{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:01:38Z","timestamp":1790280098409,"version":"4.1.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2010,10,11]],"date-time":"2010-10-11T00:00:00Z","timestamp":1286755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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. \u00a9 2011 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.275","type":"journal-article","created":{"date-parts":[[2010,10,11]],"date-time":"2010-10-11T19:39:18Z","timestamp":1286825958000},"page":"803-810","source":"Crossref","is-referenced-by-count":95,"title":["Anti-FGF-23 neutralizing antibodies ameliorate muscle weakness and decreased spontaneous movement of <i>Hyp<\/i> mice"],"prefix":"10.1093","volume":"26","author":[{"given":"Yukiko","family":"Aono","sequence":"first","affiliation":[{"name":"Pharmacological Research Laboratories, Kyowa Hakko Kirin Company, Ltd., Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Pharmacological Research Laboratories, Kyowa Hakko Kirin Company, Ltd., Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Antibody Research Laboratories, Kyowa Hakko Kirin Company, Ltd., Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Shimada","sequence":"additional","affiliation":[{"name":"Innovative Drug Research Laboratories, Kyowa Hakko Kirin Company, Ltd., Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiro","family":"Fujita","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology, Department of Medicine, University of Tokyo Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeyoshi","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Innovative Drug Research Laboratories, Kyowa Hakko Kirin Company, Ltd., Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiji","family":"Fukumoto","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology, Department of Medicine, University of Tokyo Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,10,11]]},"reference":[{"key":"2024020318071895400_bib1","first-page":"879","article-title":"A prospective trial of phosphate and 1,25-dihydroxyvitamin D3 therapy in symptomatic adults with X-linked hypophosphatemic rickets","volume":"75","author":"Sullivan","year":"1992","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020318071895400_bib2","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1097\/00005792-198911000-00002","article-title":"X-linked hypophosphatemia: a clinical, biochemical, and histopathologic assessment of morbidity in adults","volume":"68","author":"Reid","year":"1989","journal-title":"Medicine (Baltimore)."},{"key":"2024020318071895400_bib3","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1086\/499409","article-title":"SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis","volume":"78","author":"Bergwitz","year":"2006","journal-title":"Am J Hum Genet."},{"key":"2024020318071895400_bib4","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/S0140-6736(76)90428-1","article-title":"Muscle weakness in osteomalacia","volume":"1","author":"Schott","year":"1976","journal-title":"Lancet."},{"key":"2024020318071895400_bib5","doi-asserted-by":"crossref","first-page":"6500","DOI":"10.1073\/pnas.101545198","article-title":"Cloning and characterization of FGF-23 as a causative factor of tumor-induced osteomalacia","volume":"98","author":"Shimada","year":"2001","journal-title":"Proc Natl Acad Sci USA."},{"key":"2024020318071895400_bib6","doi-asserted-by":"crossref","first-page":"496514","DOI":"10.1186\/1687-9856-2009-496514","article-title":"Fibroblast growth factor 23 (FGF23) and disorders of phosphate metabolism","volume":"2009","author":"Saito","year":"2009","journal-title":"Int J Pediatr Endocrinol."},{"key":"2024020318071895400_bib7","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1172\/JCI200419081","article-title":"Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism","volume":"113","author":"Shimada","year":"2004","journal-title":"J Clin Invest."},{"key":"2024020318071895400_bib8","doi-asserted-by":"crossref","first-page":"4957","DOI":"10.1210\/jc.2002-021105","article-title":"Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets\/osteomalacia","volume":"87","author":"Yamazaki","year":"2002","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020318071895400_bib9","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1056\/NEJMoa020881","article-title":"Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia","volume":"348","author":"Jonsson","year":"2003","journal-title":"N Engl J Med."},{"key":"2024020318071895400_bib10","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1038\/ng1905","article-title":"Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism","volume":"38","author":"Feng","year":"2006","journal-title":"Nat Genet."},{"key":"2024020318071895400_bib11","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/ng1868","article-title":"DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis","volume":"38","author":"Lorenz-Depiereux","year":"2006","journal-title":"Nat Genet."