Turner model predicts that (1) fluoride uptake is positively associated with the bone remodeling rate and (2) fluoride clearance from the skeleton takes at least four times longer than fluoride uptake. A key correlate to the first prediction is that the concentration of fluoride in bone does not decrease with reduced remodeling rates. Thus, it appears that fluoride enters the bone compartment easily, correlating with bone cell activity, but that it leaves the bone compartment slowly. The model assumes that efflux occurs by bone remodeling and that resorption is reduced at high concentrations of fluoride because of hydroxyapatite solubility. Hence, it is reasonable that 99% of the fluoride in humans resides in bone and the whole body half-life, once in bone, is approximately 20 years (see Chapter 3 for more discussion of pharmacokinetic models).

The effects of fluoride on bone quality are evident but are less well characterized than its effects on bone cells. Bone quality is an encompassing term that may mean different things to different investigators. However, in general it is a description of the material properties of the skeleton that are unrelated to skeletal density. In other words, bone quality is a measure of the strength of the tissue regardless of the mass of the specimen being tested. It includes parameters such as extent of mineralization, microarchitecture, protein composition, collagen cross linking, crystal size, crystal composition, sound transmission properties, ash content, and remodeling rate. It has been known for many years that fluoride exposure can change bone quality. Franke et al. (1975) published a study indicating that industrial fluoride exposure altered hydroxyapatite crystal size and shape. Although the measurements in their report were made with relatively crude x-ray diffraction analyses, they showed a shorter and more slender crystal in subjects who were aluminum workers and known to be exposed to high concentrations of fluoride. Other reports documenting the effects of fluoride on ultrasound velocities in bone, vertebral body strength, ash content, and stiffness have shown variable results (Lees and Hanson 1992; Antich et al. 1993; Richards et al. 1994; Zerwekh et al. 1997a; Søgaard et al. 1994, 1995, 1997); however, the general conclusion is that, although there may be an increase in skeletal density, there is no consistent increase in bone strength. A carefully performed comparison study between the effects of fluoride (2 mg/kg/day) and alendronate in minipigs likely points to the true effect: “in bone with higher volume, there was less strength per unit volume, that is, … there was a deterioration in bone quality” (Lafage et al. 1995).

EFFECT OF FLUORIDE ON CELL FUNCTION

Two key cell types are responsible for bone formation and bone resorption, the osteoblast and osteoclast, respectively. Osteoprogenitor cells give rise to osteoblasts. Osteoprogenitor cells are a self-renewing population of



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