Patients with cirrhosis have elevated bone turnover but normal hepatic production of osteoprotegerin.
2021
CONTEXT Severe osteodystrophy is common in patients with liver dysfunction. Markers of bone metabolism may help in early diagnosis of osteodystrophy and in understanding underlying pathophysiological mechanisms. OBJECTIVE To elucidate changes in bone metabolism associated with cirrhosis and to determine the route of elimination for the markers. DESIGN Case-control study. SETTING Public university hospital. PATIENTS Fifty-nine patients with cirrhosis (47 alcoholic and 12 non-alcoholic cirrhosis), 20 controls. INTERVENTIONS Participants underwent catheterization of the femoral artery, and the hepatic, kidney and femoral veins with collection of blood from all four sites. MAIN OUTCOME MEASURES Regional arterio-venous differences in concentrations of bone metabolism markers were determined: procollagen of type I collagen propeptide (PINP), C-terminal cross-linking telopeptide of type I collagen (CTX), osteocalcin (OC), tartrate-resistant acid phosphatase isoform 5b (TRAcP5b), osteoprotegerin (OPG), and sclerostin and correlated with degree of disease (Child-Pugh Classification). RESULTS PINP concentration was higher (median: 87.9 µg/L) in patients with cirrhosis than in controls (52.6 µg/L)(p=0.001), while hepatic extraction was lower 4.3% vs. 14.5% (p<0.001). Both CTX and TRAcP5b were higher in cirrhotic patients (340 ng/L and 3.20 U/L) than in controls (215 ng/L and 1.60 U/L)(p<0.001 and p<0.0001). Hepatic sclerostin extraction was lower in cirrhotics (14.6%) than in controls (28.7%)(p<0.0001). In both groups OPG showed a hepatic release rate (production) of 6%. CONCLUSIONS Patients with cirrhosis have increased bone resorption, but unaltered bone formation. Sclerostin is eliminated through the liver while OPG is produced in the liver. Bone markers may prove useful in evaluating bone turnover in cirrhosis patients.
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