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 beta-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.