Treatment of postmenopausal osteoporosis with slow-release sodium fluoride: Final report of a randomized controlled trial

Objective: To test whether slow-release sodium fluoride inhibits spinal fractures and is safe to use. Design: Placebo-controlled randomized trial. Interventions: Slow-release sodium fluoride, 25 mg twice daily, in four 14- month cycles (12 months receiving sodium fluoride followed by 2 months not receiving it) compared with placebo. Calcium citrate, 400 mg calcium twice daily, continuously in both groups. Patients: 48 of 54 patients who received sodium fluoride and 51 of 56 patients who received placebo completed at least 1 year of the study. All patients had postmenopausal osteoporosis. Results: Compared with the placebo group, the fluoride group had a lower individual vertebral fracture rate (0.064 ± 0.182 per patient-year compared with 0.205 ± 0.297 per patient-year; P = 0.002), a higher unadjusted fracture-free rate (85.4% compared with 56.9%; P = 0.001), and a greater survival estimate (relative risk, 0.3 [95% CI, 0.12 to 0.76]) for new fractures. The recurrent spinal fracture rate did not differ between the two groups. The fluoride group had a substantial increase in L2-L4 bone mass of 4% to 5% per year for 4 years, a mean increase in femoral neck bone density of 2.38% ± 3.33% per year, and no change in radial shaft bone density. The frequency with which minor side effects and appendicular fractures occurred was similar in the two groups; no patients developed microfractures or gastric ulcers. Conclusion: Slow-release sodium fluoride and calcium citrate administered for 4 years inhibits new vertebral fractures (but not recurrent fractures), augments spinal and femoral neck bone mass, and is safe to use.