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Introduction: We evaluated effects of teriparatide (rDNA origin) injection [teriparatide, rhPTH (1–34), TPTD] on hip structure among a subset 558 postmenopausal women enrolled in the Fracture Prevention Trial. Methods: Patients were randomized to once-daily, self-administered subcutaneous injections of placebo (N = 189), teriparatide 20 μg (TPTD20; N = 186), or 40 μg (TPTD40; N = 183) for a median of 20 months. Repeated dual energy X-ray absorptiometry (DXA) hip scans were analyzed with the Hip Structure Analysis (HSA) program to derive structural geometry. Results and conclusions: There were no significant differences in age or body size between groups at baseline, 1 year, or study termination. At the femoral neck, teriparatide increased bone mass and improved bone geometric strength in both treatment groups compared to the placebo group, with the response being dose-related. The mean difference (95% CI) in bone cross-sectional area (CSA) in the TPTD20 was 3.5% (1.8% to 5.3%), and 6.3% (4.5% to 8.2%) in TPTD40 at study termination, compared to placebo controls. Teriparatide treatment increased bending strength, with the mean difference in section modulus being 3.6% (1.4% to 5.8%) and 6.8% (4.6% to 9.1%) greater in the TPTD20 and TPTD40 groups, respectively. Compared to placebo, local cortical instability characterized by the buckling ratio decreased by 5.5% (3.5% to 7.5%) and 8.6% (6.6% to 10.5%) in the TPTD20 and TPTD40 groups, respectively, during the study period. The changes at the intertrochanteric region were comparable to those at the narrow neck although between-group differences were slightly smaller. Except for an inconsequential (1%) improvement in section modulus in TPTD20, teriparatide effects did not reach significance at the femoral shaft. In conclusion, teriparatide treatment improved axial and bending strength, and increased cortical thickness and stability at the femoral neck and intertrochanteric region. Teriparatide treatment effects were not apparent at the purely cortical femoral shaft.

Before puberty, there are only small sex differences in body shape and composition. During adolescence, sexual dimorphism in bone, lean, and fat mass increases, giving rise to the greater size and strength of the male skeleton. The question remains as to whether there are sex differences in bone strength or simply differences in anthropometric dimensions. To test this, we applied hip structural analysis (HSA) to derive strength and geometric indices of the femoral neck using bone densitometry scans (DXA) from a 6-year longitudinal study in Canadian children. Seventy boys and sixty-eight girls were assessed annually for 6 consecutive years. At the femoral neck, cross-sectional area (CSA, an index of axial strength), subperiosteal width (SPW), and section modulus (Z, an index of bending strength) were determined, and data were analyzed using a hierarchical (random effects) modeling approach. Biological age (BA) was defined as years from age at peak height velocity (PHV). When BA, stature, and total-body lean mass (TB lean) were controlled, boys had significantly higher Z than girls at all maturity levels (P < 0.05). Controlling height and TB lean for CSA demonstrated a significant independent sex by BA interaction effect (P < 0.05). That is, CSA was greater in boys before PHV but higher in girls after PHV. The coefficients contributing the greatest proportion to the prediction of CSA, SPW, and Z were height and lean mass. Because the significant sex difference in Z was relatively small and close to the error of measurement, we questioned its biological significance. The sex difference in bending strength was therefore explained by anthropometric differences. In contrast to recent hypotheses, we conclude that the CSA-lean ratio does not imply altered mechanosensitivity in girls because bending dominates loading at the neck, and the Z -lean ratio remained similar between the sexes throughout adolescence. That is, despite the greater CSA in girls, the bone is strategically placed to resist bending; hence, the bones of girls and boys adapt to mechanical challenges in a similar way.

The purpose of this study was to evaluate the remaining effects of 12-month intervention of alendronate and exercise on selected risk factors of fragility fractures in 15-month follow-up after withdrawal of intervention among early postmenopausal women. The trial consisted four experimental groups: (1) 5 mg of alendronate daily + exercise (Al+Ex+), (2) 5 mg alendronate daily (Al+Ex-), (3) placebo + exercise (Al-Ex+), and (4) placebo (Al-Ex-). At the follow-up measurements, bone mass and physical fitness of 102 women (mean age 53.5 +/- 2.5 years) out of initial 150 subjects could be evaluated. Alendronate increased bone mass significantly [mean; 95% confidence interval (CI)] during the intervention at the lumbar spine (3.9%; 2.2% to 5.7%) and femoral neck (2.1%; 0.9% to 3.4%). After withdrawal of alendronate, bone loss resumed to the rate comparable to that evident in the placebo group. Despite the declining bone mass, the between-group mean difference (3.2%; 1.0% to 5.4%) remained at the lumbar spine. However, the benefits at the femoral neck had disappeared 15 months after the withdrawal of alendronate. The 12-month exercise training resulted in significant increases in muscle power, dynamic balance, and aerobic capacity with no benefits on bone mass. Fifteen months later, these performance variables had declined among both the exercisers and nonexercisers. Although the between-group differences were no longer statistically significant, muscle power, dynamic balance, and aerobic capacity of those who exercised still remained above the pretraining levels. In conclusion, 12-month treatment with alendronate prevented postmenopausal bone loss, and residual effect was seen 15 months after withdrawal of the drug at the lumbar spine. Similarly, exercise improved muscle power, agility, and aerobic capacity during the intervention, but the improvement was lost after the cessation of the exercise program. Based on these results, it was evident that to maintain the benefits of alendronate or exercise, therapy should be continued.

