In Men With Obesity, T2DM Is Associated With Poor Trabecular Microarchitecture and Bone Strength and Low Bone Turnover

Abstract

Introduction Obesity and type 2 Diabetes (T2D) are both associated with greater bone mineral density (BMD) but increased risk of fractures. The effect of the combination of both conditions on bone metabolism, microarchitecture and strength in the obese population remains unknown. Methods Data from 112 obese men were collected. Bone turnover and biochemical markers were measured by enzyme-linked immunosorbent assay (ELISA), body composition and BMD at all sites were assessed by dual energy X-ray absorptiometry (DXA), whereas bone microarchitecture and strength (stiffness and failure load) were measured by high-resolution peripheral computed tomography (HR-pQCT). Data were compared among metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO) with and without T2D and between obese without and with T2D. Results Compared to MHO and MUHO without T2D, MUHO with T2D had significantly lower levels of osteocalcin ((7.49±3.0 and 6.03±2.47, vs 4.24±2.72 ng/ml, respectively, p=0.003) and C-terminal telopeptide of type I collagen (CTx) (0.28±0.10 and 0.29±0.13 vs. 0.21±0.15 ng/ml, respectively, p=0.02). Dividing our subjects simply into those with and without T2D showed that obese men with T2D had significantly lower levels of osteocalcin (p=0.003) and CTx (p=0.005), greater trabecular separation at the tibia and radius (p=0.03 and p=0.04, respectively) and lower tibial failure load and stiffness (both p=0.04), relative to obese men without T2D. Conclusion In men, the combination of obesity and T2D is associated with reduced bone turnover, poorer trabecular bone microarchitecture and bone strength compared to those who are obese but without T2D suggesting worse bone disease.

Hemoglobin A1c Threshold for Reduction in Bone Turnover in Men With Type 2 Diabetes Mellitus

“…This is a secondary analysis using the baseline data from 2 clinical trials in veterans who volunteered to be screened for the study evaluating the effect polymorphisms in the CYP19A1 gene on the response to testosterone therapy in men with hypogonadism (NCT: 01378299) between October 2011 to November 6, 2016 ( 9 , 10 ) and part of the population of men who screened between May 2018 to October 2019 for the study on the effect of aromatase inhibitors and weight loss in obese men with hypogonadism (NCT: 03490513) ( 11 , 12 ). There were 105 men from the former and 112 from the latter study were included in this analysis.…”

DXA parameters, Trabecular Bone Score (TBS) and Bone Mineral Density (BMD), in fracture risk prediction in endocrine-mediated secondary osteoporosis

“…Other bone health assessments using bone density derived from high-resolution peripheral quantitative computed tomography (HR-pQCT) or other bone strength surrogates (such as bone turnover markers or advanced glycation end-products, etc.) in obese and diabetics have been shown useful at their overall bone health evaluation [29][30][31].…”

Circulating osteogenic progenitors and osteoclast precursors are associated with long-term glycemic control, sex steroids, and visceral adipose tissue in men with type 2 diabetes mellitus

“…Given the cross-talk between osteoblasts and osteoclasts with reduced bone formation, it is expected that reduction in bone resorption follows with resultant low bone turnover. In previous studies, our group also reported that men with T2DM with or without hypogonadism ( 2 ) and obese men with T2DM have reduced bone turnover compared to those without T2DM ( 29 ). Furthermore, we demonstrated in another study that glycemic control could be an important determinant of this alteration in bone turnover in T2DM patients, with poor glycemic control associated with reduction in bone turnover as compared to those with good glycemic control ( 7 ).…”

“…The strengths of this study include: 1) novelty, as this is the first study that examines the effect of glycemic control and other factors on the circulating bone precursor cells in T2DM and 2) the relatively good number participants for a flow cytometry study done on humans, which allows us to extrapolate a mechanistic understanding of previously observed trends in bone quality and geometry in patients with type 2 diabetes ( 2 , 29 ). There are several limitations to our study.…”

“…The CV for fat mass and lean mass measurements in our center is 1.5% ( 19 ). Visceral adipose tissue (VAT) volume (g/cm 2 ) was calculated from the DXA body composition scan using APEX software (version 5.5.2; Hologic Inc., Bedford, MA) as previously described ( 29 ).…”