Elevated carboxy terminal cross linked telopeptide of type I collagen in alcoholic cirrhosis: relation to liver and kidney function and bone metabolism

Abstract

Background-The carboxy terminal cross linked telopeptide of type I collagen (ICTP) has been put forward as a marker of bone resorption. Patients with alcoholic liver disease may have osteodystrophy. Aims-To assess circulating and regional concentrations of ICTP in relation to liver dysfunction, bone metabolism, and fibrosis. Methods-In 15 patients with alcoholic cirrhosis and 20 controls, hepatic venous, renal venous, and femoral arterial concentrations of ICTP, and bone mass and metabolism were measured. Results-Circulating ICTP was higher in patients with cirrhosis than in controls. No overall significant hepatic disposal or production was found in the patient or control groups but slightly increased production was found in a subset of patients with advanced disease. Significant renal extraction was observed in the controls, whereas only a borderline significant extraction was observed in the patients. Measurements of bone mass and metabolism indicated only a mild degree of osteodystrophy in the patients with cirrhosis. ICTP correlated significantly in the cirrhotic patients with hepatic and renal dysfunction and fibrosis, but not with measurements of bone mass or metabolism. Conclusions-ICTP is highly elevated in patients with cirrhosis, with no detectable hepatic net production or disposal. No relation between ICTP and markers of bone metabolism was identified, but there was a relation to indicators of liver dysfunction and fibrosis. As the cirrhotic patients conceivably only had mild osteopenia, the elevated ICTP in cirrhosis may therefore primarily reflect liver failure and hepatic fibrosis. (Gut 1999;44:417-423) Keywords: bone mineral density; carboxy terminal cross linked telopeptide of type I collagen; chronic liver disease; fibrosis; hepatic osteodystrophy; portal hypertensionThe formation and resorption of bone are dynamic processes and the amount and composition of bone depend on a balance between the two.1 The rate of the individual processes may be estimated by measuring bone matrix components released into the circulation during formation or resorption.2 Type I collagen is the most abundant protein in the human body.3 Most is present in bone and constitutes more than 90% of the organic matrix; the remainder is found in soft connective tissues all over the body, primarily in the skin.1 Several studies have shown that the carboxy terminal propeptide of type I procollagen (PICP) may be a specific marker of bone formation but not of bone resorption.4-7 The carboxy terminal cross linked telopeptide of type I collagen (ICTP) seems to represent a new marker of type I collagen degradation. 7 8 It is released into the circulation during degradation of mature type I collagen primarily in bone, and hence it appears to be a potential marker of bone resorption. 9Metabolic bone diseases have been recognised for a long time in patients with chronic liver diseases, especially when the aetiology is cholestatic or alcoholic.10-15 However, the degree of hepatic osteodystrophy and the clinical severity are...

Bone disorders

“…Markers of bone resorption include urinary excretion of deoxypyridinoline, pyridinoline, and serum type 1 collagen cross-linked N telopeptide (P1NP). In several small studies of patients with cirrhosis, both markers of bone resorption and bone formation have been found to be independently affected by the degree of liver fibrosis, severity of liver disease, and coexistent renal function [31,32]. This means that repeat BMD is currently the only way of assessing the efficacy of treatment for osteoporosis in patients with cirrhosis.…”