Serum glycine levels are associated with cortical bone properties and fractures 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 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=2,682) 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=7,543) combining MrOS Sweden data with data from three other cohorts confirmed a robust inverse association between serum glycine levels and FN-BMD (p=7.7 x 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, HR per SD increase = 1.20, 95% CI 1.03-1.40; urine HR=1.13, 95% CI 1.02-1.24). These fracture associations were only marginally reduced in models adjusted for 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.