Anti-FGF-23 neutralizing antibodies ameliorate muscle weakness and decreased spontaneous movement of Hyp mice.

Abstract

Fibroblast growth factor 23 (FGF-23) plays causative roles in the development of several hypophosphatemic rickets/osteomalacia such as X-linked hypophosphatemic rickets/osteomalacia (XLH) and tumor-induced rickets/osteomalacia. Patients with hypophosphatemic rickets/osteomalacia often complain of muscle weakness and bone pain that severely affect daily activities of these patients. The purpose of this study was to examine whether anti-FGF-23 antibodies, which have been shown to improve hypophosphatemia and rachitic changes of juvenile Hyp mice in a murine model of XLH, also ameliorate hypophosphatemic osteomalacia and affect muscle force and spontaneous motor activity in adult Hyp mice. Repeated injections of anti-FGF-23 antibodies increased serum phosphate and 1,25-dihydroxyvitmain D levels and enhanced mineralization of osteoid in adult Hyp mice, whereas bone length did not change. We found that grip strength was weaker and that spontaneous movement was less in adult Hyp mice than in wild-type mice. In addition, FGF-23 antibodies increased grip strength and spontaneous movement. These results suggest that the inhibition of excess FGF-23 action not only ameliorates hypophosphatemia and impaired mineralization of bone but also improves muscle weakness and daily activities of patients with FGF-23-related hypophosphatemic rickets/osteomalacia.

• Authors: Yukiko Aono, Hisashi Hasegawa, Yuji Yamazaki, Takashi Shimada, Toshiro Fujita, Takeyoshi Yamashita, Seiji Fukumoto
• Journal: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (J Bone Miner Res) Vol. 26 Issue 4 Pg. 803-10 (Apr 2011) ISSN: 1523-4681 [Electronic] United States
• PMID: 20939065 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Society for Bone and Mineral Research.

Chemical References

• Antibodies, Monoclonal
• Fgf23 protein, mouse
• Phosphates
• Vitamin D
• Fibroblast Growth Factors
• 1,25-dihydroxyvitamin D
• Fibroblast Growth Factor-23

Topics

• Animals
• Antibodies, Monoclonal (immunology, pharmacology, therapeutic use)
• Blood (drug effects)
• Body Weight (drug effects)
• Calcification, Physiologic (drug effects)
• Disease Models, Animal
• Familial Hypophosphatemic Rickets (blood, complications, drug therapy, physiopathology)
• Female
• Femur (anatomy & histology, diagnostic imaging, drug effects)
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors (antagonists & inhibitors, blood, immunology)
• Genetic Diseases, X-Linked
• Hand Strength (physiology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Mutant Strains
• Motor Activity (drug effects, physiology)
• Muscle Weakness (drug therapy, etiology, physiopathology)
• Phosphates (blood)
• Quadriceps Muscle (anatomy & histology, drug effects)
• Radiography
• Skull (chemistry, drug effects)
• Tibia (chemistry, drug effects)
• Vitamin D (analogs & derivatives, blood)