Vitamin D and osteocalcin levels in liver transplant recipients: Is osteocalcin a reliable marker of bone turnover in such cases?

doi:10.1016/S0168-8278(05)80093-5

Journal of Hepatology

Volume 16, Issues 1–2, 1992, Pages 50-55

https://doi.org/10.1016/S0168-8278(05)80093-5 Get rights and content

Patients with advanced liver disease are at increased risk for the development of hepatic osteodystrophy in the form of either osteomalacia or osteoporosis. The pathogenesis of these two bone diseases is multifactorial and includes, among other factors, alterations in vitamin D metabolism, malnutrition and hypogonadism. Little is known regarding vitamin D metabolism and the osteoblastic activity in liver transplant recipients. In order to clarify these issues, vitamin D metabolites and osteocalcin levels were measured prior to and 30 days following liver transplantation in 30 cirrhotic patients of various etiologies. While the mean plasma concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D of the entire group of 30 patients were significantly greater prior to orthotopic liver transplantation (OLTx) as compared to those after OLTx (11.5 ± 8.6 vs. 7.4 ± 5.8 ng/ml, p = 0.0066 and 41.0 ± 34.6 vs. 20.4 ± 11.0 pg/ml, p = 0.0003, respectively), no significant changes in osteocalcin concentrations pre- or post-transplantation could be demonstrated (5.2 ± 3.0 vs. 6.4 ± 4.1 ng/ml, p = 0.51). Furthermore, no correlation between the plasma concentration of osteocalcin and either vitamin D metabolite, the prothrombin time or cyclosporine levels was found. The reasons for the normal levels of osteocalcin prior to OLTx can be explained by the fact that in vitamin-K-deficient states osteocalcin is predominantly decarboxylated and, therefore, a smaller proportion is bound to bone and/or the synthesis of osteocalcin is partially modulated by 1,25-dihydroxyvitamin D, the level of which has been found to be normal. The effect of cyclosporine on bone formation could explain the normal levels of osteocalcin in the post-OLTx period despite the suppressive effect of corticosteroids. The reduction in vitamin D levels seen following OLTx was probably a result of the corticosteroid therapy used postoperatively. Based upon these data, it can be concluded that osteocalcin levels in liver transplant recipients treated with a combination of cyclosporine/prednisone are usually within normal limits, probably as a result of the opposite pharmacologic effects of each drug on bone remodeling. As a result, osteocalcin levels may not be a reliable marker of bone formation in liver transplant recipients, at least in the early postoperative period.

References (43)

PreeceMA et al.
A competitive protein binding assay for 25-hydroxycholecalciferol and 25-hydroxyergocalciferol in serum
Clin Chim Acta
(1974)
KrawittEL et al.
Absorption, hydroxylation, and excretion of vitamin D₃ in primary biliary cirrhosis
Lancet
(1977)
WagonfeldJB et al.
Comparison of vitamin D and 25-hydroxivitamin D in the therapy of primary biliary cirrhosis
Lancet
(1976)
SkinnerRK et al.
25-Hydroxylation of vitamin D in primary biliary cirrhosis
Lancet
(1977)
LongRG et al.
Formation of vitamin D metabolites from ³H and ¹⁴C-radiolabelled vitamin D₃ in chronic liver disease
Clin Chim Acta
(1978)
ReedJS et al.
Bone disease in primary biliary cirrhosis: reversal of osteomalacia with oral 25-hydroxyvitamin D
Gastroenterology
(1980)
LongRG
Hepatic osteodystrophy: outlook good but some problems unsolved
Gastroenterology
(1980)
KellyPJ et al.
Potential protection by cyclosporin against glucocorticoid effects on bone
Lancet
(1989)
AubiaJ et al.
Bone histology in renal transplant patients receiving cyclosporin
Lancet
(1988)
HaagsmaEB et al.
Bone disease after orthotopic liver transplantation
J Hepatol
(1988)

CompstonJE

Hepatic osteodystrophy: vitamin D metabolism in patients with liver disease

Gut

(1986)

Calcium and chronic liver disease

Lancet

(1987)

DibbleJB et al.

Osteomalacia, vitamin D deficiency and cholestasis in chronic liver disease

Q J Med

(1982)

LianJB et al.

Osteocalcin: biochemical considerations and clinical applications

Clin Orthop Rel Res

(1988)

LianJ et al.

Structure of the rat osteocalcin gene and vitamin D-dependent expression

MarkoseER et al.

Vitamin D mediated modifications in protein-DNA interactions of two promoter elements of the osteocalcin gene

KnapenMHJ et al.

The effect of vitamin K supplementation on circulating osteocalcin (bone Gla protein) and urinary calcium excretion

Ann Intern Med

(1989)

PettiforJM et al.

Congenital malformations associated with the administration of oral anticoagulants during pregnancy

J Pediatr

(1975)

ReinhardtTA et al.

A microassay for 1,25-dihydroxyvitamin D not requiring high performance liquid chromatography: application to clinical studies

J Clin Endocrinol Metab

(1984)

GundbergCM et al.

Osteocalcin: isolation, characterization and detection

Methods Enzymol

(1984)

DaviesM et al.

Vitamin D deficiency, osteomalacia, and primary biliary cirrhosis. Response to orally administered Vitamin D₃

Dig Dis Sci

(1983)

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Regular PaperVitamin D and osteocalcin levels in liver transplant recipients: Is osteocalcin a reliable marker of bone turnover in such cases?

Clin Chim Acta

Lancet

Lancet

Lancet

Clin Chim Acta

Gastroenterology

Gastroenterology

Lancet

Lancet

J Hepatol

Hepatic osteodystrophy: vitamin D metabolism in patients with liver disease

Gut

Calcium and chronic liver disease

Lancet

Osteomalacia, vitamin D deficiency and cholestasis in chronic liver disease

Q J Med

Osteocalcin: biochemical considerations and clinical applications

Clin Orthop Rel Res

Structure of the rat osteocalcin gene and vitamin D-dependent expression

Vitamin D mediated modifications in protein-DNA interactions of two promoter elements of the osteocalcin gene

The effect of vitamin K supplementation on circulating osteocalcin (bone Gla protein) and urinary calcium excretion

Ann Intern Med

Congenital malformations associated with the administration of oral anticoagulants during pregnancy

J Pediatr

A microassay for 1,25-dihydroxyvitamin D not requiring high performance liquid chromatography: application to clinical studies

J Clin Endocrinol Metab

Osteocalcin: isolation, characterization and detection

Methods Enzymol

Vitamin D deficiency, osteomalacia, and primary biliary cirrhosis. Response to orally administered Vitamin D3

Dig Dis Sci

Regular Paper
Vitamin D and osteocalcin levels in liver transplant recipients: Is osteocalcin a reliable marker of bone turnover in such cases?

Vitamin D deficiency, osteomalacia, and primary biliary cirrhosis. Response to orally administered Vitamin D₃