Impaired bone anabolic response to parathyroid hormone in Fgf2−/− and Fgf2+/− mice

Abstract

Since parathyroid hormone (PTH) increased FGF2 mRNA and protein expression in osteoblasts, and serum FGF-2 was increased in osteoporotic patients treated with PTH, we assessed whether the anabolic effect of PTH was impaired in Fgf2−/− mice. Eight-week-old Fgf2+/+ and Fgf2−/− male mice were treated with rhPTH 1–34 (80 μg/kg) for 4 weeks. Micro-CT and histomorphometry demonstrated that PTH significantly increased parameters of bone formation in femurs from Fgf2+/+ mice but the changes were smaller and not significant in Fgf2−/− mice. IGF-1 was significantly reduced in serum from PTH-treated Fgf2−/− mice. DEXA analysis of femurs from Fgf2+/+, Fgf2+/−, and Fgf2−/− mice treated with rhPTH (160 μg/kg) for 10 days showed that PTH significantly increased femoral BMD in Fgf2+/+ by 18%; by only 3% in Fgf2+/− mice and reduced by 3% in Fgf2−/− mice. We conclude that endogenous Fgf2 is important for maximum bone anabolic effect of PTH in mice.