[Assessment tools in early detection of osteoporosis in dentistry].

PubMed

Knezović Zlatarić, Dubravka; Pandurić, Josip; Korsić, Mirko; Dodig, Damir

2007-03-01

Osteoporosis, one of the major skeletal diseases in older age, is characterised by low bone mass and microarchitectural deterioration with a resulting increase in bone fragility and hence susceptibility to fracture. In this review we analyse the systemic and local factors associated with oral bone mass loss. Systemic factors most often correlated with the oral bone mass loss include osteoporosis, renal diseases, hormonal disorders, diet and the impact of different drugs on the bony structure. Chronic periodontal disease, early loss of teeth or the effect of inadequate prosthodontic appliance on the residual ridge are the local factors associated with mandibular bone loss. Different assessment tools for the assessment of mandibular oral bone loss have been proposed, such as DXA absorptiometry, quantitative computed tomography, intraoral microdensitometry, SCORE index and the assessment of the thickness and quality of the mandibular inferior cortical border. Qualitative and quantitative assessment of the mandibular bony structure is of great importance in all fields of dentistry - from periodontology to endodontics and prosthodontics, especially in dental implantology. It is important to make the correct indication prior to dental implant therapy, and taking into account the systemic and local factors mentioned above, assess both the actual quality and quantity of the mandible.

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.

[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.

Correspondence between theoretical models and dual energy x-ray absorptiometry measurements of femoral cross-sectional growth during adolescence

NASA Technical Reports Server (NTRS)

van der Meulen, M. C.; Marcus, R.; Bachrach, L. K.; Carter, D. R.

1997-01-01

We have developed an analytical model of long bone cross-sectional ontogeny in which appositional growth of the diaphysis is primarily driven by mechanical stimuli associated with increasing body mass during growth and development. In this study, our goal was to compare theoretical predictions of femoral diaphyseal structure from this model with measurements of femoral bone mineral and geometry by dual energy x-ray absorptiometry. Measurements of mid-diaphyseal femoral geometry and structure were made previously in 101 Caucasian adolescents and young adults 9-26 years of age. The data on measured bone mineral content and calculated section modulus were compared with the results of our analytical model of cross-sectional development of the human femur over the same age range. Both bone mineral content and section modulus showed good correspondence with experimental measurements when the relationships with age and body mass were examined. Strong linear relationships were evident for both parameters when examined as a function of body mass.

Effects of Habitual Physical Activity and Fitness on Tibial Cortical Bone Mass, Structure and Mass Distribution in Pre-pubertal Boys and Girls: The Look Study.

PubMed

Duckham, Rachel L; Rantalainen, Timo; Ducher, Gaele; Hill, Briony; Telford, Richard D; Telford, Rohan M; Daly, Robin M

2016-07-01

Targeted weight-bearing activities during the pre-pubertal years can improve cortical bone mass, structure and distribution, but less is known about the influence of habitual physical activity (PA) and fitness. This study examined the effects of contrasting habitual PA and fitness levels on cortical bone density, geometry and mass distribution in pre-pubertal children. Boys (n = 241) and girls (n = 245) aged 7-9 years had a pQCT scan to measure tibial mid-shaft total, cortical and medullary area, cortical thickness, density, polar strength strain index (SSIpolar) and the mass/density distribution through the bone cortex (radial distribution divided into endo-, mid- and pericortical regions) and around the centre of mass (polar distribution). Four contrasting PA and fitness groups (inactive-unfit, inactive-fit, active-unfit, active-fit) were generated based on daily step counts (pedometer, 7-days) and fitness levels (20-m shuttle test and vertical jump) for boys and girls separately. Active-fit boys had 7.3-7.7 % greater cortical area and thickness compared to inactive-unfit boys (P < 0.05), which was largely due to a 6.4-7.8 % (P < 0.05) greater cortical mass in the posterior-lateral, medial and posterior-medial 66 % tibial regions. Cortical area was not significantly different across PA-fitness categories in girls, but active-fit girls had 6.1 % (P < 0.05) greater SSIpolar compared to inactive-fit girls, which was likely due to their 6.7 % (P < 0.05) greater total bone area. There was also a small region-specific cortical mass benefit in the posterior-medial 66 % tibia cortex in active-fit girls. Higher levels of habitual PA-fitness were associated with small regional-specific gains in 66 % tibial cortical bone mass in pre-pubertal children, particularly boys.

The Role of Nutrition in the Changes in Bone and Calcium Metabolism During Space Flight

NASA Technical Reports Server (NTRS)

Morey-Holton, Emily R.; Arnaud, Sara B.

1995-01-01

On Earth, the primary purpose of the skeleton is provide structural support for the body. In space, the support function of the skeleton is reduced since, without gravity, structures have only mass and no weight. The adaptation to space flight is manifested by shifts in mineral distribution, altered bone turnover, and regional mineral deficits in weight-bearing bones. The shifts in mineral distribution appear to be related to the cephalic fluid shift. The redistribution of mineral from one bone to another or to and from areas in the same bone in response to alterations in gravitational loads is more likely to affect skeletal function than quantitative whole body losses and gains. The changes in bone turnover appear dependent upon changes in body weight with weight loss tending to increase bone resorption as well as decrease bone formation. During bedrest, the bone response to unloading varies depending upon the routine activity level of the subjects with more active subjects showing a greater suppression of bone formation in the iliac crest with inactivity. Changes in body composition during space flight are predicted by bedrest studies on Earth which show loss of lean body mass and increase tn body fat in adult males after one month. In ambulatory studies on Earth, exercising adult males of the same age, height, g weight, body mass index, and shoe size show significantly higher whole body mineral and lean body mass. than non-exercising subjects. Nutritional preference appears to change with activity level. Diet histories in exercisers and nonexercisers who maintain identical body weights show no differences in nutrients except for slightly higher carbohydrate intake in the exercisers. The absence of differences in dietary calcium in men with higher total body calcium is noteworthy. In this situation, the increased bone mineral content was facilitated by the calcium endocrine system. This regulatory system can be by-passed by raising dietary calcium. Increased calcium intake can increase the calcium content in normally loaded bone. However, bone with a higher calcium content still decreases proportionally to normal bone during unloading. Nutritional requirements in space should be reevaluated with respect to these adaptive changes to loading and physical activity.

One year of abaloparatide, a selective peptide activator of the PTH1 receptor, increased bone mass and strength in ovariectomized rats.

PubMed

Varela, Aurore; Chouinard, Luc; Lesage, Elisabeth; Guldberg, Robert; Smith, Susan Y; Kostenuik, Paul J; Hattersley, Gary

2017-02-01

Abaloparatide is a novel 34 amino acid peptide selected to be a potent and selective activator of the parathyroid hormone receptor 1 (PTHR1) signaling pathway. The effects of 12months of abaloparatide treatment on bone mass, bone strength and bone quality was assessed in osteopenic ovariectomized (OVX) rats. SD rats were subjected to OVX or sham surgery at 6months of age and left untreated for 3months to allow OVX-induced bone loss. Eighteen OVX rats were sacrificed after this bone depletion period, and the remaining OVX rats received daily s.c. injections of vehicle (n=18) or abaloparatide at 1, 5 or 25μg/kg/d (n=18/dose level) for 12months. Sham controls (n=18) received vehicle daily. Bone changes were assessed by DXA and pQCT after 0, 3, 6 or 12months of treatment, and destructive biomechanical testing was conducted at month 12 to assess bone strength and bone quality. Abaloparatide dose-dependently increased bone mass at the lumbar spine and at the proximal and diaphyseal regions of the tibia and femur. pQCT revealed that increased cortical bone volume at the tibia was a result of periosteal expansion and endocortical bone apposition. Abaloparatide dose-dependently increased structural strength of L4-L5 vertebral bodies, the femur diaphysis, and the femur neck. Increments in peak load for lumbar spine and the femur diaphysis of abaloparatide-treated rats persisted even after adjusting for treatment-related increments in BMC, and estimated material properties were maintained or increased at the femur diaphysis with abaloparatide. The abaloparatide groups also exhibited significant and positive correlations between bone mass and bone strength at these sites. These data indicate that gains in cortical and trabecular bone mass with abaloparatide are accompanied by and correlated with improvements in bone strength, resulting in maintenance or improvement in bone quality. Thus, this study demonstrated that long-term daily administration of abaloparatide to osteopenic OVX rats led to dose-dependent improvements in bone mass, geometry and strength. Copyright © 2016. Published by Elsevier Inc.

Design, synthesis, and osteogenic activity of daidzein analogs on human mesenchymal stem cells

USDA-ARS?s Scientific Manuscript database

Osteoporosis, defined by the loss of bone mass and strength, results in the loss of structural and mechanical support in bone, and leads to an increased risk of fractures. In the adult skeleton, the bone undergoes continuous resorption carried out by osteoclast cells, and formation by osteoblast cel...

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.

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

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.

[Bone Cell Biology Assessed by Microscopic Approach. Assessment of bone quality using Raman and infrared spectroscopy].

PubMed

Suda, Hiromi Kimura

2015-10-01

Bone quality, which was defined as "the sum total of characteristics of the bone that influence the bone's resistance to fracture" at the National Institute of Health (NIH) conference in 2001, contributes to bone strength in combination with bone mass. Bone mass is often measured as bone mineral density (BMD) and, consequently, can be quantified easily. On the other hand, bone quality is composed of several factors such as bone structure, bone matrix, calcification degree, microdamage, and bone turnover, and it is not easy to obtain data for the various factors. Therefore, it is difficult to quantify bone quality. We are eager to develop new measurement methods for bone quality that make it possible to determine several factors associated with bone quality at the same time. Analytic methods based on Raman and FTIR spectroscopy have attracted a good deal of attention as they can provide a good deal of chemical information about hydroxyapatite and collagen, which are the main components of bone. A lot of studies on bone quality using Raman and FTIR imaging have been reported following the development of the two imaging systems. Thus, both Raman and FTIR imaging appear to be promising new bone morphometric 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.

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

Establishment of peak bone mass.

PubMed

Mora, Stefano; Gilsanz, Vicente

2003-03-01

Among the main areas of progress in osteoporosis research during the last decade or so are the general recognition that this condition, which is the cause of so much pain in the elderly population, has its antecedents in childhood and the identification of the structural basis accounting for much of the differences in bone strength among humans. Nevertheless, current understanding of the bone mineral accrual process is far from complete. The search for genes that regulate bone mass acquisition is ongoing, and current results are not sufficient to identify subjects at risk. However, there is solid evidence that BMD measurements can be helpful for the selection of subjects that presumably would benefit from preventive interventions. The questions regarding the type of preventive interventions, their magnitude, and duration remain unanswered. Carefully designed controlled trials are needed. Nevertheless, previous experience indicates that weight-bearing activity and possibly calcium supplements are beneficial if they are begun during childhood and preferably before the onset of puberty. Modification of unhealthy lifestyles and increments in exercise or calcium assumption are logical interventions that should be implemented to improve bone mass gains in all children and adolescents who are at risk of failing to achieve an optimal peak bone mass.

rhIGF-1 Treatment Increases Bone Mineral Density and Trabecular Bone Structure in Children with PAPP-A2 Deficiency.

PubMed

Hawkins-Carranza, Federico G; Muñoz-Calvo, María T; Martos-Moreno, Gabriel Á; Allo-Miguel, Gonzalo; Del Río, Luis; Pozo, Jesús; Chowen, Julie A; Pérez-Jurado, Luis A; Argente, Jesús

2018-01-01

Our objective was to determine changes in bone mineral density (BMD), trabecular bone score (TBS), and body composition after 2 years of therapy with recombinant human insulin-like growth factor-1 (rhIGF-1) in 2 prepubertal children with a complete lack of circulating PAPP-A2 due to a homozygous mutation in PAPP-A2 (p.D643fs25*) resulting in a premature stop codon. Body composition, BMD, and bone structure were determined by dual-energy X-ray absorptiometry at baseline and after 1 and 2 years of rhIGF-1 treatment. Height increased from 132 to 145.5 cm (patient 1) and from 111.5 to 124.5 cm (patient 2). Bone mineral content increased from 933.40 to 1,057.97 and 1,152.77 g in patient 1, and from 696.12 to 773.26 and 911.51 g in patient 2, after 1 and 2 years, respectively. Whole-body BMD also increased after 2 years of rhIGF-1 from baseline 0.788 to 0.869 g/cm2 in patient 1 and from 0.763 to 0.829 g/cm2 in patient 2. After 2 years of treatment, both children had an improvement in TBS. During therapy, a slight increase in body fat mass was seen, with a concomitant increase in lean mass. No adverse effects were reported. Two years of rhIGF-1 improved growth, with a tendency to improve bone mass and bone microstructure and to modulate body composition. © 2018 S. Karger AG, Basel.

The role of the collaborative functions of the composite structure of organic and inorganic constituents and their influence on the electrical properties of human bone.

PubMed

Kohata, Kazuhiro; Itoh, Soichiro; Horiuchi, Naohiro; Yoshioka, Taro; Yamashita, Kimihiro

2016-08-12

The electrical potential, which is generated in bone by collagen displacement, has been well documented. However, the role of mineral crystals in bone piezoelectricity has not yet been elucidated. We examined the mechanism that the composite structure of organic and inorganic constituents and their collaborative functions play an important role in the electrical properties of human bone. The electrical potential and bone structure were evaluated using thermally stimulated depolarized current (TSDC) and micro computed tomography, respectively. After electrical polarization of bone specimens, the stored electrical charge was calculated using TSDC measurements. The CO3/PO4 peak ratio was calculated using attenuated total reflection to compare the content of carbonate ion in the bone specimens. The TSDC curve contained 3 peaks at 100, 300 and 500°C, which were classified into 4 patterns. The CO3/PO4 peak ratio positively correlated with the stored charges at approximately 300°C in the polarized bone. There was a positive correlation between the stored bone charge and the bone mineral density only. It is suggested that the peak at 300°C is attributed to carbonate apatite and the total bone mass of human bone, not the three-dimensional structure, affects the stored charge.

Whole bone mechanics and bone quality.

PubMed

Cole, Jacqueline H; van der Meulen, Marjolein C H

2011-08-01

The skeleton plays a critical structural role in bearing functional loads, and failure to do so results in fracture. As we evaluate new therapeutics and consider treatments to prevent skeletal fractures, understanding the basic mechanics underlying whole bone testing and the key principles and characteristics contributing to the structural strength of a bone is critical. We therefore asked: (1) How are whole bone mechanical tests performed and what are the key outcomes measured? (2) How do the intrinsic characteristics of bone tissue contribute to the mechanical properties of a whole bone? (3) What are the effects of extrinsic characteristics on whole bone mechanical behavior? (4) Do environmental factors affect whole bone mechanical properties? We conducted a PubMed search using specific search terms and limiting our included articles to those related to in vitro testing of whole bones. Basic solid mechanics concepts are summarized in the context of whole bone testing and the determinants of whole bone behavior. Whole bone mechanical tests measure structural stiffness and strength from load-deformation data. Whole bone stiffness and strength are a function of total bone mass and the tissue geometric distribution and material properties. Age, sex, genetics, diet, and activity contribute to bone structural performance and affect the incidence of skeletal fractures. Understanding and preventing skeletal fractures is clinically important. Laboratory tests of whole bone strength are currently the only measures for in vivo fracture prediction. In the future, combined imaging and engineering models may be able to predict whole bone strength noninvasively.

Calcium requirements for Asian children and adolescents.

PubMed

Lee, Warren Tak Keung; Jiang, Ji

2008-01-01

Calcium is important for bone health. Over the last 15 years, reference calcium intakes in Western countries have been revised upwards for maximizing bone mass at skeletal maturity and for prevention of osteoporotic fractures. Some of these reference figures have also been adopted for use in Asian countries. However, the scientific data based on for revising reference calcium intakes in the West was largely based on Caucasians. Limited human studies relating to calcium requirements and bone mineralization have been conducted in Asians in Asia. In children and adolescents, a trial has confirmed no effects of calcium supplementation on bone gains in adolescent girls after 7 years. A meta-analysis has also revealed that calcium supplementation has little beneficial effects on bone gain. Given that genetic factors, hormonal status, body size, bone structure, diets, physical activity, vitamin D status and adaptation could modify calcium retention and bone integrity, these factors need to be considered collectively to promote bone health in Asian populations. Furthermore, studies to identify indigenous foods rich in calcium and high in bioavailability are needed to widen sources of dietary calcium. Ethnic differences in calcium retention, hormonal status, bone structure, bone mineral accretion and peak bone mass are evident among Asians, Caucasians and Blacks in USA. Hence, reference calcium intakes for Asians are likely to be unique and different from those of Caucasians. More research has to be conducted in Asian populations in order to develop appropriate reference calcium intakes for the region.

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.

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.

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.

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.

Ethnic Differences in Bone Health

PubMed Central

Zengin, Ayse; Prentice, Ann; Ward, Kate Anna

2015-01-01

There are differences in bone health between ethnic groups in both men and in women. Variations in body size and composition are likely to contribute to reported differences. Most studies report ethnic differences in areal bone mineral density (aBMD), which do not consistently parallel ethnic patterns in fracture rates. This suggests that other parameters beside aBMD should be considered when determining fracture risk between and within populations, including other aspects of bone strength: bone structure and microarchitecture, as well as muscle strength (mass, force generation, anatomy) and fat mass. We review what is known about differences in bone-densitometry-derived outcomes between ethnic groups and the extent to which they account for the differences in fracture risk. Studies are included that were published primarily between 1994 and 2014. A “one size fits all approach” should definitely not be used to understand better ethnic differences in fracture risk. PMID:25852642

[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.

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

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.

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.

Osteoblast-Specific Overexpression of Human WNT16 Increases Both Cortical and Trabecular Bone Mass and Structure in Mice

PubMed Central

Alkhouli, Mohammed; Gerard-O'Riley, Rita L.; Wright, Weston B.; Acton, Dena; Gray, Amie K.; Patel, Bhavmik; Reilly, Austin M.; Lim, Kyung-Eun; Robling, Alexander G.; Econs, Michael J.

2016-01-01

Previous genome-wide association studies have identified common variants in genes associated with bone mineral density (BMD) and risk of fracture. Recently, we identified single nucleotide polymorphisms (SNPs) in Wingless-type mouse mammary tumor virus integration site (WNT)16 that were associated with peak BMD in premenopausal women. To further identify the role of Wnt16 in bone mass regulation, we created transgenic (TG) mice overexpressing human WNT16 in osteoblasts. We compared bone phenotypes, serum biochemistry, gene expression, and dynamic bone histomorphometry between TG and wild-type (WT) mice. Compared with WT mice, WNT16-TG mice exhibited significantly higher whole-body areal BMD and bone mineral content (BMC) at 6 and 12 weeks of age in both male and female. Microcomputer tomography analysis of trabecular bone at distal femur revealed 3-fold (male) and 14-fold (female) higher bone volume/tissue volume (BV/TV), and significantly higher trabecular number and trabecular thickness but lower trabecular separation in TG mice compared with WT littermates in both sexes. The cortical bone at femur midshaft also displayed significantly greater bone area/total area and cortical thickness in the TG mice in both sexes. Serum biochemistry analysis showed that male TG mice had higher serum alkaline phosphatase, osteocalcin, osteoprotegerin (OPG), OPG to receptor activator of NF-kB ligand (tumor necrosis family ligand superfamily, number 11; RANKL) ratio as compared with WT mice. Also, lower carboxy-terminal collagen cross-link (CTX) to tartrate-resistant acid phosphatase 5, isoform b (TRAPc5b) ratio was observed in TG mice compared with WT littermates in both male and female. Histomorphometry data demonstrated that both male and female TG mice had significantly higher cortical and trabecular mineralizing surface/bone surface and bone formation rate compared with sex-matched WT mice. Gene expression analysis demonstrated higher expression of Alp, OC, Opg, and Opg to Rankl ratio in bone tissue in the TG mice compared with WT littermates. Our data indicate that WNT16 is critical for positive regulation of both cortical and trabecular bone mass and structure and that this molecule might be targeted for therapeutic interventions to treat osteoporosis. PMID:26584014

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 ...

Skeletal phenotype of growing transgenic mice that express a function-perturbing form of beta1 integrin in osteoblasts

NASA Technical Reports Server (NTRS)

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

2005-01-01

Skeletal modeling entails the deposition of large amounts of extracellular matrix (ECM) to form structures tailored to withstand increasing mechanical loads during rapid growth. Specific ECM molecules bind to integrin receptors on the cell surface, thereby triggering a cascade of signaling events that affect critical cell functions. To evaluate the role of integrins during skeletal growth, transgenic mice were engineered to express a function-perturbing fragment of beta1 integrin consisting of the transmembrane domain and cytoplasmic tail under the control of the osteocalcin promoter (TG mice). Thus, transgene expression was targeted to mature cells of the osteoblast lineage, and herein we show that cultured cells resembling osteocytes from 90-day-old TG mice display impaired adhesion to collagen I, a ligand for beta1 integrin. To determine the influence of beta1 integrin on bones that are responsible for providing structural support during periods of rapid growth, we examined the phenotype of the appendicular skeleton in TG mice compared to wild type (WT) mice. According to radiographs, bones from mice of both genotypes between 14 and 90 days of age appeared similar in gross structure and density, although proximal tibiae from 35-90 days old TG mice were less curved than those of WT mice (72-92% TG/WT). Although there were only mild and transient differences in absolute bone mass and strength, once normalized to body mass, the tibial dry mass (79.1% TG/WT females), ash mass (78.5% TG/WT females), and femoral strength in torsion (71.6% TG/WT females) were reduced in TG mice compared to WT mice at 90 days of age. Similar effects of genotype on bone mass and curvature were observed in 1-year-old retired breeders, indicating that these phenotypic differences between TG and WT mice were stable well into adulthood. Effects of genotype on histomorphometric indices of cancellous bone turnover were minimal and evident only transiently during growth, but when present they demonstrated differences in osteoblast rather than osteoclast parameters. Together, these results suggest that integrin signals generated during growth enhance the acquisition of a skeletal mass, structure, and strength to withstand the mechanical loads generated by weight-bearing.

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

β-Ecdysone Augments Peak Bone Mass in Mice of Both Sexes.

PubMed

Dai, Weiwei; Zhang, HongLiang; Zhong, Zhendong A; Jiang, Li; Chen, Haiyan; Lay, Yu-An Evan; Kot, Alexander; Ritchie, Robert O; Lane, Nancy E; Yao, Wei

2015-08-01

One of the strongest predictors for osteoporosis is peak bone mass. Interventions to augment peak bone mass have yet to be developed. β-Ecdysone (βEcd), a natural steroid-like compound produced by arthropods to initiate metamorphosis, is believed to have androgenic effects and so may be used to augment bone mass. The purpose of this study was to use both male and female (1) gonadal-sufficient; and (2) -insufficient mice to investigate sex differences in terms of bone development and structure after βEcd administration. Two-month-old male and female Swiss-Webster mice were randomized to receive either vehicle or βEcd (0.5 mg/kg) for 3 weeks. In a separate experiment to evaluate the effects of βEcd on sex hormone-deficient mice, gonadectomy was performed in male (orchiectomy [ORX]) and female mice (ovariectomy [OVX]). Sham-operated and the ORX/OVX mice were then treated for 3 weeks with βEcd. Primary endpoints for the study were trabecular bone structure and bone strength. In male mice, the trabecular bone volume was 0.18±0.02 in the placebo-treated (PL) and 0.23±0.02 in the βEcd-treated group (p<0.05 versus PL); and 0.09±0.01 in the ORX group (p<0.05 versus PL) and 0.12±0.01 in the ORX+βEcd group. Vertebral bone strength (maximum load) was 43±2 in PL and 51±1 in the βEcd-treated group (p<0.05 versus PL); and 30±4 in the ORX group (p<0.05 versus PL) and 37±3 in the ORX+βEcd group. In female mice, trabecular bone volume was 0.23±0.02 in PL and 0.26±0.02 in the βEcd-treated group (p<0.05 versus PL); and 0.15±0.01 in the OVX group (p<0.05 versus PL) and 0.14±0.01 in the OVX+βEcd group. Maximum load of the vertebrae was 45±2 in PL and 48±4 in the βEcd-treated group; and 39±4 in the OVX group (p<0.05 versus PL) and 44±4 in the OVX+βEcd group. These findings suggest the potential use of βEcd in the augmentation of bone mass in growing male and female mice. It may also partially prevent the detrimental effects of gonadectomy on trabecular bone. Our results support the potential use of βEcd or nature products that are rich in βEcd to augment peak bone mass. βEcd may differ from the other anabolic hormone treatments that may have severe side effects such as serious cardiac complications. However, its effects on humans remain to be determined.

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.

Bone Mass and Strength are Significantly Improved in Mice Overexpressing Human WNT16 in Osteocytes.

PubMed

Alam, Imranul; Reilly, Austin M; Alkhouli, Mohammed; Gerard-O'Riley, Rita L; Kasipathi, Charishma; Oakes, Dana K; Wright, Weston B; Acton, Dena; McQueen, Amie K; Patel, Bhavmik; Lim, Kyung-Eun; Robling, Alexander G; Econs, Michael J

2017-04-01

Recently, we demonstrated that osteoblast-specific overexpression of human WNT16 increased both cortical and trabecular bone mass and structure in mice. To further identify the cell-specific role of Wnt16 in bone homeostasis, we created transgenic (TG) mice overexpressing human WNT16 in osteocytes using Dmp1 promoter (Dmp1-hWNT16 TG) on C57BL/6 (B6) background. We analyzed bone phenotypes and serum bone biomarkers, performed gene expression analysis and measured dynamic bone histomorphometry in Dmp1-hWNT16 TG and wild-type (WT) mice. Compared to WT mice, Dmp1-hWNT16 TG mice exhibited significantly higher whole-body, spine and femoral aBMD, BMC and trabecular (BV/TV, Tb.N, and Tb.Th) and cortical (bone area and thickness) parameters in both male and female at 12 weeks of age. Femur stiffness and ultimate force were also significantly improved in the Dmp1-hWNT16 TG female mice, compared to sex-matched WT littermates. In addition, female Dmp1-hWNT16 TG mice displayed significantly higher MS/BS, MAR and BFR/BS compared to the WT mice. Gene expression analysis demonstrated significantly higher mRNA level of Alp in both male and female Dmp1-hWNT16 TG mice and significantly higher levels of Osteocalcin, Opg and Rankl in the male Dmp1-hWNT16 TG mice in bone tissue compared to sex-matched WT mice. These results indicate that WNT16 plays a critical role for acquisition of both cortical and trabecular bone mass and strength. Strategies designed to use WNT16 as a target for therapeutic interventions will be valuable to treat osteoporosis and other low bone mass conditions.

Bone Mass and Strength are Significantly Improved in Mice Overexpressing Human WNT16 in Osteocytes

PubMed Central

Alam, Imranul; Reilly, Austin M.; Alkhouli, Mohammed; Gerard-O’Riley, Rita L.; Kasipathi, Charishma; Oakes, Dana K.; Wright, Weston B.; Acton, Dena; McQueen, Amie K.; Patel, Bhavmik; Lim, Kyung-Eun; Robling, Alexander G.; Econs, Michael J.

2017-01-01

Recently, we demonstrated that osteoblast-specific overexpression of human WNT16 increased both cortical and trabecular bone mass and structure in mice. To further identify the cell-specific role of Wnt16 in bone homeostasis, we created transgenic (TG) mice over-expressing human WNT16 in osteocytes using Dmp1 promoter (Dmp1-hWNT16 TG) on C57BL/6 (B6) background. We analyzed bone phenotypes and serum bone biomarkers, performed gene expression analysis and measured dynamic bone histomorphometry in Dmp1-hWNT16 TG and wild-type (WT) mice. Compared to WT mice, Dmp1-hWNT16 TG mice exhibited significantly higher whole body, spine and femoral aBMD, BMC and trabecular (BV/TV, Tb.N, and Tb.Th) and cortical (bone area and thickness) parameters in both male and female at 12 weeks of age. Femur stiffness and ultimate force were also significantly improved in the Dmp1-hWNT16 TG female mice, compared to sex-matched WT littermates. In addition, female Dmp1-hWNT16 TG mice displayed significantly higher MS/BS, MAR and BFR/BS compared to the WT mice. Gene expression analysis demonstrated significantly higher mRNA level of Alp in both male and female Dmp1-hWNT16 TG mice and significantly higher levels of Osteocalcin, Opg and Rankl in the male Dmp1-hWNT16 TG mice in bone tissue compared to sex-matched WT mice. These results indicate that WNT16 plays a critical role for acquisition of both cortical and trabecular bone mass and strength. Strategies designed to use WNT16 as a target for therapeutic interventions will be valuable to treat osteoporosis and other low bone mass conditions. PMID:28013361

Soccer helps build strong bones during growth: a systematic review and meta-analysis.

PubMed

Lozano-Berges, Gabriel; Matute-Llorente, Ángel; González-Agüero, Alejandro; Gómez-Bruton, Alejandro; Gómez-Cabello, Alba; Vicente-Rodríguez, Germán; Casajús, José A

2018-03-01

The aim of this study was to analyze the effects of soccer practice on bone in male and female children and adolescents. MEDLINE, PubMed, SPORTDiscus and Web of Science databases were searched for scientific articles published up to and including October 2016. Twenty-seven studies were included in this systematic review (13 in the meta-analysis). The meta-analysis was performed by using OpenMeta[Analyst] software. It is well documented that soccer practice during childhood provides positive effects on bone mineral content (BMC) and density (BMD) compared to sedentary behaviors and other sports, such as tennis, weightlifting, or swimming. Furthermore, soccer players present higher BMC and BMD in most weight-bearing sites such as the whole body, lumbar spine, hip, and legs. Moreover, bone differences were minimized between groups during prepuberty. Therefore, the maturity status should be considered when evaluating bone. According to meta-analysis results, soccer practice was positively associated with whole-body BMD either in males (mean difference 0.061; 95%CI, 0.042-0.079) or in females (mean difference 0.063; 95%CI, 0.026-0.099). Soccer may be considered a sport that positively affects bone mass during growth. Pubertal soccer players presented increased bone mass compared to controls or other athletes; however, these bone differences are minimized during the prepubertal stage. What is known: • It has been described that childhood and adolescence are important periods for bone mass and structure. • Previous studies have demonstrated that soccer participation improves bone mass in male and female children and adolescents. What is new: • The differences between soccer players and controls are more marked during puberty than prepuberty. • Weight-bearing sites such as lumbar spine, hip, femoral neck, trochanter, intertrochanteric region and both legs are particularly sensitive to soccer actions.

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.

Bone and muscle - The structural system in long duration space missions

NASA Technical Reports Server (NTRS)

Buchanan, Paul

1987-01-01

Losses of bone mineral and muscle mass have been observed, and in varying degrees measured, following all long duration missions in space. These observations portend an unacceptable threat to the crews' ability to return to earth, without protracted rehabilitation, following periods of a year or more in microgravity. The impact to crew capabilities and productivity in space is not well understood. Past research has dealt with bone loss and muscle atrophy as two separate problems with little discernible relationship. This paper reviews the available information on both and suggests a combined structural approach for future research.

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.

The effects of visceral obesity and androgens on bone: trenbolone protects against loss of femoral bone mineral density and structural strength in viscerally obese and testosterone-deficient male rats.

PubMed

Donner, D G; Elliott, G E; Beck, B R; Forwood, M R; Du Toit, E F

2016-03-01

In males, visceral obesity and androgen deficiency often present together and result in harmful effects on bone. Our findings show that both factors are independently associated with adverse effects on femoral bone structure and strength, and trenbolone protects rats from diet-induced visceral obesity and consequently normalises femoral bone structural strength. In light of the rapidly increasing incidence of obesity and osteoporosis globally, and recent conjecture regarding the effects of visceral adiposity and testosterone deficiency on bone health, we investigated the effects of increased visceral adipose tissue (VAT) mass on femoral bone mineral density (BMD), structure and strength in normal weight rats with testosterone deficiency. Male Wistar rats (n = 50) were fed either standard rat chow (CTRL, n = 10) or a high-fat/high-sugar diet (HF/HS, n = 40). Following 8 weeks of feeding, rats underwent sham surgery (CTRL, n = 10; HF/HS, n = 10) or orchiectomy (HF/HS + ORX, n = 30). Following a 4-week recovery period, mini-osmotic pumps containing either vehicle (CTRL, n = 10; HF/HS, n = 10; HF/HS + ORX, n = 10), 2.0 mg kg day(-1), testosterone (HF/HS + ORX + TEST, n = 10) or 2.0 mg kg day(-1) trenbolone (HF/HS + ORX + TREN, n = 10) were implanted for 8 weeks of treatment. Dual-energy X-ray absorptiometry and three-point bending tests were used to assess bone mass, structure and strength of femora. Diet-induced visceral obesity resulted in decreased bone mineral area (BMA) and content (BMC) and impaired femoral stiffness and strength. Orchiectomy further impaired BMA, BMC and BMD and reduced energy to failure in viscerally obese animals. Both TEST and TREN treatment restored BMA, BMC, BMD and energy to failure. Only TREN reduced visceral adiposity and improved femoral stiffness and strength. Findings support a role for both visceral adiposity and testosterone deficiency as independent risk factors for femoral osteoporosis, adverse bone geometry and impaired bone strength in male rats. Trenbolone may be a more effective candidate for androgen replacement therapy than testosterone in viscerally obese testosterone-deficient males.

Exercise initiated after the onset of insulin resistance improves trabecular microarchitecture and cortical bone biomechanics of the tibia in hyperphagic Otsuka Long Evans Tokushima Fatty rats.

PubMed

Ortinau, Laura C; Linden, Melissa A; Dirkes, Rebecca K; Rector, R Scott; Hinton, Pamela S

2017-10-01

The present study extends our previous findings that exercise, which prevents the onset of insulin resistance and type 2 diabetes (T2D), also prevents the detrimental effects of T2D on whole-bone and tissue-level strength. Our objective was to determine whether exercise improves bone's structural and material properties if insulin resistance is already present in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The OLETF rat is hyperphagic due to a loss-of-function mutation in cholecystokinin-1 receptor (CCK-1 receptor), which leads to progressive obesity, insulin resistance and T2D after the majority of skeletal growth is complete. Because exercise reduces body mass, which is a significant determinant of bone strength, we used a body-mass-matched caloric-restricted control to isolate body-mass-independent effects of exercise on bone. Eight-wk old, male OLETF rats were fed ad libitum until onset of hyperglycemia (20weeks of age), at which time they were randomly assigned to three groups: ad libitum fed, sedentary (O-SED); ad libitum fed, treadmill running (O-EX); or, sedentary, mild caloric restriction to match body mass of O-EX (O-CR). Long-Evans Tokushima Otsuka rats served as the normophagic, normoglycemic controls (L-SED). At 32weeks of age, O-SED rats had T2D as evidenced by hyperglycemia and a significant reduction in fasting insulin compared to OLETFs at 20weeks of age. O-SED rats also had reduced total body bone mineral content (BMC), increased C-terminal telopeptide of type I collagen (CTx)/tartrate resistant acid phosphatase isoform 5b (TRAP5b), decreased N-terminal propeptide of type I procollagen (P1NP), reduced percent cancellous bone volume (BV/TV), trabecular number (Tb.N) and increased trabecular separation (Tb.Sp) and structural model index (SMI) of the proximal tibia compared to L-SED. T2D also adversely affected biomechanical properties of the tibial diaphysis, and serum sclerostin was increased and β-catenin, runt-related transcription factor 2 (Runx2) and insulin-like growth factor-I (IGF-I) protein expression in bone were reduced in O-SED vs. L-SED. O-EX or O-CR had greater total body bone mineral density (BMD) and BMC, and BV/TV, Tb.N, Tb.Sp, and SMI compared to O-SED. O-EX had lower CTx and CR greater P1NP relative to O-SED. O-EX, not O-CR, had greater cortical thickness and area, and improved whole-bone and tissue-level biomechanical properties associated with a 4-fold increase in cortical bone β-catenin protein expression vs. O-SED. In summary, EX or CR initiated after the onset of insulin resistance preserved cancellous bone volume and structure, and EX elicited additional benefits in cortical bone. Copyright © 2017 Elsevier Inc. All rights reserved.

Deficiency of circadian clock protein BMAL1 in mice results in a low bone mass phenotype.

PubMed

Samsa, William E; Vasanji, Amit; Midura, Ronald J; Kondratov, Roman V

2016-03-01

The circadian clock is an endogenous time keeping system that controls the physiology and behavior of many organisms. The transcription factor Brain and Muscle ARNT-like Protein 1 (BMAL1) is a component of the circadian clock and necessary for clock function. Bmal1(-/-) mice display accelerated aging and many accompanying age associated pathologies. Here, we report that mice deficient for BMAL1 have a low bone mass phenotype that is absent at birth and progressively worsens over their lifespan. Accelerated aging of these mice is associated with the formation of bony bridges occurring across the metaphysis to the epiphysis, resulting in shorter long bones. Using micro-computed tomography we show that Bmal1(-/-) mice have reductions in cortical and trabecular bone volume and other micro-structural parameters and a lower bone mineral density. Histology shows a deficiency of BMAL1 results in a reduced number of active osteoblasts and osteocytes in vivo. Isolation of bone marrow derived mesenchymal stem cells from Bmal1(-/-) mice demonstrate a reduced ability to differentiate into osteoblasts in vitro, which likely explains the observed reductions in osteoblasts and osteocytes, and may contribute to the observed osteopenia. Our data support the role of the circadian clock in the regulation of bone homeostasis and shows that BMAL1 deficiency results in a low bone mass phenotype. Copyright © 2016 Elsevier Inc. All rights reserved.

Deficiency of Circadian Clock Protein BMAL1 in Mice Results in a Low Bone Mass Phenotype

PubMed Central

Samsa, William E.; Vasanji, Amit; Midura, Ronald J.; Kondratov, Roman V.

2016-01-01

The circadian clock is an endogenous time keeping system that controls the physiology and behavior of many organisms. The transcription factor Brain and Muscle ARNT-like Protein 1 (BMAL1) is a component of the circadian clock and necessary for clock function. Bmal1−/− mice display accelerated aging and many accompanying age associated pathologies. Here, we report that mice deficient for BMAL1 have a low bone mass phenotype that is absent at birth and progressively worsens over their lifespan. Accelerated aging of these mice is associated with the formation of bony bridges occurring across the metaphysis to the epiphysis, resulting in shorter long bones. Using micro-computed tomography we show that Bmal1−/− mice have reductions in cortical and trabecular bone volume and other micro-structural parameters and a lower bone mineral density. Histology shows a deficiency of BMAL1 results in a reduced number of active osteoblasts and osteocytes in vivo. Isolation of bone marrow derived mesenchymal stem cells from Bmal1−/− mice demonstrate a reduced ability to differentiate into osteoblasts in vitro, which likely explains the observed reductions in osteoblasts and osteocytes, and may contribute to the observed osteopenia. Our data support the role of the circadian clock in the regulation of bone homeostasis and shows that BMAL1 deficiency results in a low bone mass phenotype. PMID:26789548

Effects of load-bearing exercise on skeletal structure and mechanics differ between outbred populations of mice.

PubMed

Wallace, Ian J; Judex, Stefan; Demes, Brigitte

2015-03-01

Effects of load-bearing exercise on skeletal structure and mechanical properties can vary between inbred strains of mice. Here, we examine whether such variation also exists at the population level. An experiment was performed with two outbred mouse stocks that have been reproductively isolated for >120 generations (Hsd:ICR, Crl:CD1). Growing females from each stock were either treated with a treadmill-running regimen for 1 month or served as controls. Limb forces were recorded with a force plate and cage activity monitored to verify that they were similar between stocks. After the experiment, femoral cortical and trabecular bone structure were quantified with micro-CT in the mid-diaphysis and distal metaphysis, respectively, and diaphyseal structural strength was determined with mechanical testing. Among Hsd:ICR mice, running led to significant improvements in diaphyseal bone quantity, structural geometry, and mechanical properties, as well as enhanced trabecular morphology. In contrast, among Crl:CD1 mice, the same running regimen had little effect on cortical and trabecular structure and significantly reduced diaphyseal resistance to fracture. In neither stock was body mass, muscle mass, or cage activity level different between runners and controls. Given that most environmental variables were controlled in this study, the differential effects of exercise on Hsd:ICR and Crl:CD1 bones were likely due to genetic differences between stocks. These results suggest that the benefits of loading for bone may vary between human populations (e.g., ethnic groups), in which case exercise programs and technologies designed to promote bone health with mechanical signals may be more advantageous to certain populations than others. Copyright © 2014 Elsevier Inc. All rights reserved.

Gene Expression in Bone

NASA Astrophysics Data System (ADS)

D'Ambrogio, A.

Skeletal system has two main functions, to provide mechanical integrity for both locomotion and protection and to play an important role in mineral homeostasis. There is extensive evidence showing loss of bone mass during long-term Space-Flights. The loss is due to a break in the equilibrium between the activity of osteoblasts (the cells that forms bone) and the activity of osteoclasts (the cells that resorbs bone). Surprisingly, there is scanty information about the possible altered gene expression occurring in cells that form bone in microgravity.(Just 69 articles result from a "gene expression in microgravity" MedLine query.) Gene-chip or microarray technology allows to screen thousands of genes at the same time: the use of this technology on samples coming from cells exposed to microgravity could provide us with many important informations. For example, the identification of the molecules or structures which are the first sensors of the mechanical stress derived from lack of gravity, could help in understanding which is the first event leading to bone loss due to long-term exposure to microgravity. Consequently, this structure could become a target for a custom-designed drug. It is evident that bone mass loss, observed during long-time stay in Space, represents an accelerated model of what happens in aging osteoporosis. Therefore, the discovery and design of drugs able to interfere with the bone-loss process, could help also in preventing negative physiological processes normally observed on Earth. Considering the aims stated above, my research is designed to:

Monosodium glutamate-sensitive hypothalamic neurons contribute to the control of bone mass

NASA Technical Reports Server (NTRS)

Elefteriou, Florent; Takeda, Shu; Liu, Xiuyun; Armstrong, Dawna; Karsenty, Gerard

2003-01-01

Using chemical lesioning we previously identified hypothalamic neurons that are required for leptin antiosteogenic function. In the course of these studies we observed that destruction of neurons sensitive to monosodium glutamate (MSG) in arcuate nuclei did not affect bone mass. However MSG treatment leads to hypogonadism, a condition inducing bone loss. Therefore the normal bone mass of MSG-treated mice suggested that MSG-sensitive neurons may be implicated in the control of bone mass. To test this hypothesis we assessed bone resorption and bone formation parameters in MSG-treated mice. We show here that MSG-treated mice display the expected increase in bone resorption and that their normal bone mass is due to a concomitant increase in bone formation. Correction of MSG-induced hypogonadism by physiological doses of estradiol corrected the abnormal bone resorptive activity in MSG-treated mice and uncovered their high bone mass phenotype. Because neuropeptide Y (NPY) is highly expressed in MSG-sensitive neurons we tested whether NPY regulates bone formation. Surprisingly, NPY-deficient mice had a normal bone mass. This study reveals that distinct populations of hypothalamic neurons are involved in the control of bone mass and demonstrates that MSG-sensitive neurons control bone formation in a leptin-independent manner. It also indicates that NPY deficiency does not affect bone mass.

Biology of bone and how it orchestrates the form and function of the skeleton

NASA Technical Reports Server (NTRS)

Sommerfeldt, D. W.; Rubin, C. T.

2001-01-01

The principal role of the skeleton is to provide structural support for the body. While the skeleton also serves as the body's mineral reservoir, the mineralized structure is the very basis of posture, opposes muscular contraction resulting in motion, withstands functional load bearing, and protects internal organs. Although the mass and morphology of the skeleton is defined, to some extent, by genetic determinants, it is the tissue's ability to remodel--the local resorption and formation of bone--which is responsible for achieving this intricate balance between competing responsibilities. The aim of this review is to address bone's form-function relationship, beginning with extensive research in the musculoskeletal disciplines, and focusing on several recent cellular and molecular discoveries which help understand the complex interdependence of bone cells, growth factors, physical stimuli, metabolic demands, and structural responsibilities. With a clinical and spine-oriented audience in mind, the principles of bone cell and molecular biology and physiology are presented, and an attempt has been made to incorporate epidemiologic data and therapeutic implications. Bone research remains interdisciplinary by nature, and a deeper understanding of bone biology will ultimately lead to advances in the treatment of diseases and injuries to bone itself.

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

Mass Spectrometry and Antibody-Based Characterization of Blood Vessels from Brachylophosaurus canadensis

PubMed Central

Cleland, Timothy P.; Schroeter, Elena R.; Zamdborg, Leonid; Zheng, Wenxia; Lee, Ji Eun; Tran, John C.; Bern, Marshall; Duncan, Michael B.; Lebleu, Valerie S.; Ahlf, Dorothy R.; Thomas, Paul M.; Kalluri, Raghu; Kelleher, Neil L.; Schweitzer, Mary H.

2016-01-01

Structures similar to blood vessels in location, morphology, flexibility, and transparency have been recovered after demineralization of multiple dinosaur cortical bone fragments from multiple specimens, some of which are as old as 80 Ma. These structures were hypothesized to be either endogenous to the bone (i.e., of vascular origin) or the result of biofilm colonizing the empty osteonal network after degradation of original organic components. Here, we test the hypothesis that these structures are endogenous and thus retain proteins in common with extant archosaur blood vessels that can be detected with high-resolution mass spectrometry and confirmed by immunofluorescence. Two lines of evidence support this hypothesis. First, peptide sequencing of Brachylophosaurus canadensis blood vessel extracts is consistent with peptides comprising extant archosaurian blood vessels and is not consistent with a bacterial, cellular slime mold, or fungal origin. Second, proteins identified by mass spectrometry can be localized to the tissues using antibodies specific to these proteins, validating their identity. Data are available via ProteomeXchange with identifier PXD001738. PMID:26595531

Mass Spectrometry and Antibody-Based Characterization of Blood Vessels from Brachylophosaurus canadensis.

PubMed

Cleland, Timothy P; Schroeter, Elena R; Zamdborg, Leonid; Zheng, Wenxia; Lee, Ji Eun; Tran, John C; Bern, Marshall; Duncan, Michael B; Lebleu, Valerie S; Ahlf, Dorothy R; Thomas, Paul M; Kalluri, Raghu; Kelleher, Neil L; Schweitzer, Mary H

2015-12-04

Structures similar to blood vessels in location, morphology, flexibility, and transparency have been recovered after demineralization of multiple dinosaur cortical bone fragments from multiple specimens, some of which are as old as 80 Ma. These structures were hypothesized to be either endogenous to the bone (i.e., of vascular origin) or the result of biofilm colonizing the empty osteonal network after degradation of original organic components. Here, we test the hypothesis that these structures are endogenous and thus retain proteins in common with extant archosaur blood vessels that can be detected with high-resolution mass spectrometry and confirmed by immunofluorescence. Two lines of evidence support this hypothesis. First, peptide sequencing of Brachylophosaurus canadensis blood vessel extracts is consistent with peptides comprising extant archosaurian blood vessels and is not consistent with a bacterial, cellular slime mold, or fungal origin. Second, proteins identified by mass spectrometry can be localized to the tissues using antibodies specific to these proteins, validating their identity. Data are available via ProteomeXchange with identifier PXD001738.

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.

Scaling relations between bone volume and bone structure as found using 3D µCT images of the trabecular bone taken from different skeletal sites

NASA Astrophysics Data System (ADS)

Raeth, Christoph; Müller, Dirk; Sidorenko, Irina; Monetti, Roberto; Eckstein, Felix; Matsuura, Maiko; Lochmüller, Eva-Maria; Zysset, Philippe K.; Bauer, Jan

2010-03-01

According to Wolff's law bone remodels in response to the mechanical stresses it experiences so as to produce a minimal-weight structure that is adapted to its applied stresses. Here, we investigate the relations between bone volume and structure for the trabecular bone using 3D μCT images taken from different skeletal sites in vitro, namely from the distal radii (96 specimens), thoracic (73 specimens) and lumbar vertebrae (78 specimens). We determine the local structure of the trabecular network by calculating isotropic and anisotropic scaling indices (α, αz). These measures have been proven to be able to discriminate rod- from sheet-like structures and to quantify the alignment of structures with respect to a preferential direction as given by the direction of the external force. Comparing global structure measures derived from the scaling indices (mean, standard deviation) with the bone mass (BV/TV) we find that all correlations obey very accurately power laws with scaling exponents of 0.14, 0.12, 0.15 (<α>~), -0.2, -017, -0.17 (σ(αz)), 0.09, 0.05, 0.07 (<~αz>~) and -0.20, -0.11 ,-0.13 (σ(αz)) distal radius, thoracic vertebra and lumbar vertebra respectively. Thus, these relations turn out to be site-independent, albeit the mechanical stresses to which the bones of the forearm and the spine are exposed, are quite different. The similar alignment might not be in agreement with a universal validity of Wolff's law. On the other hand, such universal power law relations may allow to develop additional diagnostic means to better assess healthy and osteoporotic bone.

