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Bone Strength (bone + strength)
Selected AbstractsTargeted Deletion of the Sclerostin Gene in Mice Results in Increased Bone Formation and Bone Strength,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2008Xiaodong Li Abstract Introduction: Sclerosteosis is a rare high bone mass genetic disorder in humans caused by inactivating mutations in SOST, the gene encoding sclerostin. Based on these data, sclerostin has emerged as a key negative regulator of bone mass. We generated SOST knockout (KO) mice to gain a more detailed understanding of the effects of sclerostin deficiency on bone. Materials and Methods: Gene targeting was used to inactivate SOST and generate a line of SOST KO mice. Radiography, densitometry, ,CT, histomorphometry, and mechanical testing were used to characterize the impact of sclerostin deficiency on bone in male and female mice. Comparisons were made between same sex KO and wildtype (WT) mice. Results: The results for male and female SOST KO mice were similar, with differences only in the magnitude of some effects. SOST KO mice had increased radiodensity throughout the skeleton, with general skeletal morphology being normal in appearance. DXA analysis of lumbar vertebrae and whole leg showed that there was a significant increase in BMD (>50%) at both sites. ,CT analysis of femur showed that bone volume was significantly increased in both the trabecular and cortical compartments. Histomorphometry of trabecular bone revealed a significant increase in osteoblast surface and no significant change in osteoclast surface in SOST KO mice. The bone formation rate in SOST KO mice was significantly increased for trabecular bone (>9-fold) at the distal femur, as well as for the endocortical and periosteal surfaces of the femur midshaft. Mechanical testing of lumbar vertebrae and femur showed that bone strength was significantly increased at both sites in SOST KO mice. Conclusions:SOST KO mice have a high bone mass phenotype characterized by marked increases in BMD, bone volume, bone formation, and bone strength. These results show that sclerostin is a key negative regulator of a powerful, evolutionarily conserved bone formation pathway that acts on both trabecular and cortical bone. [source] RANKL Inhibition with Osteoprotegerin Increases Bone Strength by Improving Cortical and Trabecular bone Architecture in Ovariectomized Rats,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2008Michael S Ominsky Abstract Introduction: Ovariectomy (OVX) results in bone loss caused by increased bone resorption. RANKL is an essential mediator of bone resorption. We examined whether the RANKL inhibitor osteoprotegerin (OPG) would preserve bone volume, density, and strength in OVX rats. Materials and Methods: Rats were OVX or sham-operated at 3 mo of age. Sham controls were treated for 6 wk with vehicle (Veh, PBS). OVX rats were treated with Veh or human OPG-Fc (10 mg/kg, 2/wk). Serum RANKL and TRACP5b was measured by ELISA. BMD of lumbar vertebrae (L1,L5) and distal femur was measured by DXA. Right distal femurs were processed for bone histomorphometry. Left femurs and the fifth lumbar vertebra (L5) were analyzed by ,CT and biomechanical testing, and L6 was analyzed for ash weight. Results: OVX was associated with significantly greater serum RANKL and osteoclast surface and with reduced areal and volumetric BMD. OPG markedly reduced osteoclast surface and serum TRACP5b while completely preventing OVX-associated bone loss in the lumbar vertebrae, distal femur, and femur neck. Vertebrae from OPG-treated rats had increased dry and ash weight, with no significant differences in tissue mineralization versus OVX controls. ,CT showed that trabecular compartments in OVX-OPG rats had significantly greater bone volume fraction, vBMD, bone area, trabecular thickness, and number, whereas their cortical compartments had significantly greater bone area (p < 0.05 versus OVX-Veh). OPG improved cortical area in L5 and the femur neck to levels that were significantly greater than OVX or sham controls (p < 0.05). Biomechanical testing of L5 and femur necks showed significantly greater maximum load values in the OVX-OPG group (p < 0.05 versus OVX-Veh). Bone strength at both sites was linearly correlated with total bone area (r2 = 0.54,0.74, p < 0.0001), which was also significantly increased by OPG (p < 0.05 versus OVX). Conclusions: OPG treatment prevented bone loss, preserved trabecular architecture, and increased cortical area and bone strength in OVX rats. [source] Strontium Ranelate Treatment Improves Trabecular and Cortical Intrinsic Bone Tissue Quality, a Determinant of Bone Strength,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2007Patrick Ammann MD Abstract Beside its influence on determinants of bone strength (geometry, microarchitecture), which is likely to be related to a cellular effect, strontium ranelate improves bone tissue quality as evaluated by nanoindentation, increasing elastic modulus, hardness, and dissipated energy in vertebrae of rats treated for 104 wk with daily dose from 0 to 900 mg/kg. Introduction: We previously showed that strontium ranelate treatment improves the mechanical properties of the vertebral body and long bone midshaft in intact rats. The increased energy to failure obtained with strontium ranelate is essentially caused by an increase in plastic energy, suggesting that bone formed during treatment can withstand greater deformation before fracture. In the bone mineral phase, strontium is mainly located in the hydrated shell and could thus potentially influence intrinsic bone tissue quality. Materials and Methods: To study whether strontium ranelate treatment could positively influence intrinsic bone tissue quality (elastic modulus, hardness, and dissipated energy), nanoindentation tests were performed at the level of trabecular nodes and cortex under physiological or dry conditions in vertebrae of rats treated for 104 wk with strontium ranelate at a daily dose of 0, 225, 450, or 900 mg/kg (n = 12 per group). Ex vivo ,CT measurements and axial compression tests of adjacent vertebral bodies were also performed. Significance of difference was evaluated using ANOVA. Results: In agreement with previous results, strontium ranelate (900 mg/kg/d) significantly increased versus controls in maximal load (+23%), total energy (+71%), and plastic energy (+143%). At the level of trabecular bone, strontium ranelate treatment resulted in a significant increase in elastic modulus (+15.1%, p < 0.01), hardness (+11.5%, p < 0.05), and dissipated energy (+16.2%, p < 0.001) versus controls in physiological, but not in dry, conditions. The effect was less pronounced in cortex. Conclusions: These results show for the first time a direct action of strontium ranelate on bone tissue quality. Beside its shown influence on classical determinants of bone strength (geometry, microarchitecture), which is likely to be related to a cellular effect, strontium ranelate improves bone tissue quality. This could contribute to the increase in bone strength