title: Diagnostic accuracy of bone turnover markers as a screening tool for aseptic loosening after total hip arthroplasty.
abstract: Aseptic loosening is the most common cause of prosthesis failure after total hip arthroplasty (THA). We measured serum cross-linked carboxyterminal telopeptide of type I collagen (ICTP), tartrate-resistant acid phosphatase 5b (TRAP5b), dickkopf-1 (dkk-1) and sclerostin; and urinary α isomer of C-terminal cross-linked telopeptide of type I collagen (αCTX-I) to investigate their potential diagnostic value detecting aseptic loosening after THA. Biomarkers were measured in 24 subjects with aseptic loosening of THA versus 26 control subjects without loosening after THA. Serum ICTP in the loose group (7.04 ng/mL) was higher than controls (5.15 ng/mL), (p = 0.0007). ROC analysis demonstrated that a serum ICTP >5.5 ng/L had a sensitivity of 91% and specificity of 69% for detecting aseptic loosening (area under ROC curve = 0.77, p = 0.0001), resulting in a positive predictive value (PPV) of 73% and a negative predictive value (NPV) of 90%. Serum TRAP5b in the aseptic loosening group (4.17U/L) was higher than controls (3.44 U/L), (p = 0.03). A serum TRAP5b >2.46 U/L had sensitivity of 100% and a specificity of 31% to detect aseptic loosening (AUC 0.67, p = 0.031), resulting in a PPV of 57% and a NPV of 100%. Serum dkk-1, serum sclerostin and urinary αCTX-I were not elevated in subjects with aseptic loosening (p>0.05). Serum ICTP and TRAP5b show potential utility as screening biomarkers for excluding aseptic loosening, because of their ability to discriminate individuals without disease. Our finding of elevated ICTP, generated by the action of matrix metalloproteinases, suggests a role for this group of endopeptidases in aseptic loosening.
authors.affiliation: The University of Sheffield, Sheffield - UK.
authors.forename: Neil R
authors.initials: NR
authors.lastname: Lawrence
authors.affiliation: The University of Sheffield, Sheffield - UK.
authors.forename: Raveen L
authors.initials: RL
authors.lastname: Jayasuriya
authors.affiliation: The University of Sheffield, Sheffield - UK.
authors.forename: Fatma
authors.initials: F
authors.lastname: Gossiel
authors.affiliation: The University of Sheffield, Sheffield - UK.
authors.forename: J Mark
authors.initials: JM
authors.lastname: Wilkinson
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000369:Aged, 80 and over; D019644:Arthroplasty, Replacement, Hip; D015415:Biomarkers / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000097:blood; D016723:Bone Remodeling / Q000502:physiology*; D016022:Case-Control Studies; D024042:Collagen Type I / Q000097:blood; D005260:Female; D005819:Genetic Markers; D006622:Hip Prosthesis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D007527:Isoenzymes / Q000097:blood; D008297:Male; D015207:Osteoarthritis, Hip / Q000097:blood* / Q000601:surgery; D010455:Peptides / Q000097:blood; D011237:Predictive Value of Tests; D011475:Prosthesis Failure; D012372:ROC Curve; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; D010455:Peptides; C422903:SOST protein, human; C052929:collagen type I trimeric cross-linked peptide; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase