U-Shaped Association Between Serum 25-Hydroxyvitamin D and Fracture Risk in Older Men: Results From the Prospective Population-Based CHAMP Study

The aim of this population-based, prospective, observational study was to examine the relationship between serum levels of 25-hydroxyvitamin D (25OHD) and fracture risk in a cohort of 1662 community-dwelling men aged 70 to 97 years followed for a mean of 4.3 years. Data about mobility, muscle strength, balance, medication use, cognition, medical history, lifestyle factors, renal function, and serum 25OHD were collected at baseline. Data on radiologically verified fractures were collected every 4 months. The relationship between fractures and serum 25OHD levels was analyzed using Cox's proportional hazard regression. We accounted for bone mineral density, falls, physical activity, sun exposure, and season of blood draw, in addition to anthropometric and lifestyle factors, medical history, muscle strength, balance, and medication and supplement use. There were 123 first-incident fragility fractures. The relationship between baseline 25OHD and fracture risk was U-shaped, with increased fracture risk in men with either low or high serum 25OHD levels. In multivariate analysis, the risk of fracture was greatest in men with 25OHD levels in the lowest quintile (25OHD <= 36 nmol/L; hazard ratio [HR] = 3.5; 95% confidence interval [CI] 1.7-7.0) and in men in the highest quintile (25OHD > 72 nmol/L; HR = 2.7; 95% CI 1.4-5.4) compared with men in the 4th quintile (25OHD >= 60 to <= 72 nmol/L). These associations were not explained by lower BMD, increased physical activity, fall risk, or other lifestyle or anthropomorphic factors. In community-dwelling older men, there appears to be a healthy target range for serum 25OHD concentrations. Thus, serum 25OHD levels too high and too low may be harmful in regard to fracture risk. (C) 2014 American Society for Bone and Mineral Research.