Correlating the nanoscale mechanical and chemical properties of knockout mice bones

NASA Astrophysics Data System (ADS)

Kavukcuoglu, Nadire Beril

Bone is a mineral-organic composite where the organic matrix is mainly type I collagen plus small amounts of non-collagenous proteins including osteopontin (OPN), osteocalcin (OC) and fibrillin 2 (Fbn2). Mature bone undergoes remodeling continually so new bone is formed and old bone resorbed. Uncoupling between the bone resorption and bone formation causes an overall loss of bone mass and leads to diseases like osteoporosis and osteopenia. These are characterized by structural deterioration of the bone tissue and an increased risk of fracture. The non-collagenous bone proteins are known to have a role in regulating bone turnover and to affect the structural integrity of bone. OPN and OC play a key role in bone resorption and formation, while absence of Fbn-2 causes a connective tissue disorder (congenital contractural arachnodactyly) and has been associated with decreased bone mass. In this thesis nanoindentation and Raman-microspectroscopy techniques were used to investigate and correlate the mechanical and chemical properties of cortical femoral bones from OPN deficient (OPN-/-), OC deficient (OC-/-) and Fbn-2 deficient (Fbn2-/-) mice and their age, sex and background matched wild-type controls (OPN+/+, OC+/+ and Fbn2+/+). For OPN the hardness (H) and elastic modulus (E) of under 12 week OPN-/- bones were significantly lower than for OPN+/+ bones, but Raman showed no significant difference. Mechanical properties of bones from mice older than 12 weeks were not significantly different with genotype. However, mineralization and crystallinity from >50 week OPN-/- bones were significantly higher than for OPN+/+ bones. Mechanical properties of OPN-/- bones showed no variation with age, but mineralization, crystallinity and type-B carbonate substitution increased for both genotypes. For OC-/- intra-bone analyses showed that the hardness and crystallinity of the bones were significantly higher, especially in the mid-cortical sections, compared to OC+/+ bones. Fbn2-/- bones had significantly lower hardness and elastic modulus compared to Fbn2+/+ bones, but the crystallinity was higher. Type-B carbonate substitution decreased significantly in OC-/- and Fbn2-/- bones compared to their wild-type controls. The thesis has provided new insight into how non-collagenous proteins affect the nanomechanics and chemistry of bone tissue. This information will assist in the development of new treatments for osteopenia/osteoporosis.

Reduced Bone Strength and Muscle Force in Women 27 Years After Anorexia Nervosa.

PubMed

Mueller, Sandro Manuel; Immoos, Marilyn; Anliker, Elmar; Drobnjak, Suzana; Boutellier, Urs; Toigo, Marco

2015-08-01

A substantial body of research findings indicate that muscle mass and bone mass are reduced in populations of anorexic females, even in such populations whose anorexia nervosa had been in remission for longer periods. This study aimed to investigate whether the bone of an anorexia nervosa recovery cohort is adapted to maximal muscle forces and whether there are alterations in the structure of the tibia in this population, as compared with a control group. This was a cross-sectional study of 22 women in Switzerland who have remained in stable recovery from anorexia nervosa for an average of 27 years. The measurements were compared with those of an age- and gender-matched control group (n = 73). There were no interventions. Bone characteristics of the tibia and maximal voluntary ground reaction force (Fm1LH) were measured. The variability in volumetric bone mineral content (vBMC) at the 14% site was explained by 54.7% on the grounds of Fm1LH (P < .001). Formerly anorexic women had an 11.6% lower Fm1LH (P = .001), a significantly lower vBMC at 4% and 14% of tibia length, and an 11.9% (P = .001) lower body mass than the age- and gender-matched control population. Present body mass of the anorexia group correlated positively with vBMC at the 14% site (P < .001). Despite the fact that findings reflected an adaptation of bone to the acting forces, most results indicated that the test cohort generally suffered from a secondary bone defect. In addition, maximal muscle force was also impaired in the formerly anorexic women.

Effect of swimming exercise on three-dimensional trabecular bone microarchitecture in ovariectomized rats.

PubMed

Ju, Yong-In; Sone, Teruki; Ohnaru, Kazuhiro; Tanaka, Kensuke; Fukunaga, Masao

2015-11-01

Swimming is generally considered ineffective for increasing bone mass in humans, at least compared with weight-bearing sports. However, swimming exercise has sometimes been shown to have a strong positive effect on bone mass in small animals. This study investigated the effects of swimming on bone mass, strength, and microarchitecture in ovariectomized (OVX) rats. OVX or sham operations were performed on 18-wk-old female Fisher 344 rats. Rats were randomly divided into four groups: sham sedentary (Sham-CON), sham swimming exercised (Sham-SWI), OVX sedentary (OVX-CON), and OVX swimming exercised (OVX-SWI). Rats in exercise groups performed swimming in a water bath for 60 min/day, 5 days/wk, for 12 wk. Bone mineral density (BMD) in right femurs was analyzed using dual-energy X-ray absorptiometry. Three-dimensional trabecular architecture at the distal femoral metaphysis was analyzed using microcomputed tomography (μCT). Geometrical properties of diaphyseal cortical bone were evaluated in the midfemoral region using μCT. The biomechanical properties of femurs were analyzed using three-point bending. Femoral BMD was significantly decreased following ovariectomy. This change was suppressed by swimming. Trabecular bone thickness, number, and connectivity were decreased by ovariectomy, whereas structure model index (i.e., ratio of rod-like to plate-like trabeculae) increased. These changes were also suppressed by swimming exercise. Femurs displayed greater cortical width and maximum load in SWI groups than in CON groups. Together, these results demonstrate that swimming exercise drastically alleviated both OVX-induced decreases in bone mass and mechanical strength and the deterioration of trabecular microarchitecture in rat models of osteoporosis. Copyright © 2015 the American Physiological Society.

Peripubertal female athletes in high-impact sports show improved bone mass acquisition and bone geometry.

PubMed

Maïmoun, Laurent; Coste, Olivier; Philibert, Pascal; Briot, Karine; Mura, Thibault; Galtier, Florence; Mariano-Goulart, Denis; Paris, Françoise; Sultan, Charles

2013-08-01

Intensive physical training may have a sport-dependent effect on bone mass acquisition. This cross-sectional study evaluated bone mass acquisition in girls practicing sports that put different mechanical loads on bone. Eighty girls from 10.7 to 18.0 years old (mean 13.83 ± 1.97) were recruited: 20 artistic gymnasts (AG; high-impact activity), 20 rhythmic gymnasts (RG; medium-impact activity), 20 swimmers (SW, no-impact activity), and 20 age-matched controls (CON; leisure physical activity <3h/wk). Areal bone mineral density (aBMD) was determined using DEXA. Hip structural analysis applied at the femur evaluated cross-sectional area (CSA, cm(2)), section modulus (Z, cm(3)), and buckling ratio. Bone turnover markers and OPG/RANKL levels were analyzed. AG had higher aBMD than SW and CON at all bone sites and higher values than RG in the lumbar spine and radius. RG had higher aBMD than SW and CON only in the femoral region. CSA and mean cortical thickness were significantly higher and the buckling ratio was significantly lower in both gymnast groups compared with SW and CON. In RG only, endocortical diameter and width were reduced, while Z was only increased in AG compared with SW and CON. Reduced bone remodeling was observed in RG compared with AG only when groups were subdivided according to menarcheal status. All groups showed similar OPG concentrations, while RANKL concentrations increased with age and were decreased in SW. High-impact activity clearly had a favorable effect on aBMD and bone geometry during the growth period, although the bone health benefits seem to be more marked after menarche. Copyright © 2013 Elsevier Inc. 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

Just-in-time Design and Additive Manufacture of Patient-specific Medical Implants

NASA Astrophysics Data System (ADS)

Shidid, Darpan; Leary, Martin; Choong, Peter; Brandt, Milan

Recent advances in medical imaging and manufacturing science have enabled the design and production of complex, patient-specific orthopaedic implants. Additive Manufacture (AM) generates three-dimensional structures layer by layer, and is not subject to the constraints associated with traditional manufacturing methods. AM provides significant opportunities for the design of novel geometries and complex lattice structures with enhanced functional performance. However, the design and manufacture of patient-specific AM implant structures requires unique expertise in handling various optimization platforms. Furthermore, the design process for complex structures is computationally intensive. The primary aim of this research is to enable the just-in-time customisation of AM prosthesis; whereby AM implant design and manufacture be completed within the time constraints of a single surgical procedure, while minimising prosthesis mass and optimising the lattice structure to match the stiffness of the surrounding bone tissue. In this research, a design approach using raw CT scan data is applied to the AM manufacture of femoral prosthesis. Using the proposed just-in-time concept, the mass of the prosthesis was rapidly designed and manufactured while satisfying the associated structural requirements. Compressive testing of lattice structures manufactured using proposed method shows that the load carrying capacity of the resected composite bone can be recovered by up to 85% and the compressive stiffness of the AM prosthesis is statistically indistinguishable from the stiffness of the initial bone.

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

Stiffness of a wobbling mass models analysed by a smooth orthogonal decomposition of the skin movement relative to the underlying bone.

PubMed

Dumas, Raphaël; Jacquelin, Eric

2017-09-06

The so-called soft tissue artefacts and wobbling masses have both been widely studied in biomechanics, however most of the time separately, from either a kinematics or a dynamics point of view. As such, the estimation of the stiffness of the springs connecting the wobbling masses to the rigid-body model of the lower limb, based on the in vivo displacements of the skin relative to the underling bone, has not been performed yet. For this estimation, the displacements of the skin markers in the bone-embedded coordinate systems are viewed as a proxy for the wobbling mass movement. The present study applied a structural vibration analysis method called smooth orthogonal decomposition to estimate this stiffness from retrospective simultaneous measurements of skin and intra-cortical pin markers during running, walking, cutting and hopping. For the translations about the three axes of the bone-embedded coordinate systems, the estimated stiffness coefficients (i.e. between 2.3kN/m and 55.5kN/m) as well as the corresponding forces representing the connection between bone and skin (i.e. up to 400N) and corresponding frequencies (i.e. in the band 10-30Hz) were in agreement with the literature. Consistently with the STA descriptions, the estimated stiffness coefficients were found subject- and task-specific. Copyright © 2017 Elsevier Ltd. All rights reserved.

[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.

PTH prevents the adverse effects of focal radiation on bone architecture in young rats.

PubMed

Chandra, Abhishek; Lan, Shenghui; Zhu, Ji; Lin, Tiao; Zhang, Xianrong; Siclari, Valerie A; Altman, Allison R; Cengel, Keith A; Liu, X Sherry; Qin, Ling

2013-08-01

Radiation therapy is a common treatment regimen for cancer patients. However, its adverse effects on the neighboring bone could lead to fractures with a great impact on quality of life. The underlying mechanism is still elusive and there is no preventive or curative solution for this bone loss. Parathyroid hormone (PTH) is a current therapy for osteoporosis that has potent anabolic effects on bone. In this study, we found that focal radiation from frequent scans of the right tibiae in 1-month-old rats by micro-computed tomography severely decreased trabecular bone mass and deteriorated bone structure. Interestingly, PTH daily injections remarkably improved trabecular bone in the radiated tibiae with increases in trabecular number, thickness, connectivity, structure model index and stiffness, and a decrease in trabecular separation. Histomorphometric analysis revealed that radiation mainly decreased the number of osteoblasts and impaired their mineralization activity but had little effects on osteoclasts. PTH reversed these adverse effects and greatly increased bone formation to a similar level in both radiated and non-radiated bones. Furthermore, PTH protects bone marrow mesenchymal stem cells from radiation-induced damage, including a decrease in number and an increase in adipogenic differentiation. While radiation generated the same amount of free radicals in the bone marrow of vehicle-treated and PTH-treated animals, the percentage of apoptotic bone marrow cells was significantly attenuated in the PTH group. Taken together, our data demonstrate a radioprotective effect of PTH on bone structure and bone marrow and shed new light on a possible clinical application of anabolic treatment in radiotherapy. Copyright © 2013 Elsevier Inc. All rights reserved.

[Characteristics of bone tissue of rats after flight aboard biosputnik Kosmos-1129].

PubMed

Rogacheva, I V; Stupakov, G P; Volozhin, A I; Pavlova, M N; Poliakov, A N

1984-01-01

Bones of rats flown for 19 days onboard Cosmos-1129 were examined. The examination included bone mass, density, mineral composition, reconstruction parameters, and elemental composition at R + 1, R + 6, and R + 29. After flight the rats developed osteoporosis in the spongy structures of tubular bones and a smaller thickness of the cortical layer of the diaphysis; they showed no mineralization of the microstructures, a slight decrease of the Ca concentration, and a normal content of P. At R + 6 these changes progressively developed and at R + 29 they returned to normal.

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.

Intrauterine stress induces bone loss in adult offspring of C3H/HeJ mice having high bone mass phenotype but not C57BL/6J mice with low bone mass phenotype.

PubMed

Raygorodskaya, M; Gabet, Y; Shochat, C; Kobyliansky, E; Torchinsky, A; Karasik, D

2016-06-01

In this study we examined to what extent and how genetics may modify osteoporosis risk arising due to environmental stresses which act during the antenatal period of life and have the potential to induce bone loss in adulthood. C57Bl/6J (C57) and C3H/HeJ (C3H) mice were used as a model system. The mice were exposed to a single injection of 5-aza-2'-deoxycytidine (5-AZA) on day 10 of pregnancy and the structure and bone mineral density (BMD) of the femur and 3rd lumbar vertebra of 3- and 6-month-old male and female offspring were evaluated by micro-computed tomography (μCT). Besides, we also attempted to evaluate whether 5-AZA affects the expression of some osteogenic genes in the embryonic limb buds. The main observation of this study is that 5-AZA-induced loss of bone quality was registered in 6-mo-old C3H offspring but not in their C57 counterparts. We also observed that C57 and C3H embryos may differ in their response to 5-AZA-induced detrimental stimuli: whereas 5-AZA treated C3H embryos exhibited a decreased expression of Col1a1, C57 embryos exhibit a decreased expression of Sox9. Overall, our study, by thorough characterization of bone homeostasis in 3- and 6-month-old offspring of 5-AZA-exposed C57 and C3H mice, allows hypothesizing that the adaptive response to antenatal insults may be stronger in offspring inherently exhibiting a low bone mass phenotype than in offspring inherently exhibiting a high bone mass phenotype. Copyright © 2016 Elsevier Inc. All rights reserved.

[Characteristics of local human skeleton reactions to microgravity and drug treatment of osteoporosis in clinic].

PubMed

Oganov, V S; Skripnikova, I A; Novikov, V E; Bakulin, A V; Kabitskaia, O E; Murashko, L M

2011-01-01

Analysis of the results of long-term investigations of bones in cosmonauts flown on the orbital station MIR and International space station (n = 80) was performed. Theoretically predicted (evolutionary predefined) change in mass of different skeleton bones was found to correlate (r = 0.904) with position relatively the Earth's gravity vector. Vector dependence of bone loss ensues from local specificity of expression of bone metabolism genes which reflects mechanic prehistory of skeleton structures in the evolution of Homo erectus. Genetic polymorphism is accountable for high individual variability of bone loss attested by the dependence of bone loss rate on polymorphism of certain bone metabolism markers. Parameters of one and the other orbital vehicle did not modulate individual-specific stability of the bone loss ratio in different segments of the skeleton. This fact is considered as a phenotype fingerprint of local metabolism in the form of a locus-unique spatial structure of distribution of noncollagenous proteins responsible for position regulation of endosteal metabolism. Drug treatment of osteoporosis (n = 107) evidences that recovery rate depends on bone location; the most likely reason is different effectiveness of local osteotrophic intervention into areas of bustling resorption.

Bone loss from Wnt inhibition mitigated by concurrent alendronate therapy.

PubMed

Madan, Babita; McDonald, Mitchell J; Foxa, Gabrielle E; Diegel, Cassandra R; Williams, Bart O; Virshup, David M

2018-01-01

Dysregulated Wnt signaling is associated with the pathogenesis of cancers, fibrosis, and vascular diseases. Inhibition of Wnt signaling has shown efficacy in various pre-clinical models of these disorders. One of the key challenges in developing targeted anti-cancer drugs is to balance efficacy with on-target toxicity. Given the crucial role Wnts play in the differentiation of osteoblasts and osteoclasts, acute inhibition of Wnt signaling is likely to affect bone homeostasis. In this study, we evaluated the skeletal effect of small molecule inhibitor of an o-acyl transferase porcupine (PORCN) that prevents Wnt signaling by blocking the secretion of all Wnts. Micro-computed tomography and histomorphometric evaluation revealed that the bones of mice treated with two structurally distinct PORCN inhibitors LGK974 and ETC-1922159 (ETC-159) had loss-of-bone volume and density within 4 weeks of exposure. This decreased bone mass was associated with a significant increase in adipocytes within the bone marrow. Notably, simultaneous administration of a clinically approved anti-resorptive, alendronate, a member of the bisphosphonate family, mitigated loss-of-bone mass seen upon ETC-159 treatment by regulating activity of osteoclasts and blocking accumulation of bone marrow adipocytes. Our results support the addition of bone protective agents when treating patients with PORCN inhibitors. Mitigation of bone toxicity can extend the therapeutic utility of Wnt pathway inhibitors.

Zoledronic Acid (Reclast®, Aclasta®): A Review in Osteoporosis.

PubMed

Dhillon, Sohita

2016-11-01

Zoledronic acid (Reclast ® , Aclasta ® ) is an intravenous, highly potent aminobisphosphonate approved worldwide, including in the USA, EU and Japan for use in patients with primary or secondary osteoporosis or low bone mass (approved indications vary between countries). Its high affinity to and long half-life in bone, and long duration of action, allow for once-yearly administration, which has the potential to improve adherence to therapy. Zoledronic acid once yearly for up to 3 years improved bone mineral density (BMD) at several skeletal sites, reduced fracture risk and bone turnover, and/or preserved bone structure and mass relative to placebo in clinical studies in patients with primary or secondary osteoporosis. While additional benefits were seen when treatment was continued for up to 6 years, as evidenced by a reduced risk of vertebral fractures and higher BMD relative to 3 years' therapy, there was minimal advantage of treatment beyond 6 years. Therefore, in patients with low fracture risk, treatment discontinuation should be considered after approximately 5 years' therapy. Zoledronic acid administered annually or once in 2 years was also effective in preventing bone loss in patients with low bone mass. Zoledronic acid was generally well tolerated, with the most common adverse events (AEs) being transient, mild-to-moderate post-infusion symptoms, which decreased with subsequent infusions. To conclude, zoledronic acid once yearly is an effective and generally well tolerated treatment option for patients with osteoporosis.

Platelet Dysfunction and a High Bone Mass Phenotype in a Murine Model of Platelet-Type von Willebrand Disease

PubMed Central

Suva, Larry J.; Hartman, Eric; Dilley, Joshua D.; Russell, Susan; Akel, Nisreen S.; Skinner, Robert A.; Hogue, William R.; Budde, Ulrich; Varughese, Kottayil I.; Kanaji, Taisuke; Ware, Jerry

2008-01-01

The platelet glycoprotein Ib-IX receptor binds surface-bound von Willebrand factor and supports platelet adhesion to damaged vascular surfaces. A limited number of mutations within the glycoprotein Ib-IX complex have been described that permit a structurally altered receptor to interact with soluble von Willebrand factor, and this is the molecular basis of platelet-type von Willebrand disease. We have developed and characterized a mouse model of platelet-type von Willebrand disease (G233V) and have confirmed a platelet phenotype mimicking the human disorder. The mice have a dramatic increase in splenic megakaryocytes and splenomegaly. Recent studies have demonstrated that hematopoetic cells can influence the differentiation of osteogenic cells. Thus, we examined the skeletal phenotype of mice expressing the G233V variant complex. At 6 months of age, G233V mice exhibit a high bone mass phenotype with an approximate doubling of trabecular bone volume in both the tibia and femur. Serum measures of bone resorption were significantly decreased in G233V animals. With decreased bone resorption, cortical thickness was increased, medullary area decreased, and consequently, the mechanical strength of the femur was significantly increased. Using ex vivo bone marrow cultures, osteoclast-specific staining in the G233V mutant marrow was diminished, whereas osteoblastogenesis was unaffected. These studies provide new insights into the relationship between the regulation of megakaryocytopoiesis and bone mass. PMID:18187573

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.

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.

In vivo bone remodeling rates determination and compressive stiffness variations before, during 60 days bed rest and two years follow up: A micro-FE-analysis from HR-pQCT measurements of the berlin Bed Rest Study-2

NASA Astrophysics Data System (ADS)

Ritter, Zully; Belavy, Daniel; Baumann, Wolfgang W.; Felsenberg, Dieter

2017-03-01

Bed rest studies are used for simulation and study of physiological changes as observed in unloading/non-gravity environments. Amongst others, bone mass reduction, similar as occurring due to aging osteoporosis, combined with bio-fluids redistribution and muscle atrophy have been observed and analyzed. Advanced radiological methods of high resolution such as HR-pQCT (XtremeCT) allow 3D-visualizing in vivo bone remodeling processes occurring during absence/reduction of mechanical stimuli (0 to <1 g) as simulated by bed rest. Induced bone micro-structure (e.g. trabecular number, cortical thickness, porosity) and density variations can be quantified. However, these parameters are average values of each sample and important information regarding bone mass distribution and within bone mechanical behaviour is lost. Finite element models with hexa-elements of identical size as the HR-pQCT measurements (0.082 mm×0.082 mm×0.082 mm, ca. 7E6 elements/sample) can be used for subject-specific in vivo stiffness calculation. This technique also allows quantifying if bone microstructural changes represent a risk of mechanical bone collapse (fracture).

Favorable effect of moderate dose caffeine on the skeletal system in ovariectomized rats.

PubMed

Folwarczna, Joanna; Pytlik, Maria; Zych, Maria; Cegieła, Urszula; Kaczmarczyk-Sedlak, Ilona; Nowińska, Barbara; Sliwiński, Leszek

2013-10-01

Caffeine, a methylxanthine present in coffee, has been postulated to be responsible for an increased risk of osteoporosis in coffee drinkers; however, the data are inconsistent. The aim of the present study was to investigate the effects of a moderate dose of caffeine on the skeletal system of rats with normal and decreased estrogen level (developing osteoporosis due to estrogen deficiency). The experiments were carried out on mature nonovariectomized and ovariectomized Wistar rats, divided into control rats and rats receiving caffeine once daily, 20 mg/kg p.o., for 4 wk. Serum bone turnover markers, bone mass, mass of bone mineral, calcium and phosphorus content, histomorphometric parameters, and bone mechanical properties were examined. Caffeine favorably affected the skeletal system of ovariectomized rats, slightly inhibiting the development of bone changes induced by estrogen deficiency (increasing bone mineralization, and improving the strength and structure of cancellous bone). Moreover, it favorably affected mechanical properties of compact bone. There were no significant effects of caffeine in rats with normal estrogen levels. In conclusion, results of the present study indicate that low-to-moderate caffeine intake may exert some beneficial effects on the skeletal system of mature organisms. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Study of trabecular bone microstructure using spatial autocorrelation analysis

NASA Astrophysics Data System (ADS)

Wald, Michael J.; Vasilic, Branimir; Saha, Punam K.; Wehrli, Felix W.

2005-04-01

The spatial autocorrelation analysis method represents a powerful, new approach to quantitative characterization of structurally quasi-periodic anisotropic materials such as trabecular bone (TB). The method is applicable to grayscale images and thus does not require any preprocessing, such as segmentation which is difficult to achieve in the limited resolution regime of in vivo imaging. The 3D autocorrelation function (ACF) can be efficiently calculated using the Fourier transform. The resulting trabecular thickness and spacing measurements are robust to the presence of noise and produce values within the expected range as determined by other methods from μCT and μMRI datasets. TB features found from the ACF are shown to correlate well with those determined by the Fuzzy Distance transform (FDT) in the transverse plane, i.e. the plane orthogonal to bone"s major axis. The method is further shown to be applicable to in-vivo μMRI data. Using the ACF, we examine data acquired in a previous study aimed at evaluating the structural implications of male hypogonadism characterized by testosterone deficiency and reduced bone mass. Specifically, we consider the hypothesis that eugonadal and hypogonadal men differ in the anisotropy of their trabecular networks. The analysis indicates a significant difference in trabecular bone thickness and longitudinal spacing between the control group and the testosterone deficient group. We conclude that spatial autocorrelation analysis is able to characterize the 3D structure and anisotropy of trabecular bone and provides new insight into the structural changes associated with osteoporotic trabecular bone loss.

Relative contributions of lean and fat mass to bone strength in young Hispanic and non-Hispanic girls.

PubMed

Hetherington-Rauth, Megan; Bea, Jennifer W; Blew, Robert M; Funk, Janet L; Hingle, Melanie D; Lee, Vinson R; Roe, Denise J; Wheeler, Mark D; Lohman, Timothy G; Going, Scott B

2018-05-22

With the high prevalence of childhood obesity, especially among Hispanic children, understanding how body weight and its components of lean and fat mass affect bone development is important, given that the amount of bone mineral accrued during childhood can determine osteoporosis risk later in life. The aim of this study was to assess the independent contributions of lean and fat mass on volumetric bone mineral density (vBMD), geometry, and strength in both weight-bearing and non-weight-bearing bones of Hispanic and non-Hispanic girls. Bone vBMD, geometry, and strength were assessed at the 20% distal femur, the 4% and 66% distal tibia, and the 66% distal radius of the non-dominant limb of 326, 9- to 12-year-old girls using peripheral quantitative computed tomography (pQCT). Total body lean and fat mass were measured by dual-energy x-ray absorptiometry (DXA). Multiple linear regression was used to assess the independent relationships of fat and lean mass with pQCT bone measures while adjusting for relevant confounders. Potential interactions between ethnicity and both fat and lean mass were also tested. Lean mass was a significant positive contributor to all bone outcomes (p < 0.05) with the exception of vBMD at diaphyseal sites. Fat mass was a significant contributor to bone strength at weight bearing sites, but did not significantly contribute to bone strength at the non-weight bearing radius and was negatively associated with radius cortical content and thickness. Bone measures did not significantly differ between Hispanic and non-Hispanic girls, although there was a significant interaction between ethnicity and fat mass with total bone area at the femur (p = 0.02) and 66% tibia (p = 0.005) as well as bone strength at the femur (p = 0.03). Lean mass is the main determinant of bone strength for appendicular skeletal sites. Fat mass contributes to bone strength in the weight-bearing skeleton but does not add to bone strength in non-weight-bearing locations and may potentially be detrimental. Bone vBMD, geometry, and strength did not differ between Hispanic and non-Hispanic girls; fat mass may be a stronger contributor to bone strength in weight-bearing bones of Hispanic girls compared to non-Hispanic. Copyright © 2018. Published by Elsevier Inc.

Mid-humerus adaptation in fast pitch softballers and the impact of throwing mechanics

PubMed Central

Bogenschutz, Elizabeth D.; Smith, Heather D.; Warden, Stuart J.

2011-01-01

Purpose Throwing is a vigorous activity that generates large internal loads. There is limited evidence of the effect of these loads on bone adaptation. The aim of this study was to investigate the: 1) magnitude of bone adaptation within the midshaft humerus of female fast-pitch softball players and 2) influence of throwing mechanics (windmill vs. overhand throwing) on the magnitude of adaptation. Methods Midshaft humeral bone mass, structure and estimated strength were assessed via peripheral quantitative computed tomography in fast-pitch softball players (throwers; n=15) and matched controls (controls; n=15). The effect of throwing was examined by comparing dominant-to-nondominant differences in throwers to controls, while the influence of mechanics was determined by comparing dominant-to-nondominant differences in throwers who primarily play as pitcher (windmill thrower), catcher (overhand thrower) or fielder (overhand thrower). Results Throwers had greater dominant-to-nondominant difference in midshaft humeral bone mass, structure and estimated strength relative to controls (all P<0.05). The largest effect was for estimated torsional strength with throwers having a mean dominant-to-nondominant difference of 22.5% (range, 6.7% to 43.9%) compared to 4.4% (range, -8.3% to 17.5%) in controls (P<0.001). Throwing mechanics appeared to influence the magnitude of skeletal adaptation, with overhand throwers having more than double dominant-to-nondominant difference in midshaft humeral bone mass, structure and estimated strength than windmill throwers (all P<0.05). Conclusion Throwing induces substantial skeletal adaptation at the midshaft humerus of the dominant upper extremity. Throwing mechanics appears to the influence the magnitude of adaptation as catchers and fielders (overhand throwers) had twice as much adaptation as pitchers (windmill throwers). The latter finding may have implications for skeletal injury risk at the midshaft humerus in throwing athletes. PMID:21311354

A high-fat diet increases body weight and circulating estradiol concentrations but does not improve bone structural properties in ovariectomized mice.

PubMed

Cao, Jay J; Gregoire, Brian R

2016-04-01

Bone health is influenced by body mass and estrogen. The objective of the study was to determine whether high-fat diet-induced obesity affects bone structure and alters markers of bone turnover in ovariectomized (OVX) mice. We hypothesized that a high-fat diet would increase body weight gain and serum estradiol levels in OVX mice but would not improve bone structural parameter in OVX mice. Thirty-five C57BL/6 mice were either sham operated or OVX at the age of 4 months and then fed either a normal-fat diet (10% energy as fat) or a high-fat diet (45% energy as fat with extra fat from lard) ad libitum for 11 weeks. Ovariectomy increased body weight, serum tartrate-resistant acid phosphatase concentration, and expression of cathepsin K in bone; decreased serum estradiol concentration; and induced significant bone loss manifested by decreased bone volume/total volume (BV/TV), connectivity density (Conn.D), trabecular number, and trabecular thickness with increased trabecular separation and structural model index (P < .01). The high-fat diet increased body weight (P < .01) in OVX mice and nonsignificantly decreased BV/TV (P = .08) and Conn.D (P = .10). Despite having similar serum estradiol concentrations and higher body weight, OVX mice consuming the high-fat diet had lower BV/TV, Conn.D, trabecular number, trabecular thickness, and higher structural model index and trabecular separation than did sham mice fed the normal-fat diet. These findings indicate that increased body weight and elevated serum estradiol concentration induced by a high-fat diet do not mitigate ovariectomy-induced bone loss in mice. Published by Elsevier Inc.

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

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...

Age-related changes in the plasticity and toughness of human cortical bone at multiple length-scales

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

Zimmermann, Elizabeth A.; Schaible, Eric; Bale, Hrishikesh

2011-08-10

The structure of human cortical bone evolves over multiple length-scales from its basic constituents of collagen and hydroxyapatite at the nanoscale to osteonal structures at nearmillimeter dimensions, which all provide the basis for its mechanical properties. To resist fracture, bone’s toughness is derived intrinsically through plasticity (e.g., fibrillar sliding) at structural-scales typically below a micron and extrinsically (i.e., during crack growth) through mechanisms (e.g., crack deflection/bridging) generated at larger structural-scales. Biological factors such as aging lead to a markedly increased fracture risk, which is often associated with an age-related loss in bone mass (bone quantity). However, we find that age-relatedmore » structural changes can significantly degrade the fracture resistance (bone quality) over multiple lengthscales. Using in situ small-/wide-angle x-ray scattering/diffraction to characterize sub-micron structural changes and synchrotron x-ray computed tomography and in situ fracture-toughness measurements in the scanning electron microscope to characterize effects at micron-scales, we show how these age-related structural changes at differing size-scales degrade both the intrinsic and extrinsic toughness of bone. Specifically, we attribute the loss in toughness to increased non-enzymatic collagen cross-linking which suppresses plasticity at nanoscale dimensions and to an increased osteonal density which limits the potency of crack-bridging mechanisms at micron-scales. The link between these processes is that the increased stiffness of the cross-linked collagen requires energy to be absorbed by “plastic” deformation at higher structural levels, which occurs by the process of microcracking.« less

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.

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

Six months of disuse during hibernation does not increase intracortical porosity or decrease cortical bone geometry, strength, or mineralization in black bear (Ursus americanus) femurs

PubMed Central

McGee-Lawrence, Meghan E.; Wojda, Samantha J.; Barlow, Lindsay N.; Drummer, Thomas D.; Bunnell, Kevin; Auger, Janene; Black, Hal L.; Donahue, Seth W.

2009-01-01

Disuse typically uncouples bone formation from resorption, leading to bone loss which compromises bone mechanical properties and increases the risk of bone fracture. Previous studies suggest that bears can prevent bone loss during long periods of disuse (hibernation), but small sample sizes have limited the conclusions that can be drawn regarding the effects of hibernation on bone structure and strength in bears. Here we quantified the effects of hibernation on structural, mineral, and mechanical properties of black bear (Ursus americanus) cortical bone by studying femurs from large groups of male and female bears (with wide age ranges) killed during pre-hibernation (fall) and post-hibernation (spring) periods. Bone properties that are affected by body mass (e.g. bone geometrical properties) tended to be larger in male compared to female bears. There were no differences (p > 0.226) in bone structure, mineral content, or mechanical properties between fall and spring bears. Bone geometrical properties differed by less than 5% and bone mechanical properties differed by less than 10% between fall and spring bears. Porosity (fall: 5.5 ± 2.2%, spring: 4.8 ± 1.6%) and ash fraction (fall: 0.694 ± 0.011, spring: 0.696 ± 0.010) also showed no change (p > 0.304) between seasons. Statistical power was high (>72%) for these analyses. Furthermore, bone geometrical properties and ash fraction (a measure of mineral content) increased with age and porosity decreased with age. These results support the idea that bears possess a biological mechanism to prevent disuse and age-related osteoporoses. PMID:19450804

Bone strength in pure bending: bearing of geometric and material properties.

PubMed

Winter, Werner

2008-01-01

Osteoporosis is characterized by decreasing of bone mass and bone strength with advanced age. For characterization of material properties of dense and cellular bone the volumetric bone mineral density (vBMD) is one of the most important contributing factors to bone strength. Often bending tests of whole bone are used to get information about the state of osteoporosis. In a first step, different types of cellular structures are considered to characterize vBMD and its influence to elastic and plastic material properties. Afterwards, the classical theory of plastic bending is used to describe the non-linear moment-curvature relation of a whole bone. For bending of whole bone with sandwich structure an effective second moment of area can be defined. The shape factor as a pure geometrical value is considered to define bone strength. This factor is discussed for a bone with circular cross section and different thickness of cortical bone. The deduced relations and the decrease of material properties are used to demonstrate the influence of osteoporosis to bone bending strength. It can be shown that the elastic and plastic material properties of bone are related to a relative bone mineral density. Starting from an elastic-plastic bone behavior with an constant yield stress the non-linear moment-curvature relation in bending is related to yielding of the fibres in the cross section. The ultimate moment is characterized by a shape factor depending on the geometry of the cross section and on the change of cortical thickness.

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

Relationships among body weight, joint moments generated during functional activities, and hip bone mass in older adults

PubMed Central

Wang, Man-Ying; Flanagan, Sean P.; Song, Joo-Eun; Greendale, Gail A.; Salem, George J.

2012-01-01

Objective To investigate the relationships among hip joint moments produced during functional activities and hip bone mass in sedentary older adults. Methods Eight male and eight female older adults (70–85 yr) performed functional activities including walking, chair sit–stand–sit, and stair stepping at a self-selected pace while instrumented for biomechanical analysis. Bone mass at proximal femur, femoral neck, and greater trochanter were measured by dual-energy X-ray absorptiometry. Three-dimensional hip moments were obtained using a six-camera motion analysis system, force platforms, and inverse dynamics techniques. Pearson’s correlation coefficients were employed to assess the relationships among hip bone mass, height, weight, age, and joint moments. Stepwise regression analyses were performed to determine the factors that significantly predicted bone mass using all significant variables identified in the correlation analysis. Findings Hip bone mass was not significantly correlated with moments during activities in men. Conversely, in women bone mass at all sites were significantly correlated with weight, moments generated with stepping, and moments generated with walking (p < 0.05 to p < 0.001). Regression analysis results further indicated that the overall moments during stepping independently predicted up to 93% of the variability in bone mass at femoral neck and proximal femur; whereas weight independently predicted up to 92% of the variability in bone mass at greater trochanter. Interpretation Submaximal loading events produced during functional activities were highly correlated with hip bone mass in sedentary older women, but not men. The findings may ultimately be used to modify exercise prescription for the preservation of bone mass. PMID:16631283

Recurrent Proximal Femur Fractures in a Teenager With Osteogenesis Imperfecta on Continuous Bisphosphonate Therapy: Are We Overtreating?

PubMed

Vasanwala, Rashida F; Sanghrajka, Anish; Bishop, Nicholas J; Högler, Wolfgang

2016-07-01

Long-term bisphosphonate (BP) therapy in adults with osteoporosis is associated with atypical femoral fractures, caused by increased material bone density and prolonged suppression of bone remodeling which may reduce fracture toughness. In children with osteogenesis imperfecta (OI), long-term intravenous BP therapy improves bone structure and mass without further increasing the already hypermineralized bone matrix, and is generally regarded as safe. Here we report a teenage girl with OI type IV, who was started on cyclical intravenous pamidronate therapy at age 6 years because of recurrent fractures. Transiliac bone biopsy revealed classical structural features of OI but unusually low bone resorption surfaces. She made substantial improvements in functional ability, bone mass, and fracture rate. However, after 5 years of pamidronate therapy she started to develop recurrent, bilateral, nontraumatic, and proximal femur fractures, which satisfied the case definition for atypical femur fractures. Some fractures were preceded by periosteal reactions and prodromal pain. Pamidronate was discontinued after 7 years of therapy, following which she sustained two further nontraumatic femur fractures, and continued to show delayed tibial osteotomy healing. Despite rodding surgery, and very much in contrast to her affected, untreated, and normally mobile mother, she remains wheelchair-dependent. The case of this girl raises questions about the long-term safety of BP therapy in some children, in particular about the risk of oversuppressed bone remodeling with the potential for microcrack accumulation, delayed healing, and increased stiffness. The principal concern is whether there is point at which benefit from BP therapy could turn into harm, where fracture risk increases again. This case should stimulate debate whether current adult atypical femoral fracture guidance should apply to children, and whether low-frequency, low-dose cyclical, intermittent, or oral treatment maintenance regimens should be considered on a case-by-case basis. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

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.

Associations between body composition and bone density and structure in men and women across the adult age spectrum.

PubMed

Baker, Joshua F; Davis, Matthew; Alexander, Ruben; Zemel, Babette S; Mostoufi-Moab, Sogol; Shults, Justine; Sulik, Michael; Schiferl, Daniel J; Leonard, Mary B

2013-03-01

The objective of this study was to identify independent associations between body composition and bone outcomes, including cortical structure and cortical and trabecular volumetric bone mineral density (vBMD) across the adult age spectrum. This cross-sectional study evaluated over 400 healthy adults (48% male, 44% black race), ages 21-78years. Multivariable linear regression models evaluated associations between whole-body DXA measures of lean body mass index (LBMI) and fat mass index (FMI) and tibia peripheral quantitative CT (pQCT) measures of cortical section modulus, cortical and trabecular vBMD and muscle density (as a measure of intramuscular fat), adjusted for age, sex, and race. All associations reported below were statistically significant (p<0.05). Older age and female sex were associated with lower LBMI and muscle strength. Black race was associated with greater LBMI but lower muscle density. Greater FMI was associated with lower muscle density. Cortical section modulus was positively associated with LBMI and muscle strength and negatively associated with FMI. Adjustment for body composition eliminated the greater section modulus observed in black participants and attenuated the lower section modulus in females. Greater LBMI was associated with lower cortical BMD and greater trabecular BMD. FMI was not associated with either BMD outcome. Greater muscle density was associated with greater trabecular and cortical BMD. Associations between body composition and bone outcomes did not vary by sex (no significant tests for interaction). These data highlight age-, sex- and race-specific differences in body composition, muscle strength and muscle density, and demonstrate discrete associations with bone density and structure. These data also show that age-, sex- and race-related patterns of bone density and strength are independent of differences in body composition. Longitudinal studies are needed to examine the temporal relations between changes in bone and body composition. Published by Elsevier Inc.

Associations between Body Composition and Bone Density and Structure in Men and Women across the Adult Age Spectrum

PubMed Central

Baker, Joshua F.; Davis, Matthew; Alexander, Ruben; Zemel, Babette S.; Mostoufi-Moab, Sogol; Shults, Justine; Sulik, Michael; Schiferl, Daniel J.; Leonard, Mary B.

2012-01-01

Background/Purpose The objective of this study was identify independent associations between body composition and bone outcomes, including cortical structure and cortical and trabecular volumetric bone mineral density (vBMD) across the adult age spectrum. Methods This cross-sectional study evaluated over 400 healthy adults (48% male, 44% black race), ages 21–78 years. Multivariable linear regression models evaluated associations between whole-body DXA measures of lean body mass index (LBMI) and fat mass index (FMI) and tibia peripheral quantitative CT (pQCT) measures of cortical section modulus, cortical and trabecular vBMD and muscle density (as a measure of intramuscular fat), adjusted for age, sex, and race. All associations reported below were statistically significant (p < 0.05). Results Older age and female sex were associated with lower LBMI and muscle strength. Black race was associated with greater LBMI but lower muscle density. Greater FMI was associated with lower muscle density. Cortical section modulus was positively associated with LBMI and muscle strength and negatively associated with FMI. Adjustment for body composition eliminated the greater section modulus observed in black participants and attenuated the lower section modulus in females. Greater LBMI was associated with lower cortical BMD and greater trabecular BMD. FMI was not associated with either BMD outcome. Greater muscle density was associated with greater trabecular and cortical BMD. Associations between body composition and bone outcomes did not vary by sex (no significant tests for interaction). Conclusions These data highlight age, sex- and race-specific differences in body composition, muscle strength and muscle density, and demonstrate discrete associations with bone density and structure. These data also show that age, sex- and race- related patterns of bone density and strength are independent of differences in body composition. Longitudinal studies are needed to examine the temporal relations between changes in bone and body composition. PMID:23238122

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.

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.

Influence of physical activity on tibial bone material properties in laying hens

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

Rodriguez-Navarro, A. B.; McCormack, H. M.; Fleming, R. H.

Laying hens develop a type of osteoporosis that arises from a loss of structural bone, resulting in high incidence of fractures. In this study, a comparison of bone material properties was made for lines of hens created by divergent selection to have high and low bone strength and housed in either individual cages, with restricted mobility, or in an aviary system, with opportunity for increased mobility. Improvement of bone biomechanics in the high line hens and in aviary housing was mainly due to increased bone mass, thicker cortical bone and more medullary bone. However, bone material properties such as corticalmore » and medullary bone mineral composition and crystallinity as well as collagen maturity did not differ between lines. However, bone material properties of birds from the different type of housing were markedly different. The cortical bone in aviary birds had a lower degree of mineralization and bone mineral was less mature and less organized than in caged birds. Here, these differences can be explained by increased bone turnover rates due to the higher physical activity of aviary birds that stimulates bone formation and bone remodeling. Multivariate statistical analyses shows that both cortical and medullary bone contribute to breaking strengthThe cortical thickness was the single most important contributor while its degree of mineralization and porosity had a smaller contribution. Lastly, bone properties had poorer correlations with mechanical properties in cage birds than in aviary birds presumably due to the greater number of structural defects of cortical bone in cage birds.« less

Influence of physical activity on tibial bone material properties in laying hens

DOE PAGES

Rodriguez-Navarro, A. B.; McCormack, H. M.; Fleming, R. H.; ...

2017-11-03

Laying hens develop a type of osteoporosis that arises from a loss of structural bone, resulting in high incidence of fractures. In this study, a comparison of bone material properties was made for lines of hens created by divergent selection to have high and low bone strength and housed in either individual cages, with restricted mobility, or in an aviary system, with opportunity for increased mobility. Improvement of bone biomechanics in the high line hens and in aviary housing was mainly due to increased bone mass, thicker cortical bone and more medullary bone. However, bone material properties such as corticalmore » and medullary bone mineral composition and crystallinity as well as collagen maturity did not differ between lines. However, bone material properties of birds from the different type of housing were markedly different. The cortical bone in aviary birds had a lower degree of mineralization and bone mineral was less mature and less organized than in caged birds. Here, these differences can be explained by increased bone turnover rates due to the higher physical activity of aviary birds that stimulates bone formation and bone remodeling. Multivariate statistical analyses shows that both cortical and medullary bone contribute to breaking strengthThe cortical thickness was the single most important contributor while its degree of mineralization and porosity had a smaller contribution. Lastly, bone properties had poorer correlations with mechanical properties in cage birds than in aviary birds presumably due to the greater number of structural defects of cortical bone in cage birds.« less

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

PubMed Central

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

2014-01-01

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

ZIP4 silencing improves bone loss in pancreatic cancer

PubMed Central

Yang, Jingxuan; Ding, Hao; LeBrun, Drake; Ding, Kai; Houchen, Courtney W.; Postier, Russell G.; Ambrose, Catherine G.; Li, Zhaoshen; Bi, Xiaohong; Li, Min

2015-01-01

Metabolic bone disorders are associated with several types of human cancers. Pancreatic cancer patients usually suffer from severe nutrition deficiency, muscle wasting, and loss of bone mass. We have previously found that silencing of a zinc transporter ZIP4 prolongs the survival and reduces the severity of the cachexia in vivo. However, the role of ZIP4 in the pancreatic cancer related bone loss remains unknown. In this study we investigated the effect of ZIP4 knockdown on the bone structure, composition and mechanical properties of femurs in an orthotopic xenograft mouse model. Our data showed that silencing of ZIP4 resulted in increased bone tissue mineral density, decreased bone crystallinity and restoration of bone strength through the RANK/RANKL pathway. The results further support the impact of ZIP4 on the progression of pancreatic cancer, and suggest its potential significance as a therapeutic target for treating patients with such devastating disease and cancer related disorders. PMID:26305676

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.

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.

An Approach for Determining Quantitative Measures for Bone Volume and Bone Mass in the Pediatric Spina Bifida Population

PubMed Central

Horenstein, Rachel E.; Shefelbine, Sandra J.; Mueske, Nicole M.; Fisher, Carissa L.; Wren, Tishya A.L.

2015-01-01

Background The pediatric spina bifida population suffers from decreased mobility and recurrent fractures. This study aimed to develop a method for quantifying bone mass along the entire tibia in youth with spina bifida. This will provide information about all potential sites of bone deficiencies. Methods Computed tomography images of the tibia for 257 children (n=80 ambulatory spina bifida, n=10 non-ambulatory spina bifida, n=167 typically developing) were analyzed. Bone area was calculated at regular intervals along the entire tibia length and then weighted by calibrated pixel intensity for density weighted bone area. Integrals of density weighted bone area were used to quantify bone mass in the proximal and distal epiphyses and diaphysis. Group differences were evaluated using analysis of variance. Findings Non-ambulatory children suffer from decreased bone mass in the diaphysis and proximal and distal epiphyses compared to ambulatory and control children (P≤0.001). Ambulatory children with spina bifida showed statistically insignificant differences in bone mass in comparison to typically developing children at these sites (P>0.5). Interpretation This method provides insight into tibial bone mass distribution in the pediatric spina bifida population by incorporating information along the whole length of the bone, thereby providing more information than dual-energy x-ray absorptiometry and peripheral quantitative computed tomography. This method can be applied to any population to assess bone mass distribution across the length of any long bone. PMID:26002057

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...

Viscoelastic and Functional Properties of Cod-Bone Gelatin in the Presence of Xylitol and Stevioside

NASA Astrophysics Data System (ADS)

Nian, Linyu; Cao, Ailing; Wang, Jing; Tian, Hongyu; Liu, Yongguo; Gong, Lingxiao; Cai, Luyun; Wang, Yuhao

2018-05-01

The physical, rheological, structural and functional properties of cod bone gelatin (CBG) with various concentrations (0, 2, 4, 6, 10 and 15%) of low-calorie sweeteners (xylitol (X) and stevioside (S)) to form gels were investigated. The gel strength of CBGX increased with increased xylitol due presumably to hydrogen bonds between xylitol and gelatin, but with CBGS the highest gel strength occurred when S concentration was 4%. Viscosity of CBGS samples were higher than CBGX due to S’s high molecular mass. The viscoelasticity (G' and G″), foaming capacity and fat binding capacity of CBGX were higher while foam stability was lower. The emulsion activity and emulsion stability of CBGX were a little lower than CBGS at the same concentration. The structure of X is linear making it easier to form a dense three-dimensional network structure, while the complex cyclic structure of S had more difficulty forming a network structure with cod bone gelatin. Therefore, X may be a better choice for sweetening gelatin gels.

Viscoelastic and Functional Properties of Cod-Bone Gelatin in the Presence of Xylitol and Stevioside.

PubMed

Nian, Linyu; Cao, Ailing; Wang, Jing; Tian, Hongyu; Liu, Yongguo; Gong, Lingxiao; Cai, Luyun; Wang, Yuhao

2018-01-01

The physical, rheological, structural and functional properties of cod bone gelatin (CBG) with various concentrations (0, 2, 4, 6, 10, and 15%) of low-calorie sweeteners [xylitol (X) and stevioside (S)] to form gels were investigated. The gel strength of CBGX increased with increased xylitol due presumably to hydrogen bonds between xylitol and gelatin, but with CBGS the highest gel strength occurred when S concentration was 4%. Viscosity of CBGS samples were higher than CBGX due to S's high molecular mass. The viscoelasticity (G' and G''), foaming capacity and fat binding capacity of CBGX were higher while foam stability was lower. The emulsion activity and emulsion stability of CBGX were a little lower than CBGS at the same concentration. The structure of X is linear making it easier to form a dense three-dimensional network structure, while the complex cyclic structure of S had more difficulty forming a network structure with cod bone gelatin. Therefore, X may be a better choice for sweetening gelatin gels.

