Transient reduction in trabecular bone formation after discontinuation of administration of oestradiol-17 beta to ovariectomized rats.
While the osteopenia associated with oestrogen deficiency is thought to arise from a relative defect in bone formation with respect to resorption, oestrogen administration itself leads to a decrease, rather than an increase, in bone formation. This decrease in bone formation, which arises from oestrogen's inhibitory effect on bone turnover, presumably masks any underlying tendency of oestrogen treatment towards stimulation of bone formation. To investigate this further, we have examined the early effect of discontinuing the administration of oestradiol-17 beta (OE2; 40 micrograms/kg) on bone formation indices in ovariectomized 13-week-old rats, before the turnover-induced increase in formation occurs. Histomorphometric indices were assessed at the proximal tibial metaphysis 0, 7, 10, 13 and 16 days following discontinuation of OE2 treatment. Measurements of body weight, uterine weight and longitudinal growth rate confirmed that there were rapid effects of OE2 deficiency on these parameters. We could detect no significant increase in bone resorption, as measured by osteoclast surface and number, until 16 days after ending treatment with OE2; this was coincidental with a reduction in bone volume. Shorter periods of OE2 deficiency were associated with a marked decrease in bone formation, as assessed by dynamic histomorphometric indices. This inhibition of bone formation was largely due to a reduction in double fluorochrome-labeled trabecular surfaces, which were decreased by approximately 70%. We conclude that ending OE2 administration in ovariectomized rats caused a striking decrease in trabecular bone formation, if such indices are assessed prior to the subsequent turnover-induced increase in formation.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Histopathology, St George's Hospital Medical School, London, U.K.
J H
JH
Tobias
T J
TJ
Chambers
D000818:Animals; D001835:Body Weight; D001846:Bone Development / Q000187:drug effects* / Q000502:physiology; D001851:Bone Diseases, Metabolic / Q000517:prevention & control; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D009929:Organ Size; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D013977:Tibia / Q000254:growth & development; D014599:Uterus / Q000187:drug effects
D004958:Estradiol