title: Low-dose fluoride in postmenopausal women: a randomized controlled trial.
abstract: BACKGROUND
  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.
  
  
  METHODS
  We conducted a double-blind, placebo-controlled randomized trial over 1 year at an academic research center, in 180 postmenopausal women with osteopenia.
  
  
  METHODS
  Participants received daily treatment with tablets containing placebo, 2.5 mg fluoride, 5 mg fluoride, or 10 mg fluoride.
  
  
  METHODS
  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.
authors.affiliation: University of Auckland, Department of Medicine, Private Bag 92019, Auckland, New Zealand. a.grey@auckland.ac.nz
authors.forename: Andrew
authors.initials: A
authors.lastname: Grey
authors.forename: Sanjay
authors.initials: S
authors.lastname: Garg
authors.forename: Michael
authors.initials: M
authors.lastname: Dray
authors.forename: Lauren
authors.initials: L
authors.lastname: Purvis
authors.forename: Anne
authors.initials: A
authors.lastname: Horne
authors.forename: Karen
authors.initials: K
authors.lastname: Callon
authors.forename: Greg
authors.initials: G
authors.lastname: Gamble
authors.forename: Mark
authors.initials: M
authors.lastname: Bolland
authors.forename: Ian R
authors.initials: IR
authors.lastname: Reid
authors.forename: Tim
authors.initials: T
authors.lastname: Cundy
mesh_terms: D000368:Aged; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005459:Fluorides / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D017698:Postmenopause
chemical_list: D005459:Fluorides