise in healthy subjects against osteoporosis. In both sexes, the changes in serum trace elements significantly correlated (P<0.05) with the improvement in BAP, BMD hip, BMD spine, and body mass index in all groups. The observed changes in the levels of Ca, Mn, Cu, and Zn were shown to be positively correlated with improved bone mass density among control and osteoporosis subjects of both sexes. These results demonstrate that aerobic exercise of moderate intensity might protect bone and cartilage by regulation of body trace elements which are involved in the biosynthesis of bone matrix structures and inhibition of bone resorption process via a proposed anti-free radical mechanism.

High Dietary Protein Intake and Protein-Related Acid Load on Bone Health.

PubMed

Cao, Jay J

2017-12-01

Consumption of high-protein diets is increasingly popular due to the benefits of protein on preserving lean mass and controlling appetite and satiety. The paper is to review recent clinical research assessing dietary protein on calcium metabolism and bone health. Epidemiological studies show that long-term, high-protein intake is positively associated with bone mineral density and reduced risk of bone fracture incidence. Short-term interventional studies demonstrate that a high-protein diet does not negatively affect calcium homeostasis. Existing evidence supports that the negative effects of the acid load of protein on urinary calcium excretion are offset by the beneficial skeletal effects of high-protein intake. Future research should focus on the role and the degree of contribution of other dietary and physiological factors, such as intake of fruits and vegetables, in reducing the acid load and further enhancing the anabolic effects of protein on the musculoskeletal system.

A prospective study of change in bone mass with age in postmenopausal women.

PubMed

Hui, S L; Wiske, P S; Norton, J A; Johnston, C C

1982-01-01

For the first time a model for age-related bone loss has been developed from prospective data utilizing a new weighted least squares method. Two hundred and sixty-eight Caucasian women ranging in age from 50 to 95 were studied. A quadratic function best fit the data, and correcting for body weight and bone width reduced variance. The derived equation is: bone mass = (0.6032) (bone width) (cm) + (0.003059) (body weight) (kg) - (0.0163) (age - 50) + (0.0002249) (age - 50)2. Analysis of cross-sectional data on 583 Caucasian women of similar age showed a quadratic function with very similar coefficients. This quadratic function predicts an increase in bone mass after age 86, therefore 42 women over age 70 who had been followed for at least 2.5 yr were identified to test for this effect. of these, 13 had significantly positive regression coefficients of bone mass on age, and rate of change in bone width was positive in 40 of 42 individuals, of which 5 were significant. Since photon absorptiometry measures net changes on all bone envelopes, the most likely explanation for the observed changes is an early exponential loss of endosteal bone which ultimately slows or perhaps stops. There is a positive balance on the periosteal envelope which only becomes apparent in later years when the endosteal loss stops. These new statistical methods allow the development of models utilizing data collected at irregular intervals. The methods used are applicable to other biological data collected prospectively.

Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation

PubMed Central

McGee-Lawrence, Meghan; Buckendahl, Patricia; Carpenter, Caren; Henriksen, Kim; Vaughan, Michael; Donahue, Seth

2015-01-01

ABSTRACT Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6 months annually during hibernation without losing cortical or trabecular bone mass. Bears have been shown to preserve trabecular bone volume and architectural parameters and cortical bone strength, porosity and geometrical properties during hibernation. The mechanisms that prevent disuse osteoporosis in bears are unclear as previous studies using histological and serum markers of bone remodeling show conflicting results. However, previous studies used serum markers of bone remodeling that are known to accumulate with decreased renal function, which bears have during hibernation. Therefore, we measured serum bone remodeling markers (BSALP and TRACP) that do not accumulate with decreased renal function, in addition to the concentrations of serum calcium and hormones involved in regulating bone remodeling in hibernating and active bears. Bone resorption and formation markers were decreased during hibernation compared with when bears were physically active, and these findings were supported by histomorphometric analyses of bone biopsies. The serum concentration of cocaine and amphetamine regulated transcript (CART), a hormone known to reduce bone resorption, was 15-fold higher during hibernation. Serum calcium concentration was unchanged between hibernation and non-hibernation seasons. Suppressed and balanced bone resorption and formation in hibernating bears contributes to energy conservation, eucalcemia and the preservation of bone mass and strength, allowing bears to survive prolonged periods of extreme environmental conditions, nutritional deprivation and anuria. PMID:26157160

Inhibiting the osteocyte-specific protein sclerostin increases bone mass and fracture resistance in multiple myeloma

PubMed Central

Mohanty, Sindhu T.; Seckinger, Anja; Terry, Rachael L.; Pettitt, Jessica A.; Simic, Marija K.; Le, Lawrence M. T.; Kramer, Ina; Falank, Carolyne; Fairfield, Heather; Ghobrial, Irene M.; Baldock, Paul A.; Little, David G.; Kneissel, Michaela; Vanderkerken, Karin; Bassett, J. H. Duncan; Williams, Graham R.; Oyajobi, Babatunde O.; Hose, Dirk

2017-01-01

Multiple myeloma (MM) is a plasma cell cancer that develops in the skeleton causing profound bone destruction and fractures. The bone disease is mediated by increased osteoclastic bone resorption and suppressed bone formation. Bisphosphonates used for treatment inhibit bone resorption and prevent bone loss but fail to influence bone formation and do not replace lost bone, so patients continue to fracture. Stimulating bone formation to increase bone mass and fracture resistance is a priority; however, targeting tumor-derived modulators of bone formation has had limited success. Sclerostin is an osteocyte-specific Wnt antagonist that inhibits bone formation. We hypothesized that inhibiting sclerostin would prevent development of bone disease and increase resistance to fracture in MM. Sclerostin was expressed in osteocytes from bones from naive and myeloma-bearing mice. In contrast, sclerostin was not expressed by plasma cells from 630 patients with myeloma or 54 myeloma cell lines. Mice injected with 5TGM1-eGFP, 5T2MM, or MM1.S myeloma cells demonstrated significant bone loss, which was associated with a decrease in fracture resistance in the vertebrae. Treatment with anti-sclerostin antibody increased osteoblast numbers and bone formation rate but did not inhibit bone resorption or reduce tumor burden. Treatment with anti-sclerostin antibody prevented myeloma-induced bone loss, reduced osteolytic bone lesions, and increased fracture resistance. Treatment with anti-sclerostin antibody and zoledronic acid combined increased bone mass and fracture resistance when compared with treatment with zoledronic acid alone. This study defines a therapeutic strategy superior to the current standard of care that will reduce fractures for patients with MM. PMID:28515094

Myostatin--the holy grail for muscle, bone, and fat?

PubMed

Buehring, B; Binkley, N

2013-12-01

Myostatin, a member of the transforming growth factor beta (TGF-β) superfamily, was first described in 1997. Since then, myostatin has gained growing attention because of the discovery that myostatin inhibition leads to muscle mass accrual. Myostatin not only plays a key role in muscle homeostasis, but also affects fat and bone. This review will focus on the impact of myostatin and its inhibition on muscle mass/function, adipose tissue and bone density/geometry in humans. Although existing data are sparse, myostatin inhibition leads to increased lean mass and 1 study found a decrease in fat mass and increase in bone formation. In addition, myostatin levels are increased in sarcopenia, cachexia and bed rest whereas they are increased after resistance training, suggesting physiological regulatory of myostatin. Increased myostatin levels have also been found in obesity and levels decrease after weight loss from caloric restriction. Knowledge on the relationship of myostatin with bone is largely based on animal data where elevated myostatin levels lead to decreased BMD and myostatin inhibition improved BMD. In summary, myostatin appears to be a key factor in the integrated physiology of muscle, fat, and bone. It is unclear whether myostatin directly affects fat and bone, or indirectly via muscle. Whether via direct or indirect effects, myostatin inhibition appears to increase muscle and bone mass and decrease fat tissue-a combination that truly appears to be a holy grail. However, at this time, human data for both efficacy and safety are extremely limited. Moreover, whether increased muscle mass also leads to improved function remains to be determined. Ultimately potential beneficial effects of myostatin inhibition will need to be determined based on hard outcomes such as falls and fractures.

Association of magnetic resonance imaging findings and histologic diagnosis in dogs with nasal disease: 78 cases (2001-2004).

PubMed

Miles, Macon S; Dhaliwal, Ravinder S; Moore, Michael P; Reed, Ann L

2008-06-15

OBJECTIVE-To determine whether magnetic resonance imaging (MRI) features correlated with histologic diagnosis in dogs with nasal disease. DESIGN-Retrospective case series. ANIMALS-78 Dogs undergoing MRI for evaluation of nasal disease. PROCEDURES-Medical records and MRI reports of dogs were reviewed to identify MRI features associated with histologic diagnosis. Features evaluated were presence of a mass effect, frontal sinus involvement, sphenoid sinus involvement, maxillary recess involvement, nasopharyngeal infiltration by soft tissue, nasal turbinate destruction, vomer bone lysis, paranasal bone destruction, cribriform plate erosion, and lesion extent (ie, unilateral vs bilateral). RESULTS-33 Dogs had neoplastic disease, 38 had inflammatory rhinitis, and 7 had fungal rhinitis. Lesion extent was not significantly associated with histologic diagnosis. Absence of a mass effect was significantly associated with inflammatory disease. However, presence of a mass was not specific for neoplasia. In dogs with evidence of a mass on magnetic resonance (MR) images, nasal turbinate destruction, frontal sinus invasion, and maxillary recess invasion were not useful in distinguishing neoplastic from nonneoplastic disease, but cribriform plate erosion, vomer bone lysis, paranasal bone destruction, sphenoid sinus invasion, and nasopharyngeal invasion were. CONCLUSIONS AND CLINICAL RELEVANCE-Results suggested that in dogs with nasal disease, the lack of a mass effect on MR images was significantly associated with inflammatory disease. In dogs with a mass effect on MR images, vomer bone lysis, cribriform plate erosion, paranasal bone destruction, sphenoid sinus invasion by a mass, and nasopharyngeal invasion by a mass were significantly associated with a diagnosis of neoplasia.

Rapidly growing Brtl/+ mouse model of osteogenesis imperfecta improves bone mass and strength with sclerostin antibody treatment.

PubMed

Sinder, Benjamin P; Salemi, Joseph D; Ominsky, Michael S; Caird, Michelle S; Marini, Joan C; Kozloff, Kenneth M

2015-02-01

Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk that presents most severely in children. Anti-resorptive bisphosphonates are frequently used to treat pediatric OI and controlled clinical trials have shown that bisphosphonate therapy improves vertebral outcomes but has little benefit on long bone fracture rate. New treatments which increase bone mass throughout the pediatric OI skeleton would be beneficial. Sclerostin antibody (Scl-Ab) is a potential candidate anabolic therapy for pediatric OI and functions by stimulating osteoblastic bone formation via the canonical Wnt signaling pathway. To explore the effect of Scl-Ab on the rapidly growing OI skeleton, we treated rapidly growing 3week old Brtl/+ mice, harboring a typical heterozygous OI-causing Gly→Cys substitution on col1a1, for 5weeks with Scl-Ab. Scl-Ab had anabolic effects in Brtl/+ and led to new cortical bone formation and increased cortical bone mass. This anabolic action resulted in improved mechanical strength to WT Veh levels without altering the underlying brittle nature of the material. While Scl-Ab was anabolic in trabecular bone of the distal femur in both genotypes, the effect was less strong in these rapidly growing Brtl/+ mice compared to WT. In conclusion, Scl-Ab was able to stimulate bone formation in a rapidly growing Brtl/+ murine model of OI, and represents a potential new therapy to improve bone mass and reduce fracture risk in pediatric OI. Copyright © 2014 Elsevier Inc. All rights reserved.

Preventing and Treating Brittle Bones and Osteoporosis | NIH MedlinePlus the Magazine

MedlinePlus

... Javascript on. Feature: Osteoporosis Preventing and Treating Brittle Bones and Osteoporosis Past Issues / Winter 2011 Table of ... at high risk due to low bone mass. Bone and Bone Loss Bone is living, growing tissue. ...

BMP-2-regenerated calvarial bone: a biomechanical appraisal in a large animal model.

