title: Serum levels of total-RANKL in multiple myeloma.
abstract: BACKGROUND
  Receptor activator of nuclear factor-kappaB ligand (RANKL) plays a key role in osteoclast activation in myeloma bone disease. The increased expression of RANKL in the bone marrow microenvironment was demonstrated in several studies, but there are only rare data on circulating RANKL levels in patients with multiple myeloma (MM).
  
  
  METHODS
  In the current study, we investigated the clinical significance of serum RANKL levels, using an enzyme-linked immunosorbent assay test that detects both free and osteoprotegerin (OPG)-bound RANKL (total-RANKL, tRANKL) in patients with newly diagnosed MM (n = 93) and monoclonal gammopathy of undetermined significance (MGUS; n = 20) compared with healthy controls (n = 20).
  
  
  RESULTS
  Circulating serum tRANKL was significantly elevated in patients with MM compared with controls (P < .001) or MGUS (P < .001). Furthermore, tRANKL levels were higher in smoldering MM versus MGUS (P = .031) and in symptomatic versus smoldering MM (P < .001). Serum tRANKL increased parallel to International Staging System stages I to III (P = .004) and correlated with the presence of lytic bone lesions (P < .001). Total-RANKL was a prognostic factor for overall survival in symptomatic MM (P = .043). A significantly longer progression-free survival was observed in patients with a > 50% decrease in tRANKL levels after 3 months of combined chemotherapy and bisphosphonate treatment.
  
  
  CONCLUSIONS
  Our study demonstrates for the first time that serum tRANKL reflects advanced disease, lytic bone destruction, and poor prognosis in MM.
authors: Department of Hematology and Oncology, Charité, Universitätsmedizin Berlin, Berlin 10117, Germany.
authors: Christian
authors: C
authors: Jakob
authors: Andrea
authors: A
authors: Goerke
authors: Evangelos
authors: E
authors: Terpos
authors: Jan
authors: J
authors: Sterz
authors: Ulrike
authors: U
authors: Heider
authors: Dagmar
authors: D
authors: Kühnhardt
authors: Susanne
authors: S
authors: Ziefle
authors: Lorenz
authors: L
authors: Kleeberg
authors: Maren
authors: M
authors: Mieth
authors: Ivana von
authors: Iv
authors: Metzler
authors: Christian
authors: C
authors: Müller
authors: Orhan
authors: O
authors: Sezer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000401:mortality; D053244:Osteoprotegerin / Q000097:blood; D011379:Prognosis; D053245:RANK Ligand / Q000097:blood*
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human