Bone resorption parameters [carboxy‐terminal telopeptide of type‐I collagen (ICTP), amino‐terminal collagen type‐I telopeptide (NTx), and deoxypyridinoline (Dpd)] in MGUS and multiple myeloma

Abstract

Skeletal morbidity is a major problem in multiple myeloma. Histomorphometric studies have demonstrated that increased bone resorption can be present even in the absence of radiographic abnormalities. To overcome diagnostic problems in estimating the activity of bone resorption, new laboratory parameters that reflect bone metabolism accurately are urgently needed. We analyzed three parameters of osteoclastic bone destruction, i.e. deoxypyridinoline (Dpd) and amino-terminal collagen type-I telopeptide (NTx) in urine and carboxy-terminal telopeptide of type-I collagen (ICTP) in serum, of 75 patients with multiple myeloma (n = 57) or monoclonal gammopathy of undetermined significance (MGUS, n = 18) by ELISA/RIA techniques. Serum ICTP and urinary Dpd levels increased parallel to the stage of the disease and differed significantly (P< 0.001 for ICTP and P = 0.03 for Dpd) between MGUS, myeloma stage I, and myeloma in stages II and III according to Salmon and Durie. ICTP and Dpd were significantly elevated in patients with multiple myeloma in stage I compared to individuals with MGUS, while no significant difference was found for NTx. In this first study comparing the prognostic relevance of ICTP, NTx, and Dpd in multiple myeloma patients, ICTP was found to be a prognostic factor for overall survival in the Kaplan-Meier analysis (log-rank test: P < 0.03). Urinary NTx showed borderline significance (P = 0.05), and Dpd had no prognostic value in the survival analysis. Our data show that serum ICTP and urinary Dpd levels increase in parallel to advanced disease stages, and gives the first report on a significant difference in the bone resorption parameters ICTP and Dpd between individuals with MGUS and patients with myeloma in stage I. Among the bone resorption parameters studied serum ICTP was found to be the best prognostic factor for survival in multiple myeloma.

Biochemical markers of bone turnover in diagnosis of myeloma bone disease

“…These findings and the correlation between MIP-1a and markers of disease activity suggest that its use in the diagnosis of bone disease should be further evaluated considering its utility and low cost. The discrepancy between the levels of MIP-1a and Ctx measured in previous studies and our study may be due to the utility of different methods such as radioimmunoassay [6] for Ctx and different ELISA kits [27,28] for MIP-1a.…”

“…Previously, Ctx was shown to be both higher in MM patients with bone disease than in patients with Stages I and II disease, and to have a prognostic value in MM [6]. Ctx levels were measured by a competitive radioimmunoassay in the mentioned study.…”

“…There are a few studies about the use of biochemical markers of bone turnover in the diagnosis of myeloma bone disease. These studies generally compare the levels of these markers in MM patients with those in patients with MGUS [6] and osteoporosis [18,19], and in healthy controls [5]. In one study comparing Ctx, DPD, and BALP levels of MM patients with osteoporotic controls, only the DPD levels were found to be significantly higher in the patient group [18].…”

“…Recently, several bone-specific biochemical markers that constitute breakdown products of Type-1 collagen are being evaluated for their use in diagnosing and monitoring the activity of bone disease in MM, which demonstrate high levels of sensitivity and specificity [5,6]. They provide information about the dynamic processes of bone metabolism [5].…”

Incorporation of the bone marker carboxy-terminal telopeptide of type-1 collagen improves prognostic information of the International Staging System in newly diagnosed symptomatic multiple myeloma

“…14 In various studies, it was shown that serum carboxy-terminal telopeptide of type-1 collagen (ICTP) is a sensitive and specific marker of increased bone resorption [15][16][17] and has a prognostic impact for overall survival (OS) in MM patients. 16,18 In longitudinal studies, it was furthermore shown that ICTP had the highest predictive value for the progression of myeloma-induced bone disease in patients treated with standard chemotherapy 19 and that ICTP levels decrease in patients with MM under bisphosphonate treatment. 20 Recent studies demonstrated that bone markers, which reflect osteoclast and osteoblast activity, can be modulated by novel agents such as proteasome inhibitors or immunmodulatory drugs.…”