Immobilization and long-term recovery results in large changes in bone structure and strength but no corresponding alterations of osteocyte lacunar properties.

PubMed

Bach-Gansmo, Fiona Linnea; Wittig, Nina Kølln; Brüel, Annemarie; Thomsen, Jesper Skovhus; Birkedal, Henrik

2016-10-01

The ability of osteocytes to demineralize the perilacunar matrix, osteocytic osteolysis, and thereby participate directly in bone metabolism, is an aspect of osteocyte biology that has received increasing attention during the last couple of years. The aim of the present work was to investigate whether osteocyte lacunar properties change during immobilization and subsequent recovery. A rat cortical bone model with negligible Haversian remodeling effects was used, with temporary immobilization of one hindlimb induced by botulinum toxin. Several complementary techniques covering multiple length scales enabled correlation of osteocyte lacunar properties to changes observed on the organ and tissue level of femoral bone. Bone structural parameters measured by μCT and mechanical properties were compared to sub-micrometer resolution SR μCT data mapping an unprecedented number (1.85 million) of osteocyte lacunae. Immobilization induced a significant reduction in aBMD, bone volume, tissue volume, and load to fracture, as well as the muscle mass of rectus femoris. During the subsequent recovery period, the bone structural and mechanical properties were only partly regained in spite of a long-term (28weeks) study period. No significant changes in osteocyte lacunar volume, density, oblateness, stretch, or orientation were detected upon immobilization or subsequent recovery. In conclusion, the bone architecture and not osteocyte lacunar properties or bone material characteristics dominate the immobilization response as well as the subsequent recovery. Copyright © 2016 Elsevier Inc. All rights reserved.

INVESTIGATION OF BONE MINERALIZATION IN PATIENTS WITH CORONARY HEART DISEASE COMPLICATED BY CHRONIC HEART FAILURE, STAGE II-A.

PubMed

Krynytska, I; Marushchak, M; Zaets, T; Savchenko, I; Habor, H

2017-06-01

The majority of the studies have shown that individuals with cardiovascular diseases have a higher risk of experiencing bone loss and thus greater predisposition to risk of fracture. On the other hand there is growing evidence that individuals with low bone mass have higher mortality for cardiovascular events compared to patients with cardiovascular disease with normal bone mass. This research aims to investigate bone mineralization in patients with coronary heart disease complicated by stage II-A chronic heart failure. The study involved 33 men with coronary heart disease complicated by Stage II-A chronic heart failure. Bone mineral density was measured using dual energy x-ray densitometry of lumbar region of spine. Structural and functional changes of bone tissue of the lumbar spine have been found in 49,2% patients with coronary heart disease complicated by Stage II-A chronic heart failure, in particular, I stage of osteopenia - in 44,6%, II stage of osteopenia - in 27,7%, III stage of osteopenia - in 10,8% and osteoporosis - in 16,9%. It was established the same type of downward trend for BMD decreasing in L1 of patients with different stages of osteopenia, but in case of osteoporosis mineralization decreased equally in all vertebrae.

Genetic predisposition to low bone mass is paralleled by an enhanced sensitivity to signals anabolic to the skeleton

NASA Technical Reports Server (NTRS)

Judex, Stefan; Donahue, Leah-Rae; Rubin, Clinton

2002-01-01

The structure of the adult skeleton is determined, in large part, by its genome. Whether genetic variations may influence the effectiveness of interventions to combat skeletal diseases remains unknown. The differential response of trabecular bone to an anabolic (low-level mechanical vibration) and a catabolic (disuse) mechanical stimulus were evaluated in three strains of adult mice. In low bone-mineral-density C57BL/6J mice, the low-level mechanical signal caused significantly larger bone formation rates (BFR) in the proximal tibia, but the removal of functional weight bearing did not significantly alter BFR. In mid-density BALB/cByJ mice, mechanical stimulation also increased BFR, whereas disuse significantly decreased BFR. In contrast, neither anabolic nor catabolic mechanical signals influenced any index of bone formation in high-density C3H/HeJ mice. Together, data from this study indicate that the sensitivity of trabecular tissue to both anabolic and catabolic stimuli is influenced by the genome. Extrapolated to humans, these results may explain in part why prophylaxes for low bone mass are not universally effective, yet also indicate that there may be a genotypic indication of people who are at reduced risk of suffering from bone loss.

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.

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

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

Architectural and biochemical adaptations in skeletal muscle and bone following rotator cuff injury in a rat model.

PubMed

Sato, Eugene J; Killian, Megan L; Choi, Anthony J; Lin, Evie; Choo, Alexander D; Rodriguez-Soto, Ana E; Lim, Chanteak T; Thomopoulos, Stavros; Galatz, Leesa M; Ward, Samuel R

2015-04-01

Injury to the rotator cuff can cause irreversible changes to the structure and function of the associated muscles and bones. The temporal progression and pathomechanisms associated with these adaptations are unclear. The purpose of this study was to investigate the time course of structural muscle and osseous changes in a rat model of a massive rotator cuff tear. Supraspinatus and infraspinatus muscle architecture and biochemistry and humeral and scapular morphological parameters were measured three days, eight weeks, and sixteen weeks after dual tenotomy with and without chemical paralysis via botulinum toxin A (BTX). Muscle mass and physiological cross-sectional area increased over time in the age-matched control animals, decreased over time in the tenotomy+BTX group, and remained nearly the same in the tenotomy-alone group. Tenotomy+BTX led to increased extracellular collagen in the muscle. Changes in scapular bone morphology were observed in both experimental groups, consistent with reductions in load transmission across the joint. These data suggest that tenotomy alone interferes with normal age-related muscle growth. The addition of chemical paralysis yielded profound structural changes to the muscle and bone, potentially leading to impaired muscle function, increased muscle stiffness, and decreased bone strength. Structural musculoskeletal changes occur after tendon injury, and these changes are severely exacerbated with the addition of neuromuscular compromise. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

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.

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

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.

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.

A large extraskeletal osteochondroma of the foot.

PubMed

Estil, Jose Carlos C; Yeo, Eui-Dong; Kim, Hak Jun; Cho, Won Tae; Lee, Jeong-Ju

2013-01-01

Osteochondromas are very common benign tumors composed of cartilage and bone. They are usually found at the end of the growth plate of long bones, most often at the area of the joints, and are contiguous with the medullary cavity. Extraskeletal osteochondromas, the same as their namesake, are composed of cartilage and bone. However, unlike typical osteochondromas, extraskeletal osteochondromas are not contiguous with bone, as their name implies. They usually arise from the synovial tissue and tendon sheaths. Although rare, extraskeletal osteochondromas have been reported to occur within the knee and around the hip; however, they are more commonly reported to occur in the hands and feet. When found in the hands or feet, these new growths are often very small and only occasionally symptomatic. We present the case of a 49-year-old female who had a slow-growing mass of 4 years' duration, located on the plantar aspect of her left foot. The mass was slowly becoming more palpable as it increased in size and was progressively causing pain and discomfort during ambulation. Imaging studies revealed an ossified mass bearing no connection to any other structure on the plantar aspect of her foot. An excision biopsy was performed, and the easily dissectible mass, although much larger than its usual presentation, proved to be an extraskeletal osteochondroma. Copyright © 2013 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Constitutive β-catenin activation in osteoblasts impairs terminal osteoblast differentiation and bone quality

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

Bao, Quanwei; Chen, Sixu; Qin, Hao

Accumulating evidence suggests that Wnt/β-catenin signaling plays a central role in controlling bone mass. We previously reported that constitutive activation of β-catenin (CA-β-catenin) in osteoblasts potentially has side effects on the bone growth and bone remodeling process, although it could increase bone mass. The present study aimed to observe the effects of osteoblastic CA-β-catenin on bone quality and to investigate possible mechanisms of these effects. It was found that CA-β-catenin mice exhibited lower mineralization levels and disorganized collagen in long bones as confirmed by von Kossa staining and sirius red staining, respectively. Also, bone strength decreased significantly in CA-β-catenin mice.more » Then the effect of CA-β-catenin on biological functions of osteoblasts were investigated and it was found that the expression levels of osteocalcin, a marker for the late differentiation of osteoblasts, decreased in CA-β-catenin mice, while the expression levels of osterix and alkaline phosphatase, two markers for the early differentiation of osteoblasts, increased in CA-β-catenin mice. Furthermore, higher proliferation rate were revealed in osteoblasts that were isolated from CA-β-catenin mice. The Real-time PCR and western blot examination found that the expression level of c-myc and cyclin D1, two G1 progression-related molecules, increased in osteoblasts that were isolated from the CA-β-catenin mice, and the expression levels of CDK14 and cyclin Y, two mitotic-related molecules that can accelerate cells entering into S and G2/M phases, increased in osteoblasts that were isolated from the CA-β-catenin mice. In summary, osteoblastic CA-β-catenin kept osteoblasts in high proliferative state and impaired the terminal osteoblast differentiation, and this led to changed bone structure and decreased bone strength. - Highlights: • Wnt/β-catenin signaling plays a central role in controlling bone mass. • CA-β-catenin has side effects on the bone strength and bone qulity. • CA-β-catenin kept osteoblasts in high proliferative state. • Osteoblastic CA-β-catenin impaired the terminal osteoblast differentiation.« less

The Effects of Partial Mechanical Loading and Ibandronate on Skeletal Tissues in the Adult Rat Hindquarter Suspension Model for Microgravity

NASA Technical Reports Server (NTRS)

Schultheis, Lester W.

1999-01-01

We report initial data from a suspended rat model that quantitatively relates chronic partial weightbearing to bone loss. Chronic partial weightbearing is our simulation of the effect of limited artificial gravity aboard spacecraft or reduced planetary gravity. Preliminary analysis of bone by PQCT, histomorphometry, mechanical testing and biochemistry suggest that chronic exposure to half of Earth gravity is insufficient to prevent severe bone loss. The effect of episodic full weightbearing activity (Earth Gravity) on rats otherwise at 50% weightbearing was also explored. This has similarity to treatment by an Earth G-rated centrifuge on a spacecraft that normally maintained artificial gravity at half of Earth G. Our preliminary evidence, using the above techniques to analyze bone, indicate that 2 hours daily of full weightbearing was insufficient to prevent the bone loss observed in 50% weightbearing animals. The effectiveness of partial weightbearing and episodic full weightbearing as potential countermeasures to bone loss in spaceflight was compared with treatment by ibandronate. Ibandronate, a long-acting potent bisphosphonate proved more effective in preventing bone loss and associated functionality based upon structure than our first efforts at mechanical countermeasures. The effectiveness of ibandronate was notable by each of the testing methods we used to study bone from gross structure and strength to tissue and biochemistry. These results appear to be independent of generalized systemic stress imposed by the suspension paradigm. Preliminary evidence does not suggest that blood levels of vitamin D were affected by our countermeasures. Despite the modest theraputic benefit of mechanical countermeasures of partial weightbearing and episodic full weightbearing, we know that some appropriate mechanical signal maintains bone mass in Earth gravity. Moreover, the only mechanism that correctly assigns bone mass and strength to oppose regionally specific force applied to bone is mechanical, a process based upon bone strain. Substantial evidence indicates that the specifics of dynamic loading i.e. time-varying forces are critical. Bone strain history is a predictor of the effect that mechanical conditions have on bone structure mass and strength. Using servo-controlled force plates on suspended rats with implanted strain gauges we manipulated impact forces of ambulation in the frequency (Fourier) domain. Our results indicate that high frequency components of impact forces are particularly potent in producing bone strain independent of the magnitude of the peak force or peak energy applied to the leg. Because a servo-system responds to forces produced by the rat's own muscle activity during ambulation, the direction of ground-reaction loads act on bone through the rat's own musculature. This is in distinction to passive vibration of the floor where forces reach bone through the natural filters of soft tissue and joints. Passive vibration may also be effective, but it may or may not increase bone in the appropriate architectural pattern to oppose the forces of normal ambulatory activity. Effectiveness of high frequency mechanical stimulation in producing regional (muscle directed) bone response will be limited by 1. the sensitivity of bone to a particular range of frequencies and 2. the inertia of the muscles, limiting their response to external forces by increasing tension along insertions. We have begun mathematical modeling of normal ambulatory activity. Effectiveness of high frequency mechanical stimulation in producing regional (muscle directed) bone response will be limited by 1. the sensitivity of bone to a particular range of frequencies and 2. the inertia of the muscles, limiting their response to external forces by increasing tension along insertions. We have begun mathematical modeling of the rat forelimb as a transfer function between impact force and bone strain to predict optimal dynamic loading conditions for this system. We plan additional studies of mechanical counter-measures that incorporate improved dynamic loading, features relevant to anticipated evaluation of artificial gravity, exercise regimens and exposure to Martian gravity, The combination of mechanical countermeasures with ibandronate will also be investigated for signs of synergy.

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

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

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

Sheep model for osteoporosis: The effects of peripheral hormone therapy on centrally induced systemic bone loss in an osteoporotic sheep model.

PubMed

Oheim, Ralf; Simon, Maciej J K; Steiner, Malte; Vettorazzi, Eik; Barvencik, Florian; Ignatius, Anita; Amling, Michael; Clarke, Iain J; Pogoda, Pia; Beil, F Timo

2017-04-01

Hypothalamic-pituitary disconnection (HPD) leads to low bone turnover followed by bone loss and reduced biomechanical properties in sheep. To investigate the role of peripheral hormones in this centrally induced systemic bone loss model, we planned a hormone replacement experiment. Therefore, estrogen (OHE), thyroxin (OHT) or a combination of both (OHTE) was substituted in ovariectomized HPD sheep, as both hormones are decreased in HPD sheep and are known to have a significant but yet not fully understood impact on bone metabolism. Bone turnover and structural parameters were analyzed in comparison to different control groups - untreated sheep (C), ovariectomized (O) and ovariectomized+HPD sheep (OH). We performed histomorphometric and HR-pQCT analyses nine months after the HPD procedure, as well as biomechanical testing of all ewes studied. In HPD sheep (OH) the low bone turnover led to a significant bone loss. Treatment with thyroxin alone (OHT) mainly increased bone resorption, leading to a further reduction in bone volume. In contrast, the treatment with estrogen alone (OHE) and the combined treatment with estrogen and thyroxin (OHTE) prevented HPD-induced bone loss completely. In conclusion, peripheral hormone substitution was able to prevent HPD-induced low-turnover osteoporosis in sheep. But only the treatment with estrogen alone or in combination with thyroxin was able to completely preserve bone mass and structure. These findings demonstrate the importance of peripheral hormones for a balanced bone remodeling and a physiological bone turnover. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2013-11-01

To determine the effect of levetiracetam (LEV) Lon bone mineral density (BMD), mineral content (BMC), bone markers, body composition and bone mechanical strength in the orchidectomised (ORX) rat model. 16 orchidectomised Wistar rats were divided into control and test groups, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed with SLD enriched with LEV for 12 weeks. BMD was measured by dual energy X-ray absorptiometry at the whole body, lumbar spine and femur. Bone marker concentrations were examined of osteoprotegerin (OPG) and insulin-like growth factor 1 (IGF-1) in serum, and amino-terminal propeptide of procollagen type I (PINP), carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I), bone alkaline phosphatase (ALPL), and bone morphogenetic protein 2 (BMP-2) in bone homogenate. The femurs were used for biomechanical testing. Compared to the control group we found lower fat mass, lower BMD in the area of the left femur, lower BMC in both femurs, a reduced concentration of OPG, and an increased concentration of CTX-I of borderline statistical significance (p=0.0661). Biomechanical parameters did not differ between groups. Significant loss of BMD or BMC was seen at the left and right femur area in the LEV group. Administration of LEV in the ORX-rat model significantly decreased levels of OPG (marker of bone formation) in serum and increased levels of CTX-I (marker of bone resorption) in bone homogenate, but results in this study did not reveal any change in biomechanical bone strength. Administration of LEV in the ORX-rat model may reduce adipose tissue. Further studies in animals and humans will be needed to confirm these findings. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

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

PubMed

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

2014-05-15

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

Bone Inner Structure Suggests Increasing Aquatic Adaptations in Desmostylia (Mammalia, Afrotheria)

PubMed Central

Hayashi, Shoji; Houssaye, Alexandra; Nakajima, Yasuhisa; Chiba, Kentaro; Ando, Tatsuro; Sawamura, Hiroshi; Inuzuka, Norihisa; Kaneko, Naotomo; Osaki, Tomohiro

2013-01-01

Background The paleoecology of desmostylians has been discussed controversially with a general consensus that desmostylians were aquatic or semi-aquatic to some extent. Bone microanatomy can be used as a powerful tool to infer habitat preference of extinct animals. However, bone microanatomical studies of desmostylians are extremely scarce. Methodology/Principal Findings We analyzed the histology and microanatomy of several desmostylians using thin-sections and CT scans of ribs, humeri, femora and vertebrae. Comparisons with extant mammals allowed us to better understand the mode of life and evolutionary history of these taxa. Desmostylian ribs and long bones generally lack a medullary cavity. This trait has been interpreted as an aquatic adaptation among amniotes. Behemotops and Paleoparadoxia show osteosclerosis (i.e. increase in bone compactness), and Ashoroa pachyosteosclerosis (i.e. combined increase in bone volume and compactness). Conversely, Desmostylus differs from these desmostylians in displaying an osteoporotic-like pattern. Conclusions/Significance In living taxa, bone mass increase provides hydrostatic buoyancy and body trim control suitable for poorly efficient swimmers, while wholly spongy bones are associated with hydrodynamic buoyancy control in active swimmers. Our study suggests that all desmostylians had achieved an essentially, if not exclusively, aquatic lifestyle. Behemotops, Paleoparadoxia and Ashoroa are interpreted as shallow water swimmers, either hovering slowly at a preferred depth, or walking on the bottom, and Desmostylus as a more active swimmer with a peculiar habitat and feeding strategy within Desmostylia. Therefore, desmostylians are, with cetaceans, the second mammal group showing a shift from bone mass increase to a spongy inner organization of bones in their evolutionary history. PMID:23565143

Single dose of bisphosphonate preserves gains in bone mass following cessation of sclerostin antibody in Brtl/+ osteogenesis imperfecta model.

PubMed

Perosky, Joseph E; Khoury, Basma M; Jenks, Terese N; Ward, Ferrous S; Cortright, Kai; Meyer, Bethany; Barton, David K; Sinder, Benjamin P; Marini, Joan C; Caird, Michelle S; Kozloff, Kenneth M

2016-12-01

Sclerostin antibody has demonstrated a bone-forming effect in pre-clinical models of osteogenesis imperfecta, where mutations in collagen or collagen-associated proteins often result in high bone fragility in pediatric patients. Cessation studies in osteoporotic patients have demonstrated that sclerostin antibody, like intermittent PTH treatment, requires sequential anti-resorptive therapy to preserve the anabolic effects in adult populations. However, the persistence of anabolic gains from either drug has not been explored clinically in OI, or in any animal model. To determine whether cessation of sclerostin antibody therapy in a growing OI skeleton requires sequential anti-resorptive treatment to preserve anabolic gains in bone mass, we treated 3week old Brtl/+ and wild type mice for 5weeks with SclAb, and then withdrew treatment for an additional 6weeks. Trabecular bone loss was evident following cessation, but was preserved in a dose-dependent manner with single administration of pamidronate at the time of cessation. In vivo longitudinal near-infrared optical imaging of cathepsin K activation in the proximal tibia suggests an anti-resorptive effect of both SclAb and pamidronate which is reversed after three weeks of cessation. Cortical bone was considerably less susceptible to cessation effects, and showed no structural or functional deficits in the absence of pamidronate during this cessation period. In conclusion, while SclAb induces a considerable anabolic gain in the rapidly growing Brtl/+ murine model of OI, a single sequential dose of antiresorptive drug is required to maintain bone mass at trabecular sites for 6weeks following cessation. Copyright © 2016 Elsevier Inc. All rights reserved.

Contributions of fat mass and fat distribution to hip bone strength in healthy postmenopausal Chinese women.

PubMed

Shao, Hong Da; Li, Guan Wu; Liu, Yong; Qiu, Yu You; Yao, Jian Hua; Tang, Guang Yu

2015-09-01

The fat and bone connection is complicated, and the effect of adipose tissue on hip bone strength remains unclear. The aim of this study was to clarify the relative contribution of body fat accumulation and fat distribution to the determination of proximal femur strength in healthy postmenopausal Chinese women. This cross-sectional study enrolled 528 healthy postmenopausal women without medication history or known diseases. Total lean mass (LM), appendicular LM (ALM), percentage of lean mass (PLM), total fat mass (FM), appendicular FM (AFM), percentage of body fat (PBF), android and gynoid fat amount, android-to-gynoid fat ratio (AOI), bone mineral density (BMD), and proximal femur geometry were measured by dual energy X-ray absorptiometry. Hip structure analysis was used to compute some variables as geometric strength-related parameters by analyzing the images of the hip generated from DXA scans. Correlation analyses among anthropometrics, variables of body composition and bone mass, and geometric indices of hip bone strength were performed with stepwise linear regression analyses as well as Pearson's correlation analysis. In univariate analysis, there were significantly inverse correlations between age, years since menopause (YSM), hip BMD, and hip geometric parameters. Bone data were positively related to height, body weight, LM, ALM, FM, AFM, and PBF but negatively related to AOI and amount of android fat (all P < 0.05). AFM and AOI were significantly related to most anthropometric parameters. AFM was positively associated with height, body weight, and BMI. AFM was negatively associated with age and YSM. AOI was negatively associated with height, body weight, and BMI. AOI positively associated with age and YSM. LM, ALM, and FM had a positive relationship with anthropometric parameters (P < 0.05 for all). PLM had a negative relationship with those parameters. The correlation between LM, ALM, FM, PLM, ALM, age, and YSM was not significant. In multivariate linear regression analysis, the hip bone strength was observed to have a consistent and unchanged positive association with AFM and a negative association with AOI, whereas its association with other variables of body composition was not significant after adjusting for age, years since menopause, height, body weight, and BMI. AFM may be a positively protective effect for hip bone strength while AOI, rather than android fat, shows a strong negative association with hip bone strength after making an adjustment for confounders (age, YSM, height, body weight, and BMI) in healthy postmenopausal Chinese women. Rational weight control and AOI reduction during menopause may have vital clinical significance in decreasing postmenopausal osteoporosis.

Fat, Sugar, and Bone Health: A Complex Relationship

PubMed Central

Tian, Li; Yu, Xijie

2017-01-01

With people aging, osteoporosis is expected to increase notably. Nutritional status is a relatively easily-modified risk factor, associated with many chronic diseases, and is involved in obesity, diabetes, and coronary heart disease (CHD), along with osteoporosis. Nutrients, such as fats, sugars, and proteins, play a primary function in bone metabolism and maintaining bone health. In Western nations, diets are generally high in saturated fats, however, currently, the nutritional patterns dominating in China continue to be high in carbohydrates from starch, cereals, and sugars. Moreover, high fat or high sugar (fructose, glucose, or sucrose) impart a significant impact on bone structural integrity. Due to diet being modifiable, demonstrating the effects of nutrition on bone health can provide an approach for osteoporosis prevention. Most researchers have reported that a high-fat diet consumption is associated with bone mineral density (BMD) and, as bone strength diminishes, adverse microstructure changes occur in the cancellous bone compartment, which is involved with lipid metabolism modulation disorder and the alteration of the bone marrow environment, along with an increased inflammatory environment. Some studies, however, demonstrated that a high-fat diet contributes to achieving peak bone mass, along with microstructure, at a younger age. Contrary to these results, others have shown that a high-fructose diet consumption leads to stronger bones with a superior microarchitecture than those with the intake of a high-glucose diet and, at the same time, research indicated that a high-fat diet usually deteriorates cancellous bone parameters, and that the incorporation of fructose into a high-fat diet did not aggravate bone mass loss. High-fat/high-sucrose diets have shown both beneficial and detrimental influences on bone metabolism. Combined, these studies showed that nutrition exerts different effects on bone health. Thus, a better understanding of the regulation between dietary nutrition and bone health might provide a basis for the development of strategies to improve bone health by modifying nutritional components. PMID:28513571

Fat, Sugar, and Bone Health: A Complex Relationship.

PubMed

Tian, Li; Yu, Xijie

2017-05-17

With people aging, osteoporosis is expected to increase notably. Nutritional status is a relatively easily-modified risk factor, associated with many chronic diseases, and is involved in obesity, diabetes, and coronary heart disease (CHD), along with osteoporosis. Nutrients, such as fats, sugars, and proteins, play a primary function in bone metabolism and maintaining bone health. In Western nations, diets are generally high in saturated fats, however, currently, the nutritional patterns dominating in China continue to be high in carbohydrates from starch, cereals, and sugars. Moreover, high fat or high sugar (fructose, glucose, or sucrose) impart a significant impact on bone structural integrity. Due to diet being modifiable, demonstrating the effects of nutrition on bone health can provide an approach for osteoporosis prevention. Most researchers have reported that a high-fat diet consumption is associated with bone mineral density (BMD) and, as bone strength diminishes, adverse microstructure changes occur in the cancellous bone compartment, which is involved with lipid metabolism modulation disorder and the alteration of the bone marrow environment, along with an increased inflammatory environment. Some studies, however, demonstrated that a high-fat diet contributes to achieving peak bone mass, along with microstructure, at a younger age. Contrary to these results, others have shown that a high-fructose diet consumption leads to stronger bones with a superior microarchitecture than those with the intake of a high-glucose diet and, at the same time, research indicated that a high-fat diet usually deteriorates cancellous bone parameters, and that the incorporation of fructose into a high-fat diet did not aggravate bone mass loss. High-fat/high-sucrose diets have shown both beneficial and detrimental influences on bone metabolism. Combined, these studies showed that nutrition exerts different effects on bone health. Thus, a better understanding of the regulation between dietary nutrition and bone health might provide a basis for the development of strategies to improve bone health by modifying nutritional components.

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.

Epidemiology and treatment of osteoporosis in women: an Indian perspective

PubMed Central

Khadilkar, Anuradha V; Mandlik, Rubina M

2015-01-01

The number of women with osteoporosis, ie, with reduced bone mass and the disruption of bone architecture, is increasing in India. While data on prevalence of osteoporosis among women in India come from studies conducted in small groups spread across the country, estimates suggest that of the 230 million Indians expected to be over the age of 50 years in 2015, 20%, ie, ~46 million, are women with osteoporosis. Thus, osteoporosis is a major public health problem in Indian women. Low calcium intakes with extensive prevalence of vitamin D deficiency, increasing longevity, sex inequality, early menopause, genetic predisposition, lack of diagnostic facilities, and poor knowledge of bone health have contributed toward the high prevalence of osteoporosis. Bone health may be optimized by creating an environment to achieve peak bone mass during adolescence, maintenance of healthy bone throughout the life cycle, and prevention of bone loss postmenopausal. In Indian women, calcium, vitamin D, and bisphosphonates are the commonest first-line therapies used. The use of other drugs such as hormone replacement therapy, estrogen agonists, calcitonin, parathyroid hormone, and denosumab is decided as per the affordability and availability of treatment options. Major gaps still remain in the diagnosis and management of osteoporosis, thus highlighting the need for more structured research in this area. This review focuses on the epidemiology of osteoporosis in Indian women and available treatments. PMID:26527900

Epidemiology and treatment of osteoporosis in women: an Indian perspective.

PubMed

Khadilkar, Anuradha V; Mandlik, Rubina M

2015-01-01

The number of women with osteoporosis, ie, with reduced bone mass and the disruption of bone architecture, is increasing in India. While data on prevalence of osteoporosis among women in India come from studies conducted in small groups spread across the country, estimates suggest that of the 230 million Indians expected to be over the age of 50 years in 2015, 20%, ie, ~46 million, are women with osteoporosis. Thus, osteoporosis is a major public health problem in Indian women. Low calcium intakes with extensive prevalence of vitamin D deficiency, increasing longevity, sex inequality, early menopause, genetic predisposition, lack of diagnostic facilities, and poor knowledge of bone health have contributed toward the high prevalence of osteoporosis. Bone health may be optimized by creating an environment to achieve peak bone mass during adolescence, maintenance of healthy bone throughout the life cycle, and prevention of bone loss postmenopausal. In Indian women, calcium, vitamin D, and bisphosphonates are the commonest first-line therapies used. The use of other drugs such as hormone replacement therapy, estrogen agonists, calcitonin, parathyroid hormone, and denosumab is decided as per the affordability and availability of treatment options. Major gaps still remain in the diagnosis and management of osteoporosis, thus highlighting the need for more structured research in this area. This review focuses on the epidemiology of osteoporosis in Indian women and available treatments.

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.

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 ...

Impacts of the N-terminal fragment analog of human parathyroid hormone on structure, composition and biomechanics of bone.

PubMed

Chunxiao, Wang; Yu, Zhang; Wentao, Liu; Jingjing, Liu; Jiahui, Ye; Qingmei, Chen

2012-12-18

Osteoporosis is a skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, and it is a serious threat to human lives. We previously showed that the N-terminal peptide analog of human parathyroid hormone (Pro-Pro-PTH(1-34)) enhanced plasma calcium concentration. In this paper, we study the impact of PTH N-terminal fragment analog on the structure, component, and mechanical properties of the rat bones. Daily subcutaneous injections of Pro-Pro-hPTH (1-34) induces 26.5-32.8% increase in femur bone mineral density (BMD), 23.0-34.2% decrease the marrow cavity or increase in trabecular bone area. The peptide also increases 16.0-59.5%, 28.8-48.2% and 14.0-17.8% of bone components of calcium, phosphorus and collagen, respectively. In terms of mechanic properties, administration of the peptide elevates the bone rigidity by 45.4-76.6%, decreases the flexibility by 23.0-31.6%, and improves modulus of elasticity by 32.8-63.4%. The results suggest that Pro-Pro-hPTH (1-34) has a positive effect on bone growth and strength, and possesses anti-fracture capability, thus a potential candidate for the application for the treatment of osteoporosis. Copyright © 2012 Elsevier B.V. All rights reserved.

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

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).

Systematic review of raloxifene in postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia)

PubMed Central

Fujiwara, Saeko; Hamaya, Etsuro; Sato, Masayo; Graham-Clarke, Peita; Flynn, Jennifer A; Burge, Russel

2014-01-01

Purpose To systematically review the literature describing the efficacy, effectiveness, and safety of raloxifene for postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia). Materials and methods Medline via PubMed and Embase was systematically searched using prespecified terms. Retrieved publications were screened and included if they described randomized controlled trials or observational studies of postmenopausal Japanese women with osteoporosis or osteopenia treated with raloxifene and reported one or more outcome measures (change in bone mineral density [BMD]; fracture incidence; change in bone-turnover markers, hip structural geometry, or blood–lipid profile; occurrence of adverse events; and change in quality of life or pain). Excluded publications were case studies, editorials, letters to the editor, narrative reviews, or publications from non-peer-reviewed journals; multidrug, multicountry, or multidisease studies with no drug-, country-, or disease-level analysis; or studies of participants on dialysis. Results Of the 292 publications retrieved, 15 publications (seven randomized controlled trials, eight observational studies) were included for review. Overall findings were statistically significant increases in BMD of the lumbar spine (nine publications), but not the hip region (eight publications), a low incidence of vertebral fracture (three publications), decreases in markers of bone turnover (eleven publications), improved hip structural geometry (two publications), improved blood–lipid profiles (five publications), a low incidence of hot flushes, leg cramps, venous thromboembolism, and stroke (12 publications), and improved quality of life and pain relief (one publication). Conclusion Findings support raloxifene for reducing vertebral fracture risk by improving BMD and reducing bone turnover in postmenopausal Japanese women with osteoporosis or osteopenia. Careful consideration of fracture risk and the risk–benefit profile of antiosteoporosis medications is required when managing patients with osteoporosis. PMID:25395843

Systematic review of raloxifene in postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia).

PubMed

Fujiwara, Saeko; Hamaya, Etsuro; Sato, Masayo; Graham-Clarke, Peita; Flynn, Jennifer A; Burge, Russel

2014-01-01

To systematically review the literature describing the efficacy, effectiveness, and safety of raloxifene for postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia). Medline via PubMed and Embase was systematically searched using prespecified terms. Retrieved publications were screened and included if they described randomized controlled trials or observational studies of postmenopausal Japanese women with osteoporosis or osteopenia treated with raloxifene and reported one or more outcome measures (change in bone mineral density [BMD]; fracture incidence; change in bone-turnover markers, hip structural geometry, or blood-lipid profile; occurrence of adverse events; and change in quality of life or pain). Excluded publications were case studies, editorials, letters to the editor, narrative reviews, or publications from non-peer-reviewed journals; multidrug, multicountry, or multidisease studies with no drug-, country-, or disease-level analysis; or studies of participants on dialysis. Of the 292 publications retrieved, 15 publications (seven randomized controlled trials, eight observational studies) were included for review. Overall findings were statistically significant increases in BMD of the lumbar spine (nine publications), but not the hip region (eight publications), a low incidence of vertebral fracture (three publications), decreases in markers of bone turnover (eleven publications), improved hip structural geometry (two publications), improved blood-lipid profiles (five publications), a low incidence of hot flushes, leg cramps, venous thromboembolism, and stroke (12 publications), and improved quality of life and pain relief (one publication). Findings support raloxifene for reducing vertebral fracture risk by improving BMD and reducing bone turnover in postmenopausal Japanese women with osteoporosis or osteopenia. Careful consideration of fracture risk and the risk-benefit profile of antiosteoporosis medications is required when managing patients with osteoporosis.

[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.

Heel Ultrasound Can Assess Maintenance of Bone Mass in Women with Breast Cancer

PubMed Central

Langmann, Gabrielle A.; Vujevich, Karen T.; Medich, Donna; Miller, Megan E.; Perera, Subashan; Greenspan, Susan L.

2016-01-01

Postmenopausal women with early-stage breast cancer are at increased risk for bone loss and fractures. Bisphosphonates can prevent bone loss, but little data are available on changes in bone mass assessed by heel quantitative ultrasound (QUS). Our objectives were to determine if (1) heel QUS would provide a reliable and accessible method for evaluation of changes in bone mass in women with breast cancer as compared to the current standard of bone mass measurement, dual-energy x-ray absorptiometry (DXA), and (2) oral risedronate could affect these changes. Eighty-six newly postmenopausal (up to 8 years) women with nonmetastatic breast cancer were randomized to risedronate, 35 mg once weekly or placebo. Outcomes were changes in heel QUS bone mass measurements and conventional dual-energy x-ray absorptiometry (DXA) derived bone mineral density (BMD). Over 2 years, bone mass assessed by heel QUS remained stable in women on risedronate, while women on placebo had a 5.2% decrease (p ≤ 0.05) in heel QUS bone mass. Both total hip BMD and femoral neck BMD assessed by DXA decreased by 1.6% (p ≤ 0.05) in the placebo group and remained stable with risedronate. Spine BMD remained stable in both groups. Heel QUS was moderately associated with BMD measured by DXA at the total hip (r = 0.50), femoral neck (r = 0.40), and spine (r = 0.46) at baseline (all p ≤ 0.001). In conclusion, risedronate helps to maintain skeletal integrity as assessed by heel QUS for women with early-stage breast cancer. Heel QUS is associated with DXA-derived BMD at other major axial sites and may be used to follow skeletal health and bone mass changes in these women. PMID:22425507

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

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.

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.

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

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.

Mechanical response tissue analyzer for estimating bone strength

NASA Technical Reports Server (NTRS)

Arnaud, Sara B.; Steele, Charles; Mauriello, Anthony

1991-01-01

One of the major concerns for extended space flight is weakness of the long bones of the legs, composed primarily of cortical bone, that functions to provide mechanical support. The strength of cortical bone is due to its complex structure, described simplistically as cylinders of parallel osteons composed of layers of mineralized collagen. The reduced mechanical stresses during space flight or immobilization of bone on Earth reduces the mineral content, and changes the components of its matrix and structure so that its strength is reduced. Currently, the established clinical measures of bone strength are indirect. The measures are based on determinations of mineral density by means of radiography, photon absorptiometry, and quantitative computer tomography. While the mineral content of bone is essential to its strength, there is growing awareness of the limitations of the measurement as the sole predictor of fracture risk in metabolic bone diseases, especially limitations of the measurement as the sole predictor of fracture risk in metabolic bone diseases, especially osteoporosis. Other experimental methods in clinical trials that more directly evaluate the physical properties of bone, and do not require exposure to radiation, include ultrasound, acoustic emission, and low-frequency mechanical vibration. The last method can be considered a direct measure of the functional capacity of a long bone since it quantifies the mechanical response to a stimulus delivered directly to the bone. A low frequency vibration induces a response (impedance) curve with a minimum at the resonant frequency, that a few investigators use for the evaluation of the bone. An alternative approach, the method under consideration, is to use the response curve as the basis for determination of the bone bending stiffness EI (E is the intrinsic material property and I is the cross-sectional moment of inertia) and mass, fundamental mechanical properties of bone.

Revolutionary systems for catalytic combustion and diesel catalytic particulate traps.

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

Stuecker, John Nicholas; Witze, Peter O.; Ferrizz, Robert Matthew

2004-12-01

This report is a summary of an LDRD project completed for the development of materials and structures conducive to advancing the state of the art for catalyst supports and diesel particulate traps. An ancillary development for bio-medical bone scaffolding was also realized. Traditionally, a low-pressure drop catalyst support, such as a ceramic honeycomb monolith, is used for catalytic reactions that require high flow rates of gases at high-temperatures. A drawback to the traditional honeycomb monoliths under these operating conditions is poor mass transfer to the catalyst surface in the straight-through channels. ''Robocasting'' is a unique process developed at Sandia Nationalmore » Laboratories that can be used to manufacture ceramic monoliths with alternative 3-dimensional geometries, providing tortuous pathways to increase mass transfer while maintaining low-pressure drops. These alternative 3-dimensional geometries may also provide a foundation for the development of self-regenerating supports capable of trapping and combusting soot particles from a diesel engine exhaust stream. This report describes the structures developed and characterizes the improved catalytic performance that can result. The results show that, relative to honeycomb monolith supports, considerable improvement in mass transfer efficiency is observed for robocast samples synthesized using an FCC-like geometry of alternating rods. Also, there is clearly a trade-off between enhanced mass transfer and increased pressure drop, which can be optimized depending on the particular demands of a given application. Practical applications include the combustion of natural gas for power generation, production of syngas, and hydrogen reforming reactions. The robocast lattice structures also show practicality for diesel particulate trapping. Preliminary results for trapping efficiency are reported as well as the development of electrically resistive lattices that can regenerate the structure by combusting the trapped soot. During this project an ancillary bio-medical application was discovered for lattices of hydroxyapatite. These structures show promise as bone scaffolds for the reparation of damaged bone. A case study depicting the manufacture of a customized device that fits into a damaged mandible is described.« less

Low skeletal muscle mass is associated with poor structural parameters of bone and impaired balance in elderly men--the MINOS study.

PubMed

Szulc, Pawel; Beck, Tom J; Marchand, François; Delmas, Pierre D

2005-05-01

In 796 men, 50-85 years of age, decreased relative skeletal muscle mass index was associated with narrower bones, thinner cortices, and a consequent decreased bending strength (lower section modulus), as well as with impaired balance and an increased risk of falls. In men, appendicular skeletal muscle mass (ASM) is correlated positively with BMC and areal BMD (aBMD). In elderly men, low muscle mass and strength (sarcopenia) is associated with difficulties in daily living activities. The aim of this study was to evaluate if ASM is correlated with bone size, mechanical properties of bones, balance, and risk of falls in elderly men. This study used 796 men, 50-85 years of age, belonging to the MINOS cohort. Lifestyle factors were evaluated by standardized questionnaires. Estimates of mechanical bone properties were derived from aBMD measured by DXA. ASM was estimated by DXA. The relative skeletal muscle mass index (RASM) was calculated as ASM/(body height)(2.3). After adjustment for age, body size, tobacco smoking, professional physical activity, and 17beta-estradiol concentration, RASM was correlated positively with BMC, aBMD, external diameter, and cortical thickness (r = 0.17-0.34, p < 0.0001) but not with volumetric BMD. Consequently, RASM was correlated with section modulus (r = 0.29-0.39, p < 0.0001). Men in the lowest quartile of RASM had section modulus of femoral neck and distal radius lower by 12-18% in comparison with men in the highest quartile of RASM. In contrast, bone width was not correlated with fat mass, reflecting the load of body weight (except for L(3)), which suggests that the muscular strain may exert a direct stimulatory effect on periosteal apposition. After adjustment for confounding variables, a decrease in RASM was associated with increased risk of falls and of inability to accomplish clinical tests of muscle strength, static balance, and dynamic balance (odds ratio per 1 SD decrease in RASM, 1.31-2.23; p < 0.05-0.001). In elderly men, decreased RASM is associated with narrower bones and thinner cortices, which results in a lower bending strength. Low RASM is associated with impaired balance and with an increased risk of falls in elderly men. It remains to be studied whether low RASM is associated with decreased periosteal apposition and with increased fracture risk in elderly men, and whether the difference in skeletal muscle mass between men and women contributes to the between-sex difference in fracture incidence.

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.

Bone lead (Pb) content at the tibia is associated with thinner distal tibia cortices and lower volumetric bone density in postmenopausal women

PubMed Central

Wong, Andy K.O.; Beattie, Karen A.; Bhargava, Aakash; Cheung, Marco; Webber, Colin E.; Chettle, David R.; Papaioannou, Alexandra; Adachi, Jonathan D.

2016-01-01

Conflicting evidence suggests that bone lead or blood lead may reduce areal bone mineral density (BMD). Little is known about how lead at either compartment affects bone structure. This study examined postmenopausal women (N = 38, mean age 76 ± 8, body mass index (BMI): 26.74 ± 4.26 kg/m2) within the Hamilton cohort of the Canadian Multicentre Osteoporosis Study (CaMos), measuring bone lead at 66% of the non-dominant leg and at the calcaneus using 109Cadmium X-ray fluorescence. Volumetric BMD and structural parameters were obtained from peripheral quantitative computed tomography images (200 μm in-plane resolution, 2.3 ± 0.5 mm slice thickness) of the same 66% site and of the distal 4% site of the tibia length. Blood lead was measured using atomic absorption spectrometry and blood-to-bone lead partition coefficients (PBB, log ratio) were computed. Multivariable linear regression examined each of bone lead at the 66% tibia, calcaneus, blood lead and PBB as related to each of volumetric BMD and structural parameters, adjusting for age and BMI, diabetes or antiresorptive therapy. Regression coefficients were reported along with 95% confidence intervals. Higher amounts of bone lead at the tibia were associated with thinner distal tibia cortices (−0.972 (−1.882, −0.061) per 100 μg Pb/g of bone mineral) and integral volumetric BMD (−3.05 (−6.05, −0.05) per μg Pb/g of bone mineral). A higher PBB was associated with larger trabecular separation (0.115 (0.053, 0.178)), lower trabecular volumetric BMD (−26.83 (−50.37, −3.29)) and trabecular number (−0.08 (−0.14, −0.02)), per 100 μg Pb/g of bone mineral after adjusting for age and BMI, and remained significant while accounting for diabetes or use of antiresorptives. Total lead exposure activities related to bone lead at the calcaneus (8.29 (0.11, 16.48)) and remained significant after age and antiresorptives-adjustment. Lead accumulated in bone can have a mild insult on bone structure; but greater partitioning of lead in blood versus bone revealed more dramatic effects on both microstructure and volumetric BMD. PMID:25986335

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.

Differential effects of formononetin and cladrin on osteoblast function, peak bone mass achievement and bioavailability in rats.

PubMed

Gautam, Abnish K; Bhargavan, Biju; Tyagi, Abdul M; Srivastava, Kamini; Yadav, Dinesh K; Kumar, Manmeet; Singh, Akanksha; Mishra, Jay S; Singh, Amar Bahadur; Sanyal, Sabyasachi; Maurya, Rakesh; Manickavasagam, Lakshmi; Singh, Sheelendra P; Wahajuddin, Wahajuddin; Jain, Girish K; Chattopadhyay, Naibedya; Singh, Divya

2011-04-01

Dietary soy isoflavones including genistein and daidzein have been shown to have favorable effects during estrogen deficiency in experimental animals and humans. We have evaluated osteogenic effect of cladrin and formononetin, two structurally related methoxydaidzeins found in soy food and other natural sources. Cladrin, at as low as 10 nM, maximally stimulated both osteoblast proliferation and differentiation by activating MEK-Erk pathway. On the other hand, formononetin maximally stimulated osteoblast differentiation at 100 nM that involved p38 MAPK pathway but had no effect on osteoblast proliferation. Unlike daidzein, these two compounds neither activated estrogen receptor in osteoblast nor had any effect on osteoclast differentiation. Daily oral administration of each of these compounds at 10.0 mg kg(-1) day(-1) dose to recently weaned female Sprague-Dawley rats for 30 consecutive days, increased bone mineral density at various anatomic positions studied. By dynamic histomorphometry of bone, we observed that rats treated with cladrin exhibited increased mineral apposition and bone formation rates compared with control, while formononetin had no effect. Cladrin had much better plasma bioavailability compared with formononetin. None of these compounds exhibited estrogen agonistic effect in uteri. Our data suggest that cladrin is more potent among the two in promoting parameters of peak bone mass achievement, which could be attributed to its stimulatory effect on osteoblast proliferation and better bioavailability. To the best of our knowledge, this is the first attempt to elucidate structure-activity relationship between the methoxylated forms of daidzein and their osteogenic effects. Copyright © 2011 Elsevier Inc. 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.

Differences in bone structure between rheumatoid arthritis and psoriatic arthritis patients relative to autoantibody positivity.

PubMed

Kocijan, Roland; Finzel, Stephanie; Englbrecht, Matthias; Engelke, Klaus; Rech, Juergen; Schett, Georg

2014-11-01

To investigate whether trabecular and cortical bone structure differ between patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). So far, no study has performed a detailed comparative analysis of bone structure in patients with RA and PsA. 110 patients (60 RA, 50 PsA) received high-resolution peripheral quantitative CT of the distal radius. Demographic and disease-specific parameters including anti-rheumatic treatment, bone erosion status and previous fractures were recorded. RA and PsA patients were comparable in age, gender, body mass index, disease duration, disease activity, functional status, antirheumatic treatment and bone erosion status. No significant differences were found for volumetric bone mineral density (BMD), including total BMD (300±77 vs 316±62 mgHA/cm(3)), trabecular BMD (152±46 vs 165±40 mgHA/cm(3)) and cortical BMD (787±113 vs 818±76 mgHA/cm(3)) when comparing RA patients to PsA patients, respectively. However, in contrast to seronegative RA, seropositive RA showed significantly reduced trabecular BMD (p=0.007), bone volume per tissue volume (p=0.007) and trabecular number (p=0.044), as well as a strong trend towards higher trabecular inhomogeneity compared to PsA patients. In the regression analysis, higher age, female gender and presence of autoantibodies were independently associated with trabecular bone loss. Seropositive RA exhibits more profound changes in trabecular bone architecture than seronegative RA or PsA. The data support the concept that seropositive RA is a disease entity that is distinct from seronegative RA and PsA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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.

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.

Bone-Protective Effects of Dried Plum in Postmenopausal Women: Efficacy and Possible Mechanisms

PubMed Central

Arjmandi, Bahram H.; Johnson, Sarah A.; Pourafshar, Shirin; Navaei, Negin; George, Kelli S.; Hooshmand, Shirin; Chai, Sheau C.; Akhavan, Neda S.

2017-01-01

Osteoporosis is an age-related chronic disease characterized by a loss of bone mass and quality, and is associated with an increased risk of fragility fractures. Postmenopausal women are at the greatest risk of developing osteoporosis due to the cessation in ovarian hormone production, which causes accelerated bone loss. As the demographic shifts to a more aged population, a growing number of postmenopausal women will be afflicted with osteoporosis. Certain lifestyle factors, including nutrition and exercise, are known to reduce the risk of developing osteoporosis and therefore play an important role in bone health. In terms of nutrition, accumulating evidence suggests that dried plum (Prunus domestica L.) is potentially an efficacious intervention for preventing and reversing bone mass and structural loss in an ovariectomized rat model of osteoporosis, as well as in osteopenic postmenopausal women. Here, we provide evidence supporting the efficacy of dried plum in preventing and reversing bone loss associated with ovarian hormone deficiency in rodent models and in humans. We end with the results of a recent follow-up study demonstrating that postmenopausal women who previously consumed 100 g dried plum per day during our one-year clinical trial conducted five years earlier retained bone mineral density to a greater extent than those receiving a comparative control. Additionally, we highlight the possible mechanisms of action by which bioactive compounds in dried plum exert bone-protective effects. Overall, the findings of our studies and others strongly suggest that dried plum in its whole form is a promising and efficacious functional food therapy for preventing bone loss in postmenopausal women, with the potential for long-lasting bone-protective effects. PMID:28505102

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

Chronic administration of Glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice.

