Objective: To test whether slow-release sodium fluoride inhibits spina
l 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 g
roup, the fluoride group had a lower individual vertebral fracture rat
e (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 (re
lative risk, 0.3 [95% CI, 0.12 to 0.76]) for new fractures; The recurr
ent spinal fracture rate did not differ between the two groups. The fl
uoride 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% pet year, and no change in radial shaft bone density.
The frequency with which minor side effects and appendicular fracture
s occurred was similar in the two groups; no patients developed microf
ractures or gastric ulcers. Conclusion: Slow-release sodium fluoride a
nd calcium citrate administered for 4 years inhibits new vertebral fra
ctures (but not recurrent fractures), augments spinal and femoral neck
bone mass, and is safe to use.