Effect of fluoride on bone and bone cells in ovariectomized rats

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Abstract
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. In OVX rats DNA synthesis by cultured bone cells was markedly increased compared to sham rats. In OVX rats treated with fluoride DNA synthesis tended to be further increased compared to untreated OVX rats as evaluated by thymidine incorporation into DNA. Osteocalcin production by osteoblastic cells in vitro was comparable in the different groups. The results of this study show that oral treatment with fluoride partially prevents the bone loss induced by estrogen deficiency in OVX rats. This beneficial effect of fluoride results from a further stimulation of bone formation as shown in vivo by an increased extent of bone-forming cells and in vitro by an enhancement of the proliferative capacity of osteoblastic cells isolated from the bone surface.