The use of clodronate in multiple myeloma.

Bone metastases secondary to myeloma, are characterized by severe bone pain, pathological fractures, hypercalcaemia and hypercalciuria. Histological and biochemical investigations have shown a wide spectrum of abnormalities in bone turnover in patients with multiple myeloma. The increased osteoclast activity caused by various osteoclast activating factors secreted by myeloma cells, is responsible for the diffuse localized osteolytic lesions. These lesions are responsible for the symptoms and respond poorly to standard chemotherapy, justifying the use of a bone-sparing agent. Clodronate is a potent inhibitor of osteoclast activity and does not impair bone mineralization. Several studies have shown that clodronate can normalize serum calcium in hypercalcaemic patients with metastatic bone disease, and a similar response is seen in multiple myeloma. In a long-term (18 months) placebo-controlled study we have shown that clodronate, given orally at a daily dose of 1.6g, can decrease both the incidence of pathological fractures and the activity of osteoclasts, as judged by measurements in iliac crest biopsy. These results, along with those from two other studies, are promising and suggest that clodronate may inhibit the progression of osteolytic lesions in multiple myeloma.