Serum leptin levels are associated with bone mass in nonobese women

Both serum leptin and bone mineral density are positively correlated with body fat, generating the hypothesis that leptin may be a systemic and/or local regulator of bone mass. We investigated 214 healthy, nonobese Australian women aged 20-91 yr. Bone mineral content, projected bone area, and body fat mass were measured by dual energy x-ray absorptiometry and fasting serum leptin levels by RIA. Associations between bone mineral content (adjusted for age, body weight, body fat mass, and bone area) and the natural logarithm of serum leptin concentrations were analyzed by multiple regression techniques. There was a significant positive association at the lateral spine, two proximal femur sites (Ward's triangle and trochanter), and whole body (partial r² = 0.019 to 0.036; all P < 0.05). Similar trends were observed at the femoral neck and posterior-anterior-spine. With bone mineral density the dependent variable (adjusted for age, body weight, and body fat mass), the association with the natural logarithm of leptin remained significant at the lateral spine (partial r² = 0.030; P = 0.011), was of borderline significance at the proximal femur sites (partial r² = 0.012 to 0.017; P = 0.058 to 0.120), and was not significant at the other sites. Our results demonstrate an association between serum leptin levels and bone mass consistent with the hypothesis that circulating leptin may play a role in regulating bone mass.

Maternal vitamin D in pregnancy may influence not only offspring bone mass but other aspects of musculoskeletal health and adiposity

Osteoporotic fractures, falls and obesity are major health problems in developed nations. Evidence suggests that there are antenatal factors predisposing to these conditions. Data are emerging from Australia and elsewhere to suggest that maternal vitamin D status in pregnancy affects intrauterine skeletal mineralisation and skeletal growth together with muscle development and adiposity. Given that low levels of vitamin D have been documented in many urbanised populations, including those in countries with abundant sunlight, an important issue for public health is whether maternal vitamin D insufficiency during pregnancy has adverse effects on offspring health. The developing fetus may be exposed to low levels of vitamin D during critical phases of development as a result of maternal hypovitaminosis D. We hypothesise that this may have adverse effects on offspring musculoskeletal health and other aspects of body composition. Further research focused on the implications of poor gestational vitamin D nutrition is warranted as these developmental effects are likely to have a sustained influence on health during childhood and in adult life. We suggest that there is a clear rationale for randomised clinical trials to assess the potential benefits and harmful effects of vitamin D supplementation during pregnancy.

Energy deficiency, menstrual disturbances, and low bone mass : what do exercising Australian women know about the female athlete triad?

Purpose: Prevention of the female athlete triad is essential to protect female athletes’ health. The aim of this study was to investigate the knowledge, attitudes, and behaviors of regularly exercising adult women in Australia toward eating patterns, menstrual cycles, and bone health.
Methods: A total of 191 female exercisers, age 18–40 yr, engaging in ≥2 hr/wk of strenuous activity, completed a survey. After 11 surveys were excluded (due to incomplete answers), the 180 participants were categorized into lean-build sports (n = 82; running/ athletics, triathlon, swimming, cycling, dancing, rowing), non-lean-build sports (n = 94; basketball, netball, soccer, hockey, volleyball, tennis, trampoline, squash, Australian football), or gym/fitness activities (n = 4).
Results: Mean (± SD) training volume was 9.0 ± 5.5 hr/wk, with participants competing from local up to international level. Only 10% of respondents could name the 3 components of the female athlete triad. Regardless of reported history of stress fracture, 45% of the respondents did not think that amenorrhea (absence of menses for ≥3 months) could affect bone health, and 22% of those involved in lean-build sports would do nothing if experiencing amenorrhea (vs. 3.2% in non-lean-build sports, p = .005). Lean-build sports, history of amenorrhea, and history of stress fracture were all significantly associated with not taking action in the presence of amenorrhea (all p < .005). Conclusions: Few active Australian women are aware of the detrimental effects of menstrual dysfunction on bone health. Education programs are needed to prevent the female athlete triad and ensure that appropriate actions are taken by athletes when experiencing amenorrhea.

