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 minera l density (BMD) in the spine, but its efficacy in reducing vertebral f racture rates and its effect on BMD at cortical sites are controversia l. Objective: To study the effect of low-dose fluoride (sodium monoflu orophosphate [MFP]) plus a calcium supplement over 4 years on vertebra l fractures and BMD at the lumbar spine and total hip in postmenopausa l women with moderately low BMD of the spine. Design: Randomized, doub le-blind, controlled clinical trial. Setting: Outpatient clinic for os teoporosis at a university medical center. Patients: 200 postmenopausa l women with osteoporosis (according to the World Health Organization definition) and a T-score less than -2.5 for BMD of the spine. Interve ntion: Women were randomly assigned (100 patients per group) to contin uous daily treatment for 4 years with 1) oral MFP (20 mg of equivalent fluoride) plus 1000 mg of calcium las calcium carbonate) or 2) calciu m only. Measurements: Lateral spine radiographs were taken at enrollme nt and at each year of follow-up for detection of new vertebral fractu res (defined as a reduction greater than or equal to 20% and greater t han or equal to 4 mm from baseline in any of the heights of a vertebra l 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 vertebr al fractures during the 4 years of the study was lower in the MFP-plus -calcium group (2 of 84 patients; 2.4% [95% Cl, 0.3% to 8.3%]) than in the calcium-only group (8 of 80 patients; 10% [Cl, 4.4% to 18.8%]). T he difference between the groups was 7.6 percentage points (Cl, 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 plu s calcium compared with calcium only (P < 0.001), whereas the more mod est 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. Con clusions: Low-dose fluoride (20 mg/d) given continuously with calcium for prolonged periods can decrease vertebral fracture rates compared w ith calcium alone in patients with mild to moderate osteoporosis.