Biochemistry of bone induction and dystrophic calcification

The propensity of crosslinked collagen matrices to calcify when implanted in animals and human beings is well documented. This article demonstrates that the covalent binding of the biphosphonate, 3-amino-1-hydroxy-propane-1-1-diphosphonic acid, to active bone matrix inhibits bone formation as well as dystrophic calcification. The inhibitory effects on calcium accumulation and alkaline phosphatase activity are greater than those achieved by inactivation of the matrix by protease digestion of the bone morphogenetic factors present in demineralized bone. Whereas bone formation is a cell-mediated effect, artificially crosslinked collagen matrices calcify extensively inside diffusion chambers, reflecting a non-cell-mediated nucleation process. The fundamental differences described should shed light on new modalities to modulate these processes in living systems.