The results of slow-release
sodium fluoride (SR-NaF) treatment in two nonrandomized trials involving 65 patients with
postmenopausal osteoporosis from the primary site and 121 patients from collaborative sites were compared with those obtained from 54 treated patients and 56 patients taking placebo from a randomized controlled trial.
Spinal fracture data were analyzed separately in mild to moderate bone loss of lumbar spine (baseline L2-L4 bone density [BD] > or = 65% young normal) and in severe bone loss (BD < 65%). Since demographic and fracture data were similar among
fluoride-treated patients from the three trials at each stratum of bone loss, their data were combined. In mild to moderate bone loss, SR-NaF treatment in the combined group virtually eliminated new
spinal fractures with 96.6% of patients remaining fracture-free. The
Fluoride group had a markedly lower individual vertebral fracture rate (0.025 vs. 0.188/patient year, p = 0.0001) and group vertebral fracture rate (0.029 vs. 0.175/patient year, relative risk [RR] 0.12, p = 0.0001) than the Placebo group. In severe bone loss, the combined treated group had a significantly lower new
spinal fracture rate than the Placebo group, although the differences were not as marked (group vertebral fracture rate of 0.150 vs. 0.276/patient year, RR 0.54, p = 0.03). In the combined
fluoride-treated group, the L2-L4 bone mass rose by 4-6%/year for 4 years, and the femoral neck BD increased by 1-2%/year during first 2 years. The radial shaft BD did not change. The Placebo group did not show a change in bone mass at any site. The prevalence (percentage) of patients with related gastrointestinal side effects and nonvertebral fracture rates did not differ significantly between the combined SR-NaF group and the Placebo group (hip fracture rate of 0.0045/patient year in SR-NaF and 0.0053/patient year in Placebo; appendicular fracture other than hip (see text) rate of 0.0193/patient year in SR-NaF and 0.0159/patient year in Placebo). A subgroup analysis showed a low baseline L2-L4 BD, high prevalent
spinal fractures, and reduced
body weight to be important determinants of the development of
spinal fracture during SR-NaF treatment. Concomitant medications (
estrogen,
vitamin D,
thiazide and
thyroid hormone) were not independent predictors of the
spinal fracture risk. Only 17% of
fluoride-treated patients were nonresponders (new
spinal fractures or a fall/no change in L2-L4 bone mass). Thus, the effects of SR-NaF treatment on the
spinal fracture rate from nonrandomized trials were similar to those of the treated group of the randomized trial but different from those of the Placebo group. The similarity of response of nonrandomized trials with that of the randomized controlled trial and the resultant combined analysis further validate the efficacy and safety of SR-NaF in the treatment of
postmenopausal osteoporosis.