title: Effects of dihydrotestosterone alone and combined with estrogen on bone mineral density, bone growth, and formation rates in ovariectomized rats.
abstract: Androgens are associated with the greater skeletal mass and size in men compared with women and have been used as anabolic agents promoting skeletal growth and mineral accretion in both sexes, but specific effects on growth and bone formation in the female skeleton are not well understood. The effects of 5 alpha-dihydrotestosterone (DHT) alone, and in combination with 17 beta-estradiol on bone and bone growth were studied in female ovariectomized (OVX) rats with established osteopenia. Eight weeks after OVX, rats were given 0.1 mg 17 beta-estradiol and/or 2.5 mg or 10 mg DHT administered by controlled-release pellets for 2 months. Body weights decreased with estrogen treatment but increased with DHT. Bone mineral density increased with the highest dose of DHT relative to OVX controls and the estrogen treated group. Dry and ashed bone weights and ash/dry weight ratios increased in the estrogen and DHT treated animals compared to the baseline OVX controls. Total bone calcium was greater with DHT and estrogen combined with DHT. The percent of calcium in the ash increased in all DHT treated groups. When normalized to final body weight, the total femur calcium content was significantly increased in the estrogen and estrogen with DHT groups, but not in the DHT groups compared with the baseline OVX and OVX control groups. The periosteal bone formation rates were increased with the high dose DHT alone and combined with estrogen. OVX rats had increased endochondral bone elongation rates relative to controls but this was decreased with estrogen treatment. DHT combined with estrogen increased endochondral growth rates relative to the estrogen treated group. Trabecular bone volume was decreased in all OVX groups relative to the base line group, but there were no significant effects observed with any treatments. Cancellous bone formation rates were suppressed with estrogen treatment but were partially reversed when combined with DHT. DHT treatments also increased most cancellous bone formation indices over OVX controls. While estrogen is known to preserve skeletal mass by reducing bone turnover, DHT increased skeletal mass by promoting bone growth and formation with concomitant increases in total body mass. DHT had greater effects on cortical bone and partially mitigated the suppressive effects of estrogen on bone growth and formation in the female skeleton.
authors.affiliation: Division of Radiobiology, School of Medicine, University of Utah, Salt Lake City, USA.
authors.forename: V
authors.initials: V
authors.lastname: Coxam
authors.forename: B M
authors.initials: BM
authors.lastname: Bowman
authors.forename: M
authors.initials: M
authors.lastname: Mecham
authors.forename: C M
authors.initials: CM
authors.lastname: Roth
authors.forename: M A
authors.initials: MA
authors.lastname: Miller
authors.forename: S C
authors.initials: SC
authors.lastname: Miller
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D001846:Bone Development / Q000187:drug effects* / Q000502:physiology; D001851:Bone Diseases, Metabolic / Q000188:drug therapy*; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D013196:Dihydrotestosterone; D004958:Estradiol