Analgesic effect of bisphosphonates on bone pain in breast cancer patients: a review article.

Bisphosphonates exert their analgesic effect by several mechanisms. The long-term effects are probably due to osteoclast inhibition. The acute pain-relieving effect, which occurs within days or a week, is likely to be associated with the reduction of various potentially pain-producing substances. As regards pamidronate, several open, controlled studies have shown a significant effect on bone pain in 30-70% of breast cancer patients. The effects have been dose-dependent: a mean dose of 15 mg i.v./week is obviously suboptimal, whereas higher doses yield markedly better effects. The dose response is most evident at doses between 15 and 30 mg/week. Furthermore, the total dose per infusion is of interest: 30 mg every 2 weeks is an ineffective treatment, whereas 60 mg every 4 weeks is more effective. Thus, both the dose per week and the total dose per infusion are of importance in order to achieve optimal treatment. Patients with rapid progression of their disease require higher doses than patients with slow progression. Parenteral therapy is more effective than oral treatment. Both oral and parenteral clodronate exert a significant, positive effect on total skeletal morbidity and thus probably also on bone pain. Unfortunately, pain measurements have not been performed and evidence for pain reduction is indirect. Specific pain studies and studies of quality of life, with few exceptions, are, however, still lacking.