PubMed

Cray, James; Henderson, Sarah E; Smith, Darren M; Kinsella, Christopher R; Bykowski, Michael; Cooper, Gregory M; Almarza, Alejandro J; Losee, Joseph E

2014-11-01

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is gaining popularity in craniofacial applications. Calvarial defects are, under normal circumstances, subjected to only minimal levels of the biomechanical stresses known to play an important role in osteogenesis, yet regenerated calvarial bone must be capable of withstanding traumatic forces such that the underlying neurocapsule is protected. The aim of this study is to, for the first time, assess the biomechanical properties of calvarial bone regenerated with derivations of a commercially available rhBMP-2-based system. Standardized calvarial defects were created in 23 adult male canines. These defects were treated with rhBMP-2 on one of several carriers. After 24 weeks, the biomechanical properties of the rhBMP-2-generated bone were compared to those of controls with a modified punch-out test (Bluehill 2; Instron, Norwood, Mass) and compared using a paired nonparametric analyses (SPSS, 17.0, Chicago, Ill). In a previously published report, defects across all the rhBMP-2 therapy groups were observed to have a mean rate of 99.5% radio-opacity at 24 weeks indicating nearly full bony coverage of the calvarial defect (compared to 32.7% in surgical controls). For ultimate load, ultimate energy, and first peak energy, there were significant differences (P<0.05) with the control native bone having more robust biomechanical properties than the rhBMP-2-generated bone. We conclude from these findings that rhBMP-2-generated calvarial bone is significantly less protective against trauma than native bone at 6 months. Further investigation is required to assess the efficacy of rhBMP-2 in healing calvarial defects in the longer term.

Bone Microarchitecture Is Impaired in Adolescent Amenorrheic Athletes Compared with Eumenorrheic Athletes and Nonathletic Controls

PubMed Central

Ackerman, Kathryn E.; Nazem, Taraneh; Chapko, Dorota; Russell, Melissa; Mendes, Nara; Taylor, Alexander P.; Bouxsein, Mary L.

2011-01-01

Context: Bone mineral density (BMD) is lower in young amenorrheic athletes (AA) compared to eumenorrheic athletes (EA) and nonathletic controls and may contribute to fracture risk during a critical time of bone accrual. Abnormal bone microarchitecture is an independent determinant of fracture risk and has not been assessed in young athletes and nonathletes. Objective: We hypothesized that bone microarchitecture is impaired in AA compared to EA and nonathletes despite weight-bearing exercise. Design and Setting: We conducted this cross-sectional study at the Clinical Research Center of Massachusetts General Hospital. Subjects and Outcome Measures: We assessed BMD and bone microarchitecture in 50 subjects [16 AA, 18 EA, and 16 nonathletes (15–21 yr old)] using dual-energy x-ray absorptiometry and high-resolution peripheral quantitative computed tomography. Results: Groups did not differ for chronological age, bone age, body mass index, or vitamin D levels. Lumbar BMD Z-scores were lower in AA vs. EA and nonathletes; hip and femoral neck BMD Z-scores were highest in EA. At the weight-bearing tibia, athletes had greater total area, trabecular area, and cortical perimeter than nonathletes, whereas cortical area and thickness trended lower in AA. Trabecular number was lower and trabecular separation higher in AA vs. EA and nonathletes. At the non-weight-bearing radius, trabecular density was lower in AA vs. EA and nonathletes. Later menarchal age was an important determinant of impaired microarchitecture. After controlling for covariates, subject grouping accounted for 18–24% of the variability in tibial trabecular number and separation. Conclusion: In addition to low BMD, AA have impaired bone microarchitecture compared with EA and nonathletes. These are the first data to show abnormal bone microarchitecture in AA. PMID:21816790

Effects of the peroxisome proliferator-activated receptor (PPAR)-δ agonist GW501516 on bone and muscle in ovariectomized rats.

PubMed

Mosti, M P; Stunes, A K; Ericsson, M; Pullisaar, H; Reseland, J E; Shabestari, M; Eriksen, E F; Syversen, U

2014-06-01

Estrogen deficiency promotes bone loss and skeletal muscle dysfunction. Peroxisome proliferator-activated receptors (PPARs) have 3 subtypes (α, δ, and γ). PPARγ agonists induce bone loss, whereas PPARα agonists increase bone mass. Although PPARδ agonists are known to influence skeletal muscle metabolism, the skeletal effects are unsettled. This study investigated the musculoskeletal effects of the PPARδ agonist GW501516 in ovariectomized (OVX) rats. Female Sprague Dawley rats, 12 weeks of age, were allocated to a sham-operated group and 3 OVX groups; high-dose GW501516 (OVX-GW5), low-dose GW501516 (OVX-GW1), and a control group (OVX-CTR), respectively (n = 12 per group). Animals received GW501516 or vehicle (methylcellulose) daily for 4 months by gavage. Bone mineral density (BMD) was assessed by dual x-ray absorptiometry at the femur, spine, and whole body. Bone microarchitecture at the proximal tibia was assessed by microcomputed tomography, and dynamic histomorphometry was performed. Quadriceps muscle morphology and the relative expression of mitochondrial proteins were analyzed. Bone metabolism markers and metabolic markers were measured in plasma. After 4 months, the OVX-GW5 group displayed lower femoral BMD than OVX-CTR. Trabecular separation was higher in the GW-treated groups, compared with OVX-CTR. The OVX-GW5 group also exhibited lower cortical area fraction and a higher structure model index than OVX-CTR. These effects coincided with impaired bone formation in both GW groups. The OVX-GW5 group displayed elevated triglyceride levels and reduced adiponectin levels, whereas no effects on muscle morphology or mitochondrial gene expression appeared. In summary, the PPARδ agonist GW501516 negatively affected bone properties in OVX rats, whereas no effects were detected in skeletal muscle.

Cortical bone deficit and fat infiltration of bone marrow and skeletal muscle in ambulatory children with mild spastic cerebral palsy.

PubMed

Whitney, Daniel G; Singh, Harshvardhan; Miller, Freeman; Barbe, Mary F; Slade, Jill M; Pohlig, Ryan T; Modlesky, Christopher M

2017-01-01

Nonambulatory children with severe cerebral palsy (CP) have underdeveloped bone architecture, low bone strength and a high degree of fat infiltration in the lower extremity musculature. The present study aims to determine if such a profile exists in ambulatory children with mild CP and if excess fat infiltration extends into the bone marrow. Ambulatory children with mild spastic CP and typically developing children (4 to 11years; 12/group) were compared. Magnetic resonance imaging was used to estimate cortical bone, bone marrow and total bone volume and width, bone strength [i.e., section modulus (Z) and polar moment of inertia (J)], and bone marrow fat concentration in the midtibia, and muscle volume, intermuscular, subfascial, and subcutaneous adipose tissue (AT) volume and intramuscular fat concentration in the midleg. Accelerometer-based activity monitors worn on the ankle were used to assess physical activity. There were no group differences in age, height, body mass, body mass percentile, BMI, BMI percentile or tibia length, but children with CP had lower height percentile (19th vs. 50th percentile) and total physical activity counts (44%) than controls (both p<0.05). Children with CP also had lower cortical bone volume (30%), cortical bone width in the posterior (16%) and medial (32%) portions of the shaft, total bone width in the medial-lateral direction (15%), Z in the medial-lateral direction (34%), J (39%) and muscle volume (39%), and higher bone marrow fat concentration (82.1±1.8% vs. 80.5±1.9%), subfascial AT volume (3.3 fold) and intramuscular fat concentration (25.0±8.0% vs. 16.1±3.3%) than controls (all p<0.05). When tibia length was statistically controlled, all group differences in bone architecture, bone strength, muscle volume and fat infiltration estimates, except posterior cortical bone width, were still present (all p<0.05). Furthermore, a higher intermuscular AT volume in children with CP compared to controls emerged (p<0.05). Ambulatory children with mild spastic CP exhibit an underdeveloped bone architecture and low bone strength in the midtibia and a greater infiltration of fat in the bone marrow and surrounding musculature compared to typically developing children. Whether the deficit in the musculoskeletal system of children with CP is associated with higher chronic disease risk and whether the deficit can be mitigated requires further investigation. Copyright © 2016 Elsevier Inc. All rights reserved.

Age dependent regulation of bone-mass and renal function by the MEPE ASARM-motif

PubMed Central

Zelenchuk, Lesya V; Hedge, Anne-Marie; Rowe, Peter S N

2015-01-01

Context Mice with null mutations in Matrix Extracellular Phosphoglycoprotein (MEPE) have increased bone mass, increased trabecular density and abnormal cancellous bone (MN-mice). These defects worsen with age and MEPE over expression induces opposite effects. Also, Genome Wide Association studies show MEPE plays a major role in bone mass. We hypothesized the conserved C-terminal MEPE ASARM-motif is chiefly responsible for regulating bone mass and trabecular structure. Design To test our theory we over expressed C-terminal ASARM-peptide in MN-mice using the Col1α1 promoter (MNAt-mice). We then compared the bone and renal phenotypes of the MNAt-mouse with the MN-mouse and the X-linked hypophosphatemic rickets mouse (HYP). The HYP mouse over expresses ASARM-peptides and is defective for the PHEX gene. Results The MN-mouse developed increased bone mass, bone strength and trabecular abnormalities that worsened markedly with age. Defects in bone formation were chiefly responsible with suppressed sclerostin and increased active β-catenin. Increased uric acid levels also suggested abnormalities in purine-metabolism and a reduced fractional excretion of uric acid signaled additional renal transport changes. The MN mouse developed a worsening hyperphosphatemia and reduced FGF23 with age. An increase in the fractional excretion of phosphate (FEP) despite the hyperphosphatemia confirms an imbalance in kidney-intestinal phosphate regulation. Also, the MN mice showed an increased creatinine clearance suggesting hyperfiltration. A reversal of the MN bone-renal phenotype changes occurred with the MNAt mice including the apparent hyperfiltration. The MNAt mice also developed localized hypomineralization, hypophosphatemia and increased FGF23. Conclusions The C-terminal ASARM-motif plays a major role in regulating bone–mass and cancellous structure as mice age. In healthy mice, the processing and release of free ASARM-peptide is chiefly responsible for preserving normal bone and renal function. Free ASARM-peptide also effects renal mineral phosphate handling by influencing FGF23 expression. These findings have implications for understanding age-dependent osteoporosis, unraveling drug-targets and developing treatments. PMID:26051469

Abnormal distal renal tubular acidification in patients with low bone mass: prevalence and impact of alkali treatment.

PubMed

Sromicki, Jerzy Jan; Hess, Bernhard

2017-06-01

Chronic acid retention is known to promote bone dissolution. In this study, 23 % of patients with osteopenia/osteoporosis were diagnosed with abnormal distal renal tubular acidification (dRTA), a kidney dysfunction leading to chronic acid retention. Treating those patients with alkali-therapy shows improvement in bone density. To evaluate the prevalence of abnormal distal renal tubular acidification in patients with low bone mass (LBM) and the impact of additional alkali treatment on bone density in patients with concomitant LBM and dRTA,183 patients referred for metabolic evaluation of densitometrically proven low bone mass were screened for abnormal distal renal tubular acidification between 2006 and 2013. In all LBM urine pH (U-pH) was measured in the 2nd morning urines after 12 h of fasting. If U-pH was ≥5.80, LBM underwent a 1-day ammonium chloride loading, and U-pH was remeasured the next morning. If U-pH after acid loading did not drop below 5.45, patients were diagnosed with abnormal distal renal tubular acidification. Normal values were obtained from 21 healthy controls. All LBM with dRTA were recommended alkali citrate in addition to conventional therapy of LBM, and follow-up DXAs were obtained until 2014. 85 LBM underwent NH 4 Cl loading. 42 LBM patients were diagnosed with incomplete dRTA (idRTA; prevalence 23.0 %). During follow-up (1.6-8 years) of idRTA-LBM patients, subjects adhering to alkali treatment tended to improve BMD at all sites measured, whereas BMD of non-adherent idRTA patients worsened/remained unchanged. (1) About one out of four patients with osteopenia/osteoporosis has idRTA. (2) Upon NH 4 Cl loading, idRTA patients do not lower urine pH normally, but show signs of increased acid-buffering by bone dissolution. (3) In idRTA patients with low bone mass on conventional therapy, additional long-term alkali treatment improves bone mass at lumbar spine and potentially at other bone sites. (4) All patients with low bone mass undergoing metabolic evaluation should be screened for idRTA.

