Serum fibroblast growth factor‐23 (FGF‐23) and fracture risk in elderly men

A normal mineral metabolism is integral for skeletal development and preservation of bone integrity. Fibroblast growth factor 23 (FGF‐23) is a bone‐derived circulating factor that decreases serum concentrations of inorganic phosphorous (P i ) and 1,25‐dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]. Increased FGF‐23 expression is a direct or indirect culprit in several skeletal disorders; however, the relation between FGF‐23 and fracture risk remains undetermined. We evaluated the prospective relation between serum intact FGF‐23 (measured by a two‐site monoclonal antibody ELISA) and fracture risk employing the Swedish part of the population‐based Osteoporotic Fractures in Men Study (MrOS; n  = 2868; mean age 75.4 ± 3.2 years; median follow‐up period 3.35 years). The incidence of at least one validated fracture after baseline was 20.4 per 1000 person‐years. FGF‐23 was directly related to the overall fracture risk [age‐adjusted hazard ratio (HR) per SD increase = 1.20, 95% confidence interval (CI) 1.03–1.40] and vertebral fracture risk (HR = 1.33, 95% CI 1.02–1.75). Spline models revealed a nonlinear relation between FGF‐23 and fracture risk, with the strongest relation at FGF‐23 levels above 55.7 pg/mL. FGF‐23 levels above 55.7 pg/mL also were associated with an increased risk for hip and nonvertebral fractures (HR = 2.30, 95% CI 1.16–4.58, and HR = 1.63, 95% CI 1.01–2.63, respectively). These relations remained essentially unaltered after adjustment for bodymass index (BMI), bone mineral density (BMD), glomerular filtration rate, 25(OH) 2 D 3 , parathyroid hormone (PTH), and other fracture risk factors. In conclusion, FGF‐23 is a novel predictor of fracture risk in elderly men. © 2011 American Society for Bone and Mineral Research.