Fat, adipokines, bone structure and bone regulatory factors associations in obesity.

Context: Obese (OB) adults (BMI ≥ 30) have a higher bone mineral density (BMD) and more favourable bone microarchitecture than normal-weight (NW) adults (BMI 18.5-24.9). Objective: The objective of this study was to identify which fat compartments have the strongest association with bone density and bone turnover and whether biochemical factors (adipokines, hormones and bone regulators) are likely to be important mediators of the effect of obesity on bone. Design: This was a cross-sectional, observational, matched case-control study. Setting: Participants were recruited from the local community. Participants: Two hundred healthy men and women aged 25-40 or 55-75 were recruited in individually matched OB and NW pairs. Body composition, BMD and bone microarchitecture were determined by dual-energy X-ray absorptiometry (DXA), computed tomography (CT) and high-resolution peripheral CT (HR-pQCT). Bone turnover and potential regulators such as C-terminal cross-linking telopeptide (CTX), type 1 procollagen N-terminal peptide (PINP), sclerostin, periostin, parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), insulin-like growth factor 1 (IGF1), adiponectin, leptin and insulin were assessed. Main outcome: Planned exploratory analysis of the relationships between fat compartments, areal and volumetric BMD, bone microarchitecture, bone turnover markers and bone regulators. Results: Compared with NW, OB had lower CTX, PINP, adiponectin, IGF1, and 25OHD and higher leptin, PTH and insulin (all P < 0.05). CTX and subcutaneous adipose tissue (SAT) were the bone marker and fat compartment most consistently associated with areal and volumetric BMD. In regression models, SAT was negatively associated with CTX (P < 0.001). When leptin was added to the model, SAT was no longer associated with CTX, but leptin (P < 0.05) was negatively associated with CTX. Conclusions: SAT is associated with lower bone resorption and properties favourable for bone strength in obesity. Leptin may be an important mediator of the effects of SAT on the skeleton.