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 less than 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 microM fluoride. Linear correlations were observed between dietary NaF and serum fluoride (r = 0.996, P less than 0.001), and serum fluoride and bone fluoride concentrations (r = 0.98, P less than 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 less than 0.03), the serum fluoride concentration and the tibial ash weight (r = 0.93, P less than 0.01), and the bone fluoride concentration and tibial ash weight (r = 0.95, P less than 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 less than 0.01 for each).(ABSTRACT TRUNCATED AT 250 WORDS)