Factors associated with bone turnover and speed of sound in early and late-pubertal females.

PubMed

Klentrou, Panagiota; Ludwa, Izabella A; Falk, Bareket

2011-10-01

This cross-sectional study examines whether maturity, body composition, physical activity, dietary intake, and hormonal concentrations are related to markers of bone turnover and tibial speed of sound (tSOS) in premenarcheal (n = 20, 10.1 ± 1.1 years) and postmenarcheal girls (n = 28, aged 15.0 ± 1.4 years). Somatic maturity was evaluated using years from age of peak height velocity (aPHV). Daily dietary intake was assessed with a 24-h recall interview, and moderate to very vigorous physical activity (MVPA) was measured using accelerometry. Plasma levels of 25-OH vitamin D, serum levels of insulin-like growth-factor 1 (IGF-1) and leptin, and serum levels of bone turnover markers including osteocalcin (OC), bone-specific alkaline phosphatase (BAP) and cross-linked N-teleopeptide of type I collagen (NTX) were measured using ELISA. OC, BAP, and NTX were significantly higher while IGF-1 and tSOS were lower in the premenarcheal group. The premenarcheal girls were more active and had higher daily energy intake relative to their body mass but there were no group differences in body mass index percentile. Maturity predicted 40%-57% of the variance in bone turnover markers. Additionally, daily energy intake was a significant predictor of OC, especially in the postmenarcheal group. IGF-1 and MVPA were significant predictors of BAP in the group as a whole. However, examined separately, IGF-1 was a predictor of BAP in the premenarcheal group while MVPA was a predictor in the postmenarcheal group. Adiposity and leptin were both negative predictors of tSOS, with leptin being specifically predictive in the postmenarcheal group. In conclusion, while maturity was the strongest predictor of bone markers and tSOS, dietary intake, physical activity, body composition, and hormonal factors further contribute to the variance in bone turnover and bone SOS in young Caucasian females. Further, the predicting factors of bone turnover and tSOS were different within each maturity group.

Increases in IGF-1 After Anti-TNF-α Therapy Are Associated With Bone and Muscle Accrual in Pediatric Crohn Disease.

PubMed

DeBoer, Mark D; Lee, Arthur M; Herbert, Kirabo; Long, Jin; Thayu, Meena; Griffin, Lindsay M; Baldassano, Robert N; Denson, Lee A; Zemel, Babette S; Denburg, Michelle R; Herskovitz, Rita; Leonard, Mary B

2018-03-01

Low levels of insulinlike growth factor 1 (IGF-1) in pediatric and adolescent Crohn disease (CD) likely contribute to bone and muscle deficits. Assess changes in IGF-1 levels and associations with bone and muscle accrual following initiation of anti-tumor necrosis factor α (TNF-α) therapy in pediatric and adolescent CD. Participants (n = 75, age 5 to 21 years) with CD were enrolled in a prospective cohort study; 63 completed the 12-month visit. IGF-1 levels at baseline and 10 weeks, as well as dual-energy x-ray absorptiometry (DXA) and tibia peripheral quantitative computed tomography (pQCT) measures of bone and muscle at baseline and 12 months after initiation of anti-TNF-α therapy. Outcomes were expressed as sex-specific z scores. IGF-1 z scores increased from a median (interquartile range) of -1.0 (-1.58 to -0.17) to -0.36 (-1.04 to 0.36) over 10 weeks (P < 0.001). Lesser disease severity and systemic inflammation, as well as greater estradiol z scores (in girls), was significantly associated with greater IGF-1 z scores over time. DXA whole-body bone mineral content, leg lean mass, and total hip and femoral neck bone mineral density (BMD) z scores were low at baseline (P < 0.0001 vs reference data) and increased significantly (P < 0.001) over 12 months. Greater increases in IGF-1 z scores over 10 weeks predicted improvement in DXA bone and muscle outcomes and pQCT trabecular BMD and cortical area. Adjustment for changes in muscle mass markedly attenuated the associations between IGF-1 levels and bone outcomes. Short-term improvements in IGF-1 z scores predicted recovery of bone and muscle outcomes following initiation of anti-TNF-α therapy in pediatric CD. These data suggest that disease effects on growth hormone metabolism contribute to musculoskeletal deficits in CD.

Effect of selective serotonin reuptake inhibitors on bone mineral density: a systematic review and meta-analysis.

PubMed

Zhou, C; Fang, L; Chen, Y; Zhong, J; Wang, H; Xie, P

2018-02-12

Our work is the first systematic meta-analysis to investigate the effect of selective serotonin reuptake inhibitor (SSRI) medication on bone mineral density. Through meta-analyzed 11 studies, our findings suggested that compared with nonusers, use of SSRIs was significantly associated with lumbar spine BMD reduction, particularly for old people. The use of selective serotonin reuptake inhibitors (SSRIs) has already been associated with bone mass loss. Their effects on bone mineral density (BMD) for the different bone sections have, however, thus been inconsistent. Here, we aim to assess the effects of SSRIs on BMD using a meta-analysis. We searched PubMed, Scopus, ISI Web of Knowledge, the Cochrane Library, and PsycINFO for all English-written studies investigating the effects of SSRIs on BMD and published before November 2017. BMD was compared between non-SSRI users and SSRI users using a random-effect model with standardized mean differences (SMD) and 95% confidence intervals (CIs). Furthermore, subgroup analyses were performed based on study design, age, and sex in order to find the origins of high heterogeneity. Eleven studies met the inclusion criteria and were used for the meta-analysis. Our study demonstrated that the use of SSRIs was significantly associated with lower BMD values (SMD - 0.40; 95% CI - 0.79 to 0.00; p = 0.05) and BMD Z-scores (SMD - 0.28; 95% CI - 0.50 to - 0.05; p = 0.02) of the lumbar spine, but not of the total hip and femoral neck. In addition, SSRI use was associated with a greater bone loss in older people. SSRI use is a risk factor of lower BMD of the lumbar spine, especially for older people. Future studies into the relationship between SSRI use and bone metabolism and bone mass need to be conducted with larger sample sizes for both men and women at different bone sites.

Impact of long-term exposure to the tyrosine kinase inhibitor imatinib on the skeleton of growing rats.

PubMed

Tauer, Josephine T; Hofbauer, Lorenz C; Jung, Roland; Gerdes, Sebastian; Glauche, Ingmar; Erben, Reinhold G; Suttorp, Meinolf

2015-01-01

The tyrosine kinase (TK) inhibitor imatinib provides a highly effective therapy for chronic myeloid leukemia (CML) via inhibition of the oncogenic TK BCR-ABL1. However, off-target TKs like platelet-derived growth factor receptors (PDGF-R) and colony-stimulating factor-1 receptor (c-fms), involved in bone remodeling, are also inhibited. Thus, pediatric patients with CML on imatinib exhibit altered bone metabolism, leading to linear growth failure. As TKI treatment might be necessary for a lifetime, long-term effects exerted on bone in children are of major concern. Therefore, we studied the skeletal long-term effects of continuous and intermittent imatinib exposure in a juvenile rat model. Four-weeks-old male Wistar rats were chronically exposed to imatinib via drinking water over a period of 10 weeks. Animals were exposed to a standard and high imatinib dosage continuously and to the high imatinib dose intermittently. Bone mass and strength were assessed using pQCT, micro-computed tomography (μCT), and biomechanical testing at the prepubertal, pubertal, and postpubertal age. Bone length and vertebral height as well as biochemical markers of bone turnover were analyzed. Femoral and tibial bone length were dose-dependently reduced by up to 24% (p<0.0001), femoral and tibial trabecular bone mass density (BMD) were reduced by up to 25% (p<0.01), and femoral breaking strength was lowered by up to 20% (p<0.05). Intermittent exposure mitigated these skeletal effects. Long-term exposure resulted in reduced vertebral height by 15% and lower trabecular BMD by 5%. Skeletal changes were associated with suppressed serum osteocalcin (p<0.01) and non-significantly elevated serum CTX-I and PINP levels. In conclusion, imatinib mainly impaired longitudinal growth of long bones rather than the vertebrae of growing rats. Interestingly, intermittent imatinib exposure has less skeletal side effects, which may be beneficial in pediatric patients taking imatinib.

Osteoporosis in premenopausal women.

PubMed

Langdahl, Bente L

2017-07-01

The scope of this review was to review the newest developments in the context of the existing knowledge on premenopausal bone fragility. Fragility fractures are common in postmenopausal women and men and diagnostic criteria for osteoporosis have been agreed and multiple pharmacological treatments have been developed over the last 25 years. In premenopausal women, fragility fractures and very low bone mass are uncommon and osteoporosis in premenopausal women has therefore attracted much less interest. Recent studies have highlighted that lifestyle and dietary habits affect premenopausal bone mass. Bone mass may be improved by sufficient intake of calcium and vitamin D together with increased physical activity in premenopausal women with idiopathic osteoporosis. If pharmacological treatment is needed, teriparatide has been demonstrated to efficiently increase bone mass; however, no fracture studies and no comparative studies against antiresorptive therapies have been conducted. Pregnancy affects bone turnover and mass significantly, but pregnancy-associated osteoporosis is a rare and heterogeneous condition. The diagnosis of osteoporosis should only be considered in premenopausal women with existing fragility fractures, diseases or treatments known to cause bone loss or fractures. Secondary causes of osteoporosis should be corrected or treated if possible. The women should be recommended sufficient intake of calcium and vitamin and physical activity. In women with recurrent fractures or secondary causes that cannot be eliminated, for example glucocorticoid or cancer treatment, pharmacological intervention with bisphosphonates or teriparatide (not in the case of cancer) may be considered.

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.

An Evaluation of Select Physical Activity Exercise Classes on Bone Metabolism.

PubMed

Stone, Tori M; Wingo, Jonathan E; Young, John C; Navalta, James W

2018-01-01

Weight-bearing physical activity can optimize bone mass early in life and prevent the development of osteoporosis. However, less is known about the potential benefits of non-weight-bearing activities. The purpose of this study was to assess the efficacy of structured physical activity classes on bone metabolism. Twenty-eight premenopausal women, aged 18-35 years who were either enrolled in a yoga class (n=14) or cardio-kickboxing class (n=14) voluntarily consented to participate. Both classes were introductory classes meeting twice per week for 50 min per session for 12 weeks. Anteroposterior spine (L1-L4), hip (dual femur), and total body bone mineral density (BMD) was measured in both groups pre and post intervention using dual-energy X-ray absorptiometry (DXA). Pre and post blood samples were drawn for measurement of serum osteocalcin (OC) by enzyme-linked immunosorbent assay (ELISA) in each group. Baseline subject characteristics including age, height, weight, body fat percentage, and lean body mass did not differ between groups. BMD levels did not increase but were held stable over the course of the intervention. Yoga increased OC by 68% (P < 0.001) and cardio-kickboxing increased OC by 67% (P < 0.001) over the course of the 12-week classes. While 12 weeks of yoga and cardio-kickboxing were insufficient to induce BMD changes, OC levels reflect the bone formation process was initiated, but not yet complete. Increased OC levels suggest the selected physical activity classes provided enough of a stimulus to precipitate a future response of bone growth, assuming exercise training remains constant.

Gluteal muscle attachment during proximal femoral reconstruction in a canine model.

PubMed

Pluhar, G Elizabeth; Manley, Paul A; Heiner, John P; Vanderby, Ray; Markel, Mark D

2007-02-01

In this 18 month in vivo canine study we compared three methods of attaching the gluteal muscles to the proximal femur during hip reconstruction with an allograft-prosthesis composite (APC). All three methods are commonly practiced in human hip revision surgery and data on their effectiveness in dogs is directly relevant to human treatment. The methods compared were host gluteal tendon sutured to allograft tendon, host greater trochanter apposed to allograft using a cable grip system, and host cortical bone shells around the allograft secured with cerclage wires. For each method, we assessed changes in allograft-host bone fusion, weight bearing, gluteal muscle mass, and structural properties through qualitative radiography, gait analysis, histology, and biomechanical testing. Hip reconstruction using the WRAP method resulted in the greatest limb use with complete resolution of gluteal muscle atrophy 18 months after surgery. This method yielded a stronger, more stable hip joint that allowed for more normal limb function. These hips had the more rapid rate of bony union at the host bone-allograft junction and little resorption of the graft. The increased limb use and resultant larger gluteal muscle mass conferred to the WRAP hip composites the greatest tensile strength and stiffness when tested 18 months after reconstruction. There was a large amount of new bone formation on the periosteal surface where the WRAP reconstructions had an overlay of live bone that resulted in a more rapid union and increased cortical width at the level of the osteotomy. New bone also penetrated into the allograft a greater distance from the osteotomy in the WRAP group.

