CORTICAL REMODELING FOLLOWING SUPPRESSION OF ENDOGENOUS ESTROGEN WITHANALOGS OF GONADOTROPIN-RELEASING-HORMONE

The effects of estrogen suppression on osteonal remodeling in young wo men was investigated using transiliac biopsies (eight paired biopsies + four single pre; three single post biopsies) taken before and after treatment for endometriosis (6 months) with analogs of gonadotrophin r eleasing hormone (GnRH), Estrogen withdrawal increased the proportion of Haversian canals with an eroded surface (106%, p = 0.047), a double label (238%, p = 0.004), osteoid (71%, p = 0.002), and alkaline phosp hatase (ALP) (116%, p = 0.043) but not those showing tartrate-resistan t acid phosphatase (TRAP) activity (p = 0.25) or a single label (p = 0 .30), Estrogen withdrawal increased TRAP activity in individual osteoc lasts in canals with diameters greater than 50 mu m (p = 0.0089) and a lso the number of osteons with diameters over 250 mu m (P = 0.049). AL P activity in individual osteoblasts was increased but not significant ly following treatment (p = 0.051), Wall thickness was significantly c orrelated,vith osteon diameter (p < 0.001). In a separate group of pat ients (four pairs + one post biopsy) on concurrent treatment with tibo lone, there was no significant increase in the osteon density, cortica l porosity, median canal diameter, or the markers of bone formation an d resorption, Enzyme activities and numbers of active canals were also not increased with the concurrent treatment, but there was still an i ncrease in the osteon diameter, As previously shown for cancellous bon e, estrogen withdrawal increased cortical bone turnover, We have now s hown that resorption depth within Haversian systems was also increased with treatment. The enhanced TRAP activity in individual osteoclasts supports the concept that osteoclasts are more active following estrog en withdrawal in agreement with theoretical arguments advanced previou sly, Understanding the cellular and biochemical mechanisms responsible for increased depth of osteoclast resorption when estrogen is withdra wn may allow the development of new strategies for preventing postmeno pausal bone loss.