Osteoprotegerin and sRANKL serum levels in multiple myeloma patients

Abstract




Background: Receptor activator of NF-κB (RANK) is a TNF receptor superfamily member expressed on the surface of osteoclasts and their precursors that mediates their differentiation, survival, and activation upon interaction with its ligand, RANKL, expressed by osteoblasts, stromal cells and multiple myeloma (MM) plasma cells. RANKL is produced as a membrane bound protein and cleaved into a soluble form by a metalloprotease. The primary secreted form is produced by activated T-lymphocytes. Osteoprotegerin (OPG) is a secreted TNFR, it acts as a decoy receptor for RANKL and inhibitor of RANK-RANKL interaction. Recent studies suggest that MM triggers osteoclastogenesis by disrupting the balance between RANKL and its natural inhibitor, OPG. Therefore in this study we analyzed the concentrations of serum OPG and sRANKL in MM patients at diagnosis.


Material and methods: Determinations of serum OPG and sRANKL concentrations were performed in 25 healthy subjects and 44 MM patients (6 at stage I, 2-II, 29-IIIA, 7-IIIB acc. to DS.; 33 had lytic lesions at skeletal X-ray survey; monoclonal protein IgG was in 33 patients, IgA-6, Bence Jones – 4, nonsecretory-1) by means of ELISA method using Osteoprotegerin ELISA and sRANKL ELISA kits (Biomedica GmbH, Vienna, Austria).


Results:In the whole group of MM patients, OPG concentrations in particular patients ranged from 42 to 346 pg/ml with a mean concentration of 111±69, median 88 pg/ml while in healthy age- and sex- matched controls OPG levels ranged from 49 to 130 pg/ml, mean 77±22, median 74 pg/ml (p=0,0208). In MM patients with renal failure mean level of OPG was 164±78, median 130 pg/ml while in MM patients with normal renal function they were 101±64 and 85 pg/ml respectively (p=0,0094). There were differences in OPG concentrations depending on stage of disease: stage I – 68±20, median 64, stage III-120±73, median 96 pg/ml (p=0,017). In MM patients sRANKL concentrations in particular patients ranged from 0 to 19 pg/ml with a mean concentration of 3,4±4,9, median 0 pg/ml while in healthy persons sRANKL levels ranged from 0 to 43 pg/ml, mean 5,0±10, median 0 pg/ml (p=0,65).


Conclusions: In some (20%) of MM patients at diagnosis serum OPG level is elevated; it may be a compensative reaction in relation to increased bone destruction. Significantly increased OPG concentrations in MM patients with renal failure may be related to its decreased elimination. In half of MM patients serum sRANKL is undetectable.