New Diphosphonates to Block Bone Resorption

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Abstract
Pathologic increases in bone resorption produce pain, fracture, hypercalcemia, and decreased bone mass in many disorders. In malignant diseases, particularly multiple myeloma and breast cancer, the ability of neoplastic cells to release factors that stimulate osteoclast resorption or direct resorption of bone not only produces symptoms but may also determine the localization and enhance the growth of the tumor. Thus, there is a need for safe and effective agents to block resorption. The usefulness of the agents currently available for this purpose is limited. Phosphate can produce soft-tissue calcification and secondary hyperparathyroidism, mithramycin is too cytotoxic for prolonged use, and . . .