Effect of Fluoride Treatment on the Fracture Rate in Postmenopausal Women with Osteoporosis

Abstract

Although fluoride increases bone mass, the newly formed bone may have reduced strength. To assess the effect of fluoride treatment on the fracture rate in osteoporosis, we conducted a four-year prospective clinical trial in 202 postmenopausal women with osteoporosis and vertebral fractures who were randomly assigned to receive sodium fluoride (75 mg per day) or placebo. All received a calcium supplement (1500 mg per day). Sixty-six women in the fluoride group and 69 women in the placebo group completed the trial. As compared with the placebo group, the treatment group had increases in median bone mineral density of 35 percent (P less than 0.0001) in the lumbar spine (predominantly cancellous bone), 12 percent (P less than 0.0001) in the femoral neck, and 10 percent (P less than 0.0001) in the femoral trochanter (sites of mixed cortical and cancellous bone), but the bone mineral density decreased by 4 percent (P less than 0.02) in the shaft of the radius (predominantly cortical bone). The number of new vertebral fractures was similar in the treatment and placebo groups (163 and 136, respectively; P not significant), but the number of nonvertebral fractures was higher in the treatment group (72 vs. 24; P less than 0.01). Fifty-four women in the fluoride group and 24 in the placebo group had side effects sufficiently severe to warrant dose reduction; the major side effects were gastrointestinal symptoms and lower-extremity pain. We conclude that fluoride therapy increases cancellous but decreases cortical bone mineral density and increases skeletal fragility. Thus, under the conditions of this study, the fluoride-calcium regimen was not effective treatment for postmenopausal osteoporosis.

Osteoblasts in osteoporosis: past, emerging, and future anabolic targets

“…Also, treatment with NaF was shown to increase osteoblast number and bone formation in ovariectomized (OVX) rats (13) and osteoporotic patients (14,15). However, treatment with NaF did not reduce fracture risk in patients with osteoporosis despite marked increase in vertebral bone mineral density and thus was dismissed as a useful drug for osteoporosis (15,16). Discrepancy in the biological effects of NaF on bone mass and bone strength is caused by the accumulation of abnormal and unmineralized matrix (17,18).…”

How to perform a critical analysis of a randomised controlled trial

“…17 The effectiveness of the use of sodium fluoride is a good example of a misleading conclusion: the treatment substantially increases bone mineral density but does not prevent fractures. 18 Surrogate outcomes are widely used because observing a difference in a surrogate measure requires a much smaller sample size and shorter follow-up than a clinical outcome. Trials designed to observe changes in bone mineral density require only a few hundred participants, whereas those designed to observe a fracture endpoint require many thousands of participants.…”

Evaluation of <i>Epimedium brevicornum</i> Maxim extract for anti-osteoporosis activity in rats

“…Decreased BMD is believed to exert harmful impact on bone strength, leading to increased susceptibility to fractures [17]. Thus, measurement of BMD is can provide information for evaluating bone fracture risk [18,19].…”