Pathophysiology of myeloma bone disease.
Multiple myeloma is a tumor of terminally differentiated plasma cells that home to and expand in the bone marrow. It is the second most common hematologic malignancy, with approximately 16,000 new cases per year, and accounts for an estimated 11,000 deaths in the USA. It is the most common cancer to metastasize to bone, with up to 90% of patients developing bone lesions. The bone lesions are purely osteolytic in nature, and up to 60% of patients develop a pathologic fracture over the course of their disease. Bone disease is a hallmark of multiple myeloma, and the bone disease differs from other bone metastasis caused by other tumors. Although both myeloma and other osteolytic metastasis induce increased osteoclastic bone resorption, in contrast to other tumors, osteoblast activity in myeloma is either severely decreased or absent. The basis for this severe imbalance between increased osteoclastic bone resorption and decreased bone formation resulting from suppressed osteoblastic activity has been a topic of extensive investigation during the last several years. The clinical consequences of this extensive accelerated and imbalanced bone destruction process include bone pain, pathologic fractures, hypercalcemia and spinal cord compression syndromes, which can be devastating for patients and significantly impact overall quality of life and expected survival. In this chapter, we will discuss the pathophysiology underlying bone disease in myeloma. This results from the uncoupling of bone remodeling and is characterized by markedly increased activity of osteoclasts and profound decreased activity of osteoblasts. In addition, we also review the emerging data on novel targeted therapies aimed at ameliorating myeloma bone disease.
Esteve
Flavia R
FR
University of Pittsburgh, Medicine/Hematology-Oncology, 5150 Centre Avenue, Pittsburgh, PA 15213, USA.
Roodman
G David
GD
D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001862:Bone Resorption / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D009101:Multiple Myeloma / Q000503:physiopathology*; D010010:Osteoclasts / Q000502:physiology; D053245:RANK Ligand / Q000187:drug effects / Q000502:physiology
D050071:Bone Density Conservation Agents; D053245:RANK Ligand