Estimating fat-free mass in elite-level male rowers: a four-compartment model validation of laboratory and field methods.

PubMed

Kendall, Kristina L; Fukuda, David H; Hyde, Parker N; Smith-Ryan, Abbie E; Moon, Jordon R; Stout, Jeffrey R

2017-04-01

The purpose of this study was to investigate the accuracy of fat-free mass (FFM) estimates from two-compartment (2C) models including air displacement plethysmography (ADP), ultrasound (US), near-infrared interactance (NIR), and the Jackson and Pollock skinfold equation (SKF) against a criterion four-compartment (4C) model in elite male rowers. Twenty-three elite-level male rowers (mean± SD; age 24.6 ± 2.2 years; stature: 191.4 ± 7.2 cm; mass: 87.2 ± 11.2 kg) participated in this investigation. All body composition assessments were performed on the same day in random order, except for hydrostatic weighing (HW), which was measured last. FFM was evaluated using a 4C model, which included total body water from bioimpedance spectroscopy, body volume from HW, and total body bone mineral via dual-energy X-ray absorptiometry. The major findings of the study were that the 2C models evaluated overestimated FFM and should be considered with caution for the assessment of FFM in elite male rowers. Future studies should use multiple-compartment models, with measurement of TBW and bone mineral content, for the estimation of FFM.

A multi-method assessment of bone maintenance and loss in an Imperial Roman population: Implications for future studies of age-related bone loss in the past.

PubMed

Beauchesne, Patrick; Agarwal, Sabrina C

2017-09-01

One of the hallmarks of contemporary osteoporosis and bone loss is dramatically higher prevalence of loss and fragility in females post-menopause. In contrast, bioarchaeological studies of bone loss have found a greater diversity of age- and sex-related patterns of bone loss in past populations. We argue that the differing findings may relate to the fact that most studies use only a single methodology to quantify bone loss and do not account for the heterogeneity and complexity of bone maintenance across the skeleton and over the life course. We test the hypothesis that bone mass and maintenance in trabecular bone sites versus cortical bone sites will show differing patterns of age-related bone loss, with cortical bone sites showing sex difference in bone loss that are similar to contemporary Western populations, and trabecular bone loss at earlier ages. We investigated this hypothesis in the Imperial Roman population of Velia using three methods: radiogrammetry of the second metacarpal (N = 71), bone histology of ribs (N = 70), and computerized tomography of trabecular bone architecture (N = 47). All three methods were used to explore sex and age differences in patterns of bone loss. The suite of methods utilized reveal differences in the timing of bone loss with age, but all methods found no statistically significant differences in age-related bone loss. We argue that a multi-method approach reduces the influence of confounding factors by building a reconstruction of bone turnover over the life cycle that a limited single-method project cannot provide. The implications of using multiple methods beyond studies of bone loss are also discussed. © 2017 Wiley Periodicals, Inc.

Effect of vitamin K2 on cortical and cancellous bone mass and hepatic lipids in rats with combined methionine-choline deficiency.

PubMed

Iwamoto, Jun; Seki, Azusa; Sato, Yoshihiro; Matsumoto, Hideo; Takeda, Tsuyoshi; Yeh, James K

2011-05-01

The present study examined changes of cancellous and cortical bone in rats with combined methionine-choline deficiency (MCD). In addition, the effects of vitamin K2 on cortical and cancellous bone mass and hepatic lipids were investigated in rats with MCD. Six-week-old male Sprague-Dawley rats were randomized into three groups of ten, including an age-matched control (standard diet) group, an MCD diet group, and an MCD diet+vitamin K2 (menatetrenone at 30mg/kg/d orally, 5 times a week) group. After the one-month experimental period, histomorphometric analysis was performed on cortical and cancellous bone from the tibial diaphysis and proximal metaphysis, respectively, while histological examination of the liver was performed after staining with hematoxylin and eosin and Oil Red O. MCD rats displayed weight loss, diffuse and centrilobular fatty changes of the liver, and a decrease of the cancellous bone volume per tissue volume (BV/TV) and percent cortical area (Ct Ar) as a result of decreased trabecular, periosteal, and endocortical bone formation along with increased trabecular and endocortical bone resorption. Administration of vitamin K2 to rats with MCD attenuated weight loss, accelerated the decrease of cancellous BV/TV due to an increase of bone remodeling, and ameliorated the decrease of percent Ct Ar by increasing periosteal and endocortical bone formation. Vitamin K2 administration also prevented MCD-induced diffuse fatty change of the liver. These findings suggest a beneficial effect of vitamin K2 on cortical bone mass and hepatic lipid metabolism in rats with MCD. The loss of cancellous bone mass could possibly have been due to re-distribution of minerals to cortical bone. Copyright © 2011 Elsevier Inc. All rights reserved.

The Endocrine Role of Estrogens on Human Male Skeleton

PubMed Central

Rochira, Vincenzo; Kara, Elda; Carani, Cesare

2015-01-01

Before the characterization of human and animal models of estrogen deficiency, estrogen action was confined in the context of the female bone. These interesting models uncovered a wide spectrum of unexpected estrogen actions on bone in males, allowing the formulation of an estrogen-centric theory useful to explain how sex steroids act on bone in men. Most of the principal physiological events that take place in the developing and mature male bone are now considered to be under the control of estrogen. Estrogen determines the acceleration of bone elongation at puberty, epiphyseal closure, harmonic skeletal proportions, the achievement of peak bone mass, and the maintenance of bone mass. Furthermore, it seems to crosstalk with androgen even in the determination of bone size, a more androgen-dependent phenomenon. At puberty, epiphyseal closure and growth arrest occur when a critical number of estrogens is reached. The same mechanism based on a critical threshold of serum estradiol seems to operate in men during adulthood for bone mass maintenance via the modulation of bone formation and resorption in men. This threshold should be better identified in-between the ranges of 15 and 25 pg/mL. Future basic and clinical research will optimize strategies for the management of bone diseases related to estrogen deficiency in men. PMID:25873947

Sprint Interval Training Induces A Sexual Dimorphism but does not Improve Peak Bone Mass in Young and Healthy Mice

PubMed Central

Koenen, Kathrin; Knepper, Isabell; Klodt, Madlen; Osterberg, Anja; Stratos, Ioannis; Mittlmeier, Thomas; Histing, Tina; Menger, Michael D.; Vollmar, Brigitte; Bruhn, Sven; Müller-Hilke, Brigitte

2017-01-01

Elevated peak bone mass in early adulthood reduces the risk for osteoporotic fractures at old age. As sports participation has been correlated with elevated peak bone masses, we aimed to establish a training program that would efficiently stimulate bone accrual in healthy young mice. We combined voluntary treadmill running with sprint interval training modalities that were tailored to the individual performance limits and were of either high or intermediate intensity. Adolescent male and female STR/ort mice underwent 8 weeks of training before the hind legs were analyzed for cortical and trabecular bone parameters and biomechanical strength. Sprint interval training led to increased running speeds, confirming an efficient training. However, males and females responded differently. The males improved their running speeds in response to intermediate intensities only and accrued cortical bone at the expense of mechanical strength. High training intensities induced a significant loss of trabecular bone. The female bones showed neither adverse nor beneficial effects in response to either training intensities. Speculations about the failure to improve geometric alongside mechanical bone properties include the possibility that our training lacked sufficient axial loading, that high cardio-vascular strains adversely affect bone growth and that there are physiological limits to bone accrual. PMID:28303909

Alcohol and bone: review of dose effects and mechanisms.

PubMed

Maurel, D B; Boisseau, N; Benhamou, C L; Jaffre, C

2012-01-01

Alcohol is widely consumed across the world. It is consumed in both social and cultural settings. Until recently, two types of alcohol consumption were recognized: heavy chronic alcohol consumption or light consumption. Today, there is a new pattern of consumption among teenagers and young adults namely: binge drinking. Heavy alcohol consumption is detrimental to many organs and tissues, including bones, and is known to induce secondary osteoporosis. Some studies, however, have reported benefits from light alcohol consumption on bone parameters. To date, little is known regarding the effects of binge drinking on bone health. Here, we review the effects of three different means of alcohol consumption: light, heavy, and binge drinking. We also review the detailed literature on the different mechanisms by which alcohol intake may decrease bone mass and strength. The effects of alcohol on bone are thought to be both direct and indirect. The decrease in bone mass and strength following alcohol consumption is mainly due to a bone remodeling imbalance, with a predominant decrease in bone formation. Recent studies, however, have reported new mechanisms by which alcohol may act on bone remodeling, including osteocyte apoptosis, oxidative stress, and Wnt signalling pathway modulation. The roles of reduced total fat mass, increased lipid content in bone marrow, and a hypoleptinemia are also discussed.

Bone growth and turnover in progesterone receptor knockout mice.

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

Rickard, David J.; Iwaniec, Urszula T.; Evans, Glenda

2008-05-01

The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through the PR is necessary for normal bone growth and turnover, we performed histomorphometric and mCT analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 weeks of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain and tibia longitudinal bone growth was normal in PRKO mice. In contrast, total and cortical bone mass were increased in long bonesmore » of post-pubertal (12 and 26-week-old) PRKO mice, whereas cancellous bone mass was normal in the tibia but increased in the humerus. The striking 57% decrease in cancellous bone from the proximal tibia metaphysis which occurred between 6 and 26 weeks in WT mice was abolished in PRKO mice. The improved bone balance in aging PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice attenuates the accumulation of cortical bone mass during adolescence and is required for early age-related loss of cancellous bone.« less

Lead exposure affects health indices in free-ranging ducks in Argentina.

PubMed

Ferreyra, Hebe; Beldomenico, Pablo M; Marchese, Krysten; Romano, Marcelo; Caselli, Andrea; Correa, Ana I; Uhart, Marcela

2015-05-01

Numerous experiments under controlled conditions and extensive investigation of waterfowl die-offs have demonstrated that exposure to lead from spent gunshot is highly detrimental to the health of waterfowl. However, few studies have focused on examining the more subtle sub-lethal effects of lead toxicity on ducks in non-experimental settings. In our study, the health of ducks exposed to varying amounts of lead under natural conditions was assessed by correlating individual lead exposure with relevant indices of health. Based on hunter-killed wild ducks in Argentina, we measured spleen mass, body condition, examined bone marrow smears, and determined Ca and P in bone tissue. In free-ranging live-trapped ducks we determined basic hematology and aminolevulinic acid dehydratase activity. Using multivariate analyses, we found that, when controlling for the potential confounding effect of site type, year, duck species, body mass and age, lead levels in the liver were negatively associated with body condition and spleen mass. Spleen mass was also lower in ducks with higher lead levels in their bones. In live ducks, high blood lead levels were associated with low packed cell volume and red cell morphologic abnormalities. These findings suggest that, despite the lack of recorded lead-induced mortality in the region, lead exposure results in less conspicuous but still significant impacts on the health of ducks, which could have serious implications for their conservation. Moreover, this evidence further supports the need for urgently banning lead shot in the region.

[Diet, nutrition and bone health].

