Abstract
Two Diphosphonates, ethane-1-hydroxy-1,1-diphosphonate (EHDP) and dichloromethylene diphosphonate (Cl2MDP) inhibitin vitro bone resorption, which is either stimulated by parathyroid hormone or intrinsic in a bone remodeling culture system. While Cl2MDP is more effective than EHDP in inhibiting resorption, it also appears to result in a related diminution in osteoid formation. This effect causes a marked biochemical and morphological depression of bone remodelling with Cl2MDP at a concentration equivalent to 10-μg-phosphorus/ml of culture medium. The difference in activity between EHDP and Cl2MDP may be related to their relative affinities for the bone mineral surfaces and hence their effective free concentration in the bone extracellular fluid. It is hypothesized that diphosphonates may also affect bone formation indirectly if one assumes that the degree of mineralization of the matrix is important in the induction and regulation of osteoblastic activity in remodelling bone.
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