MON-382 Bone Quality and Strength in Obese Men with Type 2 Diabetes Mellitus Are Impaired and Negatively Influenced by Adiposity

Abstract

Background: Obesity and type 2 diabetes mellitus (T2DM) are both associated with normal to above average bone mineral density (BMD) but increased risk of fragility fractures. The impact of T2DM on bone mechanical and microarchitectural features in the obese population is unknown. We hypothesize that obese diabetics have lower bone quality compared to obese nondiabetic individuals. In this study, we investigated the microarchitectural features and mechanical properties of bone of obese men with and without T2DM along with the independent predictors of bone strength. Methods: Ninety-seven obese men (BMI >30) aged 35-65 years-old of which 38 had T2DM were included in the analysis. BMD and body composition were evaluated by DXA and bone microarchitecture of the tibia by high-resolution peripheral quantitative computed tomography. Bone strength was assessed by micro finite element analysis-derived parameters as failure load (f. load) and stiffness. Serum testosterone and estradiol were measured by LC-MS. Serum SHBG, osteocalcin (OCN), C-telopeptide (CTx) and sclerostin (SCL) were measured by ELISA. Results: OCN is lower in obese men with T2DM compared to those without T2DM (4.8 ± 2.8 vs 6.2 ± 2.6 ng/mL p=0.03, respectively), with also a trend for reduced CTx and SCL in the former. BMD at all sites was reduced in obese men with T2DM, but there were no differences in body composition. Obese diabetics also had lower tibial total volumetric BMD (vBMD) (p=0.04) and trabecular vBMD (p=0.01) with greater trabecular spacing (p=0.005). F. load (13.3 ± 2.1 vs 14.5 ± 2.3 kN, p= 0.02) and stiffness (24.7± 4.2 vs 27 ± 4.6 kN/mm, p=0.02) were reduced in men with T2DM relative to men without T2DM, respectively. F. load and stiffness were positively correlated with BMD at all sites, fat free mass (FFM), lean mass, free testosterone, free estradiol and SCL, but negatively correlated with % total body fat and visceral adipose tissue (VAT). FFM, BMD of the total hip, femoral neck and lumbar spine and free testosterone were significant independent predictors of bone strength in the entire group (model: R2: 65.01 p< 0.0001 for f. load and model: R2:63.21 p < 0.0001 for stiffness), whereas age and lumbar spine BMD were found to be independent predictors of bone strength in the non-diabetic group (model R2: 54.6 p< 0.0001 for both f. load and stiffness). Analysis limited to the diabetic subgroup showed that BMD at the femoral neck and total hip, % total body fat, VAT volume, SCL and free estradiol were independent predictors of bone strength (model: R2: 88.4 and p< 0.0001 for f. load and model: R2: 85.3 and p<0.0001 for stiffness). Interleukin-6 was comparable between groups. Conclusions: Obese men with T2DM have lower bone formation and impaired bone quality and strength compared to those without T2DM. In addition to BMD and gonadal hormones, adiposity is an important predictor of bone strength in obese men with T2DM.