PubMed

Miggiano, G A D; Gagliardi, L

2005-01-01

Nutrition is an important "modifiable" factor in the development and maintenance of bone mass and in the prevention of osteoporosis. The improvement of calcium intake in prepuberal age translates to gain in bone mass and, with genetic factor, to achievement of Peak Bone Mass (PBM), the higher level of bone mass reached at the completion of physiological growth. Individuals with higher PBM achieved in early adulthood will be at lower risk for developing osteoporosis later in life. Achieved the PBM, it is important maintain the bone mass gained and reduce the loss. This is possible adopting a correct behaviour eating associated to regular physical activity and correct life style. The diet is nutritionally balanced with caloric intake adequate to requirement of individual. This is moderate in protein (1 g/kg/die), normal in fat and the carbohydrates provide 55-60% of the caloric intake. A moderate intake of proteins is associated with normal calcium metabolism and presumably does'nt alter bone turnover. An adequate intake of alkali-rich foods may help promote a favorable effect of dietary protein on the skeleton. Lactose intolerance may determinate calcium malabsorption or may decrease calcium intake by elimination of milk and dairy products. Omega3 fatty acids may "down-regulate" pro-inflammatory cytokines and protect against bone loss by decreasing osteoclast activation and bone reabsorption. The diet is characterized by food containing high amount of calcium, potassium, magnesium and low amount of sodium. If it is impossible to reach the requirement with only diet, it is need the supplement of calcium and vitamin D. Other vitamins (Vit. A, C, E, K) and mineral (phosphorus, fluoride, iron, zinc, copper and boron) are required for normal bone metabolism, thus it is need adequate intake of these dietary components. It is advisable reduce ethanol, caffeine, fibers, phytic and ossalic acid intake. The efficacy of phytoestrogens is actually under investigation. Some drugs may interfere with calcium and other nutrients and produce an unfavourable effect on bone health.

Muscle and Bone Impairment in Children With Marfan Syndrome: Correlation With Age and FBN1 Genotype.

PubMed

Haine, Elsa; Salles, Jean-Pierre; Khau Van Kien, Philippe; Conte-Auriol, Françoise; Gennero, Isabelle; Plancke, Aurélie; Julia, Sophie; Dulac, Yves; Tauber, Maithé; Edouard, Thomas

2015-08-01

Marfan syndrome (MFS) is a rare connective tissue disorder caused by mutation in the gene encoding the extracellular matrix protein fibrillin-1 (FBN1), leading to transforming growth factor-beta (TGF-β) signaling dysregulation. Although decreased axial and peripheral bone mineral density (BMD) has been reported in adults with MFS, data about the evolution of bone mass during childhood and adolescence are limited. The aim of the present study was to evaluate bone and muscle characteristics in children, adolescents, and young adults with MFS. The study population included 48 children and young adults (22 girls) with MFS with a median age of 11.9 years (range 5.3 to 25.2 years). The axial skeleton was analyzed at the lumbar spine using dual-energy X-ray absorptiometry (DXA), whereas the appendicular skeleton (hand) was evaluated using the BoneXpert system (with the calculation of the Bone Health Index). Muscle mass was measured by DXA. Compared with healthy age-matched controls, bone mass at the axial and appendicular levels and muscle mass were decreased in children with MFS and worsened from childhood to adulthood. Vitamin D deficiency (<50 nmol/L) was found in about a quarter of patients. Serum vitamin D levels were negatively correlated with age and positively correlated with lumbar spine areal and volumetric BMD. Lean body mass (LBM) Z-scores were positively associated with total body bone mineral content (TB-BMC) Z-scores, and LBM was an independent predictor of TB-BMC values, suggesting that muscle hypoplasia could explain at least in part the bone loss in MFS. Patients with a FBN1 premature termination codon mutation had a more severe musculoskeletal phenotype than patients with an inframe mutation, suggesting the involvement of TGF-β signaling dysregulation in the pathophysiologic mechanisms. In light of these results, we recommend that measurement of bone mineral status should be part of the longitudinal clinical investigation of MFS children. © 2015 American Society for Bone and Mineral Research.

Bone pulsating metastasis due to renal cell carcinoma.

PubMed

Cınar, Murat; Derincek, Alihan; Karan, Belgin; Akpınar, Sercan; Tuncay, Cengiz

2010-11-01

Pulsation on the bone cortex surface is a rare condition. Pulsative palpation of the superficial-located bone tumors can be misperceived as an aneurysm. Fifty-eight-year-old man is presented with pulsating bone mass in his proximal tibia. During angiographic examination, hypervascular masses were diagnosed both at right kidney and at right proximal tibia. Renal cell carcinoma was diagnosed after abdominal CT scan. Proximal tibia biopsy was complicated with projectile bleeding.

Growth Hormone and Craniofacial Tissues. An update

PubMed Central

Litsas, George

2015-01-01

Growth hormone is an important regulator of bone homeostasis. In childhood, it determines the longitudinal bone growth, skeletal maturation, and acquisition of bone mass. In adulthood, it is necessary to maintain bone mass throughout life. Although an association between craniofacial and somatic development has been clearly established, craniofacial growth involves complex interactions of genes, hormones and environment. Moreover, as an anabolic hormone seems to have an important role in the regulation of bone remodeling, muscle enhancement and tooth development. In this paper the influence of growth hormone on oral tissues is reviewed. PMID:25674165

[Secondary osteoporosis and glucocorticoid-induced osteoporosis].

PubMed

Orcel, P; Krane, S M

2000-10-01

In order to assess properly the diagnosis of osteoporosis, a short clinical investigation is required to address potential causes for bone loss. Osteoporosis used to be suspected in a patient with vertebral demineralization, but nowadays it is often diagnosed in a patient with a low bone mass on a screening dual-energy X-ray absorptiometry (DEXA). In this setting, it is important for the clinician to look for secondary osteoporosis, especially in men in whom secondary osteoporosis is more frequent than in women, before discussing any specific therapy. The major causes are longterm glucocorticoid therapy, endocrine (hypogonadism, primary hyperparathyroidism, hyperthyroidism), or digestive diseases.

Using the Abitibi Greenstone Belt to Understand Martian Hydrothermal Systems and the Potential for Biosignature Preservation in High Temperature Aqueous Environments

NASA Technical Reports Server (NTRS)

Hurowitz, J.; Abelson, J.; Allwood, A.; Anderson, R.; Atkinson, B.; Beaty, D.; Bristow, T.; Ehlmann, B.; Eigenbrode, J.; Grotzinger, J.;

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.

Identification and characterization of glycation adducts on osteocalcin

PubMed Central

Thomas, Corinne J.; Cleland, Timothy P.; Zhang, Sheng; Gundberg, Caren M.; Vashishth, Deepak

2017-01-01

Osteocalcin is an important extracellular matrix bone protein that contributes to the structural properties of bone through its interactions with hydroxyapatite mineral and with collagen I. This role may be affected by glycation, a labile modification the levels of which has been shown to correlate with bone fragility. Glycation starts with the spontaneous addition of a sugar onto a free amine group on a protein, forming an Amadori product, and then proceeds through several environment-dependent stages resulting in the formation of an advanced glycation end product. Here, we induce the first step of this modification on synthetic osteocalcin, and then use multiple mass spectrometry fragmentation techniques to determine the location of this modification. Collision-induced dissociation resulted in spectra dominated by neutral loss, and was unable to identify Amadori products. Electron-transfer dissociation showed that the Amadori product formed solely on osteocalcin’s N-terminus. This suggests that the glycation of osteocalcin is unlikely to interfere with osteocalcin’s interaction with hydroxyapatite. Instead, glycation may interfere with its interaction with collagen I or another bone protein, osteopontin. Potentially, the levels of glycated osteocalcin fragments released from bone during bone resorption could be used to assess bone quality, should the N-terminal fragments be targeted. PMID:28237256

Prevention of arterial calcification corrects the low bone mass phenotype in MGP-deficient mice.

PubMed

Marulanda, Juliana; Gao, Chan; Roman, Hassem; Henderson, Janet E; Murshed, Monzur

2013-12-01

Matrix gla protein (MGP), a potent inhibitor of extracellular matrix (ECM) mineralization, is primarily produced by vascular smooth muscle cells (VSMCs) and chondrocytes. Consistent with its expression profile, MGP deficiency in mice (Mgp-/- mice) results in extensive mineralization of all arteries and cartilaginous ECMs. Interestingly, we observed a progressive loss of body weight in Mgp-/- mice, which becomes apparent by the third week of age. Taking into account the new paradigm linking the metabolic regulators of energy metabolism and body mass to that of bone remodeling, we compared the bone volume in Mgp-/- mice to that of their wild type littermates by micro-CT and bone histomorphometry. We found a decrease of bone volume over tissue volume in Mgp-/- mice caused by an impaired osteoblast function. In culture, early differentiation of Mgp-/- primary osteoblasts was not affected; however there was a significant upregulation of the late osteogenic marker Bglap (osteocalcin). We examined whether the prevention of arterial calcification in Mgp-/- mice could correct the low bone mass phenotype. The bones of two different genetic models: Mgp-/-;SM22-Mgp and Mgp-/-;Eln+/- mice were analyzed. In the former strain, vascular calcification was fully rescued by transgenic overexpression of Mgp in the VSMCs, while in the latter, elastin haploinsufficiency significantly impeded the deposition of minerals in the arterial walls. In both models, the low mass phenotype seen in Mgp-/- mice was rescued. Our data support the hypothesis that the arterial calcification, not MGP deficiency itself, causes the low bone mass phenotype in Mgp-/- mice. Taken together, we provide evidence that arterial calcification affects bone remodeling and pave the way for further mechanistic studies to identify the pathway(s) regulating this process. © 2013.

Evaluating the relationship between muscle and bone modeling response in older adults.

PubMed

Reider, Lisa; Beck, Thomas; Alley, Dawn; Miller, Ram; Shardell, Michelle; Schumacher, John; Magaziner, Jay; Cawthon, Peggy M; Barbour, Kamil E; Cauley, Jane A; Harris, Tamara

2016-09-01

Bone modeling, the process that continually adjusts bone strength in response to prevalent muscle-loading forces throughout an individual's lifespan, may play an important role in bone fragility with age. Femoral stress, an index of bone modeling response, can be estimated using measurements of DXA derived bone geometry and loading information incorporated into an engineering model. Assuming that individuals have adapted to habitual muscle loading forces, greater stresses indicate a diminished response and a weaker bone. The purpose of this paper was to evaluate the associations of lean mass and muscle strength with the femoral stress measure generated from the engineering model and to examine the extent to which lean mass and muscle strength account for variation in femoral stress among 2539 healthy older adults participating in the Health ABC study using linear regression. Mean femoral stress was higher in women (9.51, SD=1.85Mpa) than in men (8.02, SD=1.43Mpa). Percent lean mass explained more of the variation in femoral stress than did knee strength adjusted for body size (R(2)=0.187 vs. 0.055 in men; R(2)=0.237 vs. 0.095 in women). In models adjusted for potential confounders, for every percent increase in lean mass, mean femoral stress was 0.121Mpa lower (95% CI: -0.138, -0.104; p<0.001) in men and 0.139Mpa lower (95% CI: -0.158, -0.121; p<0.001) in women. The inverse association of femoral stress with lean mass and with knee strength did not differ by category of BMI. Results from this study provide insight into bone modeling differences as measured by femoral stress among older men and women and indicate that lean mass may capture elements of bone's response to load. Copyright © 2016 Elsevier Inc. All rights reserved.

Non-elite gymnastics participation is associated with greater bone strength, muscle size, and function in pre- and early pubertal girls.

PubMed

Burt, L A; Naughton, G A; Greene, D A; Courteix, D; Ducher, G

2012-04-01

Recent reports indicate an increase in forearm fractures in children. Bone geometric properties are an important determinant of bone strength and therefore fracture risk. Participation in non-elite gymnastics appears to contribute to improving young girls' musculoskeletal health, more specifically in the upper body. The primary aim of this study was to determine the association between non-elite gymnastics participation and upper limb bone mass, geometry, and strength in addition to muscle size and function in young girls. Eighty-eight pre- and early pubertal girls (30 high-training gymnasts [HGYM, 6-16 hr/ wk], 29 low-training gymnasts [LGYM, 1-5 h r/wk] and 29 non-gymnasts [NONGYM]), aged 6-11 years were recruited. Upper limb lean mass, BMD and BMC were derived from a whole body DXA scan. Forearm volumetric BMD, bone geometry, estimated strength, and muscle CSA were determined using peripheral QCT. Upper body muscle function was investigated with muscle strength, explosive power, and muscle endurance tasks. HGYM showed greater forearm bone strength compared with NGYM, as well as greater arm lean mass, BMC, and muscle function (+5% to +103%, p < 0.05). LGYM displayed greater arm lean mass, BMC, muscle power, and endurance than NGYM (+4% to +46%, p < 0.05); however, the difference in bone strength did not reach significance. Estimated fracture risk at the distal radius, which accounted for body weight, was lower in both groups of gymnasts. Compared with NONGYM, HGYM tended to show larger skeletal differences than LGYM; yet, the two groups of gymnasts only differed for arm lean mass and muscle CSA. Non-elite gymnastics participation was associated with musculoskeletal benefits in upper limb bone geometry, strength and muscle function. Differences between the two gymnastic groups emerged for arm lean mass and muscle CSA, but not for bone strength.

