Add time:08/14/2019         Source:sciencedirect.com

A newly synthesized diphosphonate, difluoromethylene diphosphonate (cas 10596-32-4) (F2MDP), was studied for its effects on bone resorption, as measured by the release of previously incorporated 45Ca. F2MDP (10 μM to 1000 μM) effectively inhibited both unstimulated and parathyroid hormonestimulated resorption, and the amount of 45Ca release decreased with time. Dichloromethylene diphosphonate (Cl2MDP) and ethane- 1-hydroxyl-1,1-diphosphonate (EHDP) inhibited resorption to similar extents with two exceptions: At concentrations of 10 μM and 100 μM F2MDP was more effective than EHDP and less effective than Cl2MDP. No greater inhibition was observed when bones had been stimulated with PTH prior to the addition of F2MDP In addition, bones treated with F2MDP only during the first half of the incubation period exhibited reductions in tha amount of 45Ca released during the second half similar to that observed when F2MDP was continuously in the medium, indicating a prolonged effect. Morphologic alterations of osteoclasts suggestive of cell degeneration were observed in F2MDP-treated bones, which were similar to those observed in bones treated with Cl2MDP and EHDP. Due to the presence of fluorine, F2MDP may be useful as an experimental tool to investigate the mode of action of all diphosphonates, in addition to its possible use as a therapeutic agent for diseases of increased bone resorption.

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