Endocrine Abstracts

Objective: In type 2 diabetes mellitus, fracture risk is increased despite preserved BMD. This might in part be due to insulin resistance affecting bone geometry; however, studies investigating the associations of insulin sensitivity with bone geometry are lacking. We aimed to explore this relationship in a cohort of healthy, young adult men.

Methods: In 1001 healthy men aged 25–45 years, cortical bone geometry was assessed using pQCT (radius and tibia, 66% from distal end point). Insulin and glucose were measured from fasting serum samples; insulin resistance was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR).

Results: In age and BMI-adjusted analyses, HOMA-IR and insulin levels correlated inversely with periosteal circumference (PC), endosteal circumference (EC) and polar strength-strain index (SSIp) at both the radius (PC: both ß=−0.13, P<0.001; EC: ß=−0.08, P≤0.031; SSIp: ß=−0.14 and ß=−0.16, P<0.001) and tibia (PC: ß=−0.12, P<0.001; EC: ß=−0.10 and ß=−0.09, P≤0.007; SSIp: ß=−0.10, P≤0.003). Moreover, insulin levels but not HOMA-IR correlated inversely with cortical thickness at the radius (ß=−0.07, P=0.048). After adjustment for DXA-derived body composition (total fat and lean body mass) instead of BMI, the associations of HOMA-IR and insulin with PC and SSIp at both the radius and tibia and with EC at the tibia remained significant (ß≥−0.11, P≤0.019), whereas the associations of HOMA-IR and insulin with EC and the association of insulin with cortical thickness at the radius lost significance.

Conclusion: In this cohort of healthy young men, insulin sensitivity correlates with cortical bone size at least in part independently of body composition. Given the important contribution of bone geometry to overall bone strength, this might contribute to the paradoxically increased fracture risk in patients with type 2 diabetes mellitus. Whether this association is a direct consequence of impaired insulin signaling in bone tissue or reflects indirect effects through modulation of the muscle-bone relationship remains to be established.