and thus be involved in the reduction of fracture risk in postmenopausal osteoporotic patients treated with strontium ranelate. [source] Is a School-Based Physical Activity Intervention Effective for Increasing Tibial Bone Strength in Boys and Girls?,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2007Heather M Macdonald Abstract This 16-month randomized, controlled school-based study compared change in tibial bone strength between 281 boys and girls participating in a daily program of physical activity (Action Schools! BC) and 129 same-sex controls. The simple, pragmatic intervention increased distal tibia bone strength in prepubertal boys; it had no effect in early pubertal boys or pre or early pubertal girls. Introduction: Numerous school-based exercise interventions have proven effective for enhancing BMC, but none have used pQCT to evaluate the effects of increased loading on bone strength during growth. Thus, our aim was to determine whether a daily program of physical activity, Action Schools! BC (AS! BC) would improve tibial bone strength in boys and girls who were pre- (Tanner stage 1) or early pubertal (Tanner stage 2 or 3) at baseline. Materials and Methods: Ten schools were randomized to intervention (INT, 7 schools) or control (CON, 3 schools). The bone-loading component of AS! BC included a daily jumping program (Bounce at the Bell) plus 15 minutes/day of classroom physical activity in addition to regular physical education. We used pQCT to compare 16-month change in bone strength index (BSI, mg2/mm4) at the distal tibia (8% site) and polar strength strain index (SSIp, mm3) at the tibial midshaft (50% site) in 281 boys and girls participating in AS! BC and 129 same-sex controls. We used a linear mixed effects model to analyze our data. Results: Children were 10.2 ± 0.6 years at baseline. Intervention boys tended to have a greater increase in BSI (+774.6 mg2/mm4; 95% CI: 672.7, 876.4) than CON boys (+650.9 mg2/mm4; 95% CI: 496.4, 805.4), but the difference was only significant in prepubertal boys (p = 0.03 for group × maturity interaction). Intervention boys also tended to have a greater increase in SSIp (+198.6 mm3; 95% CI: 182.9, 214.3) than CON boys (+177.1 mm3; 95% CI: 153.5, 200.7). Change in BSI and SSIp was similar between CON and INT girls. Conclusions: Our findings suggest that a simple, pragmatic program of daily activity enhances bone strength at the distal tibia in prepubertal boys. The precise exercise prescription needed to elicit a similar response in more mature boys or in girls might be best addressed in a dose,response trial. [source] Whole-Genome Scan for Linkage to Bone Strength and Structure in Inbred Fischer 344 and Lewis Rats,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2005Imranul Alam Abstract A genome-wide genetic linkage analysis identified several chromosomal regions influencing bone strength and structure in F2 progeny of Fischer 344 x Lewis inbred rats. Introduction: Inbred Fischer 344 (F344) and Lewis (LEW) rats are similar in body size, but the F344 rats have significantly lower BMD and biomechanical strength of the femur and spine compared with LEW rats. The goal of this study was to identify quantitative trait loci (QTL) linked to bone strength and structure in adult female F2 rats from F344 and LEW progenitors. Materials and Methods: The 595 F2 progeny from F344 x LEW rats were phenotyped for measures of bone strength (ultimate force {Fu}; energy to break {U}; stiffness {S}) of the femur and lumbar vertebra and structure (femur midshaft polar moment of inertia {Ip}; femur midshaft cortical area; vertebral area). A genome-wide scan was completed in the F2 rats using 118 microsatellite markers at an average interval of 20 cM. Multipoint quantitative linkage analysis was performed to identify chromosomal regions that harbor QTL for bone strength and structure phenotypes. Results: Evidence of linkage for femur and lumbar strength was observed on chromosomes (Chrs) 1, 2, 5, 10, and 19. Significant linkage for femoral structure was detected on Chrs 2, 4, 5, 7, and 15. QTLs affecting femoral strength on Chrs 2 and 5 were also found to influence femur structure. Unique QTLs on Chrs 1, 10, and 19 were found that contributed to variability in bone strength but had no significant effect on structure. Also, unique QTLs were observed on Chrs 4, 7, and 15 that affected only bone structure without any effect on biomechanics. Conclusion: We showed multiple genetic loci influencing bone strength and structure in F344 x LEW F2 rats. Some of these loci are homologous to mouse and human chromosomes previously linked to related bone phenotypes. [source] Revival of Bone Strength: The Bottom LineJOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2005Teppo LN Järvinen MD First page of article [source] Vibration and Components of Bone StrengthJOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2004Toshihiro Sugiyama No abstract is available for this article. [source] Determinants of Bone StrengthJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2003Gary M. Kiebzak No abstract is available for this article. [source] Architecture Is One of the Determinants of Bone StrengthJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2003Babul Borah No abstract is available for this article. [source] Tower Climbing Exercise Started 3 Months After Ovariectomy Recovers Bone Strength of the Femur and Lumbar Vertebrae in Aged Osteopenic Rats,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2003Takuya Notomi Abstract To determine both the preventive and recovery effects of tower climbing exercise on mass, strength, and local turnover of bone in ovariectomized (OVX) rats, we carried out two experiments. In experiment I, 60 Sprague-Dawley rats, 12 months of age, were assigned to four groups: a Baseline Control, Sham-Operated Sedentary, OVX-Sedentary and OVX-Exercise rats. Rats voluntarily climbed a 200-cm tower to drink water from a bottle set at the top. At 3 months, OVX elevated both the femoral cortex and lumbar trabecular turnover, leading to a reduction in bone mass and strength. However, in OVX-Exercise rats, those values were maintained at the same level as in the Sham-Sedentary rats. Thus, the climbing exercise, started after 3 days of OVX, prevented OVX-induced cortical and trabecular bone loss by depressing turnover elevation. After confirming the preventive effect, we evaluated the recovery effect of exercise. In experiment II, 90 Sprague-Dawley rats, 12 months of age, were assigned to six groups: a Baseline control, two groups of Sham-Operated Sedentary and OVX-Sedentary, and OVX-Exercise rats. The exercise started 3 months after the OVX operation. At 3 months, OVX increased the trabecular bone formation rate and osteoclast surface, leading to a decrease in compressive strength. In the midfemur, the cross-sectional area, moment of inertia, and bending load values decreased. At 6 months, in the OVX-Exercise rats, the parameters of breaking load in both the lumbar and midfemur, lumbar bone mass, and the total cross-sectional area recovered to the same