Hormone replacement therapy prevents osteoclastic hyperactivity: A histomorphometric study in early postmenopausal women

In a randomized, double blind, clinical prospective trial comprising 35 wom en treated with either hormone replacement therapy (HRT) (cyclic estradiol/ norethisterone acetate) or placebo we performed histomorphometric studies o n paired bone biopsies obtained before and after 2 years of treatment. Untr eated women developed a progressively more negative balance at individual b one multicellular units (BMUs) (i.e., wall thickness-erosion depth) (2.2 +/ - 1.7 mu m vs. -5.7 +/- 1.4 mu m; p < 0.01), while women on HRT displayed p reservation of bone balance (2.4 +/- 2.4 mu m vs. 2.5 +/- 2.5 mu m; NS). No significant differences in wall thickness between the two groups were demo nstrable, but the untreated women developed a pronounced increase in erosio n depth over 2 Bears (46.9 +/- 1.8 mu m vs. 52.0 +/- 1.9 mu m; p < 0.05), w hile the HRT group revealed no change (47.8 +/- 2.7 mu m vs. 44.6 +/- 1.7 m u m; NS). Furthermore, the placebo group displayed an increased osteoclasti c erosion depth (17.8 +/- 1.6 mu m vs. 25.0 +/- 1.7 mu m; p < 0.001), compa red with unchanged values in the HRT group (20.0 +/- 1.6 mu m vs. 16.9 +/- 1.4 mu m/day; NS). While the placebo group revealed a slight increase in vo lume referent resorption rate (35 +/- 8% vs. 38 +/- 8%; NS) the HRT group r evealed a pronounced decrease (46 +/- 8% vs. 28 +/- 5%; p < 0.05). No signi ficant changes in marrow star volume tan index of trabecular perforations) were demonstrable in either group. Our results demonstrate that bone remode ling in early postmenopausal women is characterized by progressive osteocla stic hyperactivity, which is reduced by cyclic HRT. This reduction of resor ptive activity at the BMU level after HRT seems to precede the reduction in activation frequency demonstrated in previous studies on older postmenopau sal women.