Accessible Requires Authentication Published by De Gruyter September 21, 2011

Systemic levels of interleukin-6 and matrix metalloproteinase-9 in patients with multiple myeloma may be useful as prognostic indexes of bone disease

Aikaterini Sfiridaki, Spiros Miyakis, George Tsirakis, Athanassios Alegakis, Andreas M. Passam, Ermioni Kandidaki, Andrew N. Margioris and Michael G. Alexandrakis


Multiple myeloma is characterized by accelerated production of the proteolytic enzyme matrix metalloproteinase (MMP)-9. We hypothesized that myeloma-produced MMP-9 may influence the rate of bone turnover in a paracrine manner. Thus, we examined the correlations of MMP-9 levels, disease severity, and bone turnover rate as evaluated by markers of bone formation and resorption.

Thirty-seven newly diagnosed multiple myeloma patients (nine of Durie-Salmon stage I, 12 of stage II and 16 of stage III) and 12 age-matched controls were studied. Serum MMP-9 levels were significantly higher at stage II compared to stage I (188.78±91.27 vs. 59.25±33.09 ng/mL, p<0.004). Additionally, free urine pyridinolines (F-Pyd), free urine deoxy-pyridinolines (F-Dpd) and urine N-telopeptide fragment (NTx) were elevated, their level correlating with disease stage (p<0.001, p<0.03, p<0.001, respectively), as were bone marrow infiltration and serum interleukin-6 (IL-6) levels (p<0.0001, p<0.01, respectively). MMP-9 levels were lower in patients compared with controls (p<0.001), whereas IL-6 and bone resorption marker levels were higher in patients than in controls (p<0.001 in all cases). Significant correlation was found between infiltration, MMP-9, free urine pyd, free urine dpd and NTx for each stage of the disease (p<0.03, p<0.003, p<0.002, p<0.003 and p<0.001, respectively). Levels of MMP-9 and of IL-6 in multiple myeloma correlate well with bone turnover rate and may be useful in disease evaluation.

Corresponding author: Michael G. Alexandrakis, Assistant Professor of Medicine, Department of Haematology, University Hospital of Heraklion, P.O. Box 1352, Heraklion, Crete, Greece Phone: +30-28-1039-2426, Fax: +30-28-1024-4883,


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Received: 2005-5-12
Accepted: 2005-7-3
Published Online: 2011-9-21
Published in Print: 2005-9-1

©2005 by Walter de Gruyter Berlin New York