Osteogenic Actions of Fluoride: Its Therapeutic Use for Established Osteoporosis

Fluoride ion is an important trace element in humans and, at minute concentrations, plays important roles in modulating cellular functions of various tissues and organs by regulating the activity of a number of enzymes. Fluoride is widely distributed throughout the environment, and high fluoride concentrations can be found naturally in water in various regions of the world. Fluoride is used extensively in industry. Airborne fluoride can be absorbed through the respiratory tract in people living or working in areas where air contains dusts rich in fluoride.1 Thus, humans can be exposed to fluoride at a wide range of concentrations from various environmental sources. Earlier studies in the 1930s have revealed that: 1) prolonged industrial exposure to excessive doses of fluoride led to the development of skeletal fluorosis, a condition characterized by osteosclerosis and calcification of ligaments and tendons, particularly of the vertebral column, and 2) the severity of skeletal fluorosis correlated with the extent and duration of exposure to fluoride.2,3 Skeletal fluorosis is characterized by an unbalanced coupling in favor of bone formation. These observations prompted Rich and co-workers, in 1961, to advance the concept that lower doses of fluoride may be used therapeutically in humans to increase bone formation and thereby strengthen the skeleton without development of severe osteosclerosis and other skeletal side effects.4-6 They found that low doses of fluoride did increase calcium balance,4,5 and subsequently bone morphometric evidence has revealed that the effects of fluoride to increase bone mass was due to an increase in bone formation and not to a reduction in bone resorption, and that the increase in bone formation was mediated through a fluoride-dependent increase in the osteoblast number.7,8 These findings led to intense investigations into the potential application of fluoride therapy for osteoporosis.