PubMed

Pereira, M; Jeyabalan, J; Jørgensen, C S; Hopkinson, M; Al-Jazzar, A; Roux, J P; Chavassieux, P; Orriss, I R; Cleasby, M E; Chenu, C

2015-12-01

Some anti-diabetic therapies can have adverse effects on bone health and increase fracture risk. In this study, we tested the skeletal effects of chronic administration of two Glucagon-like peptide-1 receptor agonists (GLP-1RA), increasingly used for type 2 diabetes treatment, in a model of osteoporosis associated bone loss and examined the expression and activation of GLP-1R in bone cells. Mice were ovariectomised (OVX) to induce bone loss and four weeks later they were treated with Liraglutide (LIR) 0.3mg/kg/day, Exenatide (Ex-4) 10 μg/kg/day or saline for four weeks. Mice were injected with calcein and alizarin red prior to euthanasia, to label bone-mineralising surfaces. Tibial micro-architecture was determined by micro-CT and bone formation and resorption parameters measured by histomorphometric analysis. Serum was collected to measure calcitonin and sclerostin levels, inhibitors of bone resorption and formation, respectively. GLP-1R mRNA and protein expression were evaluated in the bone, bone marrow and bone cells using RT-PCR and immunohistochemistry. Primary osteoclasts and osteoblasts were cultured to evaluate the effect of GLP-1RA on bone resorption and formation in vitro. GLP-1RA significantly increased trabecular bone mass, connectivity and structure parameters but had no effect on cortical bone. There was no effect of GLP-1RA on bone formation in vivo but an increase in osteoclast number and osteoclast surfaces was observed with Ex-4. GLP-1R was expressed in bone marrow cells, primary osteoclasts and osteoblasts and in late osteocytic cell line. Both Ex-4 and LIR stimulated osteoclastic differentiation in vitro but slightly reduced the area resorbed per osteoclast. They had no effect on bone nodule formation in vitro. Serum calcitonin levels were increased and sclerostin levels decreased by Ex-4 but not by LIR. Thus, GLP-1RA can have beneficial effects on bone and the expression of GLP-1R in bone cells may imply that these effects are exerted directly on the tissue. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain

PubMed Central

Pacheco-Costa, Rafael; Davis, Hannah M.; Sorenson, Chad; Hon, Mary C.; Hassan, Iraj; Reginato, Rejane D.; Allen, Matthew R.; Bellido, Teresita; Plotkin, Lilian I.

2015-01-01

Connexin43 (Cx43) forms gap junction channels and hemichannels that allow the communication among osteocytes, osteoblasts, and osteoclasts. Cx43 carboxy-terminal (CT) domain regulates channel opening and intracellular signaling by acting as a scaffold for structural and signaling proteins. To determine the role of Cx43 CT domain in bone, mice in which one allele of full length Cx43 was replaced by a mutant lacking the CT domain (Cx43ΔCT/fl) were studied. Cx43ΔCT/fl mice exhibit lower cancellous bone volume but higher cortical thickness than Cx43fl/fl controls, indicating that the CT domain is involved in normal cancellous bone gain but opposes cortical bone acquisition. Further, Cx43ΔCT is able to exert the functions of full length osteocytic Cx43 on cortical bone geometry and mechanical properties, demonstrating that domains other than the CT are responsible for Cx43 function in cortical bone. In addition, parathyroid hormone (PTH) failed to increase endocortical bone formation or energy to failure, a mechanical property that indicates resistance to fracture, in cortical bone in Cx43ΔCT mice with or without osteocytic full length Cx43. On the other hand, bone mass and bone formation markers were increased by the hormone in all mouse models, regardless of whether full length or Cx43ΔCT were or not expressed. We conclude that Cx43 CT domain is involved in proper bone acquisition; and that Cx43 expression in osteocytes is dispensable for some but not all PTH anabolic actions. PMID:26409319

Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain.

PubMed

Pacheco-Costa, Rafael; Davis, Hannah M; Sorenson, Chad; Hon, Mary C; Hassan, Iraj; Reginato, Rejane D; Allen, Matthew R; Bellido, Teresita; Plotkin, Lilian I

2015-12-01

Connexin 43 (Cx43) forms gap junction channels and hemichannels that allow the communication among osteocytes, osteoblasts, and osteoclasts. Cx43 carboxy-terminal (CT) domain regulates channel opening and intracellular signaling by acting as a scaffold for structural and signaling proteins. To determine the role of Cx43 CT domain in bone, mice in which one allele of full length Cx43 was replaced by a mutant lacking the CT domain (Cx43(ΔCT/fl)) were studied. Cx43(ΔCT/fl) mice exhibit lower cancellous bone volume but higher cortical thickness than Cx43(fl/fl) controls, indicating that the CT domain is involved in normal cancellous bone gain but opposes cortical bone acquisition. Further, Cx43(ΔCT) is able to exert the functions of full length osteocytic Cx43 on cortical bone geometry and mechanical properties, demonstrating that domains other than the CT are responsible for Cx43 function in cortical bone. In addition, parathyroid hormone (PTH) failed to increase endocortical bone formation or energy to failure, a mechanical property that indicates resistance to fracture, in cortical bone in Cx43(ΔCT) mice with or without osteocytic full length Cx43. On the other hand, bone mass and bone formation markers were increased by the hormone in all mouse models, regardless of whether full length or Cx43(ΔCT) were or not expressed. We conclude that Cx43 CT domain is involved in proper bone acquisition; and that Cx43 expression in osteocytes is dispensable for some but not all PTH anabolic actions. Copyright © 2015 Elsevier Inc. All rights reserved.

Reduced diaphyseal strength associated with high intracortical vascular porosity within long bones of children with Osteogenesis Imperfecta

PubMed Central

Jameson, John; Smith, Peter; Harris, Gerald

2015-01-01

Osteogenesis Imperfecta is a genetic disorder resulting in bone fragility. The mechanisms behind this fragility are not well understood. In addition to characteristic bone mass deficiencies, research suggests that bone material properties are compromised in individuals with this disorder. However, little data exists regarding bone properties beyond the microstructural scale in individuals with this disorder. Specimens were obtained from long bone diaphyses of nine children with osteogenesis imperfecta during routine osteotomy procedures. Small rectangular beams, oriented longitudinally and transversely to the diaphyseal axis, were machined from these specimens and elastic modulus, yield strength, and maximum strength were measured in three-point bending. Intracortical vascular porosity, bone volume fraction, osteocyte lacuna density, and volumetric tissue mineral density were determined by synchrotron micro-computed tomography, and relationships among these mechanical properties and structural parameters were explored. Modulus and strength were on average 64–68% lower in the transverse vs. longitudinal beams (P<0.001, linear mixed model). Vascular porosity ranged between 3–42% of total bone volume. Longitudinal properties were associated negatively with porosity (P≤0.006, linear regressions). Mechanical properties, however, were not associated with osteocyte lacuna density or volumetric tissue mineral density (P≥0.167). Bone properties and structural parameters were not associated significantly with donor age (p≥0.225, linear mixed models). This study presents novel data regarding bone material strength in children with osteogenesis imperfecta. Results confirm that these properties are anisotropic. Elevated vascular porosity was observed in most specimens, and this parameter was associated with reduced bone material strength. These results offer insight towards understanding bone fragility and the role of intracortical porosity on the strength of bone tissue in children with osteogenesis imperfecta. PMID:24928496

Reduced diaphyseal strength associated with high intracortical vascular porosity within long bones of children with osteogenesis imperfecta.

PubMed

Albert, Carolyne; Jameson, John; Smith, Peter; Harris, Gerald

2014-09-01

Osteogenesis imperfecta is a genetic disorder resulting in bone fragility. The mechanisms behind this fragility are not well understood. In addition to characteristic bone mass deficiencies, research suggests that bone material properties are compromised in individuals with this disorder. However, little data exists regarding bone properties beyond the microstructural scale in individuals with this disorder. Specimens were obtained from long bone diaphyses of nine children with osteogenesis imperfecta during routine osteotomy procedures. Small rectangular beams, oriented longitudinally and transversely to the diaphyseal axis, were machined from these specimens and elastic modulus, yield strength, and maximum strength were measured in three-point bending. Intracortical vascular porosity, bone volume fraction, osteocyte lacuna density, and volumetric tissue mineral density were determined by synchrotron micro-computed tomography, and relationships among these mechanical properties and structural parameters were explored. Modulus and strength were on average 64-68% lower in the transverse vs. longitudinal beams (P<0.001, linear mixed model). Vascular porosity ranged between 3 and 42% of total bone volume. Longitudinal properties were associated negatively with porosity (P≤0.006, linear regressions). Mechanical properties, however, were not associated with osteocyte lacuna density or volumetric tissue mineral density (P≥0.167). Bone properties and structural parameters were not associated significantly with donor age (P≥0.225, linear mixed models). This study presents novel data regarding bone material strength in children with osteogenesis imperfecta. Results confirm that these properties are anisotropic. Elevated vascular porosity was observed in most specimens, and this parameter was associated with reduced bone material strength. These results offer insight toward understanding bone fragility and the role of intracortical porosity on the strength of bone tissue in children with osteogenesis imperfecta. Copyright © 2014 Elsevier Inc. All rights reserved.

Dietary Pseudopurpurin Improves Bone Geometry Architecture and Metabolism in Red-Bone Guishan Goats

PubMed Central

Han, TieSuo; Li, Peng; Wang, JianGuo; Liu, GuoWen; Wang, Zhe; Ge, ChangRong; Gao, ShiZheng

2012-01-01

Red-colored bones were found initially in some Guishan goats in the 1980s, and they were designated red-boned goats. However, it is not understood what causes the red color in the bone, or whether the red material changes the bone geometry, architecture, and metabolism of red-boned goats. Pseudopurpurin was identified in the red-colored material of the bone in red-boned goats by high-performance liquid chromatography–electrospray ionization–mass spetrometry and nuclear magnetic resonance analysis. Pseudopurpurin is one of the main constituents of Rubia cordifolia L, which is eaten by the goats. The assessment of the mechanical properties and micro-computed tomography showed that the red-boned goats displayed an increase in the trabecular volume fraction, trabecular thickness, and the number of trabeculae in the distal femur. The mean thickness, inner perimeter, outer perimeter, and area of the femoral diaphysis were also increased. In addition, the trabecular separation and structure model index of the distal femur were decreased, but the bone mineral density of the whole femur and the mechanical properties of the femoral diaphysis were enhanced in the red-boned goats. Meanwhile, expression of alkaline phosphatase and osteocalcin mRNA was higher, and the ratio of the receptor activator of the nuclear factor kappa B ligand to osteoprotegerin was markedly lower in the bone marrow of the red-boned goats compared with common goats. To confirm further the effect of pseudopurpurin on bone geometry, architecture, and metabolism, Wistar rats were fed diets to which pseudopurpurin was added for 5 months. Similar changes were observed in the femurs of the treated rats. The above results demonstrate that pseudopurpurin has a close affinity with the mineral salts of bone, and consequently a high level of mineral salts in the bone cause an improvement in bone strength and an enhancement in the structure and metabolic functions of the bone. PMID:22624037

Polycystin-1 interacts with TAZ to stimulate osteoblastogenesis and inhibit adipogenesis

DOE PAGES

Xiao, Zhousheng; Baudry, Jerome; Cao, Li; ...

2017-11-27

The molecular mechanisms that transduce the osteoblast response to physical forces in the bone microenvironment are poorly understood. In this paper, we used genetic and pharmacological experiments to determine whether the polycystins PC1 and PC2 (encoded by Pkd1 and Pkd2) and the transcriptional coactivator TAZ form a mechanosensing complex in osteoblasts. Compound-heterozygous mice lacking 1 copy of Pkd1 and Taz exhibited additive decrements in bone mass, impaired osteoblast-mediated bone formation, and enhanced bone marrow fat accumulation. Bone marrow stromal cells and osteoblasts derived from these mice showed impaired osteoblastogenesis and enhanced adipogenesis. Increased extracellular matrix stiffness and application of mechanicalmore » stretch to multipotent mesenchymal cells stimulated the nuclear translocation of the PC1 C-terminal tail/TAZ (PC1-CTT/TAZ) complex, leading to increased runt-related transcription factor 2–mediated (Runx2-mediated) osteogenic and decreased PPARγ-dependent adipogenic gene expression. Using structure-based virtual screening, we identified a compound predicted to bind to PC2 in the PC1:PC2 C-terminal tail region with helix:helix interaction. This molecule stimulated polycystin- and TAZ-dependent osteoblastogenesis and inhibited adipogenesis. Therefore, we show that polycystins and TAZ integrate at the molecular level to reciprocally regulate osteoblast and adipocyte differentiation, indicating that the polycystins/TAZ complex may be a potential therapeutic target to increase bone mass.« less

Polycystin-1 interacts with TAZ to stimulate osteoblastogenesis and inhibit adipogenesis

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

Xiao, Zhousheng; Baudry, Jerome; Cao, Li

The molecular mechanisms that transduce the osteoblast response to physical forces in the bone microenvironment are poorly understood. In this paper, we used genetic and pharmacological experiments to determine whether the polycystins PC1 and PC2 (encoded by Pkd1 and Pkd2) and the transcriptional coactivator TAZ form a mechanosensing complex in osteoblasts. Compound-heterozygous mice lacking 1 copy of Pkd1 and Taz exhibited additive decrements in bone mass, impaired osteoblast-mediated bone formation, and enhanced bone marrow fat accumulation. Bone marrow stromal cells and osteoblasts derived from these mice showed impaired osteoblastogenesis and enhanced adipogenesis. Increased extracellular matrix stiffness and application of mechanicalmore » stretch to multipotent mesenchymal cells stimulated the nuclear translocation of the PC1 C-terminal tail/TAZ (PC1-CTT/TAZ) complex, leading to increased runt-related transcription factor 2–mediated (Runx2-mediated) osteogenic and decreased PPARγ-dependent adipogenic gene expression. Using structure-based virtual screening, we identified a compound predicted to bind to PC2 in the PC1:PC2 C-terminal tail region with helix:helix interaction. This molecule stimulated polycystin- and TAZ-dependent osteoblastogenesis and inhibited adipogenesis. Therefore, we show that polycystins and TAZ integrate at the molecular level to reciprocally regulate osteoblast and adipocyte differentiation, indicating that the polycystins/TAZ complex may be a potential therapeutic target to increase bone mass.« less

Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta

PubMed Central

Oestreich, Arin K.; Kamp, William M.; McCray, Marcus G.; Carleton, Stephanie M.; Karasseva, Natalia; Lenz, Kristin L.; Jeong, Youngjae; Daghlas, Salah A.; Yao, Xiaomei; Wang, Yong; Pfeiffer, Ferris M.; Ellersieck, Mark R.; Schulz, Laura C.; Phillips, Charlotte L.

2016-01-01

During fetal development, the uterine environment can have effects on offspring bone architecture and integrity that persist into adulthood; however, the biochemical and molecular mechanisms remain unknown. Myostatin is a negative regulator of muscle mass. Parental myostatin deficiency (Mstntm1Sjl/+) increases muscle mass in wild-type offspring, suggesting an intrauterine programming effect. Here, we hypothesized that Mstntm1Sjl/+ dams would also confer increased bone strength. In wild-type offspring, maternal myostatin deficiency altered fetal growth and calvarial collagen content of newborn mice and conferred a lasting impact on bone geometry and biomechanical integrity of offspring at 4 mo of age, the age of peak bone mass. Second, we sought to apply maternal myostatin deficiency to a mouse model with osteogenesis imperfecta (Col1a2oim), a heritable connective tissue disorder caused by abnormalities in the structure and/or synthesis of type I collagen. Femora of male Col1a2oim/+ offspring from natural mating of Mstntm1Sjl/+ dams to Col1a2oim/+sires had a 15% increase in torsional ultimate strength, a 29% increase in tensile strength, and a 24% increase in energy to failure compared with age, sex, and genotype-matched offspring from natural mating of Col1a2oim/+ dams to Col1a2oim/+ sires. Finally, increased bone biomechanical strength of Col1a2oim/+ offspring that had been transferred into Mstntm1Sjl/+ dams as blastocysts demonstrated that the effects of maternal myostatin deficiency were conferred by the postimplantation environment. Thus, targeting the gestational environment, and specifically prenatal myostatin pathways, provides a potential therapeutic window and an approach for treating osteogenesis imperfecta. PMID:27821779

Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta.

PubMed

Oestreich, Arin K; Kamp, William M; McCray, Marcus G; Carleton, Stephanie M; Karasseva, Natalia; Lenz, Kristin L; Jeong, Youngjae; Daghlas, Salah A; Yao, Xiaomei; Wang, Yong; Pfeiffer, Ferris M; Ellersieck, Mark R; Schulz, Laura C; Phillips, Charlotte L

2016-11-22

During fetal development, the uterine environment can have effects on offspring bone architecture and integrity that persist into adulthood; however, the biochemical and molecular mechanisms remain unknown. Myostatin is a negative regulator of muscle mass. Parental myostatin deficiency (Mstn tm1Sjl/+ ) increases muscle mass in wild-type offspring, suggesting an intrauterine programming effect. Here, we hypothesized that Mstn tm1Sjl/+ dams would also confer increased bone strength. In wild-type offspring, maternal myostatin deficiency altered fetal growth and calvarial collagen content of newborn mice and conferred a lasting impact on bone geometry and biomechanical integrity of offspring at 4 mo of age, the age of peak bone mass. Second, we sought to apply maternal myostatin deficiency to a mouse model with osteogenesis imperfecta (Col1a2 oim ), a heritable connective tissue disorder caused by abnormalities in the structure and/or synthesis of type I collagen. Femora of male Col1a2 oim/+ offspring from natural mating of Mstn tm1Sjl/+ dams to Col1a2 oim/+ sires had a 15% increase in torsional ultimate strength, a 29% increase in tensile strength, and a 24% increase in energy to failure compared with age, sex, and genotype-matched offspring from natural mating of Col1a2 oim/+ dams to Col1a2 oim/+ sires. Finally, increased bone biomechanical strength of Col1a2 oim/+ offspring that had been transferred into Mstn tm1Sjl/+ dams as blastocysts demonstrated that the effects of maternal myostatin deficiency were conferred by the postimplantation environment. Thus, targeting the gestational environment, and specifically prenatal myostatin pathways, provides a potential therapeutic window and an approach for treating osteogenesis imperfecta.

Classification of trabeculae into three-dimensional rodlike and platelike structures via local inertial anisotropy.

PubMed

Vasilić, Branimir; Rajapakse, Chamith S; Wehrli, Felix W

2009-07-01

Trabecular bone microarchitecture is a significant determinant of the bone's mechanical properties and is thus of major clinical relevance in predicting fracture risk. The three-dimensional nature of trabecular bone is characterized by parameters describing scale, topology, and orientation of structural elements. However, none of the current methods calculates all three types of parameters simultaneously and in three dimensions. Here the authors present a method that produces a continuous classification of voxels as belonging to platelike or rodlike structures that determines their orientation and estimates their thickness. The method, dubbed local inertial anisotropy (LIA), treats the image as a distribution of mass density and the orientation of trabeculae is determined from a locally calculated tensor of inertia at each voxel. The orientation entropies of rods and plates are introduced, which can provide new information about microarchitecture not captured by existing parameters. The robustness of the method to noise corruption, resolution reduction, and image rotation is demonstrated. Further, the method is compared with established three-dimensional parameters including the structure-model index and topological surface-to-curve ratio. Finally, the method is applied to data acquired in a previous translational pilot study showing that the trabecular bone of untreated hypogonadal men is less platelike than that of their eugonadal peers.

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.

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.

Optimally oriented grooves on dental implants improve bone quality around implants under repetitive mechanical loading.

PubMed

Kuroshima, Shinichiro; Nakano, Takayoshi; Ishimoto, Takuya; Sasaki, Muneteru; Inoue, Maaya; Yasutake, Munenori; Sawase, Takashi

2017-01-15

The aim was to investigate the effect of groove designs on bone quality under controlled-repetitive load conditions for optimizing dental implant design. Anodized Ti-6Al-4V alloy implants with -60° and +60° grooves around the neck were placed in the proximal tibial metaphysis of rabbits. The application of a repetitive mechanical load was initiated via the implants (50N, 3Hz, 1800 cycles, 2days/week) at 12weeks after surgery for 8weeks. Bone quality, defined as osteocyte density and degree of biological apatite (BAp) c-axis/collagen fibers, was then evaluated. Groove designs did not affect bone quality without mechanical loading; however, repetitive mechanical loading significantly increased bone-to-implant contact, bone mass, and bone mineral density (BMD). In +60° grooves, the BAp c-axis/collagen fibers preferentially aligned along the groove direction with mechanical loading. Moreover, osteocyte density was significantly higher both inside and in the adjacent region of the +60° grooves, but not -60° grooves. These results suggest that the +60° grooves successfully transmitted the load to the bone tissues surrounding implants through the grooves. An optimally oriented groove structure on the implant surface was shown to be a promising way for achieving bone tissue with appropriate bone quality. This is the first report to propose the optimal design of grooves on the necks of dental implants for improving bone quality parameters as well as BMD. The findings suggest that not only BMD, but also bone quality, could be a useful clinical parameter in implant dentistry. Although the paradigm of bone quality has shifted from density-based assessments to structural evaluations of bone, clarifying bone quality based on structural bone evaluations remains challenging in implant dentistry. In this study, we firstly demonstrated that the optimal design of dental implant necks improved bone quality defined as osteocytes and the preferential alignment degree of biological apatite c-axis/collagen fibers using light microscopy, polarized light microscopy, and a microbeam X-ray diffractometer system, after application of controlled mechanical load. Our new findings suggest that bone quality around dental implants could become a new clinical parameter as well as bone mineral density in order to completely account for bone strength in implant dentistry. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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.

Computed tomographic analysis of the internal structure of the metacarpals and its implications for hand use, pathology, and surgical intervention.

PubMed

Wong, Alison L; Meals, Clifton G; Ruff, Christopher B

2018-03-01

The variation of bone structure and biomechanics between the metacarpals is not well characterized. It was hypothesized that their structure would reflect their common patterns of use (i.e., patterns of hand grip), specifically that trabecular bone density would be greater on the volar aspect of all metacarpal bases, that this would be most pronounced in the thumb, and that the thumb diaphysis would have the greatest bending strength. Cross-sections at basal and mid-diaphyseal locations of 50 metacarpals from 10 human hands were obtained by peripheral quantitative computed tomography. The volar and dorsal trabecular densities of each base were measured and characterized using the volar/dorsal density ratio. The polar stress-strain index (SSIp), a surrogate measure of torsional/bending strength, was measured for each diaphysis and standardized for bone length and mass. Comparisons were made using mixed-model analyses of variance (ANOVAs) and post hoc tests. Volar/dorsal trabecular density ratios showed even distribution in all metacarpal bases except for the thumb, which showed greater values on the volar aspect. The thumb, second, and third metacarpals all had high bending strength (SSIp), but the thumb's SSIp relative to its length and trabecular mass was much higher than those of the other metacarpals. Trabecular density of the metacarpal bases was evenly distributed except in the thumb, which also showed higher bending strength relative to its length and mass. Understanding of how these indicators of strength differ across metacarpals may improve both fracture diagnosis and treatment and lays the groundwork for investigating changes with age, hand dominance, and occupation.

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.

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.

Sacral Bone Mass Distribution Assessed by Averaged Three-Dimensional CT Models: Implications for Pathogenesis and Treatment of Fragility Fractures of the Sacrum.

PubMed

Wagner, Daniel; Kamer, Lukas; Sawaguchi, Takeshi; Richards, R Geoff; Noser, Hansrudi; Rommens, Pol M

2016-04-06

Fragility fractures of the sacrum are increasing in prevalence due to osteoporosis and epidemiological changes and are challenging in their treatment. They exhibit specific fracture patterns with unilateral or bilateral fractures lateral to the sacral foramina, and sometimes an additional transverse fracture leads to spinopelvic dissociation. The goal of this study was to assess sacral bone mass distribution and corresponding changes with decreased general bone mass. Clinical computed tomography (CT) scans of intact pelves in ninety-one individuals (mean age and standard deviation, 61.5 ± 11.3 years) were used to generate three-dimensional (3D) models of the sacrum averaging bone mass in Hounsfield units (HU). Individuals with decreased general bone mass were identified by measuring bone mass in L5 (group 1 with <100 HU; in contrast to group 2 with ≥100 HU). In group 1, a large zone of negative Hounsfield units was located in the paraforaminal lateral region from S1 to S3. Along the trans-sacral corridors, a Hounsfield unit peak was observed laterally, corresponding to cortical bone of the auricular surface. The lowest Hounsfield unit values were found in the paraforaminal lateral region in the sacral ala. An intermediate level of bone mass was observed in the area of the vertebral bodies, which also demonstrated the largest difference between groups 1 and 2. Overall, the Hounsfield units were lower at S2 than S1. The models of averaged bone mass in the sacrum revealed a distinct 3D distribution pattern. The negative values in the paraforaminal lateral region may explain the specific fracture patterns in fragility fractures of the sacrum involving the lateral areas of the sacrum. Transverse fractures located between S1 and S2 leading to spinopelvic dissociation may occur because of decreased bone mass in S2. The largest difference between the studied groups was found in the vertebral bodies and might support the use of transsacral or cement-augmented implants. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

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.

Loss of BMP signaling through BMPR1A in osteoblasts leads to greater collagen cross-link maturation and material-level mechanical properties in mouse femoral trabecular compartments

PubMed Central

Zhang, Yanshuai; McNerny, Erin Gatenby; Terajima, Masahiko; Raghavan, Mekhala; Romanowicz, Genevieve; Zhang, Zhanpeng; Zhang, Honghao; Kamiya, Nobuhiro; Tantillo, Margaret; Zhu, Peizhi; Scott, Gregory J.; Ray, Manas K.; Lynch, Michelle; Ma, Peter X.; Morris, Michael D.; Yamauchi, Mitsuo; Kohn, David H.; Mishina, Yuji

2016-01-01

Bone morphogenetic protein (BMP) signaling pathways play critical roles in skeletal development and new bone formation. Our previous study, however, showed a negative impact of BMP signaling on bone mass because of the osteoblast-specific loss of a BMP receptor (i.e. BMPR1A) showing increased trabecular bone volume and mineral density in mice. Here, we investigated the bone quality and biomechanical properties of the higher bone mass associated with BMPR1A deficiency using the osteoblast-specific Bmpr1a conditional knockout (cKO) mouse model. Collagen biochemical analysis revealed greater levels of the mature cross-link pyridinoline in the cKO bones, in parallel with upregulation of collagen modifying enzymes. Raman spectroscopy distinguished increases in the mature to immature cross-link ratio and mineral to matrix ratio in the trabecular compartments of cKO femora, but not in the cortical compartments. The mineral crystallinity was unchanged in the cKO in either the trabecular or cortical compartments. Further, we tested the intrinsic material properties by nanoindentation and found significantly higher hardness and elastic modulus in the cKO trabecular compartments, but not in the cortical compartments. Four point bending tests of cortical compartments showed lower structural biomechanical properties (i.e. strength and stiffness) in the cKO bones due to the smaller cortical areas. However, there were no significant differences in biomechanical performance at the material level, which was consistent with the nanoindentation test results on the cortical compartment. These studies emphasize the pivotal role of BMPR1A in the determination of bone quality and mechanical integrity under physiological conditions, with different impact on femoral cortical and trabecular compartments. PMID:27113526

Microarchitecture and Bone Quality in the Human Calcaneus; Local Variations of Fabric Anisotropy

PubMed Central

Souzanchi, M F; Palacio-Mancheno, P E; Borisov, Y; Cardoso, L; Cowin, SC

2012-01-01

The local variability of microarchitecture of human trabecular calcaneus bone is investigated using high resolution microCT scanning. The fabric tensor is employed as the measure of the microarchitecture of the pore structure of a porous medium. It is hypothesized that a fabric tensor-dependent poroelastic ultrasound approach will more effectively predict the data variance than will porosity alone. The specific aims of the present study are i) to quantify the morphology and local anisotropy of the calcaneus microarchitecture with respect to anatomical directions, ii) to determine the interdependence, or lack thereof, of microarchitecture parameters, fabric, and volumetric bone mineral density (vBMD), and iii) to determine the relative ability of vBMD and fabric measurements in evaluating the variance in ultrasound wave velocity measurements along orthogonal directions in the human calcaneus. Our results show that the microarchitecture in the analyzed regions of human calcanei is anisotropic, with a preferred alignment along the posterior-anterior direction. Strong correlation was found between most scalar architectural parameters and vBMD. However, no statistical correlation was found between vBMD and the fabric components, the measures of the pore microstructure orientation. Therefore, among the parameters usually considered for cancellous bone (i.e., classic histomorphometric parameters such as porosity, trabecular thickness, number and separation), only fabric components explain the data variance that cannot be explained by vBMD, a global mass measurement, which lacks the sensitivity and selectivity to distinguish osteoporotic from healthy subjects because it is insensitive to directional changes in bone architecture. This study demonstrates that a multi-directional, fabric-dependent poroelastic ultrasound approach has the capability of characterizing anisotropic bone properties (bone quality) beyond bone mass, and could help to better understand anisotropic changes in bone architecture using ultrasound. PMID:22807141

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.

New mechanisms and targets in the treatment of bone fragility.

PubMed

Martin, T John; Seeman, Ego

2007-01-01

Bone modelling and remodelling are cell-mediated processes responsible for the construction and reconstruction of the skeleton throughout life. These processes are chiefly mediated by locally generated cytokines and growth factors that regulate the differentiation, activation, work and life span of osteoblasts and osteoclasts, the cells that co-ordinate the volumes of bone resorbed and formed. In this way, the material composition and structural design of bone is regulated in accordance with its loading requirements. Abnormalities in this regulatory system compromise the material and structural determinants of bone strength producing bone fragility. Understanding the intercellular control processes that regulate bone modelling and remodelling is essential in planning therapeutic approaches to prevention and treatment of bone fragility. A great deal has been learnt in the last decade. Clinical trials carried out exclusively with drugs that inhibit bone resorption have identified the importance of reducing the rate of bone remodelling and so the progression of bone fragility to achieved fracture reductions of approx. 50%. These trials have also identified limitations that should be placed upon interpretation of bone mineral density changes in relation to treatment. New resorption inhibitors are being developed, based on mechanisms of action that are different from existing drugs. Some of these might offer resorption inhibition without reducing bone formation. More recent research has provided the first effective anabolic therapy for bone reconstruction. Daily injections of PTH (parathyroid hormone)-(1-34) have been shown in preclinical studies and in a large clinical trial to increase bone tissue mass and reduce the risk of fractures. The action of PTH differs from that of the resorption inhibitors, but whether it is more effective in fracture reduction is not known. Understanding the cellular and molecular mechanisms of PTH action, particularly its interactions with other pathways in determining bone formation, is likely to lead to new therapeutic developments. The recent discovery through mouse genetics that PTHrP (PTH-related protein) is a crucial bone-derived paracrine regulator of remodelling offers new and interesting therapeutic targets.

R-spondins: novel matricellular regulators of the skeleton.

PubMed

Knight, M Noelle; Hankenson, Kurt D

2014-07-01

R-spondins are a family of four matricellular proteins produced by a variety of cell-types. Structurally, R-spondins contain a TSR1 domain that retains the tryptophan structure and a modified cysteine-rich CSVCTG region. In addition, the R-spondins contain two furin repeats implicated in canonical Wnt signaling. R-spondins positively regulate canonical Wnt signaling by reducing Wnt receptor turnover and thereby increasing beta-catenin stabilization. R-spondins are prominently expressed in the developing skeleton and contribute to limb formation, particularly of the distal digit. Additionally, results suggest that R-spondins may contribute to the maintenance of adult bone mass by regulating osteoblastogenesis and bone formation. Copyright © 2014. Published by Elsevier B.V.

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.

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.

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.

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.

Edentulation alters material properties of cortical bone in the human craniofacial skeleton: functional implications for craniofacial structure in primate evolution

PubMed Central

Dechow, Paul C.; Wang, Qian; Peterson, Jill

2011-01-01

Skeletal adaptations to reduced function are an important source of skeletal variation and may be indicative of environmental pressures that lead to evolutionary changes. Humans serve as a model animal to investigate the effects of loss of craniofacial function through edentulation. In the human maxilla, it is known that edentulation leads to significant changes in skeletal structure such as residual ridge resorption and loss of cortical thickness. However, little is known about changes in bone tissue structure and material properties, which are also important for understanding skeletal mechanics but are often ignored. The aims of this study were to determine cortical material properties in edentulous crania and to evaluate differences with dentate crania and thus examine the effects of loss of function on craniofacial structure. Cortical bone samples from fifteen edentulous human skulls were measured for thickness and density. Elastic properties and directions of maximum stiffness were determined by using ultrasonic techniques. These data were compared to those from dentate crania reported in a previous investigation. Cortical bone from all regions of the facial skeleton of edentulous individuals is thinner than in dentate skulls. Elastic and shear moduli, and density are similar or greater in the zygoma and cranial vault of edentulous individuals, while these properties are less in the maxilla. Most cortical bone, especially in edentulous maxillae, has reduced directional orientation. The loss of significant occlusal loads following edentulation may contribute to the change in material properties and the loss of orientation over time during the normal process of bone remodeling. These results suggest that area-specific cortical microstructural changes accompany bone resorption following edentulation. They also suggest that functional forces are important for maintaining bone mass throughout the craniofacial skeleton, even in areas such as the browridges, which have been thought to be little affected by function, because of low in vivo strains found there in several primate studies. PMID:20235319

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 ...

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.

Fundamental differences in axial and appendicular bone density in stress fractured and uninjured Royal Marine recruits--a matched case-control study.

PubMed

Davey, Trish; Lanham-New, Susan A; Shaw, Anneliese M; Cobley, Rosalyn; Allsopp, Adrian J; Hajjawi, Mark O R; Arnett, Timothy R; Taylor, Pat; Cooper, Cyrus; Fallowfield, Joanne L

2015-04-01

Stress fracture is a common overuse injury within military training, resulting in significant economic losses to the military worldwide. Studies to date have failed to fully identify the bone density and bone structural differences between stress fractured personnel and controls due to inadequate adjustment for key confounding factors; namely age, body size and physical fitness; and poor sample size. The aim of this study was to investigate bone differences between male Royal Marine recruits who suffered a stress fracture during the 32 weeks of training and uninjured control recruits, matched for age, body weight, height and aerobic fitness. A total of 1090 recruits were followed through training and 78 recruits suffered at least one stress fracture. Bone mineral density (BMD) was measured at the lumbar spine (LS), femoral neck (FN) and whole body (WB) using Dual X-ray Absorptiometry in 62 matched pairs; tibial bone parameters were measured using peripheral Quantitative Computer Tomography in 51 matched pairs. Serum C-terminal peptide concentration was measured as a marker of bone resorption at baseline, week-15 and week-32. ANCOVA was used to determine differences between stress fractured recruits and controls. BMD at the LS, WB and FN sites was consistently lower in the stress fracture group (P<0.001). Structural differences between the stress fracture recruits and controls were evident in all slices of the tibia, with the most prominent differences seen at the 38% tibial slice. There was a negative correlation between the bone cross-sectional area and BMD at the 38% tibial slice. There was no difference in serum CTx concentration between stress fracture recruits and matched controls at any stage of training. These results show evidence of fundamental differences in bone mass and structure in stress fracture recruits, and provide useful data on bone risk factor profiles for stress fracture within a healthy military population. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Osteoporosis presenting in pregnancy, puerperium, and lactation.

PubMed

Kovacs, Christopher S

2014-12-01

To describe our current state of knowledge about the pathophysiology, incidence, and treatment of osteoporosis that presents during pregnancy, puerperium, and lactation. When vertebral fractures occur in pregnant or lactating women, it is usually unknown whether the skeleton was normal before pregnancy. Maternal adaptations increase bone resorption modestly during pregnancy but markedly during lactation. The net bone loss may occasionally precipitate fractures, especially in women who have underlying low bone mass or skeletal fragility prior to pregnancy. Bone mass and strength are normally restored postweaning. Transient osteoporosis of the hip is a sporadic disorder localized to one or both femoral heads; it is not due to generalized skeletal resorption. Anecdotal reports have used bisphosphonates, strontium ranelate, teriparatide, or vertebroplasty/kyphoplasty to treat postpartum vertebral fractures, but it is unclear whether these therapies had any added benefit over the spontaneous skeletal recovery that normally occurs after weaning. These relatively rare fragility fractures result from multifactorial causes, including skeletal disorders that precede pregnancy, and structural and metabolic stresses that can compromise skeletal strength during pregnancy and lactation. Further study is needed to determine when pharmacological or surgical therapy is warranted instead of conservative or expectant management.

Multimodal correlative investigation of the interplaying micro-architecture, chemical composition and mechanical properties of human cortical bone tissue reveals predominant role of fibrillar organization in determining microelastic tissue properties.

PubMed

Schrof, Susanne; Varga, Peter; Hesse, Bernhard; Schöne, Martin; Schütz, Roman; Masic, Admir; Raum, Kay

2016-10-15

The mechanical competence of bone is crucially determined by its material composition and structural design. To investigate the interaction of the complex hierarchical architecture, the chemical composition and the resulting elastic properties of healthy femoral bone at the level of single bone lamellae and entire structural units, we combined polarized Raman spectroscopy (PRS), scanning acoustic microscopy (SAM) and synchrotron X-ray phase contrast nano tomography (SR-nanoCT). In line with earlier studies, mutual correlation analysis strongly suggested that the characteristic elastic modulations of bone lamellae within single units are the result of the twisting fibrillar orientation, rather than compositional variations, modulations of the mineral particle maturity, or mass density deviations. Furthermore, we show that predominant fibril orientations in entire tissue units can be rapidly assessed from Raman parameter maps. Coexisting twisted and oscillating fibril patterns were observed in all investigated tissue domains. Ultimately, our findings demonstrate in particular the potential of combined PRS and SAM measurements in providing multi-scalar analysis of correlated fundamental tissue properties. In future studies, the presented approach can be applied for non-destructive investigation of small pathologic samples from bone biopsies and a broad range of biological materials and tissues. Bone is a complex structured composite material consisting of collagen fibrils and mineral particles. Various studies have shown that not only composition, maturation, and packing of its components, but also their structural arrangement determine the mechanical performance of the tissue. However, prominent methodologies are usually not able to concurrently describe these factors on the micron scale and complementary tissue characterization remains challenging. In this study we combine X-ray nanoCT, polarized Raman imaging and scanning acoustic microscopy and propose a protocol for fast and easy assessment of predominant fibril orientations in bone. Based on our site-matched analysis of cortical bone, we conclude that the elastic modulations of bone lamellae are mainly determined by the fibril arrangement. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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.

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.

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

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.

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.

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.

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.

Vertebral Development in Paleozoic and Mesozoic Tetrapods Revealed by Paleohistological Data

PubMed Central

Danto, Marylène; Witzmann, Florian; Fröbisch, Nadia B.

2016-01-01

Basal tetrapods display a wide spectrum of vertebral centrum morphologies that can be used to distinguish different tetrapod groups. The vertebral types range from multipartite centra in stem-tetrapods, temnospondyls, and seymouriamorphs up to monospondylous centra in lepospondyls and have been drawn upon for reconstructing major evolutionary trends in tetrapods that are now considered textbook knowledge. Two modes of vertebral formation have been postulated: the multipartite vertebrae formed first as cartilaginous elements with subsequent ossification. The monospondylous centrum, in contrast, was formed by direct ossification without a cartilaginous precursor. This study describes centrum morphogenesis in basal tetrapods for the first time, based on bone histology. Our results show that the intercentra of the investigated stem-tetrapods consist of a small band of periosteal bone and a dense network of endochondral bone. In stereospondyl temnospondyls, high amounts of calcified cartilage are preserved in the endochondral trabeculae. Notably, the periosteal region is thickened and highly vascularized in the plagiosaurid stereospondyls. Among “microsaur” lepospondyls, the thickened periosteal region is composed of compact bone and the notochordal canal is surrounded by large cell lacunae. In nectridean lepospondyls, the periosteal region has a spongy structure with large intertrabecular spaces, whereas the endochondral region has a highly cancellous structure. Our observations indicate that regardless of whether multipartite or monospondylous, the centra of basal tetrapods display first endochondral and subsequently periosteal ossification. A high interspecific variability is observed in growth rate, organization, and initiation of periosteal ossification. Moreover, vertebral development and structure reflect different lifestyles. The bottom-dwelling Plagiosauridae increase their skeletal mass by hyperplasy of the periosteal region. In nectrideans, the skeletal mass decreases, as the microstructure is spongy and lightly built. Additionally, we observed that vertebral structure is influenced by miniaturization in some groups. The phylogenetic information that can be drawn from vertebral development, however, is limited. PMID:27074015

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.

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.

Structural Strength Benefits Observed at the Hip of Premenarcheal Gymnasts Are Maintained Into Young Adulthood 10 Years After Retirement From the Sport.

PubMed

Erlandson, Marta C; Runalls, Shonah B; Jackowski, Stefan A; Faulkner, Robert A; Baxter-Jones, Adam D G

2017-11-01

Premenarcheal female gymnasts have been consistently found to have greater bone mass and structural advantages. However, little is known about whether these structural advantages are maintained after the loading stimulus is removed. Therefore, the purpose of this study was to investigate the structural properties at the hip after long-term retirement from gymnastics. Structural properties were derived from dual-energy X-ray absorptiometry scans using the hip structural analysis program for the same 24 gymnasts and 21 nongymnasts both in adolescence (8-15 y) and adulthood (22-30 y). Structural measures were obtained at the narrow neck, intertrochanter, and femoral shaft and included cross-sectional area, section modulus, and buckling ratio. Multivariate analysis of covariance was used to assess differences between groups in bone measures while controlling for size, age, maturity, and physical activity. Gymnasts were found to have structural advantages at the narrow neck in adolescence (16% greater cross-sectional area, 17% greater section modulus, and 25% lower buckling ratio) and 14 years later (13% greater cross-sectional area and 26% lower buckling ratio). Benefits were also found at the intertrochanter and femoral shaft sites in adolescence and adulthood. Ten years after retirement from gymnastics, former gymnasts' maintained significantly better hip bone structure than females who did not participate in gymnastics during growth.

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

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.

Composition and structure of porcine digital flexor tendon-bone insertion tissues.

PubMed

Chandrasekaran, Sandhya; Pankow, Mark; Peters, Kara; Huang, Hsiao-Ying Shadow

2017-11-01

Tendon-bone insertion is a functionally graded tissue, transitioning from 200 MPa tensile modulus at the tendon end to 20 GPa tensile modulus at the bone, across just a few hundred micrometers. In this study, we examine the porcine digital flexor tendon insertion tissue to provide a quantitative description of its collagen orientation and mineral concentration by using Fast Fourier Transform (FFT) based image analysis and mass spectrometry, respectively. Histological results revealed uniformity in global collagen orientation at all depths, indicative of mechanical anisotropy, although at mid-depth, the highest fiber density, least amount of dispersion, and least cellular circularity were evident. Collagen orientation distribution obtained through 2D FFT of histological imaging data from fluorescent microscopy agreed with past measurements based on polarized light microscopy. Results revealed global fiber orientation across the tendon-bone insertion to be preserved along direction of physiologic tension. Gradation in the fiber distribution orientation index across the insertion was reflective of a decrease in anisotropy from the tendon to the bone. We provided elemental maps across the fibrocartilage for its organic and inorganic constituents through time-of-flight secondary ion mass spectrometry (TOF-SIMS). The apatite intensity distribution from the tendon to bone was shown to follow a linear trend, supporting past results based on Raman microprobe analysis. The merit of this study lies in the image-based simplified approach to fiber distribution quantification and in the high spatial resolution of the compositional analysis. In conjunction with the mechanical properties of the insertion tissue, fiber, and mineral distribution results for the insertion from this may potentially be incorporated into the development of a structural constitutive approach toward computational modeling. Characterizing the properties of the native insertion tissue would provide the microstructural basis for developing biomimetic scaffolds to recreate the graded morphology of a fibrocartilaginous insertion. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3050-3058, 2017. © 2017 Wiley Periodicals, Inc.

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

Hip Structural Analysis in Adolescent Boys With Anorexia Nervosa and Controls

PubMed Central

Katzman, Debra K.; Clarke, Hannah; Snelgrove, Deirdre; Brigham, Kathryn; Miller, Karen K.; Klibanski, Anne

2013-01-01

Context: We have reported lower hip bone mineral density (BMD) in adolescent boys with anorexia nervosa (AN) compared with controls. Although studies have described bone structure in girls with AN, these data are not available for boys. Hip structural analysis (HSA) using dual-energy x-ray absorptiometry is a validated technique to assess hip geometry and strength while avoiding radiation associated with quantitative computed tomography. Objective: We hypothesized that boys with AN would have impaired hip structure/strength (assessed by HSA) compared with controls. Design and Setting: We conducted a cross-sectional study at a clinical research center. Subjects and Intervention: We used HSA techniques on hip dual-energy x-ray absorptiometry scans in 31 previously enrolled boys, 15 with AN and 16 normal-weight controls, 12 to 19 years old. Results: AN boys had lower body mass index SD score (P < .0001), testosterone (P = .0005), and estradiol (P = .006) than controls. A larger proportion of AN boys had BMD Z-scores <−1 at the femoral neck (60% vs 12.5%, P = 0008). Using HSA, at the narrow neck and trochanter region, boys with AN had lower cross-sectional area (P = .03, 0.02) and cortical thickness (P = .02, 0.03). Buckling ratio at the trochanter region was higher in AN (P = .008). After controlling for age and height, subperiosteal width at the femoral shaft, cross-sectional moment of inertia (narrow neck and femoral shaft), and section modulus (all sites) were lower in AN. The strongest associations of HSA measures were observed with lean mass, testosterone, and estradiol. On multivariate analysis, lean mass remained associated with most HSA measures. Conclusions: Boys with AN have impaired hip geometric parameters, associated with lower lean mass. PMID:23653430

Biomechanical properties of the mid-shaft femur in middle-aged hypophysectomized rats as assessed by bending test.

PubMed

Bozzini, Clarisa; Picasso, Emilio O; Champin, Graciela M; Alippi, Rosa María; Bozzini, Carlos E

2012-10-01

Both stiffness and strength of bones are thought to be controlled by the "bone mechanostat". Its natural stimuli would be the strains of bone tissue (sensed by osteocytes) that are induced by both gravitational forces (body weight) and contraction of regional muscles. Body weight and muscle mass increase with age. Biomechanical performance of load-bearing bones must adapt to these growth-induced changes. Hypophysectomy in the rat slows the rate of body growth. With time, a great difference in body size is established between a hypophysectomized rat and its age-matched control, which makes it difficult to establish the real effect of pituitary ablation on bone biomechanics. The purpose of the present investigation was to compare mid-shaft femoral mechanical properties between hypophysectomized and weight-matched normal rats, which will show similar sizes and thus will be exposed to similar habitual loads. Two groups of 10 female rats each (H and C) were established. H rats were 12-month-old that had been hypophysectomized 11 months before. C rats were 2.5-month-old normals. Right femur mechanical properties were tested in 3-point bending. Structural (load-bearing capacity and stiffness), geometric (cross-sectional area, cortical sectional area, and moment of inertia), and material (modulus of elasticity and maximum elastic stress) properties were evaluated. The left femur was ashed for calcium content. Comparisons between parameters were performed by the Student's t test. Average body weight, body length, femur weight, femur length, and gastrocnemius weight were not significantly different between H and C rats. Calcium content in ashes was significantly higher in H than in C rats. Cross-sectional area, medullary area, and cross-sectional moment of inertia were higher in C rats, whereas cortical area did not differ between groups. Structural properties (diaphyseal stiffness, elastic limit, and load at fracture) were about four times higher in hypophysectomized rats, as were the bone material stiffness or Young's modulus and the maximal elastic stress (about 7×). The femur obtained from a middle-aged H rat was stronger and stiffer than the femur obtained from a young-adult C rat, both specimens showing similar size and bone mass and almost equal geometric properties. The higher than normal structural properties shown by the hypophysectomized femur were entirely due to changes in the intrinsic properties of the bone; it was thus stronger at the tissue level. The change of the femoral bone tissue was associated with a high mineral content and an unusual high modulus of elasticity and was probably due to a diminished bone and collagen turnover.

Identification and structural characterization of avian beta-defensin 2 peptides from pheasant and quail

USDA-ARS?s Scientific Manuscript database

Pheasant and quail orthologues of avian ß-defensin 2 (AVBD2) were identified in methanol extracts of heterophil and bone marrow using matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). We used comparative pattern profiling before and after reduction/alkyla...

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.

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.

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…

Growth-dependent effects of dietary protein concentration and quality on the biomechanical properties of the diaphyseal rat femur.

