Urinary N‐telopeptide levels in multiple myeloma patients, correlation with Tc‐99m‐sestaMIBI scintigraphy and other biochemical markers of disease activity

Alexandrakis, M.G.; Kyriakou, Despina; Passam, Freda; Malliaraki, Niki; Vlachonikolis, Ioannis G.; Karkavitsas, Nikolaos

doi:10.1002/hon.700

Cited by 9 publications

(5 citation statements)

References 25 publications

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“…Several studies speculated on the possible prognostic impact of 99mTc‐MIBI scintigraphy for MM patients (Pace et al , 2001, 2005a,b, 2006; Alexandrakis et al , 2002, 2003; Athanasoulis et al , 2003). Alexandrakis et al (2002) first investigated the 99mTc‐MIBI potential predictive value in patients with MM.…”

Section: Discussionmentioning

confidence: 99%

“…Tc‐99 sestamibi (99mTc‐MIBI) scanning is a nuclear method used to detect a variety of malignant tumours, including sarcomas, lung, thyroid, breast and brain cancer (Alonso et al , 1998; Maurea et al , 1998; Balleari et al , 2001; Svaldi et al , 2001). Recently, several preliminary studies have shown that 99mTc‐MIBI is also actively concentrated in myeloma tissue, identifying sites of active myeloma disease and bone lesions with both high sensitivity and specificity (Adams et al , 1996; Tirovola et al , 1996; Pace et al , 1998; Di Gennaro et al , 1999; Fisher et al , 2000; Alexandrakis et al , 2001, 2003; Balleari et al , 2001; Fonti et al , 2001; Svaldi et al , 2001; Ak et al , 2003; Alper et al , 2003; Mileshkin et al , 2004; Pace et al , 2005a).…”

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confidence: 99%

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Technetium‐99m sestamibi scintigraphy is sensitive and specific for the staging and the follow‐up of patients with multiple myeloma: a multicentre study on 397 scans

et al. 2007

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SummaryWe evaluated the additional benefit of Technetium 99 -sestamibi (99mTc-MIBI) scanning in comparison with standard X-ray techniques for multiple myeloma patients either at diagnosis or during follow-up. Between February 2001 and January 2005, 397 whole body scans were acquired. On 229 scans performed at diagnosis, 146 (64%) were positive and 81 cases have discordant X-ray results. The sensitivity of 99mTc-MIBI and X-ray were 77% and 45% respectively. As a result of 99mTc-MIBI, 40% of asymptomatic myeloma patients were up-staged. The positivity of 99mTc-MIBI correlated significantly with all of the most relevant clinical and biological parameters. Multivariate analysis selected only high reactive C protein (P ¼ 0AE0005), bone marrow infiltration (P ¼ 0AE02) and bone pain (P ¼ 0AE002) as factors affecting 99mTc-MIBI pattern. In 22 patients with solitary myeloma, 99mTc-MIBI was positive in 86% of cases and detected more disease sites than X-ray. Among 168 scans performed during follow-up, 99mTc-MIBI presented high specificity in patients showing a complete response (CR; 86%), and correlated with myeloma activity and with response to therapy. At multivariate analysis, a positive pattern correlated with bone marrow infiltration (P ¼ 0AE002) and disease status other than CR (P ¼ 0AE03). We conclude that 99mTc-MIBI scanning is an additional diagnostic tool with a high specificity for the staging and the follow-up of multiple myeloma patients.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Technetium‐99m sestamibi scintigraphy is sensitive and specific for the staging and the follow‐up of patients with multiple myeloma: a multicentre study on 397 scans

et al. 2007

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“…65 Urinary NTX also correlated with the overall score of skeletal involvement as measured by Tc-99m-MIBI scintigraphy and bone marrow infiltration by plasma cells. 66 Coleman et al showed in 210 MM patients that high or intermediate urinary NTX correlated with an increased risk for SRE development compared with low NTX values (risk ratio (RR) 2.25, P ¼ 0.032 and RR 1.75, P ¼ 0.016, respectively). 57 High NTX values also correlated with a three-fold increased risk for developing a first SRE (Figure 2), whereas there was also a trend toward increased risk for progression of osteolytic lesions in the high NTX group (P ¼ 0.08).…”

Section: Markers Of Bone Remodeling In Myeloma Bone Diseasementioning

confidence: 99%

The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group

et al. 2010

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Lytic bone disease is a frequent complication of multiple myeloma (MM). Lytic lesions rarely heal and X-rays are of limited value in monitoring bone destruction during antimyeloma or anti-resorptive treatment. Biochemical markers of bone resorption (amino-and carboxy-terminal cross-linking telopeptide of type I collagen (NTX and CTX, respectively) or CTX generated by matrix metalloproteinases (ICTP)) and bone formation provide information on bone dynamics and reflect disease activity in bone. These markers have been investigated as tools for evaluating the extent of bone disease, risk of skeletal morbidity and response to anti-resorptive treatment in MM. Urinary NTX, serum CTX and serum ICTP are elevated in myeloma patients with osteolytic lesions and correlate with advanced disease stage. Furthermore, urinary NTX and serum ICTP correlate with risk for skeletal complications, disease progression and overall survival. Bone markers have also been used for the early diagnosis of bone lesions. This International Myeloma Working Group report summarizes the existing data for the role of bone markers in assessing the extent of MM bone disease and in monitoring bone turnover during anti-myeloma therapies and provides information on novel markers that may be of particular interest in the near future.

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“…We and others have shown that there is an enhancement of osteoclastic activity in MM patients (3,4,20). This process is mediated by factors produced locally by malignant and non-malignant cells in the microenvironment of bones.…”

Section: Discussionmentioning

confidence: 84%

“…Skeletal morbidity in MM correlates well with the degree of plasma cell infiltration (3,4). The progression of the disease involves the production by the tumor cells of a specific class of extracellular matrix-degrading metalloenzymes, including matrix metalloproteinase (MMP)-9, a 92-kDa type IV collagenase (5,6).…”

Section: Introductionmentioning

confidence: 99%

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

Sfiridaki¹,

Miyakis²,

Tsirakis³

et al. 2005

Clinical Chemistry and Laboratory Medicine (CCLM)

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M. (2005). Systemic levels of interleukin-6 and matrix metalloproteinase-9 in patients with multiple myeloma may be useful as prognostic indexes of bone disease. Clinical Chemical Laboratory Medicine, 43 (9), 934-938.Systemic levels of interleukin-6 and matrix metalloproteinase-9 in patients with multiple myeloma may be useful as prognostic indexes of bone disease AbstractMultiple 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. 2005/166Article in press -uncorrected proof Systemic levels of interleukin-6 and matrix metalloproteinase-9 in patients with multiple myeloma may be useful as prognostic indexes of bone disease AbstractMultiple 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, res...

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Urinary N‐telopeptide levels in multiple myeloma patients, correlation with Tc‐99m‐sestaMIBI scintigraphy and other biochemical markers of disease activity

Cited by 9 publications

References 25 publications

Technetium‐99m sestamibi scintigraphy is sensitive and specific for the staging and the follow‐up of patients with multiple myeloma: a multicentre study on 397 scans

Technetium‐99m sestamibi scintigraphy is sensitive and specific for the staging and the follow‐up of patients with multiple myeloma: a multicentre study on 397 scans

The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group

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

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