levels as those in the Sham-Sedentary rats. However, the cortical bone area did not recover. Periosteal bone formation increased, while endosteal bone formation decreased. These results showed that the climbing exercise had both a preventive and recovery effect on bone strength in OVX rats. In the mid-femur, effects on bone formation were site-specific, and the cross-sectional morphology was improved without an increase in cortical bone area, supporting cortical drift by mechanical stimulation. [source] The Structural and Hormonal Basis of Sex Differences in Peak Appendicular Bone Strength in Rats,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2003Bom-Taeck Kim Abstract To identify the structural and hormonal basis for the lower incidence of fractures in males than females, sex differences in femoral mid-shaft geometry and breaking strength were studied in growth hormone (GH)-replete and -deficient male and female rats. Sexual dimorphism appeared during growth. Cortical thickening occurred almost entirely by acquisition of bone on the outer (periosteal) surface in males and mainly on the inner (endocortical) surface in females. By 8 months of age, males had 22% greater bone width and 33% greater breaking strength than females. Gonadectomy (Gx) at 6 weeks reduced sex differences in bone width to 7% and strength to 21% by halving periosteal bone formation in males and doubling it in females. Gx had no net effect on the endocortical surface in males but abolished endocortical bone acquisition in females. GH deficiency halved periosteal bone formation and had no net effect on the endocortical surface in males, but abolished bone acquisition on both surfaces in females, leaving males with 17% greater bone width and 44% greater breaking strength than females. Sex hormone deficiency produces greater bone fragility in males than females by removing a stimulator of periosteal growth in males and removing an inhibitor of periosteal growth in females. GH deficiency produces less bone fragility in males than females because males retain androgen-dependent periosteal bone formation while bone acquisition on both surfaces is abolished in females. Thus, periosteal growth is independently and additively stimulated by androgens and GH in males, inhibited by estrogen, and stimulated by GH in females. The hormonal regulation of bone surfaces establishes the amount and spatial distribution of bone and so the sexual dimorphism in its strength. [source] Bone Strength at Clinically Relevant Sites Displays Substantial Heterogeneity and Is Best Predicted From Site-Specific Bone DensitometryJOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2002Felix Eckstein Ph.D. Abstract In this study we test the hypotheses that mechanical bone strength in elderly individuals displays substantial heterogeneity among clinically relevant skeletal sites, that ex situ dual-energy X-ray absorptiometry (DXA) provides better estimates of bone strength than in situ DXA, but that a site-specific approach of bone densitometry is nevertheless superior for optimal prediction of bone failure under in situ conditions. DXA measurements were obtained of the lumbar spine, the left femur, the left radius, and the total body in 110 human cadavers (age, 80.6 ± 10.5 years; 72 female, 38 male), including the skin and soft tissues. The bones were then excised, spinal and femoral DXA being repeated ex situ. Mechanical failure tests were performed on thoracic vertebra 10 and lumbar vertebra 3 (compressive loading of a functional unit), the left and right femur (side impact and vertical loading configuration), and the left and right distal radius (fall configuration, axial compression, and 3-point-bending). The failure loads displayed only very moderate correlation among sites (r = 0.39 to 0.63). Ex situ DXA displayed slightly higher correlations with failure loads compared with those of in situ DXA, but the differences were not significant and relatively small. Under in situ conditions, DXA predicted 50-60% of the variability in bone failure loads at identical (or closely adjacent) sites, but only around 20-35% at distant sites, advocating a site-specific approach of densitometry. These data suggest that mechanical competence in the elderly is governed by strong regional variation, and that its loss in osteoporosis may not represent a strictly systemic process. [source] Lasofoxifene (CP-336,156) Protects Against the Age-Related Changes in Bone Mass, Bone Strength, and Total Serum Cholesterol in Intact Aged Male RatsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2001Hua Zhu Ke Abstract The purpose of this study was to evaluate if long-term (6 months) treatment with lasofoxifene (LAS), a new selective estrogen receptor modulator (SERM), can protect against age-related changes in bone mass and bone strength in intact aged male rats. Sprague-Dawley male rats at 15 months of age were treated (daily oral gavage) with either vehicle (n = 12) or LAS at 0.01 mg/kg per day (n = 12) or 0.1 mg/kg per day (n = 11) for 6 months. A group of 15 rats was necropsied at 15 months of age and served as basal controls. No significant change was found in body weight between basal and vehicle controls. However, an age-related increase in fat body mass (+42%) and decrease in lean body mass (,8.5%) was observed in controls. Compared with vehicle controls, LAS at both doses significantly decreased body weight and fat body mass but did not affect lean body mass. No significant difference was found in prostate wet weight among all groups. Total serum cholesterol was significantly decreased in all LAS-treated rats compared with both the basal and the vehicle controls. Both doses of LAS treatment completely prevented the age-related increase in serum osteocalcin. Peripheral quantitative computerized tomography (pQCT) analysis at the distal femoral metaphysis indicated that the age-related decrease in total density, trabecular density, and cortical thickness was completely prevented by treatment with LAS at 0.01 mg/kg per day or 0.1 mg/kg per day. Histomorphometric analysis of proximal tibial cancellous bone showed an age-related decrease in trabecular bone volume (TBV; ,46%), trabecular number (Tb.N), wall thickness (W.Th), mineral apposition rate, and bone formation rate-tissue area referent. Moreover, an age-related increase in trabecular separation (Tb.Sp) and eroded surface was observed. LAS at 0.01 mg/kg per day or 0.1 mg/kg per day completely prevented these age-related changes in bone mass, bone structure, and bone turnover. Similarly, the age-related decrease in TBV and trabecular thickness (Tb.Th) and the age-related increase in osteoclast number (Oc.N) and osteoclast surface (Oc.S) in the third lumbar vertebral cancellous bone were completely prevented by treatment with LAS at both doses. Further, LAS at both doses completely prevented the age-related decrease in ultimate strength (,47%) and stiffness (,37%) of the fifth lumbar vertebral body. These results show that treatment with LAS for 6 months in male rats completely prevents the age-related decreases in bone