Influence of age and gender on associations of body mass index with bone mineral density, bone turnover markers and circulating calcium-regulating and bone-active sex hormones.

Although it is well known that body mass index (BMI) and bone mineral density (BMD) are positively correlated, the mechanisms by which adiposity reduces the risk of osteoporotic fractures are not fully understood. The present study was initiated to gain deeper insight into the mechanisms underlying the osteoprotective effect of adiposity, and to assess particularly the relevance that BMI-associated changes in circulating hormone levels could have for the build-up of additional bone mineral density. Using data from a previous study on a large cohort of healthy adult Austrians, we analyzed correlations of BMI with (i) BMD at sites in the lumbar spine and hip region, (ii) bone resorption and formation markers, (iii) circulating levels of vitamin D, parathyroid hormone, testosterone and estrogen, and (iv) rates of daily vitamin D and calcium intake. After adjustment for age, positive correlations between BMI and BMD were highly significant (P<0.0001) at all skeletal sites across the entire study cohort. Associations were stronger in post-menopausal women than in pre-menopausal women and in men. In absolute values, the gain in BMD at the lumbar spine from an incremental rise of BMI in post-menopausal women was 1.5-fold higher than in pre-menopausal women, and three times of that observed in men (P<0.05). Inverse relations between BMI and β-crosslaps were consistently found in men (P<0.01) and in women before and after menopause (P<0.01 and P<0.05, respectively), suggesting that inhibition of osteoclastic bone resorption is responsible at least in part for the positive effect of high BMI on BMD. Sub-group analysis revealed that increasing BMI was associated with a significant fall of testosterone in men (P<0.05), and of 25-(OH)D in pre- and post-menopausal women (P<0.001 and P<0.05, respectively), but with a significant rise in PTH (P<0.01) in women before menopause. Since all these hormonal changes would cause bone loss, this excludes their playing any role in the osteoprotective effect of adiposity.