In postmenopausal osteoporosis the bone increasing effect of monofluorophosphate is not dependent on serum fluoride

ABSTRACT

According to previous pharmacokinetic studies the biovailability of fluorine (F) from sodium monofluorophosphate (MFP) doubles that of sodium fluoride (NaF). This paper reports a study designed to verify whether the vertebral bone mass increasing effect of NaF (30 mg F/day) was comparable to that of MFP (15 mg F/day), given for 18 months to osteoporotic postmenopausal women. The BMD of lumbar vertebrae of both groups showed significant increases (MFP: 60 + 15 mg/cm2, NaF: and 71 + 12 mg/cm2) over basal levels (P < 0.001). The difference between treatments was not significant (P = 0.532). The serum levels of ionic F (the mitogenic species on osteoblasts) were not related to the above mentioned effects. In NaF-treated patients, the fasting levels of total serum F increased significantly (6.7 + 0.9 muM vs. Basal: 2.0 + 0.8 muM; P < 0.001). This phenomenon was accounted for by ionic fluoride that increased over 20-fold (6.5 + 1.9 muM vs. Basal: 0.3 + 0.04 muM). In MFP-treated patients the fasting serum levels of total (7.0 + 0.7 muM vs. Basal: 2.2 + 0.9 M) and diffusible F (0.5 + 0.02 muM vs. Basal 0.2 + 0.02 muM) increased significantly (P < 0.001). The increase in the non diffussible F fraction is accounted for by proteinboud F, probably by the complexes formed between MFP and alpha2-macroglobulin and C3. Serum diffusible F was formed by two fractions: ionic F and F bound to low molecular weight macromolecule/s (2 200 + 600 Da), in approximately equal amounts. The general information afforded by the present observations support the hypothesis that ionic F is released progressively during the metabolism of MFP bound to alpha2-macroglobulin and C3. These phenomena explain why comparable effects to those obtained with 30 mg F/d of NaF could by obtained with one half the dose of MFP.