Droloxifene prevents ovariectomy-induced bone loss in tibiae and femora of aged female rats: a dual-energy X-ray absorptiometric and histomorphometric study.
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 17 beta-estradiol (E2) in preventing OVX-induced bone loss in tibiae and femora of 19-month-old rats to determine whether DRO had similar skeletal effects as E2 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), E2 at 30 micrograms/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 E2 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Chen
H K
HK
Division of Radiobiology, University of Utah School of Medicine, Salt Lake City, USA.
Ke
H Z
HZ
Jee
W S
WS
Ma
Y F
YF
Pirie
C M
CM
Simmons
H A
HA
Thompson
D D
DD
D015502:Absorptiometry, Photon; D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015519:Bone Density / Q000187:drug effects*; D001846:Bone Development / Q000187:drug effects; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005269:Femur / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D010052:Ovariectomy / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013977:Tibia / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology; D014599:Uterus / Q000187:drug effects / Q000473:pathology
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D013629:Tamoxifen; C038345:droloxifene; D004958:Estradiol