Aetiology of bone disease and the role of bisphosphonates in multiple myeloma.
Osteolytic bone disease is a major cause of morbidity in patients with multiple myeloma. Our understanding of the pathophysiology of multiple myeloma has increased substantially during the past decade. However the underlying mechanisms of bone destruction and the treatments available have, until recently, received relatively little specific attention. In this review, we provide an overview of the RANK/RANKL/osteoprotegerin system; we describe its interaction with other cellular mechanisms, through which malignant plasma cells drive osteolysis, and explain how bisphosphonates can be used to block this action. We also review the supporting evidence for bisphosphonates as the treatment of choice for patients with bone complications related to multiple myeloma, and discuss possible developments for targeted therapy in the future.
Ashcroft
Andrew J
AJ
Epidemiology and Genetics Unit, University of Leeds, UK. johna@lrf.leeds.ac.uk
Davies
Faith E
FE
Morgan
Gareth J
GJ
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015519:Bone Density; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D002986:Clinical Trials as Topic; D004002:Clodronic Acid / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006934:Hypercalcemia / Q000517:prevention & control; D007093:Imidazoles / Q000494:pharmacology; D009101:Multiple Myeloma / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D010014:Osteolysis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D018579:Patient Selection; D016896:Treatment Outcome; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D018925:Chemokines; D016207:Cytokines; D004164:Diphosphonates; D007093:Imidazoles; D004002:Clodronic Acid; D000077211:Zoledronic Acid