PubMed

Alippi, Rosa M; Picasso, Emilio; Huygens, Patricia; Bozzini, Carlos E; Bozzini, Clarisa

2012-01-01

This study compares the effects of feeding growing rats with increasing concentrations of casein (C) and wheat gluten (G), proteins that show different biological qualities, on the morphometrical and biomechanical properties of the femoral diaphysis. Female rats were fed with one of ten diets containing different concentrations (5-30%) of C and G between the 30th and 90th days of life (Control=C-20%). Biomechanical structural properties of the right femur middiaphysis were estimated using a 3-point bending mechanical test with calculation of some indicators of bone material properties. Body weight and length were affected by treatments, values being highest in rats fed the C-20% diet. G diets affected negatively both parameters. Changes in cross-sectional geometry (mid-diaphyseal cross-sectional and cortical areas, femoral volume, and rectangular moment of inertia) were positively related to the C content of the diet, while they were severely and negatively affected by G diets. Similar behaviors were observed in the bone structural properties (fracture load, yielding load, diaphyseal stiffness and elastic energy absorption). When values of strength and stiffness were normalized for body weight, the differences disappeared. The bone material quality indicators (elastic modulus, yielding stress, elastic energy absorption/volume) did not differ significantly among all studied groups. Femoral calcium concentration in ashes was not significantly different among groups. The clear differences in strength and stiffness of bone beams induced by dietary protein concentration and quality seemed to be the result of an induced subnormal gain in bone structural properties as a consequence of a correlative subnormal gain in bone growth and mass, yet not in bone material properties. Copyright © 2011 SEEN. Published by Elsevier Espana. All rights reserved.

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.

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.

Discovery and therapeutic promise of selective androgen receptor modulators.

PubMed

Chen, Jiyun; Kim, Juhyun; Dalton, James T

2005-06-01

Androgens are essential for male development and the maintenance of male secondary characteristics, such as bone mass, muscle mass, body composition, and spermatogenesis. The main disadvantages of steroidal androgens are their undesirable physicochemical and pharmacokinetic properties. The recent discovery of nonsteroidal selective androgen receptor modulators (SARMs) provides a promising alternative for testosterone replacement therapies with advantages including oral bioavailability, flexibility of structural modification, androgen receptor specificity, tissue selectivity, and the lack of steroid-related side effects.

Discovery AND Therapeutic Promise OF Selective Androgen Receptor Modulators

PubMed Central

Chen, Jiyun; Kim, Juhyun; Dalton, James T.

2007-01-01

Androgens are essential for male development and the maintenance of male secondary characteristics, such as bone mass, muscle mass, body composition, and spermatogenesis. The main disadvantages of steroidal androgens are their undesirable physicochemical and pharmacokinetic properties. The recent discovery of nonsteroidal selective androgen receptor modulators (SARMs) provides a promising alternative for testosterone replacement therapies with advantages including oral bioavailability, flexibility of structural modification, androgen receptor specificity, tissue selectivity, and the lack of steroid-related side effects. PMID:15994457

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...

Exercise-Induced Changes in the Cortical Bone of Growing Mice Are Bone and Gender Specific

PubMed Central

Wallace, Joseph M.; Rajachar, Rupak M.; Allen, Matthew R.; Bloomfield, Susan A.; Robey, Pamela G.; Young, Marian F.; Kohn, David H.

2009-01-01

Fracture risk and mechanical competence of bone are functions of bone mass and tissue quality, which in turn are dependent on the bone’s mechanical environment. Male mice have a greater response to non weight-bearing exercise than females, resulting in larger, stronger bones compared with control animals. The aim of this study was to test the hypothesis that short-term weight-bearing running during growth (21 days starting at 8 weeks of age; 30 minutes/day; 12 meters/minute; 5° incline; 7 days/week) would similarly have a greater impact on cross sectional geometry and mechanical competence in the femora and tibiae of male mice versus females. Based on the orientation of the legs during running and the proximity of the tibia to the point of impact, this response was hypothesized to be greatest in the tibia. Exercise-related changes relative to controls were assayed by four-point bending tests, while volumetric bone mineral density and cross-sectional geometry were also assessed. The response to running was bone and gender-specific, with male tibiae demonstrating the greatest effects. In male tibiae, periosteal perimeter, endocortical perimeter, cortical area, medial-lateral width and bending moment of inertia increased versus control mice suggesting that while growth is occurring in these mice between 8 and 11 weeks of age, exercise accelerated this growth resulting in a greater increase in bone tissue over the 3 weeks of the study. Exercise increased tissue-level strain-to-failure and structural post-yield deformation in the male tibiae, but these post-yield benefits came at the expense of decreased yield deformation, structural and tissue-level yield strength and tissue-level ultimate strength. These results suggest that exercise superimposed upon growth accelerated growth-related increases in tibial cross-sectional dimensions. Exercise also influenced the quality of this forming bone, significantly impacting structural and tissue-level mechanical properties. PMID:17240210

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.

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

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

Comparison of two interpolation methods for empirical mode decomposition based evaluation of radiographic femur bone images.

PubMed

Udhayakumar, Ganesan; Sujatha, Chinnaswamy Manoharan; Ramakrishnan, Swaminathan

2013-01-01

Analysis of bone strength in radiographic images is an important component of estimation of bone quality in diseases such as osteoporosis. Conventional radiographic femur bone images are used to analyze its architecture using bi-dimensional empirical mode decomposition method. Surface interpolation of local maxima and minima points of an image is a crucial part of bi-dimensional empirical mode decomposition method and the choice of appropriate interpolation depends on specific structure of the problem. In this work, two interpolation methods of bi-dimensional empirical mode decomposition are analyzed to characterize the trabecular femur bone architecture of radiographic images. The trabecular bone regions of normal and osteoporotic femur bone images (N = 40) recorded under standard condition are used for this study. The compressive and tensile strength regions of the images are delineated using pre-processing procedures. The delineated images are decomposed into their corresponding intrinsic mode functions using interpolation methods such as Radial basis function multiquadratic and hierarchical b-spline techniques. Results show that bi-dimensional empirical mode decomposition analyses using both interpolations are able to represent architectural variations of femur bone radiographic images. As the strength of the bone depends on architectural variation in addition to bone mass, this study seems to be clinically useful.

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

[Alterations of bone metabolism in children and adolescents with diabetes mellitus type 1].

PubMed

Pater, Agnieszka; Odrowąż-Sypniewska, Grażyna

2011-01-01

Diabetes mellitus type 1 is one of the most common chronic diseases in children and adolescents. The incidence of diabetes mellitus type 1 is increasing rapidly worldwide. Recently, the largest rate of increase is observed in children aged 0-4 years. Chronic hyperglycemia leads to microvascular and macrovascular complications including retinopathy, nephropathy, neuropathy and cardiomyopathy. Pathological changes occur in the bone structure. The lack of diagnosis and treatment of alterations of the bone tIssue metabolism may lead to osteoporosis, which is characterized by much reduced bone mineral density and changes in the microarchitecture of the bone tIssue, which in consequence results in increased susceptibility to fractures. Diabetes mellitus type 1 most often starts before achieving peak bone mass, which constitutes a point of reference for predicting risk of fractures in a later period of life. Mechanisms responsible for loss of the bone tIssue in diabetes of type 1 still remain unexplained. Many research findings indicate the anabolic role of insulin and insulin-like growth factors, mainly IGF-1. The aim of this manuscript is to review recent papers about alterations of bone metabolism in children and adolescents with diabetes mellitus type 1.

Small molecules for bone diseases.

PubMed

Masuya, Keiichi; Teno, Naoki

2010-04-01

Bones play many roles in the body, providing structure, protecting organs, anchoring muscles and storing calcium. Over 100 million people worldwide suffer from bone diseases, mainly osteoporosis, cancer-related bone loss, osteoarthritis and inflammatory arthritis. Osteoporosis itself has no specific symptoms, and the main consequence is the increased risk of bone fractures. Therefore, the prevention of bone diseases is important to maintain the quality of life in the human society. However, treatment options are still insufficient. This review article gives a summary of the low molecular mass modulators of bone diseases targets disclosed in patent applications and articles, mainly during the last 5 years. Readers will rapidly gain an overview of these modulators not only for historical targets, but also of emerging and re-visited targets. Readers will also be able to see the current research trend and the main players in this field. Drug discovery for bone diseases has made progress in the last years. The research area has dynamically shifted from historical targets (bisphosphonate, parathyroid hormone and calcitonin) to newly confirmed targets or targets re-visited which were biologically validated in the past. Cathepsin K inhibitors should be very close to launching in the market.

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

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.

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.

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

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.

Vps35 loss promotes hyperresorptive osteoclastogenesis and osteoporosis via sustained RANKL signaling

PubMed Central

Xia, Wen-Fang; Tang, Fu-Lei; Xiong, Lei; Xiong, Shan; Jung, Ji-Ung; Lee, Dae-Hoon; Li, Xing-Sheng; Feng, Xu; Mei, Lin

2013-01-01

Receptor activator of NF-κB (RANK) plays a critical role in osteoclastogenesis, an essential process for the initiation of bone remodeling to maintain healthy bone mass and structure. Although the signaling and function of RANK have been investigated extensively, much less is known about the negative regulatory mechanisms of its signaling. We demonstrate in this paper that RANK trafficking, signaling, and function are regulated by VPS35, a major component of the retromer essential for selective endosome to Golgi retrieval of membrane proteins. VPS35 loss of function altered RANK ligand (RANKL)–induced RANK distribution, enhanced RANKL sensitivity, sustained RANKL signaling, and increased hyperresorptive osteoclast (OC) formation. Hemizygous deletion of the Vps35 gene in mice promoted hyperresorptive osteoclastogenesis, decreased bone formation, and caused a subsequent osteoporotic deficit, including decreased trabecular bone volumes and reduced trabecular thickness and density in long bones. These results indicate that VPS35 critically deregulates RANK signaling, thus restraining increased formation of hyperresorptive OCs and preventing osteoporotic deficits. PMID:23509071

viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia.

PubMed

Amir, El-ad David; Davis, Kara L; Tadmor, Michelle D; Simonds, Erin F; Levine, Jacob H; Bendall, Sean C; Shenfeld, Daniel K; Krishnaswamy, Smita; Nolan, Garry P; Pe'er, Dana

2013-06-01

New high-dimensional, single-cell technologies offer unprecedented resolution in the analysis of heterogeneous tissues. However, because these technologies can measure dozens of parameters simultaneously in individual cells, data interpretation can be challenging. Here we present viSNE, a tool that allows one to map high-dimensional cytometry data onto two dimensions, yet conserve the high-dimensional structure of the data. viSNE plots individual cells in a visual similar to a scatter plot, while using all pairwise distances in high dimension to determine each cell's location in the plot. We integrated mass cytometry with viSNE to map healthy and cancerous bone marrow samples. Healthy bone marrow automatically maps into a consistent shape, whereas leukemia samples map into malformed shapes that are distinct from healthy bone marrow and from each other. We also use viSNE and mass cytometry to compare leukemia diagnosis and relapse samples, and to identify a rare leukemia population reminiscent of minimal residual disease. viSNE can be applied to any multi-dimensional single-cell technology.

Marrow Adipose Tissue Expansion Coincides with Insulin Resistance in MAGP1-Deficient Mice

PubMed Central

Walji, Tezin A.; Turecamo, Sarah E.; Sanchez, Alejandro Coca; Anthony, Bryan A.; Abou-Ezzi, Grazia; Scheller, Erica L.; Link, Daniel C.; Mecham, Robert P.; Craft, Clarissa S.

2016-01-01

Marrow adipose tissue (MAT) is an endocrine organ with the potential to influence skeletal remodeling and hematopoiesis. Pathologic MAT expansion has been studied in the context of severe metabolic challenge, including caloric restriction, high fat diet feeding, and leptin deficiency. However, the rapid change in peripheral fat and glucose metabolism associated with these models impedes our ability to examine which metabolic parameters precede or coincide with MAT expansion. Microfibril-associated glycoprotein-1 (MAGP1) is a matricellular protein that influences cellular processes by tethering signaling molecules to extracellular matrix structures. MAGP1-deficient (Mfap2−/−) mice display a progressive excess adiposity phenotype, which precedes insulin resistance and occurs without changes in caloric intake or ambulation. Mfap2−/− mice were, therefore, used as a model to associate parameters of metabolic disease, bone remodeling, and hematopoiesis with MAT expansion. Marrow adiposity was normal in Mfap2−/− mice until 6 months of age; however, by 10 months, marrow fat volume had increased fivefold relative to wild-type control at the same age. Increased gonadal fat pad mass and hyperglycemia were detectable in Mfap2−/− mice by 2 months, but peaked by 6 months. The development of insulin resistance coincided with MAT expansion. Longitudinal characterization of bone mass demonstrated a disconnection in MAT volume and bone volume. Specifically, Mfap2−/− mice had reduced trabecular bone volume by 2 months, but this phenotype did not progress with age or MAT expansion. Interestingly, MAT expansion in the 10-month-old Mfap2−/− mice was associated with modest alterations in basal hematopoiesis, including a shift from granulopoiesis to B lymphopoiesis. Together, these findings indicate MAT expansion is coincident with insulin resistance, but not excess peripheral adiposity or hyperglycemia in Mfap2−/− mice; and substantial MAT accumulation does not necessitate a proportional decrease in either bone mass or bone marrow cellularity. PMID:27445989

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.

Bone matrix, cellularity, and structural changes in a rat model with high-turnover osteoporosis induced by combined ovariectomy and a multiple-deficient diet.

PubMed

Govindarajan, Parameswari; Böcker, Wolfgang; El Khassawna, Thaqif; Kampschulte, Marian; Schlewitz, Gudrun; Huerter, Britta; Sommer, Ursula; Dürselen, Lutz; Ignatius, Anita; Bauer, Natali; Szalay, Gabor; Wenisch, Sabine; Lips, Katrin S; Schnettler, Reinhard; Langheinrich, Alexander; Heiss, Christian

2014-03-01

In estrogen-deficient, postmenopausal women, vitamin D and calcium deficiency increase osteoporotic fracture risk. Therefore, a new rat model of combined ovariectomy and multiple-deficient diet was established to mimic human postmenopausal osteoporotic conditions under nutrient deficiency. Sprague-Dawley rats were untreated (control), laparatomized (sham), or ovariectomized and received a deficient diet (OVX-Diet). Multiple analyses involving structure (micro-computed tomography and biomechanics), cellularity (osteoblasts and osteoclasts), bone matrix (mRNA expression and IHC), and mineralization were investigated for a detailed characterization of osteoporosis. The study involved long-term observation up to 14 months (M14) after laparotomy or after OVX-Diet, with intermediate time points at M3 and M12. OVX-Diet rats showed enhanced osteoblastogenesis and osteoclastogenesis. Bone matrix markers (biglycan, COL1A1, tenascin C, and fibronectin) and low-density lipoprotein-5 (bone mass marker) were down-regulated at M12 in OVX-Diet rats. However, up-regulation of matrix markers and existence of unmineralized osteoid were seen at M3 and M14. Osteoclast markers (matrix metallopeptidase 9 and cathepsin K) were up-regulated at M14. Micro-computed tomography and biomechanics confirmed bone fragility of OVX-Diet rats, and quantitative RT-PCR revealed a higher turnover rate in the humerus than in lumbar vertebrae, suggesting enhanced bone formation and resorption in OVX-Diet rats. Such bone remodeling caused disturbed bone mineralization and severe bone loss, as reported in patients with high-turnover, postmenopausal osteoporosis. Therefore, this rat model may serve as a suitable tool to evaluate osteoporotic drugs and new biomaterials or fracture implants. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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.

Dual-source dual-power electrospinning and characteristics of multifunctional scaffolds for bone tissue engineering.

PubMed

Wang, Chong; Wang, Min

2012-10-01

Electrospun tissue engineering scaffolds are attractive due to their distinctive advantages over other types of scaffolds. As both osteoinductivity and osteoconductivity play crucial roles in bone tissue engineering, scaffolds possessing both properties are desirable. In this investigation, novel bicomponent scaffolds were constructed via dual-source dual-power electrospinning (DSDPES). One scaffold component was emulsion electrospun poly(D,L-lactic acid) (PDLLA) nanofibers containing recombinant human bone morphogenetic protein (rhBMP-2), and the other scaffold component was electrospun calcium phosphate (Ca-P) particle/poly(lactic-co-glycolic acid) (PLGA) nanocomposite fibers. The mass ratio of rhBMP-2/PDLLA fibers to Ca-P/PLGA fibers in bicomponent scaffolds could be controlled in the DSDPES process by adjusting the number of syringes used to supply solutions for electrospinning. Through process optimization, both types of fibers could be evenly distributed in bicomponent scaffolds. The structure and properties of each type of fibers in the scaffolds were studied. The morphological and structural properties and wettability of scaffolds were assessed. The effects of emulsion composition for rhBMP-2/PDLLA fibers and mass ratio of fibrous components in bicomponent scaffolds on in vitro release of rhBMP-2 from scaffolds were investigated. In vitro degradation of scaffolds was also studied by monitoring their morphological changes, weight losses and decreases in average molecular weight of fiber matrix polymers.

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.

Trabecular architecture in the sciuromorph femoral head: allometry and functional adaptation.

PubMed

Mielke, Maja; Wölfer, Jan; Arnold, Patrick; van Heteren, Anneke H; Amson, Eli; Nyakatura, John A

2018-01-01

Sciuromorpha (squirrels and close relatives) are diverse in terms of body size and locomotor behavior. Individual species are specialized to perform climbing, gliding or digging behavior, the latter being the result of multiple independent evolutionary acquisitions. Each lifestyle involves characteristic loading patterns acting on the bones of sciuromorphs. Trabecular bone, as part of the bone inner structure, adapts to such loading patterns. This network of thin bony struts is subject to bone modeling, and therefore reflects habitual loading throughout lifetime. The present study investigates the effect of body size and lifestyle on trabecular structure in Sciuromorpha. Based upon high-resolution computed tomography scans, the femoral head 3D inner microstructure of 69 sciuromorph species was analyzed. Species were assigned to one of the following lifestyle categories: arboreal, aerial, fossorial and semifossorial. A cubic volume of interest was selected in the center of each femoral head and analyzed by extraction of various parameters that characterize trabecular architecture (degree of anisotropy, bone volume fraction, connectivity density, trabecular thickness, trabecular separation, bone surface density and main trabecular orientation). Our analysis included evaluation of the allometric signals and lifestyle-related adaptation in the trabecular parameters. We show that bone surface density, bone volume fraction, and connectivity density are subject to positive allometry, and degree of anisotropy, trabecular thickness, and trabecular separation to negative allometry. The parameters connectivity density, bone surface density, trabecular thickness, and trabecular separation show functional signals which are related to locomotor behavior. Aerial species are distinguished from fossorial ones by a higher trabecular thickness, lower connectivity density and lower bone surface density. Arboreal species are distinguished from semifossorial ones by a higher trabecular separation. This study on sciuromorph trabeculae supplements the few non-primate studies on lifestyle-related functional adaptation of trabecular bone. We show that the architecture of the femoral head trabeculae in Sciuromorpha correlates with body mass and locomotor habits. Our findings provide a new basis for experimental research focused on functional significance of bone inner microstructure.

Cortical and Trabecular Bone Microstructure Did Not Recover at Weight-Bearing Skeletal Sites and Progressively Deteriorated at Non-Weight-Bearing Sites During the Year Following International Space Station Missions.

PubMed

Vico, Laurence; van Rietbergen, Bert; Vilayphiou, Nicolas; Linossier, Marie-Thérèse; Locrelle, Hervé; Normand, Myriam; Zouch, Mohamed; Gerbaix, Maude; Bonnet, Nicolas; Novikov, Valery; Thomas, Thierry; Vassilieva, Galina

2017-10-01

Risk for premature osteoporosis is a major health concern in astronauts and cosmonauts; the reversibility of the bone lost at the weight-bearing bone sites is not established, although it is suspected to take longer than the mission length. The bone three-dimensional structure and strength that could be uniquely affected by weightlessness is currently unknown. Our objective is to evaluate bone mass, microarchitecture, and strength of weight-bearing and non-weight-bearing bone in 13 cosmonauts before and for 12 months after a 4-month to 6-month sojourn in the International Space Station (ISS). Standard and advanced evaluations of trabecular and cortical parameters were performed using high-resolution peripheral quantitative computed tomography. In particular, cortical analyses involved determination of the largest common volume of each successive individual scan to improve the precision of cortical porosity and density measurements. Bone resorption and formation serum markers, and markers reflecting osteocyte activity or periosteal metabolism (sclerostin, periostin) were evaluated. At the tibia, in addition to decreased bone mineral densities at cortical and trabecular compartments, a 4% decrease in cortical thickness and a 15% increase in cortical porosity were observed at landing. Cortical size and density subsequently recovered and serum periostin changes were associated with cortical recovery during the year after landing. However, tibial cortical porosity or trabecular bone failed to recover, resulting in compromised strength. The radius, preserved at landing, unexpectedly developed postflight fragility, from 3 months post-landing onward, particularly in its cortical structure. Remodeling markers, uncoupled in favor of bone resorption at landing, returned to preflight values within 6 months, then declined farther to lower than preflight values. Our findings highlight the need for specific protective measures not only during, but also after spaceflight, because of continuing uncertainties regarding skeletal recovery long after landing. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

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...

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.

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

Whole body BMC in pediatric Crohn disease: independent effects of altered growth, maturation, and body composition.

PubMed

Burnham, Jon M; Shults, Justine; Semeao, Edisio; Foster, Bethany; Zemel, Babette S; Stallings, Virginia A; Leonard, Mary B

2004-12-01

Whole body BMC was assessed in 104 children and young adults with CD and 233 healthy controls. CD was associated with significant deficits in BMC and lean mass, relative to height. Adjustment for lean mass eliminated the bone deficit in CD. Steroid exposure was associated with short stature but not bone deficits relative to height. Children with Crohn disease (CD) have multiple risk factors for impaired bone accrual. The confounding effects of poor growth and delayed maturation limit the interpretation of prior studies of bone health in CD. The objective of this study was to assess BMC relative to growth, body composition, and maturation in CD compared with controls. Whole body BMC and lean mass were assessed by DXA in 104 CD subjects and 233 healthy controls, 4-26 years of age. Multivariable linear regression models were developed to sequentially adjust for differences in skeletal size, pubertal maturation, and muscle mass. BMC-for-height z scores were derived to determine CD-specific covariates associated with bone deficits. Subjects with CD had significantly lower height z score, body mass index z score, and lean mass relative to height compared with controls (all p < 0.0001). After adjustment for group differences in age, height, and race, the ratio of BMC in CD relative to controls was significantly reduced in males (0.86; 95% CI, 0.83, 0.94) and females (0.91; 95% CI, 0.85, 0.98) with CD. Adjustment for pubertal maturation did not alter the estimate; however, addition of lean mass to the model eliminated the bone deficit. Steroid exposure was associated with short stature but not bone deficits. This study shows the importance of considering differences in body size and composition when interpreting DXA data in children with chronic inflammatory conditions and shows an association between deficits in muscle mass and bone in pediatric CD.

Milk thistle: a future potential anti-osteoporotic and fracture healing agent.

PubMed

Mohd Fozi, Nur Farhana; Mazlan, Mazliadiyana; Shuid, Ahmad Nazrun; Isa Naina, Mohamed

2013-12-01

Osteoporosis is a progressive disease of the skeleton characterised by bone fragility due to a reduction in bone mass and possibly to alteration in bone architecture that lead to a propensity to fracture with minimum trauma. Most osteoporotic fractures occur at locations rich in trabecular or cancellous bone and usually related to post menopausal women. Recently, silymarin received attention due to its alternative beneficial effect on bone formation. It is a mixture of flavonoids with powerful antioxidant properties. This review focuses on the use of milk thistle or silymarin for the treatment of osteoporosis that may be related to fracture bone. Silymarin shows potent antioxidant herb that may modulate multiple genes in favour of helping to build bone and prevent bone loss. In the mouse fracture healing model, silymarin supplementation improved tibial healing with elevated BMD and serum levels of ALP and osteocalcin. Silymarin also demonstrated clear estrogenic antiosteoporotic effects in bone structure. Silymarin appears to play a crucial role to prevent bone loss and might regulate osteogenesis and may be beneficial for fracture healing. If silymarin is considered for the use of post menopausal women, it may be used for the treatment of osteoporosis. It would be of great benefit to postmenopausal women to develop an oestrogen antagonist that is as potent and efficacious as oestrogen in preventing bone loss without the major side effect associated with HRT.

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…

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.

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.

Skeletal structure in postmenopausal women with osteopenia and fractures is characterized by abnormal trabecular plates and cortical thinning.

PubMed

Stein, Emily M; Kepley, Anna; Walker, Marcella; Nickolas, Thomas L; Nishiyama, Kyle; Zhou, Bin; Liu, X Sherry; McMahon, Donald J; Zhang, Chiyuan; Boutroy, Stephanie; Cosman, Felicia; Nieves, Jeri; Guo, X Edward; Shane, Elizabeth

2014-01-01

The majority of fragility fractures occur in women with osteopenia rather than osteoporosis as determined by dual‐energy X‐ray absorptiometry (DXA). However, it is difficult to identify which women with osteopenia are at greatest risk. We performed this study to determine whether osteopenic women with and without fractures had differences in trabecular morphology and biomechanical properties of bone. We hypothesized that women with fractures would have fewer trabecular plates, less trabecular connectivity, and lower stiffness. We enrolled 117 postmenopausal women with osteopenia by DXA (mean age 66 years; 58 with fragility fractures and 59 nonfractured controls). All had areal bone mineral density (aBMD) measured by DXA. Trabecular and cortical volumetric bone mineral density (vBMD), trabecular microarchitecture, and cortical porosity were measured by high‐resolution peripheral computed tomography (HR‐pQCT) of the distal radius and tibia. HR‐pQCT scans were subjected to finite element analysis to estimate whole bone stiffness and individual trabecula segmentation (ITS) to evaluate trabecular type (as plate or rod), orientation, and connectivity.Groups had similar age, race, body mass index (BMI), and mean T‐scores. Fracture subjects had lower cortical and trabecular vBMD, thinner cortices, and thinner, more widely separated trabeculae. By ITS, fracture subjects had fewer trabecular plates, less axially aligned trabeculae, and less trabecular connectivity. Whole bone stiffness was lower in women with fractures. Cortical porosity did not differ. Differences in cortical bone were found at both sites, whereas trabecular differences were more pronounced at the radius.In summary, postmenopausal women with osteopenia and fractures had lower cortical and trabecular vBMD; thinner, more widely separated and rodlike trabecular structure; less trabecular connectivity; and lower whole bone stiffness compared with controls,despite similar aBMD by DXA. Our results suggest that in addition to trabecular and cortical bone loss, changes in plate and rod structure may be important mechanisms of fracture in postmenopausal women with osteopenia.

Deficiency of retinaldehyde dehydrogenase 1 induces BMP2 and increases bone mass in vivo.

PubMed

Nallamshetty, Shriram; Wang, Hong; Rhee, Eun-Jung; Kiefer, Florian W; Brown, Jonathan D; Lotinun, Sutada; Le, Phuong; Baron, Roland; Rosen, Clifford J; Plutzky, Jorge

2013-01-01

The effects of retinoids, the structural derivatives of vitamin A (retinol), on post-natal peak bone density acquisition and skeletal remodeling are complex and compartment specific. Emerging data indicates that retinoids, such as all trans retinoic acid (ATRA) and its precursor all trans retinaldehyde (Rald), exhibit distinct and divergent transcriptional effects in metabolism. Despite these observations, the role of enzymes that control retinoid metabolism in bone remains undefined. In this study, we examined the skeletal phenotype of mice deficient in retinaldehyde dehydrogenase 1 (Aldh1a1), the enzyme responsible for converting Rald to ATRA in adult animals. Bone densitometry and micro-computed tomography (µCT) demonstrated that Aldh1a1-deficient (Aldh1a1(-/-) ) female mice had higher trabecular and cortical bone mass compared to age and sex-matched control C57Bl/6 wild type (WT) mice at multiple time points. Histomorphometry confirmed increased cortical bone thickness and demonstrated significantly higher bone marrow adiposity in Aldh1a1(-/-) mice. In serum assays, Aldh1a1(-/-) mice also had higher serum IGF-1 levels. In vitro, primary Aldh1a1(-/-) mesenchymal stem cells (MSCs) expressed significantly higher levels of bone morphogenetic protein 2 (BMP2) and demonstrated enhanced osteoblastogenesis and adipogenesis versus WT MSCs. BMP2 was also expressed at higher levels in the femurs and tibias of Aldh1a1(-/-) mice with accompanying induction of BMP2-regulated responses, including expression of Runx2 and alkaline phosphatase, and Smad phosphorylation. In vitro, Rald, which accumulates in Aldh1a1(-/-) mice, potently induced BMP2 in WT MSCs in a retinoic acid receptor (RAR)-dependent manner, suggesting that Rald is involved in the BMP2 increases seen in Aldh1a1 deficiency in vivo. Collectively, these data implicate Aldh1a1 as a novel determinant of cortical bone density and marrow adiposity in the skeleton in vivo through modulation of BMP signaling.

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.

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

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.

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.

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.

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

[Calcium and bone metabolism across women's life stages. Pathophysiology, adiagnosis and treatment of post-pregnancy osteoporosis.

PubMed

Kurabayashi, Takumi

Post-pregnancy osteoporosis is a rare condition with little known pathophysiology. Most cases are diagnosed in the late stage of pregnancy or in the post-partum while breastfeeding, particularly in first pregnancy. Vertebral fractures are most commonly observed and characterized by prolonged severe pain and functional limitations. Measurements of bone mineral density(BMD)of the lumbar spine and proximal femur with dual energy X-ray absorptiometry(DXA)are the clinical methods most commonly used for no fracture women. Conventional radiography will confirm the fracture in most cases, and magnetic resonance(MR), which can be safely used during pregnancy, is effective in detecting vertebral fractures and bone marrow edema. Although the bone resorption increased at the end of pregnancy and lactation, the bone formation increases and the bone structure is almost recovered after cessation of lactating in postpartum. There is much uncertainty about whether pharmacological treatments should be used for osteoporosis that presents during pregnancy and lactation. This is partly because of the lack of a firm evidence base for treatment and also because there is a spontaneous recovery of bone mass and strength after pregnancy or weaning.

The development of inter-strain variation in cortical and trabecular traits during growth of the mouse lumbar vertebral body.

PubMed

Ramcharan, M A; Faillace, M E; Guengerich, Z; Williams, V A; Jepsen, K J

2017-03-01

How cortical and trabecular bone co-develop to establish a mechanically functional structure is not well understood. Comparing early postnatal differences in morphology of lumbar vertebral bodies for three inbred mouse strains identified coordinated changes within and between cortical and trabecular traits. These early coordinate changes defined the phenotypic differences among the inbred mouse strains. Age-related changes in cortical and trabecular traits have been well studied; however, very little is known about how these bone tissues co-develop from day 1 of postnatal growth to establish functional structures by adulthood. In this study, we aimed to establish how cortical and trabecular tissues within the lumbar vertebral body change during growth for three inbred mouse strains that express wide variation in adult bone structure and function. Bone traits were quantified for lumbar vertebral bodies of female A/J, C57BL/6J (B6), and C3H/HeJ (C3H) inbred mouse strains from 1 to 105 days of age (n = 6-10 mice/age/strain). Inter-strain differences in external bone size were observed as early as 1 day of age. Reciprocal and rapid changes in the trabecular bone volume fraction and alignment in the direction of axial compression were observed by 7 days of age. Importantly, the inter-strain difference in adult trabecular bone volume fraction was established by 7 days of age. Early variation in external bone size and trabecular architecture was followed by progressive increases in cortical area between 28 and 105 days of age, with the greatest increases in cortical area seen in the mouse strain with the lowest trabecular mass. Establishing the temporal changes in bone morphology for three inbred mouse strains revealed that genetic variation in adult trabecular traits were established early in postnatal development. Early variation in trabecular architecture preceded strain-specific increases in cortical area and changes in cortical thickness. This study established the sequence of how cortical and trabecular traits co-develop during growth, which is important for identifying critical early ages to further focus on intervention studies that optimize adult bone strength.

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.

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

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.

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.

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

Agreement between bioelectrical impedance and dual energy X-ray absorptiometry in assessing fat, lean and bone mass changes in adults after a lifestyle intervention.

PubMed

Macfarlane, Duncan J; Chan, Natalie T-Y; Tse, Michael A; Joe, Glen M

2016-01-01

We aimed to assess the agreement of a commercially available bioelectrical impedance analysis (BIA) device in measuring changes in fat, lean and bone mass over a 10-week lifestyle intervention, with dual energy X-ray absorptiometry (DXA) as reference. A sample of 136 volunteers (18-66 years) underwent a physical activity intervention to enhance lean mass and reduce fat mass. BIA (Tanita BC545) and DXA (Hologic Explorer) measures of whole-body composition were taken at baseline and at the end of the intervention. After an average of 74 ± 18 days intervention, DXA showed significant changes in 2 of 3 outcome variables: reduced fat mass of 0.802 ± 1.092 kg (P < 0.001), increased lean mass of 0.477 ± 0.966 kg (P < 0.001); minor non-significant increase of 0.007 ± 0.041 kg of bone mass (P = 0.052). The respective changes in BIA measures were a significant reduction of 0.486 ± 1.539 kg fat (P < 0.001), but non-significant increases of 0.084 ± 1.201 kg lean mass (P = 0.425), and 0.014 ± 0.091 kg bone (P = 0.074). Significant, but moderately weak, correlations were seen in absolute mass changes between DXA and BIA: 0.511 (fat), 0.362 (lean) and 0.172 (bone). Compared to DXA, BIA demonstrated mediocre agreement to changes in fat mass, but poor agreement to lean mass changes. BIA significantly underestimated the magnitude of changes in fat and lean mass compared to DXA.

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.

The Mice Drawer System Tissue Sharing Program (MDS-TSP): osteobiology in microgravity

NASA Astrophysics Data System (ADS)

Ruggiu, Alessandra; Cancedda, Ranieri; Biticchi, Roberta; Cilli, Michele; Cotronei, Vittorio; Costa, Delfina; Liu, Yi; Piccardi, Federica; Pignataro, Salvatore; Tasso, Roberta; Tavella, Sara

The capacity of bone tissue to alter its mass and architecture in response to mechanical request has long been known. Bone not only develops as a structure designed specifically for mechanical demands, but it can adapt during life toward more efficient mechanical performance. In partic-ular, the skeletal effects of microgravity result in the development of an osteoporotic phenotype with several bone defects including a bone mass decrease resembling the bone modifications occurring in elder people and in bed rest conditions. This is particularly true for weight bearing bones such as spine, femur and tibiae. In contrast non-weight bearing bones like calvaria etc didn't show bone mineral density decrease in weightlessness. Given the interest of our labora-tory in the microgravity induced skeleton alterations, we focused our attention on a transgenic mouse overexpressing pleiotrophin (PTN) under the control of the bone specific human os-teocalcin promoter. This protein is a heparin-binding cytokine with different functions. In particular PTN-transgenic mice (PTN-Tg) show an increase in the bone mass and mineral-ization, with a calcium content/mg bone of 10We used this mouse model in the MDS flight experiment to study the PTN potential role in counteracting bone loss in microgravity. Three PTN-transgenic mice (Tg) and three wild type (Wt) mice were housed in the MDS (Mouse Drawer System) at the ISS for three months. During these three months two wt and one tg mice died and therefore could be only frozen for subsequent skeletal analysis. The other three mice, daily checked for their health status, were viable and in good condition throughout the all three months at the ISS. At the end of November 2009 the three mice came back to Earth and after blood collection were immediately sacrificed and the different bones isolated. From blood cell analysis no major hematological alterations were noticed in the blood cell count except a slight increase in the number of erythrocytes. The serum collected from these mice is being used in a Luminex panel assay for several cytokine and bone metabolism markers. A ground replica of the flight experiment ("ground control") was performed at the University of Genova from November 2009 to the second week of February 2010 during which we collected the bone samples. To study the microgravity effects on both wt and PTN-Tg mice we are performing morphological analysis by classical histological technique. A finer microarchitectural study by synchrotron and bench microCT has been initiated both at the Grenoble and the Trieste facil-ities. With this last technique we are analyzing both weight and non-weight bearing bones and we are evaluating bone mineral density, mineralization amount, trabecular architecture. We are also in the process of obtaining a holotomographic reconstruction of the trabecular and cortical bone from both the flight and the ground control mice. In addition we extracted RNA from long bones and bone marrow of the same mice and we are performing Real-time PCR analysis to determine the expression of bone marker such as osteocalcin, runx2, bone sialoprotein and of markers of bone turnover such as RankL, TRAP, cathepsin K, IL6 in the different animals.

Statistical analysis of biomechanical properties of the adult skull and age-related structural changes by sex in a Japanese forensic sample.

PubMed

Torimitsu, Suguru; Nishida, Yoshifumi; Takano, Tachio; Koizumi, Yoshinori; Makino, Yohsuke; Yajima, Daisuke; Hayakawa, Mutsumi; Inokuchi, Go; Motomura, Ayumi; Chiba, Fumiko; Otsuka, Katsura; Kobayashi, Kazuhiro; Odo, Yuriko; Iwase, Hirotaro

2014-01-01

The purpose of this research was to investigate the biomechanical properties of the adult human skull and the structural changes that occur with age in both sexes. The heads of 94 Japanese cadavers (54 male cadavers, 40 female cadavers) autopsied in our department were used in this research. A total of 376 cranial samples, four from each skull, were collected. Sample fracture load was measured by a bending test. A statistically significant negative correlation between the sample fracture load and cadaver age was found. This indicates that the stiffness of cranial bones in Japanese individuals decreases with age, and the risk of skull fracture thus probably increases with age. Prior to the bending test, the sample mass, the sample thickness, the ratio of the sample thickness to cadaver stature (ST/CS), and the sample density were measured and calculated. Significant negative correlations between cadaver age and sample thickness, ST/CS, and the sample density were observed only among the female samples. Computerized tomographic (CT) images of 358 cranial samples were available. The computed tomography value (CT value) of cancellous bone which refers to a quantitative scale for describing radiodensity, cancellous bone thickness and cortical bone thickness were measured and calculated. Significant negative correlation between cadaver age and the CT value or cortical bone thickness was observed only among the female samples. These findings suggest that the skull is substantially affected by decreased bone metabolism resulting from osteoporosis. Therefore, osteoporosis prevention and treatment may increase cranial stiffness and reinforce the skull structure, leading to a decrease in the risk of skull fractures. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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.

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

Low bone mass prevalence and osteoporosis risk factor assessment in African American Wisconsin women.

PubMed

Kidambi, Srividya; Partington, Susan; Binkley, Neil

2005-11-01

Post-menopausal osteoporosis is seen in all racial groups. With the increasing population and longevity of minority groups, osteoporosis is becoming an important health concern. Data regarding risk factors for, and prevalence of, low bone mass and awareness of osteoporosis risk in African American (AA) women are limited. This article evaluates the risk factors for, and prevalence of, low bone mass in a population of urban AA women in Wisconsin and assesses this group's perceived risk for osteoporosis. One hundred fifty consecutive community-dwelling AA women > or = 45 years old from Milwaukee, Wis were asked to complete a questionnaire based on currently accepted osteoporosis risk factors. Additionally, their perception of osteoporosis risk was assessed using a Likert scale. All subjects underwent quantitative calcaneal ultrasound. Subject mean age was 54 +/- 7 years. Mean T- and Z-scores were 0.5 and 0.4, respectively. Applying World Health Organization criteria, osteopenia (bone mineral density T-score <-1.0) was present in 23.3% and osteoporosis (bone mineral density <-2.5) in 9.3%. Multivariate analysis of risk factors showed that lifetime incidence of at least 1 fracture, multiparity (>2 children), postmenopausal state, and current smoking were associated with lower calcaneal bone mass. Higher education and presence of diabetes were associated with a higher bone mass. Only 25% of the women surveyed thought they were at moderate to high risk for osteoporosis. Low bone mass was present in 33% of these AA women despite their relative young age. Many AA women do not perceive osteoporosis as a health risk. It is necessary to develop strategies to educate AA women regarding osteoporosis risk.

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.

Treatment of Radix Dipsaci extract prevents long bone loss induced by modeled microgravity in hindlimb unloading rats.

PubMed

Niu, Yinbo; Li, Chenrui; Pan, Yalei; Li, Yuhua; Kong, Xianghe; Wang, Shuo; Zhai, YuanKun; Wu, Xianglong; Fan, Wutu; Mei, Qibing

2015-01-01

Radix Dipsaci is a kidney tonifying herbal medicine with a long history of safe use for treatment of bone fractures and joint diseases in China. Previous studies have shown that Radix Dipsaci extract (RDE) could prevent bone loss in ovariectomized rats. This study investigates the effect of RDE against bone loss induced by simulated microgravity. A hindlimb unloading rat model was established to determine the effect of RDE on bone mineral density and bone microarchitecture. Twenty-four male Sprague-Dawley rats were divided into four groups (n = 6 per group): control (CON), hindlimb unloading with vehicle (HLU), hindlimb unloading treated with alendronate (HLU-ALN, 2.0 mg/kg/d), and hindlimb unloading treated with RDE (HLU-RDE, 500 mg/kg/d). RDE or ALN was administrated orally for 4 weeks. Treatment with RDE had a positive effect on mechanical strength, BMD, BMC, bone turnover markers, and the changes in urinary calcium and phosphorus excretion. MicroCT analysis showed that RDE significantly prevented the reduction of the bone volume fraction, connectivity density, trabecular number, thickness, tissue mineral density, and tissue mineral content as well as improved the trabecular separation and structure model index. RDE was demonstrated to prevent the loss of bone mass induced by HLU treatment, which suggests the potential application of RDE in the treatment of microgravity-induced bone loss.

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. ...

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.

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.

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.

Sclerostin's role in bone's adaptive response to mechanical loading.

PubMed

Galea, Gabriel L; Lanyon, Lance E; Price, Joanna S

2017-03-01

Mechanical loading is the primary functional determinant of bone mass and architecture, and osteocytes play a key role in translating mechanical signals into (re)modelling responses. Although the precise mechanisms remain unclear, Wnt signalling pathway components, and the anti-osteogenic canonical Wnt inhibitor Sost/sclerostin in particular, play an important role in regulating bone's adaptive response to loading. Increases in loading-engendered strains down-regulate osteocyte sclerostin expression, whereas reduced strains, as in disuse, are associated with increased sclerostin production and bone loss. However, while sclerostin up-regulation appears to be necessary for the loss of bone with disuse, the role of sclerostin in the osteogenic response to loading is more complex. While mice unable to down-regulate sclerostin do not gain bone with loading, Sost knockout mice have an enhanced osteogenic response to loading. The molecular mechanisms by which osteocytes sense and transduce loading-related stimuli into changes in sclerostin expression remain unclear but include several, potentially interlinked, signalling cascades involving periostin/integrin, prostaglandin, estrogen receptor, calcium/NO and Igf signalling. Deciphering the mechanisms by which changes in the mechanical environment regulate sclerostin production may lead to the development of therapeutic strategies that can reverse the skeletal structural deterioration characteristic of disuse and age-related osteoporosis and enhance bones' functional adaptation to loading. By enhancing the osteogenic potential of the context in which individual therapies such as sclerostin antibodies act it may become possible to both prevent and reverse the age-related skeletal structural deterioration characteristic of osteoporosis. Copyright © 2016 The Authors. Published by 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.

From Milk to Bones, Moving Calcium Through the Body: Calcium Kinetics During Space Flight

NASA Technical Reports Server (NTRS)

Smith, Scott; Bloomberg, Jacob; Lee, Angie (Technical Monitor)

2002-01-01

Did you know that when astronauts are in space, their height increases about two inches? This happens because the weightlessness of space allows the spine, usually compressed in Earth's gravity, to expand. While this change is relatively harmless, other more serious things can happen with extended stays in weightlessness, notably bone loss. From previous experiments, scientists have observed that astronauts lose bone mass at a rate of about one percent per month during flight. Scientists know that bone is a dynamic tissue - continually being made and repaired by specialized bone cells throughout life. Certain cells produce new bone, while other cells are responsible for removing and replacing old bone. Research on the mechanisms of bone metabolism and the effects of space flight on its formation and repair are part of the exciting studies that will be performed during STS-107. Calcium plays a central role because 1) it gives strength and structure to bone and 2) all types of cells require it to function normally. Ninety-nine percent of calcium in the body is stored in the skeleton. However, calcium may be released, or resorbed, from bone to provide for other tissues when you are not eating. To better understand how and why weightlessness induces bone loss, astronauts will participate in a study of calcium kinetics - that is, the movement of calcium through the body, including absorption from food, and its role in the formation and breakdown of bone.

Primary Hyperparathyroidism: The Influence of Bone Marrow Adipose Tissue on Bone Loss and of Osteocalcin on Insulin Resistance

PubMed Central

Mendonça, Maira L.; Batista, Sérgio L.; Nogueira-Barbosa, Marcello H.; Salmon, Carlos E.G.; de Paula, Francisco J.A.

2016-01-01

OBJECTIVES: Bone marrow adipose tissue has been associated with low bone mineral density. However, no data exist regarding marrow adipose tissue in primary hyperparathyroidism, a disorder associated with bone loss in conditions of high bone turnover. The objective of the present study was to investigate the relationship between marrow adipose tissue, bone mass and parathyroid hormone. The influence of osteocalcin on the homeostasis model assessment of insulin resistance was also evaluated. METHODS: This was a cross-sectional study conducted at a university hospital, involving 18 patients with primary hyperparathyroidism (PHPT) and 21 controls (CG). Bone mass was assessed by dual-energy x-ray absorptiometry and marrow adipose tissue was assessed by 1H magnetic resonance spectroscopy. The biochemical evaluation included the determination of parathyroid hormone, osteocalcin, glucose and insulin levels. RESULTS: A negative association was found between the bone mass at the 1/3 radius and parathyroid hormone levels (r = -0.69; p<0.01). Marrow adipose tissue was not significantly increased in patients (CG = 32.8±11.2% vs PHPT = 38.6±12%). The serum levels of osteocalcin were higher in patients (CG = 8.6±3.6 ng/mL vs PHPT = 36.5±38.4 ng/mL; p<0.005), but no associations were observed between osteocalcin and insulin or between insulin and both marrow adipose tissue and bone mass. CONCLUSION: These results suggest that the increment of adipogenesis in the bone marrow microenvironment under conditions of high bone turnover due to primary hyperparathyroidism is limited. Despite the increased serum levels of osteocalcin due to primary hyperparathyroidism, these patients tend to have impaired insulin sensitivity. PMID:27626477

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

Material heterogeneity in cancellous bone promotes deformation recovery after mechanical failure.

PubMed

Torres, Ashley M; Matheny, Jonathan B; Keaveny, Tony M; Taylor, David; Rimnac, Clare M; Hernandez, Christopher J

2016-03-15

Many natural structures use a foam core and solid outer shell to achieve high strength and stiffness with relatively small amounts of mass. Biological foams, however, must also resist crack growth. The process of crack propagation within the struts of a foam is not well understood and is complicated by the foam microstructure. We demonstrate that in cancellous bone, the foam-like component of whole bones, damage propagation during cyclic loading is dictated not by local tissue stresses but by heterogeneity of material properties associated with increased ductility of strut surfaces. The increase in surface ductility is unexpected because it is the opposite pattern generated by surface treatments to increase fatigue life in man-made materials, which often result in reduced surface ductility. We show that the more ductile surfaces of cancellous bone are a result of reduced accumulation of advanced glycation end products compared with the strut interior. Damage is therefore likely to accumulate in strut centers making cancellous bone more tolerant of stress concentrations at strut surfaces. Hence, the structure is able to recover more deformation after failure and return to a closer approximation of its original shape. Increased recovery of deformation is a passive mechanism seen in biology for setting a broken bone that allows for a better approximation of initial shape during healing processes and is likely the most important mechanical function. Our findings suggest a previously unidentified biomimetic design strategy in which tissue level material heterogeneity in foams can be used to improve deformation recovery after failure.

Association Analysis of WNT10B With Bone Mass and Structure Among Individuals of African Ancestry

PubMed Central

Zmuda, Joseph M; Yerges, Laura M; Kammerer, Candace M; Cauley, Jane A; Wang, Xiaojing; Nestlerode, Cara S; Wheeler, Victor W; Patrick, Alan L; Bunker, ClareAnn H; Moffett, Susan P; Ferrell, Robert E

2009-01-01

Wnts comprise a family of secreted growth factors that regulate the development and maintenance of many organs. Recently, Wnt10b was shown to stimulate osteoblastogenesis and bone formation in mice. To evaluate further the role of Wnt10b in bone health in humans, we performed bidirectional sequencing of ∼8 kb of the WNT10B gene region in 192 individuals (96 African, 96 white) to identify single nucleotide polymorphisms (SNPs). We identified 19 SNPs with minor allele frequency (MAF) ≥0.01. Ten of these SNPs were not present in the NCBI dbSNP database (build 127), whereas 10 of the 20 SNPs (50%) reported in dbSNP were not verified. We initially genotyped seven tagging SNPs that captured common (MAF ≥ 0.05) variation in the region with r 2 > 0.80 and a potentially functional SNP in exon 5 in 1035 Afro-Caribbean men ≥40 yr of age. Association analysis showed three SNPs in a 3′ region of linkage disequilibrium that were associated with DXA measures of hip BMD. Associations between two of these three SNPs (rs1051886, rs3741627) with hip BMD were replicated in an additional 980 Afro-Caribbean men (p < 0.05), in the combined sample of 2015 men (p ≤ 0.006), and in 416 individuals ≥18 yr of age (mean, 44 yr) belonging to eight extended, multigenerational Afro-Caribbean families with mean family size >50 (3535 relative pairs; p < 0.05). Further analysis showed that rs1051886 and rs3741627 were associated with cortical cross-sectional area, periosteal circumference, and BMC in the radius, such that individuals with the minor alleles had lower biomechanical indices of long-bone bending strength. This analysis implicates the WNT10B locus as a genetic element in the regulation of bone mass and structural geometry. PMID:19016593

Association analysis of WNT10B with bone mass and structure among individuals of African ancestry.