mass and bone strength by inhibiting the increased bone resorption and bone turnover associated with aging. Further, LAS reduced total serum cholesterol and did not affect the prostate weight in these rats. Our data support the potential use of a SERM for protecting against the age-related changes in bone and serum cholesterol in elderly men. [source] Intermittently Administered Human Parathyroid Hormone(1,34) Treatment Increases Intracortical Bone Turnover and Porosity Without Reducing Bone Strength in the Humerus of Ovariectomized Cynomolgus MonkeysJOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2001David B. Burr Abstract Cortical porosity in patients with hyperparathyroidism has raised the concern that intermittent parathyroid hormone (PTH) given to treat osteoporotic patients may weaken cortical bone by increasing its porosity. We hypothesized that treatment of ovariectomized (OVX) cynomolgus monkeys for up to 18 months with recombinant human PTH(1,34) [hPTH(1,34)] LY333334 would significantly increase porosity in the midshaft of the humerus but would not have a significant effect on the strength or stiffness of the humerus. We also hypothesized that withdrawal of PTH for 6 months after a 12-month treatment period would return porosity to control OVX values. OVX female cynomolgus monkeys were given once daily subcutaneous (sc) injections of recombinant hPTH(1,34) LY333334 at 1.0 ,g/kg (PTH1), 5.0 ,g/kg (PTH5), or 0.1 ml/kg per day of phosphate-buffered saline (OVX). Sham OVX animals (sham) were also given vehicle. After 12 months, PTH treatment was withdrawn from half of the monkeys in each treatment group (PTH1-W and PTH5-W), and they were treated for the remaining 6 months with vehicle. Double calcein labels were given before death at 18 months. After death, static and dynamic histomorphometric measurements were made intracortically and on periosteal and endocortical surfaces of sections from the middiaphysis of the left humerus. Bone mechanical properties were measured in the right humeral middiaphysis. PTH dose dependently increased intracortical porosity. However, the increased porosity did not have a significant detrimental effect on the mechanical properties of the bone. Most porosity was concentrated near the endocortical surface where its mechanical effect is small. In PTH5 monkeys, cortical area (Ct.Ar) and cortical thickness (Ct.Th) increased because of a significantly increased endocortical mineralizing surface. After withdrawal of treatment, porosity in PTH1-W animals declined to sham values, but porosity in PTH5-W animals remained significantly elevated compared with OVX and sham. We conclude that intermittently administered PTH(1,34) increases intracortical porosity in a dose-dependent manner but does not reduce the strength or stiffness of cortical bone. [source] RANKL Inhibition with Osteoprotegerin Increases Bone Strength by Improving Cortical and Trabecular bone Architecture in Ovariectomized Rats,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2008Michael S Ominsky Abstract Introduction: Ovariectomy (OVX) results in bone loss caused by increased bone resorption. RANKL is an essential mediator of bone resorption. We examined whether the RANKL inhibitor osteoprotegerin (OPG) would preserve bone volume, density, and strength in OVX rats. Materials and Methods: Rats were OVX or sham-operated at 3 mo of age. Sham controls were treated for 6 wk with vehicle (Veh, PBS). OVX rats were treated with Veh or human OPG-Fc (10 mg/kg, 2/wk). Serum RANKL and TRACP5b was measured by ELISA. BMD of lumbar vertebrae (L1,L5) and distal femur was measured by DXA. Right distal femurs were processed for bone histomorphometry. Left femurs and the fifth lumbar vertebra (L5) were analyzed by ,CT and biomechanical testing, and L6 was analyzed for ash weight. Results: OVX was associated with significantly greater serum RANKL and osteoclast surface and with reduced areal and volumetric BMD. OPG markedly reduced osteoclast surface and serum TRACP5b while completely preventing OVX-associated bone loss in the lumbar vertebrae, distal femur, and femur neck. Vertebrae from OPG-treated rats had increased dry and ash weight, with no significant differences in tissue mineralization versus OVX controls. ,CT showed that trabecular compartments in OVX-OPG rats had significantly greater bone volume fraction, vBMD, bone area, trabecular thickness, and number, whereas their cortical compartments had significantly greater bone area (p < 0.05 versus OVX-Veh). OPG improved cortical area in L5 and the femur neck to levels that were significantly greater than OVX or sham controls (p < 0.05). Biomechanical testing of L5 and femur necks showed significantly greater maximum load values in the OVX-OPG group (p < 0.05 versus OVX-Veh). Bone strength at both sites was linearly correlated with total bone area (r2 = 0.54,0.74, p < 0.0001), which was also significantly increased by OPG (p < 0.05 versus OVX). Conclusions: OPG treatment prevented bone loss, preserved trabecular architecture, and increased cortical area and bone strength in OVX rats. [source] Capsaicin-Sensitive Sensory Neurons Contribute to the Maintenance of Trabecular Bone Integrity,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2005Sarah C Offley Abstract This investigation used capsaicin to selectively lesion unmyelinated sensory neurons in rats. Neuronal lesioning induced a loss of trabecular integrity, reduced bone mass and strength, and depleted neuropeptides in nerve and bone. These data suggest that capsaicin-sensitive sensory nerves contribute to trabecular bone integrity. Introduction: Familial dysautomia is an autosomal recessive disease in which patients suffer from unmyelinated sensory neuron loss, reduced BMD, and frequent fractures. It has been proposed that the loss of neurotransmitters synthesized by unmyelinated neurons adversely affects bone integrity in this hereditary syndrome. The purpose of this study was to determine whether small sensory neurons are required for the maintenance of bone integrity in rats. Materials and Methods: Ten-month-old male Sprague-Dawley rats were treated with either capsaicin or vehicle. In vivo DXA scanning and ,CT scanning, and histomorphometry were used to evaluate BMD, structure, and cellular activity. Bone strength was measured in distal femoral sections. Body weight and gastrocnemius/soleus weights were measured and spontaneous locomotor activity was monitored. Peroneal nerve morphometry was evaluated using light and electron microscopy. Substance P and calcitonin gene-related peptide (CGRP) content in the sciatic nerve and proximal tibia were determined by enzyme immunoassay (EIA). Substance P signaling was measured using a sciatic nerve stimulation extravasation assay. Results: Four weeks after capsaicin treatment, there was a loss of BMD in the metaphyses of the tibia and femur. In the proximal tibia, the osteoclast number and surface increased, osteoblast activity and bone formation were impaired, and trabecular bone volume and connectivity were diminished. There was also a loss of bone