An altered hormonal profile and elevated rate of bone loss are associated with low bone mass in professional horse-racing jockeys.

PubMed

Dolan, Eimear; McGoldrick, Adrian; Davenport, Colin; Kelleher, Grainne; Byrne, Brendan; Tormey, William; Smith, Diarmuid; Warrington, Giles D

2012-09-01

Horse-racing jockeys are a group of weight-restricted athletes, who have been suggested as undertaking rapid and extreme weight cycling practices in order to comply with stipulated body-mass standards. The aim of this study was to examine bone mass, turnover and endocrine function in jockeys and to compare this group with age, gender and body mass index matched controls. Twenty male professional jockeys and 20 healthy male controls participated. Dual energy X-ray absorptiometry scans and early morning fasting blood and urine samples were used to measure bone mass, turnover and a hormonal profile. Total body bone mineral density (BMD) was significantly lower in jockeys (1.143 ± 0.05 vs. 1.27 ± 0.06 g cm(-3), p < 0.01). Bone resorptive activity was elevated in the jockey group as indicated by significantly higher urinary NTx/creatinine (76.94 ± 29.52 vs. 55.9 ± 13.9 nmol mmol(-1), p < 0.01), resulting in a significantly negative uncoupling index between bone resorption and formation. Sex hormone binding globulin (SHBG) levels were significantly higher in jockeys (41.21 ± 9.77 vs. 28.24 ± 9.98 nmol L(-1), p < 0.01) with a lower percentage of bioavailable testosterone (48.89 ± 7.38 vs. 59.18 ± 6.74 %, p < 0.01). SHBG and insulin-like growth factor-1 were independent predictors of total body and femoral neck BMD, respectively (p < 0.05). In conclusion, it appears that professional jockeys have an elevated rate of bone loss and reduced bone mass that appears to be associated with disrupted hormonal activity. It is likely that this may have occurred in response to the chronic weight cycling habitually experienced by this group.

[Is there a relation between weight in rats, bone density, ash weight and histomorphometric indicators of trabecular volume and thickness in the bones of extremities?].

PubMed

Zák, J; Kapitola, J; Povýsil, C

2003-01-01

Authors deal with question, if there is possibility to infer bone histological structure (described by histomorphometric parameters of trabecular bone volume and trabecular thickness) from bone density, ash weight or even from weight of animal (rat). Both tibias of each of 30 intact male rats, 90 days old, were processed. Left tibia was utilized to the determination of histomorphometric parameters of undecalcified bone tissue patterns by automatic image analysis. Right tibia was used to the determination of values of bone density, using Archimedes' principle. Values of bone density, ash weight, ash weight related to bone volume and animal weight were correlated with histomorphometric parameters (trabecular bone volume, trabecular thickness) by Pearson's correlation test. One could presume the existence of relation between data, describing bone mass at the histological level (trabecular bone of tibia) and other data, describing mass of whole bone or even animal mass (weight). But no statistically significant correlation was found. The reason of the present results could be in the deviations of trabecular density in marrow of tibia. Because of higher trabecular bone density in metaphyseal and epiphyseal regions, the histomorphometric analysis of trabecular bone is preferentially done in these areas. It is possible, that this irregularity of trabecular tibial density could be the source of the deviations, which could influence the results of correlations determined. The values of bone density, ash weight and animal weight do not influence trabecular bone volume and vice versa: static histomorphometric parameters of trabecular bone do not reflect bone density, ash weight and weight of animal.

Disruption of Lrp4 function by genetic deletion or pharmacological blockade increases bone mass and serum sclerostin levels

PubMed Central

Chang, Ming-Kang; Kramer, Ina; Huber, Thomas; Kinzel, Bernd; Guth-Gundel, Sabine; Leupin, Olivier; Kneissel, Michaela

2014-01-01

We identified previously in vitro LRP4 (low-density lipoprotein receptor-related protein 4) as a facilitator of the WNT (Wingless-type) antagonist sclerostin and found mutations disrupting this function to be associated with high bone mass in humans similar to patients lacking sclerostin. To further delineate the role of LRP4 in bone in vivo, we generated mice lacking Lrp4 in osteoblasts/osteocytes or osteocytes only. Lrp4 deficiency promoted progressive cancellous and cortical bone gain in both mutants, although more pronouncedly in mice deficient in osteoblast/osteocyte Lrp4, consistent with our observation in human bone that LRP4 is most strongly expressed by osteoblasts and early osteocytes. Bone gain was related primarily to increased bone formation. Interestingly, Lrp4 deficiency in bone dramatically elevated serum sclerostin levels whereas bone expression of Sost encoding for sclerostin was unaltered, indicating that osteoblastic Lrp4 retains sclerostin within bone. Moreover, we generated anti-LRP4 antibodies selectively blocking sclerostin facilitator function while leaving unperturbed LRP4–agrin interaction, which is essential for neuromuscular junction function. These antibodies increased bone formation and thus cancellous and cortical bone mass in skeletally mature rodents. Together, we demonstrate a pivotal role of LRP4 in bone homeostasis by retaining and facilitating sclerostin action locally and provide a novel avenue to bone anabolic therapy by antagonizing LRP4 sclerostin facilitator function. PMID:25404300

MicroRNA-29a mitigates glucocorticoid induction of bone loss and fatty marrow by rescuing Runx2 acetylation.

PubMed

Ko, Jih-Yang; Chuang, Pei-Chin; Ke, Huei-Jin; Chen, Yu-Shan; Sun, Yi-Chih; Wang, Feng-Sheng

2015-12-01

Glucocorticoid treatment reportedly increases the morbidity of osteoporotic or osteonecrotic disorders. Exacerbated bone acquisition and escalated marrow adipogenesis are prominent pathological features of glucocorticoid-mediated skeletal disorders. MicroRNAs reportedly modulate tissue metabolism and remodeling. This study was undertaken to investigate the biological roles of microRNA-29a (miR-29a) in skeletal and fat metabolism in the pathogenesis of glucocorticoid-induced osteoporosis. Transgenic mice overexpressing miR-29a precursor or wild-type mice were given methylprednisolone. Bone mass, microarchitecture and histology were assessed by dual energy X-ray absorptiometry, μCT and histomorphometry. Differential gene expression and signaling components were delineated by quantitative RT-PCR and immunoblotting. Glucocorticoid treatment accelerated bone loss and marrow fat accumulation in association with decreased miR-29a expression. The miR-29a transgenic mice had high bone mineral density, trabecular microarchitecture and cortical thickness. miR-29a overexpression mitigated the glucocorticoid-induced impediment of bone mass, skeletal microstructure integrity and mineralization reaction and attenuated fatty marrow histopathology. Ex vivo, miR-29a increased osteogenic differentiation capacity and alleviated the glucocorticoid-induced promotion of adipocyte formation in primary bone-marrow mesenchymal progenitor cell cultures. Through inhibition of histone deacetylase 4 (HDAC4) expression, miR-29a restored acetylated Runx2 and β-catenin abundances and reduced RANKL, leptin and glucocorticoid receptor expression in glucocorticoid-mediated osteoporosis bone tissues. Taken together, glucocorticoid suppression of miR-29a signaling disturbed the balances between osteogenic and adipogenic activities, and thereby interrupted bone formation and skeletal homeostasis. miR-29a inhibition of HDAC4 stabilized the acetylation state of Runx2 and β-catenin that ameliorated the detrimental effects of glucocorticoid on mineralization and lipogenesis reactions in bone tissue microenvironments. This study highlighted emerging skeletal-anabolic actions of miR-29a signaling in the progression of glucocorticoid-induced bone tissue destruction. Sustaining miR-29a actions is beneficial in protecting against glucocorticoid-mediated osteoporosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Does graded reaming affect the composition of reaming products in intramedullary nailing of long bones?

PubMed

Kouzelis, Antonis Th; Kourea, Helen; Megas, Panagiotis; Panagiotopoulos, Elias; Marangos, Markos; Lambiris, Elias

2004-08-01

Reaming products taken during intramedullary nailing were examined to identify possible differences in their composition depending on the reaming percentage. Reaming products were taken from 39 fresh closed tibial and femoral diaphyseal fractures in patients with an average age of 29 years. According to histology, reaming products mainly consisted of bone trabeculae, viable or nonviable, and bone marrow stroma. A statistically significant reverse correlation exists between viable bone mass percentage and reaming progress. Reaming 1 mm less than the minimum canal diameter provides a higher viable bone mass percentage, which might be an important factor in the bone healing process.

Weight loss and bone mineral density.

PubMed

Hunter, Gary R; Plaisance, Eric P; Fisher, Gordon

2014-10-01

Despite evidence that energy deficit produces multiple physiological and metabolic benefits, clinicians are often reluctant to prescribe weight loss in older individuals or those with low bone mineral density (BMD), fearing BMD will be decreased. Confusion exists concerning the effects that weight loss has on bone health. Bone density is more closely associated with lean mass than total body mass and fat mass. Although rapid or large weight loss is often associated with loss of bone density, slower or smaller weight loss is much less apt to adversely affect BMD, especially when it is accompanied with high intensity resistance and/or impact loading training. Maintenance of calcium and vitamin D intake seems to positively affect BMD during weight loss. Although dual energy X-ray absorptiometry is normally used to evaluate bone density, it may overestimate BMD loss following massive weight loss. Volumetric quantitative computed tomography may be more accurate for tracking bone density changes following large weight loss. Moderate weight loss does not necessarily compromise bone health, especially when exercise training is involved. Training strategies that include heavy resistance training and high impact loading that occur with jump training may be especially productive in maintaining, or even increasing bone density with weight loss.

Association between body composition and pulmonary function in children and young people with cystic fibrosis.

PubMed

Calella, Patrizia; Valerio, Giuliana; Thomas, Matt; McCabe, Helen; Taylor, Jake; Brodlie, Malcolm; Siervo, Mario

2018-04-01

Body mass index (BMI) has significant limitations when assessing nutritional status in pediatric patients with cystic fibrosis (CF). We evaluated whether measurements of lean body mass (LBM) and fat mass (FM) are more sensitive nutritional parameters by testing their association with pulmonary function in adolescent patients with CF. Sixty-nine male and female adolescents with CF were studied (age: 14.5 ± 2.3, BMI: 19.5 ± 2.3 kg/m 2 ). Dual-energy x-ray absorptiometry (DXA) was used to measure total and segmental (appendicular, truncal) body composition (FM, LBM bone mineral density, and content) as routine care to monitor bone health. Correlation and multiple regression analyses were performed to assess the association among body composition variables and forced expiratory volume in 1 s (FEV 1 ). We also evaluated the influence of the F508del mutation on body composition. FEV 1 was significantly associated with total (r = 0.68, P <0.001), truncal (r = 0.71, P <0.001), and appendicular (r = 0.67, P <0.001) LBM, whereas it was not associated with total (r = 0.02, P = 0.89) and truncal (r = 0.04, P = 0.77) FM. BMI had a significant but weaker correlation with FEV 1 (r = 0.52, P <0.001) compared with LBM. LBM was the only significant predictor of FEV 1 in fully adjusted regression models. LBM is a significant predictor of pulmonary function in CF adolescent patients. DXA scanning performed as part of routine bone health monitoring in CF can provide important body composition data relevant to clinical interventions that optimize nutritional status. DXA reference data for LBM in non-adult populations are needed to enhance diagnostic assessment and monitor clinical progression of CF. Copyright © 2017 Elsevier Inc. All rights reserved.

Later Age at Onset of Independent Walking Is Associated With Lower Bone Strength at Fracture-Prone Sites in Older Men.