PubMed

Zmuda, Joseph M; Yerges, Laura M; Kammerer, Candace M; Cauley, Jane A; Wang, Xiaojing; Nestlerode, Cara S; Wheeler, Victor W; Patrick, Alan L; Bunker, ClareAnn H; Moffett, Susan P; Ferrell, Robert E

2009-03-01

Wnts comprise a family of secreted growth factors that regulate the development and maintenance of many organs. Recently, Wnt10b was shown to stimulate osteoblastogenesis and bone formation in mice. To evaluate further the role of Wnt10b in bone health in humans, we performed bidirectional sequencing of approximately 8 kb of the WNT10B gene region in 192 individuals (96 African, 96 white) to identify single nucleotide polymorphisms (SNPs). We identified 19 SNPs with minor allele frequency (MAF) > or =0.01. Ten of these SNPs were not present in the NCBI dbSNP database (build 127), whereas 10 of the 20 SNPs (50%) reported in dbSNP were not verified. We initially genotyped seven tagging SNPs that captured common (MAF > or = 0.05) variation in the region with r (2) > 0.80 and a potentially functional SNP in exon 5 in 1035 Afro-Caribbean men > or =40 yr of age. Association analysis showed three SNPs in a 3' region of linkage disequilibrium that were associated with DXA measures of hip BMD. Associations between two of these three SNPs (rs1051886, rs3741627) with hip BMD were replicated in an additional 980 Afro-Caribbean men (p < 0.05), in the combined sample of 2015 men (p < or = 0.006), and in 416 individuals > or =18 yr of age (mean, 44 yr) belonging to eight extended, multigenerational Afro-Caribbean families with mean family size >50 (3535 relative pairs; p < 0.05). Further analysis showed that rs1051886 and rs3741627 were associated with cortical cross-sectional area, periosteal circumference, and BMC in the radius, such that individuals with the minor alleles had lower biomechanical indices of long-bone bending strength. This analysis implicates the WNT10B locus as a genetic element in the regulation of bone mass and structural geometry.

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.

[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

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.

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

Three-Dimensional Geometric Analysis of Felid Limb Bone Allometry

PubMed Central

Doube, Michael; Conroy, Alexis Wiktorowicz; Christiansen, Per; Hutchinson, John R.; Shefelbine, Sandra

2009-01-01

Background Studies of bone allometry typically use simple measurements taken in a small number of locations per bone; often the midshaft diameter or joint surface area is compared to body mass or bone length. However, bones must fulfil multiple roles simultaneously with minimum cost to the animal while meeting the structural requirements imposed by behaviour and locomotion, and not exceeding its capacity for adaptation and repair. We use entire bone volumes from the forelimbs and hindlimbs of Felidae (cats) to investigate regional complexities in bone allometry. Method/Principal Findings Computed tomographic (CT) images (16435 slices in 116 stacks) were made of 9 limb bones from each of 13 individuals of 9 feline species ranging in size from domestic cat (Felis catus) to tiger (Panthera tigris). Eleven geometric parameters were calculated for every CT slice and scaling exponents calculated at 5% increments along the entire length of each bone. Three-dimensional moments of inertia were calculated for each bone volume, and spherical radii were measured in the glenoid cavity, humeral head and femoral head. Allometry of the midshaft, moments of inertia and joint radii were determined. Allometry was highly variable and related to local bone function, with joint surfaces and muscle attachment sites generally showing stronger positive allometry than the midshaft. Conclusions/Significance Examining whole bones revealed that bone allometry is strongly affected by regional variations in bone function, presumably through mechanical effects on bone modelling. Bone's phenotypic plasticity may be an advantage during rapid evolutionary divergence by allowing exploitation of the full size range that a morphotype can occupy. Felids show bone allometry rather than postural change across their size range, unlike similar-sized animals. PMID:19270749

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.

Bone Blood Flow During Simulated Microgravity: Physiological and Molecular Mechanisms

NASA Technical Reports Server (NTRS)

Bloomfield, Susan A.

1999-01-01

Blood flow to bone has been shown to affect bone mass and presumably bone strength. Preliminary data indicate that blood flow to the rat femur decreases after 14 days of simulated microgravity, using hindlimb suspension (HLS). If adult rats subjected to HLS are given dobutamine, a synthetic catecholamine which can cause peripheral vasodilation and increased blood flow, the loss of cortical bone area usually observed is prevented. Further, mechanisms exist at the molecular level to link changes in bone blood flow to changes in bone cell activity, particularly for vasoactive agents like nitric oxide (NO). The decreases in fluid shear stress created by fluid flow associated with the shifts of plasma volume during microgravity may result in alterations in expression of vasoactive agents such as NO, producing important functional effects on bone cells. The primary aim of this project is to characterize changes in 1) bone blood flow, 2) indices of bone mass, geometry, and strength, and 3) changes in gene expression for modulators of nitric oxide activity (e.g., nitric oxide synthase) and other candidate genes involved in signal transduction of mechanical loading after 3, 7, 14, 21, and 28 days of HLS in the adult rat. Using a rat of at least 5 months of age avoids inadvertently studying effects of simulated microgravity on growing, rather than adult, bone. Utilizing the results of these studies, we will then define how altered blood flow contributes to changes in bone with simulated microgravity by administering a vasodilatory agent (which increases blood flow to tissues) during hindlimb suspension. In all studies, responses in the unloaded hindlimb bones (tibial shaft, femoral neck) will be compared with those in the weightbearing humeral shaft and the non-weightbearing calvarium (skull) from the same animal. Bone volumetric mineral density and geometry will be quantified by peripheral quantitative CT; structural and material properties of the long bones will be determined by 3-point bending (tibia, humerus) or compression (femoral neck) testing to failure. A unique aspect of these studies will be defining the time course of changes in gene expression in bone cell populations with unloading, accomplished with Northern blots, in situ hybridization, and immunohistochemistry. These studies have high relevance for concurrent protocols being proposed by investigators on NSBRI Cardiovascular and Muscle teams, with blood flow data available on a number of tissues other than bone. Further, dobutamine and other Beta-agonists have been tested as countermeasures for altered muscle and cardiovascular function. Results of the intervention tested in our studies have potential relevance for a number of systemic changes seen with prolonged spaceflight.

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.

Structural distinction of diacyl-, alkylacyl, and alk-1-enylacyl glycerophosphocholines as [M - 15]⁻ ions by multiple-stage linear ion-trap mass spectrometry with electrospray ionization.

PubMed

Hsu, Fong-Fu; Lodhi, Irfan J; Turk, John; Semenkovich, Clay F

2014-08-01

We describe a linear ion-trap (LIT) multiple-stage (MS(n)) mass spectrometric approach towards differentiation of alkylacyl, alk-1-enylacyl- and diacyl-glycerophoscholines (PCs) as the [M - 15]⁻ ions desorbed by electrospray ionization (ESI) in the negative-ion mode. The MS⁴ mass spectra of the [M - 15 - R²'CH = CO]⁻ ions originated from the three PC subfamilies are readily distinguishable, resulting in unambiguous distinction of the lipid classes. This method is applied to two alkyl ether rich PC mixtures isolated from murine bone marrow neutrophils and kidney, respectively, to explore its utility in the characterization of complex PC mixture of biological origin, resulting in the realization of the detailed structures of the PC species, including various classes and many minor isobaric isomers.

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.

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.

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.

Contributions of Severe Burn and Disuse to Bone Structure and Strength in Rats

PubMed Central

Baer, L.A.; Wu, X.; Tou, J. C.; Johnson, E.; Wolf, S.E.; Wade, C.E.

2012-01-01

Burn and disuse results in metabolic and bone changes associated with substantial and sustained bone loss. Such loss can lead to an increased fracture incidence and osteopenia. We studied the independent effects of burn and disuse on bone morphology, composition and strength, and microstructure of the bone alterations 14 days after injury. Sprague-Dawley rats were randomized into four groups: Sham/Ambulatory (SA), Burn/Ambulatory (BA), Sham/Hindlimb Unloaded (SH) and Burn/Hindlimb Unloaded (BH). Burn groups received a 40% total body surface area full-thickness scald burn. Disuse by hindlimb unloading was initiated immediately following injury. Bone turnover was determined in plasma and urine. Femur biomechanical parameters were measured by three-point bending tests and bone microarchitecture was determined by microcomputed tomography (uCT). On day 14, a significant reduction in body mass was observed as a result of burn, disuse and a combination of both. In terms of bone health, disuse alone and in combination affected femur weight, length and bone mineral content. Bending failure energy, an index of femur strength, was significantly reduced in all groups and maximum bending stress was lower when burn and disuse were combined. Osteocalcin was reduced in BA compared to the other groups, indicating influence of burn. The reductions observed in femur weight, BMC, biomechanical parameters and indices of bone formation are primarily responses to the combination of burn and disuse. These results offer insight into bone degradation following severe injury and disuse. PMID:23142361

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

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.

Degeneration of the osteocyte network in the C57BL/6 mouse model of aging.

PubMed

Tiede-Lewis, LeAnn M; Xie, Yixia; Hulbert, Molly A; Campos, Richard; Dallas, Mark R; Dusevich, Vladimir; Bonewald, Lynda F; Dallas, Sarah L

2017-10-26

Age-related bone loss and associated fracture risk are major problems in musculoskeletal health. Osteocytes have emerged as key regulators of bone mass and as a therapeutic target for preventing bone loss. As aging is associated with changes in the osteocyte lacunocanalicular system, we focused on the responsible cellular mechanisms in osteocytes. Bone phenotypic analysis was performed in young-(5mo) and aged-(22mo) C57BL/6 mice and changes in bone structure/geometry correlated with alterations in osteocyte parameters determined using novel multiplexed-3D-confocal imaging techniques. Age-related bone changes analogous to those in humans were observed, including increased cortical diameter, decreased cortical thickness, reduced trabecular BV/TV and cortical porosities. This was associated with a dramatic reduction in osteocyte dendrite number and cell density, particularly in females, where osteocyte dendricity decreased linearly from 5, 12, 18 to 22mo and correlated significantly with cortical bone parameters. Reduced dendricity preceded decreased osteocyte number, suggesting dendrite loss may trigger loss of viability. Age-related degeneration of osteocyte networks may impair bone anabolic responses to loading and gender differences in osteocyte cell body and lacunar fluid volumes we observed in aged mice may lead to gender-related differences in mechanosensitivity. Therapies to preserve osteocyte dendricity and viability may be beneficial for bone health in aging.

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.

Body size and pubertal development explain ethnic differences in structural geometry at the femur in Asian, Hispanic, and white early adolescent girls living in the U.S.

PubMed Central

Osborne, D.L.; Weaver, C.M.; McCabe, L.D.; McCabe, G.M.; Novotny, R.; Van Loan, M.D.; Going, S.; Matkovic, V.; Boushey, C.J.; Savaiano, D.A.

2012-01-01

Variation in structural geometry is present in adulthood, but when this variation arises and what influences this variation prior to adulthood remains poorly understood. Ethnicity is commonly the focus of research of skeletal integrity and appears to explain some of the variation in quantification of bone tissue. However, why ethnicity explains variation in skeletal integrity is unclear. Methods Here we examine predictors of bone cross sectional area (CSA) and section modulus (Z), measured using dual-energy X-ray absorptiometry (DXA) and the Advanced Hip Analysis (AHA) program at the narrow neck of the femur in adolescent (9–14 yr) girls (n=479) living in the United States who were classified as Asian, Hispanic, or white if the subject was 75% of a given group based on parental reported ethnicity. Protocols for measuring height and weight follow standardized procedures. Total body lean mass (LM) and total body fat mass (FM) were quantified in kilograms using DXA. Total dietary and total dairy calcium intakes from the previous month were estimated by the use of an electronic semi-quantitative food frequency questionnaire (eFFQ). Physical activity was estimated for the previous year by a validated self-administered modifiable activity questionnaire for adolescents with energy expenditure calculated from the metabolic equivalent (MET) values from the Compendium of Physical Activities. Multiple regression models were developed to predict CSA and Z. Results Age, time from menarche, total body lean mass (LM), total body fat mass (FM), height, total calcium, and total dairy calcium all shared a significant (p<0.05), positive relationship with CSA. Age, time from menarche, LM, FM, and height shared significant (p<0.05), positive relationships with Z. For both CSA and Z, LM was the most important covariate. Physical activity was not a significant predictor of geometry at the femoral neck (p≥0.339), even after removing LM as a covariate. After adjusting for covariates, ethnicity was not a significant predictor in regression models for CSA and Z. Conclusion Variability in bone geometry at the narrow neck of the femur is best explained by body size and pubertal maturation. After controlling for these covariates there were no differences in bone geometry between ethnic groups. PMID:22944607

Body size and pubertal development explain ethnic differences in structural geometry at the femur in Asian, Hispanic, and white early adolescent girls living in the U.S.

PubMed

Osborne, D L; Weaver, C M; McCabe, L D; McCabe, G P; Novotny, R; Van Loan, M D; Going, S; Matkovic, V; Boushey, C J; Savaiano, D A

2012-11-01

Variation in structural geometry is present in adulthood, but when this variation arises and what influences this variation prior to adulthood remains poorly understood. Ethnicity is commonly the focus of research of skeletal integrity and appears to explain some of the variation in quantification of bone tissue. However, why ethnicity explains variation in skeletal integrity is unclear. Here we examine predictors of bone cross sectional area (CSA) and section modulus (Z), measured using dual-energy X-ray absorptiometry (DXA) and the Advanced Hip Analysis (AHA) program at the narrow neck of the femur in adolescent (9-14 years) girls (n=479) living in the United States who were classified as Asian, Hispanic, or white if the subject was 75% of a given group based on parental reported ethnicity. Protocols for measuring height and weight follow standardized procedures. Total body lean mass (LM) and total body fat mass (FM) were quantified in kilograms using DXA. Total dietary and total dairy calcium intakes from the previous month were estimated by the use of an electronic semi-quantitative food frequency questionnaire (eFFQ). Physical activity was estimated for the previous year by a validated self-administered modifiable activity questionnaire for adolescents with energy expenditure calculated from the metabolic equivalent (MET) values from the Compendium of Physical Activities. Multiple regression models were developed to predict CSA and Z. Age, time from menarche, total body lean mass (LM), total body fat mass (FM), height, total calcium, and total dairy calcium all shared a significant (p<0.05), positive relationship with CSA. Age, time from menarche, LM, FM, and height shared significant (p<0.05), positive relationships with Z. For both CSA and Z, LM was the most important covariate. Physical activity was not a significant predictor of geometry at the femoral neck (p≥0.339), even after removing LM as a covariate. After adjusting for covariates, ethnicity was not a significant predictor in regression models for CSA and Z. Variability in bone geometry at the narrow neck of the femur is best explained by body size and pubertal maturation. After controlling for these covariates there were no differences in bone geometry between ethnic groups. Published by Elsevier Inc.

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.

Antibody-based inhibition of circulating DLK1 protects from estrogen deficiency-induced bone loss in mice.

PubMed

Figeac, Florence; Andersen, Ditte C; Nipper Nielsen, Casper A; Ditzel, Nicholas; Sheikh, Søren P; Skjødt, Karsten; Kassem, Moustapha; Jensen, Charlotte H; Abdallah, Basem M

2018-05-01

Soluble delta-like 1 homolog (DLK1) is a circulating protein that belongs to the Notch/Serrate/delta family, which regulates many differentiation processes including osteogenesis and adipogenesis. We have previously demonstrated an inhibitory effect of DLK1 on bone mass via stimulation of bone resorption and inhibition of bone formation. Further, serum DLK1 levels are elevated and positively correlated to bone turnover markers in estrogen (E)-deficient rodents and women. In this report, we examined whether inhibition of serum DLK1 activity using a neutralizing monoclonal antibody protects from E deficiency-associated bone loss in mice. Thus, we generated mouse monoclonal anti-mouse DLK1 antibodies (MAb DLK1) that enabled us to reduce and also quantitate the levels of bioavailable serum DLK1 in vivo. Ovariectomized (ovx) mice were injected intraperitoneally twice weekly with MAb DLK1 over a period of one month. DEXA-, microCT scanning, and bone histomorphometric analyses were performed. Compared to controls, MAb DLK1 treated ovx mice were protected against ovx-induced bone loss, as revealed by significantly increased total bone mass (BMD) due to increased trabecular bone volume fraction (BV/TV) and inhibition of bone resorption. No significant changes were observed in total fat mass or in the number of bone marrow adipocytes. These results support the potential use of anti-DLK1 antibody therapy as a novel intervention to protect from E deficiency associated bone loss. Copyright © 2018 Elsevier Inc. All rights reserved.

The synergistic effect of TiO2 nanoporous modification and platelet-rich plasma treatment on titanium-implant stability in ovariectomized rats.

PubMed

Jiang, Nan; Du, Pinggong; Qu, Weidong; Li, Lin; Liu, Zhonghao; Zhu, Songsong

For several decades, titanium and its alloys have been commonly utilized for endosseous implantable materials, because of their good mechanical properties, chemical resistance, and biocompatibility. But associated low bone mass, wear and loss characteristics, and high coefficients of friction have limited their long-term stable performance, especially in certain abnormal bone-metabolism conditions, such as postmenopausal osteoporosis. In this study, we investigated the effects of platelet-rich plasma (PRP) treatment and TiO 2 nanoporous modification on the stability of titanium implants in osteoporotic bone. After surface morphology, topographical structure, and chemical changes of implant surface had been detected by scanning electron microscopy (SEM), atomic force microscopy, contact-angle measurement, and X-ray diffraction, we firstly assessed in vivo the effect of PRP treatment on osseointegration of TiO 2 -modified implants in ovariectomized rats by microcomputed tomography examinations, histology, biomechanical testing, and SEM observation. Meanwhile, the potential molecular mechanism involved in peri-implant osseous enhancement was also determined by quantitative real-time polymerase chain reaction. The results showed that this TiO 2 -modified surface was able to lead to improve bone implant contact, while PRP treatment was able to increase the implant surrounding bone mass. The synergistic effect of both was able to enhance the terminal force of implants drastically in biomechanical testing. Compared with surface modification, PRP treatment promoted earlier osteogenesis with increased expression of the RUNX2 and COL1 genes and suppressed osteoclastogenesis with increased expression of OPG and decreased levels of RANKL. These promising results show that PRP treatment combined with a TiO 2 -nanomodified surface can improve titanium-implant biomechanical stability in ovariectomized rats, suggesting a beneficial effect to support the success of implants in osteoporotic bone.

The synergistic effect of TiO2 nanoporous modification and platelet-rich plasma treatment on titanium-implant stability in ovariectomized rats

PubMed Central

Jiang, Nan; Du, Pinggong; Qu, Weidong; Li, Lin; Liu, Zhonghao; Zhu, Songsong

2016-01-01

For several decades, titanium and its alloys have been commonly utilized for endosseous implantable materials, because of their good mechanical properties, chemical resistance, and biocompatibility. But associated low bone mass, wear and loss characteristics, and high coefficients of friction have limited their long-term stable performance, especially in certain abnormal bone-metabolism conditions, such as postmenopausal osteoporosis. In this study, we investigated the effects of platelet-rich plasma (PRP) treatment and TiO2 nanoporous modification on the stability of titanium implants in osteoporotic bone. After surface morphology, topographical structure, and chemical changes of implant surface had been detected by scanning electron microscopy (SEM), atomic force microscopy, contact-angle measurement, and X-ray diffraction, we firstly assessed in vivo the effect of PRP treatment on osseointegration of TiO2-modified implants in ovariectomized rats by microcomputed tomography examinations, histology, biomechanical testing, and SEM observation. Meanwhile, the potential molecular mechanism involved in peri-implant osseous enhancement was also determined by quantitative real-time polymerase chain reaction. The results showed that this TiO2-modified surface was able to lead to improve bone implant contact, while PRP treatment was able to increase the implant surrounding bone mass. The synergistic effect of both was able to enhance the terminal force of implants drastically in biomechanical testing. Compared with surface modification, PRP treatment promoted earlier osteogenesis with increased expression of the RUNX2 and COL1 genes and suppressed osteoclastogenesis with increased expression of OPG and decreased levels of RANKL. These promising results show that PRP treatment combined with a TiO2-nanomodified surface can improve titanium-implant biomechanical stability in ovariectomized rats, suggesting a beneficial effect to support the success of implants in osteoporotic bone. PMID:27695328

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.

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.

Chronic High Dose Alcohol Induces Osteopenia via Activation of mTOR Signaling in Bone Marrow Mesenchymal Stem Cells.

PubMed

Liu, Yao; Kou, Xiaoxing; Chen, Chider; Yu, Wenjing; Su, Yingying; Kim, Yong; Shi, Songtao; Liu, Yi

2016-08-01

Chronic consumption of excessive alcohol results in reduced bone mass, impaired bone structure, and increased risk of bone fracture. However, the mechanisms underlying alcohol-induced osteoporosis are not fully understood. Here, we show that high dose chronic alcohol consumption reduces osteogenic differentiation and enhances adipogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs), leading to osteopenia in a mouse model. Mechanistically, impaired osteo/adipogenic lineage differentiation of BMMSCs is due to activation of a phosphatidylinositide 3-kinase/AKT/mammalian target of rapamycin (mTOR) signaling cascade, resulting in downregulation of runt-related transcription factor 2 and upregulation of peroxisome proliferator-activated receptor gamma via activation of p70 ribosomal protein S6 kinase. Blockage of the mTOR pathway by rapamycin treatment ameliorates alcohol-induced osteopenia by rescuing impaired osteo/adipogenic lineage differentiation of BMMSCs. In this study, we identify a previously unknown mechanism by which alcohol impairs BMMSC lineage differentiation and reveal a potential rapamycin-based drug therapy for alcohol-induced osteoporosis. Stem Cells 2016;34:2157-2168. © 2016 AlphaMed Press.

Failure to generate bone marrow adipocytes does not protect mice from ovariectomy-induced osteopenia.

PubMed

Iwaniec, Urszula T; Turner, Russell T

2013-03-01

A reciprocal association between bone marrow fat and bone mass has been reported in ovariectomized rodents, suggesting that bone marrow adipogenesis has a negative effect on bone growth and turnover balance. Mice with loss of function mutations in kit receptor (kit(W/W-v)) have no bone marrow adipocytes in tibia or lumbar vertebra. We therefore tested the hypothesis that marrow fat contributes to the development of osteopenia by comparing the skeletal response to ovariectomy (ovx) in growing wild type (WT) and bone marrow adipocyte-deficient kit(W/W-v) mice. Mice were ovx at 4 weeks of age and sacrificed 4 or 10 weeks post-surgery. Body composition was measured at necropsy by dual-energy X-ray absorptiometry. Cortical (tibia) and cancellous (tibia and lumbar vertebra) bone architecture were evaluated by microcomputed tomography. Bone marrow adipocyte size and density, osteoblast- and osteoclast-lined bone perimeters, and bone formation were determined by histomorphometry. Ovx resulted in an increase in total body fat mass at 10 weeks post-ovx in both genotypes, but the response was attenuated in the in kit(W/W-v) mice. Adipocytes were present in bone marrow of tibia and lumbar vertebra in WT mice and bone marrow adiposity increased following ovx. In contrast, marrow adipocytes were not detected in either intact or ovx kit(W/W-v) mice. However, ovx in WT and kit(W/W-v) mice resulted in statistically indistinguishable changes in cortical and cancellous bone mass, cortical and cancellous bone formation rate, and cancellous osteoblast and osteoclast-lined bone perimeters. In conclusion, our findings do not support a causal role for increased bone marrow fat as a mediator of ovx-induced osteopenia in mice. Copyright © 2012 Elsevier Inc. All rights reserved.

Fabric dependence of wave propagation in anisotropic porous media

PubMed Central

Cowin, Stephen C.; Cardoso, Luis

2012-01-01

Current diagnosis of bone loss and osteoporosis is based on the measurement of the Bone Mineral Density (BMD) or the apparent mass density. Unfortunately, in most clinical ultrasound densitometers: 1) measurements are often performed in a single anatomical direction, 2) only the first wave arriving to the ultrasound probe is characterized, and 3) the analysis of bone status is based on empirical relationships between measurable quantities such as Speed of Sound (SOS) and Broadband Ultrasound Attenuation (BUA) and the density of the porous medium. However, the existence of a second wave in cancellous bone has been reported, which is an unequivocal signature of poroelastic media, as predicted by Biot’s poroelastic wave propagation theory. In this paper the governing equations for wave motion in the linear theory of anisotropic poroelastic materials are developed and extended to include the dependence of the constitutive relations upon fabric - a quantitative stereological measure of the degree of structural anisotropy in the pore architecture of a porous medium. This fabric-dependent anisotropic poroelastic approach is a theoretical framework to describe the microarchitectural-dependent relationship between measurable wave properties and the elastic constants of trabecular bone, and thus represents an alternative for bone quality assessment beyond BMD alone. PMID:20461539

Effects of short-term step aerobics exercise on bone metabolism and functional fitness in postmenopausal women with low bone mass.

PubMed

Wen, H J; Huang, T H; Li, T L; Chong, P N; Ang, B S

2017-02-01

Measurement of bone turnover markers is an alternative way to determine the effects of exercise on bone health. A 10-week group-based step aerobics exercise significantly improved functional fitness in postmenopausal women with low bone mass, and showed a positive trend in reducing resorption activity via bone turnover markers. The major goal of this study was to determine the effects of short-term group-based step aerobics (GBSA) exercise on the bone metabolism, bone mineral density (BMD), and functional fitness of postmenopausal women (PMW) with low bone mass. Forty-eight PMW (aged 58.2 ± 3.5 years) with low bone mass (lumbar spine BMD T-score of -2.00 ± 0.67) were recruited and randomly assigned to an exercise group (EG) or to a control group (CG). Participants from the EG attended a progressive 10-week GBSA exercise at an intensity of 75-85 % of heart rate reserve, 90 min per session, and three sessions per week. Serum bone metabolic markers (C-terminal telopeptide of type 1 collagen [CTX] and osteocalcin), BMD, and functional fitness components were measured before and after the training program. Mixed-models repeated measures method was used to compare differences between the groups (α = 0.05). After the 10-week intervention period, there was no significant exercise program by time interaction for CTX; however, the percent change for CTX was significantly different between the groups (EG = -13.1 ± 24.4 % vs. CG = 11.0 ± 51.5 %, P < 0.05). While there was no significant change of osteocalcin in both groups. As expected, there was no significant change of BMD in both groups. In addition, the functional fitness components in the EG were significantly improved, as demonstrated by substantial enhancement in both lower- and upper-limb muscular strength and cardiovascular endurance (P < 0.05). The current short-term GBSA exercise benefited to bone metabolism and general health by significantly reduced bone resorption activity and improved functional fitness in PMW with low bone mass. This suggested GBSA could be adopted as a form of group-based exercise for senior community.

Anabolic Responses of an Adult Cancellous Bone Site to Prostaglandin E2 in the Rat

NASA Technical Reports Server (NTRS)

Ito, Hiroshi; Ke, Hua Zhu; Jee, Webster S. S.; Sakou, Takashi

1993-01-01

The objects of this study were to determine: (1) the response of a non-growing cancellous bone site to daily prostaglandin E2 (PGE2) administration; and (2) the differences in the effects of daily PGE2, administration in growing (proximal tibial metaphysis, PTM) and non-growing cancellous bone sites (distal tibial metaphysis, DTM). Seven-month-old male Sprague-Dawley rats were given daily subcutaneous injections of 0, 1, 3 and 6 mg PGE2/kg per day for 60, 120 and 180 days. The static and dynamic histomorphometric analyses were performed on double-fluorescent labeled undecalcified distal tibial metaphyses (DTM). No age-related changes were found in static and dynamic histomorphometry of DTM cancellous bone between 7 and 13 months of age. The DTM of 7-month-old (basal controls) rats consisted of a 24.5 +/- 7.61%-metaphyseal cancellous bone mass, and a thick trabeculae (92 +/- 12 micro-m). It also had a very low tissue-base bone formation rate (3.0 +/- 7.31%/year). Exogenous PGE2 administration produced the following transient changes in a dose-response manner between zero and 60 days: (1) increased trabecular bone mass and improved architecture (increased trabecular bone area, width and number, and decreased trabecular separation); (2) increased trabecular interconnections: (3) increased bone formation parameters; and (4) decreased eroded perimeter. A new steady state with more cancellous bone mass and higher bone turnover was observed from day 60 onward, The elevated bone mass induced by the first 60 days of PGE2 treatment was maintained by another 60 and 120 days with continuous daily PGE2 treatment. When these findings were compared to those previously reported for the PTM, we found that the DTM was much more responsive to PGE2 treatment than the PTM. Percent trabecular bone area and tissue based bone formation rate increased significantly more in DTM as compared to PTM after the 60 days of 6 mg PGE2 treatment. These observations indicate that a non-growing cancellous bone site is more responsive than growing bone site to long-term daily administration of PGE2.

Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus.

PubMed

Medina-Gomez, Carolina; Kemp, John P; Dimou, Niki L; Kreiner, Eskil; Chesi, Alessandra; Zemel, Babette S; Bønnelykke, Klaus; Boer, Cindy G; Ahluwalia, Tarunveer S; Bisgaard, Hans; Evangelou, Evangelos; Heppe, Denise H M; Bonewald, Lynda F; Gorski, Jeffrey P; Ghanbari, Mohsen; Demissie, Serkalem; Duque, Gustavo; Maurano, Matthew T; Kiel, Douglas P; Hsu, Yi-Hsiang; C J van der Eerden, Bram; Ackert-Bicknell, Cheryl; Reppe, Sjur; Gautvik, Kaare M; Raastad, Truls; Karasik, David; van de Peppel, Jeroen; Jaddoe, Vincent W V; Uitterlinden, André G; Tobias, Jonathan H; Grant, Struan F A; Bagos, Pantelis G; Evans, David M; Rivadeneira, Fernando

2017-07-25

Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% (95% CI: 34-52%) for TBLH-BMD, and 39% (95% CI: 30-48%) for TB-LM, with a shared genetic component of 43% (95% CI: 29-56%). We identify variants with pleiotropic effects in eight loci, including seven established bone mineral density loci: WNT4, GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3, and PPP6R3/LRP5. Variants in the TOM1L2/SREBF1 locus exert opposing effects TB-LM and TBLH-BMD, and have a stronger association with the former trait. We show that SREBF1 is expressed in murine and human osteoblasts, as well as in human muscle tissue. This is the first bivariate GWAS meta-analysis to demonstrate genetic factors with pleiotropic effects on bone mineral density and lean mass.Bone mineral density and lean skeletal mass are heritable traits. Here, Medina-Gomez and colleagues perform bivariate GWAS analyses of total body lean mass and bone mass density in children, and show genetic loci with pleiotropic effects on both traits.

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.

Spontaneous telangiectatic osteosarcoma in a rhesus macaque (Macaca mulatta).

PubMed

Goldschmidt, B; Calado, M I Z; Resende, F C; Caldas, R M; Pinto, L W; Lopes, C A A; França, F G O; Meireles, B S; Souza, I V

2017-04-01

Osteosarcoma (OS) is the most common type of bone cancer, especially in young. Telangiectatic osteosarcoma (TO) is a rare variant of OS, and hence, its occurrence, presentation, and prognosis are poorly understood. A 4-year-old female rhesus monkey presenting lameness and swelling was examined for a mass on the right humerus. Radiography revealed fracture and disorganized structure of bone tissue. Histopathological examination revealed malignant neoplasm composed of anaplastic osteoblasts, which invaded the bone marrow and surrounded blood-filled cysts in the epiphysis and diaphysis forming septa. Cytogenetic analysis showed aneuploid cells, supernumerary AgNORs, and a marker fragment. The neoplasm was diagnosed as TO. To our knowledge, the occurrence of TO and its cytogenetic analysis were reported for the first time in non-human primates. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Ontogeny of the Human Pelvis.

PubMed

Verbruggen, Stefaan W; Nowlan, Niamh C

2017-04-01

The human pelvis has evolved over time into a remarkable structure, optimised into an intricate architecture that transfers the entire load of the upper body into the lower limbs, while also facilitating bipedal movement. The pelvic girdle is composed of two hip bones, os coxae, themselves each formed from the gradual fusion of the ischium, ilium and pubis bones. Unlike the development of the classical long bones, a complex timeline of events must occur in order for the pelvis to arise from the embryonic limb buds. An initial blastemal structure forms from the mesenchyme, with chondrification of this mass leading to the first recognisable elements of the pelvis. Primary ossification centres initiate in utero, followed post-natally by secondary ossification at a range of locations, with these processes not complete until adulthood. This cascade of events can vary between individuals, with recent evidence suggesting that fetal activity can affect the normal development of the pelvis. This review surveys the current literature on the ontogeny of the human pelvis. Anat Rec, 300:643-652, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Osteoporosis and low bone mass at the femur neck or lumbar spine in older adults: United States, 2005-2008

USDA-ARS?s Scientific Manuscript database

Many current clinical guidelines recommend that assessment of osteoporosis or low bone mass, as defined by the World Health Organization (WHO) (1), be based on bone mineral density at either the femur neck region of the proximal femur (hip) or the lumbar spine (2,3). This data brief presents the mos...

Loading and Skeletal Development and Maintenance

PubMed Central

Bergmann, P.; Body, J. J.; Boonen, S.; Boutsen, Y.; Devogelaer, J. P.; Goemaere, S.; Kaufman, J.; Reginster, J. Y.; Rozenberg, S.

2011-01-01

Mechanical loading is a major regulator of bone mass and geometry. The osteocytes network is considered the main sensor of loads, through the shear stress generated by strain induced fluid flow in the lacuno-canalicular system. Intracellular transduction implies several kinases and phosphorylation of the estrogen receptor. Several extra-cellular mediators, among which NO and prostaglandins are transducing the signal to the effector cells. Disuse results in osteocytes apoptosis and rapid imbalanced bone resorption, leading to severe osteoporosis. Exercising during growth increases peak bone mass, and could be beneficial with regards to osteoporosis later in life, but the gain could be lost if training is abandoned. Exercise programs in adults and seniors have barely significant effects on bone mass and geometry at least at short term. There are few data on a possible additive effect of exercise and drugs in osteoporosis treatment, but disuse could decrease drugs action. Exercise programs proposed for bone health are tedious and compliance is usually low. The most practical advice for patients is to walk a minimum of 30 to 60 minutes per day. Other exercises like swimming or cycling have less effect on bone, but could reduce fracture risk indirectly by maintaining muscle mass and force. PMID:21209784

Age-associated bone loss and intraskeletal variability in the Imperial Romans.

PubMed

Cho, Helen; Stout, Sam Darrel

2011-01-01

An Imperial Roman sample from the Isola Sacra necropolis (100-300 A.D.) offered an opportunity to histologically examine bone loss and intraskeletal variability in an urban archaeological population. Rib and femur samples were analyzed for static indices of bone remodeling and measures of bone mass. The Imperial Romans experienced normal age-associated bone loss via increased intracortical porosity and endosteal expansion, with females exhibiting greater bone loss and bone turnover rates than in males. Life events such as menopause and lactation coupled with cultural attitudes and practices regarding gender and food may have led to increased bone loss in females. Remodeling dynamics differ between the rib and femur and the higher remodeling rates in the rib may be attributed to different effective age of the adult compacta or loading environment. This study demonstrates that combining multiple methodologies to examine bone loss is necessary to shed light on the biocultural factors that influence bone mass and bone loss.

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.

Androgens and estrogens in skeletal sexual dimorphism

PubMed Central

Laurent, Michaël; Antonio, Leen; Sinnesael, Mieke; Dubois, Vanessa; Gielen, Evelien; Classens, Frank; Vanderschueren, Dirk

2014-01-01

Bone is an endocrine tissue expressing androgen and estrogen receptors as well as steroid metabolizing enzymes. The bioactivity of circulating sex steroids is modulated by sex hormone-binding globulin and local conversion in bone tissue, for example, from testosterone (T) to estradiol (E2) by aromatase, or to dihydrotestosterone by 5α-reductase enzymes. Our understanding of the structural basis for gender differences in bone strength has advanced considerably over recent years due to increasing use of (high resolution) peripheral computed tomography. These microarchitectural insights form the basis to understand sex steroid influences on male peak bone mass and turnover in cortical vs trabecular bone. Recent studies using Cre/LoxP technology have further refined our mechanistic insights from global knockout mice into the direct contributions of sex steroids and their respective nuclear receptors in osteoblasts, osteoclasts, osteocytes, and other cells to male osteoporosis. At the same time, these studies have reinforced the notion that androgen and estrogen deficiency have both direct and pleiotropic effects via interaction with, for example, insulin-like growth factor 1, inflammation, oxidative stress, central nervous system control of bone metabolism, adaptation to mechanical loading, etc., This review will summarize recent advances on these issues in the field of sex steroid actions in male bone homeostasis. PMID:24385015

[New methods for the evaluation of bone quality. Bone anabolic agents and bone quality.

PubMed

Yamamoto, Norio; Tsuchiya, Hiroyuki

Teriparatide(TPTD)products that can be used clinically in Japan include a daily subcutaneous injection form produced by genetic engineering and a weekly subcutaneous injectable TPTD acetate form produced by chemical synthesis. Published reports indicate that both forms exhibit excellent antifracture efficacy, and as the only anabolic agents that promote osteogenesis, TPTD products now occupy a prominent position. However, the two forms differ considerably, not only in frequency of administration, but also in mechanism of action. The daily form stimulates osteogenesis and accompanying resorption through more radical high bone turnover, and early in the course of treatment, intracortical porosity and apatite crystallization decrease, while immature collagen crosslinking increases. However, because daily formulations also produce an increase in cortical surface area or cortical thickness, the effects are counterbalanced, and bone strength is maintained. In contrast, the weekly form prioritizes osteogenesis, and by concurrently lowering turnover below pretreatment levels, improves trabecular bone mass and structure, and enhances strength without leading to cortical porosity and other undesirable phenomena. Abaloparatide, a PTHrP(1-34)analog that is homologous with the biologically active site of PTH drugs, is currently under development, and we eagerly anticipate further clarification of the mechanism of action of each formulation on bone.

Improved bone status by the beta-blocker propranolol in an animal model of nutritional growth retardation.

PubMed

Lezón, Christian E; Olivera, María I; Bozzini, Clarisa; Mandalunis, Patricia; Alippi, Rosa M; Boyer, Patricia M

2009-06-01

The aim of the present research was to study if the beta-blocker propranolol, which is known to increase bone mass, could reverse the adverse skeletal effects of mild chronic food restriction in weanling rats. Male Wistar rats were divided into four groups: control, control+propranolol (CP), nutritional growth retardation (NGR) and nutritional growth retardation+propranolol (NGRP). Control and CP rats were fed freely with the standard diet. NGR and NGRP rats received, for 4 weeks, 80 % of the amount of food consumed by the control and CP rats, respectively. Results were expressed as mean values and sem. Food restriction induced detrimental effects on body and femur weight and length (P < 0.05) and bone structural and geometrical properties (P < 0.001), confirming results previously shown in our laboratory. However, the beta-blocker overcame the deleterious effect of nutritional stress on load-bearing capacity, yielding load, bone stiffness, cross-sectional cortical bone area and second moment of inertia of the cross-section in relation to the horizontal axis without affecting anthropometric, histomorphometric and bone morphometric parameters. The results suggest that propranolol administration to mildly chronically undernourished rats markedly attenuates the impaired bone status in this animal model of growth retardation.

Effects of obesity on bone metabolism.

PubMed

Cao, Jay J

2011-06-15

Obesity is traditionally viewed to be beneficial to bone health because of well-established positive effect of mechanical loading conferred by body weight on bone formation, despite being a risk factor for many other chronic health disorders. Although body mass has a positive effect on bone formation, whether the mass derived from an obesity condition or excessive fat accumulation is beneficial to bone remains controversial. The underline pathophysiological relationship between obesity and bone is complex and continues to be an active research area. Recent data from epidemiological and animal studies strongly support that fat accumulation is detrimental to bone mass. To our knowledge, obesity possibly affects bone metabolism through several mechanisms. Because both adipocytes and osteoblasts are derived from a common multipotential mesenchymal stem cell, obesity may increase adipocyte differentiation and fat accumulation while decrease osteoblast differentiation and bone formation. Obesity is associated with chronic inflammation. The increased circulating and tissue proinflammatory cytokines in obesity may promote osteoclast activity and bone resorption through modifying the receptor activator of NF-κB (RANK)/RANK ligand/osteoprotegerin pathway. Furthermore, the excessive secretion of leptin and/or decreased production of adiponectin by adipocytes in obesity may either directly affect bone formation or indirectly affect bone resorption through up-regulated proinflammatory cytokine production. Finally, high-fat intake may interfere with intestinal calcium absorption and therefore decrease calcium availability for bone formation. Unraveling the relationship between fat and bone metabolism at molecular level may help us to develop therapeutic agents to prevent or treat both obesity and osteoporosis. Obesity, defined as having a body mass index ≥ 30 kg/m2, is a condition in which excessive body fat accumulates to a degree that adversely affects health. The rates of obesity rates have doubled since 1980 and as of 2007, 33% of men and 35% of women in the US are obese. Obesity is positively associated to many chronic disorders such as hypertension, dyslipidemia, type 2 diabetes mellitus, coronary heart disease, and certain cancers. It is estimated that the direct medical cost associated with obesity in the United States is ~$100 billion per year.Bone mass and strength decrease during adulthood, especially in women after menopause. These changes can culminate in osteoporosis, a disease characterized by low bone mass and microarchitectural deterioration resulting in increased bone fracture risk. It is estimated that there are about 10 million Americans over the age of 50 who have osteoporosis while another 34 million people are at risk of developing the disease. In 2001, osteoporosis alone accounted for some $17 billion in direct annual healthcare expenditure. Several lines of evidence suggest that obesity and bone metabolism are interrelated. First, both osteoblasts (bone forming cells) and adipocytes (energy storing cells) are derived from a common mesenchymal stem cell and agents inhibiting adipogenesis stimulated osteoblast differentiation and vice versa, those inhibiting osteoblastogenesis increased adipogenesis. Second, decreased bone marrow osteoblastogenesis with aging is usually accompanied with increased marrow adipogenesis. Third, chronic use of steroid hormone, such as glucocorticoid, results in obesity accompanied by rapid bone loss. Fourth, both obesity and osteoporosis are associated with elevated oxidative stress and increased production of proinflammatory cytokines. At present, the mechanisms for the effects of obesity on bone metabolism are not well defined and will be the focus of this review.

Consensus and controversy regarding osteoporosis in the pediatric population.

PubMed

Bachrach, Laura Keyes

2007-09-01

To review current consensus and controversy surrounding the diagnosis and treatment of osteoporosis in childhood and adolescence. The medical literature was reviewed with emphasis on the importance of early skeletal health, risk factors for bone fragility, and the diagnosis and management of children at risk for osteoporosis. Childhood and adolescence are critical periods for optimizing bone growth and mineral accrual. Bone strength is determined by bone size, geometry, quality, and mass-variables that are influenced by genetic factors, activity, nutrition, and hormones. For children with genetic skeletal disorders or chronic disease, bone growth and mineral accrual may be compromised, increasing the lifetime risk of osteoporosis. The goal for the clinician is to identify children at greatest risk for future fragility fracture. Bone densitometry and turnover markers are challenging to interpret in children. Prevention and treatment of bone fragility in children are less well established than in adults. Optimizing nutrition and activity may not restore bone health, but the drug armamentarium is limited. Sex steroid replacement has not proven effective in restoring bone mass in patients with anorexia nervosa or exercise-associated amenorrhea. Bisphosphonates can increase bone mass and may reduce bone pain and fractures, most convincingly in patients with osteogenesis imperfecta. Further studies are needed to establish the safety, efficacy, and optimal drug, duration, and dosage in pediatric patients. Bone health during the first 2 decades contributes to the lifetime risk of osteoporosis. Further research is needed to develop evidence-based recommendations for the diagnosis and treatment of osteoporosis in childhood.

A potential mechanism for allometric trabecular bone scaling in terrestrial mammals.

PubMed

Christen, Patrik; Ito, Keita; van Rietbergen, Bert

2015-03-01

Trabecular bone microstructural parameters, including trabecular thickness, spacing, and number, have been reported to scale with animal size with negative allometry, whereas bone volume fraction is animal size-invariant in terrestrial mammals. As for the majority of scaling patterns described in animals, its underlying mechanism is unknown. However, it has also been found that osteocyte density is inversely related to animal size, possibly adapted to metabolic rate, which shows a negative relationship as well. In addition, the signalling reach of osteocytes is limited by the extent of the lacuno-canalicular network, depending on trabecular dimensions and thus also on animal size. Here we propose animal size-dependent variations in osteocyte density and their signalling influence distance as a potential mechanism for negative allometric trabecular bone scaling in terrestrial mammals. Using an established and tested computational model of bone modelling and remodelling, we run simulations with different osteocyte densities and influence distances mimicking six terrestrial mammals covering a large range of body masses. Simulated trabecular structures revealed negative allometric scaling for trabecular thickness, spacing, and number, constant bone volume fraction, and bone turnover rates inversely related to animal size. These results are in agreement with previous observations supporting our proposal of osteocyte density and influence distance variation as a potential mechanism for negative allometric trabecular bone scaling in terrestrial mammals. The inverse relationship between bone turnover rates and animal size further indicates that trabecular bone scaling may be linked to metabolic rather than mechanical adaptations. © 2015 Anatomical Society.

Determination of bone mineral mass in vivo

NASA Technical Reports Server (NTRS)

Cameron, J. R.; Judy, P. F.

1975-01-01

Radiographic equipment incorporates two radiation sources, generating high-energy and low-energy beams. Recording equipment measures amount of radiation that has penetrated limb. Data are fed into computer that determines mass of the examined bone.

Sympathetic control of bone mass regulated by osteopontin

PubMed Central

Nagao, Masashi; Feinstein, Timothy N.; Ezura, Yoichi; Hayata, Tadayoshi; Notomi, Takuya; Saita, Yoshitomo; Hanyu, Ryo; Hemmi, Hiroaki; Izu, Yayoi; Takeda, Shu; Wang, Kathryn; Rittling, Susan; Nakamoto, Tetsuya; Kaneko, Kazuo; Kurosawa, Hisashi; Karsenty, Gerard; Denhardt, David T.; Vilardaga, Jean-Pierre; Noda, Masaki

2011-01-01

The sympathetic nervous system suppresses bone mass by mechanisms that remain incompletely elucidated. Using cell-based and murine genetics approaches, we show that this activity of the sympathetic nervous system requires osteopontin (OPN), a cytokine and one of the major members of the noncollagenous extracellular matrix proteins of bone. In this work, we found that the stimulation of the sympathetic tone by isoproterenol increased the level of OPN expression in the plasma and bone and that mice lacking OPN (OPN-KO) suppressed the isoproterenol-induced bone loss by preventing reduced osteoblastic and enhanced osteoclastic activities. In addition, we found that OPN is necessary for changes in the expression of genes related to bone resorption and bone formation that are induced by activation of the sympathetic tone. At the cellular level, we showed that intracellular OPN modulated the capacity of the β2-adrenergic receptor to generate cAMP with a corresponding modulation of cAMP-response element binding (CREB) phosphorylation and associated transcriptional events inside the cell. Our results indicate that OPN plays a critical role in sympathetic tone regulation of bone mass and that this OPN regulation is taking place through modulation of the β2-adrenergic receptor/cAMP signaling system. PMID:21990347

Histone deacetylase 3 is required for maintenance of bone mass during aging

PubMed Central

McGee-Lawrence, Meghan E.; Bradley, Elizabeth W.; Dudakovic, Amel; Carlson, Samuel W.; Ryan, Zachary C.; Kumar, Rajiv; Dadsetan, Mahrokh; Yaszemski, Michael J.; Chen, Qingshan; An, Kai-Nan; Westendorf, Jennifer J.

2012-01-01

Histone deacetylase 3 (Hdac3) is a nuclear enzyme that removes acetyl groups from lysine residues in histones and other proteins to epigenetically regulate gene expression. Hdac3 interacts with bone-related transcription factors and co-factors such as Runx2 and Zfp521, and thus is poised to play a key role in the skeletal system. To understand the role of Hdac3 in osteoblasts and osteocytes, Hdac3 conditional knockout (CKO) mice were created with the Osteocalcin (OCN) promoter driving Cre expression. Hdac3 CKOOCN mice were of normal size and weight, but progressively lost trabecular and cortical bone mass with age. The Hdac3 CKOOCN mice exhibited reduced cortical bone mineralization and material properties and suffered frequent fractures. Bone resorption was lower, not higher, in the Hdac3 CKOOCN mice, suggesting that primary defects in osteoblasts caused the reduced bone mass. Indeed, reductions in bone formation were observed. Osteoblasts and osteocytes from Hdac3 CKOOCN mice showed increased DNA damage and reduced functional activity in vivo and in vitro. Thus, Hdac3 expression in osteoblasts and osteocytes is essential for bone maintenance during aging. PMID:23085085

A high-fat diet induces bone loss in mice lacking the Alox5 gene.

