title: FGF23 neutralization improves bone quality and osseointegration of titanium implants in chronic kidney disease mice.
abstract: Chronic kidney disease (CKD) is a worldwide health problem. Serum levels of FGF23, a phosphaturic hormone, increase at the earliest stages of CKD, and have been found to be independently associated with the mortality and morbidity of CKD patients. The purpose of this study was to evaluate whether FGF23 neutralization was able to improve bone quality and osseointegration of titanium implants. Uremia was induced by 5/6 nephrectomy in adult female mice. Postsurgery, the mice were injected with vehicle or FGF23 neutralizing antibody (5 mg/kg body weight) 3 times a week. Experimental titanium implants were inserted in the distal end of the femurs. FGF23 neutralization significantly increased serum phosphate, 1,25(OH)2D and BUN, and decreased serum PTH and FGF23, relative to vehicle-treated CKD mice. Histomorphometric analysis of the tibiae indicated that FGF23 neutralization normalized the osteoidosis observed in vehicle-treated CKD mice. Although bone-implant contact ratio remained unchanged by anti-FGF23 antibody treatment, the strength of osseointegration, as evidenced by a biomechanical push-in test, was significantly improved by FGF23 neutralization. Our findings revealed that FGF23 neutralization effectively improves bone quality and osseointegration of titanium implants in CKD mice, suggesting FGF23 as a key factor of CKD related bone diseases.
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors: Ningyuan
authors: N
authors: Sun
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors: Yuchen
authors: Y
authors: Guo
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors: Weiqing
authors: W
authors: Liu
authors: Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA.
authors: Michael
authors: M
authors: Densmore
authors: Amgen Inc., Thousand Oaks, CA, USA.
authors: Victoria
authors: V
authors: Shalhoub
authors: Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria.
authors: Reinhold G
authors: RG
authors: Erben
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors: Ling
authors: L
authors: Ye
authors: Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA.
authors: Beate
authors: B
authors: Lanske
authors: 1] State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China [2] Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA.
authors: Quan
authors: Q
authors: Yuan
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020007:Implants, Experimental; D051379:Mice; D016348:Osseointegration / Q000187:drug effects*; D051436:Renal Insufficiency, Chronic / Q000378:metabolism* / Q000473:pathology; D013977:Tibia / Q000378:metabolism / Q000473:pathology; D014025:Titanium
chemical_list: D057134:Antibodies, Neutralizing; C000717428:Fgf23 protein, mouse; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D014025:Titanium