title: Decrease in serum FGF23 levels after intravenous infusion of pamidronate in patients with osteogenesis imperfecta.
abstract: Fibroblast growth factor 23 (FGF23) plays a central role in phosphate (P) homeostasis. However, the precise mechanism of how FGF23 secretion is regulated remains to be elucidated. In the present study, we examined the effect of intravenous pamidronate administration on serum levels of FGF23. Thirteen patients with osteogenesis imperfecta were treated with two cycles of 3-day pamidronate infusion. Blood samples at pre- and post-drip pamidronate infusion were evaluated for serum calcium, P, intact PTH (iPTH), 1,25(OH)(2)D, intact FGF23 (FGF23), type I collagen cross-linked N-telopeptides (NTx), bone-specific alkaline phosphatase (BAP), and TmP/GFR. During the two cycles, FGF23 levels decreased significantly preceding the decline in P levels. Although the change in P levels became less apparent during the second cycle, the reduction in FGF23 levels was similar during both cycles. Moreover, absence of correlation between FGF23 and P indicates that FGF23 attenuation is independent of the decrease in P levels during pamidronate infusion. Significant correlation between NTx suppression and the decrease in FGF23 levels during the 1st cycle (r = 0.665, P = 0.013) suggests that inhibition of osteoclast function may have some role in suppressing FGF23 levels. Because pamidronate dose was most associated with the decrease in FGF23 levels during the second cycle, pamidronate may directly attenuate osteocyte/osteoblast-mediated FGF23 production. This is the first evidence of a rapid fall in FGF23 levels following pamidronate infusion, raising the possibility that inhibition of bone resorption and/or direct effects of pamidronate may suppress secretion of FGF23.
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Kitaoka
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Namba
authors.forename: Kohji
authors.initials: K
authors.lastname: Miura
authors.forename: Takuo
authors.initials: T
authors.lastname: Kubota
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Ohata
authors.forename: Makoto
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Hirai
authors.forename: Takehisa
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ozono
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004164:Diphosphonates / Q000008:administration & dosage* / Q000627:therapeutic use*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D010013:Osteogenesis Imperfecta / Q000097:blood* / Q000188:drug therapy*; D000077268:Pamidronate
chemical_list: D004164:Diphosphonates; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D000077268:Pamidronate