Bone Loss Prevention in Cancer: New Developments and Perspectives

Abstract

In patients with cancer, accelerated bone loss is common and usually the result of one or both of the following: the use of hormonal therapies as part of anticancer treatment, and the invasion of the cancer to bone. The combined subsets of patients who are either being treated with hormonal therapy or who have skeletal involvement constitute a major proportion of all cancer patients. While hormonal therapies are commonly used in patients with breast or prostate cancer, bone metastases are a common complication in all patients with advanced cancer—particularly in patients with breast, prostate, and lung disease, 1–3 which are the most prevalent of cancers in men and women. Compared with the numbers of patients receiving hormonal therapies for breast and prostate cancer, bone metastases affect a smaller, though important, population. Indeed, the true incidence of bone metastases is a matter of contention and some estimate the annual incidence rate in the United States alone to be as high as 350,000. 2 Hormonal therapies primarily enhance osteoclastmediated bone resorption. In contrast, metabolically active tumor cells invade and colonize bone tissues, secreting factors that alter both bone resorption and formation. Both hormonal therapy and tumor metastasis result in accelerated bone turnover and compromise the structural integrity of the bone in patients with solid tumors. This is also true for patients with multiple myeloma, where malignant bone disease can seriously diminish bone strength. Consequently, a high proportion of patients with cancer experience skeletal-related events (SREs), including the need for surgery or palliative radiation to the bone, fractures, spinal cord compression, and hypercalcemia of malignancy. Of these, the most commonly reported SREs include the need for palliative radiation to the bone and pathologic fractures. In addition to the substantial economic burden incurred as a result of the clinical management of bone metastases and SREs, these events are associated with deterioration in patient quality of life and poor treatment outcome. Bisphosphonates are a unique class of drugs particularly suited to their bone-conserving role because they are inherently site-directed by virtue of their affinity for bone mineral and because they are strong inhibitors of bone resorption (dissolution). Thus, both cancer and bisphosphonates share bone as a common target, and this relatively confined (v systemic) antagonism is a desirable feature of bisphosphonate therapy. Bisphosphonates have been shown to be an effective treatment for the prevention of bone loss and SREs. Multiple studies in patients with malignant bone disease have demonstrated that bisphosphonates ameliorate the risk and symptoms of SREs. Zoledronic acid is the most widely approved bisphosphonate, and recently, new data have indicated that bisphosphonates might also improve cancer-related outcomes. 4 Given that bisphosphonates already have been proven to be well tolerated