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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Editorial Board Member: Gillery, Philippe / Kazmierczak, Steven / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Schlattmann, Peter / Whitfield, John B.

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

Aikaterini Sfiridaki1 / Spiros Miyakis2 / George Tsirakis3 / Athanassios Alegakis4 / Andreas M. Passam5 / Ermioni Kandidaki6 / Andrew N. Margioris7 / Michael G. Alexandrakis8









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,

Citation Information: Clinical Chemical Laboratory Medicine. Volume 43, Issue 9, Pages 934–938, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/CCLM.2005.160, September 2005

Publication History

May 12, 2005
July 3, 2005


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.

Keywords: matrix metalloproteinases; multiple myeloma; N-telopeptide

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