In vitro exposure to sodium fluoride does not modify activity or proliferation of human osteoblastic cells in primary cultures

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Abstract
The anabolic effects of sodium fluoride (NaF) on trabecular bone mass in osteoporosis is now well established. In vivo histologic studies performed in humans and other animals have shown that fluoride induces an increase in osteoblast number at the tissue level. To determine the mechanisms of action of fluoride on osteoblasts, we studied the effects of NaF on short- and long-term cultures of human osteoblastic cells derived from bone explants obtained from 21 donors. In short-term experiments, bone-derived cells were exposed to NaF for 4 days. At doses ranging from 10−11 to 10−5 M, NaF did not modify the alkaline phosphatase (AP) activity or osteocalcin secretion. In long-term experiments, half the bone samples from 15 donors were cultured for 4 months in the presence of 10−5 M NaF and the other half were maintained in NaF-free medium. Observations by light and electron microscopy disclosed no morphologic modification in bone ex-plants after 4 months of exposure to NaF, despite an increase in the bone fluoride content. After the first month of culture, slight but not significant increases were noted in 6 of 10 cases for AP activity, 4 of 10 for osteocalcin secretion, and 5 of 7 for [3H]thymidine incorporation. After 4 months of culture in the presence of NaF, no change in AP activity or cell proliferation was noted. In contrast, the osteocalcin secretion significantly decreased (p < 0.05). These data suggest that, in vitro, under the conditions of this study, there is no direct effect of fluoride on the proliferation or activity (AP activity and osteocalcin secretion) of human osteoblastic cells and that this effect is very likely mediated by a cofactor.