S. Bord et al., Megakaryocyte population in human bone marrow increases with estrogen treatment: A role in bone remodeling?, BONE, 27(3), 2000, pp. 397-401
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.