Minodronic acid (ONO-5920/YM529) prevents decrease in bone mineral density and bone strength, and improves bone microarchitecture in ovariectomized cynomolgus monkeys

Bone
Hiroshi MoriToshitaka Nakamura

Abstract

This study examined the effect of the highly potent nitrogen-containing bisphosphonate, minodronic acid (ONO-5920/YM529), on bone mineral density (BMD), bone turnover, bone microarchitecture and bone strength in ovariectomized (OVX) cynomolgus monkeys. Skeletally mature female cynomolgus monkeys, aged 9-17 years, were ovariectomized or sham-operated. Minodronic acid was administered orally once a day in doses of 0, 0.015, and 0.15 mg/kg from the day after surgery for 17 months. Bone resorption markers (urinary N-terminal cross-linking telopeptide of type I collagen and deoxypyridinoline), bone formation markers (serum osteocalcin and bone alkaline phosphatase) and lumbar vertebral BMD were measured at baseline and at 4, 8, 12 and 16 months after surgery. Treatment with minodronic acid dose-dependently inhibited OVX-induced increase in bone turnover markers and decrease in lumbar vertebral BMD, and minodronic acid at 0.15 mg/kg completely prevented these changes. At 17 months after surgery, minodronic acid also suppressed bone resorption (Oc.S/BS and N.Oc/BS) and bone formation (OS/BS, MS/BS, MAR, BFR/BS, and BFR/BV) in the lumbar vertebral bodies and tibia. In the mechanical tests, ultimate load on lumbar vertebral bodies and f...Continue Reading

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Citations

Nov 26, 2009·Journal of Bone and Mineral Metabolism·Masako ItoMasao Fukunaga
Feb 9, 2011·Journal of Bone and Mineral Metabolism·Masako Ito
Sep 15, 2009·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Makoto TanakaKeiji Miyata
Jun 6, 2009·American Journal of Primatology·S Y SmithC H Turner
Jun 3, 2009·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Yuji KataeToshitaka Nakamura
Sep 24, 2016·The Journal of Organic Chemistry·Chitrakar RaviSubbarayappa Adimurthy
May 20, 2014·Organic Letters·Chitrakar RaviSubbarayappa Adimurthy
Jun 29, 2013·Organic Letters·Orazio A AttanasiFabio Mantellini
Jan 8, 2013·The Journal of Organic Chemistry·Darapaneni Chandra MohanSubbarayappa Adimurthy

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