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

• Published in: Journal of bone and mineral research Vol. 26; no. 4; pp. 803 - 810
• Main Authors: Aono, Yukiko, Hasegawa, Hisashi, Yamazaki, Yuji, Shimada, Takashi, Fujita, Toshiro, Yamashita, Takeyoshi, Fukumoto, Seiji
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-04-2011; Wiley; Wiley Subscription Services, Inc
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Biological and medical sciences; Blood - drug effects; Body Weight - drug effects; Calcification, Physiologic - drug effects; Disease Models, Animal; Familial Hypophosphatemic Rickets - blood; Familial Hypophosphatemic Rickets - complications; Familial Hypophosphatemic Rickets - drug therapy; Familial Hypophosphatemic Rickets - physiopathology; Female; Femur - anatomy & histology; Femur - diagnostic imaging; Femur - drug effects; FIBROBLAST GROWTH FACTOR 23; Fibroblast Growth Factors - antagonists & inhibitors; Fibroblast Growth Factors - blood; Fibroblast Growth Factors - immunology; Fundamental and applied biological sciences. Psychology; Genetic Diseases, X-Linked; Hand Strength - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Motor Activity - drug effects; Motor Activity - physiology; Muscle Weakness - drug therapy; Muscle Weakness - etiology; Muscle Weakness - physiopathology; NEUTRALIZING ANTIBODY; Phosphates - blood; PHOSPHATONIN; Quadriceps Muscle - anatomy & histology; Quadriceps Muscle - drug effects; Radiography; Skeleton and joints; Skull - chemistry; Skull - drug effects; Tibia - chemistry; Tibia - drug effects; Vertebrates: osteoarticular system, musculoskeletal system; Vitamin D - analogs & derivatives; Vitamin D - blood; X‐LINKED HYPOPHOSPHATEMIA; Fibroblast growth factor; Hydroelectrolytic balance disorder; NEUTRALIZING ANTIBODY; X-LINKED HYPOPHOSPHATEMIA; Rodentia; Phosphorus; Striated muscle; FIBROBLAST GROWTH FACTOR 23; Inorganic element; Osteoarticular system; Metabolic disorder; Vertebrata; Mammalia; Mouse; PHOSPHATONIN; Hypophosphatemia
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1002/jbmr.275

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. © 2011 American Society for Bone and Mineral Research.