Linked Life Data

8988345

Source:http://linkedlifedata.com/resource/pubmed/id/8988345

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-3-24
pubmed:abstractText
The purpose of this study was to compare the effects of droloxifene (DRO), tamoxifen (TAM), and 17 alpha-ethynyl estradiol (EE) on bone mineral density, bone histomorphometry, total serum cholesterol, and uterine histology in the ovariectomized (ovx) rat model. Sprague-Dawley female rats at five months of age were sham-operated and treated orally with vehicle (n = 8), or ovx (n = 56) and treated (p.o.) with either vehicle, DRO at 0.1 or 1.0 mg/kg daily, TAM at 0.1 or 1 mg/kg daily, or EE at 3 or 30 micrograms/kg daily for 4 weeks. The uterine wet weight and uterine histologic parameters (cross-sectional tissue area, stromal thickness, and luminal epithelial thickness) were determined. Femoral and lumbar vertebral bone mineral density was determined ex vivo using dual energy x-ray absorptiometry. Static and dynamic cancellous bone histomorphometry was performed on double-labeled, undecalcified longitudinal sections from proximal tibial metaphyses. Furthermore, the changes in total serum cholesterol and body weight gain were also determined. Compared to sham controls, ovx for four weeks significantly decreased uterine weight (-72%), uterine cross-sectional tissue area (-74%), stromal thickness (-52%), and luminal epithelial thickness (-53%). ovx rats treated with EE at 30 micrograms/kg/day maintained these parameters at the levels of sham controls. Uterine weight and uterine cross-sectional tissue area in 3 micrograms/kg/day of EE treated ovx rats were higher than that of vehicle-treated ovx rats. In ovx rats treated with TAM at both 0.1 and 1 mg/kg/day, these parameters were significantly less than sham controls but significantly higher than ovx controls. DRO at 0.1 mg/kg/day had no effects on all above parameters. Uterine weight and cross-sectional tissue area in 1 mg/kg/day of DRO treated ovx rats was slightly but significantly higher than that in ovx controls. However, DRO at 1 mg/kg/day had no effects on uterine stromal thickness and luminal epithelial thickness compared to ovx controls. The ovx-induced decrease in femoral and lumbar vertebral bone mineral density was prevented by treatment with EE at 30 micrograms/kg/day, TAM at both 0.1 and 1 mg/kg/day, or DRO at 1 mg/kg/day. Similarly, the decrease in bone mass and the increase in bone resorption and bone turnover in proximal tibial metaphyses were prevented by treatment with EE at 30 micrograms/kg/day or TAM at both 0.1 and 1 mg/kg/day, or DRO at 1 mg/kg/day. Total serum cholesterol decreased significantly in ovx rats treated with either EE, DRO, or TAM at all dose levels compared to vehicle treated ovx controls (-32% to -56%). The ovx-induced body weight gain was completely prevented by EE at 30 micrograms/kg/day, and partially prevented by DRO at 1 mg/kg/day. TAM at both 0.1 and 1 mg doses caused a significant decrease in body weight compared to both sham and ovx controls. Our results indicated that DRO prevented ovx-induced bone loss and lowered total serum cholesterol with an ED50 less than 1 mg/kg/day. The bone protective and cholesterol lowering effects of DRO were comparable to those observed with TAM and EE. However, DRO differed from TAM and EE in its lack of significant estrogenic effects on uterine tissue at doses which were bone protective. These data suggest that DRO may be a significant alternative to EE and TAM for prevention and treatment of postmenopausal osteoporosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
8756-3282
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
31-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:8988345-Absorptiometry, Photon, pubmed-meshheading:8988345-Administration, Oral, pubmed-meshheading:8988345-Analysis of Variance, pubmed-meshheading:8988345-Animals, pubmed-meshheading:8988345-Bone Density, pubmed-meshheading:8988345-Bone Resorption, pubmed-meshheading:8988345-Cholesterol, pubmed-meshheading:8988345-Disease Models, Animal, pubmed-meshheading:8988345-Estradiol Congeners, pubmed-meshheading:8988345-Estrogen Antagonists, pubmed-meshheading:8988345-Ethinyl Estradiol, pubmed-meshheading:8988345-Female, pubmed-meshheading:8988345-Femur, pubmed-meshheading:8988345-Humans, pubmed-meshheading:8988345-Lumbar Vertebrae, pubmed-meshheading:8988345-Osteoporosis, Postmenopausal, pubmed-meshheading:8988345-Ovariectomy, pubmed-meshheading:8988345-Rats, pubmed-meshheading:8988345-Rats, Sprague-Dawley, pubmed-meshheading:8988345-Tamoxifen, pubmed-meshheading:8988345-Tibia, pubmed-meshheading:8988345-Uterus, pubmed-meshheading:8988345-Weight Gain
pubmed:year
1997
pubmed:articleTitle
Comparative effects of droloxifene, tamoxifen, and estrogen on bone, serum cholesterol, and uterine histology in the ovariectomized rat model.
pubmed:affiliation
Department of Metabolic Diseases, Central Research Division, Pfizer Inc., Groton, CT 06340, USA.
pubmed:publicationType
Journal Article, Comparative Study