Osteopaenia - a marker of low bone mass and fracture risk

Areal bone mineral density is commonly categorised into normal bone mineral density, osteopaenia and osteoporosis on the basis of nominal thresholds recommended by the World Health Organization. However, bone mineral density is a continuous variable and there is a strong association between lower bone mineral density and greater risk for fracture. Fracture risk is not negligible in persons with moderate deficits in bone mineral density. Although absolute fracture risk is greatest for individuals with osteoporosis, more than half of the fractures arise from those with osteopaenia, and even normal bone mineral density, a probable consequence of greater numbers of individuals at risk in these categories. However, areal bone mineral density measurements used commonly in clinical practice do not detect differences in bone tissue properties, geometry and microarchitecture, which contribute to bone strength. Newer technologies such as high-resolution peripheral computed tomography have the advantage of assessing trabecular and cortical components of bone separately, in addition to geometric characteristics of the skeleton. Quantifying these parameters and considering clinical risk factors that affect fracture risk independent of bone quantity and quality, may better discriminate between high- and low-risk individuals. This would improve the decision-making for targeting appropriate interventions, either lifestyle or medication, to reduce thepublic health burden of fractures.

Effects of a specialist-led, school physical education program on bone mass, structure and strength in primary school children: a 4-year cluster randomised controlled trial

This 4-year cluster randomised controlled trial of 365 boys and 362 girls (mean age 8.1 ± 0.3 years) from grade 2 in 29 primary schools investigated the effects of a specialist-taught physical education (PE) program on bone strength and body composition. All children received 150 min/week of common practice (CP) PE from general classroom teachers but in 13 schools 100 min/week of CP PE was replaced by specialized-led PE (SPE) by teachers who emphasized more vigorous exercise/games combined with static and dynamic postural activities involving muscle strength. Outcome measures assessed in grades 2, 4, and 6 included: total body bone mineral content (BMC), lean mass (LM) and fat mass (FM) by DXA, and radius and tibia (4% and 66% sites) bone structure, volumetric density and strength, and muscle cross-sectional area (CSA) by pQCT. After 4-years, gains in total body BMC, FM and muscle CSA were similar between the groups in both sexes, but girls in the SPE group experienced a greater gain in total body LM [mean (95%CI), 1.0kg (0.2, 1.9)]. Compared to CP, girls in the SPE group also had greater gains in cortical area (CoA) and cortical thickness (CoTh) at the mid-tibia [CoA, 5.0% (0.2, 1.9); CoTh 7.5% (2.4, 12.6)] and mid-radius [CoA, 9.3% (3.5, 15.1); CoTh 14.4% (6.1, 22.7)], while SPE boys had a 5.2% (0.4, 10.0) greater gain in mid-tibia CoTh. These benefits were due to reduced endocortical expansion. There were no significant benefits of SPE on total bone area, cortical density or bone strength at the mid-shaft sites, nor any appreciable effects at the distal skeletal sites. This study indicates that a specialist-led school-based PE program improves cortical bone structure, due to reduced endocortical expansion. This finding challenges the notion that periosteal apposition is the predominant response of bone to loading during the pre- and early-pubertal period. This article is protected by copyright. All rights reserved.

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

BACKGROUND: We evaluated which aspects of neuromuscular performance are associated with bone mass, density, strength and geometry. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Effects of habitual physical activity and fitness on tibial cortical bone mass structure and mass distribution in pre-pubertal boys and girl: the look study

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 relationship between muscle size and bone geometry during growth and in response to exercise

As muscles become larger and stronger during growth and in response to increased loading, bones should adapt by adding mass, size, and strength. In this unilateral model, we tested the hypothesis that (1) the relationship between muscle size and bone mass and geometry (nonplaying arm) would not change during different stages of puberty and (2) exercise would not alter the relationship between muscle and bone, that is, additional loading would result in a similar unit increment in both muscle and bone mass, bone size, and bending strength during growth. We studied 47 competitive female tennis players aged 8–17 years. Total, cortical, and medullary cross-sectional areas, muscle area, and the polar second moment of area (Ip) were calculated in the playing and nonplaying arms using magnetic resonance imaging (MRI); BMC was assessed by DXA. Growth effects: In the nonplaying arm in pre-, peri- and post-pubertal players, muscle area was linearly associated BMC, total and cortical area, and Ip (r = 0.56–0.81, P < 0.09 to < 0.001), independent of age. No detectable differences were found between pubertal groups for the slope of the relationship between muscle and bone traits. Post-pubertal players, however, had a higher BMC and cortical area relative to muscle area (i.e., higher intercept) than pre- and peri-pubertal players (P < 0.05 to < 0.01), independent of age; pre- and peri-pubertal players had a greater medullary area relative to muscle area than post-pubertal players (P < 0.05 to < 0.01). Exercise effects: Comparison of the side-to-side differences revealed that muscle and bone traits were 6–13% greater in the playing arm in pre-pubertal players, and did not increase with advancing maturation. In all players, the percent (and absolute) side-to-side differences in muscle area were positively correlated with the percent (and absolute) differences in BMC, total and cortical area, and Ip (r = 0.36–0.40, P < 0.05 to < 0.001). However, the side-to-side differences in muscle area only accounted for 11.8–15.9% of the variance of the differences in bone mass, bone size, and bending strength. This suggests that other factors associated with loading distinct from muscle size itself contributed to the bones adaptive response during growth. Therefore, the unifying hypothesis that larger muscles induced by exercise led to a proportional increase in bone mass, bone size, and bending strength appears to be simplistic and denies the influence of other factors in the development of bone mass and bone shape.

