A normal mineral metabolism is integral for skeletal development and preservation of bone integrity. Fibroblast growth factor-23 (FGF23) is a bone-derived, circulating factor that decreases serum concentrations of inorganic phosphorous (Pi) and 1,25-dihydroxy vitamin D3 (1,25(OH)2D3). Increased FGF23 expression is a direct or indirect culprit in several skeletal disorders, however the relation between FGF23 and fracture risk remains undetermined. We evaluated the prospective relation between serum intact FGF23 (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; median follow-up period 3.35 years). The incidence of at least one validated fracture after baseline was 20.4 per 1000-person-years. FGF23 was directly related to the over-all fracture risk (age-adjusted hazard ratio [HR] per SD increase, 1.20; 95% CI, 1.03-1.40) and vertebral fracture risk (HR, 1.33; 95% CI, 1.02-1.75). Spline models revealed a non-linear relation between FGF23 and fracture risk with the strongest relation at FGF23 levels above 55.7 pg/mL. FGF23 levels above 55.7 pg/mL were also associated with an increased risk for hip and non-vertebral 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 BMI, BMD, glomerular filtration rate, 25(OH)D3, PTH and other fracture risk factors. In conclusion, FGF23 is a novel predictor of fracture risk in elderly men.
2011. Vol. 26, no 4, 857-864 p.