PubMed

Ireland, Alex; Muthuri, Stella; Rittweger, Joern; Adams, Judith E; Ward, Kate A; Kuh, Diana; Cooper, Rachel

2017-06-01

Later age at onset of independent walking is associated with lower leg bone strength in childhood and adolescence. However, it is unknown whether these associations persist into older age or whether they are evident at axial (central) or upper limb sites. Therefore, we examined walking age obtained at age 2 years and bone outcomes obtained by dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) scans at ages 60 to 64 years in a nationally representative cohort study of British people, the MRC National Survey of Health and Development. It was hypothesized that later walking age would be associated with lower bone strength at all sites. Later independent walking age was associated with lower height-adjusted hip (standardized regression coefficients with 95% confidence interval [CI] -0.179 [-0.251 to -0.107]), spine (-0.157 [-0.232 to -0.082]), and distal radius (-0.159 [-0.245 to -0.073]) bone mineral content (BMC, indicating bone compressive strength) in men (all p < 0.001). Adjustment for covariates partially attenuated these associations, primarily because of lower lean mass and adolescent sporting ability in later walkers. These associations were also evident for a number of hip geometric parameters (including cross-sectional moment of inertia [CSMI], indicating bone bending/torsional strength) assessed by hip structural analysis (HSA) from DXA scans. Similar height-adjusted associations were also observed in women for several hip, spine, and upper limb outcomes, although adjustment for fat or lean mass led to complete attenuation for most outcomes, with the exception of femoral shaft CSMI and spine bone area (BA). In conclusion, later independent walking age appears to have a lifelong association with bone strength across multiple skeletal sites in men. These effects may result from direct effects of early life loading on bone growth and mediation by adult body composition. Results suggest that late walking age may represent a novel risk factor for subsequent low bone strength. Existing interventions effective in hastening walking age may have positive effects on bone across life. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

Biochemical markers of bone turnover in children with clinical bone fragility.

PubMed

Bowden, Sasigarn A; Akusoba, Chiazor I; Hayes, John R; Mahan, John D

2016-06-01

The role of biochemical bone turnover markers (BTMs) in assessing low bone mass and monitoring bisphosphonate treatment in pediatric patients with clinical bone fragility is not well established. The aim of the study was to examine the correlations of BTMs and the bone mineral density (BMD), and evaluate the effects of bisphosphonates therapy on BTMs in children with clinical bone fragility. Clinical data of 115 patients with clinical bone fragility (mean age 9.7±5.8 years), 102 of whom received bisphosphonates, were studied. Serum alkaline phosphatase (ALP), osteocalcin (OC), urine pyridinoline (PD) and deoxypyridinoline (DPD), BMD at baseline and subsequent years were analyzed. There was a significant negative correlation between urine PD and lumbar BMD (slope=-0.29, p<0.001). There were no correlations between BTMs and lumbar BMD Z-score. There was a significant positive correlation between serum OC and serum ALP, urine PD and DPD (p<0.001). Serum OC, urine PD and DPD index, as expressed as measured value/upper limit of normal value for age, decreased during the first 3 years of bisphosphonate therapy. In children with clinical bone fragility, BTMs correlated with each other, but not with lumbar BMD Z-score. While they were not reliable predictors of degree of low BMD, the bone markers showed suppression during bisphosphonate therapy and may be helpful in monitoring the response to therapy.

Effects of Exercise on Bone Status in Female Subjects, from Young Girls to Postmenopausal Women: An Overview of Systematic Reviews and Meta-Analyses.

PubMed

Xu, Jincheng; Lombardi, Giovanni; Jiao, Wei; Banfi, Giuseppe

2016-08-01

Osteoporosis and postmenopausal bone loss pose a huge social and economic burden worldwide. Regular exercise and physical activity are effective interventions for maximizing or maintaining peak bone mass and preventing bone loss in the elderly; however, most recommendations are addressed to the general public and lack specific indications for girls and women, the segment of the population most at risk for developing osteoporosis. The aim of this overview of systematic reviews and meta-analyses was to summarize current evidence for the effects of exercise and physical activity interventions on bone status in girls and women, and to explore whether specific exercise programs exist for improving or maintaining bone mass or bone strength in females. The PubMed, EMBASE, PEDro, and Cochrane Library databases were searched from January 2009, updated to 22 June 2015, using the following groups of search terms: (i) 'physical activity' and 'exercise'; and (ii) 'bone', 'bone health', 'bone strength', 'bone structure', 'bone metabolism', 'bone turnover', and 'bone biomarkers'. Searches and screening were limited to systematic reviews or meta-analyses of studies in females and published in English. Our final analysis included 12 articles that met the inclusion criteria. Combined-impact exercise protocols (impact exercise with resistance training) are the best choice to preserve/improve bone mineral density in pre- and postmenopausal women. Peak bone mass in young girls can be improved with short bouts of school-based high-impact plyometric exercise programs. Whole-body vibration exercises have no beneficial effects on bone in postmenopausal or elderly women. Lifelong exercise, specific for age, is an effective way to sustain bone health in girls and women.

Relationship between ultrasound bone parameters, lung function, and body mass index in healthy student population.

PubMed

Cvijetić, Selma; Pipinić, Ivana Sabolić; Varnai, Veda Maria; Macan, Jelena

2017-03-01

Low bone mineral density has been reported in paediatric and adult patients with different lung diseases, but limited data are available on the association between lung function and bone density in a healthy young population. We explored the predictors of association between bone mass and pulmonary function in healthy first-year university students, focusing on body mass index (BMI). In this cross-sectional study we measured bone density with ultrasound and lung function with spirometry in 370 university students (271 girls and 99 boys). Information on lifestyle habits, such as physical activity, smoking, and alcohol consumption were obtained with a questionnaire. All lung function and bone parameters were significantly higher in boys than in girls (P<0.001). Underweight students had a significantly lower forced vital capacity (FVC%) (P=0.001 girls; P=0.012 boys), while overweight students had a significantly higher FVC% than normal weight students (P=0.024 girls; P=0.001 boys). BMI significantly correlated with FVC% (P=0.001) and forced expiratory volume in 1 second (FEV1 %) in both genders (P=0.001 girls; P=0.018 boys) and with broadband ultrasound attenuation (BUA) in boys. There were no significant associations between any of the bone and lung function parameters either in boys or girls. The most important determinant of lung function and ultrasound bone parameters in our study population was body mass index, with no direct association between bone density and lung function.

Central genes, pathways and modules that regulate bone mass.

PubMed

Quiros-Gonzalez, Isabel; Yadav, Vijay K

2014-11-01

Bones are structures that give the shape and defined features to vertebrates, protect several soft organs and perform multiple endocrine influences on other organs. To achieve these functions bones are first modeled early during life and then constantly remodeled throughout life. The process of bone (re)modeling happens simultaneously at multitude of locations in the skeleton and ensures that vertebrates have a mechanically strong yet a flexible skeleton to the most part of their life. Given the extent of its occurrence in the body, bone remodeling is a highly energy demanding process and is co-ordinated with other physiological processes as diverse as energy metabolism, sleep-wake cycle and reproduction. Neuronal circuits in the brain play a very important role in the coordination of bone remodeling with other organ system functions, and perform this function in sync with environmental and peripheral hormonal cues. In this review, we will focus on the roles of hormonal signals and neural circuits that originate in, or impinge on, the brain in the regulation of bone mass. We will provide herein an updated view of how advances in molecular genetics have refined the neural circuits involved in the regulation of bone mass, from the whole brain level to the specific neuronal populations and their neurotransmitters. This will help to understand the mechanisms whereby vertebrate brain regulates bone mass by fine-tuning metabolic signals that originate in the brain or elsewhere in the body. Copyright © 2014 Elsevier Inc. All rights reserved.

Mutations in Known Monogenic High Bone Mass Loci Only Explain a Small Proportion of High Bone Mass Cases

PubMed Central

Wheeler, Lawrie; Hardcastle, Sarah A; Appleton, Louise H; Addison, Kathryn A; Brugmans, Marieke; Clark, Graeme R; Ward, Kate A; Paggiosi, Margaret; Stone, Mike; Thomas, Joegi; Agarwal, Rohan; Poole, Kenneth ES; McCloskey, Eugene; Fraser, William D; Williams, Eleanor; Bullock, Alex N; Davey Smith, George; Brown, Matthew A; Tobias, Jon H; Duncan, Emma L

2015-01-01

ABSTRACT High bone mass (HBM) can be an incidental clinical finding; however, monogenic HBM disorders (eg, LRP5 or SOST mutations) are rare. We aimed to determine to what extent HBM is explained by mutations in known HBM genes. A total of 258 unrelated HBM cases were identified from a review of 335,115 DXA scans from 13 UK centers. Cases were assessed clinically and underwent sequencing of known anabolic HBM loci: LRP5 (exons 2, 3, 4), LRP4 (exons 25, 26), SOST (exons 1, 2, and the van Buchem's disease [VBD] 52‐kb intronic deletion 3′). Family members were assessed for HBM segregation with identified variants. Three‐dimensional protein models were constructed for identified variants. Two novel missense LRP5 HBM mutations ([c.518C>T; p.Thr173Met], [c.796C>T; p.Arg266Cys]) were identified, plus three previously reported missense LRP5 mutations ([c.593A>G; p.Asn198Ser], [c.724G>A; p.Ala242Thr], [c.266A>G; p.Gln89Arg]), associated with HBM in 11 adults from seven families. Individuals with LRP5 HBM (∼prevalence 5/100,000) displayed a variable phenotype of skeletal dysplasia with increased trabecular BMD and cortical thickness on HRpQCT, and gynoid fat mass accumulation on DXA, compared with both non‐LRP5 HBM and controls. One mostly asymptomatic woman carried a novel heterozygous nonsense SOST mutation (c.530C>A; p.Ser177X) predicted to prematurely truncate sclerostin. Protein modeling suggests the severity of the LRP5‐HBM phenotype corresponds to the degree of protein disruption and the consequent effect on SOST‐LRP5 binding. We predict p.Asn198Ser and p.Ala242Thr directly disrupt SOST binding; both correspond to severe HBM phenotypes (BMD Z‐scores +3.1 to +12.2, inability to float). Less disruptive structural alterations predicted from p.Arg266Cys, p.Thr173Met, and p.Gln89Arg were associated with less severe phenotypes (Z‐scores +2.4 to +6.2, ability to float). In conclusion, although mutations in known HBM loci may be asymptomatic, they only account for a very small proportion (∼3%) of HBM individuals, suggesting the great majority are explained by either unknown monogenic causes or polygenic inheritance. © 2015 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR). PMID:26348019

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.

Enhanced Wnt signaling improves bone mass and strength, but not brittleness, in the Col1a1(+/mov13) mouse model of type I Osteogenesis Imperfecta.

PubMed

Jacobsen, Christina M; Schwartz, Marissa A; Roberts, Heather J; Lim, Kyung-Eun; Spevak, Lyudmila; Boskey, Adele L; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

2016-09-01

Osteogenesis Imperfecta (OI) comprises a group of genetic skeletal fragility disorders. The mildest form of OI, Osteogenesis Imperfecta type I, is frequently caused by haploinsufficiency mutations in COL1A1, the gene encoding the α1(I) chain of type 1 collagen. Children with OI type I have a 95-fold higher fracture rate compared to unaffected children. Therapies for OI type I in the pediatric population are limited to anti-catabolic agents. In adults with osteoporosis, anabolic therapies that enhance Wnt signaling in bone improve bone mass, and ongoing clinical trials are determining if these therapies also reduce fracture risk. We performed a proof-of-principle experiment in mice to determine whether enhancing Wnt signaling in bone could benefit children with OI type I. We crossed a mouse model of OI type I (Col1a1(+/Mov13)) with a high bone mass (HBM) mouse (Lrp5(+/p.A214V)) that has increased bone strength from enhanced Wnt signaling. Offspring that inherited the OI and HBM alleles had higher bone mass and strength than mice that inherited the OI allele alone. However, OI+HBM and OI mice still had bones with lower ductility compared to wild-type mice. We conclude that enhancing Wnt signaling does not make OI bone normal, but does improve bone properties that could reduce fracture risk. Therefore, agents that enhance Wnt signaling are likely to benefit children and adults with OI type 1. Copyright © 2016 Elsevier Inc. All rights reserved.

Rictor/mTORC2 loss in osteoblasts impairs bone mass and strength.

