Title: ICTP as a Diagnostic Marker of Bone Resorption and Its Relation to Disease Progression and Treatment Response in Multiple Myeloma
Authors: Salwa Saad Khoudair, Gehan Mostafa Hamed
DOI: http://dx.doi.org/10.18535/jmscr/v4i5.28
Abstract
Aim: To assess the significance of collagen type I carboxy terminal telopeptide (ICTP) as a diagnostic marker of osteolysis, as well as its relation to disease progression and response to treatment in multiple myeloma (MM).
Subject and methods: ICTP was measured in 40 newly diagnosed MM patients (including 22 patients with osteolytic lesion), and 20 age- and sex- matched controls. Patients were followed up for detection of their response to treatment.
Results: The median and IQR levels of ICTP were significantly elevated in MM patients compared with controls (0.65 [0.15-0.8] ng/mL versus 0.05 [0.04-0.07] ng/mL, p<0.001), with significant higher median levels among patients with osteolytic lesion compared with myeloma patients without osteolytic lesion (0.7 [0.65 – 1.0] ng/mL versus 0.1 [0.1 -0.2] ng/mL, p<0.001). According to ROC curve analysis, ICTP at a cutoff 0.3 ng/mL could detect osteolytic lesion with high sensitivity and specificity. ICTP was positively correlated with markers of renal impairment, hypercalcemia, anemia, thrombocytopenia and poor prognostic factors; lactate dehydrogenase (LDH), C reactive protein (CRP), hypoalbuminaemia, and β2-microglobulin (β2M) (p<0.05). Using logistic regression analysis, ICTP was found to be a significant predictor of osteolysis. Moreover, initial ICTP levels were higher in progressive/relapsed myeloma patients compared with responsive/stable patients (p<0.001).
Conclusion: We suggest that ICTP is a reliable marker that can be used in the diagnosis and prediction of osteolytic lesion and prediction of treatment response in MM.
Key words: Multiple myeloma, ICTP, osteolytic marker, disease progression, response to treatment.
References
1. Turesson I, Velez R, Kristinsson SY, Landgren O. Pattern of MM during the last 5 decades: stable incidence rates for all groups in the population but rapidly changing age distribution in the clinic. Mayo Clinic Proceedings. 2010;85:225-230.
2. Palumbo A, Kenneth Anderson. Multiple Myeloma. N Engl J Med. 2011;364:1046-1060.
3. Dimopoulos MA, Terpos E. Renal insufficiency and failure. Hematology Am Soc Hematol Educ Program 2010; 2010: 431–436.
4. Hinge M, Lund T, Delaisse J, Plesner T. Bone disease in Multiple Myeloma. INTECH Open Access Publisher, 2013.
5. San-Miguel J, Bladé J. Multiple Myeloma. In: Hoffbrand AV, Catovsky D, Tuddenham E, Green A (eds). Post Graduate Hematology. 6th edn. NJ, USA: Blackwell Publishing Ltd;2011,pp:577-597.
6. Abildgaard N, Glerup H, Rungby J, dix-Hansen K, Kassem M, Brixen K. Biochemical markers of bone metabolism reflect osteoclastic and osteoblastic activity in multiple myeloma. Eur J Hematol 2010;84:412–420.
7. Lombardi G, Lanteri P, Colombini A, Banfi G. Blood biochemical markers of bone turnover: Pre- analytical and technical aspects of sample collection and handling. Clin Chem Lab Med.2012; 50:771-789.
8. Gordon MK, Hahn RA. Collagens. Cell Tissue Res 2010; 339:247-257.
9. Chopin F, Biver E, Funck-Brentano T, Bouvard B, Coiffier G, Garnero P, Thomas T. Prognostic interest of bone turnover markers in the management of postmenopausal osteoporosis. Joint Bone Spine.2012;79:26-31.
10. Tezvergil A, Mutluay M, Seseogullari R, Agee K, Key W, Scheffel D, et al. Effect of phosphoric acid on the degradation of human dentin matrix. J Dent Res 2013;92: 87-91.
11. Torres P. Biological parameters for the diagnosis of bone turnover in dialysis patient. Nephrology and Clinical Chemistry: The Essential Link. 2012:106-121.
12. McKenna RW, Kyle RA, Kuehi WM, Grogan TM, Harris NL, Coupland RW. Plasma cell myeloma In: Steven HS, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (eds). WHO Classification of tumours of hematology and lymphoid tissues.4 th edn. Lyon, France:International agency for research on cancer (IARC) 2008, 200-213.
13. Kyle R, Rajkumar S. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, UK. 2009;23(1):3-9.
14. Djunic I, Elezovic I, Marinkovic M, Suvajdzic-Vukovic N, Tomin D, Jankovic G, et al. Osteolytic lesions marker in multiple myeloma. Med Oncol.2011;28:237-240.
15. Kuliszkiewicz-Janus M, Malecki R, Zóltaszek A, Zastawny M. The significance of carboxy-terminal telopeptide of type I collagen (ICTP) and osteocalcin (OC) in assessment of bone disease in patients with multiple myeloma. Leuk Lymphoma 2005; 46:1749–1753.
16. Terpos E, Szydlo R, Apperley JF, Hatjiharissi E, Politou M, Meletis J, et al. Soluble receptor activator of nuclear factor κB ligand osteoprotegerin ratio predicts survival in multiple myeloma: proposal for a novel prognostic index. Blood 2003;102:1064-1069.
17. Jakob C, Zavirski I, Heider U, Bollow M, Schulz CO, Fleissner C, et al. Serum levels of carboxyterminal telopeptide of type-I collagen are elevated in patients with multiple myeloma showing skeletal manifestations in magnetic resonance imaging but lacking lytic bone lesions in conventional radiography. Clin Cancer Res. 2003;9:3047–3051.
18. Batallie R, Chappard D, Marcelli C, Rossi JF, Dessauw P, Baldet P, et al. Osteoblast stimulation in multiple myeloma lacking lytic bone lesions. Br J Haematol.1990;76:484–487.
19. Abilgaard N, Glerup H, Rungby J, Bendix-Hansen K, Kassem M, Brixen K et al. Biochemical markers of bone metabolism reflect osteoclastic and osteoblastic activity in multiple myeloma. Eur J Haematol. 2000;64:124–129.
20. Bačovský J, Ščudla V, Vytřasová M, Budíková M, Mysliveček M. Monitoring of bone resorption and bone formation in multiple myeloma. Biomed Paper.2002;146:59–61.
21. Abildgaard N, Brixen K, Eriksen EF, Kristensen JE, Nielsen JL, Heickendorff L. Sequential analysis of biochemical markers of bone resorption and bone densitometry in multiple myeloma. Haematologica 2004;89:567–577.