Bone effects of fluoride in animal models in vivo. A review and a recent study

The effects of fluoride on bone in various animal models are reviewed. In these studies, the doses of fluoride varied from those equivalent to therapeutic doses to toxic doses, and the duration of the treatment was from 15 days to 33 months. No significant modification in serum calcium, phosphorus, and alkaline phosphatase was reported. An increased serum osteocalcin level was noted in ewes. Evidence for hyperparathyroidism was found in some but not all animal models. Studies performed in the rat reported that fluoride had different effects on the periosteal and endosteal bone. An increase in the extent of eroded surfaces was observed in all experimental studies, except one in the mouse. Increases in osteoid parameters and in the number of osteoblasts were noted in mouse, cat, pig, and ewe. Only one study, carried out in dogs, mentioned a decrease in osteoid parameters. Most of the authors reported a mineralization defect due either to a modification in the composition of the bone matrix or to a low calcium intake. The formation period was augmented during fluoride treatment but, at a fluoride dose equivalent to therapeutic doses, this augmentation was mainly due to an increased active formation period. In contrast, at a fivefold greater dose, it was due to an increased inactive formation period. The augmentation of bone volume after fluoride treatment was attributed to an unbalanced coupling between resorption and formation in favor of formation. All these experimental studies support the conclusion that fluoride induces a stimulation of the birthrate of osteoblasts, but at high doses decreases their activity.