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

Ann Intern Med. 1995 Sep 15;123(6):401-8. doi: 10.7326/0003-4819-123-6-199509150-00001.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antacids / therapeutic use
  • Body Height / physiology
  • Bone Density
  • Citrates / therapeutic use
  • Citric Acid
  • Delayed-Action Preparations
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Fractures, Spontaneous / prevention & control*
  • Humans
  • Middle Aged
  • Osteoporosis, Postmenopausal / blood
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporosis, Postmenopausal / physiopathology
  • Recurrence
  • Sodium Fluoride / adverse effects
  • Sodium Fluoride / metabolism
  • Sodium Fluoride / therapeutic use*
  • Spinal Injuries / prevention & control*
  • Survival Analysis


  • Antacids
  • Citrates
  • Delayed-Action Preparations
  • Citric Acid
  • Sodium Fluoride