title: Soluble receptor activator of nuclear factor kappaB ligand-osteoprotegerin ratio predicts survival in multiple myeloma: proposal for a novel prognostic index.
abstract: Interaction between receptor activator of nuclear factor kappaB ligand (RANKL) and RANK/osteoprotegerin (OPG) plays a dominant role in osteoclast activation and possibly in plasma cell survival in multiple myeloma (MM). We measured soluble RANKL (sRANKL), OPG, and bone remodeling markers in 121 patients with newly diagnosed MM to evaluate their role in bone disease and survival. Serum levels of sRANKL were elevated in patients with MM and correlated with bone disease. The sRANKL/OPG ratio was also increased and correlated with markers of bone resorption, osteolytic lesions, and markers of disease activity. The sRANKL/OPG ratio, C-reactive protein (CRP), and beta2-microglobulin were the only independent prognostic factors predicting survival in multivariate analysis. We generated a prognostic index based on these factors that divided our patients into 3 risk groups. The low-risk group had a 96% probability of survival at 5 years, whereas the intermediate-risk and the high-risk groups had probabilities of survival of 52% and 0%, respectively. Not only do these results confirm for the first time in humans the importance of sRANKL/OPG in the development of bone disease, they also highlight the role of this pathway in the biology of plasma cell growth as reflected by its influence on survival.
authors.affiliation: Department of Hematology, Faculty of Medicine Imperial College, Hammersmith Hospital, Du Cane Road, W12 0NN, London, United Kingdom. e.terpos@imperial.ac.uk
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.forename: Richard
authors.initials: R
authors.lastname: Szydlo
authors.forename: Jane F
authors.initials: JF
authors.lastname: Apperley
authors.forename: Evdoxia
authors.initials: E
authors.lastname: Hatjiharissi
authors.forename: Marianna
authors.initials: M
authors.lastname: Politou
authors.forename: John
authors.initials: J
authors.lastname: Meletis
authors.forename: Nora
authors.initials: N
authors.lastname: Viniou
authors.forename: Xenophon
authors.initials: X
authors.lastname: Yataganas
authors.forename: John M
authors.initials: JM
authors.lastname: Goldman
authors.forename: Amin
authors.initials: A
authors.lastname: Rahemtulla
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001847:Bone Diseases / Q000175:diagnosis / Q000209:etiology; D016723:Bone Remodeling; D002097:C-Reactive Protein / Q000032:analysis; D002352:Carrier Proteins / Q000097:blood*; D002470:Cell Survival; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D015999:Multivariate Analysis; D053244:Osteoprotegerin; D011379:Prognosis; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor; D012720:Severity of Illness Index; D012995:Solubility; D016019:Survival Analysis; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D001613:beta 2-Microglobulin; D002097:C-Reactive Protein