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

Abstract

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.