The effects of bazedoxifene in the ovariectomized aged cynomolgus monkey
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| 024 | 7 | 0 | |a 10.1007/s00774-014-0580-z |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s00774-014-0580-z | ||
| 245 | 0 | 4 | |a The effects of bazedoxifene in the ovariectomized aged cynomolgus monkey |h [Elektronische Daten] |c [Susan Smith, Jacquelin Jolette, Luc Chouinard, Barry Komm] |
| 520 | 3 | |a Bazedoxifene (BZA) is a novel selective estrogen receptor modulator in clinical development for the prevention and treatment of postmenopausal osteoporosis. This preclinical study evaluated the efficacy and safety of BZA in preventing ovariectomy (OVX)-induced bone loss in aged cynomolgus monkeys. Animals (18 per group) underwent OVX and were administered BZA (0.2, 0.5, 1, 5, or 25mg/kg/day) or vehicle, or were sham-operated and administered vehicle, by daily oral gavage for 18months. Biochemical markers of bone turnover were assessed at 6, 12, and 18months, along with bone densitometry using dual energy X-ray absorptiometry and peripheral quantitative computed tomography. Animals were killed after 18months. Uterine and pituitary weights were determined, and histomorphometric and biomechanical measurements were performed. OVX vehicle controls showed increases in bone turnover associated with cancellous and cortical bone osteopenia (in vivo), and slight decreases (not statistically significant) in biomechanical strength parameters at the lumbar spine and femoral neck. BZA partially preserved cortical and cancellous bone mass by preventing the OVX-induced increases in bone turnover. Although the response was often similar among BZA-treated groups, the strongest efficacy was generally seen at 25mg/kg/day. Treatment with BZA did not adversely affect measures of bone strength and was well tolerated; there was no evidence of uterotrophic activity, mammary tissue was unaffected, and there were no adverse effects on plasma lipids. Treatment of ovariectomized animals with BZA partially prevented changes in bone remodeling that correlated with increases in bone mineral density, while maintaining bone strength and a favorable safety profile. | |
| 540 | |a The Japanese Society for Bone and Mineral Research and Springer Japan, 2014 | ||
| 690 | 7 | |a Osteoporosis |2 nationallicence | |
| 690 | 7 | |a Selective estrogen receptor modulator |2 nationallicence | |
| 690 | 7 | |a Bazedoxifene |2 nationallicence | |
| 690 | 7 | |a Treatment |2 nationallicence | |
| 690 | 7 | |a Prevention |2 nationallicence | |
| 700 | 1 | |a Smith |D Susan |u Charles River Preclinical Services, 22022 Transcanadienne, H9X 3R3, Senneville, QC, Canada |4 aut | |
| 700 | 1 | |a Jolette |D Jacquelin |u Charles River Preclinical Services, 22022 Transcanadienne, H9X 3R3, Senneville, QC, Canada |4 aut | |
| 700 | 1 | |a Chouinard |D Luc |u Charles River Preclinical Services, 22022 Transcanadienne, H9X 3R3, Senneville, QC, Canada |4 aut | |
| 700 | 1 | |a Komm |D Barry |u Pfizer Inc, 500 Arcola Road, 19426, Collegeville, PA, USA |4 aut | |
| 773 | 0 | |t Journal of Bone and Mineral Metabolism |d Springer Japan |g 33/2(2015-03-01), 161-172 |x 0914-8779 |q 33:2<161 |1 2015 |2 33 |o 774 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00774-014-0580-z |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s00774-014-0580-z |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Smith |D Susan |u Charles River Preclinical Services, 22022 Transcanadienne, H9X 3R3, Senneville, QC, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Jolette |D Jacquelin |u Charles River Preclinical Services, 22022 Transcanadienne, H9X 3R3, Senneville, QC, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Chouinard |D Luc |u Charles River Preclinical Services, 22022 Transcanadienne, H9X 3R3, Senneville, QC, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Komm |D Barry |u Pfizer Inc, 500 Arcola Road, 19426, Collegeville, PA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Journal of Bone and Mineral Metabolism |d Springer Japan |g 33/2(2015-03-01), 161-172 |x 0914-8779 |q 33:2<161 |1 2015 |2 33 |o 774 | ||