strength in the distal femur. No changes occurred in body weight, 24-h grid-crossing activity, weight bearing, or muscle mass after capsaicin treatment, indicating that skeletal unloading did not contribute to the loss of bone integrity. Capsaicin treatment destroyed 57% of the unmyelinated sensory axons, reduced the substance P and CGRP content in the sciatic nerve and proximal tibia, and inhibited neurogenic extravasation. Conclusion: These results support the hypothesis that capsaicin-sensitive sensory neurons contribute to the maintenance of trabecular bone integrity. Capsaicin-sensitive neurons have efferent functions in the tissues they innervate, effects mediated by transmitters released from the peripheral nerve terminals. We postulate that the deleterious effects of capsaicin treatment on trabecular bone are mediated by reductions in local neurotransmitter content and release. [source] Ultrasound parameters of bone health and related physical measurement indicators for the community-dwelling elderly in JapanGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 2 2007Wei Sun Deteriorated bone strength, which approaches osteoporosis, increases the likelihood that an elderly person will not able to live independently. However, few data are available pertaining to bone health and various physical objective indicators. The aim of the present study was to objectively assess bone health by quantitative ultrasound (QUS) and identify related physical measurement indicators among the elderly to aid the health promotion strategies in Japan. A cross-sectional study was performed at five welfare centers for the aged in the suburban area of Takatsuki city, Japan. Subjects comprised community-dwelling persons (134 men, 240 women) aged ,60 years and registered at welfare centers. QUS of the right-heel was conducted and recorded as stiffness index (SI). Physical factors including body components (fat and muscle mass), handgrip strength, daily physical activity, daily walking steps, maximum and usual walking speed and maximum bite force were examined objectively during the period May,June 2005. SI in women was lower than that in men (P < 0.01) and decreased significantly with age (P < 0.01). The SI correlated with six physical items in men and with all items in women. Multiple linear regression analysis showed that muscle mass, usual walking speed and maximum bite force were the strongest physical indicators of male SI; and muscle mass, maximum walking speed and maximum bite force were the strongest indicators of female SI. Muscle training, daily walking exercise and oral health care should be included in health promotion programs for the bone health of elderly women and men in Japan. [source] Compensatory bone remodelling in moose: a study of age, sex, and cross-sectional cortical bone dimensions in moose at Isle Royale National ParkINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 5 2002Mary Hindelang Abstract We studied interrelationships among age, sex, and cross-sectional cortical bone dimensions using quantitative computed tomography (QCT) scans of metatarsal bones of 180 moose (Alces alces) that died in Isle Royale National Park, Michigan. As a large-bodied quadruped with demanding ecological constraints on movement and behaviour, a moose experiences different weight-bearing and mechanical stressors than humans, to whom most existing studies of mechanical adaptations of bone pertain. In moose, both sexes showed significant subperiosteal expansion and an increase in medullary area, with an overall increase in cortical bone area over time. Female moose did not exhibit cortical thinning or reduction in cross-sectional area with age, rather they showed an increase in cortical bone area with periosteal apposition exceeding endosteal resorption, similar to the males. We also found that moose undergo changes in bone geometry through remodelling of bone similar to humans, suggesting a compensatory mechanism for increasing bone strength under conditions of decline in bone mineral density with age. Copyright © 2002 John Wiley & Sons, Ltd. [source] Black bear femoral geometry and cortical porosity are not adversely affected by ageing despite annual periods of disuse (hibernation)JOURNAL OF ANATOMY, Issue 2 2007Meghan E. McGee Abstract Disuse (i.e. inactivity) causes bone loss, and a recovery period that is 2,3 times longer than the inactive period is usually required to recover lost bone. However, black bears experience annual disuse (hibernation) and remobilization periods that are approximately equal in length, yet bears maintain or increase cortical bone material properties and whole bone mechanical properties with age. In this study, we investigated the architectural properties of bear femurs to determine whether cortical structure is preserved with age in bears. We showed that cross-sectional geometric properties increase with age, but porosity and resorption cavity density do not change with age in skeletally immature male and female bears. These findings suggest that structural properties substantially contribute to increasing whole bone strength with age in bears, particularly during skeletal maturation. Porosity was not different between skeletally immature and mature bears, and showed minimal regional variations between anatomical quadrants and radial positions that were similar in pattern and magnitude between skeletally immature and mature bears. We also found gender dimorphisms in bear cortical bone properties: females have smaller, less porous bones than males. Our results provide further support for the idea that black bears possess a biological mechanism to prevent disuse osteoporosis. [source] Bone microstructure at the distal tibia provides a strength advantage to males in late puberty: An HR-pQCT studyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2010Melonie Burrows Abstract Bone is a complex structure with many levels of organization. Advanced imaging tools such as high-resolution (HR) peripheral quantitative computed tomography (pQCT) provide the opportunity to investigate how components of bone microstructure differ between the sexes and across developmental periods. The aim of this study was to quantify the age- and sex-related differences in bone microstructure and bone strength in adolescent males and females. We used HR-pQCT (XtremeCT, Scanco Medical, Geneva, Switzerland) to assess total bone area (ToA), total bone density (ToD), trabecular bone density (TrD), cortical bone density (CoD), cortical thickness (Cort.Th), trabecular bone volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular spacing standard deviation (Tb.Sp SD), and bone strength index (BSI, mg2/mm4) at the distal tibia in 133 females and 146 males (15 to 20 years of age). We used a general linear model to determine differences by age- and sex-group and age,×,sex interactions (p,<,0.05). Across age categories, ToD, CoD, Cort.Th, and BSI were significantly lower at 15 and 16 years compared with 17 to 18 and 19 to 20 years in males and females. There were no differences in ToA, TrD, and BV/TV across