Fluoride therapy for osteoporosis: Characterization of the skeletal response by serial measurements of serum alkaline phosphatase activity

Abstract

Optimum use of fluoride therapy for osteoporosis requires a sensitive and convenient index of the skeletal response to fluoride. Since previous studies had shown that serum alkaline phosphatase activity (SALP) was increased in response to fluoride therapy, we examined serial measurmeents of SALP in 53 osteoporotics treated with 66 to 110 mg of sodium fluoride (NaF) for 12 to 91 months. SALP was increased in 87% of the subjects during therapy with fluoride. The increase in SALP was thought to reflect the osteogenic action of fluoride based on the findings that SALP (1) correlated with both trabecular bone area ( r = .81, P < .001) and osteoid length ( r = .67, P < .01) in iliac creast biopsies, (2) predicted increased bone density on spinal radiographs in response to fluoride therapy with an 87% accuracy, and (3) predicted decreased back pain in response to fluoride with a 91% accuracy. In addition, the SALP response to fluoride was seen earlier than other therapeutic responses as indicated by the findings that the τ 1 2 for the SALP response (ie, time for 1 2 of the patients to show a significant response) was significantly less (1.2 ± 0.3 yr) than that for the pain response (1.6 ± 0.3 yr, P < .05) or that for the radiographic response (3.7 ± 0.5 yr, P < .001). Although most patients responded to fluoride with an increase in SALP, evaluation of the kinetics of the SALP response to fluoride revealed marked interpatient variation. The time to the first significant increase in SALP ranged from two to 54 months, and the first peak increase in SALP ranged from 35% to 264% above basal. Efforts to discover the cause of the variable SALP response disclosed that these variations were not related to variations in the dose of fluoride, osteoporosis etiology, age, sex, or the inclusion of other drugs. However, at least part of the variable SALP response to fluoride was related to variation in the pretreatment SALP. Basal SALP correlated with both the rate of increase ( r = .49, P < .001) and the first peak increase ( r = .63, P < .001) in SALP. We conclude that (1) most osteoporotics show increased SALP in response to fluoride therapy, although the extent of the response is quite variable and (2) measurements of alkaline phosphatase activity in serum may serve as a valuable tool for convenient monitoring of the skeletal response to fluoride.