Serum markers of bone metabolism in multiple myeloma: prognostic value of the carboxy‐terminal telopeptide of type I collagen (ICTP)

Abstract

Summary. This study was performed to evaluate the prognostic significance of serum markers of bone and collagen metabolism in multiple myeloma. Serum C-terminal telopeptide of type I collagen (ICTP) reflects degradation of bone, whereas serum osteocalcin, together with serum Cterminal propeptide of procollagen type I (PICP) and serum bone-specific alkaline phosphatase (bAP) reflect synthesis of bone matrix. The N-terminal propeptide of procollagen type III (PIIINP) in serum reflects synthesis of type III collagen. We analysed frozen sera from 109 patients with newly diagnosed multiple myeloma. g/l). Serum PICP was generally within the reference limits, whereas serum osteocalcin and serum bAP were elevated in 19% and 37%, respectively. Serum ICTP correlated with serum PIIINP, serum 2 -microglobulin ( 2 m), serum calcium, performance status, and stage. In univariate analysis, the test variables serum ICTP (P 0 . 026) and serum osteocalcin (P 0 . 036) were found to be of prognostic value, but PIIINP, PICP, or bAP in serum were not. Serum ICTP and serum 2 m had a similar prognostic value. In multivariate analysis, serum calcium showed the highest prognostic significance, and serum 2 m was the only other variable of independent prognostic value. However, in normocalcaemic patients, serum ICTP showed the highest prognostic significance, followed by serum osteocalcin. Thus, the serum levels of ICTP and osteocalcin seem related to bone turnover and calcium metabolism, and provide further information about myeloma activity, particularly in normocalcaemic patients.

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

“…Serum ICTP and urinary NTX were higher in myeloma stage II/III than in stage I disease. 44,48,53 High DPD urinary levels also correlated with advanced myeloma stage. 51,52 In 121 newly diagnosed myeloma patients, NTX and TRACP-5b, but not OC or bALP, strongly correlated with disease stage.…”

“…Table 3 summarizes the results of the most important studies to date regarding the levels of bone markers in MM patients. [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] As has been shown in multiple studies, urine levels of PYD, DPD and NTX and serum levels of CTX, ICTP and TRACP-5b were elevated in MM patients compared with healthy controls, and correlated with the extent of osteolytic disease. 46,48,[51][52][53][54][55][56][58][59][60] Urinary NTX levels were increased even in myeloma patients who had reached a clinical plateau phase of their disease, 61 whereas PYD, DPD and NTX were also elevated in myeloma patients before autologous transplantation.…”

“…[43][44][45][46][48][49][50][51]53,55,56 In some studies, bALP and OC were elevated in myeloma patients compared with controls, whereas in others they were either reduced or within normal limits. In a study by Fonseca et al, which included a large number of myeloma patients (n ¼ 313), serum bALP correlated with bone pain, lesions and fractures, whereas OC levels were lower in myeloma patients than in controls but did not correlate with the extent of bone disease.…”

“…PICP values do not seem to reflect the extent of myeloma bone disease. [43][44][45][46]48 As shown in Table 3, although markers of bone formation may be of some value in myeloma, they do not appear to reflect the extent of myeloma bone destruction. Thus at present, their clinical utility is doubtful.…”

“…48,51 Markers of bone remodeling have also correlated with wellcharacterized markers of disease activity, such as b2-microglobulin and interleukin-6 48,51,55,64 and also with overall survival (OS). 44,46,48,52,68,69 Fonseca et al showed that the median survival was 4.1 and 3.5 years for patients who received CC and had low or high ICTP levels, respectively (P ¼ 0.02). 48 Jakob et al also reported that ICTP is a prognostic factor for OS in MM patients treated with CC (Po0.03), whereas urinary NTX was only of borderline prognostic value (P ¼ 0.05).…”