SPINAL FRACTURES DURING FLUORIDE THERAPY FOR OSTEOPOROSIS - RELATIONSHIP TO SPINAL BONE-DENSITY

Recent studies report that fluoride therapy for osteoporosis increases spinal bone density without improving vertebral fracture rate, challenging the notion that restoration of bone mass improves bone fragility. To further evaluate this issue, the relationship between spinal bone density and vertebral fracture rate was examined in a large number of fluoride-treated, osteoporotic patients. A retrospective assessment was made of clinical data collected from our observations of 389 osteoporotics treated with fluoride 30 +/- 8 mg/day (mean +/- SD) (equivalent to 66 +/- 17 mg NaF/day) and calcium 1500 mg/day for 28 +/- 18 months. Fracture rate and bone density were assessed in the same region of the spine (i.e., T12 through L4) using quantitative computed tomography (QCT). Spinal bone density increased with time on fluoride, but the relationship was hyperbolic (r = 0.99, p<0.0001; asymptote = 167 mg/cc on double-reciprocal plot), suggesting a plateau in the response. The spinal fracture rate decreased as a function of time on therapy (r = -0.83, p<0.01), and was inversely related to spinal bone density during fluoride therapy (r = 0.70, p<0.001 on arithmetic plot; r = -0.79, p<0.001 on semi-log plot). The subgroup of patients who responded to treatment with a significant increase in spinal bone density had a 48% reduction in spinal fracture rate compared with non-responders (p<0.001). The subgroup of patients who sustained a fracture during fluoride therapy not only had a slower rate of increase in spinal bone density in response to fluoride therapy, but were also significantly older, had more fractures prior to fluoride therapy, and had a lower pretreatment spinal bone density; consequently, spinal bone density after treatment with fluoride was also lower in this subgroup of patients compared with those who did not sustain a fracture (p<0.001). These findings are consistent with both the general hypothesis that bone density is an important determinant of fracture risk in osteoporosis, and the specific hypothesis that an increase in spinal bone density in response to fluoride treatment is associated with a decrease in the risk for vertebral fractures.