Megakaryocyte population in human bone marrow increases with estrogen treatment: A role in bone remodeling?

Skeletal effects of conventional hormone replacement therapy (HRT) are pred ominately antiresorptive, while high doses of estrogen have anabolic effect s, The mechanisms mediating those effects are unclear but may involve cells in the hone marrow. We have investigated the in vivo effects of estrogen o n the megakaryocyte (MK) population in bone marrow in 10 postmenopausal wom en before and after 2 years of conventional HRT, in 11 women after long-ter m, high-dose estradiol therapy, and in 2 premenopausal and 4 postmenopausal women who had received no previous estrogen treatment. Transiliac crest bi opsies were halved and either decalcified and paraffin wax embedded for imm unolocalization studies or dehydrated and embedded in LR White resin for hi stology, MKs were identified morphologically, and the bent! marrow cell pop ulation and MK number quantified by cell counting in a defined area of view (1 mm(2)) from 5 randomly selected fields of bone marrow, Compared with pr etreatment values, significantly higher MK numbers were found after convent ional HRT treatment (before treatment, mean +/- SEM; 7.3 +/- 1.1 vs, after treatment, 18.0 +/- 1.6/5 mm(2); p < 0.0001), while the greatest MK number was associated with long-term, high-dose estradiol treatment (32.8 +/- 2.1/ 5 mm(2); p < 0.001), Total bone marrow cell number did not differ significa ntly between groups. Immunolocalization studies revealed more intense estro gen receptor (ER)beta expression in MKs in the high-dose estradiol-treated group but similar levels of weak ER alpha staining in MKs in the control an d high-dose estrogen-treated groups. Positive immunoreactivity for transfor ming growth factor (TGF)beta 1, 2, and 3 and TGF beta receptor I, II, and I II was detected in MKs, with more intense staining being demonstrated in th e high-dose estradiol-treated group, particularly for TGF beta 2 and TGF be ta RI and II. Our results demonstrate an increase in the MK population in b ent: marrow from women treated with estrogen, The ability of MKs to express ERs and synthesise TGF beta, a potent mitogen in osteoblast differentiatio n, suggests that these cells may play a role in mediating estrogen-induced effects on bone. (C) 2000 by Elsevier Science Inc, All rights reserved.