Patients with multiple myeloma (MM) experience pathologic fractures, bone pain, hypercalcemia, neurologic symptoms, and renal insufficiency with substantial morbidity and mortality. Bisphosphonates have been used successfully for the management of MM-related bone disease. Increased incidence of osteonecrosis of the jaw has been observed in patients with cancer receiving bisphosphonate therapy. Recent advances in the pathobiology of MM-related bone disease and other cancer-related bone metastases have led to the identification of novel therapeutic targets, such as receptor activator of nuclear factor-κB (RANK); its ligand (RANKL); and a decoy receptor, osteoprotegerin, for the development of potential targeted agents. Initial studies have demonstrated that targeting RANK/RANKL signaling with the fully human monoclonal antibody denosumab prevented skeletal complications in patients with MM and other cancers with bone metastases. Ongoing studies evaluating the clinical utility of denosumab in cancer-related bone destruction have been discussed. In addition, several potential targets, such as macrophage inflammatory protein-1α, chemokine receptors 1 and 5, interleukin-3, and Wnt signaling, are briefly described.
- Macrophage inflammatory protein-1α
- Wnt signaling pathway
ASJC Scopus subject areas
- Cancer Research