The role of bisphosphonates for the treatment of bone disease in multiple myeloma

Palliative therapy is often st major objective for clinicians while treating advanced cancer. This is particularly true in multiple myeloma (MM), where bone involvement markedly influences the quality of life of patients. Bisphosphonates (BP) are a new class of drugs regulating bone turnover, which exert their activity mainly by inhibiting osteoclast bone resorption. Three BP (etidronate, ETD; clodronate, CDN; pamidronate, PMD) have so far been investigated in the clinical setting for treating bone disease in patients with MM. The results of these trials, including our own experience, are reviewed here. Although all three BP were effective in lowering hypercalcemia of MM patients, PMD, a second generation BP, clearly had the most substantial long term clinical benefits regarding bony complications, pain and quality of life. CDN also showed some activity in reducing the development of new lytic lesions, while no significant beneficial effect was seen in patients using ETD. Interestingly, some studies have reported an improved survival in subsets of MM patients receiving BP and this is in agreement with recent evidence of possible direct anti-neoplastic activities of these drugs mediated through reduction of IL-6 production and stimulation of neoplastic cell apoptosis.