Clinical utility of C‐terminal telopeptide of type 1 collagen in multiple myeloma

Abstract

Myeloma bone disease (MBD) is a major cause of morbidity in multiple myeloma (MM). We investigated bone turnover markers (BTM) as relapse predictors and biomarkers for monitoring MBD. We measured C-terminal telopeptide of type I collagen (CTX-1), and Procollagen type 1 N Propeptide (P1NP) in 86 MM patients and 26 controls. CTX-1 was higher in newly diagnosed patients compared to control, remission and relapse (P < 0·05), and decreased following treatment. In the setting of relapse, a CTX-1 rise greater than the calculated least significant change (LSC) was observed in 26% of patients 3-6 months prior to relapse (P = 0·007), and in 60·8% up to 3 months before relapse (P = 0·015). Statistically significant changes in CTX-1 levels were also observed in patients who were with and without bisphosphonate therapy at the time of relapse. In patients with normal renal function, mean CTX-1 level was highest in the newly diagnosed group (0·771 ± 0·400 μg/l), and lowest in the remission group (0·099 ± 0·070 μg/l) (P < 0·0001). P1NP levels were not statistically different across the patient groups. We conclude that CTX-1, measured on an automated hospital laboratory platform, has a role in routine treatment monitoring and predicting relapse of MBD, even in patients on bisphosphonates.

Modern markers for evaluating bone disease in multiple myeloma (Review)

“…Ting et al presented in a research paper, a significantly elevated level of CTX-1 in patients with lytic lesions, whose MRI showed no bone marrow abnormalities or lytic bone destruction. The study conclusions highlight the important role of CTX-1 in predicting subclinical bone disease before lithic bone destruction occurs (38).…”

“…The degree of imbalance between bone resorption and bone formation can be expressed by the ratio of β-CTx/PINP (type I procollagen amino terminal propeptide). Studies have shown that CTx and PINP are important parameters values for clinical evaluation of osteoclast and osteoblast activity (38).…”

“…In myeloma bone disease (MBD), an increased RANKL production in the bone microenvironment of MM, alters the RANKL/OPG ratio, leading to increased collagen degradation in the osteoclastic-mediated bone matrix. Bone resorption markers obtained from type I collagen degradation are type I C-terminal cross-linking telopeptide (CTX-1) and type 1 N-terminal cross-linking telopeptide (NTX-1) (38,42).…”

Advanced Imaging of Multiple Myeloma Bone Disease

“…MGUS and SMM are associated with osteopenia, altered bone microstructure, and an increased rate of bone resorption and overall fracture risk ( 11 , 12 , 20 ). Biochemical markers of bone resorption such as serum carboxy-terminal telopeptide of type-I collagen (CTX-1) and urine deoxypyridinoline (DPD) correlate with disease burden in patients with MGUS as compared with MM ( 21 , 22 ), and MGUS patients have reduced levels of bone-specific alkaline phosphatase, a cell membrane-associated enzyme produced by osteoblasts, as compared to patients with non-malignant osteoporosis ( 23 ).…”

Mielomas pacientu bioķīmisko marķieru un morfoloģisko rādītāju prognostiskās nozīmes analīze kaulu slimības attīstībā. Promocijas darbs

“…Marķieri ir prognostiski faktori, kas var paredzēt ar skeletu saistītu notikumu attīstības risku un kaulu bojājumu progresiju MM pacientiem. Tos izmanto arī antirezorbtīvās terapijas efekta noteikšanā un pacientu ar augstu slimības progresijas risku identifikācijai(Lipton et al, 2007(Lipton et al, , 2010Chu et al, 2016;Ting et al, 2013Ting et al, , 2016. Šie tipi savukārt ir iedalīti 3 mielomas šūnu prognostiskās grupās: zemas malignitātes (Maršalko un sīko/mazo šūnu), vidējas malignitātes (šķelto šūnu, polimorfo un asinhrono) un augstas malignitātes pakāpes (plazmoblastisko šūnu tips)(Bartl et al, 1987).Bisfosfonāti nesamazina jau esošus kaulu bojājumus, bet tie novērš un aizkavē jaunu bojājumu veidošanos.…”