PubMed

Le, Phuong; Kawai, Masanobu; Bornstein, Sheila; DeMambro, Victoria E; Horowitz, Mark C; Rosen, Clifford J

2012-01-01

5-Lipoxygenase catalyzes leukotriene generation from arachidonic acid. The gene that encodes 5-lipoxygenase, Alox5, has been identified in genome-wide association and mouse Quantitative Trait Locus studies as a candidate gene for obesity and low bone mass. Thus, we tested the hypothesis that Alox5(-/-) mice would exhibit metabolic and skeletal changes when challenged by a high-fat diet (HFD). On a regular diet, Alox5(-/-) mice did not differ in total body weight, percent fat mass, or bone mineral density compared with wild-type (WT) controls (P < 0.05). However, when placed on a HFD, Alox5(-/-) gained more fat mass and lost greater areal bone mass vs. WT (P < 0.05). Microarchitectural analyses revealed that on a HFD, WT showed increases in cortical area (P < 0.01) and trabecular thickness (P < 0.01), whereas Alox5(-/-) showed no change in cortical parameters but a decrease in trabecular number (P < 0.05) and bone volume fraction compared with WT controls (P < 0.05). By histomorphometry, a HFD did not change bone formation rates of either strain but produced an increase in osteoclast number per bone perimeter in Alox5(-/-) mice (P < 0.03). In vitro, osteoclastogenesis of marrow stromal cells was enhanced in mutant but not WT mice fed a HFD. Gene expression for Rankl, Pparg, and Cox-2 was greater in the femur of Alox5(-/-) than WT mice on a HFD (P < 0.01), but these increases were suppressed in the Alox5(-/-) mice after 8 wk of treatment with celecoxib, a cyclooxygenase-2 inhibitor. In sum, there is a strong gene by environmental interaction for bone mass when mice lacking the Alox5 gene are fed a HFD.

Decreased Bone Formation and Osteopenia in Lamin A/C-Deficient Mice

PubMed Central

Vidal, Christopher; McCorquodale, Thomas; Herrmann, Markus; Fatkin, Diane; Duque, Gustavo

2011-01-01

Age-related bone loss is associated with changes in bone cellularity with characteristically low levels of osteoblastogenesis. The mechanisms that explain these changes remain unclear. Although recent in vitro evidence has suggested a new role for proteins of the nuclear envelope in osteoblastogenesis, the role of these proteins in bone cells differentiation and bone metabolism in vivo remains unknown. In this study, we used the lamin A/C null (Lmna −/−) mice to identify the role of lamin A/C in bone turnover and bone structure in vivo. At three weeks of age, histological and micro computed tomography measurements of femurs in Lmna −/− mice revealed a significant decrease in bone mass and microarchitecture in Lmna −/− mice as compared with their wild type littermates. Furthermore, quantification of cell numbers after normalization with bone surface revealed a significant reduction in osteoblast and osteocyte numbers in Lmna −/− mice compared with their WT littermates. In addition, Lmna −/− mice have significantly lower osteoclast number, which show aberrant changes in their shape and size. Finally, mechanistic analysis demonstrated that absence of lamin A/C is associated with increase expression of MAN-1 a protein of the nuclear envelope closely regulated by lamin A/C, which also colocalizes with Runx2 thus affecting its capacity as osteogenic transcription factor. In summary, these data clearly indicate that the presence of lamin A/C is necessary for normal bone turnover in vivo and that absence of lamin A/C induces low bone turnover osteopenia resembling the cellular changes of age-related bone loss. PMID:21547077

Evidence for a Role for Nanoporosity and Pyridinoline Content in Human Mild Osteogenesis Imperfecta.

PubMed

Paschalis, Eleftherios P; Gamsjaeger, Sonja; Fratzl-Zelman, Nadja; Roschger, Paul; Masic, Admir; Brozek, Wolfgang; Hassler, Norbert; Glorieux, Francis H; Rauch, Frank; Klaushofer, Klaus; Fratzl, Peter

2016-05-01

Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous connective tissue disorder characterized by bone fragility that arises from decreased bone mass and abnormalities in bone material quality. OI type I represents the milder form of the disease and according to the original Sillence classification is characterized by minimal skeletal deformities and near-normal stature. Raman microspectroscopy is a vibrational spectroscopic technique that allows the determination of bone material properties in bone biopsy blocks with a spatial resolution of ∼1 µm, as a function of tissue age. In the present study, we used Raman microspectroscopy to evaluate bone material quality in transiliac bone biopsies from children with a mild form of OI, either attributable to collagen haploinsufficiency OI type I (OI-Quant; n = 11) or aberrant collagen structure (OI-Qual; n = 5), as a function of tissue age, and compared it against the previously published values established in a cohort of biopsies from healthy children (n = 54, ages 1 to 23 years). The results indicated significant differences in bone material compositional characteristics between OI-Quant patients and healthy controls, whereas fewer were evident in the OI-Qual patients. Differences in both subgroups of OI compared with healthy children were evident for nanoporosity, mineral maturity/crystallinity as determined by maxima of the v1 PO4 Raman band, and pyridinoline (albeit in different direction) content. These alterations in bone material compositional properties most likely contribute to the bone fragility characterizing this disease. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Effects of Vitamin K2 on the Development of Osteopenia in Rats as the Models of Osteoporosis

PubMed Central

Takeda, Tsuyoshi; Sato, Yoshihiro

2006-01-01

Vitamin K2 is widely used for the treatment of osteoporosis in Japan. To understand the effects of vitamin K2 on bone mass and bone metabolism, we reviewed its effects on the development of osteopenia in rats, which characterizes models of osteoporosis. Vitamin K2 was found to attenuate the increase in bone resorption and/or maintain bone formation, reduce bone loss, protect against the loss of trabecular bone mass and its connectivity, and prevent the decrease in strength of the long bone in ovariectomized rats. However, combined treatment of bisphosphonates and vitamin K2 had an additive effect in preventing the deterioration of the trabecular bone architecture in ovariectomized rats, while the combined treatment of raloxifene and vitamin K2 improved the bone strength of the femoral neck. The use of vitamin K2 alone suppressed the increase in trabecular bone turnover and endocortical bone resorption, which attenuated the development of cancellous and cortical osteopenia in orchidectomized rats. In addition, vitamin K2 inhibited the decrease in bone formation in prednisolone-treated rats, thereby preventing cancellous and cortical osteopenia. In sciatic neurectomized rats, vitamin K2 suppressed endocortical bone resorption and stimulated bone formation, delaying the reduction of the trabecular thickness and retarding the development of cortical osteopenia. Vitamin K2 also prevented the acceleration of bone resorption and the reduction in bone formation in tail-suspended rats, which counteracted cancellous bone loss. Concomitant use of vitamin K2 with a bisphosphonate ameliorated the suppression of bone formation and more effectively prevented cancellous bone loss in tail-suspended rats. Vitamin K2 stimulated renal calcium reabsorption, retarded the increase in serum parathyroid hormone levels, and attenuated cortical bone loss primarily by suppressing bone resorption in calcium-deficient rats while maintaining the strength of the long bone in rats with magnesium deficiency. These findings suggest that vitamin K2 may not only stimulate bone formation, but may also suppress bone resorption. Thus, vitamin K2 could regulate bone metabolism in rats, which represented the various models of osteoporosis. However, the effects of vitamin K2 on bone mass and bone metabolism seem to be modest. PMID:16642543

Discovery, clinical development, and therapeutic uses of bisphosphonates.

PubMed

Licata, Angelo A

2005-04-01

To review the literature concerning the history, development, and therapeutic uses of bisphosphonates. English-language articles were identified through a search of MEDLINE (through December 2004) using the key word bisphosphonate. Reference lists of pivotal studies, reviews, and full prescribing information for the approved agents were also examined. Selected studies included those that discussed the discovery and initial applications of bisphosphonates, as well as their historical development, pharmacokinetic and pharmacodynamic properties, and current therapeutic uses. Bisphosphonates structurally resemble pyrophosphates (naturally occurring polyphosphates) and have demonstrated similar physicochemical effects to pyrophosphates. In addition, bisphosphonates reduce bone turnover and resist hydrolysis when administered orally. The information gained from initial work with etidronate generated a considerable scientific effort to design new and more effective bisphosphonates. The PCP moiety in the general bisphosphonate structure is essential for binding to hydroxyapatite and allows for a number of chemical variations by changing the 2 lateral side chains (designated R(1) and R(2)). The R(1) side chain determines binding affinity to hydroxyapatite, and the R(2) side chain determines antiresorptive potency. Accordingly, each bisphosphonate has its own characteristic profile of activity. The bisphosphonates reduce bone turnover, increase bone mass, and decrease fracture risk and therefore have a significant place in the management of skeletal disorders including osteoporosis, Paget's disease, bone metastases, osteogenesis imperfecta, and heterotopic ossification.

Box-modeling of bone and tooth phosphate oxygen isotope compositions as a function of environmental and physiological parameters.

PubMed

Langlois, C; Simon, L; Lécuyer, Ch

2003-12-01

A time-dependent box model is developed to calculate oxygen isotope compositions of bone phosphate as a function of environmental and physiological parameters. Input and output oxygen fluxes related to body water and bone reservoirs are scaled to the body mass. The oxygen fluxes are evaluated by stoichiometric scaling to the calcium accretion and resorption rates, assuming a pure hydroxylapatite composition for the bone and tooth mineral. The model shows how the diet composition, body mass, ambient relative humidity and temperature may control the oxygen isotope composition of bone phosphate. The model also computes how bones and teeth record short-term variations in relative humidity, air temperature and delta18O of drinking water, depending on body mass. The documented diversity of oxygen isotope fractionation equations for vertebrates is accounted for by our model when for each specimen the physiological and diet parameters are adjusted in the living range of environmental conditions.

Bone mass improved effect of icariin for postmenopausal osteoporosis in ovariectomy-induced rats: a meta-analysis and systematic review.

PubMed

Xu, Jin-Hai; Yao, Min; Ye, Jie; Wang, Guo-Dong; Wang, Jing; Cui, Xue-Jun; Mo, Wen

2016-10-01

Ovariectomy (OVX)-induced rats are the most frequently used animal model to research postmenopausal osteoporosis. Our objective was to summarize and critically assess the bone mass improved effect of icariin (ICA) for treatment of postmenopausal osteoporosis in an OVX-induced rat model. The PUBMED, EMBASE, and Chinese databases were searched from their inception date to February 2015. Two reviewers independently selected animal studies that evaluated the bone mass improved effect of ICA compared with control in OVX-induced rats. Extracted data were analyzed by RevMan statistical software, and the methodological quality of each study was assessed. Seven studies with adequate randomization were included in the systematic review. Overall, ICA seemed to significantly improve bone mass as assessed using the bone mineral density (seven studies, n = 169; weighted mean difference, 0.02; 95% CI, 0.01-0.02, I = 77%, P < 0.00001) using a random-effects model. There is no significant difference between ICA and estrogen (E) (six studies, n = 128; weighted mean difference, 0.00; 95% CI, -0.00 to 0.01, I = 54%, P = 0.01). Bone mass improved effect of ICA for postmenopausal osteoporosis was observed in OVX-induced rats. Assessment of the methodological quality of studies involving OVX-induced animal models is required, and good methodological quality should be valued in systematic reviews of animal studies.

Alterations in markers of bone metabolism and adipokines following a 3-month lifestyle intervention induced weight loss in obese prepubertal children.

PubMed

Gajewska, J; Weker, H; Ambroszkiewicz, J; Szamotulska, K; Chełchowska, M; Franek, E; Laskowska-Klita, T

2013-08-01

Adipokines may influence bone metabolism in children, but this phenomenon is not well understood. Therefore, we studied the relationships between bone markers and adipokines during weight loss in obese children. We determined serum leptin, soluble leptin receptor (sOB-R), adiponectin, BALP (bone alkaline phosphatase), CTX-I (C-terminal telopeptide of type I collagen), body composition and bone mineral density (by dual-energy X-ray absorptiometry) in 100 obese prepubertal children before and after 3 months of lifestyle intervention (low-energy diet, physical activity). The control group consisted of 70 non-obese children. Obese children had higher BALP activity by about 20% (p<0.001) and similar value of CTX-I compared with non-obese children. After weight loss (-0.96 BMI-SDS mean change), the BALP value in obese patients decreased (p<0.001), whereas CTX-I concentration was unchanged. Changes in BALP were positively correlated with changes in BMI (Body Mass Index) (r=0.352, p<0.001), but not associated with adipokine levels. Trend analysis using SDS-BMI subgroups showed that greater reduction of body mass was associated with a greater decrease of BALP (p=0.035) and leptin values (p<0.001), as well as a greater increase of sOB-R (p<0.003). Obesity during the prepubertal period is associated with an alteration in the adipokines profile and greater whole-body bone mass as a result of increased bone formation rather than reduced bone resorption. Changes in bone metabolism during lifestyle intervention seem to be related to weight loss but not to changes in adipokines. Further studies should elucidate the influence of long-term therapy on bone mass in childhood. © Georg Thieme Verlag KG Stuttgart · New York.

The Relationship Between Lower Limb Bone and Muscle in Military Recruits, Response to Physical Training, and Influence of Smoking Status

PubMed Central

Puthucheary, Zudin; Kordi, Mehdi; Rawal, Jai; Eleftheriou, Kyriacos I.; Payne, John; Montgomery, Hugh E.

2015-01-01

The relationship between bone and skeletal muscle mass may be affected by physical training. No studies have prospectively examined the bone and skeletal muscle responses to a short controlled exercise-training programme. We hypothesised that a short exercise-training period would affect muscle and bone mass together. Methods: Femoral bone and Rectus femoris Volumes (RFVOL) were determined by magnetic resonance imaging in 215 healthy army recruits, and bone mineral density (BMD) by Dual X-Ray Absorptiometry (DXA) and repeated after 12 weeks of regulated physical training. Results: Pre-training, RFVOL was smaller in smokers than non-smokers (100.9 ± 20.2 vs. 108.7 ± 24.5, p = 0.018; 96.2 ± 16.9 vs. 104.8 ± 21.3, p = 0.002 for dominant/non-dominant limbs), although increases in RFVOL with training (of 14.2 ± 14.5% and 13.2 ± 15.6%] respectively, p < 0.001) were independent of prior smoking status. Pre-training RFVOL was related to bone cortical volume (r2 = 0.21 and 0.30, p < 0.001 for dominant and non-dominant legs), and specifically to periosteal (r2 = 0.21 and 0.23, p < 0.001) volume. Pre-training dominant RFVOL was independently associated with Total Hip BMD (p < 0.001). Training-related increases in RFVOL and bone volumes were related. Whilst smokers demonstrated lower muscle mass than non-smokers, differences were abolished with training. Training-related increases in muscle mass were related to increases in periosteal bone volume in both dominant and non-dominant legs. PMID:25792356

[Therapeutic agents for disorders of bone and calcium metabolism--Parathyroid hormone in weekly subcutaneous injection].

PubMed

Uzawa, Toyonobu

2007-01-01

The parathyroid hormone (PTH) that is marketed outside Japan is for daily administration. It has been proven to increase bone mass and prevent fractures, and the effects are very strong. However, data suggest that daily administration of PTH increases bone resorption. By contrast, weekly administration of PTH, which is being developed in Japan, actually decreases bone resorption, and data suggest that this regimen maintains a good balance between bone formation (predominant) and bone resorption. Furthermore, it has been reported that weekly administration of PTH increases bone mass as much as every day administration of PTH, and as such, weekly administration of PTH has the potential to be a useful regimen with characteristics that are different from those of daily administration of PTH.

Dietary isoflavones act on bone marrow osteoprogenitor cells and stimulate ovary development before influencing bone mass in pre-pubertal piglets.

PubMed

De Wilde, Anne; Maria Rassi, Claudia; Cournot, Giulia; Colin, Colette; Lacroix, Herminie C; Chaumaz, Gilles; Coxam, Veronique; Bennetau-Pelissero, Catherine; Pointillart, Alain; Lieberherr, Michele

2007-07-01

Food containing soybeans provide isoflavone phytoestrogens that can preserve bone mass in postmenopausal women, and prevent bone loss in ovariectomized rats. But their effects on bone remain unclear, particularly on bone formation during growth. Two groups of eight pre-pubertal piglets were fed a basal or an isoflavone-enriched (S800) diet for 6 weeks. The S800 diet contained 800 mg SoyLifetrade mark/kg, providing 2.8 mg isoflavones/kg body weight/day. Several bones were collected and tested for bone strength and density. Bone marrow was collected from humeri together with blood samples and genital tracts. The plasma concentrations of isoflavones were increased in the pigs fed S800, but growth rate, body weight, plasma bone markers, bone mineral density, and strength were all unaffected. In contrast, cultured stromal cells from S800 pigs had more alkaline phosphatase-rich cells and mineralized nodules, secreted more osteocalcin, osteoprotegerin and RANK-L, synthesized more osteoprotegerin, and RANK-L. Cultured mononucleated nonadherent bone marrow cells from S800 pigs developed fewer tartrate-resistant acid phosphatase mononucleated cells (osteoclast progenitors) when cultured with 1,25(OH)(2)D(3), and resorbed a smaller area of dentine slices. Freshly isolated bone marrow osteoclast progenitors from S800 pigs had more caspase-3 cleavage activity, and synthesized less RANK. Both osteoclast and osteoblast progenitors had ERalpha and ERbeta, whose syntheses were stimulated by the S800 diet. The S800 piglets had heavier ovaries with more follicles, but their uterus weight was unaffected. We conclude that dietary isoflavones have no detectable effect on the bone mass of growing female piglets, but act on bone marrow osteoprogenitors via ERs--mainly ERbeta, and stimulate ovary development.

Partial Loss of Anabolic Effect of Prostaglandin E(sub 2) on Bone After Its Withdrawal in Rats

NASA Technical Reports Server (NTRS)

Ke, H. Z.; Li, X. J.; Jee, W. S. S.

1991-01-01

The object of this study was to determine the fate of PGE(sub 2)-induced new bone mass after withdrawal of PGE(sub 2) administration. Seven-month-old male Sprague-Dawley rats were given subcutaneous injections of 1, 3, and 6 mg PGE(sub 2),/kg/d for 60 days and then withdrawn for 60 and 120 days. Histomorphometric analyses were performed on double fluorescent labeled undecalcified proximal tibial bone specimens. After 60 days of PGE(sub 2) treatment, a new steady state of increased trabecular bone area (+67% and +81% with 3 and 6 mg PGE(sub 2)/kg/d) from woven bone and stimulated lamellar bone formation, elevated bone turnover, and shortened remodeling periods were achieved compared to age-matched controls. In contrast, after 60 and 120 days withdrawal of PGE(sub 2), a new steady state characterized by less trabecular bone area (+40% to +60% of controls with 3 and 6 mg/kg/d doses), normal lamellar bone formation, no woven bone formation from controls, and eroded surface greater than those seen in controls and previously in 60-day PGE(sub 2) treated rats. The decrease in new bone mass after withdrawal of PGE(sub 2), was due to a further elevation of bone resorption above that induced by the PGE(sub 2) treatment and a reduction in PGE(sub 2), stimulated bone formation activities. Although there is more trabecular bone than in controls after 120 days withdrawal of PGE(sub 2), we postulate that the skeletal adaptation to mechanical usage will eventually reduce the bone mass to control levels. Thus, it is conservative to conclude that the anabolic effect of PGE(sub 2) was dependent upon continuous daily administration of PGE(sub 2) in these older rats.

Partial Loss of Anabolic Effect of Prostaglandin E2 on Bone After Its Withdrawal in Rats

NASA Technical Reports Server (NTRS)

Ke, H. Z.; Li, X. J.; Jee, Webster S. S.

1991-01-01

The object of this study was to determine the fate of PGE(sub 2)-induced new bone mass after withdrawal of PGE(sub 2) administration. Seven-month-old male Sprague-Dawley rats were given subcutaneous injections of 1, 3, and 6 mg PGE(sub 2)/kg/d for 60 days and then withdrawn for 60 and 120 days. Histomorphometric analyses were performed on double fluorescent labeled undecalcified proximal tibial bone specimens. After 60 days of PGE(sub 2) treatment, a new steady state of increased trabecular bone area (+67% and +81% with 3 and 6 mg PGE(sub 2)/kg/d) from woven bone and stimulated lamellar bone formation, elevated bone turnover, and shortened remodeling periods were achieved compared to age-matched controls. In contrast, after 60 and 120 days withdrawal of PGE(sub 2), a new steady state characterized by less trabecular bone area (+40% to +60% of controls with 3 and 6 mg/kg/d doses), normal lamellar bone formation, no woven bone formation from controls, and eroded surface greater than those seen in controls and previously in 60-day PGE(sub 2) treated rats. The decrease in new bone mass after withdrawal of PGE(sub 2) was due to a further elevation of bone resorption above that induced by the PGE(sub 2) treatment and a reduction in PGE(sub 2) stimulated bone formation activities. Although there is more trabecular bone than in controls after 120 days' withdrawal of PGE(sub 2), we postulate that the skeletal adaptation to mechanical usage will eventually reduce the bone mass to control levels. Thus, it is conservative to conclude that the anabolic effect of PGE(sub 2) was dependent upon continuous daily administration of PGE(sub 2) in these older rats.

A link between central kynurenine metabolism and bone strength in rats with chronic kidney disease

PubMed Central

Pawlak, Krystyna; Oksztulska-Kolanek, Ewa; Domaniewski, Tomasz; Znorko, Beata; Karbowska, Malgorzata; Citkowska, Aleksandra; Rogalska, Joanna; Roszczenko, Alicja; Brzoska, Malgorzata M.; Pawlak, Dariusz

2017-01-01

Background Disturbances in mineral and bone metabolism represent one of the most complex complications of chronic kidney disease (CKD). Serotonin, a monoamine synthesized from tryptophan, may play a potential role in bone metabolism. Brain-derived serotonin exerts a positive effect on the bone structure by limiting bone resorption and enhancing bone formation. Tryptophan is the precursor not only to the serotonin but also and primarily to kynurenine metabolites. The ultimate aim of the present study was to determine the association between central kynurenine metabolism and biomechanical as well as geometrical properties of bone in the experimental model of the early stage of CKD. Methods Thirty-three Wistar rats were randomly divided into two groups (sham-operated and subtotal nephrectomized animals). Three months after surgery, serum samples were obtained for the determination of biochemical parameters, bone turnover biomarkers, and kynurenine pathway metabolites; tibias were collected for bone biomechanical, bone geometrical, and bone mass density analysis; brains were removed and divided into five regions for the determination of kynurenine pathway metabolites. Results Subtotal nephrectomized rats presented higher serum concentrations of creatinine, urea nitrogen, and parathyroid hormone, and developed hypocalcemia. Several biomechanical and geometrical parameters were significantly elevated in rats with experimentally induced CKD. Subtotal nephrectomized rats presented significantly higher kynurenine concentrations and kynurenine/tryptophan ratio and significantly lower tryptophan levels in all studied parts of the brain. Kynurenine in the frontal cortex and tryptophan in the hypothalamus and striatum correlated positively with the main parameters of bone biomechanics and bone geometry. Discussion In addition to the complex mineral, hormone, and metabolite changes, intensified central kynurenine turnover may play an important role in the development of bone changes in the course of CKD. PMID:28439468

Racial differences in cortical bone and their relationship to biochemical variables in black and white children in the early stages of puberty

PubMed Central

Warden, Stuart J.; Hill, Kathleen M.; Ferira, Ashley J.; Laing, Emma M.; Martin, Berdine R.; Hausman, Dorothy B.; Weaver, Connie M.; Peacock, Munro; Lewis, Richard D.

2014-01-01

Introduction Racial differences in bone structure likely have roots in childhood as bone size develops predominantly during growth. This study aimed to compare cortical bone health within the tibial diaphysis of black and white children in the early stages of puberty, and explore the contributions of biochemical variables in explaining racial variation in cortical bone properties. Methods A cross-sectional study was performed comparing peripheral quantitative computed tomography-derived cortical bone measures of the tibial diaphysis and biochemical variables in 314 participants (n=155 males; n=164 blacks) in the early stages of puberty. Results Blacks had greater cortical volumetric bone mineral density, mass and size compared to whites (all p<0.01), contributing to blacks having 17.0% greater tibial strength (polar strength-strain index [SSIP]) (p<0.001). Turnover markers indicated blacks had higher bone formation (osteocalcin [OC] and bone specific alkaline phosphatase) and lower bone resorption (N-terminal telopeptide) than whites (all p<0.01). Blacks also had lower 25-hydroxyvitamin D [25(OH)D], and higher 1,25-dihydroxyvitamin D [1,25(OH)2D] and parathyroid hormone (PTH) (all p<0.05). There were no correlations between tibial bone properties, and 25(OH)D and PTH in whites (all p≥0.10); however, SSIP was negatively and positively correlated with 25(OH)D and PTH in blacks, respectively (all p≤0.02). Variation in bone cross-sectional area and SSIP attributable to race was partially explained by tibial length, 25(OH)D/PTH and OC. Conclusions Divergence in tibial cortical bone properties between blacks and whites is established by the early stages of puberty with the enhanced cortical bone properties in black children possibly being explained by higher PTH and OC. PMID:23093348

Solitary Bone Plasmacytoma Progressing into Retroperitoneal Plasma Cell Myeloma with No Related End Organ or Tissue Impairment: A Case Report and Review of the Literature

PubMed Central

Tikku, Gargi; Jain, Monica; Mridha, Asit; Grover, Rajesh

2014-01-01

Solitary bone plasmacytomas and plasma cell myeloma are clonal proliferations of plasma cells. Many patients with solitary bone plasmacytomas develop plasma cell myeloma on follow-up. We present a case of a 70-year-old man who presented with fracture and a lytic lesion in the subtrochanteric region of the left femur and was assigned a diagnosis of solitary bone plasmacytoma. He received local curative radiotherapy. However, 4 months later his serum M protein and β2-microglobulin levels increased to 2.31 g/dL and 5.965 mg/L, respectively. He complained of abdominal fullness and constipation. Ultrasound and non-contrast CT imaging revealed multiple retroperitoneal masses. Colonoscopic examination was normal. Biopsy of the a retroperitoneal mass confirmed it to be a plasmacytoma. Repeat hemogram, blood urea, serum creatinine, skeletal survey, and bone marrow examination revealed no abnormalities. This is an unusual presentation of plasma cell myeloma, which manifested as multiple huge extramedullary retroperitoneal masses and arose from a solitary bone plasmacytoma, without related end organ or tissue impairment and bone marrow plasmacytosis. The patient succumbed to his disease 8 months after the appearance of the retroperitoneal masses. This case highlights the importance of close monitoring of patients diagnosed with solitary bone plasmacytoma with increased serum M protein and serum β2-microglobulin levels, so that early therapy can be instituted to prevent conversion to plasma cell myeloma. PMID:25330522

IMPACT OF DEFICIENT NUTRITION IN BONE MASS AFTER BARIATRIC SURGERY.

PubMed

Costa, Tatiana Munhoz da Rocha Lemos; Paganoto, Mariana; Radominski, Rosana Bento; Borba, Victoria Zeghbi Cochenski

2016-03-01

Essential nutrients are considered for the prevention of the bone loss that occurs after bariatric surgery. Evaluate nutrients involved in bone metabolism, and relate to serum concentrations of calcium, vitamin D, and parathyroid hormone, and the use of supplements and sun exposure on the bone mass of patients who had undergone gastric bypass surgery. An observational study, with patients who had undergone the surgery 12 or more months previously, operated group (OG), compared to a control group (CG). Were included 56 in OG and 27 in the CG. The mean age was 36.4±8.5 years. The individuals in the OG, compared to CG, consumed inadequate amounts of protein and daily calcium. The OG had a higher prevalence of low sun exposure, lower levels of 25OH Vitamin D (21.3±10.9 vs. 32.1±11.8 ng/dl), and increased serum levels of parathyroid hormone (68.1±32.9 vs. 39.9±11.9 pg/ml, p<0.001). Secondary hyperparathyroidism was present only in the OG (41.7%). The mean lumbar spine bone mineral density was lower in the OG. Four individuals from the OG had low bone mineral density for chronological age, and no one from the CG. The dietary components that affect bone mass in patients undergoing bariatric surgery were inadequate. The supplementation was insufficient and the sun exposure was low. These changes were accompanied by secondary hyperparathyroidism and a high prevalence of low bone mass in lumbar spine in these subjects.

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.

Maintaining Restored Bone with Bisphoshonate in the Ovariectomized Rat Skeleton: Dynamic Histomorphometry of Changes in Bone Mass

NASA Technical Reports Server (NTRS)

Jee, W. S. S.; Tang, L.; Ke, H. Z.; Setterberg, R. B.; Kimmel, D. B.

1993-01-01

This experiment contains the crucial data for the Lose, Restore and Maintain (LRM) concept, a practical approach for reversing existing osteoporosis. The LRM concept uses ovariectomy (ox) to lose bone, an anabolic agent to restore bone mass and then switches to an anti-resorptive agent to maintain bone mass. We ox'd or sham-ox'd rats for 150 days (Loss Phase), treated them with 6 mg PGE2/kg/d for 75 days to restore lost cancellous bone mass (Restore Phase) and then stopped PGE2 treatment and began treatment with 1 or 5 micro-g/kg Risedronate, a bisphosphonate twice a week for 60 days (Maintain Phase). During the Loss Phase, cancellous bone volumes of the proximal tibial metaphysis (PTM) in the ox'd rat fell to 19% of initial controls. During the Restore Phase, the PTM bone volume in ox'd rats doubled. However, when PGE2 treatment was stopped, the PGE2-induced cancellous bone disappeared. In contrast, 5 micro-g of Risedronate inhibited the bone loss and maintained it at the PGE2 treatment level. The key dynamic histomorphometry value for the restore (R) and maintenance (M) phases was the ratio of bone formation to resorption rates. The ratio was elevated to 5.8 in the R phase and depressed to 0.4 for no and 1 micro-g Risedronate treated M phase and to a ratio of near unity of 1.1 for the 5 micro-g Risedronate treatment. These findings indicate that we were successful in maintaining the new PTM bone induced by PGE2 after discontinuing PGE2 by administering enough Risedronate, a resorption inhibitor. We concluded that the LRM concept is correct and such an approach should be considered when employing anabolic agents or growth factors in the treatment of osteoporosis. Continued use of an anabolic agent may not be appropriate because of cost, potential adverse side effects and a loss of efficacy.

Maintaining Restored Bone with Bisphosphonate in the Ovariectomized Rat Skeleton: Dynamic Histomorphometry of Changes in Bone Mass

NASA Technical Reports Server (NTRS)

Jee, W. S. S.; Tang, L.; Ke, H. Z.; Setterberg, R. B.; Kimmel, D. B.

1993-01-01

This experiment contains the crucial data for the Lose, Restore and Maintain (LRM) concept, a practical approach for reversing existing osteoporosis. The LRM concept uses ovariectomy (ox) to lose bone, an anabolic agent to restore bone mass and then switches to an antiresorptive agent to maintain bone mass. We ox'd or sham-ox'd rats for 150 days (Loss Phase), treated them with 6 mg PGE(sub 2)kg/d for 75 days to restore lost cancellous bone mass (Restore Phase) and then stopped PGE(sub 2) treatment and began treatment with 1 or 5 micrograms/kg Risedronate, a bisphosphonate twice a week for 60 days (Maintain Phase). During the Loss Phase, cancellous bone volumes of the Proximal Tibial Metaphysis (PTM) in the ox'd rat fell to 19% of initial controls. During the Restore Phase, the PTM bone volume in ox'd rats doubled. However, when PGE(sub 2) treatment was stopped, the PGE(sub 2)-induced cancellous bone disappeared. In contrast, 5 miligrams of Risedronate inhibited the bone loss and maintained it at the PGE(sub 2) treatment level. The key dynamic histomorphometry value for the Restore (R) and Maintenance (M) phases was the ratio of bone formation to resorption rates. The ratio was elevated to 5.8 in the R phase and depressed to 0.4 for no and 1 miligram Risedronate treated M phase and to a ratio of near unity of 1.1 for the 5miligrams Risedronate treatment. These findings indicate that we were successful in maintaining the new PTM bone induced by PGE(sub 2) after discontinuing PGE(sub 2) by administering enough Risedronate, a resorption inhibitor. We concluded that the LRM concept is correct and such an approach should be considered when employing anabolic agents or growth factors in the treatment of osteoporosis. Continued use of an anabolic agent may not be appropriate because of cost, potential adverse side effects and a loss of efficacy.

Material heterogeneity in cancellous bone promotes deformation recovery after mechanical failure

PubMed Central

Torres, Ashley M.; Matheny, Jonathan B.; Keaveny, Tony M.; Taylor, David; Rimnac, Clare M.; Hernandez, Christopher J.

2016-01-01

Many natural structures use a foam core and solid outer shell to achieve high strength and stiffness with relatively small amounts of mass. Biological foams, however, must also resist crack growth. The process of crack propagation within the struts of a foam is not well understood and is complicated by the foam microstructure. We demonstrate that in cancellous bone, the foam-like component of whole bones, damage propagation during cyclic loading is dictated not by local tissue stresses but by heterogeneity of material properties associated with increased ductility of strut surfaces. The increase in surface ductility is unexpected because it is the opposite pattern generated by surface treatments to increase fatigue life in man-made materials, which often result in reduced surface ductility. We show that the more ductile surfaces of cancellous bone are a result of reduced accumulation of advanced glycation end products compared with the strut interior. Damage is therefore likely to accumulate in strut centers making cancellous bone more tolerant of stress concentrations at strut surfaces. Hence, the structure is able to recover more deformation after failure and return to a closer approximation of its original shape. Increased recovery of deformation is a passive mechanism seen in biology for setting a broken bone that allows for a better approximation of initial shape during healing processes and is likely the most important mechanical function. Our findings suggest a previously unidentified biomimetic design strategy in which tissue level material heterogeneity in foams can be used to improve deformation recovery after failure. PMID:26929343

Glenoid bone grafting in primary reverse total shoulder arthroplasty.

PubMed

Ernstbrunner, Lukas; Werthel, Jean-David; Wagner, Eric; Hatta, Taku; Sperling, John W; Cofield, Robert H

2017-08-01

Severe glenoid bone loss remains a challenge in patients requiring shoulder arthroplasty and may necessitate glenoid bone grafting. The purpose of this study was to determine results, complications, and rates of failure of glenoid bone grafting in primary reverse shoulder arthroplasty. Forty-one shoulders that underwent primary reverse arthroplasty between 2006 and 2013 with a minimum follow-up of 2 years (mean, 2.8 years; range, 2-6 years) were reviewed. Thirty-four (83%) received corticocancellous grafts and 7 (17%) structural grafts. Active range of motion and pain levels were significantly improved (P < .001), with mean American Shoulder and Elbow Surgeons score of 77, Simple Shoulder Test score of 9, and patient satisfaction of 93% at the most recent follow-up. Preoperative severe glenoid erosion and increasing body mass index were significantly associated with worse American Shoulder and Elbow Surgeons scores (P = .04). On radiographic evaluation, 7 patients (18%) had grade 1 or grade 2 glenoid lucency. Glenoid bone graft incorporation was observed in 31 patients (78%). Twelve patients (30%) suffered from grade 1 or grade 2 scapular notching. All of the patients with structural grafts showed graft incorporation and no signs of glenoid lucency. Although glenoid lucency, glenoid graft resorption, and scapular notching were present at short-term to midterm follow-up, none of the patients needed revision surgery. Primary reverse shoulder arthroplasty with glenoid reconstruction using bone graft relieved pain and restored shoulder function and stability. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

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.

Naringin ameliorates bone loss induced by sciatic neurectomy and increases Semaphorin 3A expression in denervated bone.

PubMed

Ma, Xinlong; Lv, Jianwei; Sun, Xiaolei; Ma, Jianxiong; Xing, Guosheng; Wang, Ying; Sun, Lei; Wang, Jianbao; Li, Fengbo; Li, Yanjun; Zhao, Zhihu

2016-04-25

Naringin maintains bone mass in various osteoporosis models, while its effect on bone in disuse osteoporosis has not been reported. The present study explores whether naringin can prevent disuse osteoporosis induced by unilateral sciatic neurectomy (USN) and whether the Semaphorin 3A-induced Wnt/β-catenin signalling pathway is involved in the osteoprotection of naringin. Naringin dose-dependently prevented the deterioration of bone mineral density (BMD), trabecular structure and biomechanical strength in femur due to USN. Naringin increased bone formation but inhibited resorption, as indicated by bone-turnover markers in blood and urine and the histological staining of Osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) in femur. Semaphorin 3A (Sema3A) and active β-catenin protein decreased after USN and could be restored by naringin to the levels of the sham-operated rats. In addition, naringin in vitro promoted the differentiation of osteoblasts and inhibited osteoclastic differentiation. Our studies suggest that the down-regulation of Sema3A and the subsequent inactivation of Wnt/β-catenin signalling may be some of the mechanisms involved in USN-induced osteoporosis. Naringin could increase the expression of Sema3A and the activation of Wnt/β-catenin signalling to prevent disuse osteoporosis induced by denervation. Thus, naringin functions in bone maintenance and could be a promising therapeutic alternative in preventing disuse osteoporosis.

Naringin ameliorates bone loss induced by sciatic neurectomy and increases Semaphorin 3A expression in denervated bone

PubMed Central

Ma, Xinlong; Lv, Jianwei; Sun, Xiaolei; Ma, Jianxiong; Xing, Guosheng; Wang, Ying; Sun, Lei; Wang, Jianbao; Li, Fengbo; Li, Yanjun; Zhao, Zhihu

2016-01-01

Naringin maintains bone mass in various osteoporosis models, while its effect on bone in disuse osteoporosis has not been reported. The present study explores whether naringin can prevent disuse osteoporosis induced by unilateral sciatic neurectomy (USN) and whether the Semaphorin 3A-induced Wnt/β-catenin signalling pathway is involved in the osteoprotection of naringin. Naringin dose-dependently prevented the deterioration of bone mineral density (BMD), trabecular structure and biomechanical strength in femur due to USN. Naringin increased bone formation but inhibited resorption, as indicated by bone-turnover markers in blood and urine and the histological staining of Osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) in femur. Semaphorin 3A (Sema3A) and active β-catenin protein decreased after USN and could be restored by naringin to the levels of the sham-operated rats. In addition, naringin in vitro promoted the differentiation of osteoblasts and inhibited osteoclastic differentiation. Our studies suggest that the down-regulation of Sema3A and the subsequent inactivation of Wnt/β-catenin signalling may be some of the mechanisms involved in USN-induced osteoporosis. Naringin could increase the expression of Sema3A and the activation of Wnt/β-catenin signalling to prevent disuse osteoporosis induced by denervation. Thus, naringin functions in bone maintenance and could be a promising therapeutic alternative in preventing disuse osteoporosis. PMID:27109829

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.

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.

Deficiency of Retinaldehyde Dehydrogenase 1 Induces BMP2 and Increases Bone Mass In Vivo

PubMed Central

Nallamshetty, Shriram; Wang, Hong; Rhee, Eun-Jung; Kiefer, Florian W.; Brown, Jonathan D.; Lotinun, Sutada; Le, Phuong; Baron, Roland; Rosen, Clifford J.; Plutzky, Jorge

2013-01-01

The effects of retinoids, the structural derivatives of vitamin A (retinol), on post-natal peak bone density acquisition and skeletal remodeling are complex and compartment specific. Emerging data indicates that retinoids, such as all trans retinoic acid (ATRA) and its precursor all trans retinaldehyde (Rald), exhibit distinct and divergent transcriptional effects in metabolism. Despite these observations, the role of enzymes that control retinoid metabolism in bone remains undefined. In this study, we examined the skeletal phenotype of mice deficient in retinaldehyde dehydrogenase 1 (Aldh1a1), the enzyme responsible for converting Rald to ATRA in adult animals. Bone densitometry and micro-computed tomography (µCT) demonstrated that Aldh1a1-deficient (Aldh1a1−/−) female mice had higher trabecular and cortical bone mass compared to age and sex-matched control C57Bl/6 wild type (WT) mice at multiple time points. Histomorphometry confirmed increased cortical bone thickness and demonstrated significantly higher bone marrow adiposity in Aldh1a1−/− mice. In serum assays, Aldh1a1−/− mice also had higher serum IGF-1 levels. In vitro, primary Aldh1a1−/− mesenchymal stem cells (MSCs) expressed significantly higher levels of bone morphogenetic protein 2 (BMP2) and demonstrated enhanced osteoblastogenesis and adipogenesis versus WT MSCs. BMP2 was also expressed at higher levels in the femurs and tibias of Aldh1a1−/− mice with accompanying induction of BMP2-regulated responses, including expression of Runx2 and alkaline phosphatase, and Smad phosphorylation. In vitro, Rald, which accumulates in Aldh1a1−/− mice, potently induced BMP2 in WT MSCs in a retinoic acid receptor (RAR)-dependent manner, suggesting that Rald is involved in the BMP2 increases seen in Aldh1a1 deficiency in vivo. Collectively, these data implicate Aldh1a1 as a novel determinant of cortical bone density and marrow adiposity in the skeleton in vivo through modulation of BMP signaling. PMID:23951127

Phenotypic integration among trabecular and cortical bone traits establishes mechanical functionality of inbred mouse vertebrae.

PubMed

Tommasini, Steven M; Hu, Bin; Nadeau, Joseph H; Jepsen, Karl J

2009-04-01

Conventional approaches to identifying quantitative trait loci (QTLs) regulating bone mass and fragility are limited because they examine cortical and trabecular traits independently. Prior work examining long bones from young adult mice and humans indicated that skeletal traits are functionally related and that compensatory interactions among morphological and compositional traits are critical for establishing mechanical function. However, it is not known whether trait covariation (i.e., phenotypic integration) also is important for establishing mechanical function in more complex, corticocancellous structures. Covariation among trabecular, cortical, and compositional bone traits was examined in the context of mechanical functionality for L(4) vertebral bodies across a panel of 16-wk-old female AXB/BXA recombinant inbred (RI) mouse strains. The unique pattern of randomization of the A/J and C57BL/6J (B6) genome among the RI panel provides a powerful tool that can be used to measure the tendency for different traits to covary and to study the biology of complex traits. We tested the hypothesis that genetic variants affecting vertebral size and mass are buffered by changes in the relative amounts of cortical and trabecular bone and overall mineralization. Despite inheriting random sets of A/J and B6 genomes, the RI strains inherited nonrandom sets of cortical and trabecular bone traits. Path analysis, which is a multivariate analysis that shows how multiple traits covary simultaneously when confounding variables like body size are taken into consideration, showed that RI strains that tended to have smaller vertebrae relative to body size achieved mechanical functionality by increasing mineralization and the relative amounts of cortical and trabecular bone. The interdependence among corticocancellous traits in the vertebral body indicated that variation in trabecular bone traits among inbred mouse strains, which is often thought to arise from genetic factors, is also determined in part by the adaptive response to variation in traits describing the cortical shell. The covariation among corticocancellous traits has important implications for genetic analyses and for interpreting the response of bone to genetic and environmental perturbations.

Serum myostatin in central south Chinese postmenopausal women: Relationship with body composition, lipids and bone mineral density.

PubMed

Ma, Yulin; Li, Xianping; Zhang, Hongbin; Ou, Yangna; Zhang, Zhimin; Li, Shuang; Wu, Feng; Sheng, Zhifeng; Liao, Eryuan

2016-08-01

Previous data suggest that myostatin has direct effects on the proliferation and differentiation of osteoprogenitor cells. The relationships between serum myostatin, body composition lipids and bone mineral density in postmenopausal women remain unclear. The aim of this study is to elucidate the relationships between serum myostatin, body composition, lipids and bone mineral density in central south Chinese postmenopausal women. A cross-sectional study was conducted in 175 healthy postmenopausal women, aged 51-75 years old. Bone mineral density (BMD) and body composition were measured by double energy X-ray absorptiometry (DXA). Serum myostatin, 25-dihydroxyvitamin D(25OH-D), parathyroid hormone (PTH), bone alkaline phosphatase (BAP) and carboxy-terminal telopeptide of type I collagen (CTX) were measured by enzyme-linked immunoabsorbent assay (ELISA). In contrast to the osteoporotic women, the women without osteoporosis had higher BMI, fat mass and lean mass (P<0.01). The osteoporotic women were older than women without osteoporosis (P<0.01). There were no differences between two groups with regard to serum BAP, CTX, (25OH-D), PTH, lipids and myostatin after adjusted by age. BMD at each site was positively correlated with age at menopause, fat mass and lean mass, and also negatively correlated with age and serum BAP. Serum myostatin was positively correlated with tryglicerides, not correlated with either body composition or BMD at each site. Our data indicated that serum myostatin concentration did not correlate with muscle and bone mass. Further studies are needed to demonstrate the role of myostatin in regulating the bone metabolism.

[Effect of different bone cement dispersion types in the treatment of osteoporotic vertebral compression fracture].

PubMed

Zhao, Yong-Sheng; Li, Qiang; Li, Qiang; Zheng, Yan-Ping

2017-05-25

To observe different bone cement dispersion types of PVP, PKP and manipulative reduction PVP and their effects in the treatment of senile osteoporotic vertebral compression fractures and the bone cement leakage rate. The clinical data of patients with osteoporotic vertebral compression fractures who underwent unilateral vertebroplasty from January 2012 to January 2015 was retrospectively analyzed. Of them, 56 cases including 22 males and 34 females aged from 60 to 78 years old were treated by PVP operation; Fouty-eight cases including 17 males and 31 females aged from 61 to 79 years old were treated by PKP operation; Forty-three cases including 15 males and 28 females aged from 60 to 76 years old were treated by manipulative reduction PVP operation. AP and lateral DR films were taken after the operation; the vertebral bone cement diffusion district area and mass district area were calculated with AutoCAD graphics processing software by AP and lateral DR picture, then ratio(K) of average diffusion area and mass area were calculated, defining K<50% as mass type, 50%<=K<=100% as mixed type and K>100% as diffusion type. Different bone cement dispersion types of PVP, PKP and manipulative reduction PVP operation were analyzed. According to bone cement dispersion types, patients were divided into diffusion type, mixed type and mass type groups.Visual analogue scale (VAS), vertebral body compression rate, JOA score and bone cement leakage rate were observed. All patients were followed up for 12-24 months with an average of 17.2 months. There was significant difference in bone cement dispersion type among three groups ( P <0.05). The constituent ratio of diffusion type, mixed type and mass type in PVP operation was 46.43%, 35.71%, 17.86%, in PKP was 16.67%, 37.50% , 45.83%, and in manipulative reduction PVP was 37.21%, 44.19% and 18.60%, respectively. PVP operation and manipulative reduction PVP were mainly composed of diffusion type and mixed type, while PKP was mainly composed of mass type and mixed type. There was no significant difference in VAS score, JOA score and bone cement leakage rate among three groups. There was statistically significant difference in postoperative vertebral body compression rate among three bone cement dispersion types( P <0.05), postoperative vertebral body compression rate in diffusion type group at 24 h postoperatively and final follow-up was (17.31±5.06)% and(18.58±4.91)%, respectively. In mixed type group, it was(14.21±5.15)% and(14.59±5.07)%, respectively. In mass type group, it was(13.89±5.02)% and(14.28±4.94)%, respectively. Bone cement dispersion type is different in PVP, PKP and manipulative reduction PVP operation. The bone cement dispersion of mass type and mixed type to recovery of compressed vertebral body is better than diffusion type, and there is no obvious difference in clinical effect in different bone cement dispersion type early and middle term.

[The relationship between the parameters of mineral density of bone tissue and somatotype in women residing in the Republic of Karelia].

PubMed

Pashkova, I G; Gaivoronskiy, I V; Aleksina, L A; Kornev, M A

2014-01-01

Comprehensive anthropometric and densitometric study using the dual x-ray absorptiometry was conducted to determine the relationship between the mineral density of bone tissue and somatotype in 360 women aged 20 to 87 years, permanently residing in the Republic of Karelia. Significant direct correlation was detected between the somatotype and the amount of mineral substances in the vertebrae, bone mineral density and the area of the lumbar vertebrae. Bone mineral density level of the lumbar vertebrae was higher in women with europlastic and athletic somatotypes, which were characterized by high values of body mass and length, body muscle and fat mass. Low values of bone mineral density of vertebrae were identified in women belonging to subathletic, mesoplastic and stenoplastic somatotypes. The risk of developing osteopenia and osteoporosis is increased in women with low body muscle mass.

Evaluation of cortical bone mass, thickness and density by z-scores in osteopenic conditions and in relation to menopause and estrogen treatment

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

Meema, S.; Meema, H.E.

1982-08-01

Z-scores express, differences from normals in standard deviation units, and are particularly useful for comparison of changes where normal values are age- and sex-dependent. We determined z-scores for bone mineral mass, cortical thickness, and bone mineral density in the radius in various conditions and diseases in both sexes. In the males, z-scores were calculated for age, but in the females z-scores for menopausal status (years postmenopausal exclusive of years on estrogen treatment) were found to be more appropriate. With few exceptions, changes in a disease were of a similar order in both sexes. For bone minerals mass few mean z-scoresmore » were significantly increased, but diseases with significantly decreased mean z-scores were numerous. The usefulness of z-scores in diagnosis and study of metabolic bone disease is discussed.« less

Obesity is a concern for bone health with aging.

