Droloxifene prevents ovariectomy‐induced bone loss in tibiae and femora of aged female rats: A dual‐energy X‐ray absorptiometric and histomorphometric study

作者: Hong Ka Chen , Hua Zhu Ke , Webster S. S. Jee , Yan Fei Ma , Christine M. Pirie

DOI: 10.1002/JBMR.5650100816

关键词: EstrogenEndocrinologyBone mineralBone remodelingInternal medicineOsteoporosisOvariectomized ratCancellous boneMedicineAppositionBone disease

摘要: Our previous studies indicated that droloxifene (DRO), a tissue-specific estrogen antagonist/agonist, prevented bone loss without causing uterine hypertrophy in growing ovariectomized (OVX) rats. Using dual-energy X-ray absorptiometry (DXA) and histomorphometry, the current study compared efficacy of DRO to 17βestradiol (E 2 ) preventing OVX-induced tibiae femora 19-month-old rats determine whether had similar skeletal effects as E aged female Sprague-Dawley were OVX or sham-operated (sham) at 19 months age. The treated with vehicle (oral), while 30 μg/kg/day (sc), 2.5, 5, 10 mg/kg/day (oral) for 8 weeks. Bone mineral density (BMD) whole (WF), distal femoral metaphyses (DFM), shafts (FS), proximal (PF) was determined using DXA. Static dynamic cancellous histomorphometric analyses performed double-labeled undecalcified longitudinal sections from tibial metaphyses. Ovariectomy weeks significantly reduced BMD WF, DFM, FS, PF (from -6 - 15%). Treatment completely decreases WF DFM no significant FS decrease induced by treatment all dose levels. In addition, PF. Furthermore, results showed decreased trabecular volume 34% increased activation frequency 104% it nonsignificantly other indices including percent eroded perimeter, apposition rate, formation rate per controls. levels increases turnover, indicating is an agonist Together findings inhibited body weight gain, total serum cholesterol, effect on weight, we conclude efficacious inhibiting turnover but estrogenic These data suggest may be superior postmenopausal senile osteoporoses. (J Miner Res 1995 ;10 :1256-1262)

参考文章(24)
Riggs Bl, Overview of osteoporosis. Western Journal of Medicine. ,vol. 154, pp. 63- 77 ,(1991)
ROBERT LINDSAY, FELICIA COSMAN, Estrogen in prevention and treatment of osteoporosis. Annals of the New York Academy of Sciences. ,vol. 592, pp. 326- 333 ,(1990) , 10.1111/J.1749-6632.1990.TB30343.X
T. J. Wronski, L. M. Dann, K. S. Scott, M. Cintrón, Long-term effects of ovariectomy and aging on the rat skeleton Calcified Tissue International. ,vol. 45, pp. 360- 366 ,(1989) , 10.1007/BF02556007
DIKE N. KALU, CHUNG-CHING LIU, ROBERT R. HARDIN, BRUCE W. HOLLIS, The Aged Rat Model of Ovarian Hormone Deficiency Bone Loss Endocrinology. ,vol. 124, pp. 7- 16 ,(1989) , 10.1210/ENDO-124-1-7
M Dukes, R Chester, L Yarwood, A E Wakeling, Effects of a non-steroidal pure antioestrogen, ZM 189,154, on oestrogen target organs of the rat including bones. Journal of Endocrinology. ,vol. 141, pp. 335- 341 ,(1994) , 10.1677/JOE.0.1410335
Urs Eppenberger, Katja Wosikowski, Willy Küng, Pharmacologic and biologic properties of droloxifene, a new antiestrogen. American Journal of Clinical Oncology. ,vol. 14, pp. 5- 14 ,(1991) , 10.1097/00000421-199112002-00004
W.S.S. Jee, H.M. Frost, On the rat model of human osteopenias and osteoporoses Bone and Mineral. ,vol. 18, pp. 227- 236 ,(1992) , 10.1016/0169-6009(92)90809-R
L J Black, M Sato, E R Rowley, D E Magee, A Bekele, D C Williams, G J Cullinan, R Bendele, R F Kauffman, W R Bensch, Raloxifene (LY139481 HCI) Prevents Bone Loss and Reduces Serum Cholesterol without Causing Uterine Hypertrophy in Ovariectomized Rats Journal of Clinical Investigation. ,vol. 93, pp. 63- 69 ,(1994) , 10.1172/JCI116985
Masahiko Sato, Cindy McClintock, John Kim, Charles H. Turner, Henry U. Bryant, David Magee, Charles W. Slemenda, Dual-energy x-ray absorptiometry of raloxifene effects on the lumbar vertebrae and femora of ovariectomized rats. Journal of Bone and Mineral Research. ,vol. 9, pp. 715- 724 ,(2009) , 10.1002/JBMR.5650090517
RUSSELL T. TURNER, B. LAWRENCE RIGGS, THOMAS C. SPELSBERG, Skeletal Effects of Estrogen Endocrine Reviews. ,vol. 15, pp. 275- 300 ,(1994) , 10.1210/EDRV-15-3-275