Twenty five RCTs (n=2,348) were included in the review: 12 RCTs scored 5 points on the Jadad scale; two scored 4 points; 10 scored 3 points; and one scored 2 points.
Effects on BMD: Spine BMD increased by 7.9 per cent (95% CI: 5.4%, 10.5%, p<0.001, n=1,774) and hip BMD by 2.1 per cent (95% CI: 0.9%, 3.4%, p<0.01, n=1,434) after treatment with fluoride, but with evidence of significant heterogeneity (p<0.01).
Meta-regression analysis showed an increase in spine BMD with increasing duration of treatment (5.04 +/- 2.16 per cent per year of treatment).
Effects on fractures: There were no statistically significant effects of fluoride treatment on the risk of vertebral or non-vertebral fracture risk, but with evidence of significant heterogeneity (p<0.01).
Meta-regression analysis for non-vertebral fracture risk showed an increase of fracture risk with increasing fluoride dose (OR 0.14 per mg, p<0.01). There was no effect of treatment duration. Sub-group analysis showed that with a daily dose of 20 mg or less of fluoride equivalents there was a statistically significant reduction for both vertebral fracture risk (OR 0.28; 95% CI: 0.09, 0.87, six studies, n=593) and for non-vertebral fracture risk (OR 0.52; 95% CI: 0.28, 0.76, six studies, n=768). A daily dose of 20 mg or more of fluoride equivalents showed a non-statistically significant increase in the risk of both vertebral fractures (OR 1.26; 95% CI: 0.78, 2.04, 11 studies) and non-vertebral fracture (OR 1.46, 95% CI: 0.77, 2.76, seven studies).
Funnel plots showed no signs of significant publication bias.
There were no significant differences for the frequency of gastrointestinal symptoms between fluoride and control groups (14 studies). There was a significantly higher risk of pain for fluoride treated groups compared to controls (OR 2.76; 95% CI: 1.35, 5.65). There were similar increases in pain with doses of 20 mg fluoride or less and doses of 20 mg or more.