The effect of sodium monofluorophosphate plus calcium on vertebral fracture rate in postmenopausal women with moderate osteoporosis. A randomized, controlled trial.

BACKGROUND

Fluoride is effective in increasing trabecular bone mineral density (BMD) in the spine, but its efficacy in reducing vertebral fracture rates and its effect on BMD at cortical sites are controversial.

OBJECTIVE

To study the effect of low-dose fluoride (sodium monofluorophosphate [MFP]) plus a calcium supplement over 4 years on vertebral fractures and BMD at the lumbar spine and total hip in postmenopausal women with moderately low BMD of the spine.

DESIGN

Randomized, double-blind, controlled clinical trial.

SETTING

Outpatient clinic for osteoporosis at a university medical center.

PATIENTS

200 postmenopausal women with osteoporosis (according to the World Health Organization definition) and a T-score less than -2.5 for BMD of the spine.

INTERVENTION

Women were randomly assigned (100 patients per group) to continuous daily treatment for 4 years with 1) oral MFP (20 mg of equivalent fluoride) plus 1000 mg of calcium (as calcium carbonate) or 2) calcium only.

MEASUREMENTS

Lateral spine radiographs were taken at enrollment and at each year of follow-up for detection of new vertebral fractures (defined as a reduction > or =20% and > or =4 mm from baseline in any of the heights of a vertebral body). Nonvertebral fractures were also recorded. All analyses were done with the intention-to-treat approach.

RESULTS

Radiologic follow-up was possible for 164 of 200 patients (82%). The rate of new vertebral fractures during the 4 years of the study was lower in the MFP-plus-calcium group (2 of 84 patients; 2.4% [95% CI, 0.3% to 8.3%]) than in the calcium-only group (8 of 80 patients; 10% [CI, 4.4% to 18.8%]). The difference between the groups was 7.6 percentage points (CI, 0.3 to 15 percentage points) (P = 0.05). A moderate but progressive increase in BMD of the spine (10.0% +/- 1.5% at 4 years) was found for MFP plus calcium compared with calcium only (P < 0.001), whereas the more modest increase in BMD of the total hip seen with MFP plus calcium (1.8% +/- 0.6%) did not differ from the increase seen with calcium only.

CONCLUSIONS

Low-dose fluoride (20 mg/d) given continuously with calcium for prolonged periods can decrease vertebral fracture rates compared with calcium alone in patients with mild to moderate osteoporosis.