},{"key":"2024020318071895400_bib12","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1210\/jcem.86.2.7408","article-title":"The autosomal dominant hypophosphatemic rickets (ADHR) gene is a secreted polypeptide overexpressed by tumors that cause phosphate wasting","volume":"86","author":"White","year":"2001","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020318071895400_bib13","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1172\/JCI18399","article-title":"FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting","volume":"112","author":"Riminucci","year":"2003","journal-title":"J Clin Invest."},{"key":"2024020318071895400_bib14","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s00774-004-0589-9","article-title":"The role of fibroblast growth factor 23 for hypophosphatemia and abnormal regulation of vitamin D metabolism in patients with McCune-Albright syndrome","volume":"23","author":"Yamamoto","year":"2005","journal-title":"J Bone Miner Metab."},{"key":"2024020318071895400_bib15","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1210\/jc.2008-2396","article-title":"FGF23 elevation and hypophosphatemia after intravenous iron polymaltose: a prospective study","volume":"94","author":"Schouten","year":"2009","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020318071895400_bib16","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.bone.2009.06.017","article-title":"Hypophosphatemia induced by intravenous administration of saccharated ferric oxide: another form of FGF23-related hypophosphatemia","volume":"45","author":"Shimizu","year":"2009","journal-title":"Bone."},{"key":"2024020318071895400_bib17","doi-asserted-by":"crossref","first-page":"658","DOI":"10.2215\/CJN.04981107","article-title":"Calcimimetics as an adjuvant treatment for familial hypophosphatemic rickets","volume":"3","author":"Alon","year":"2008","journal-title":"Clin J Am Soc Nephrol."},{"key":"2024020318071895400_bib18","doi-asserted-by":"crossref","first-page":"468","DOI":"10.2169\/internalmedicine.39.468","article-title":"Tertiary hyperparathyroidism in X-linked hypophosphatemic rickets","volume":"39","author":"Wu","year":"2000","journal-title":"Intern Med."},{"key":"2024020318071895400_bib19","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1359\/jbmr.080417","article-title":"Anti-FGF23 neutralizing antibodies show the physiological role and structural features of FGF23","volume":"23","author":"Yamazaki","year":"2008","journal-title":"J Bone Miner Res."},{"key":"2024020318071895400_bib20","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1359\/jbmr.090509","article-title":"Therapeutic effects of anti-FGF23 antibodies in hypophosphatemic rickets\/osteomalacia","volume":"24","author":"Aono","year":"2009","journal-title":"J Bone Miner Res."},{"key":"2024020318071895400_bib21","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1172\/JCI119276","article-title":"Pex\/PEX tissue distribution and evidence for a deletion in the 3' region of the Pex gene in X-linked hypophosphatemic mice","volume":"99","author":"Beck","year":"1997","journal-title":"J Clin Invest."},{"key":"2024020318071895400_bib22","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1254\/jjp.87.195","article-title":"Deterioration of spatial learning performances in lipopolysaccharide-treated mice","volume":"87","author":"Arai","year":"2001","journal-title":"Jpn J Pharmacol."},{"key":"2024020318071895400_bib23","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1093\/hmg\/9.9.1393","article-title":"Myopathy phenotype of transgenic mice expressing active site-mutated inactive p94 skeletal muscle-specific calpain, the gene product responsible for limb girdle muscular dystrophy type 2A","volume":"9","author":"Tagawa","year":"2000","journal-title":"Hum Mol Genet."},{"key":"2024020318071895400_bib24","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S1385-299X(97)00005-6","article-title":"A novel method for counting spontaneous motor activity in the rat","volume":"1","author":"Masuo","year":"1997","journal-title":"Brain Res Brain Res Protoc."},{"key":"2024020318071895400_bib25","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1093\/hmg\/ddm380","article-title":"An Actn3 knockout mouse provides mechanistic insights into the association between alpha-actinin-3 deficiency and human athletic performance","volume":"17","author":"MacArthur","year":"2008","journal-title":"Hum Mol Genet."},{"key":"2024020318071895400_bib26","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.2353\/ajpath.2008.071042","article-title":"Preservation of muscle force in Mdx3cv mice correlates with low-level expression of a near full-length dystrophin protein","volume":"172","author":"Li","year":"2008","journal-title":"Am J Pathol."},{"key":"2024020318071895400_bib27","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S0892-0362(03)00073-4","article-title":"Factors affecting grip strength testing","volume":"25","author":"Maurissen","year":"2003","journal-title":"Neurotoxicol Teratol."},{"key":"2024020318071895400_bib28","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1006\/phrs.2000.0760","article-title":"Automated behavioural analysis in animal pain studies","volume":"43","author":"Jourdan","year":"2001","journal-title":"Pharmacol Res."