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Droloxifene prevents ovariectomy‐induced bone loss in tibiae and femora of aged female rats: A dual‐energy X‐ray absorptiometric and histomorphometric study
Author(s) -
Chen Hong Ka,
Ke Hua Zhu,
Jee Webster S. S.,
Ma Yan Fei,
Pirie Christine M.,
Simmons Hollis A.,
Thompson David D.
Publication year - 1995
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650100816
Subject(s) - endocrinology , medicine , cancellous bone , ovariectomized rat , bone mineral , dual energy x ray absorptiometry , osteopenia , bone density , estrogen , osteoporosis , metaphysis , bone remodeling , anatomy
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 bone histomorphometry, the current study compared the efficacy of DRO to 17β‐estradiol (E 2 ) in preventing OVX‐induced bone loss in tibiae and femora of 19‐month‐old rats to determine whether DRO had similar skeletal effects as E 2 in aged female rats. Sprague‐Dawley female rats were OVX or sham‐operated (sham) at 19 months of age. The sham‐operated rats were treated with vehicle (oral), while the OVX rats were treated with vehicle (oral), E 2 at 30 μg/kg/day (sc), or DRO at 2.5, 5, or 10 mg/kg/day (oral) for 8 weeks. Bone mineral density (BMD) of whole femora (WF), distal femoral metaphyses (DFM), femoral shafts (FS), and proximal femora (PF) was determined using DXA. Static and dynamic cancellous bone histomorphometric analyses were performed in double‐labeled undecalcified longitudinal sections from proximal tibial metaphyses. Ovariectomy for 8 weeks significantly reduced the BMD of WF, DFM, FS, and PF (from −6 to −15%). Treatment with E 2 completely prevented the decreases in BMD of WF and DFM and had no significant effects in BMD of FS and PF in aged OVX rats. The decrease in BMD of DFM induced by OVX was prevented by treatment with DRO at all dose levels. In addition, DRO at 10 mg/kg/day prevented OVX‐induced decreases in BMD of WF, FS, and PF. Furthermore, proximal tibial cancellous bone histomorphometric results showed that OVX significantly decreased the trabecular bone volume by 34% and increased the activation frequency by 104% while it nonsignificantly increased other indices including percent eroded perimeter, mineral apposition rate, and bone formation rate per bone volume compared with sham‐operated controls. Treatment with E 2 or DRO at all dose levels completely prevented the OVX‐induced decreases in trabecular bone volume and increases in bone turnover, indicating that DRO is an estrogen agonist in bone in aged OVX rats. Together with the previous findings that DRO inhibited body weight gain, reduced total serum cholesterol, and had no effect on uterine weight, we conclude that DRO is as efficacious as E 2 in preventing OVX‐induced bone loss and inhibiting bone turnover but without estrogenic uterine effects in aged OVX rats. These data suggest that DRO may be superior to E 2 for the treatment of postmenopausal and senile osteoporoses.