We investigated the local in vivo action of lipopolysaccharide (LPS), a potent monocyte activator, and of macrophage colony-stimulating factor (M-CSF), a hemopoietic growth factor influencing monocyte differentiation, on bone resorption in normal female 8-wk-old rats. LPS (2 injections of 0.5 microgram), M-CSF (2 injections of either 12.5, 25, 100, or 500 ng), or vehicle was injected into bone marrow space through a thin catheter implanted, under hydrochloride anesthesia, in the distal end of the right femur. Histomorphometry was performed after staining of the tartrate-resistant acid phosphatase (TRAP). The number of osteoclasts and of TRAP-positive marrow cells (considered as osteoclast precursors) were counted in the secondary spongiosa. LPS caused a 3-fold increase in osteoclast surface, a 4.5-fold increase in the number of osteoclasts, but no change in the number of TRAP-positive marrow cells. M-CSF induced a striking dose-dependent biphasic effect on the number of TRAP-positive marrow cells and on bone resorption (no change with the lowest or with the highest concentrations, although the two intermediate doses significantly increased resorption surfaces and the number of osteoclasts). Our results demonstrate a local in vivo effect of LPS and of M-CSF on bone resorption and suggest that these substances act at different stages of osteoclast development and function.

We have evaluated the in vivo and in vitro changes in osteoblast characteristics induced by estrogen deficiency and 17 beta-estradiol (E2) treatment in ovariectomized (OVX) rats. Estrogen deficiency induced osteopenia and increased bone turnover, as evidenced by bone histomorphometry at 1, 3, and 6 mo postovariectomy. Bone surface osteoblastic cells (OB) isolated from tibias of OVX rats, OVX rats treated with E2 (10 micrograms/kg body wt), and sham rats showed no difference in alkaline phosphatase activity and osteocalcin production in vitro. In contrast the proliferation rate of OB cells was higher in OVX rats compared with sham rats at all time points post-surgery, as shown by [3H]thymidine incorporation and cell number. The proliferation rate of alkaline phosphatase-positive marrow cells was also higher in OVX rats compared with sham rats. E2 treatment of OVX rats corrected histologic indexes of bone resorption and formation and normalized OB cell proliferation. induced by estrogen deficiency in OVX rats is related to an increased proliferation of osteoblast precursor cells present in the marrow stroma and along the endosteal bone surface.

To evaluate whether treatment with a mitogenic agent may increase bone formation and bone mass in osteopenia induced by estrogen deficiency, we determined the effect of oral fluoride treatment on bone and bone cells in ovariectomized rats. Sodium fluoride (NaF) was administered to 3-month-old ovariectomized rats 1 day after ovariectomy (OVX) for 1, 3, and 6 months. NaF was given in drinking water at the dose of 1 mg/kg body weight per day. Fluoride administration led to a partial prevention of the bone loss induced by OVX as shown by histologic analysis of tibial metaphysis and by evaluation of femoral calcium content. These beneficial effects of fluoride were more striking at early time points (1 and 3 months postovariectomy) than after 6 months of treatment. The increase in trabecular bone volume in OVX rats treated with fluoride was associated with a rise in the osteoblast surface, which was increased by 60, 72, and 235% at 1, 3, and 6 months postovariectomy compared to untreated OVX rats. In OVX rats and in sham-operated rats plasma osteocalcin was increased in correlation with the osteoblast surface. However, these two parameters were not correlated in OVX rats treated with fluoride. The heat-labile bone-specific alkaline phosphatase in plasma was decreased in OVX rats treated with fluoride compared to OVX rats, suggesting that both the number and the activity of osteoblasts were affected by NaF treatment. To examine the effect of fluoride on the osteocalcin production and the proliferative capacity of bone cells, osteoblastic cells were isolated by collagenase digestion from the bone surface of tibia in treated and untreated OVX rats.(ABSTRACT TRUNCATED AT 250 WORDS)