The purpose of this cohort study was to focus on factors associated with bone mass and structure of lower limbs and physical performance after menopause. Eighty nonsmoking women with a mean age of 62.1 (SD 0.8) years participated in the study. They were classified into two groups by their use of hormone replacement therapy (HRT), either the current users (n = 43) or the never or discontinued users (n = 37). The tibial shaft and distal tibia were scanned with peripheral computed tomography. For the shaft region, the bone mineral content (BMC, g), cortical density (CoD, g/cm(3)), cortical area (CoA, mm(2)), and section modulus (BSI, mm(3)) were determined. For the distal part, the evaluated variables were BMC, total area (ToA), ratio of cortical to total area (CoA/ToA), trabecular density (TrD, g/mm(3)), cortical thickness, BSI, and buckling ratio. Isometric and dynamic muscle strength of the leg extensors, agility and postural sway, and cardiorespiratory capacity (VO(2max)) were measured. Unadjusted values for all bone variables were slightly higher among the HRT users compared to nonusers, with the exception of TrD with no difference. After controlling for body weight, the mean differences (95% confidence interval) remained significant for CoD of the tibial shaft and BSI of the distal tibia, the mean between-group differences being 1.5% (0.4 to 2.5%) and 23.0% (7.1 to 41.3%), respectively. Underlying the greater bending strength, HRT users had thicker cortices and a greater ratio of CoA/ToA. No differences existed between the two study groups for lower limb isometric or dynamic power, cardiorespiratory capacity, or postural balance or sway. HRT may offer protection against bone loss and maintain bone strength, although its ability to improve physical performance is not evident.

Weight loss is claimed to cause bone loss. This prospective 12-month study evaluated effects of 3-month group-based weight loss with VLED on body composition, bone mass and strength (DXA and pQCT), muscle performance and biomarkers of bone turnover. The assessments were done at baseline and at 3 and 12 months. Sixty-two women of the recruited 75 obese (BMI>30) premenopausal women who completed the study were divided into 3 groups based on the tertiles of weight loss at 3 months. The group means of weight losses were 15.5% (Large), 10.5% (Medium) and 5.9% (Low). Statistical analyses were based on analysis of covariance. Bone turnover increased during the weight reduction period in all groups but practically returned to baseline during the weight maintenance phase. In general, mean bone changes remained marginal (approximately +/-1%) and the amount of weight reduction was not associated with bone loss. The only notable change was the 4% decline in bending strength at the distal radius. These results indicate that in obese premenopausal women, 3-month weight reduction resulted in increased bone turnover but was not deleterious for bone mass or strength at 3 months or after 9-month weight maintenance.

Introduction Fracture risk is associated with bone mineral density (BMD) and with other indices of bone strength, including hip geometry. While the heritability and associated fracture risk of BMD are well described, less is known about genetic influences of bone geometry. We derived hip structural phenotypes using the Hip Structural Analysis program (HSA) and performed autosome-wide linkage analysis of hip geometric structural phenotypes. Materials and methods The Amish Family Osteoporosis Study was designed to identify genes affecting bone health. BMD was measured at the hip using dual X-ray absorptiometry (DXA) in 879 participants (mean age ± SD = 49.8 ± 16.1 years, range 18–91 years) from large multigenerational families. From DXA scans, we computed structural measures of hip geometry at the femoral neck (NN) and shaft (S) by HSA, including cross-sectional area (CSA), endocortical or inner diameter (ID), outer diameter (OD) buckling ratio (BR) and section modulus (Z). Genotyping of 731 highly polymorphic microsatellite markers (average spacing of 5.4 cM) and autosome-wide multipoint linkage analysis was performed. Results The heritability of HSA-derived hip phenotypes ranged from 40 to 84%. In the group as a whole, autosome-wide linkage analysis suggested evidence of linkage for QTLs related to NN_Z on chromosome 1p36 (LOD = 2.36). In subgroup analysis, ten additional suggestive regions of linkage were found on chromosomes 1, 2, 5, 6, 11, 12, 14, 15 and 17, all with LOD > 2.3 except for our linkage at 17q11.2-13 for men and women age 50 and under for NN_CSA, which had a lower LOD of 2.16, but confirmed a previous linkage report. Conclusions We found HSA-derived measures of hip structure to be highly heritable independent of BMD. No strong evidence of linkage was found for any phenotype. Confirmatory evidence of linkage was found on chromosome 17q11.2-12 for NN_CSA. Modest evidence was found for genes affecting hip structural phenotypes at ten other chromosomal locations.

