To investigate the relationship of the hematopoietic system to the los
s of bone due to ovarian hormone deficiency, we examined the effects o
f ovariectomy and estrogen administration on the thymus, spleen and th
e bone marrow, and on the proliferation of marrow progenitor's of oste
oclasts. We also assessed the effects of daily administration of inter
leukin-l receptor antagonist (IL-1ra) on bone loss due to ovarian horm
one deficiency. Ovariectomy resulted in decreased cancellous bone volu
me, increased trabecular osteoblast and osteoclast numbers, and increa
sed serum alkaline phosphatase levels that were prevented by 17 beta-e
stradiol treatment. Thymus weight, spleen weight, thymus and spleen ly
mphocytes, and bone marrow monocytes and lymphocytes also increased si
gnificantly following ovariectomy, and the increases were suppressed b
y 17 beta-estradiol. Ovariectomy, in addition, caused a 4-fold increas
e in the number of tartrate resistant acid phosphatase (TRAP)-positive
multinucleated cells formed in cultures of marrow cells and the incre
ase was partially inhibited by 17 beta-estradiol. IL-1ra administratio
n did not prevent the bone loss due to ovariectomy. Our findings indic
ate that ovariectomy-induced bone loss in the rat is accompanied by ma
rked changes in the hematopoietic system, and that these changes are m
odulated by estrogen administration. In spite of the negative finding
with IL-1ra, the nature of the involvement of the hematopoietic system
in the pathogenesis of bone loss due to ovarian hormone deficiency me
rits continued exploration.