PubMed

Shapses, Sue A; Pop, L Claudia; Wang, Yang

2017-03-01

Accumulating evidence supports a complex relationship between adiposity and osteoporosis in overweight/obese individuals, with local interactions and endocrine regulation by adipose tissue on bone metabolism and fracture risk in elderly populations. This review was conducted to summarize existing evidence to test the hypothesis that obesity is a risk factor for bone health in aging individuals. Mechanisms by which obesity adversely affects bone health are believed to be multiple, such as an alteration of bone-regulating hormones, inflammation, oxidative stress, the endocannabinoid system, that affect bone cell metabolism are discussed. In addition, evidence on the effect of fat mass and distribution on bone mass and quality is reviewed together with findings relating energy and fat intake with bone health. In summary, studies indicate that the positive effects of body weight on bone mineral density cannot counteract the detrimental effects of obesity on bone quality. However, the exact mechanism underlying bone deterioration in the obese is not clear yet and further research is required to elucidate the effect of adipose depots on bone and fracture risk in the obese population. Copyright © 2017 Elsevier Inc. All rights reserved.

Obesity is a concern for bone health with aging

PubMed Central

Shapses, Sue A.; Pop, L. Claudia; Wang, Yang

2017-01-01

Accumulating evidence supports a complex relationship between adiposity and osteoporosis in overweight/obese individuals, with local interactions and endocrine regulation by adipose tissue on bone metabolism and fracture risk in elderly populations. This review was conducted to summarize existing evidence to test the hypothesis that obesity is a risk factor for bone health in aging individuals. Mechanisms by which obesity adversely affects bone health are believed to be multiple, such as an alteration of bone-regulating hormones, inflammation, oxidative stress, the endocannabinoid system, that affect bone cell metabolism are discussed. In addition, evidence on the effect of fat mass and distribution on bone mass and quality is reviewed together with findings relating energy and fat intake with bone health. In summary, studies indicate that the positive effects of body weight on bone mineral density cannot counteract the detrimental effects of obesity on bone quality. However, the exact mechanism underlying bone deterioration in the obese is not clear yet and further research is required to elucidate the effect of adipose depots on bone and fracture risk in the obese population. PMID:28385284

[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.

Effects of spaceflight on trabecular bone in rats

NASA Technical Reports Server (NTRS)

Jee, W. S. S.; Wronski, T. J.; Morey, E. R.; Kimmel, D. B.

1983-01-01

Alterations in trabecular bone were observed in growing male Wistar rats after 18.5 days of orbital flight on the COSMOS 1129 biosatellite. Spaceflight induced a decreased mass of mineralized tissue and an increased fat content of the bone marrow in the proximal tibial and humeral metaphyses. The osteoblast population appeared to decline immediately adjacent to the growth cartilage-metaphyseal junction, but osteoclast numbers were unchanged. These results suggested that bone formation may have been inhibited during spaceflight, but resorption remained constant. With the exception of trabecular bone mass in the proximal tibia, the observed skeletal changes returned to normal during a 29-day postflight period.

Prader-Willi Critical Region, a Non-Translated, Imprinted Central Regulator of Bone Mass: Possible Role in Skeletal Abnormalities in Prader-Willi Syndrome.

PubMed

Khor, Ee-Cheng; Fanshawe, Bruce; Qi, Yue; Zolotukhin, Sergei; Kulkarni, Rishikesh N; Enriquez, Ronaldo F; Purtell, Louise; Lee, Nicola J; Wee, Natalie K; Croucher, Peter I; Campbell, Lesley; Herzog, Herbert; Baldock, Paul A

2016-01-01

Prader-Willi Syndrome (PWS), a maternally imprinted disorder and leading cause of obesity, is characterised by insatiable appetite, poor muscle development, cognitive impairment, endocrine disturbance, short stature and osteoporosis. A number of causative loci have been located within the imprinted Prader-Willi Critical Region (PWCR), including a set of small non-translated nucleolar RNA's (snoRNA). Recently, micro-deletions in humans identified the snoRNA Snord116 as a critical contributor to the development of PWS exhibiting many of the classical symptoms of PWS. Here we show that loss of the PWCR which includes Snord116 in mice leads to a reduced bone mass phenotype, similar to that observed in humans. Consistent with reduced stature in PWS, PWCR KO mice showed delayed skeletal development, with shorter femurs and vertebrae, reduced bone size and mass in both sexes. The reduction in bone mass in PWCR KO mice was associated with deficiencies in cortical bone volume and cortical mineral apposition rate, with no change in cancellous bone. Importantly, while the length difference was corrected in aged mice, consistent with continued growth in rodents, reduced cortical bone formation was still evident, indicating continued osteoblastic suppression by loss of PWCR expression in skeletally mature mice. Interestingly, deletion of this region included deletion of the exclusively brain expressed Snord116 cluster and resulted in an upregulation in expression of both NPY and POMC mRNA in the arcuate nucleus. Importantly, the selective deletion of the PWCR only in NPY expressing neurons replicated the bone phenotype of PWCR KO mice. Taken together, PWCR deletion in mice, and specifically in NPY neurons, recapitulates the short stature and low BMD and aspects of the hormonal imbalance of PWS individuals. Moreover, it demonstrates for the first time, that a region encoding non-translated RNAs, expressed solely within the brain, can regulate bone mass in health and disease.

Vitamin B12–dependent taurine synthesis regulates growth and bone mass

PubMed Central

Roman-Garcia, Pablo; Quiros-Gonzalez, Isabel; Mottram, Lynda; Lieben, Liesbet; Sharan, Kunal; Wangwiwatsin, Arporn; Tubio, Jose; Lewis, Kirsty; Wilkinson, Debbie; Santhanam, Balaji; Sarper, Nazan; Clare, Simon; Vassiliou, George S.; Velagapudi, Vidya R.; Dougan, Gordon; Yadav, Vijay K.

2014-01-01

Both maternal and offspring-derived factors contribute to lifelong growth and bone mass accrual, although the specific role of maternal deficiencies in the growth and bone mass of offspring is poorly understood. In the present study, we have shown that vitamin B12 (B12) deficiency in a murine genetic model results in severe postweaning growth retardation and osteoporosis, and the severity and time of onset of this phenotype in the offspring depends on the maternal genotype. Using integrated physiological and metabolomic analysis, we determined that B12 deficiency in the offspring decreases liver taurine production and associates with abrogation of a growth hormone/insulin-like growth factor 1 (GH/IGF1) axis. Taurine increased GH-dependent IGF1 synthesis in the liver, which subsequently enhanced osteoblast function, and in B12-deficient offspring, oral administration of taurine rescued their growth retardation and osteoporosis phenotypes. These results identify B12 as an essential vitamin that positively regulates postweaning growth and bone formation through taurine synthesis and suggests potential therapies to increase bone mass. PMID:24911144

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

Bisphosphonates Improve Trabecular Bone Mass and Normalize Cortical Thickness in Ovariectomized, Osteoblast Connexin43 Deficient Mice

PubMed Central

Watkins, Marcus P.; Norris, Jin Yi; Grimston, Susan K.; Zhang, Xiaowen; Phipps, Roger J.; Ebetino, Frank H.; Civitelli, Roberto

2012-01-01

The gap junction protein, connexin43 (Cx43) controls both bone formation and osteoclastogenesis via osteoblasts and/or osteocytes. Cx43 has also been proposed to mediate an anti-apoptotic effect of bisphosphonates, potent inhibitors of bone resorption. We studied whether bisphosphonates are effective in protecting mice with a conditional Cx43 gene deletion in osteoblasts and osteocytes (cKO) from the consequences of ovariectomy on bone mass and strength. Ovariectomy resulted in rapid loss of trabecular bone followed by a slight recovery in wild type (WT) mice, and a similar degree of trabecular bone loss, albeit slightly delayed, occurred in cKO mice. Treatment with either risedronate (20µg/kg) or alendronate (40µg/kg) prevented ovariectomy-induced bone loss in both genotypes. In basal conditions, bones of cKO mice have larger marrow area, higher endocortical osteoclast number, and lower cortical thickness and strength relative to WT. Ovariectomy increased endocortical osteoclast number in WT but not in cKO mice. Both bisphosphonates prevented these increases in WT mice, and normalized endocortical osteoclast number, cortical thickness and bone strength in cKO mice. Thus, lack of osteoblast/osteocyte Cx43 does not alter bisphosphonate action on bone mass and strength in estrogen deficiency. These results support the notion that one of the main functions of Cx43 in cortical bone is to restrain osteoblast and/or osteocytes from inducing osteoclastogenesis at the endocortical surface. PMID:22750450

Role and mechanism of action of Sclerostin in bone

PubMed Central

Delgado-Calle, Jesus; Sato, Amy Y.; Bellido, Teresita

2016-01-01

After discovering that lack of Sost/sclerostin expression is the cause of the high bone mass human syndromes Van Buchem disease and sclerosteosis, extensive animal experimentation and clinical studies demonstrated that sclerostin plays a critical role in bone homeostasis and that its deficiency or pharmacological neutralization increases bone formation. Dysregulation of sclerostin expression also underlies the pathophysiology of skeletal disorders characterized by loss of bone mass as well as the damaging effects of some cancers in bone. Thus, sclerostin has quickly become a promising molecular target for the treatment of osteoporosis and other skeletal diseases, and beneficial skeletal outcomes are observed in animal studies and clinical trials using neutralizing antibodies against sclerostin. However, the anabolic effect of blocking sclerostin decreases with time, bone mass accrual is also accompanied by anti-catabolic effects, and there is bone loss over time after therapy discontinuation. Further, the cellular source of sclerostin in the bone/bone marrow microenvironment under physiological and pathological conditions, the pathways that regulate sclerostin expression and the mechanisms by which sclerostin modulates the activity of osteocytes, osteoblasts, and osteoclasts remain unclear. In this review, we highlight the current knowledge on the regulation of Sost/sclerotin expression and its mechanism(s) of action, discuss novel observations regarding its role in signaling pathways activated by hormones and mechanical stimuli in bone, and propose future research needed to understand the full potential of therapeutic interventions that modulate Sost/sclerostin expression. PMID:27742498

Peripheral-specific y2 receptor knockdown protects mice from high-fat diet-induced obesity.

PubMed

Shi, Yan-Chuan; Lin, Shu; Castillo, Lesley; Aljanova, Aygul; Enriquez, Ronaldo F; Nguyen, Amy D; Baldock, Paul A; Zhang, Lei; Bijker, Martijn S; Macia, Laurence; Yulyaningsih, Ernie; Zhang, Hui; Lau, Jackie; Sainsbury, Amanda; Herzog, Herbert

2011-11-01

Y2 receptors, particularly those in the brain, have been implicated in neuropeptide Y (NPY)-mediated effects on energy homeostasis and bone mass. Recent evidence also indicates a role for Y2 receptors in peripheral tissues in this process by promoting adipose tissue accretion; however their effects on energy balance remain unclear. Here, we show that adult-onset conditional knockdown of Y2 receptors predominantly in peripheral tissues results in protection against diet-induced obesity accompanied by significantly reduced weight gain, marked reduction in adiposity and improvements in glucose tolerance without any adverse effect on lean mass or bone. These changes occur in association with significant increases in energy expenditure, respiratory exchange ratio, and physical activity and despite concurrent hyperphagia. On a chow diet, knockdown of peripheral Y2 receptors results in increased respiratory exchange ratio and physical activity with no effect on lean or bone mass, but decreases energy expenditure without effecting body weight or food intake. These results suggest that peripheral Y2 receptor signaling is critical in the regulation of oxidative fuel selection and physical activity and protects against the diet-induced obesity. The lack of effects on bone mass seen in this model further indicates that bone mass is primarily controlled by non-peripheral Y2 receptors. This study provides evidence that novel drugs that target peripheral rather than central Y2 receptors could provide benefits for the treatment of obesity and glucose intolerance without adverse effects on lean and bone mass, with the additional benefit of avoiding side effects often associated with pharmaceuticals that act on the central nervous system.

Body composition and bone mineral density of collegiate American football players

PubMed Central

Turnagöl, Hüseyin Hüsrev

2016-01-01

Abstract The aim of this study was to compare whole and segmental body composition and bone mineral density of collegiate American football players by playing positions. Forty collegiate American football players voluntarily participated in this study. Participants were categorized by playing positions into one of five categories i.e., defensive linemen, offensive linemen, defensive secondary players, offensive secondary players and receivers. Whole body composition and bone mineral density were measured by dual x-ray absorptiometry. Offensive and defensive linemen had higher body mass, a body mass index, lean mass and a fat mass index compared to the remaining three positions and a higher lean mass index compared to offensive secondary players and receivers. Offensive linemen had a higher body fat percentage and lower values of upper to lower lean mass than offensive and defensive secondary players and receivers, and higher total mass to the lean mass ratio and fat mass to the lean mass ratio compared to the other players. Offensive linemen had a higher fat mass index and fat mass to the lean mass ratio than defensive linemen. However, in all other measures they were similar. Offensive and defensive secondary players and receivers were similar with respect to the measured variables. Bone mineral density of the players was within the normal range and no difference in lean mass was observed between the legs. In conclusion, findings of this study showed that the total and segmental body composition profile of collegiate American football players reflected the demands of particular playing positions. PMID:28149373

Leptin: a potential mediator for protective effects of fat mass on bone tissue.

PubMed

Thomas, Thierry

2003-02-01

Body weight is among the most powerful predictors of bone status, and adipose tissue plays a substantial role in weight-related protective effects on bone. An understanding of the mechanisms underlying the relation between adipose tissue and bone may open up new perspectives for treatment. Leptin, which is known to regulate appetite and energy expenditures, may also contribute to mediate the effects of fat mass on bone. Although reported data are somewhat conflicting, there is some evidence that leptin may decrease bone formation via a central nervous effect and may stimulate both bone formation and bone resorption via direct peripheral effects on stromal precursor cells. The net result of these central and peripheral effects may depend on serum leptin levels and blood-brain barrier permeability, of which the first increase and the second decrease as obesity develops. Further work is needed to improve our understanding of these effects.

Diagnosis and treatment of common metabolic spinal disorders in the geriatric population.

PubMed

Eck, J C; Humphreys, S C

1998-12-01

Bone is constantly resorbed and remodeled throughout life. After approximately age 30, there is a net loss of bone mass. This places the geriatric population at an increased risk of pathologic bone disorders that can lead to fractures and deformity. In this paper, we review bone metabolism and remodeling and introduce the proper diagnostic techniques. The most common pathologic spinal disorders are introduced, with emphasis on presentation and treatment options. To prevent excessive bone loss, patients should be educated on proper nutrition (calcium and vitamin D requirements) and lifestyle (avoiding alcohol and cigarette smoking). Sex hormone and drug therapies are available to reduce bone loss. New bisphosphonates such as alendronate sodium (Fosamax) have been effective in increasing bone mass. Early diagnosis and proper treatment of pathologic bone disorders can reduce the incidence of fracture and allow the patient a more productive and comfortable life.

Sclerostin Blockade and Zoledronic Acid Improve Bone Mass and Strength in Male Mice With Exogenous Hyperthyroidism.

PubMed

Tsourdi, Elena; Lademann, Franziska; Ominsky, Michael S; Rijntjes, Eddy; Köhrle, Josef; Misof, Barbara M; Roschger, Paul; Klaushofer, Klaus; Hofbauer, Lorenz C; Rauner, Martina

2017-11-01

Hyperthyroidism in mice is associated with low bone mass, high bone turnover, and high concentrations of sclerostin, a potent Wnt inhibitor. Here, we explored the effects of either increasing bone formation with sclerostin antibodies (Scl-Ab) or reducing bone turnover with bisphosphonates on bone mass and strength in hyperthyroid mice. Twelve-week-old C57BL/6 male mice were rendered hyperthyroid using l-thyroxine (T4; 1.2 µg/mL added to the drinking water) and treated with 20 mg/kg Scl-Ab twice weekly or 100 µg/kg zoledronic acid (ZOL) once weekly or phosphate-buffered saline for 4 weeks. Hyperthyroid mice displayed a lower trabecular bone volume at the spine (-42%, P < 0.05) and the distal femur (-55%, P < 0.05) compared with euthyroid controls. Scl-Ab and ZOL treatment of hyperthyroid mice increased trabecular bone volume at the spine by threefold and twofold, respectively. Serum bone formation and resorption markers were increased in hyperthyroid mice and suppressed by treatment with ZOL but not Scl-Ab. Trabecular bone stiffness at the lumbar vertebra was 63% lower in hyperthyroid mice (P < 0.05) and was increased fourfold by Sci-Ab (P < 0.001) and threefold by ZOL treatment (P < 0.01). Bone strength based on ultimate load, which was 10% lower in hyperthyroidism, was increased by Scl-Ab by 71% and ZOL by 22% (both P < 0.001). Increased proportion of low mineralized bone seen in hyperthyroid mice was restored by treatment with Scl-Ab and ZOL. Thus, bone-forming and antiresorptive drugs prevent bone loss in hyperthyroid mice via different mechanisms. Copyright © 2017 Endocrine Society.

Gain-of-function mutation in FGFR3 in mice leads to decreased bone mass by affecting both osteoblastogenesis and osteoclastogenesis

PubMed Central

Su, Nan; Sun, Qidi; Li, Can; Lu, Xiumin; Qi, Huabing; Chen, Siyu; Yang, Jing; Du, Xiaolan; Zhao, Ling; He, Qifen; Jin, Min; Shen, Yue; Chen, Di; Chen, Lin

2010-01-01

Achondroplasia (ACH) is a short-limbed dwarfism resulting from gain-of-function mutations in fibroblast growth factor receptor 3 (FGFR3). Previous studies have shown that ACH patients have impaired chondrogenesis, but the effects of FGFR3 on bone formation and bone remodeling at adult stages of ACH have not been fully investigated. Using micro-computed tomography and histomorphometric analyses, we found that 2-month-old Fgfr3G369C/+ mice (mouse model mimicking human ACH) showed decreased bone mass due to reduced trabecular bone volume and bone mineral density, defect in bone mineralization and increased osteoclast numbers and activity. Compared with primary cultures of bone marrow stromal cells (BMSCs) from wild-type mice, Fgfr3G369C/+ cultures showed decreased cell proliferation, increased osteogenic differentiation including up-regulation of alkaline phosphatase activity and expressions of osteoblast marker genes, and reduced bone matrix mineralization. Furthermore, our studies also suggest that decreased cell proliferation and enhanced osteogenic differentiation observed in Fgfr3G369C/+ BMSCs are caused by up-regulation of p38 phosphorylation and that enhanced Erk1/2 activity is responsible for the impaired bone matrix mineralization. In addition, in vitro osteoclast formation and bone resorption assays demonstrated that osteoclast numbers and bone resorption area were increased in cultured bone marrow cells derived from Fgfr3G369C/+ mice. These findings demonstrate that gain-of-function mutation in FGFR3 leads to decreased bone mass by regulating both osteoblast and osteoclast activities. Our studies provide new insight into the mechanism underlying the development of ACH. PMID:20053668

Bone mass, microarchitecture and strength are influenced by race/ethnicity in young adult men and women.

PubMed

Popp, Kristin L; Hughes, Julie M; Martinez-Betancourt, Adriana; Scott, Matthew; Turkington, Victoria; Caksa, Signe; Guerriere, Katelyn I; Ackerman, Kathryn E; Xu, Chun; Unnikrishnan, Ginu; Reifman, Jaques; Bouxsein, Mary L

2017-10-01

Lower rates of fracture in both Blacks compared to Whites, and men compared to women are not completely explained by differences in bone mineral density (BMD). Prior evidence suggests that more favorable cortical bone microarchitecture may contribute to reduced fracture rates in older Black compared to White women, however it is not known whether these differences are established in young adulthood or develop during aging. Moreover, prior studies using high-resolution pQCT (HR-pQCT) have reported outcomes from a fixed-scan location, which may confound sex- and race/ethnicity-related differences in bone structure. We determined differences in bone mass, microarchitecture and strength between young adult Black and White men and women. We enrolled 185 young adult (24.2±3.4yrs) women (n=51 Black, n=50 White) and men (n=34 Black, n=50 White) in this cross-sectional study. We used dual-energy X-ray absorptiometry (DXA) to determine areal BMD (aBMD) at the femoral neck (FN), total hip (TH) and lumbar spine (LS), as well as HR-pQCT to assess bone microarchitecture and failure load by micro-finite element analysis (μFEA) at the distal tibia (4% of tibial length). We used two-way ANOVA to compare bone outcomes, adjusted for age, height, weight and physical activity. The effect of race/ethnicity on bone outcomes did not differ by sex, and the effect of sex on bone outcomes did not differ by race/ethnicty. After adjusting for covariates, Blacks had significantly greater FN, TH and LS aBMD compared to Whites (p<0.05 for all). Blacks also had greater cortical area, vBMD, and thickness, and lower cortical porosity, with greater trabecular thickness and total vBMD compared to Whites. μFEA-estimated FL was significantly higher among Blacks compared to Whites. Men had significantly greater total vBMD, trabecular thickness and cortical area and thickness, but greater cortical porosity than women, the net effects being a higher failure load in men than women. These findings demonstrate that more favorable bone microarchitecture in Blacks compared to Whites and in men compared to women is established by young adulthood. Advantageous bone strength among Blacks and men likely contributes to their lower risk of fractures throughout life compared to their White and women counterparts. Copyright © 2017 Elsevier Inc. All rights reserved.

Impaired bone formation in ovariectomized mice reduces implant integration as indicated by longitudinal in vivo micro-computed tomography.

PubMed

Li, Zihui; Kuhn, Gisela; Schirmer, Michael; Müller, Ralph; Ruffoni, Davide

2017-01-01

Although osteoporotic bone, with low bone mass and deteriorated bone architecture, provides a less favorable mechanical environment than healthy bone for implant fixation, there is no general agreement on the impact of osteoporosis on peri-implant bone (re)modeling, which is ultimately responsible for the long term stability of the bone-implant system. Here, we inserted an implant in a mouse model mimicking estrogen deficiency-induced bone loss and we monitored with longitudinal in vivo micro-computed tomography the spatio-temporal changes in bone (re)modeling and architecture, considering the separate contributions of trabecular, endocortical and periosteal surfaces. Specifically, 12 week-old C57BL/6J mice underwent OVX/SHM surgery; 9 weeks after we inserted special metal-ceramics implants into the 6th caudal vertebra and we measured bone response with in vivo micro-CT weekly for the following 6 weeks. Our results indicated that ovariectomized mice showed a reduced ability to increase the thickness of the cortical shell close to the implant because of impaired peri-implant bone formation, especially at the periosteal surface. Moreover, we observed that healthy mice had a significantly higher loss of trabecular bone far from the implant than estrogen depleted animals. Such behavior suggests that, in healthy mice, the substantial increase in peri-implant bone formation which rapidly thickened the cortex to secure the implant may raise bone resorption elsewhere and, specifically, in the trabecular network of the same bone but far from the implant. Considering the already deteriorated bone structure of estrogen depleted mice, further bone loss seemed to be hindered. The obtained knowledge on the dynamic response of diseased bone following implant insertion should provide useful guidelines to develop advanced treatments for osteoporotic fracture fixation based on local and selective manipulation of bone turnover in the peri-implant region.

Impaired bone formation in ovariectomized mice reduces implant integration as indicated by longitudinal in vivo micro-computed tomography

PubMed Central

Li, Zihui; Kuhn, Gisela; Schirmer, Michael; Müller, Ralph

2017-01-01

Although osteoporotic bone, with low bone mass and deteriorated bone architecture, provides a less favorable mechanical environment than healthy bone for implant fixation, there is no general agreement on the impact of osteoporosis on peri-implant bone (re)modeling, which is ultimately responsible for the long term stability of the bone-implant system. Here, we inserted an implant in a mouse model mimicking estrogen deficiency-induced bone loss and we monitored with longitudinal in vivo micro-computed tomography the spatio-temporal changes in bone (re)modeling and architecture, considering the separate contributions of trabecular, endocortical and periosteal surfaces. Specifically, 12 week-old C57BL/6J mice underwent OVX/SHM surgery; 9 weeks after we inserted special metal-ceramics implants into the 6th caudal vertebra and we measured bone response with in vivo micro-CT weekly for the following 6 weeks. Our results indicated that ovariectomized mice showed a reduced ability to increase the thickness of the cortical shell close to the implant because of impaired peri-implant bone formation, especially at the periosteal surface. Moreover, we observed that healthy mice had a significantly higher loss of trabecular bone far from the implant than estrogen depleted animals. Such behavior suggests that, in healthy mice, the substantial increase in peri-implant bone formation which rapidly thickened the cortex to secure the implant may raise bone resorption elsewhere and, specifically, in the trabecular network of the same bone but far from the implant. Considering the already deteriorated bone structure of estrogen depleted mice, further bone loss seemed to be hindered. The obtained knowledge on the dynamic response of diseased bone following implant insertion should provide useful guidelines to develop advanced treatments for osteoporotic fracture fixation based on local and selective manipulation of bone turnover in the peri-implant region. PMID:28910363

NF-κB RelB Negatively Regulates Osteoblast Differentiation and Bone Formation

PubMed Central

Yao, Zhenqiang; Li, Yanyun; Yin, Xiaoxiang; Dong, Yufeng; Xing, Lianping; Boyce, Brendan F.

2013-01-01

RelA-mediated NF-κB canonical signaling promotes mesenchymal progenitor cell (MPC) proliferation, but inhibits differentiation of mature osteoblasts (OBs) and thus negatively regulates bone formation. Previous studies suggest that NF-κB RelB may also negatively regulate bone formation through non-canonical signaling, but they involved a complex knockout mouse model and the molecular mechanisms involved were not investigated. Here, we report that RelB−/− mice develop age-related increased trabecular bone mass associated with increased bone formation. RelB−/− bone marrow stromal cells expanded faster in vitro and have enhanced OB differentiation associated with increased expression of the osteoblastogenic transcription factor, Runx2. In addition, RelB directly targeted the Runx2 promoter to inhibit its activation. Importantly, RelB−/− bone-derived MPCs formed bone more rapidly than wild-type cells after they were injected into a murine tibial bone defect model. Our findings indicate that RelB negatively regulates bone mass as mice age and limits bone formation in healing bone defects, suggesting that inhibition of RelB could reduce age-related bone loss and enhance bone repair. PMID:24115294

Strategies to reverse bone loss in women with functional hypothalamic amenorrhea: a systematic review of the literature.

PubMed

Vescovi, J D; Jamal, S A; De Souza, M J

2008-04-01

Functional hypothalamic amenorrhea (FHA) impairs the attainment of peak bone mass and as such can increase the risk of fractures later in life. To document available treatment strategies, we conducted a systematic review of the literature. We report that hormonal therapies have limited effectiveness in increasing bone mass, whereas increased caloric intake resulting in weight gain and/or resumption of menses is an essential strategy for restoring bone mass in women with FHA. Women with functional hypothalamic amenorrhea (FHA) may not achieve peak bone mass (PBM), which increases the risk of stress fractures, and may increase the risk of osteoporotic fractures in later life. To identify effective treatment strategies for women with FHA, we conducted a systematic review of the literature. We included randomized controlled trials (RCTs), cross-sectional studies, and case studies that reported on the effects of pharmacological and non-pharmacological interventions on bone mineral density (BMD) or bone turnover in women with FHA. Most published studies (n=26) were designed to treat the hormonal abnormalities observed in women with FHA (such as low estrogen, leptin, insulin-like growth factor-1, and DHEA); however none of these treatments demonstrated consistent improvements in BMD. Therapies containing an estrogen given for 8-24 months resulted in variable improvements (1.0-19.0%) in BMD, but failed to restore bone mass to that of age-matched controls. Three studies reported on the use of bisphosphonates (3-12 months) in anorexic women, which appear to have limited effectiveness to improve BMD compared to nutritional treatments. Another three investigations showed no improvements in BMD after androgen therapy (DHEA and testosterone) in anorexic women. In contrast, reports (n=9) describing an increase in caloric intake that results in weight gain and/or the resumption of menses reported a 1.1-16.9% increase in BMD concomitant with an improvement in bone formation and reduction in bone resorption markers. Our literature review indicates that the most successful, and indeed essential strategy for improving BMD in women with FHA is to increase caloric intake such that body mass is increased and there is a resumption of menses. Further long-term studies to determine the persistence of this effect and to determine the effects of this and other strategies on fracture risk are needed.

Relative Importance of Lean and Fat Mass on Bone Mineral Density in Iranian Children and Adolescents.

PubMed

Jeddi, Marjan; Dabbaghmanesh, Mohammad Hossein; Ranjbar Omrani, Gholamhossein; Ayatollahi, Sayed Mohammad Taghi; Bagheri, Zahra; Bakhshayeshkaram, Marzieh

2015-07-01

Body weight is made up of lean and fat mass and both are involved in growth and development. Impression of these two components in bone density accrual has been controversial. The aim of this study was to evaluate the relationship between fat and lean mass and bone density in Iranian children and adolescents. A cross-sectional study was performed on 472 subjects (235 girls, 237 boys) aged 9-18 years old in Fars Province. The participants' weight, height, waist circumference, stage of puberty, and level of physical activity were recorded. Bone Mineral Content (BMC), Bone Mineral Density (BMD), total body fat and lean mass were measured using dual-energy X-ray absorptiometry. Results showed that 12.2% of boys and 12.3% of girls were overweight and 5.5% of boys and 4.7% of girls were obese. Obese individuals had greater total body BMD (0.96 ± 0.11) than normal-weight ones (0.86 ± 0.11) (P < 0.001). We found the greatest correlation between total body BMD and total body lean mass (R = 0.78. P < 0.001) and the least correlation with total body fat percentage (R = 0.03, P = 0.44). Total lean mass in more active boys was 38.1 ± 10.9 and in less active boys was 32.3 ± 11.0 (P < 0.001). The results of multiple regression analysis showed that age and total body lean mass were independent factors of BMD in growing children and adolescents. These findings suggest that lean mass was the most important predictor of BMD in both genders. Physical activity appears to positively impact on lean mass and needs to be considered in physical education and health-enhancing programs in Iranian school children.

Setup of a bone aging experimental model in the rabbit comparing changes in cortical and trabecular bone: Morphological and morphometric study in the femur.

PubMed

Pazzaglia, Ugo E; Sibilia, Valeria; Congiu, Terenzio; Pagani, Francesca; Ravanelli, Marco; Zarattini, Guido

2015-07-01

Bone aging was studied in an experimental model (rabbit femur) in three populations aged 0.5, 1.5, and 7.5 years. Cortical bone histology was compared with a data set from a 1.5-month-old population of an earlier published paper. From 0.5-year-old onward, the mean femur length did not increase further. Thereafter, the mean marrow area increased and the cortical area decreased significantly with aging. This was associated with a structural pattern transformation from plexiform to laminar and then Haversian-like type. The distal meta-epiphysis bone trabecular density of the oldest populations also was significantly lower in specific regions of interest (ROI). Percentage sealed primary vascular canals in laminar bone significantly increased with aging without variation of percentage sealed secondary osteons. Remodeling rate reflected by the density of cutting cones did not significantly change among the age populations. These data suggest that laminar bone vascular pattern is more functional in the fast diaphyseal expansion but not much streamlined with the renewal of blood flow during secondary remodeling. Bone aging was characterized by: 1) secondary remodeling subendosteally; 2) increment of sealed primary vascular canals number; 3) increased calcium content of the cortex; 4) cortical and trabecular bone mass loss in specific ROIs. Taken together, the present data may give a morphological and morphometric basis to perform comparative studies on experimental models of osteoporosis in the rabbit. © 2015 Wiley Periodicals, Inc.

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

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.

Clinical value of bone densitometry.

PubMed

Sartoris, D J

1994-07-01

The purpose of this article is to provide insight into the long-standing controversy over the clinical value of noninvasive measurement of bone mass. Results of recent studies have increasingly supported the judicious use of bone densitometry as a clinical tool [1]. These reports contradict editorials on the limitations of bone densitometry that have appeared in a variety of subspecialty publications [2,3]. The importance of bone mass measurement is underscored by the lack of success in predicting bone density from various combinations of anthropometric and historical variables. Growing evidence suggests that densitometry is a useful tool for determining which women near menopause are at risk for osteoporosis and, therefore, are candidates for estrogen-replacement therapy. This article summarizes current concepts on the subject and attempts to prove that bone densitometry is a beneficial and indicated procedure for selected patients.

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.

A 21-Week Bone Deposition Promoting Exercise Programme Increases Bone Mass in Young People with Down Syndrome

ERIC Educational Resources Information Center

Gonzalez-Aguero, Alejandro; Vicente-Rodriguez, German; Gomez-Cabello, Alba; Ara, Ignacio; Moreno, Luis A.; Casajus, Jose A.

2012-01-01

Aim: To determine whether the bone mass of young people with Down syndrome may increase, following a 21-week conditioning training programme including plyometric jumps. Method: Twenty-eight participants with Down syndrome (13 females, 15 males) aged 10 to 19 years were divided into exercise (DS-E; n = 14; eight females, six males mean age 13y 8mo,…

The temporal response of bone to unloading

NASA Technical Reports Server (NTRS)

Globus, R. K.; Bikle, D. D.; Morey-Holton, E.

1984-01-01

Rats were suspended by their tails with the forelimbs bearing the weight load to simulate the weightlessness of space flight. Growth in bone mass ceased by 1 week in the hindlimbs and lumbar vertebrae in growing rats, while growth in the forelimbs and cervical vertebrae remained unaffected. The effects of selective skeletal unloading on bone formation during 2 weeks of suspension was investigated using radio iostope incorporation (with Ca-45 and H-3 proline) and histomorphometry (with tetracycline labeling). The results of these studies were confirmed by histomorphometric measurements of bone formation using triple tetracycline labeling. This model of simulated weightlessness results in an initial inhibition of bone formation in the unloaded bones. This temporary cessation of bone formation is followed in the accretion of bone mass, which then resumes at a normal rate by 14 days, despite continued skeletal unloading. This cycle of inhibition and resumption of bone formation has profound implication for understanding bone dynamics durng space flight, immobilization, or bed rest and offers an opportunity to study the hormonal and mechanical factors that regulate bone formation.

Osteoinductive effects of glyceollins on adult mesenchymal stromal/stem cells from adipose tissue and bone marrow

USDA-ARS?s Scientific Manuscript database

Osteoporosis is characterized by destruction of bone architecture, resulting in decreased bone mass density (BMD) and increased fracture susceptibility. While current therapies focus on reducing bone resorption, the development of therapies to regenerate bone may also be beneficial. Promising anabol...

Time course of disassociation of bone formation signals with bone mass and bone strength in sclerostin antibody treated ovariectomized rats.

PubMed

Ma, Yanfei L; Hamang, Matthew; Lucchesi, Jonathan; Bivi, Nicoletta; Zeng, Qianqiang; Adrian, Mary D; Raines, Sarah E; Li, Jiliang; Kuhstoss, Stuart A; Obungu, Victor; Bryant, Henry U; Krishnan, Venkatesh

2017-04-01

Sclerostin antibodies increase bone mass by stimulating bone formation. However, human and animal studies show that bone formation increases transiently and returns to pre-treatment level despite ongoing antibody treatment. To understand its mechanism of action, we studied the time course of bone formation, correlating the rate and extent of accrual of bone mass and strength after sclerostin antibody treatment. Ovariectomized (OVX) rats were treated with a sclerostin-antibody (Scle-ab) at 20mg/kg sc once weekly and sacrificed at baseline and 2, 3, 4, 6, and 8weeks post-treatment. In Scle-ab treated rats, serum PINP and OCN rapidly increased at week 1, peaked around week 3, and returned to OVX control levels by week 6. Transcript analyses from the distal femur revealed an early increase in bone formation followed by a sustained decrease in bone resorption genes. Lumbar vertebral (LV) osteoblast surface increased 88% by week 2, and bone formation rate (BFR/BS) increased 138% by week 4. Both parameters were below OVX control by week 8. Bone formation was primarily a result of modeling based formation. Endocortical and periosteal BFR/BS peaked around week 4 at 313% and 585% of OVX control, respectively. BFR/BS then declined but remained higher than OVX control on both surfaces through week 8. Histomorphometric analyses showed LV-BV/TV did not further increase after week 4, while BMD continued to increase at LV, mid femur (MF), and femoral neck (FN) through week 8. Biomechanical tests showed a similar improvement in bone strength through 8weeks in MF and FN, but bone strength plateaued between weeks 6 and 8 for LV. Our data suggest that bone formation with Scle-ab treatment is rapid and modeling formation dominated in OVX rats. Although transient, the bone formation response persists longer in cortical than trabecular bone. Copyright © 2016 Elsevier Inc. All rights reserved.

Reduced energy availability: implications for bone health in physically active populations.

PubMed

Papageorgiou, Maria; Dolan, Eimear; Elliott-Sale, Kirsty J; Sale, Craig

2018-04-01

The present review critically evaluates existing literature on the effects of short- and long-term low energy availability (EA) on bone metabolism and health in physically active individuals. We reviewed the literature on the short-term effects of low EA on markers of bone metabolism and the long-term effects of low EA on outcomes relating to bone health (bone mass, microarchitecture and strength, bone metabolic markers and stress fracture injury risk) in physically active individuals. Available evidence indicates that short-term low EA may increase markers of bone resorption and decrease markers of bone formation in physically active women. Bone metabolic marker responses to low EA are less well known in physically active men. Cross-sectional studies investigating the effects of long-term low EA suggest that physically active individuals who have low EA present with lower bone mass, altered bone metabolism (favouring bone resorption), reduced bone strength and increased risk for stress fracture injuries. Reduced EA has a negative influence on bone in both the short- and long-term, and every effort should be made to reduce its occurrence in physically active individuals. Future interventions are needed to explore the effects of long-term reduced EA on bone health outcomes, while short-term low EA studies are also required to give insight into the pathophysiology of bone alterations.

Central Depletion of Brain-Derived Neurotrophic Factor in Mice Results in High Bone Mass and Metabolic Phenotype

PubMed Central

Zayzafoon, M.; Rymaszewski, M.; Heiny, J.; Rios, M.; Hauschka, P. V.

2012-01-01

Brain-derived neurotrophic factor (BDNF) plays important roles in neuronal differentiation/survival, the regulation of food intake, and the pathobiology of obesity and type 2 diabetes mellitus. BDNF and its receptor are expressed in osteoblasts and chondrocyte. BDNF in vitro has a positive effect on bone; whether central BDNF affects bone mass in vivo is not known. We therefore examined bone mass and energy use in brain-targeted BDNF conditional knockout mice (Bdnf2lox/2lox/93). The deletion of BDNF in the brain led to a metabolic phenotype characterized by hyperphagia, obesity, and increased abdominal white adipose tissue. Central BDNF deletion produces a marked skeletal phenotype characterized by increased femur length, elevated whole bone mineral density, and bone mineral content. The skeletal changes are developmentally regulated and appear concurrently with the metabolic phenotype, suggesting that the metabolic and skeletal actions of BDNF are linked. The increased bone development is evident in both the cortical and trabecular regions. Compared with control, Bdnf2lox/2lox/93 mice show greater trabecular bone volume (+50% for distal femur, P < 0.001; +35% for vertebral body, P < 0.001) and midfemoral cortical thickness (+11 to 17%, P < 0.05), measured at 3 and 6 months of age. The skeletal and metabolic phenotypes were gender dependent, with female being more affected than male mice. However, uncoupling protein-1 expression in brown fat, a marker of sympathetic tone, was not different between genotypes. We show that deletion of central BDNF expression in mice results in increased bone mass and white adipose tissue, with no significant changes in sympathetic signaling or peripheral serotonin, associated with hyperphagia, obesity, and leptin resistance. PMID:23011922

Urbanization of black South African women may increase risk of low bone mass due to low vitamin D status, low calcium intake, and high bone turnover.

PubMed

Kruger, Marlena C; Kruger, Iolanthé M; Wentzel-Viljoen, Edelweiss; Kruger, Annamarie

2011-10-01

Globally, rural to urban migration is accompanied by changes in dietary patterns and lifestyle that have serious health implications, including development of low bone mass. We hypothesized that serum 25 (OH) vitamin D3 (25[OH]D3) levels will be lower, bone turnover higher, and nutrition inadequate in urban postmenopausal black women, increasing risk for low bone mass. We aimed to assess the prevalence of risk factors for low bone mass in 1261 black women from rural and urban areas in the North West Province of South Africa (Prospective Urban and Rural Epidemiology-South Africa project). Fasting blood samples were taken; and participants were interviewed to complete questionnaires on self-reported diseases, fractures, and dietary intakes. Bone health markers were assessed in a subgroup of 658 women older than 45 years. Specific lifestyle risk factors identified were inactivity, smoking, injectable progestin contraception use, and high alcohol consumption. Dietary risk factors identified were low calcium and high animal protein, phosphorous, and sodium intakes. The 25(OH)D3 and C-terminal telopeptide (CTX) levels were significantly higher in the rural vs the urban women older than 50 years. Parathyroid hormone (PTH) levels increased with age in both groups. The 25(OH)D levels were inversely correlated with CTX and PTH in rural women. In urban women, PTH and CTX were correlated while dietary calcium was inversely correlated with CTX and PTH with 25(OH)D3. The combination of low dietary calcium (<230 mg/d), marginally insufficient 25(OH)D3 status, and raised PTH may result in increased bone resorption. Further research is required to assess bone health and fracture risk in black African women. Copyright © 2011 Elsevier Inc. All rights reserved.

Role of subchondral bone properties and changes in development of load-induced osteoarthritis in mice.

PubMed

Adebayo, O O; Ko, F C; Wan, P T; Goldring, S R; Goldring, M B; Wright, T M; van der Meulen, M C H

2017-12-01

Animal models recapitulating post-traumatic osteoarthritis (OA) suggest that subchondral bone (SCB) properties and remodeling may play major roles in disease initiation and progression. Thus, we investigated the role of SCB properties and its effects on load-induced OA progression by applying a tibial loading model on two distinct mouse strains treated with alendronate (ALN). Cyclic compression was applied to the left tibia of 26-week-old male C57Bl/6 (B6, low bone mass) and FVB (high bone mass) mice. Mice were treated with ALN (26 μg/kg/day) or vehicle (VEH) for loading durations of 1, 2, or 6 weeks. Changes in articular cartilage and subchondral and epiphyseal cancellous bone were analyzed using histology and microcomputed tomography. FVB mice exhibited thicker cartilage, a thicker SCB plate, and higher epiphyseal cancellous bone mass and tissue mineral density than B6 mice. Loading induced cartilage pathology, osteophyte formation, and SCB changes; however, lower initial SCB mass and stiffness in B6 mice did not attenuate load-induced OA severity compared to FVB mice. By contrast, FVB mice exhibited less cartilage damage, and slower-growing and less mature osteophytes. In B6 mice, inhibiting bone remodeling via ALN treatment exacerbated cartilage pathology after 6 weeks of loading, while in FVB mice, inhibiting bone remodeling protected limbs from load-induced cartilage loss. Intrinsically lower SCB properties were not associated with attenuated load-induced cartilage loss. However, inhibiting bone remodeling produced differential patterns of OA pathology in animals with low compared to high SCB properties, indicating that these factors do influence load-induced OA progression. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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.

[New methods for the evaluation of bone quality. Assessment of bone structural property using imaging.

PubMed

Ito, Masako

Structural property of bone includes micro- or nano-structural property of the trabecular and cortical bone, and macroscopic geometry. Radiological technique is useful to analyze the bone structural property;multi-detector row CT(MDCT)or high-resolution peripheral QCT(HR-pQCT)is available to analyze human bone in vivo . For the analysis of hip geometry, CT-based hip structure analysis(HSA)is available as well as DXA-based HSA. These structural parameters are related to biomechanical property, and these assessment tools provide information of pathological changes or the effects of anti-osteoporotic agents on bone.

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.

[Issues related to secondary osteoporosis associated with growth hormone deficiency in adulthood].

PubMed

Kužma, Martin; Jackuliak, Peter; Killinger, Zdenko; Vaňuga, Peter; Payer, Juraj

Growth hormone (GH) increases linear bone growth through complex hormonal reactions, mainly mediated by insulin like growth factor 1 (IGF1) that is produced mostly by hepatocytes under influence of GH and stimulates differentiation of epiphyseal prechondrocytes. IGF1 and GH play a key role in the linear bone growth after birth and regulation of bone remodelation during the entire lifespan. It is known that adult GH deficient (GHD) patients have decreased BMD and increased risk of low-impact fractures. Most data gathered thus far on the effect of GH replacement on bone status comprise the measurement of quantitative changes of bone mass. Some animal studies with GHD showed that the bone microarchitecture, measured using computed tomography methods, is significantly compromised and improve after GH replacement. However, human studies did not show significantly decreased bone microarchitecture, but limited methodological quality does not allow firm conclusions on this subject.Key words: bone mass - bone quality - fracture - growth hormone - IGF1.

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

Bone morphogenetic protein type IA receptor signaling regulates postnatal osteoblast function and bone remodeling.

PubMed

Mishina, Yuji; Starbuck, Michael W; Gentile, Michael A; Fukuda, Tomokazu; Kasparcova, Viera; Seedor, J Gregory; Hanks, Mark C; Amling, Michael; Pinero, Gerald J; Harada, Shun-ichi; Behringer, Richard R

2004-06-25

Bone morphogenetic proteins (BMPs) function during various aspects of embryonic development including skeletogenesis. However, their biological functions after birth are less understood. To investigate the role of BMPs during bone remodeling, we generated a postnatal osteoblast-specific disruption of Bmpr1a that encodes the type IA receptor for BMPs in mice. Mutant mice were smaller than controls up to 6 months after birth. Irregular calcification and low bone mass were observed, but there were normal numbers of osteoblasts. The ability of the mutant osteoblasts to form mineralized nodules in culture was severely reduced. Interestingly, bone mass was increased in aged mutant mice due to reduced bone resorption evidenced by reduced bone turnover. The mutant mice lost more bone after ovariectomy likely resulting from decreased osteoblast function which could not overcome ovariectomy-induced bone resorption. In organ culture of bones from aged mice, ablation of the Bmpr1a gene by adenoviral Cre recombinase abolished the stimulatory effects of BMP4 on the expression of lysosomal enzymes essential for osteoclastic bone resorption. These results demonstrate essential and age-dependent roles for BMP signaling mediated by BMPRIA (a type IA receptor for BMP) in osteoblasts for bone remodeling.

[Osteoporosis in all young daughters of a mother with multiple osteoporotic fractures. A case of familial osteoporosis].

PubMed

Parisi, M S; Díaz, A G; Oliveri, M B; Di Gregorio, S; Mautalen, C A

2001-01-01

We herein describe a family whose female members are all osteoporotic: a postmenopausal mother and her three premenopausal daughters. The mother aged 60 presented axial and peripheral fractures, and very low bone mineral density (BMD). She reported that her grandmother had suffered a hip fracture. The eldest daughter aged 30 suffered multiple vertebral fractures during pregnancy and lactation associated with very low BMD. In view of these observations, the other two daughters aged 29 and 27 years respectively were evaluated. BMD was found to be severely diminished according to densitometric values for osteoporosis established by WHO, but they had no history of bone fractures. Probably the strong genetic component in bone mass is responsible for the severely diminished BMD observed in all the women in this family, as well as the occurrence of bone fractures in two of them. To our knowledge, there are no similar reports in the literature. Our results evidence the importance of evaluating bone mass in the offspring of an individual presenting severe osteoporosis, in order to detect family members with low bone mass and at high risk of developing bone fractures.

Childhood growth predicts higher bone mass and greater bone area in early old age: findings among a subgroup of women from the Helsinki Birth Cohort Study.

PubMed

Mikkola, T M; von Bonsdorff, M B; Osmond, C; Salonen, M K; Kajantie, E; Cooper, C; Välimäki, M J; Eriksson, J G

2017-09-01

We examined the associations between childhood growth and bone properties among women at early old age. Early growth in height predicted greater bone area and higher bone mineral mass. However, information on growth did not improve prediction of bone properties beyond that predicted by body size at early old age. We examined the associations between body size at birth and childhood growth with bone area, bone mineral content (BMC), and areal bone mineral density (aBMD) in early old age. A subgroup of women (n = 178, mean 60.4 years) from the Helsinki Birth Cohort Study, born 1934-1944, participated in dual-energy X-ray absorptiometry (DXA) measurements of the lumbar spine and hip. Height and weight at 0, 2, 7, and 11 years, obtained from health care records, were reconstructed into conditional variables representing growth velocity independent of earlier growth. Weight was adjusted for corresponding height. Linear regression models were adjusted for multiple confounders. Birth length and growth in height before 7 years of age were positively associated with femoral neck area (p < 0.05) and growth in height at all age periods studied with spine bone area (p < 0.01). Growth in height before the age of 7 years was associated with BMC in the femoral neck (p < 0.01) and birth length and growth in height before the age of 7 years were associated with BMC in the spine (p < 0.05). After entering adult height into the models, nearly all associations disappeared. Weight gain during childhood was not associated with bone area or BMC, and aBMD was not associated with early growth. Optimal growth in height in girls is important for obtaining larger skeleton and consequently higher bone mass. However, when predicting bone mineral mass among elderly women, information on early growth does not improve prediction beyond that predicted by current height and weight.