High plasma leptin is not associated with higher bone mineral density in insulin-resistant premenopausal obese women

Obesity's protective effect on bone density may be mediated through increased muscle mass, fat mass, increased estrogen, and possibly insulin and leptin levels. To determine the impact of leptin and insulin on bone metabolism, we studied 48 obese normally cycling premenopausal women ( age, 31 +/- 10 yr; body mass index, 35.7 +/- 5 kg/m(2)): 28 insulin resistant (IR) and 20 insulin sensitive ( IS) by McAuley index. Anthropometric, body composition, and bone mineral density (BMD) measurements were made, and serum leptin, insulin, free testosterone, IGF-I, bone remodeling markers, and calciotropic hormones were measured. Anthropometric, lifestyle, and biochemical markers were similar in the two groups. Despite higher circulating insulin and leptin levels, IR subjects had similarmeanvalues of serum osteocalcin but higher C-telopeptide ( P = 0.052). They had similar BMD at all skeletal sites compared with IS subjects. In the IR group, fat mass but not lean mass, serum leptin, insulin, testosterone, and IGF-I levels correlated positively with hip and/or total-body bone density with R varying between 0.38 and 0.65; no correlations were observed at the spine. Conversely, in the IS group, lean mass, but not fat mass, and only IGF-I correlated with hip BMD/total-body bone mineral content. In conclusion, there is a dichotomy in the impact of body composition parameters and insulin and leptin levels on bone parameters in obese individuals. The interaction between the fat-related endocrine system and bone seems to be complex and may be modulated by local resistance to the putative protective effect of insulin and leptin on bone.