},{"key":"2024020318071895400_bib29","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.lfs.2009.06.006","article-title":"Targeting pain-depressed behaviors in preclinical assays of pain and analgesia: drug effects on acetic acid-depressed locomotor activity in ICR mice","volume":"85","author":"Stevenson","year":"2009","journal-title":"Life Sci."},{"key":"2024020318071895400_bib30","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1124\/jpet.106.109736","article-title":"Inflammation-induced reduction of spontaneous activity by adjuvant: A novel model to study the effect of analgesics in rats","volume":"320","author":"Matson","year":"2007","journal-title":"J Pharmacol Exp Ther."},{"key":"2024020318071895400_bib31","doi-asserted-by":"crossref","first-page":"3470","DOI":"10.1002\/art.21403","article-title":"Circadian pattern of spontaneous behavior in monarthritic rats: a novel global approach to evaluation of chronic pain and treatment effectiveness","volume":"52","author":"Millecamps","year":"2005","journal-title":"Arthritis Rheum."},{"key":"2024020318071895400_bib32","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1097\/00000542-200407000-00030","article-title":"Effects of laparotomy on spontaneous exploratory activity and conditioned operant responding in the rat: a model for postoperative pain","volume":"101","author":"Martin","year":"2004","journal-title":"Anesthesiology."},{"key":"2024020318071895400_bib33","doi-asserted-by":"crossref","first-page":"E38","DOI":"10.1152\/ajpendo.00008.2006","article-title":"Pathogenic role of Fgf23 in Hyp mice","volume":"291","author":"Liu","year":"2006","journal-title":"Am J Physiol Endocrinol Metab."},{"key":"2024020318071895400_bib34","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/0002-9343(82)90522-8","article-title":"Neuromuscular manifestations of electrolyte disorders","volume":"72","author":"Knochel","year":"1982","journal-title":"Am J Med."},{"key":"2024020318071895400_bib35","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/0960-8966(93)90063-P","article-title":"Oral phosphate supplements reverse skeletal muscle abnormalities in a case of chronic fatigue with idiopathic renal hypophosphatemia","volume":"3","author":"Land","year":"1993","journal-title":"Neuromuscul Disord."},{"key":"2024020318071895400_bib36","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/S0272-6386(99)70045-4","article-title":"Metabolic aspects of phosphate replacement therapy for hypophosphatemia after renal transplantation: impact on muscular phosphate content, mineral metabolism, and acid\/base homeostasis","volume":"34","author":"Ambuhl","year":"1999","journal-title":"Am J Kidney Dis."},{"key":"2024020318071895400_bib37","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1111\/j.1460-9568.2007.05411.x","article-title":"Dorsolateral cervical spinal injury differentially affects forelimb and hindlimb action in rats","volume":"25","author":"Muir","year":"2007","journal-title":"Eur J Neurosci."},{"key":"2024020318071895400_bib38","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00213-004-2048-7","article-title":"Forced swimming test in mice: a review of antidepressant activity","volume":"177","author":"Petit-Demouliere","year":"2005","journal-title":"Psychopharmacology (Berl)."},{"key":"2024020318071895400_bib39","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/1471-2202-8-76","article-title":"Chronologically overlapping occurrences of nicotine-induced anxiety- and depression-related behavioral symptoms: effects of anxiolytic and cannabinoid drugs","volume":"8","author":"Hayase","year":"2007","journal-title":"BMC Neurosci."},{"key":"2024020318071895400_bib40","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/nature05315","article-title":"Klotho converts canonical FGF receptor into a specific receptor for FGF23","volume":"444","author":"Urakawa","year":"2006","journal-title":"Nature."},{"key":"2024020318071895400_bib41","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.abb.2010.05.029","article-title":"Hypophosphatemia is responsible for skeletal muscle weakness of vitamin D deficiency","volume":"500","author":"Shubert","year":"2010","journal-title":"Arch Biochem Biophy."}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.275","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/26\/4\/803\/56559060\/275_ftp.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/26\/4\/803\/56559060\/275_ftp.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:55:31Z","timestamp":1710341731000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/26\/4\/803-810\/7598115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,10,11]]},"references-count":41,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2010,10,11]]},"published-print":{"date-parts":[[2011,4,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.275","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,4,1]]},"published":{"date-parts":[[2010,10,11]]}}}