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, BMI 35.7 ± 5 kg/m²) : 28 Insulin Resistant (IR) and 20 Insulin Sensitive (IS) by McAuley index. Anthropometric, body composition, bone mineral density (BMD) measurements, serum leptin, insulin, free testosterone, IGF1, 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 similar mean values of serum osteocalcin, but higher C-telopeptide (CTX) (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 IGF1 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 IGF1 correlated with hip BMD/total body BMC.

In conclusion, there is a dichotomy in the impact of body composition parameters, 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.