The Effect of Sodium Fluoride on the Rates of Synthesis and Degradation of Bone Collagen in Tissue Culture ∗

Abstract

Despite a number of studies on patients and experimental animals, the effect of fluoride on bone remodelling is not yet clear. The ingestion of large amounts of fluoride by experimental animals (500 ppm of fluoride in the drinking water) was reported to stimulate bone resorption 1 , and in addition to cause the formation of exostotic bony outgrowths 2 . On the other hand, several studies showed that the administration of relatively high doses of sodium fluoride (up to 100 mg/day) to patients with osteoporosis or Paget's disease of bone, leads to an increased retention of calcium, increased mineralization of bone, and relief of bone pain 3 , 4 , 5 , 6 , 7 . Other studies suggested, partly on the basis that fluoride increases the crystallinity, perfection, and size of the mineral crystallites in bone 8 , 9 , 10 that the first effect of fluoride is to decrease bone resorption. This would tend to lower serum calcium, which in turn would stimulate the secretion of parathyroid hormone, with the result that both bone formation and resorption would be eventually increased 11 , 12 , 13 .

Tissue culture techniques were used by Goldhaber 14 who reported that low concentrations of fluoride in the tissue culture medium inhibit bone resorption, without any apparent effect on bone formation, but that at higher concentrations of fluoride, bone formation and bone resorption are both inhibited. The present study extends these morphological observations by directly measuring the rates of bone collagen synthesis and degradation using the incorporation of proline-³H to hydroxyproline-³H, and the increase in total hydroxyproline as an index of bone collagen synthesis, and the release of ³H-labeled hydroxyproline and hydroxyproline into the tissue culture medium as an index of bone collagen resorption.