Hormone Replacement Therapy Prevents Osteoclastic Hyperactivity: A Histomorphometric Study in Early Postmenopausal Women

Abstract

In a randomized, double blind, clinical prospective trial comprising 35 women treated with either hormone replacement therapy (HRT) (cyclic estradiol/norethisterone acetate) or placebo we performed histomorphometric studies on paired bone biopsies obtained before and after 2 years of treatment. Untreated women developed a progressively more negative balance at individual bone multicellular units (BMUs) (i.e., wall thickness-erosion depth) (2.2 ± 1.7 µm vs. −5.7 ± 1.4 µm; p < 0.01), while women on HRT displayed preservation of bone balance (2.4 ± 2.4 µm vs. 2.5 ± 2.5 µm; NS). No significant differences in wall thickness between the two groups were demonstrable, but the untreated women developed a pronounced increase in erosion depth over 2 years (46.9 ± 1.8 µm vs. 52.0 ± 1.9 µm; p < 0.05), while the HRT group revealed no change (47.8 ± 2.7 µm vs. 44.6 ± 1.7 µm; NS). Furthermore, the placebo group displayed an increased osteoclastic erosion depth (17.8 ± 1.6 µm vs. 25.0 ± 1.7 µm; p < 0.001), compared with unchanged values in the HRT group (20.0 ± 1.6 µm vs. 16.9 ± 1.4 µm/day; NS). While the placebo group revealed a slight increase in volume referent resorption rate (35 ± 8% vs. 38 ± 8%; NS) the HRT group revealed a pronounced decrease (46 ± 8% vs. 28 ± 5%; p < 0.05). No significant changes in marrow star volume (an index of trabecular perforations) were demonstrable in either group. Our results demonstrate that bone remodeling in early postmenopausal women is characterized by progressive osteoclastic hyperactivity, which is reduced by cyclic HRT. This reduction of resorptive activity at the BMU level after HRT seems to precede the reduction in activation frequency demonstrated in previous studies on older postmenopausal women. (J Bone Miner

Estrogen deficiency and bone loss: an inflammatory tale

“…Estrogen deficiency leads to dramatic elevations in the number of BMUs through increased activation frequency, which is the number of new remodeling units activated in each unit of time (19). Enhanced activation frequency expands the remodeling space, increases cortical porosity, and enlarges the resorption area on trabecular surfaces.…”

Irreversible Deterioration of Cortical and Trabecular Microstructure Associated With Breastfeeding

“…(5) The rapid remodeling also reduces matrix mineralization density by replacing older, more mineralized bone with young, less completely mineralized bone. (4)(5)(6) Breastfeeding is an estrogen-deficient state associated with bone loss. (6)(7)(8)(9) Bone remodeling accelerates and may also become unbalanced.…”

“…(4)(5)(6) Breastfeeding is an estrogen-deficient state associated with bone loss. (6)(7)(8)(9) Bone remodeling accelerates and may also become unbalanced. Studies in rodent and other animal models demonstrate that trabeculae perforate, their numbers decrease, and cortical porosity increases.…”

Influencing the Effect of Treatment of Diseases Related to Bone Remodelling by Dynamic Loading

“…As a result, loss of estrogen increases not only the number of active BMUs, but also the lifespan of osteoclasts while reducing the lifespan of osteoblasts and osteocytes. The increased lifespan of the osteoclasts, in particular, is thought responsible for the deepening of resorption cavities (Eriksen et al, 1999) and trabecular perforation leads to microstructural weakness of bone and increased fracture risk in women in the early postmenopausal period (Rucker et al, 2002). In contrast to postmenopausal bone loss resulting from osteoclast hyperactivity, the inexorable bone loss seen with senescence in both sexes is thought to be osteoblast mediated.…”