Serum Glycine Levels Are Associated with Cortical Bone Properties and Fracture Risk in Men

Context: In a recent study a pattern of 27 metabolites, including serum glycine, associated with bone mineral density (BMD). Objective: To investigate associations for serum and urinary glycine levels with BMD, bone microstructure, and fracture risk in men. Methods: In the population-based Osteoporotic Fractures in Men (MrOS) Sweden study (men, 69-81 years) serum glycine and BMD were measured at baseline (n†=†965) and 5-year follow-up (n†=†546). Cortical and trabecular bone parameters of the distal tibia were measured at follow-up using high-resolution peripheral quantitative computed tomography. Urinary (n†=†2682) glycine was analyzed at baseline. X-ray-validated fractures (n†=†594) were ascertained during a median follow-up of 9.6 years. Associations were evaluated using linear regression (bone parameters) or Cox regression (fractures). Results: Circulating glycine levels were inversely associated with femoral neck (FN)-BMD. A meta-analysis (n†=†7543) combining MrOS Sweden data with data from 3 other cohorts confirmed a robust inverse association between serum glycine levels and FN-BMD (P†=†7.7†×†10-9). Serum glycine was inversely associated with the bone strength parameter failure load in the distal tibia (P†=†0.002), mainly as a consequence of an inverse association with cortical cross-sectional area and a direct association with cortical porosity. Both serum and urinary glycine levels predicted major osteoporotic fractures (serum: hazard ratio [HR] per SD increase†=†1.22, 95% CI, 1.05-1.43; urine: HR†=†1.13, 95% CI, 1.02-1.24). These fracture associations were only marginally reduced in models adjusted by FRAX with BMD. Conclusions: Serum and urinary glycine are indirectly associated with FN-BMD and cortical bone strength, and directly associated with fracture risk in men.