caa a22 4500 605521042 CHVBK 20210128100738.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00223-014-9937-5 doi (NATIONALLICENCE)springer-10.1007/s00223-014-9937-5 Long-Term Treatment with Eldecalcitol (1 α , 25-Dihydroxy-2 β - (3-hydroxypropyloxy) Vitamin D3) Suppresses Bone Turnover and Leads to Prevention of Bone Loss and Bone Fragility in Ovariectomized Rats [Elektronische Daten] [Satoshi Takeda, Susan Smith, Tatsuya Tamura, Hitoshi Saito, Fumiaki Takahashi, Rana Samadfam, Solomon Haile, Nancy Doyle, Koichi Endo] The purpose of this study is to estimate the efficacy of eldecalcitol (1α, 25-Dihydroxy-2β- (3-hydroxypropyloxy) vitamin D3; ELD) on bone metabolism after long-term administration. Six-month-old Wistar-Imamichi rats were ovariectomized (OVX) and administered ELD orally at doses of 7.5, 15, or 30ng/kg daily. Bone mineral density (BMD), urinary excretion of deoxypyridinoline (DPD), a bone resorption marker, and serum total alkaline phosphatase (ALP), a surrogate marker of bone formation, were assessed after 3, 6, and 12months of treatment. After 12months of treatment, the biomechanical strength of the L4 lumbar vertebra and femoral shaft was measured, and bone histomorphometry was performed on the L3 lumbar vertebra and the tibia diaphysis. ELD prevented OVX-induced decreases in BMD of the lumbar vertebrae and femur throughout the treatment period. ELD significantly suppressed OVX-induced increases in urinary DPD excretion throughout the treatment period with minimal effects on ALP. OVX resulted in significant decreases in ultimate load and stiffness of the L4 lumbar vertebra and femoral shaft, and ELD significantly prevented the reduction in these biomechanical parameters. Bone histomorphometry at the L3 lumbar vertebra revealed that OVX induced increases in bone resorption parameters (osteoclast surface and osteoclast number) and bone formation parameters (osteoblast surface, osteoid surface, and bone formation rate), and ELD suppressed these parameters after 12months treatment. Activation frequency, which was elevated in the OVX/vehicle group, was significantly suppressed to baseline levels in ELD-treated groups, indicating that ELD maintained bone turnover at a normal level. ELD also prevented OVX-induced deterioration of microstructure in trabecular and cortical bone. These results indicated that long-term treatment of OVX rats with ELD suppressed bone turnover, and prevented OVX-induced bone loss, deterioration of bone microstructure, and reduction in bone biomechanical strength. Springer Science+Business Media New York, 2014 Vitamin D nationallicence Eldecalcitol nationallicence Bone biomechanical strength nationallicence Bone turnover nationallicence Bone mineral density nationallicence Bone resorption nationallicence Takeda Satoshi Product Research Department, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, 412-8513, Gotemba, Shizuoka, Japan aut Smith Susan Musculoskeletal Research, Charles River Laboratories Preclinical Services, Montreal, QC, Canada aut Tamura Tatsuya Discovery Pharmacology Department 1, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan aut Saito Hitoshi Medical Science Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan aut Takahashi Fumiaki Primary Lifecycle Management Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan aut Samadfam Rana Musculoskeletal Research, Charles River Laboratories Preclinical Services, Montreal, QC, Canada aut Haile Solomon Pathology Department, Charles River Laboratories Preclinical Services, Montreal, QC, Canada aut Doyle Nancy Musculoskeletal Research, Charles River Laboratories Preclinical Services, Montreal, QC, Canada aut Endo Koichi Product Research Department, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, 412-8513, Gotemba, Shizuoka, Japan aut Calcified Tissue International Springer US; http://www.springer-ny.com 96/1(2015-01-01), 45-55 0171-967X 96:1<45 2015 96 223 https://doi.org/10.1007/s00223-014-9937-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00223-014-9937-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Takeda Satoshi Product Research Department, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, 412-8513, Gotemba, Shizuoka, Japan aut NATIONALLICENCE 700 1- Smith Susan Musculoskeletal Research, Charles River Laboratories Preclinical Services, Montreal, QC, Canada aut NATIONALLICENCE 700 1- Tamura Tatsuya Discovery Pharmacology Department 1, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan aut NATIONALLICENCE 700 1- Saito Hitoshi Medical Science Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan aut NATIONALLICENCE 700 1- Takahashi Fumiaki Primary Lifecycle Management Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan aut NATIONALLICENCE 700 1- Samadfam Rana Musculoskeletal Research, Charles River Laboratories Preclinical Services, Montreal, QC, Canada aut NATIONALLICENCE 700 1- Haile Solomon Pathology Department, Charles River Laboratories Preclinical Services, Montreal, QC, Canada aut NATIONALLICENCE 700 1- Doyle Nancy Musculoskeletal Research, Charles River Laboratories Preclinical Services, Montreal, QC, Canada aut NATIONALLICENCE 700 1- Endo Koichi Product Research Department, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, 412-8513, Gotemba, Shizuoka, Japan aut NATIONALLICENCE 773 0- Calcified Tissue International Springer US; http://www.springer-ny.com 96/1(2015-01-01), 45-55 0171-967X 96:1<45 2015 96 223