title: The proportion of carboxylated to total or intact osteocalcin in serum discriminates warfarin-treated patients from control subjects.
abstract: We assessed the serum concentration of gamma-carboxylated osteocalcin (OC), total OC, and full-length OC in a clinical setting of 37 patients on continuous warfarin treatment (international normalized ratio 2.0-3.8). A comparison was done with the results from 30 untreated age-matched controls. Four monoclonal antibodies, previously generated and characterized as to their ability to recognize different human OC forms and fragments, were used in three two-site immunofluorometric assays. The warfarin-treated patients had significantly lower levels of carboxylated OC 4.9 +/- 3.8 (+/- 1 SD) ng/ml compared with the controls 13.1 +/- 9.7 (p < 0.0001). There was no difference in the levels of total OC or full-length OC between the two groups of patients. A strong correlation was found between the serum concentration of carboxylated OC and total OC, both for the warfarin-treated patients (r = 0.98) and for the controls (r = 0.99). There was a distinct cut-off level at 0.80, in the quotient carboxylated OC/total OC, at which all warfarin-treated patients fell below and all controls above this level. Hence, the concentration or ratio of serum gamma-carboxylated OC in clinical settings such as warfarin-treated patients could be measured using two-site immunoassays.
authors.affiliation: Department of Orthopaedics, Lund University, University Hospital, Malmö, Sweden.
authors.forename: K J
authors.initials: KJ
authors.lastname: Obrant
authors.forename: S M
authors.initials: SM
authors.lastname: Käkönen
authors.forename: J
authors.initials: J
authors.lastname: Astermark
authors.forename: H
authors.initials: H
authors.lastname: Lilja
authors.forename: T
authors.initials: T
authors.lastname: Lövgren
authors.forename: K
authors.initials: K
authors.lastname: Akesson
authors.forename: K
authors.initials: K
authors.lastname: Pettersson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D002264:Carboxylic Acids / Q000737:chemistry; D016022:Case-Control Studies; D005260:Female; D050723:Fractures, Bone / Q000209:etiology; D006331:Heart Diseases / Q000097:blood / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D012307:Risk Factors; D013923:Thromboembolism / Q000097:blood / Q000188:drug therapy; D014859:Warfarin / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D002264:Carboxylic Acids; D015675:Osteocalcin; D014859:Warfarin