Abstract

The aim of the study is to analyse the osteoprotegerin (OPG) level in patients with multiple myeloma (MM), primary renal diseases with renal failure (PRD with RF) and healthy controls and to assess the influence of RF on the correlations of OPG with basic parameters for MM. Serum levels of OPG (ELISA kits, Biomedica, Vienna) were studied in 66 newly diagnosed patients with MM, 51 with PRD and RF and 32 controls. In MM patients OPG is presented also as OPG/creatinin ratio and is studied acc to the clinical stage (Durie and Salmon), bone marrow infiltration, grade of myeloma bone disease (MBD) using the Merlini scale, b2-microglobulin and LDH. Statistics were done by SPSS v 11.0 (variative, alternative, correlative, non-parametric analyses, Mann-Whitney test, one-way ANOVA; at p<0,05). OPG levels in MM patients do not differ from PRD with RF group but are significantly higher compared with the controls (tabl.1). OPG/creatinin eliminates the difference between the MM patients and controls: 0,043±0,003 vs 0,037 ± 0,001, p>0,05. In patients with PRD OPG is significantly higher in II gr. RF (p<0,02) while in MM patients its level does not depend on the grade of RF. In I clinical stage OPG is significantly higher than in III stage (6,34 ± 0,724 vs 4,245 ±0,407 pmol/l, p<0,03). MM patients with RF have significantly higher OPG than these without RF. The proportion of MM patients with RF and elevated OPG >6,0pmol/l is about 2,5 times higher (68,7%) than the proportion of patients with low OPG<3,44pmol/l (25,0%), p<0,05. MM patients with minimal and no bone lesions+RF have significantly higher OPG than these with severe MBD + RF (9,97 ± 2,42 vs 4,92 ± 0,62 pmol/l, p<0,05). The correlations of OPG are stronger for OPG/creatinin and are most expressed in the MM group without RF. RF “masques” the clinical correlations of OPG (tabl.2). OPG levels in MM show phase dynamics: initial elevation in early clinical stages and low grade bone lesions (successful counteraction to intensive bone resorbtion) followed by decrease in the advanced stages and severe MBD. These data we explain with the combined but opposite effects of RF (elevates OPG providing skeletal resistance in uremia) and the specific, not-possible-to overcome action of myeloma tumor burden (directly degrades OPG and inhibits osteoblast function).

OPG levels in patients with MM, PRD and controls

GroupsNOPG pmol/l mean±SEMP
*vs controls 
Controls 32 3,77 ± 0,33 0,01 
MM 66 5,36± 0,45  
MM without RF 39 4,51 ± 0,30 0,001 
MM with RF 27 6,60 ± 1,00  
MM with I gr RF (cr 166–353 mol/l) μ 18 6,73 ± 1,37 NS 
MM with II gr RF (cr 353– 707 mol/l) μ 6,20 ± 1,32  
PRD with RF 51 5,74± 0,36 0,001* 
PRD with I gr RF 23 4,50± 0,32 0.02 
PRD with II gr RF 28 6,75± 0,51  
GroupsNOPG pmol/l mean±SEMP
*vs controls 
Controls 32 3,77 ± 0,33 0,01 
MM 66 5,36± 0,45  
MM without RF 39 4,51 ± 0,30 0,001 
MM with RF 27 6,60 ± 1,00  
MM with I gr RF (cr 166–353 mol/l) μ 18 6,73 ± 1,37 NS 
MM with II gr RF (cr 353– 707 mol/l) μ 6,20 ± 1,32  
PRD with RF 51 5,74± 0,36 0,001* 
PRD with I gr RF 23 4,50± 0,32 0.02 
PRD with II gr RF 28 6,75± 0,51  

Correlation coefficients of OPG in MM and eliminating the influence of renal function

ParameterOPG pmol/lOPG/creatininOPG pmol/l (without RF)
prprpr
Clinical stage <0,05 −0,275 <0,001 −0,616 <0,001 − 0,669 
MBD <0,05 −0,323 <0,001 −0,521 <0,001 − 0,556 
m. infiltration N.S.  <0,001 −0,530 <0,001 − 0,562 
ß2-microglobulin <0,05 +0,375 N.S  N.S  
LDH N.S  N.S  <0,05 −0,338 
ParameterOPG pmol/lOPG/creatininOPG pmol/l (without RF)
prprpr
Clinical stage <0,05 −0,275 <0,001 −0,616 <0,001 − 0,669 
MBD <0,05 −0,323 <0,001 −0,521 <0,001 − 0,556 
m. infiltration N.S.  <0,001 −0,530 <0,001 − 0,562 
ß2-microglobulin <0,05 +0,375 N.S  N.S  
LDH N.S  N.S  <0,05 −0,338 

Disclosure: No relevant conflicts of interest to declare.

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