CLINICAL-TRIAL OF FLUORIDE THERAPY IN POSTMENOPAUSAL OSTEOPOROTIC WOMEN - EXTENDED OBSERVATIONS AND ADDITIONAL ANALYSIS

In a 4 year clinical trial in 202 postmenopausal osteoporotic women re ceiving NaF at 15 mg/day or placebo (both groups received supplementar y calcium at 1500 mg/day), we found (N Engl J Med 322:801, 1990) that NaF increased bone mineral density in the lumbar spine (LS-BMD) substa ntially but did not decrease vertebral fracture rate (VFR), and it inc reased the nonvertebral fracture rate. Additional analyses and extende d observations are now available on 50 women from the NaF group follow ed for up to 6 years of treatment. In these women, LS-BMD increased li nearly over the 6 years (median rate, 8.7%/year or 0.063 g/cm(2)/year) . Because during the 4 year trial the NaF dosage was decreased (becaus e of side effects) in 54 of the 101 women randomized to NaF, dose-resp onse relationships could be evaluated. For the entire study population , serum F level correlated directly with increase in LS-BMD (r = 0.61, P < 0.001). When individual person-years of observation were grouped by deciles of LS-BMD, VFR (per 100 person-years) decreased to a nadir of 24 as mean LS-BMD for the group increased from 0.6 to 1.2 g/cm(2) a nd then doubled to 52 in the group with mean LS-BMD of 1.6 g/cm(2). Mu ltivariate analyses and inspection of three-dimensional plots revealed a complex pattern in which VFR was influenced by interaction of sever al variables. When the effects of LS-BMD, changes in LS-BMD, and serum F were assessed simultaneously, VFR was seen to decrease with increas ing LS-BMD except when the higher LS-BMD was associated with rapid rat e of increase in LS-BMD or a large increase from baseline serum F. For some patients (noncompliers or nonresponders), serum F or LS-BMD fail ed to increase. Thus, it is possible that lower dosages of NaF produce moderate decreases in VFR.