title: Circulating fibroblast growth factor-23 increases following intermittent parathyroid hormone (1-34) in postmenopausal osteoporosis: association with biomarker of bone formation.
abstract: 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)(2)vitamin 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)(2)vitamin 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.
authors.affiliation: Osteoporosis Clinic, Guy's Hospital, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Sridharan
authors.forename: J
authors.initials: J
authors.lastname: Cheung
authors.forename: A E
authors.initials: AE
authors.lastname: Moore
authors.forename: M L
authors.initials: ML
authors.lastname: Frost
authors.forename: W D
authors.initials: WD
authors.lastname: Fraser
authors.forename: I
authors.initials: I
authors.lastname: Fogelman
authors.forename: G
authors.initials: G
authors.lastname: Hampson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D019379:Teriparatide / Q000031:analogs & derivatives* / Q000494:pharmacology; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; C000717427:FGF23 protein, human; D010446:Peptide Fragments; D019379:Teriparatide; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; C035748:parathyroid hormone (1-34)amide