Serum fluoride and serum osteocalcin levels in response to a novel sustained-release monofluorophosphate preparation: comparison with plain monofluorophosphate.

In a previous study we found that sustained-release monofluorophosphate (MFP-SR), a novel, sustained-release MFP preparation, acutely maintained the basal therapeutic serum fluoride levels without causing the high serum peak levels associated with plain MFP administration. The objective of the present study was to determine (a) whether chronic MFP-SR administration would provide therapeutic serum fluoride levels, and (b) whether treatment with this new preparation would result in an increase in bone formation similar to that achieved with plain MFP. Bone formation was assessed by serum osteocalcin (OC) determination. We studied 17 postmenopausal women older than 60 years and suffering from primary osteoporosis. All had received a minimum of 6 months of continuous treatment with plain MFP at a dose of 152 mg/day (76 mg b.i.d.). Upon entering the study, the subjects were randomized, in a double-masked protocol, to receive either MFP-SR (76 mg b.i.d.) (n = 9) or placebo (n = 8) for 2 months, after which all subjects returned to the original plain MFP regimen. Serum fluoride and serum OC levels were determined monthly for 3 months. At the beginning of the study serum fluoride levels were in the accepted therapeutic range (5-10 microM) in all patients. Serum fluoride levels were maintained in the patients switched to MFP-SR. In contrast, serum fluoride levels decreased significantly (p < 0.005) in the placebo-treated control subjects and returned to therapeutic levels upon switching back to plain MFP. Similarly, serum OC levels remained elevated in the subjects switched to MFP-SR but dropped significantly (p < 0.001) in the placebo-treated group. Our results demonstrate that chronic MFP-SR administration, at a dose of 152 mg/day, results in maintenance of therapeutic serum fluoride levels and in stimulation of bone formation. Because we have previously reported that high, supratherapeutic post-absorptive serum fluoride levels are avoided by MFP-SR administration, this novel preparation may prevent side effects associated with plain MFP by reducing the amount of fluoride deposited in bone.

RCT Entities:   Population Interventions Outcomes