Characterization of a rapidly responding animal model for fluoride-stimulated bone formation

Sodium fluoride (NaF) is the single most effective agent for increasing bone volume in the osteoporotic skeleton. However, the mechanism of fluoride-stimulated bone formation is not known, and investigation has been hampered by the lack of a suitable animal model. Young chicks show a rapid skeletal response to NaF that resembles the human skeletal response. This occurs at serum fluoride concentrations comparable to those obtained in humans. Fourteen-day-old chicks treated with NaF (4.2 mM NaF in the drinking water) for 2 weeks showed increases in bone-forming surface in the tibial metaphysis (130% of untreated controls, P < 0.002), with no change in the number of osteoblasts per length of forming surface (104% of control). The NaF dose dependence of the change in bone-forming surface was biphasic, being optimal at 23 μM fluoride. Linear correlations were observed between dietary NaF and serum fluoride ( r = 0.996, P < 0.001), and serum fluoride and bone fluoride concentrations ( r = 0.98, P < 0.001). Correlations were also observed between the amount of alkaline phosphatase activity in the tibia and the serum fluoride concentration ( r = 0.88, P < 0.03), the serum fluoride concentration and the tibial ash weight ( r = 0.93, P < 0.01), and the bone fluoride concentration and tibial ash weight ( r = 0.95, P < 0.01). Preliminary studies of the time dependence of the skeletal fluoride response in young chicks revealed no difference between 2 weeks and 4 weeks of treatment (bone-forming surface increased to 124% and 139% of controls in separate studies, P < 0.01 for each). The rapidly growing chick skeleton differs in some respects from the remodeling human skeleton with osteoporosis. Nevertheless, chicks, like humans, respond to NaF treatment with an increase in bone-forming surface, suggesting that the young chick may be a useful model to study the mechanisms of fluoride-stimulated bone formation in vivo.