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

Autor: Naoto Hamano, Masafumi Fukagawa, Takehiko Wada, Michio Nakamura, Hirotaka Komaba, Hideyuki Yamato, Kaichiro Sawada, Hiroaki Ishida
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Bone disease
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
030209 endocrinology & metabolism
Nephrectomy
Bone and Bones
Bone remodeling
Blood Urea Nitrogen
Rats
Sprague-Dawley
03 medical and health sciences
Hyperphosphatemia
0302 clinical medicine
Endocrinology
Internal medicine
medicine
Animals
Humans
Orthopedics and Sports Medicine
Renal osteodystrophy
Chronic Kidney Disease-Mineral and Bone Disorder
Minerals
business.industry
Phosphorus
General Medicine
Bisphosphonate
medicine.disease
Peptide Fragments
Biomechanical Phenomena
Disease Models
Animal
Fibroblast Growth Factor-23
medicine.anatomical_structure
Gene Expression Regulation
Creatinine
Cortical bone
Secondary hyperparathyroidism
Calcium
030101 anatomy & morphology
Bone Remodeling
business
Risedronic Acid
Procollagen
Kidney disease
Zdroj: Journal of bone and mineral metabolism. 38(4)
ISSN: 1435-5604
Popis: 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. 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. 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. 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.
Databáze: OpenAIRE
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