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Effect of administration and subsequent cessation of buserelin on cancellous bone of female rats
Author(s) -
Tobias J.H.,
Chambers T.J.,
Gallagher A.
Publication year - 1994
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650091211
Subject(s) - buserelin , cancellous bone , medicine , ovariectomized rat , endocrinology , hypoestrogenism , estrogen , agonist , surgery , receptor
Abstract Although hormone replacement therapy is effective in preventing postmenopausal bone loss, it fails to cause a return of bone mass to normal in patients with established osteoporosis. Similarly, in the ovariectomized rat, estrogen administration protects the skeleton from bone loss but fails to reverse this once it has occurred. However, physiologically produced sex steroids may, in contrast to conventional methods of sex steroid administration, be capable of restoring bone mass in osteopenic states. To investigate this question, we analyzed the effect of treatment with the LHRH agonist buserelin for varying durations, and subsequent cessation thereof, on histomorphometric indices of rat cancellous bone. Female rats 13 weeks old were given daily SC injections of vehicle or buserelin as follows: vehicle days 1‐90; vehicle days 1‐150; vehicle days 1‐60, buserelin days 61‐90; vehicle days 1‐60, buserelin days 61‐90, vehicle days 91‐150; vehicle days 1‐30, buserelin days 31‐90; vehicle days 1‐30, buserelin days 31‐90, vehicle days 91‐150; buserelin days 1‐90; buserelin days 1‐90, vehicle days 91‐150. At the end of the treatment period, animals were killed, tibiae removed, and histomorphometric indices assessed at the secondary spongiosa of the proximal metaphysis. Analysis of vaginal smears confirmed that buserelin rapidly suppressed ovulation, which quickly returned once treatment was stopped. We found that administration of buserelin for 30, 60, or 90 days reduced cancellous bone volume because of a reduction in both the number and thickness of trabeculae. The bone loss was at least partly a result of increased bone resorption, because buserelin significantly increased osteoclast surface and number. After cessation of buserelin administration, trabecular number remained unchanged but trabecular thickness increased in all groups, returning to that of vehicle‐treated animals. We conclude that buserelin reduces cancellous bone volume in female rats by decreasing trabecular number and thickness and that the latter, but not the former, is restored to normal by the return of ovulation on stopping treatment.