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Patients with cirrhosis have elevated bone turnover but normal hepatic production of osteoprotegerin

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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.

METHODS: Case-control study at a public university hospital. Fifty-nine patients with cirrhosis (47 alcoholic and 12 nonalcoholic cirrhosis) and 20 controls were included. Participants underwent catheterization of the femoral artery, and the hepatic, renal, and femoral veins with collection of blood from all 4 sites. Regional arteriovenous 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, 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 = .001), while hepatic extraction was lower (4.3% vs 14.5%) (P < .001). Both CTX and TRAcP5b were higher in patients with cirrhosis (340 ng/L and 3.20 U/L) than in controls (215 ng/L and 1.60 U/L) (P < .001 and P < .0001). Hepatic sclerostin extraction was lower in patients with cirrhosis (14.6%) than in controls (28.7%) (P < .0001). In both groups OPG showed a hepatic release rate (production) of 6%.

CONCLUSION: 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 patients with cirrhosis.

TidsskriftThe Journal of clinical endocrinology and metabolism
Udgave nummer3
Sider (fra-til)e980-e995
Antal sider16
StatusUdgivet - 1 mar. 2022

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© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail:

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