Chapter 75 - A New Perspective on Fluoride Therapy

Abstract

This chapter provides the careful reviews of pharmacokinetic studies and randomized clinical trials of new flouride therapies. Reviews of pharmacokinetic studies and randomized clinical trials with fluoride disclosed a biphasic action of fluoride. From 19 single-dose bioavailability studies, fluoride absorption and peak-to-basal variation in serum fluoride were calculated. From these pharmacokinetic parameters, it was possible to estimate the peak fluoride concentration in serum after multiple dosing and skeletal fluoride content after 4 years of treatment. For sustained-release sodium fluoride (NaF), for which normally mineralized bone formation has been reported, the estimated peak fluoride concentration in serum was kept within the therapeutic window and the skeletal fluoride was below the toxic threshold. However, for more bioavailable fluoride preparations (such as plain NaF for which abnormal bone formation has been reported), both peak serum fluoride and bone fluoride exceeded the toxic threshold. A review of 12 randomized clinical trials with fluoride showed a clear dependence of skeletal fracture outcome on fluoride exposure. In trials with fluoride preparations that conferred toxic fluoride exposure, spinal fracture rate was similar between fluoride and placebo groups, and the hip and total appendicular fracture rates were generally numerically higher in the fluoride group. A moderate fluoride exposure yielded a modest decline or no change in spinal fracture rate, and no change in hip or appendicular fracture rates. A low fluoride exposure caused a marked reduction in spinal fracture rate, with lower hip and total appendicular fracture rates. The relative risk of spinal and total appendicular fracture rates was directly and significantly correlated with relative fluoride absorption.