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.

Klotho/FGF23 Axis in Chronic Kidney Disease and Cardiovascular Disease

“…Another beneficial effect of FGF23-neutralizing antibody was to attenuate bone disease and improve bone quality [99] . Such ''negative'' consequences following neutralizing antibody do not discourage one's effort to explore the clinical potential of FGF23, but rather they stimulate one to define FGF23's pathophysiological action and especially delineate the narrow window between adaptation and maladaptation of high FGF23 in the CKD scenario [100] .…”

FGF23 Neutralizing Antibody Ameliorates Hypophosphatemia and Impaired FGF Receptor Signaling in Kidneys of HMWFGF2 Transgenic Mice

“…Overexpression of FGF23, a bone‐derived hormone caused Pi wasting, hypophosphatemia, and rickets (Larsson et al, ). Multiple studies in rodents have shown (Shalhoub et al, ; Shimada and Fukumoto, ; Sun et al, ) that FGF23 neutralization improves bone quality and phosphate homeostasis.…”

Evaluation of FGF‐23 and 25(OH)D3 levels in peri‐implant sulcus fluid in peri‐implant health and diseases

“…Sun et al showed that FGF-23 neutralization in animal model with chronic kidney disease developed the bone quality and osseointegration of titanium implants. 33 Zou showed that in the histomorphometric analysis of implants placed in experimental animals with chronic kidney disease was characterized by an increase in FGF-23, osseointegration, and the bone-implant contact decreased in the early 2 weeks but reached a comparable level in 4 weeks. 34 To the best of our knowledge, this is the first study in which FGF-23 was evaluated clinically in peri-implant diseases.…”