Circulating Fibroblast Growth Factor-23 Increases Following Intermittent Parathyroid Hormone (1–34) in Postmenopausal Osteoporosis: Association with Biomarker of Bone Formation

Uncertainties exist regarding whether FGF-23 production is influenced by PTH and its involvement in bone formation. We evaluated FGF-23 response and its relation to changes in biomarkers of bone formation following intermittent PTH treatment. Twenty-seven women with a mean [SD] age of 75.8 [5.4] years with postmenopausal osteoporosis were treated with PTH(1–34) for 18 months. Bone mineral density (BMD) was measured at 6 and 18 months at the lumbar spine (LS) and total hip (TH). Blood samples were obtained at baseline, 1–3, 6–9, and 12–18 months. Serum calcium, phosphate, PTH, 25(OH)vitamin D, 1,25(OH)2vitamin D, markers of bone turnover, FGF-23, and sclerostin were measured. BMD increased at both the LS (11.6%, P < 0.001) and TH (2.5%, P < 0.01). The bone formation marker P1NP increased early (baseline mean [SD] 39.9 [24.4] μg/l, 1–3 months 88 [37.9] μg/l; P < 0.001) and remained higher than baseline throughout 18 months. FGF-23 also increased, with a peak response at 6–9 months (increase 65%, P = 0.002). Serum phosphate remained stable. A significant increase in 1.25(OH)2vitamin D (P = 0.02) was seen at 1–3 months only. A small but significant reduction in sclerostin was seen at 6–9 (P = 0.02) and 12–18 months (P = 0.06). There was a positive correlation between changes in P1NP and FGF-23 (6–9 months r = 0.78, P < 0.001). FGF-23 is increased by intermittent PTH(1–34). This is related to early changes in P1NP, suggesting that the skeletal effects of PTH may involve FGF-23. Further studies are required to elucidate this.