Dichloromethylene diphosphonate

The changes in calvarial phosphatase activities observed in animals treated with 25-(OH)D3 are totally different from those obtained with either 1.25-(OH)2D3 or 24.25—(OH)2D3. This fact indicates that physiological doses of 25-(OH)D3 may have an effect on cellular activity, independent of the conversion of this metabolite into these dihydroxyderivatives. The various effects of these vitamin D3 metabolites cannot be correlated with changes in serum calcium and/or phosphate concentrations. Among those factors other than serum calcium and phosphate concentrations that may be involved in the mechanism of action of vitamin D3 metabolites on bone phosphatase activities, the parathyroid hormone is of importance. This hormone is known to be a potent activator of bone phosphatases223,224,228. Parathormone increases the content of alkaline, neutral and acid phosphatases in mouse calvaria in vitro. Calcitonin does not prevent the increase of those enzymes while dichloromethylene diphosphonate causes a decrease in acid phosphatase and pyrophosphatase226. ... 

Van der Veen, G., Broersma, L., Dijkstra, C. D., et al. (1994), Prevention of corneal allograft rejection in rats treated with subconjunctival injections of liposomes containing dichloromethylene diphosphonate, Invest. Ophthalmol. Vis. Sci., 35, 3505-3515. 

Minaire P, Berard E, Meunier PJ, Edouard C, Goedert G, Pilonchery G. Effects of disodium dichloromethylene diphosphonate on bone loss in paraplegic patients. J Clin Invest 1981 68(4) 1086-92. 

Van Rooijen N, Van Nieuwmegen R (1984) Elimination of phagocytic cells in the spleen after intravenous injection of liposome encapsulated dichloromethylene -diphosphonate. An enzyme-histochemical study. Cell Tissue Res 238 355... 

Van Rooijen N, Kors N, Van den Ende M, Dijkstra CD (1990) Depletion and repopulation of macrophages in spleen and liver of rat after intravenous treatment with liposome encapsulated dichloromethylene diphosphonate. Cell Tissue Res 260 215... 

For the same purpose of targeting bone tumors with boron-containing phosphonates, carbabora-nylbis- and -polyphosphonic acids were described by Benedict in a patent application. Two examples of the prepared compounds (37, 38) are shown in Figure 2.4. The gcm-bisphosphonate 37 was subjected to a crystal growth inhibition test to determine its potential to reduce calcium phosphate deposition. This showed that the capability of 37 to retard the formation of calcium phosphate is on the same order as the known inhibitor dichloromethylene diphosphonate. Furthermore, it was found to exhibit high skeletal affinity in an animal skeletal uptake test. 

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