age for either sex. Between sexes, males had significantly greater ToA, TrD, Cort.Th, BV/TV, Tb.N, and BSI compared with females; CoD and Tb.Sp SD were significantly greater for females in every age category. Males' larger and denser bones confer a bone-strength advantage from a young age compared with females. These structural differences could represent bones that are less able to withstand loads in compression in females. © 2010 American Society for Bone and Mineral Research [source] The shifting trajectory of growth in femur length during gestationJOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2010Åshild Bjørnerem Abstract Bone size is a determinant of bone strength and tracks in its percentile of origin during childhood and adolescence. We hypothesized that the ranking of an individual's femur length (FL) is established in early gestation and tracks thereafter. Fetal FL was measured serially using 2D ultrasound in 625 Norwegian fetuses. Tracking was assessed using Pearson correlation, a generalized estimating equation model, and by calculating the proportion of fetuses whose FL remained within the same quartile. Baseline FL Z -score (weeks 10 to 19) and later measurements correlated, but more weakly as gestation advanced: r,=,0.59 (weeks 20 to 26); r,=,0.45 (weeks 27 to 33); and r,=,0.32 (weeks 34 to 39) (p,<,0.001). Tracking within the same quartile throughout gestation occurred in 13% of fetuses. Of the 87% deviating, 21% returned to the quartile of origin, so 34% began and ended in the same quartile, 38% deviated by one quartile, and 28% deviated by two or more quartiles by the end of gestation. A standard deviation higher baseline FL Z -score, placental weight (150,g), maternal height (5,cm), and weight (10,kg), was associated with a 0.25, 0.15, 0.10, and 0.05 SD higher FL Z -score at the end of gestation, respectively (p ranging from <0.001 to 0.02). Tracking within the same percentile throughout the whole of gestation, as suggest by growth charts, is uncommon. Deviation from tracking is more common and is the result of changes in growth velocity within and between fetuses and is partly influenced by maternal, fetal, and placental factors. © 2010 American Society for Bone and Mineral Research [source] Severity of Vertebral Fractures Is Associated With Alterations of Cortical Architecture in Postmenopausal Women,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2009Elisabeth Sornay-Rendu Abstract Patients with vertebral fractures (VFx) have trabecular architectural disruption on iliac biopsies. Because cortical bone is an important determinant of bone strength, we assessed cortical and trabecular microarchitecture at peripheral sites in patients with VFx of varying number (N) and severity (S). Bone architecture and volumetric density (vBMD) were assessed at the distal radius and tibia with HR-pQCT (XTreme CT; Scanco Medical, Bassersdorf, Switzerland) in 100 women with VFx (age, 74 ± 9 yr) of different S (GI, n = 23; GII, n = 35; GIII, n = 42) and in 362 women (age, 69 ± 7 yr) without peripheral or VFx (G0) from the OFELY study. Spine areal BMD (aBMD) was assessed by DXA. Among all women, at the radius and after adjustment for age and aBMD, there were significant trends in lower vBMD, cortical thickness (Cort.Th), trabecular number (Tb.N) and thickness (Tb.Th), higher trabecular separation (Tb.Sp), and distribution of separation (Tb.Sp.SD) with greater VFx S and N. Among women with VFx, lower Cort.Th and cortical vBMD (D.Cort) were associated with severe (GIII) and multiple (n > 2) VFx (p < 0.05). The age-adjusted OR for each SD decrease of Cort.Th was 2.04 (95% CI, 1.02,4.00) after adjustment for aBMD. At the tibia, there were trends for lower vBMD, Tb.N, Tb.Th, and higher Tb.Sp and Tb.Sp.SD with greater VFx S and N (p < 0.001). Among women with VFx, lower Cort.Th and D.Cort were associated with severe and multiple (n > 3) VFx (p < 0.01). In postmenopausal women, VFx are associated with low vBMD and architectural decay of trabecular and cortical bone at the radius and tibia, independently of spine aBMD. Severe and multiple VFx are associated with even more alterations of cortical bone. [source] Hip Fractures and the Contribution of Cortical Versus Trabecular Bone to Femoral Neck Strength,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2009Gerold Holzer Abstract Osteoporotic fractures are caused by both cortical thinning and trabecular bone loss. Both are seen to be important for bone fragility. The relative contributions of cortical versus trabecular bone have not been established. The aim of this study was to test the contribution of cortical versus trabecular bone to femoral neck stability in bone strength. In one femur from each pair of 18 human cadaver femurs (5 female; 4 male), trabecular bone was completely removed from the femoral neck, providing one bone with intact and the other without any trabecular structure in the femoral neck. Geometrical, X-ray, and DXA measurements were carried out before biomechanical testing (forces to fracture). Femoral necks were osteotomized, slices were analyzed for cross-sectional area (CSA) and cross-sectional moment of inertia (CSMI), and results were compared with biomechanical testing data. Differences between forces needed to fracture excavated and intact femurs (,F/F mean) was 7.0% on the average (range, 4.6,17.3%). CSA of removed spongiosa did not correlate with difference of fracture load (,F/F mean), nor did BMD. The relative contribution of trabecular versus cortical bone in respect to bone strength in the femoral neck seems to be marginal and seems to explain the subordinate role of trabecular bone and its changes in fracture risk and the effects of treatment options in preventing fractures. [source] A Bivariate Whole Genome Linkage Study Identified Genomic Regions Influencing Both BMD and Bone Structure,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2008Xiao-Gang Liu Abstract Areal BMD (aBMD) and areal bone size (ABS) are biologically correlated traits and are each important determinants of bone strength and risk of fractures. Studies showed that aBMD and ABS are genetically correlated, indicating that they may share some common genetic factors, which, however, are largely unknown. To study the genetic factors influencing both aBMD and ABS, bivariate whole genome linkage analyses were conducted for aBMD-ABS at the femoral neck (FN), lumbar spine (LS), and ultradistal (UD)-forearm in a large sample of 451 white pedigrees made up of 4498 individuals. We detected significant linkage on chromosome Xq27 (LOD = 4.89) for LS aBMD-ABS. In addition, we detected suggestive linkages at 20q11 (LOD = 3.65) and Xp11 (LOD = 2.96) for FN aBMD-ABS; at 12p11 (LOD = 3.39) and 17q21 (LOD = 2.94) for LS aBMD-ABS; and at 5q23 (LOD = 3.54), 7p15 (LOD = 3.45), Xq27 (LOD = 2.93), and 12p11 (LOD = 2.92) for UD-forearm aBMD-ABS. Subsequent discrimination analyses indicated that quantitative trait loci (QTLs) at 12p11 and 17q21 may have pleiotropic effects on aBMD and ABS. This study identified several genomic regions that may contain QTLs