Skeletal and mineral metabolic effects of risedronate in a rat model of high-turnover renal osteodystrophy.

Abstract

INTRODUCTION:

High-turnover bone disease is a major consequence of SHPT and may explain the high risk for fracture in patients with advanced chronic kidney disease (CKD). Bisphosphonates suppress bone turnover and improve bone strength, but their effects have not been fully characterized in advanced CKD with severe SHPT. Bisphosphonates also increase 1,25-dihydroxyvitamin D levels in normal and uremic rats, but the underlying mechanism remains to be determined.

MATERIALS AND METHODS:

We investigated the skeletal and mineral metabolic effects of RIS, a pyridinyl bisphosphonate, in rats with severe SHPT induced by 5/6 nephrectomy plus a high phosphate diet.

RESULTS:

Nephrectomized rats developed severe SHPT, along with hyperphosphatemia, low 1,25-dihydroxyvitamin D, and markedly increased FGF23. Moreover, these rats exhibited characteristic features of high-turnover renal osteodystrophy, including increased indices of trabecular bone turnover, decreased cortical bone thickness, inferior cortical biomechanical properties, and a prominent increase in peritrabecular fibrosis. RIS treatment increased bone volume and partially attenuated trabecular bone remodeling, cortical bone loss, and mechanical properties, whereas it produced a marked improvement in peritrabecular fibrosis along with a corresponding decrease in osteogenic gene markers. RIS treatment also suppressed the elevation of FGF23, which was associated with increased 1,25-dihydroxyvitamin D.

CONCLUSIONS:

In a rat model of severe SHPT, treatment with RIS partially attenuated histological manifestations of high-turnover bone disease. RIS treatment also suppressed the elevation of FGF23, which may explain the increased 1,25-dihydroxyvitamin D production during the treatment.

• Authors: Hiroaki Ishida, Hirotaka Komaba, Naoto Hamano, Hideyuki Yamato, Kaichiro Sawada, Takehiko Wada, Michio Nakamura, Masafumi Fukagawa
• Journal: Journal of bone and mineral metabolism (J Bone Miner Metab) Vol. 38 Issue 4 Pg. 501-510 (Jul 2020) ISSN: 1435-5604 [Electronic] Japan
• PMID: 32140785 (Publication Type: Journal Article)

Chemical References

• FGF23 protein, human
• Minerals
• Peptide Fragments
• Procollagen
• procollagen Type I N-terminal peptide
• Phosphorus
• Fibroblast Growth Factor-23
• Creatinine
• Risedronic Acid
• Calcium

Topics

• Animals
• Biomechanical Phenomena
• Blood Urea Nitrogen
• Bone Remodeling (drug effects)
• Bone and Bones (drug effects, pathology, physiopathology)
• Calcium (blood)
• Chronic Kidney Disease-Mineral and Bone Disorder (blood, drug therapy, physiopathology)
• Creatinine (blood)
• Disease Models, Animal
• Fibroblast Growth Factor-23
• Gene Expression Regulation (drug effects)
• Humans
• Male
• Minerals (metabolism)
• Nephrectomy
• Peptide Fragments (blood)
• Phosphorus (blood)
• Procollagen (blood)
• Rats, Sprague-Dawley
• Risedronic Acid (pharmacology, therapeutic use)