Use of Bisphosphonates in the Treatment of Multiple Myeloma

Bone pain is the single most common presenting complaint in myeloma. Although first-line chemotherapy has a marked effect on bone pain, skeletal disease frequently continues to progress throughout the course of the disease and the incidence of skeletal events remains high. The underlying pathology in myeloma constitutes mainly increased osteoclastic activity but also reduced osteoblastic activity. Any agent that inhibits osteoclast activity potentially provides some degree of skeletal protection although only the bisphosphonates have achieved widespread use. Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption and evidence of bone protection and modification of skeletal disease progression has been greatest with clodronate and pamidronate. The MRC VIth Myeloma Trial is, to date, by far the largest randomised placebo-controlled trial of bisphosphonates in myeloma. Current evidence suggests that bisphosphonate treatment should begin as early as possible and continue indefinitely, and probably should be considered for all patients with myeloma. The additional costs of clodronate therapy in the management of myeloma patients were around 17% higher than in controls which is moderate when considering the significant reductions in hypercalcaemic episodes and in vertebral and non-vertebral fractures.