important for both aBMD and ABS. Further endeavors are necessary to follow these regions to eventually pinpoint the genetic variants affecting bone strength and risk of fractures. [source] Theoretical Implications of the Biomechanical Fracture ThresholdJOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2008Tony M Keaveny Abstract Because of the dichotomous nature of a bone fracture, when ,, the ratio of the applied impact force to the bone strength, is greater than a critical value,the biomechanical fracture threshold,fracture should occur. We sought to elucidate the conceptual implications of this biomechanical fracture threshold with application to hip fracture. We used data from the PaTH study, a 2-yr clinical trial in postmenopausal women treated with alendronate, PTH, or their combination. Outcomes included the force applied to the hip in a sideways fall as estimated from subject height and weight; femoral strength as determined by QCT-based finite element analysis; the load-to-strength ratio ,; and total hip areal BMD from DXA. Results indicated that those with "very low" femoral strength (<2000 N) invariably had load-to-strength ratio , values well above the theoretical biomechanical fracture threshold (, = 1), but those with "moderately low" femoral strength (2000,4000 N) displayed , values both above and below the theoretical biomechanical fracture threshold. This finding implies that the risk of a hip fracture can be high in those with only moderately low BMD because femoral strength can be low relative to fall impact forces. The observed weak correlation between areal BMD and the load-to-strength ratio , (r2 = 0.14) suggests that consideration of the biomechanical fracture threshold may improve fracture risk assessment, particularly for those in the osteopenic range. Regarding treatment effects, only those subjects having load-to-strength ratio , values within a relatively narrow "transition zone" of ±20% of the assumed biomechanical fracture threshold at baseline were predicted to change fracture status during the trial. In theory, outcomes of fracture trials may be dominated by the responses of those within the "transition zone" at baseline, and treatment benefits in terms of fracture efficacy may depend the patient's baseline status with respect to the biomechanical fracture threshold. We conclude that consideration of the theoretical implications of the biomechanical fracture threshold may lead to new insights and advances in the assessment and treatment of osteoporosis. [source] Targeted Deletion of the Sclerostin Gene in Mice Results in Increased Bone Formation and Bone Strength,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2008Xiaodong Li Abstract Introduction: Sclerosteosis is a rare high bone mass genetic disorder in humans caused by inactivating mutations in SOST, the gene encoding sclerostin. Based on these data, sclerostin has emerged as a key negative regulator of bone mass. We generated SOST knockout (KO) mice to gain a more detailed understanding of the effects of sclerostin deficiency on bone. Materials and Methods: Gene targeting was used to inactivate SOST and generate a line of SOST KO mice. Radiography, densitometry, ,CT, histomorphometry, and mechanical testing were used to characterize the impact of sclerostin deficiency on bone in male and female mice. Comparisons were made between same sex KO and wildtype (WT) mice. Results: The results for male and female SOST KO mice were similar, with differences only in the magnitude of some effects. SOST KO mice had increased radiodensity throughout the skeleton, with general skeletal morphology being normal in appearance. DXA analysis of lumbar vertebrae and whole leg showed that there was a significant increase in BMD (>50%) at both sites. ,CT analysis of femur showed that bone volume was significantly increased in both the trabecular and cortical compartments. Histomorphometry of trabecular bone revealed a significant increase in osteoblast surface and no significant change in osteoclast surface in SOST KO mice. The bone formation rate in SOST KO mice was significantly increased for trabecular bone (>9-fold) at the distal femur, as well as for the endocortical and periosteal surfaces of the femur midshaft. Mechanical testing of lumbar vertebrae and femur showed that bone strength was significantly increased at both sites in SOST KO mice. Conclusions:SOST KO mice have a high bone mass phenotype characterized by marked increases in BMD, bone volume, bone formation, and bone strength. These results show that sclerostin is a key negative regulator of a powerful, evolutionarily conserved bone formation pathway that acts on both trabecular and cortical bone. [source] RANKL Inhibition with Osteoprotegerin Increases Bone Strength by Improving Cortical and Trabecular bone Architecture in Ovariectomized Rats,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2008Michael S Ominsky Abstract Introduction: Ovariectomy (OVX) results in bone loss caused by increased bone resorption. RANKL is an essential mediator of bone resorption. We examined whether the RANKL inhibitor osteoprotegerin (OPG) would preserve bone volume, density, and strength in OVX rats. Materials and Methods: Rats were OVX or sham-operated at 3 mo of age. Sham controls were treated for 6 wk with vehicle (Veh, PBS). OVX rats were treated with Veh or human OPG-Fc (10 mg/kg, 2/wk). Serum RANKL and TRACP5b was measured by ELISA. BMD of lumbar vertebrae (L1,L5) and distal femur was measured by DXA. Right distal femurs were processed for bone histomorphometry. Left femurs and the fifth lumbar vertebra (L5) were analyzed by ,CT and biomechanical testing, and L6 was analyzed for ash weight. Results: OVX was associated with significantly greater serum RANKL and osteoclast surface and with reduced areal and volumetric BMD. OPG markedly reduced osteoclast surface and serum TRACP5b while completely preventing OVX-associated bone loss in the lumbar vertebrae, distal femur, and femur neck. Vertebrae from OPG-treated rats had increased dry and ash weight, with no significant differences in tissue mineralization versus OVX controls. ,CT showed that trabecular compartments in OVX-OPG rats had significantly greater bone volume fraction, vBMD, bone area, trabecular thickness, and number, whereas their cortical compartments had significantly greater bone area (p < 0.05 versus OVX-Veh). OPG improved cortical area in L5 and the femur neck to levels that were significantly greater than OVX or sham controls (p < 0.05). Biomechanical testing of L5 and femur necks showed significantly greater maximum load values in the OVX-OPG group (p < 0.05 versus OVX-Veh). Bone strength at both sites was linearly correlated with total bone area (r2 = 0.54,0.74, p < 0.0001), which was also significantly increased by OPG (p < 0.05 versus OVX). Conclusions: OPG treatment prevented bone loss, preserved trabecular architecture, and increased cortical area and bone strength in OVX rats. [source] Perspective: Quantifying Osteoblast and Osteocyte Apoptosis: Challenges and