Degradation Product Of Collagen Type 1 Carboxy Terminal Telopeptide (ICTP) as a Novel Bone Resorption Marker In Multiple Myeloma

Abstract

Multiple myeloma (MM) is a B-cell malignancy characterized by proliferation of monoclonal plasma cells in the bone marrow. The reason for the high incidence of bone disease in MM is that the myeloma cells produce several factors that stimulate osteoclast (OC) formation and activity and inhibit osteoblast (OB) function and bone formation. Substantial damage may have occurred in bone before the patient becomes symptomatic and progressive bone disease is detected. Biochemical markers of bone turnover may represent an interesting complementary of radiological examination to evaluate the bone status of myeloma patients. They are not harmful and are compatible with monthly monitoring. They have the potential to detect the destructive process as soon as it starts and may be even before a lesion becomes detectable through conventional radiography. Despite their potential interest, markers of bone remodeling are not used in everyday practice, and their usefulness to detect progressive osteolysis in relapsing patients has not yet evaluated of special importance. This gap appears to be as the typical patient with MM undergoes relapses and remissions multiple times. One of the biochemical markers is ICTP, which is the degradation product of the chain C telopeptide of type 1 collagen the main extracellular matrix component, it is assessed by ELISA and levels of which are supposed to reflect changes in the extracellular matrix and is categorized as a bone resorption marker. This study aims to determine the significance of collagen type I carboxy terminal telopeptide (ICTP) as a marker of osteolysis, and as a predictor of bone lesions compared with the standard prognostic factors of MM. Our study included 20 newly diagnosed MM patients and 20 age and sex matched healthy individuals as a control, the osteolytic marker ICTP was significantly higher in MM patients compared to controls. According to the radiological findings MM patients were divided into two groups (group A) including patients with osteolytic lesion and (group B) including patients without osteolytic lesion. ICTP levels were found to be correlated with radiological findings being significantly higher in patients with osteolytic lesion. Significant positive correlation was found between ICTP levels and the level of hypercalcemia as a marker of osteolysis, also ICTP levels correlated with markers of renal impairmentincludingelevated serum creatinine and elevated serum BUN while regarding hematological data we found significant negative correlation between ICTP and the degree of anemia and thrombocytopenia. Regarding the prognostic factors of MM, results of our study revealed the presence of significant positive correlation between ICTP level and the standard prognostic factors of MM including β2M, CRP and LDH, suggestingthat ICTP may be regarded as poor prognostic factor in MM. On the other hand, significant negative correlation was found between ICTP level and hypoalbuminaemia indicating the significance of ICTP level as a marker of disease severity. While no significant correlation was found between ICTP level and pattern and degree of plasma cells infiltration in trephine biopsy. By using logistic regression in analysis of ICTP, β2M and CRP as predictors of osteolysis our study revealed that ICTP, B2M and CRP were significant predictors of osteolysis. ICTP was statistically the most significant predictor of osteolytic changes.