High-affinity nuclear binding sites for 17β-estradiol (17βE2) were recently found in bone cells; however, the mechanism by which estrogen exerts its effect on bone in vivo is still unknown. To study if estrogen acts on bone directly, we used an experimental model in which test substances are infused locally into rat femur trabecular bone. Sprague-Dawley rats weighing 150-160 g were ovariectomized (OVX) and 14 days later a polyethylene tube (1 mm in diameter) connected to an Alzet osmotic minipump was implanted into the distal femur 9 mm from the joint. 17βE2 (24 μl/day at 0.01-1 nM), 17α-estradiol (17αE2) (24 μl/day at 1 nM), or phosphate-buffered saline (NaCl, 8 g/liter; KCl, 0.2 g/liter; KH2PO4, 0.2 g/liter; Na2HPO4·7H2O, 2.16 g/liter) was infused for 8 days. The contralateral limb remained intact. Animals were sacrificed and bones were examined by histomorphometry. Ovariectomy caused a 50% loss in trabecular bone volume (TBV) in the secondary spongiosa (from 20.3% ± 1.7% to 9.6% ± 1.1%; mean ± SEM), a 2-fold increase in osteoclast number (to 4.0 ± 0.4 per mm), a 3-fold increase in relative resorption surfaces (to 24.8% ± 2.9%), a 9-fold increase in osteoblast number (to 11.3 ± 2.1 per mm), and an 8-fold increase in relative osteoid surface (to 9.6% ± 1.7%). The local infusion of 17βE2 for 8 days into OVX rats (i) restored the TBV dose dependently to 75% and 85% of control (non-OVX) levels, at 0.1 nM and 1 nM 17βE2, respectively; (ii) decreased osteoclast number and the relative resorption surface to control (non-OVX) levels; and (iii) further increased osteoblast number and the relative osteoid surface dose dependently (by 5-fold at 1 nM 17βE2). Phosphate-buffered saline infusion was without effect. Infusion of 17αE2 had no effect on TBV, osteoclast number, or resorption surface but increased slightly the osteoblast number and the osteoid surface. Its potency was 1/100 that of 17βE2. The local infusion of 17βE2 or 17αE2 had no effect on body or uterine weight. We conclude from these findings that estrogen delivered directly to the bone of OVX rats in vivo at 2.4 and 24 fmol/day acted locally to inhibit bone resorption and stimulate bone formation.
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Publication status||Published - 1990 Mar|
- Bone histomorphometry
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