The efficacy of fluoride therapy of osteoporosis remains a controversial issue, specially in clinical trials. The effect of fluoride on heterotopic bone formation in mice was analyzed with respect to the dose of the drug administered. Thirty days after implantation of demineralized bone matrix, the ash weight and mineral content of implants from animals receiving the highest dose of fluoride was approximately 49 % lower than that of the controls. Thirty days of fluoride administration had no effect on blood composition. On the other hand, small concentrations of fluoride ions increased the dry and ash weight of implants (36 %) and promoted bone mineralization. The results derived from this study may be directly applicable to the treatment of osteoporosis with fluoride and support our clinical trials.