Near normalisation of lumbar spine bone density in young women with osteopenia recovered from adolescent onset anorexia nervosa: a longitudinal study

To investigate the effect of the progression of adolescent onset anorexia nervosa (AN) on bone parameters we followed two cohorts (Disease cohort and recovered cohort) of adolescents for a total of 5.2 years. In the 'Disease' cohort (n = 18), lumbar spine bone density (BMD) was reduced by 0.6 SD after 0.8 years of disease and was reduced a further 1.0 SD after a total 2.5 years of disease (p < 0.001). At the third lumbar vertebra there was bone loss (-3.7%, p < 0.05) resulting in reduced volumetric BMD (-5.1%, p < 0.08). In the 'recovered' cohort, lumbar spine BMD was reduced by 1.9 SD after 1.7 years of disease, and increased by 1.5 SD after 2.7 years of recovery (p < 0.001). At the third lumbar vertebra there was an increase in bone mass (20.5%, p < 0.001) and bone volume (14.1%, p < 0.001), resulting in increased volumetric BMD (6.3%, p < 0.08). Normalisation of lumbar spine BMD may be achieved in patients with adolescent onset AN when the successful recovery of body weight is combined with the return of regular menses.

Determinants of bone density in 30- to 65-year-old women: A co-twin study

Introduction: Reported effects of body composition and lifestyle of bone mineral density in pre-elderly adult women have been inconsistent.

Methods: In a co-twin study of 146 female twin pairs aged 30 to 65 years, DXA was used to measure bone mineral density at the lumbar spine, total hip, and forearm, total body bone mineral content, and lean and fat mass. Height and weight were measured. Menopausal status, dietary calcium intake, physical activity, current tobacco use, and alcohol consumption were determined by questionnaire. Within-pair differences in bone measures were regressed through the origin against within-pair differences in putative determinants.

Results: Lean mass and fat mass were associated with greater bone mass at all sites. A discordance of 10 pack-years smoking was related to a 2.3-3.3% (SE, 0.8-1.0) decrease in bone density at all sites except the forearm, with the effects more evident in postmenopausal women. In all women, a 0.8% (SE, 0.3) difference in hip bone mineral density was associated with each hour per week difference in sporting activity, with effects more evident in premenopausal women. Daily dietary calcium intake was related to total body bone mineral content and forearm bone mineral density (1.4 ± 0.7% increase for every 1000 mg). Lifetime alcohol consumption and walking were not consistently related to bone mass.

Conclusion: Several lifestyle and dietary factors, in particular tobacco use, were related to bone mineral density. Effect sizes varied by site. Characterization of determinants of bone mineral density in midlife and thereafter may lead to interventions that could minimize postmenopausal bone loss and reduce osteoporotic fracture risk.

Changes in body composition as determinants of longitudinal changes in bone mineral measures in 8 to 26 year old female twins