This cross-sectional study of adult female athletes assessed whether the apparent loading-related differences in bone structure are primarily associated with the loading type or the muscle performance-related joint moments. Several structural variables at shaft sites of the tibia, radius and humerus, and distal sites of the tibia and radius were measured with peripheral quantitative computed tomography (pQCT) among 113 female national level athletes (representing hurdling, volleyball, soccer, racket-sports and swimming) and their 30 nonathletic referents. For the weight-bearing lower extremities, the loading modalities of the above sports were classified into high-impact (hurdling, volleyball), odd-impact (soccer, racket-sports) and repetitive, nonimpact (swimming) loadings; and for the nonweight-bearing upper extremities into high magnitude (functional weightlifting in hurdling and soccer), impact (volleyball, racket-sports) and repetitive, nonimpact (swimming) loadings. As expected, athletes' bone mass was substantially higher at loaded bone sites compared with the nonathletic referents, but more pertinently to the locomotive perspective, the loading-induced additional bone mass seemed to be used to build mechanically strong and appropriate bone structures. Compared with controls, the weight-bearing bone structures of female athletes (swimmers excluded) were characterized by larger diaphysis, thicker cortices and somewhat denser trabecular bone. The athletes' bones at the nonweight-bearing upper extremity were generally larger in cross-sectional area. The estimated indices of joint moment (muscle force x estimated lever arm) were explained from 29% to 50%, and the loading modalities from 8% to 25%, of the variance in most bone variables (P < 0.05) of the tibia (shaft and distal site). In contrast to the weight-bearing tibia, only the estimated joint moment was positively associated (P < 0.05) with the structural characteristics of the radius and humerus, accounting for 6% to 26% of the variance in bone variables of the shafts of these bones. Such association was not observed at the distal radius. In conclusion, at the weight-bearing lower extremity, the strong bone structure of the female athletes was attributable to muscle performance-related estimated joint moments and impact loading modality. At the shaft sites of the nonweight-bearing upper extremity, the strong bone structure was mainly attributable to the estimated joint moments. Thus, different loading history and other features of loading seemed to govern the skeletal adaptation at the upper and lower extremity.

In this randomized, double-blind, placebo-controlled 12-month trial we evaluated effects of weight- bearing jumping exercise and oral alendronate, alone or in combination, on the mass and structure of bone, risk factors for falling (muscle strength and power, postural sway, and dynamic balance), and cardiorespiratory fitness in postmenopausal women. A total of 164 healthy, sedentary, early postmenopausal women were randomly assigned to one of four experimental groups: (1) 5 mg of alendronate daily plus progressive jumping exercise, (2) 5 mg alendronate, (3) placebo plus progressive jumping exercise, or (4) placebo. The primary endpoint was 12-month change in bone mass and geometry (measured with dual-energy X-ray absorptiometry and peripheral computed tomography at several axial and limb sites) and physical performance; the secondary endpoint was change in biochemical markers of bone turnover. The jumping exercise was conducted an average 1.6 +/- 0.9 (mean +/- SD) times a week. Alendronate daily was effective in increasing bone mass at the lumbar spine (alendronate vs placebo 3.5%; 95% CI, 2.2-4.9%) and femoral neck (1.3%; 95% CI, 0.2-2.4%) but did not affect other bone sites. Exercise alone had no effect on bone mass at the lumbar spine or femoral neck; it had neither an additive nor an interactive effect with alendronate at these bone sites. However, at the distal tibia the mean increase of 3.6% (0.3-7.1%) in the section modulus (that is, bone strength) and 3.7% (0.1-7.3%) increase in the ratio of cortical bone to total bone area were statistically significant in the exercise group compared to the nonexercise group, indicating exercise-induced thickening of the bone cortex. Bone turnover was reduced in alendronate groups only. Alendronate had no effect on physical performance while the jumping exercise improved leg extensor power, dynamic balance, and cardiorespiratory fitness. As conclusion Alendronate is effective in increasing bone mass at the lumbar spine and femoral neck, while exercise is effective in increasing the mechanical properties of bone at some of the most loaded bone sites, as well as improving the participants' muscular performance and dynamic balance. Together alendronate and exercise may effectively decrease the risk of osteoporotic fractures.