PubMed

Liu, Dong-Mei; Zhao, Lin; Liu, Ting-Ting; Jiao, Pei-Lin; Zhao, Dian-Dian; Shih, Mei-Shu; Tao, Bei; Sun, Li-Hao; Zhao, Hong-Yan; Liu, Jian-Min

2016-09-01

Mammalian target of rapamycin (mTOR) is a Ser/Thr kinase conserved through evolution that coordinates extra cellular signals associated with cell growth. Main functions of mTOR present in the form of two complexes, namely mTORC1 and mTORC2, which are distinct in their unique components, raptor and rictor. In the current study, using a Cre/loxp system, we found an anabolic effect of mTORC2 signaling on skeleton. Osteoblast differentiation was reduced, with down-regulation of mTORC2 signaling activity in primary cultures of osteoblasts that did not contain rictor. Mice with a specific deletion of rictor in mature osteoblasts showed a significant reduction in lean mass and bone mineral density by dual energy x-ray absorptiometry analysis. Micro-computed tomography, histomorphometric, and molecular biological analyses revealed a marked impairment of the cortical bone mass and microarchitecture, as well as minor changes in trabecular bone, of the Rictorob(-/-) mice. Cortical bone mass and thickness of the femoral mid-shaft were dramatically reduced, with unusual increases in porosity and marrow area in Rictorob(-/-) mice. Thinner trabeculae were found in the L4 vertebrae with relatively normal structural indices of trabecular numbers and separation. A lower rate of bone turnover was observed, as the consequence of the decreased individual osteoblast activity and bone resorption. Furthermore, these changes were associated with significantly decreased bone biomechanical properties. In conclusion, expression of rictor in osteoblasts is essential for the maintenance of normal bone remodeling and microarchitecture, especially for the maintenance of the cortical bone. Copyright © 2016 Elsevier Inc. All rights reserved.

Physical development and swimming performance during biological maturation in young female swimmers.

PubMed

Lätt, Evelin; Jürimäe, Jaak; Haljaste, Kaja; Cicchella, Antonio; Purge, Priit; Jürimäe, Toivo

2009-03-01

The present study analyzed the development of physiological, biomechanical and anthropometrical parameters in young female swimmers and assessed the effect of these parameters on swimming performance during biological maturation. In total, 26 female swimmers participated in the study in which data were annually collected for two consecutive years. Body composition, basic anthropometrical parameters and biological age were measured. During the 400-m front-crawl swimming, the energy cost of swimming and stroking parameters were assessed. Peak oxygen consumption (VO2(peak)) was assessed by means of the backward-extrapolation technique recording VO2 during the first 20 sec of the recovery period after a maximal trial of 400-m distance. During the 2-year follow-up study period, age, height, body mass, body fat %, fat free mass, bone mineral mass, total bone mineral density, arm span and biological maturation values significantly increased during each year (p < 0.05). The tracking of the physical characteristics measured over the 2-year study period was relatively high (r > 0.694), except for the body fat% (r > 0.554). The tracking of the Tanner stages was also high (r = 0.759-0.780). Stepwise regression analyses showed that biomechanical factors (R2 > 0.322; p < 0.05) best characterized the 400-metre swimming performance in young female swimmers, followed by bioenergetical (R2 > 0.311; p < 0.05) and physical (R2 > 0.203; p < 0.05) factors during all three measurement times.

Influence of Body Weight on Bone Mass, Architecture, and Turnover

PubMed Central

Iwaniec, Urszula T.; Turner, Russell T.

2016-01-01

Weight-dependent loading of the skeleton plays an important role in establishing and maintaining bone mass and strength. This review focuses on mechanical signaling induced by body weight as an essential mechanism for maintaining bone health. In addition, the skeletal effects of deviation from normal weight are discussed. The magnitude of mechanical strain experienced by bone during normal activities is remarkably similar among vertebrates, regardless of size, supporting the existence of a conserved regulatory mechanism, or mechanostat, that senses mechanical strain. The mechanostat functions as an adaptive mechanism to optimize bone mass and architecture based on prevailing mechanical strain. Changes in weight, due to altered mass, weightlessness (spaceflight), and hypergravity (modeled by centrifugation), induce an adaptive skeletal response. However, the precise mechanisms governing the skeletal response are incompletely understood. Furthermore, establishing whether the adaptive response maintains the mechanical competence of the skeleton has proven difficult, necessitating development of surrogate measures of bone quality. The mechanostat is influenced by regulatory inputs to facilitate non-mechanical functions of the skeleton, such as mineral homeostasis, as well as hormones and energy/nutrient availability that support bone metabolism. While the skeleton is very capable of adapting to changes in weight, the mechanostat has limits. At the limits, extreme deviations from normal weight and body composition are associated with impaired optimization of bone strength to prevailing body size. PMID:27352896

Bone mineral density in human immunodeficiency virus-1 infected men with hypogonadism prior to highly-active-antiretroviral-therapy (HAART)

PubMed Central

2009-01-01

Alterations of bone metabolism have been observed in numerous studies of HIV-infected patients. Sex steroids are known to profoundly influence bone mass and bone turnover. Hypogonadism is common in HIV-infection. Therefore, we performed a cross sectional study of 80 male HIV-infected patients without wasting syndrome, and 20 healthy male controls, in whom we analyzed urine and serum samples for both calciotropic hormones and markers of bone metabolism and of endocrine testicular function. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry both in the lumbar spine and Ward's triangle of the left hip. None of the patients received highly-active-antiretroviral-therapy (HAART). Compared to eugonadal HIV-infected patients, subjects with hypogonadism (n = 32; 40%) showed statistically significant decrease of serum osteocalcin (p < 0.05) and elevated urinary excretion of crosslinks (p < 0.05). However, we found 13 and 15, respectively, patients with osteopenia (t-score -1.0 to -2.5 SD below normal) of the lumbar spine. The dissociation between bone formation and resorption and the reduction of of BMD (p < 0.05) is stronger expressed in patients with hypogonadism. Habitual hypogonadism appears to be of additional relevance for bone metabolism of male HIV-positive patients prior to HAART. PMID:19258214

Effects of growth hormone administration for 6 months on bone turnover and bone marrow fat in obese premenopausal women.

PubMed

Bredella, Miriam A; Gerweck, Anu V; Barber, Lauren A; Breggia, Anne; Rosen, Clifford J; Torriani, Martin; Miller, Karen K

2014-05-01

Abdominal adiposity is associated with low BMD and decreased growth hormone (GH) secretion, an important regulator of bone homeostasis. The purpose of our study was to determine the effects of a short course of GH on markers of bone turnover and bone marrow fat in premenopausal women with abdominal adiposity. In a 6-month, randomized, double-blind, placebo-controlled trial we studied 79 abdominally obese premenopausal women (21-45 y) who underwent daily sc injections of GH vs. placebo. Main outcome measures were body composition by DXA and CT, bone marrow fat by proton MR spectroscopy, P1NP, CTX, 25(OH)D, hsCRP, undercarboxylated osteocalcin (ucOC), preadipocyte factor 1 (Pref 1), apolipoprotein B (ApoB), and IGF-1. GH increased IGF-1, P1NP, 25(OH)D, ucOC, bone marrow fat and lean mass, and decreased abdominal fat, hsCRP, and ApoB compared with placebo (p<0.05). There was a trend toward an increase in CTX and Pref-1. Among all participants, a 6-month increase in IGF-1 correlated with 6-month increase in P1NP (p=0.0005), suggesting that subjects with the greatest increases in IGF-1 experienced the greatest increases in bone formation. A six-month decrease in abdominal fat, hsCRP, and ApoB inversely predicted 6-month change in P1NP, and 6-month increase in lean mass and 25(OH)D positively predicted 6-month change in P1NP (p≤0.05), suggesting that subjects with greatest decreases in abdominal fat, inflammation and ApoB, and the greatest increases in lean mass and 25(OH)D experienced the greatest increases in bone formation. A six-month increase in bone marrow fat correlated with 6-month increase in P1NP (trend), suggesting that subjects with the greatest increases in bone formation experienced the greatest increases in bone marrow fat. Forward stepwise regression analysis indicated that increase in lean mass and decrease in abdominal fat were positive predictors of P1NP. When IGF-1 was added to the model, it became the only predictor of P1NP. GH replacement in abdominally obese premenopausal women for 6 months increased bone turnover and bone marrow fat. Reductions in abdominal fat, and inflammation, and increases in IGF-1, lean mass and vitamin D were associated with increased bone formation. The increase in bone marrow fat may reflect changes in energy demand from increased bone turnover. Copyright © 2014 Elsevier Inc. All rights reserved.

Identifying sex-specific risk factors for low bone mineral density in adolescent runners.

PubMed

Tenforde, Adam Sebastian; Fredericson, Michael; Sayres, Lauren Carter; Cutti, Phil; Sainani, Kristin Lynn

2015-06-01

Adolescent runners may be at risk for low bone mineral density (BMD) associated with sports participation. Few prior investigations have evaluated bone health in young runners, particularly males. To characterize sex-specific risk factors for low BMD in adolescent runners. Cross-sectional study; Level of evidence, 3. Training characteristics, fracture history, eating behaviors and attitudes, and menstrual history were measured using online questionnaires. A food frequency questionnaire was used to identify dietary patterns and measure calcium intake. Runners (female: n = 94, male: n = 42) completed dual-energy x-ray absorptiometry (DXA) to measure lumbar spine (LS) and total body less head (TBLH) BMD and body composition values, including android-to-gynoid (A:G) fat mass ratio. The BMD was standardized to Z-scores using age, sex, and race/ethnicity reference values. Questionnaire values were combined with DXA values to determine risk factors associated with differences in BMD Z-scores in LS and TBLH and low bone mass (defined as BMD Z-score ≤-1). In multivariable analyses, risk factors for lower LS BMD Z-scores in girls included lower A:G ratio, being shorter, and the combination of (interaction between) current menstrual irregularity and a history of fracture (all P < .01). Later age of menarche, lower A:G ratio, lower lean mass, and drinking less milk were associated with lower TBLH BMD Z-scores (P < .01). In boys, lower body mass index (BMI) Z-scores and the belief that being thinner improves performance were associated with lower LS and TBLH BMD Z-scores (all P < .05); lower A:G ratio was additionally associated with lower TBLH Z-scores (P < .01). Thirteen girls (14%) and 9 boys (21%) had low bone mass. Girls with a BMI ≤17.5 kg/m(2) or both menstrual irregularity and a history of fracture were significantly more likely to have low bone mass. Boys with a BMI ≤17.5 kg/m(2) and belief that thinness improves performance were significantly more likely to have low bone mass. This study identified sex-specific risk factors for impaired bone mass in adolescent runners. These risk factors can be helpful to guide sports medicine professionals in evaluation and management of young runners at risk for impaired bone health. © 2015 The Author(s).

Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis.

PubMed

Langdahl, Bente; Ferrari, Serge; Dempster, David W

2016-12-01

The adult skeleton is renewed by remodeling throughout life. Bone remodeling is a process where osteoclasts and osteoblasts work sequentially in the same bone remodeling unit. After the attainment of peak bone mass, bone remodeling is balanced and bone mass is stable for one or two decades until age-related bone loss begins. Age-related bone loss is caused by increases in resorptive activity and reduced bone formation. The relative importance of cortical remodeling increases with age as cancellous bone is lost and remodeling activity in both compartments increases. Bone modeling describes the process whereby bones are shaped or reshaped by the independent action of osteoblast and osteoclasts. The activities of osteoblasts and osteoclasts are not necessarily coupled anatomically or temporally. Bone modeling defines skeletal development and growth but continues throughout life. Modeling-based bone formation contributes to the periosteal expansion, just as remodeling-based resorption is responsible for the medullary expansion seen at the long bones with aging. Existing and upcoming treatments affect remodeling as well as modeling. Teriparatide stimulates bone formation, 70% of which is remodeling based and 20-30% is modeling based. The vast majority of modeling represents overflow from remodeling units rather than de novo modeling. Denosumab inhibits bone remodeling but is permissive for modeling at cortex. Odanacatib inhibits bone resorption by inhibiting cathepsin K activity, whereas modeling-based bone formation is stimulated at periosteal surfaces. Inhibition of sclerostin stimulates bone formation and histomorphometric analysis demonstrated that bone formation is predominantly modeling based. The bone-mass response to some osteoporosis treatments in humans certainly suggests that nonremodeling mechanisms contribute to this response and bone modeling may be such a mechanism. To date, this has only been demonstrated for teriparatide, however, it is clear that rediscovering a phenomenon that was first observed more half a century ago will have an important impact on our understanding of how new antifracture treatments work.