Bisphosphonates are a class of drugs that are structural analogs of endogenous pyrophosphate.15 Carbon substitution for the central oxygen atom makes the molecule resistant to hydrolysis and allows for the addition of two side chains necessary for calcium crystal and bone mineral affinity.15 Bisphosphonates are selectively deposited to sites of increased bone turnover and are ingested by osteoclasts, causing inhibition their resorp-tive capacity.4849 Currently, two bisphosphonates, pamidronate (Aredia; Novartis Pharmaceuticals, East Hanover, NJ) and zoledronate (Zometa; Novartis Pharmaceuticals, East Hanover, NJ), are Food and Drug Administration (FDA) approved in the United States for use in MM patients with lytic bone disease.

Bisphosphonates have been extensively studied in patients with MM (see Table 91.2). In general, no overall survival benefit has been observed with their use; rather, significant reductions in clinically measurable skeletal related events (SREs) can be achieved.15 In larger trials, an SRE is defined as pathologic fracture, spinal cord compression, or need for radiation or surgical intervention.5051 In addition to these clinical endpoints, some studies have included hypercalcemia as an SRE.52'53

When given to MM patients undergoing chemotherapy, pamidronate 90 mg IV over 4 hours monthly can significantly reduce serum and urinary markers of bone

Table 91.2 Randomized trials of bisphosphonate therapy in multiple myeloma

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