Context: In type 2 diabetes mellitus, fracture risk is increased despite preserved areal bone mineral density. Although this apparent paradox may in part be explained by insulin resistance affecting bone structure and/or material properties, few studies have investigated the association between insulin resistance and bone geometry.Objective: We aimed to explore this association in a cohort of nondiabetic men at the age of peak bone mass.Design, Setting, and Participants: Nine hundred ninety-six nondiabetic men aged 25 to 45 years were recruited in a cross-sectional, population-based sibling pair study at a university research center.Main Outcome Measures: Insulin resistance was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR), with insulin and glucose measured from fasting serum samples. Bone geometry was assessed using peripheral quantitative computed tomography at the distal radius and the radial and tibial shafts.Results: In age-, height-, and weight-adjusted analyses, HOMA-IR was inversely associated with trabecular area at the distal radius and with cortical area, periosteal and endosteal circumference, and polar strength strain index at the radial and tibial shafts ( b # 20.13, P , 0.001). These associations remained essentially unchanged after additional adjustment for dual-energy X-ray absorptiometry-derived body composition, bone turnover markers, muscle size or function measurements, or adiponectin, leptin, insulin-like growth factor 1, or sex steroid levels.
Conclusion:In this cohort of nondiabetic men at the age of peak bone mass, insulin resistance is inversely associated with trabecular and cortical bone size. These associations persist after adjustment for body composition, muscle size or function, or sex steroid levels, suggesting an independent effect of insulin resistance on bone geometry. (J Clin Endocrinol Metab 102: [1807][1808][1809][1810][1811][1812][1813][1814][1815] 2017) T he prevalence of type 2 diabetes mellitus (T2DM) has reached epidemic proportions. In addition to wellknown microvascular and macrovascular complications, skeletal fragility is being increasingly recognized as another important diabetes-associated condition. Indeed, despite having a comparable areal bone mineral density (aBMD) as measured by dual-energy X-ray absorptiometry (DXA), individuals with T2DM present with an Abbreviations: 25(OH)D, 25-hydroxyvitamin D; aBMD, areal bone mineral density; CSA, cross-sectional area; CTX, C-terminal telopeptide of type I collagen; CV, coefficient of variation; DXA, dual-energy X-ray absorptiometry; EC PC , endosteal circumference additionally adjusted for periosteal circumference; FE2, free estradiol; FT, free testosterone; HOMA-IR, homeostasis model assessment of insulin resistance; IGF-1, insulin-like growth factor 1; P1NP, procollagen type 1 N-terminal propeptide; pQCT, peripheral quantitative computed tomography; PTH, parathyroid hormone; SHBG, sex hormone-binding globulin; SSIp, polar strength strain index; T2DM, type 2 diabetes mellitus; v...