title: Myeloma bone disease: pathophysiology and management.
abstract: Bone disease is a major feature of multiple myeloma. Myeloma-induced bone destruction is the result of an increased activity of osteoclasts, which is not accompanied by a comparable increase of osteoblast function. Recent studies have revealed that new molecules such as the receptor activator of nuclear factor-kappa B (RANK), its ligand (RANKL), osteoprotegerin (OPG), and macrophage inflammatory protein-1alpha are implicated in osteoclast activation and differentiation, while proteins such as dickkopf-1 inhibit osteoblastic bone formation. These new molecules seem to interfere not only with the biology of myeloma bone destruction but also with tumour growth and survival, creating novel targets for the development of new antimyeloma treatment. Currently, bisphosphonates play a major role in the management of myeloma bone disease. Clodronate, pamidronate and zoledronic acid are the most effective bisphosphonates in symptomatic myeloma patients. Biochemical markers of bone remodeling have been used in an attempt to identify patients more likely to benefit from early treatment with bisphosphonates. Furthermore, using microarray techniques, myeloma patients may be subdivided into molecular subgroups with certain clinical characteristics, such as propensity for lytic lesions that may need early prophylactic treatment. Recent phase I studies with recombinant OPG and monoclonal antibodies to RANKL appear promising.
authors.affiliation: Department of Hematology, 251 General Airforce Hospital, Athens, Greece. e.terpos@imperial.ac.uk
authors.forename: E
authors.initials: E
authors.lastname: Terpos
authors.forename: M-A
authors.initials: MA
authors.lastname: Dimopoulos
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D006801:Humans; D009101:Multiple Myeloma / Q000503:physiopathology* / Q000628:therapy*; D010010:Osteoclasts / Q000187:drug effects; D010014:Osteolysis / Q000517:prevention & control*
chemical_list: D000970:Antineoplastic Agents