Biphasic Sodium Fluoride Effects on Bone and Bone Mineral: A Review

This paper reviews the clinical and experimental findings on the effects of sodium fluoride (NaF) on human and animal bone. NaF has been shown to cause a significant increase in axial skeletal bone mass. However, there is concern that the new bone may not provide the desired increase in bone strength. Yet, NaF remains the most commonly used agent capable of stimulating bone formation in most patients (30% non-responders).. But whether NaF reduces vertebral fracture rate (VFR) remains controversial. For a given treatment duration, the effect of F on bone quality appears to depend on dose: there is a marked detrimental effect on bone strength at high dose but there tends to be a beneficial effect at low dose. This biphasic NaF effect on bone strength has also been observed in fluoridated rat femurs. Unlike a study on young female rats which shows a linear dependence of cancellous bone volume (Cn-BV /TV) on NaF dose, a short-term study on young male rats, together with studies on chicks and dogs show biphasic NaF effects. Biphasic character is also observed in the effect of NaF on the packing of canine cortical bone mineral. When taken together, the animal models that show biphasic NaF effects seem to suggest that NaF at low dose improves Cn-BV/TV and bone strength and at high dose undermines them. These findings are in agreement with the clinical observations that high NaF dose does not help reduce VFR but low dose seems to help.