Tumor bone disease

Abstract

The propensity of breast cancer cells to metastasize in bone could notably be due to the rich supply of relevant growth factors present in the skeletal microenvironment, which increases breast cancer cell growth. Bone destruction is essentially mediated by osteoclast activation. Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption that now constitute a standard non-cytotoxic treatment of bone metastases. They have become the optimal therapy for tumor-induced hypercalcemia, and at adequate doses (90 mg) the efficacy of pamidronate is not influenced significantly by the tumor type or the degree of metastatic bone involvement. Regular 90-mg pamidronate infusions can also relieve bone pain in about one-half of cases, and an objective sclerosis of osteolytic lesions can be seen in one-quarter of patients. Most importantly, the prolonged administration of oral or intravenous bisphosphonates can delay and reduce the frequency of morbid skeletal events in breast cancer metastatic to bone and in multiple myeloma by one-quarter to one-half. Intravenous bisphosphonates appear to produce larger and more rapid effects than available oral compounds. Newer, more potent bisphosphonates, such as ibandronate (6 mg) and zoledronate (4 mg), appear to produce similar results to pamidronate but are more convenient to administer. They could, nevertheless, be more potent in conditions characterized by severe osteolysis. Zoledronate has thus been shown to be superior to pamidronate in moderate to severe hypercalcemia. Therapy with bisphosphonates also has the advantage of preventing postmenopausal osteoporosis in women cured from breast cancer and for whom ERT is still considered to be contraindicated.