title: Systemic levels of interleukin-6 and matrix metalloproteinase-9 in patients with multiple myeloma may be useful as prognostic indexes of bone disease.
abstract: 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.
authors.affiliation: Blood Bank Center, Venizelion General Hospital Heraklion, Crete, Greece.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Sfiridaki
authors.forename: Spiros
authors.initials: S
authors.lastname: Miyakis
authors.forename: George
authors.initials: G
authors.lastname: Tsirakis
authors.forename: Athanassios
authors.initials: A
authors.lastname: Alegakis
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Passam
authors.forename: Ermioni
authors.initials: E
authors.lastname: Kandidaki
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Margioris
authors.forename: Michael G
authors.initials: MG
authors.lastname: Alexandrakis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001862:Bone Resorption / Q000097:blood* / Q000201:enzymology; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000145:classification / Q000201:enzymology / Q000652:urine; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: D015850:Interleukin-6; D020780:Matrix Metalloproteinase 9