Androstenedione treatment reduces loss of cancellous bone volume in ovariectomised rats in a dose-responsive manner and the effect is not mediated by oestrogen.
We have tested the hypothesis that androstenedione (administered as 21-day, slow-release pellets) is converted to active sex steroids and reduces bone turnover in the ovariectomised rat model. We found that ovariectomy resulted in a minor but significant reduction in plasma concentrations of androstenedione and testosterone and a more significant reduction in oestrone (E1) and oestradiol (E2). This was associated with the expected substantial loss of metaphyseal cancellous bone volume. Androstenedione (1.5-100 mg) pellets increased the plasma concentrations of androstenedione and testosterone above those in the ovariectomised (ovx) rats in a dose-responsive manner, whereas E2 plasma concentrations were increased to a minor but significant degree above those in the ovx animals. Androstenedione reduced loss of cancellous bone volume in a dose-dependent fashion by reducing bone turnover. The 1.5, 5 and 100 mg androstenedione-induced effect on bone turnover was not abrogated by simultaneous treatment with Arimidex, an aromatase inhibitor. This implies that the skeletal-protective effect of androstenedione was not oestrogen-mediated.
Lea
C K
CK
Department of Histopathology, Imperial College of Medicine at St Mary's, London, UK.
Moxham
V
V
Reed
M J
MJ
Flanagan
A M
AM
D000735:Androstenedione / Q000097:blood / Q000627:therapeutic use*; D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000097:blood
D003692:Delayed-Action Preparations; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol