Rs. Weinstein et al., THE EFFECTS OF ANDROGEN DEFICIENCY ON MURINE BONE REMODELING AND BONE-MINERAL DENSITY ARE MEDIATED VIA CELLS OF THE OSTEOBLASTIC LINEAGE, Endocrinology, 138(9), 1997, pp. 4013-4021
Both estrogens and androgens act on bone marrow stromal/osteoblastic c
ells to inhibit the production of local factors that promote osteoclas
t development. Based on this and the evidence that loss of sex steroid
s up-regulates not only osteoclastogenesis but also osteoblastogenesis
, we have hypothesized that cells of the osteoblastic lineage are the
mediators of the adverse effects of sex steroid deficiency on bone. To
test this hypothesis, we used the senescence-accelerated mouse (SAMP6
), a model of defective osteoblast development, and examined the effec
ts of orchidectomy on static and dynamic histological features of bone
remodeling and on bone mineral density. After orchidectomy in SAMP6 m
ice, the expected increases in osteoblast precursors, cancellous osteo
clasts and osteoblasts, frequency of remodeling events, trabecular spa
cing, and rate of bone formation were absent or greatly attenuated. Mo
reover, whereas bone mineral density decreased in orchidectomized cont
rols, it did not change in SAMP6. Our data indicate that when osteobla
st development is defective, orchidectomy fails to result in bone loss
. This evidence suggests that cells of the osteoblastic lineage are es
sential mediators of the changes in the rate of bone remodeling and lo
ss of bone mass that ensue following loss of androgens.