أعرض في EDS

Effects of eight-month treatment with ONO-5334, a cathepsin K inhibitor, on bone metabolism, strength and microstructure in ovariectomized cynomolgus monkeys

التفاصيل البيبلوغرافية
العنوان: Effects of eight-month treatment with ONO-5334, a cathepsin K inhibitor, on bone metabolism, strength and microstructure in ovariectomized cynomolgus monkeys
المؤلفون: Makoto Tanaka, Akiko Kunishige, Yasuaki Hashimoto, Hiroyuki Yamada, Kazuhito Kawabata, Yasuo Ochi, Satoshi Nishikawa, Hiroshi Mori, Masafumi Sugitani, Naoki Kawada, Ryoji Kayasuga, Yasutomo Nakanishi
المصدر: Bone. 65:1-8
بيانات النشر: Elsevier BV, 2014.
سنة النشر: 2014
مصطلحات موضوعية: medicine.medical_specialty, Histology, Physiology, Ovariectomy, Endocrinology, Diabetes and Metabolism, Cathepsin K, Osteoporosis, Cysteine Proteinase Inhibitors, Bone and Bones, Bone remodeling, Absorptiometry, Photon, N-terminal telopeptide, Internal medicine, medicine, Animals, Quantitative computed tomography, Femoral neck, medicine.diagnostic_test, business.industry, medicine.disease, Macaca fascicularis, medicine.anatomical_structure, Endocrinology, Ovariectomized rat, Thiazolidines, Female, business, Type I collagen
الوصف: This study examined the effect of ONO-5334, a cathepsin K inhibitor, on bone turnover, mineral density (BMD), mechanical strength and microstructure in ovariectomized (OVX) cynomolgus monkeys. Vehicle, ONO-5334 (3, 10 or 30 mg/kg) or alendronate (0.5 mg/kg) was orally administered for eight months to sham- and OVX-operated monkeys. ONO-5334 dose-dependently suppressed OVX-induced increase in bone turnover markers (urinary C-terminal cross-linking telopeptide of type I collagen (CTX) and serum osteocalcin). At the dose of 30 mg/kg, ONO-5334 maintained urinary CTX at nearly zero level and kept serum osteocalcin around the level of the sham animals. Marker levels in the alendronate-treated animals were similar to those in the sham animals throughout the study. ONO-5334 dose-dependently reversed the effect of OVX on vertebral BMD as measured by dual-energy X-ray absorptiometry (DXA) with improvement of bone mechanical strength. Both ONO-5334 and alendronate suppressed OVX-induced changes in vertebral microstructure and turnover state. In the femoral neck, peripheral quantitative computed tomography (pQCT) analysis showed that ONO-5334 increased total and cortical BMD. In particular, ONO-5334 significantly increased cortical BMD with improvement of bone mechanical strength. In microstructural analysis, alendronate suppressed OVX-induced increase in femoral mid-shaft osteonal bone formation rate (BFR) to a level below that recorded in the sham group, whereas ONO-5334 at 30 mg/kg did not suppress periosteal, osteonal and endocortical BFR. This finding supports the significant effect of ONO-5334 on cortical BMD and mechanical strength in the femoral neck. The results of this study suggest that ONO-5334 has good therapeutic potential for the treatment of osteoporosis.
تدمد: 8756-3282
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::450debfddc0964571e7a0dd89d80f3d7
https://doi.org/10.1016/j.bone.2014.04.023
حقوق: CLOSED
رقم الأكسشن: edsair.doi.dedup.....450debfddc0964571e7a0dd89d80f3d7
قاعدة البيانات: OpenAIRE
الوصف
تدمد:87563282