Reid IR et al. (2007) Addition of monofluorophosphate to estrogen therapy in postmenopausal osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab 92: 2446–2452

Fluoride increases BMD, but does not seem to reduce fracture rates in patients with osteoporosis, possibly because fluoride alone has no effect on bone resorption. Antiresorptives are effective for fracture prevention; Reid et al. hypothesized that combining low-dose fluoride with an antiresorptive agent might improve the efficacy of fracture prevention treatment. In a randomized trial, the New Zealand research team added glutamine monofluorophosphate (MFP; 20 mg/day) or placebo to hormone replacement therapy with calcium supplementation in 80 postmenopausal women with osteoporosis.

After 4 years, BMD in the lumbar spine had increased by 22% in the MFP group, compared with 6% in the placebo group. In the femoral neck, BMD had increased by 4.6% in the MFP group, but decreased slightly in the placebo group. There were significantly fewer new vertebral fractures in the MFP group (hazard ratio 0.2 for MFP vs placebo). There were, however, more nonvertebral fractures in the MFP group than in the placebo group. Analysis of bone turnover markers showed significant stimulation of bone formation by MFP; however, MFP was associated with hyperosteoidosis in five of seven patients who provided bone biopsies.

The authors conclude that fluoride treatment has potent effects on bone formation, but causes unacceptable bone mineralization abnormalities at the 20 mg/day dose used in the study. They recommend further trials of lower doses of MFP.