Low-dose fluoride in postmenopausal women: a randomized controlled trial.

CONTEXT

Trials of high-dose fluoride have reported increased bone formation and bone mineral density (BMD), but impaired bone mineralization and either adverse or neutral effects on fracture risk. Meta-analysis of a heterogeneous dataset of small trials suggests that daily doses of <20 mg fluoride might reduce fracture risk, but it is not known whether low doses of fluoride are safely anabolic to bone.

OBJECTIVE

We set out to investigate the skeletal effects of low doses of fluoride.

DESIGN, SETTING, AND PARTICIPANTS: We conducted a double-blind, placebo-controlled randomized trial over 1 year at an academic research center, in 180 postmenopausal women with osteopenia.

INTERVENTION

Participants received daily treatment with tablets containing placebo, 2.5 mg fluoride, 5 mg fluoride, or 10 mg fluoride.

MAIN OUTCOME MEASURES

The primary endpoint was a change in lumbar spine BMD at 1 year; secondary endpoints were hip and forearm BMD, and markers of bone turnover. Safety was assessed by histomorphometric analysis of transiliac bone biopsies from a subset of participants.

RESULTS

Compared to placebo, none of the doses of fluoride altered BMD at any site. The bone formation marker, procollagen type I N-terminal propeptide, increased significantly in the 5 mg and 10 mg fluoride groups compared to placebo (P = .04 and .005, respectively). No differences were observed between placebo and any of the fluoride groups in levels of β-C-terminal telopeptide of type I collagen.

CONCLUSIONS

Low-dose fluoride does not induce substantial effects on surrogates of skeletal health and is unlikely to be an effective therapy for osteoporosis.