Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Slow-release sodium fluoride with calcium prevented new spinal fractures

ACP J Club. 1996 Mar-April;124:34. doi:10.7326/ACPJC-1996-124-2-034


Source Citation

Pak CY, Sakhaee K, Adams-Huet B, et al. Treatment of postmenopausal osteoporosis with slow-release sodium fluoride. Final report of a randomized controlled trial. Ann Intern Med. 1995 Sep 15;123:401-8. [PubMed ID: 7639438]


Abstract

Objective

To evaluate the safety and efficacy of slow-release sodium fluoride in women with postmenopausal osteoporosis.

Design

Randomized, placebo-controlled trial with mean 3.5-year follow-up.

Setting

2 outpatient specialty clinics in Texas.

Patients

110 postmenopausal women (mean age 68 y) who had radiologic evidence of osteopenia and osteoporosis, ≥ 1 nontraumatic vertebral fracture, and no secondary cause of bone loss. 99 patients (90%) completed at least 1 year of treatment.

Intervention

Patients were stratified according to estrogen treatment and allocated to slow-release sodium fluoride, 25 mg twice daily (n = 54), or placebo (n = 56). The treatment was administered in repeated 14-month cycles (12 months of treatment followed by 2 months without treatment). Patients in both groups received calcium citrate containing 400 mg calcium twice daily. 29 patients were concurrently treated with estrogen.

Main Outcome Measures

Individual vertebral fracture rate; fracture-free rate; adjusted relative risk (RR) for a new spinal fracture; change in bone mass of the lumbar spine, femoral neck, and radius; and adverse symptom score.

Main Results

The mean individual new vertebral fracture rate was lower in patients in the fluoride group than in patients in the placebo group (0.06 vs 0.21 fractures/patient-year {95% CI for the mean difference 0.05 to 0.24}*). After a mean of 3 years' follow-up, 85% of patients who received fluoride were free of new spinal fractures compared with 57% of patients who received placebo (P = 0.001) (Table). The groups did not differ for recurrent fractures. The L2-L4 bone mineral content increased by 4% to 6% per year in each year of treatment in patients in the fluoride group compared with no substantial change in patients in the placebo group (mean change overall 4.8% vs 0.15%/y, P < 0.001). Femoral neck bone density increased by a mean of 2.4%/y (P < 0.001) in patients in the fluoride group compared with 0.98%/y (P = 0.73) in patients in the placebo group. No change occurred in radial bone density in either group. The differences between groups for side effects did not reach statistical significance.

Conclusion

In women with postmenopausal osteoporosis, intermittent slow-release sodium fluoride with continuous calcium supplementation prevented new spinal fractures, increased bone mineral content and femoral neck bone density, and was safe.

Source of funding: In part, United States Public Health Service.

For article reprint: Dr. C.Y. Pak, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-8885, USA. FAX 214-648-2526.


Table. Slow-release sodium fluoride with calcium for the prevention of new spinal fractures†

Outcome at mean 3.5 y Sodium fluoride Placebo RBI (95% CI) NNT (CI)
Free of new spinal fractures 85% 57% 33% (14 to 50) 4 (2 to 9)

†Abbreviations defined in Glossary; RBI, NNT, and CI calculated from data in article.


Commentary

Osteoporosis is an increasing cause of morbidity and mortality in our aging society. Therefore, it is important to look at methods that prevent fractures, such as the maintenance of bone mass and the prevention of falls. Adequate calcium and vitamin D intake and hormone replacement therapy are important in the maintenance of bone mass. Exercise and avoidance of sedative medication may reduce falls and fractures.

Despite these preventive measures, many persons develop osteoporosis, necessitating treatment regimens. Previous literature on fluoride treatment has produced mixed results. Riggs and colleagues (1) used high doses of sodium fluoride and showed substantial increases in bone mineral density but not a reduction in vertebral fracture rates. Nonvertebral fracture rates were substantially higher in the group treated with fluoride. Using similar doses of fluoride, Kleerekoper and colleagues (2) found no differences in bone mineral density or fracture rates but observed an increase in gastrointestinal symptoms and painful lower extremities.

Mamelle and colleagues (3) randomly allocated participants to low doses of fluoride or to an accepted alternative therapy. The group treated with fluoride had a lower rate of new vertebral fractures. The risk for nonvertebral fractures was not increased, and gastrointestinal intolerance was similar in both groups.

In this report, Pak and colleagues provide further evidence to show that low doses of fluoride cause increased bone mass and reduced fracture rates. The cyclical regimen may add to the safety of this treatment.

For many physicians, the use of fluoride will remain controversial. One could conclude, however, that high doses of fluoride increase bone mass but do not reduce vertebral fracture rates and are accompanied by unacceptably high rates of side effects, whereas lower doses are beneficial for increasing bone mass and reducing vertebral fracture rates.

Jonathan D. Adachi, MD
St. Joseph's Hospital-McMaster UniversityHamilton, Ontario, Canada


References

1. Riggs BL, Hodgson SF, O'Fallon WM, et al. Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis. N Engl J Med. 1990;332:802-9.

2. Kleerekoper M, Peterson EL, Nelson DA, et al. A randomized trial of sodium fluoride as a treatment for postmenopausal osteoporosis. Osteoporos Int. 1991;1:155-61.

3. Mamelle N, Meunier PJ, Dusan R, et al. Risk-benefit ratio of sodium fluoride treatment in primary vertebral osteoporosis. Lancet. 1988;2:361-5.