Rewards,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2007Robert L Jilka Abstract Since the initial demonstration of the phenomenon in murine and human bone sections ,10 yr ago, appreciation of the biologic significance of osteoblast apoptosis has contributed greatly not only to understanding the regulation of osteoblast number during physiologic bone remodeling, but also the pathogenesis of metabolic bone diseases and the pharmacology of some of the drugs used for their treatment. It is now appreciated that all major regulators of bone metabolism including bone morphogenetic proteins (BMPs), Wnts, other growth factors and cytokines, integrins, estrogens, androgens, glucocorticoids, PTH and PTH-related protein (PTHrP), immobilization, and the oxidative stress associated with aging contribute to the regulation of osteoblast and osteocyte life span by modulating apoptosis. Moreover, osteocyte apoptosis has emerged as an important regulator of remodeling on the bone surface and a critical determinant of bone strength, independently of bone mass. The detection of apoptotic osteoblasts in bone sections remains challenging because apoptosis represents only a tiny fraction of the life span of osteoblasts, not unlike a 6-mo -long terminal illness in the life of a 75-yr -old human. Importantly, the phenomenon is 50 times less common in human bone biopsies because human osteoblasts live longer and are fewer in number. Be that as it may, well-controlled assays of apoptosis can yield accurate and reproducible estimates of the prevalence of the event, particularly in rodents where there is an abundance of osteoblasts for inspection. In this perspective, we focus on the biological significance of the phenomenon for understanding basic bone biology and the pathogenesis and treatment of metabolic bone diseases and discuss limitations of existing techniques for quantifying osteoblast apoptosis in human biopsies and their methodologic pitfalls. [source] Strontium Ranelate Treatment Improves Trabecular and Cortical Intrinsic Bone Tissue Quality, a Determinant of Bone Strength,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2007Patrick Ammann MD Abstract Beside its influence on determinants of bone strength (geometry, microarchitecture), which is likely to be related to a cellular effect, strontium ranelate improves bone tissue quality as evaluated by nanoindentation, increasing elastic modulus, hardness, and dissipated energy in vertebrae of rats treated for 104 wk with daily dose from 0 to 900 mg/kg. Introduction: We previously showed that strontium ranelate treatment improves the mechanical properties of the vertebral body and long bone midshaft in intact rats. The increased energy to failure obtained with strontium ranelate is essentially caused by an increase in plastic energy, suggesting that bone formed during treatment can withstand greater deformation before fracture. In the bone mineral phase, strontium is mainly located in the hydrated shell and could thus potentially influence intrinsic bone tissue quality. Materials and Methods: To study whether strontium ranelate treatment could positively influence intrinsic bone tissue quality (elastic modulus, hardness, and dissipated energy), nanoindentation tests were performed at the level of trabecular nodes and cortex under physiological or dry conditions in vertebrae of rats treated for 104 wk with strontium ranelate at a daily dose of 0, 225, 450, or 900 mg/kg (n = 12 per group). Ex vivo ,CT measurements and axial compression tests of adjacent vertebral bodies were also performed. Significance of difference was evaluated using ANOVA. Results: In agreement with previous results, strontium ranelate (900 mg/kg/d) significantly increased versus controls in maximal load (+23%), total energy (+71%), and plastic energy (+143%). At the level of trabecular bone, strontium ranelate treatment resulted in a significant increase in elastic modulus (+15.1%, p < 0.01), hardness (+11.5%, p < 0.05), and dissipated energy (+16.2%, p < 0.001) versus controls in physiological, but not in dry, conditions. The effect was less pronounced in cortex. Conclusions: These results show for the first time a direct action of strontium ranelate on bone tissue quality. Beside its shown influence on classical determinants of bone strength (geometry, microarchitecture), which is likely to be related to a cellular effect, strontium ranelate improves bone tissue quality. This could contribute to the increase in bone strength and thus be involved in the reduction of fracture risk in postmenopausal osteoporotic patients treated with strontium ranelate. [source] Is a School-Based Physical Activity Intervention Effective for Increasing Tibial Bone Strength in Boys and Girls?,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2007Heather M Macdonald Abstract This 16-month randomized, controlled school-based study compared change in tibial bone strength between 281 boys and girls participating in a daily program of physical activity (Action Schools! BC) and 129 same-sex controls. The simple, pragmatic intervention increased distal tibia bone strength in prepubertal boys; it had no effect in early pubertal boys or pre or early pubertal girls. Introduction: Numerous school-based exercise interventions have proven effective for enhancing BMC, but none have used pQCT to evaluate the effects of increased loading on bone strength during growth. Thus, our aim was to determine whether a daily program of physical activity, Action Schools! BC (AS! BC) would improve tibial bone strength in boys and girls who were pre- (Tanner stage 1) or early pubertal (Tanner stage 2 or 3) at baseline. Materials and Methods: Ten schools were randomized to intervention (INT, 7 schools) or control (CON, 3 schools). The bone-loading component of AS! BC included a daily jumping program (Bounce at the Bell) plus 15 minutes/day of classroom physical activity in addition to regular physical education. We used pQCT to compare 16-month change in bone strength index (BSI, mg2/mm4) at the distal tibia (8% site) and polar strength strain index (SSIp, mm3) at the tibial midshaft (50% site) in 281 boys and girls participating in AS! BC and 129 same-sex controls. We used a linear mixed effects model to analyze our data. Results: Children were 10.2 ± 0.6 years at baseline. Intervention boys tended to have a greater increase in BSI (+774.6 mg2/mm4; 95% CI: 672.7, 876.4) than CON boys (+650.9 mg2/mm4; 95% CI: 496.4, 805.4), but the difference was only significant in prepubertal boys (p = 0.03 for group × maturity interaction). Intervention boys also tended to have a greater increase in SSIp (+198.6 mm3; 95% CI: 182.9, 214.3) than CON boys (+177.1 mm3; 95% CI: 153.5, 200.7). Change in BSI and SSIp was similar between CON and INT girls. Conclusions: Our findings suggest that a simple, pragmatic program of daily activity enhances bone strength at the distal tibia in prepubertal boys. The precise exercise prescription needed to elicit a similar response in more mature boys or in girls might be best addressed in a dose,response trial. [source] | ||||||||||||||||