Between 1990 and 1998, we conducted a longitudinal study of 286 female twins aged 8 to 25 years at baseline (60 monozygotic (MZ) pairs, 44 dizygotic (DZ) pairs and 78 unpaired twins), measured on average 2.4 times (range 2–6) with an average of 1.8 years between measurements (range 0.7–6.7 years). Areal bone mineral density (ABMD) at the lumbar spine, total hip and femoral neck, total body bone mineral content (BMC), total body soft tissue composition (lean mass and fat mass) were measured by dual-energy X-ray absorptiometry, and height and menarchial status were also recorded. Median annual changes in height were negligible at 4 years post-menarche. During the “linear growth” period up to 4 years post-menarche, ABMD at the lumbar spine, total hip and femoral neck increased with annual change in lean mass by 1.7 (S.E. 0.1), 1.4 (0.1) and 1.0 (0.1) percent per kilogram per year, respectively (all p<0.001), independently of changes in fat mass or height. During the “post-linear growth” period, ABMD at the total hip and femoral neck increased with annual change in fat mass by 0.3 (0.1) and 0.5 (0.1) percent per kilogram per year (all p<0.01), independent of change in lean mass. Annual changes in total body BMC were associated with annual changes in lean mass (1.9 (0.2) percent per kilogram), in fat mass (1.3 (0.2) percent per kilogram) and in height (0.7) (0.2) percent per centimeter) during linear growth, and in fat mass (1.0 (0.1)) and lean mass (0.6 (0.1)) percent per kilogram post-linear growth (all p<0.001). We conclude that changes in bone mineral measures are strongly associated with changes in lean mass during linear growth, while post-linear growth, changes in fat mass are the predominant, although weaker, predictor. These findings suggest that the strong cross-sectional association between bone mineral measures and lean mass is established during growth and development, and that fat mass emerges as a more powerful determinant of bone change in healthy adult females.

Selective reduction in body fat mass and plasma leptin induced by angiotensin-converting enzyme inhibition in rats

Objective: There is emerging evidence that angiotensin stimulates adipocyte differentiation and lipogenesis. This study tested the hypothesis that inhibition of angiotensin II by treatment with an angiotensin-converting enzyme inhibitor, perindopril, would reduce fat mass in rats. Design: After a 12-day baseline, rats were divided into two groups: one was untreated and the other received perindopril (1.2 mg kg⁻¹ per day) in drinking water for 26 days.Subjects: In total, 16 male Sprague–Dawley rats aged 10 weeks at the start of the study. Measurements: Plasma leptin was measured in samples collected at baseline, half-way through and at the end of treatment. Body weight, food and water intake were measured daily throughout the experiment. Body fat mass, bone and lean mass were determined by dual energy X-ray absorptiometry (DEXA) at the end of the treatment period. Results: Daily food intake was the same in both groups throughout the study. By the end of treatment, animals receiving perindopril showed a modest reduction in weight gain relative to the untreated animals (62.4±5.0 g vs 73.0±4.0 g; P<0.05). DEXA analysis showed that body composition was greatly altered and the perindopril-treated group had 26% less body fat mass than the untreated group (61.0±5.2 g vs 44.4±4.2 g; P<0.01). The reduction in body fat mass was correlated with reductions in the weight of both the epididymal and retroperitoneal fat pads (P<0.001). Similarly, plasma leptin was reduced by perindopril treatment (4.64±0.56 ng ml⁻¹) compared to the untreated group (8.27±1.03 ng ml⁻¹; P<0.001). In contrast, there were no differences in lean or bone mass between the two groups.Conclusion: Oral treatment with perindopril selectively reduced body fat mass without influencing daily food intake. In contrast, there were no differences in lean or bone mass between the two groups

Overweight children have poor bone strength relative to body weight, placing them at greater risk for forearm fractures

Introduction: Obesity is thought to be a protective factor for bones in adults but not in children based on the evidence of the greater incidence of forearm fractures in obese children. Our objective was to investigate the effect of adiposity on bone strength in relation to the mechanical challenge placed onto the forearm bones in case of a fall.

Methods: Cross sectional areas (CSA) were obtained at the mid- and distal radius by peripheral quantitative computed tomography in 486 children (241 boys), mean age 8.3 years (range 6.9–9.7), participating in the LOOK Project. The following parameters were measured: bone mass and bone CSA (both sites), and muscle and fat CSA (mid-forearm only). Bone strength indices combining bone size and total volumetric density were calculated at each site.

Results/Discussion: Overweight children (BMI > percentile equivalent to 25 kg/m² in adults) have higher bone parameters than normal-weight peers (Z-scores +0.6 to +0.9SD, p < 0.0001). These differences disappear after adjustment for muscle CSA. Adiposity (fat CSA/muscle CSA) was negatively correlated with bone mass, size and strength at the distal radius only (r = −0.1, p < 0.05). After adjustment for body weight (estimate of the load during a fall), the negative correlations were stronger and observed at both the mid- and distal radius (r = −0.37 to −0.55, p < 0.0001).

Conclusion. Overweight children have stronger bones due to greater muscle size. However, children with high fat mass relative to muscle mass (increased adiposity) have poorer bone strength, independent of weight, which may contribute to the increased risk of fracture in obese children.