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Variation in the secreted frizzled-related protein-3 gene and risk of Osteolysis and heterotopic ossification after total hip arthroplasty

Lookup NU author(s): Professor John LoughlinORCiD


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Secreted frizzled-related protein-3 (sFRP3) antagonizes ligands that promote new bone formation in adult tissues. We examined whether variation in the FRZB gene that encodes sFRP3 is associated with development of osteolysis or heterotopic ossification (HO) after total hip arthroplasty (THA). Genomic DNA was extracted from 609 subjects (osteolysis group n = 268) at a mean of 11 years following cemented THA for idiopathic osteoarthritis and genotyped for the FRZB Arg200Trp and Arg324Gly polymorphisms. The Brooker classification was used to assess HO following primary THA in 563 of the subjects. The carriage rate of the FRZB 200Trp allele was 14.2% in subjects with osteolysis versus 21.0% in controls (p = 0.041). The carriage rate of this allele was 21.7% in subjects with HO (n = 299) versus 12.0% in those without HO (p = 0.063). The odds ratio for osteolysis with carriage of FRZB 200Trp was 0.62 (95% CI 0.38 to 0.99; p = 0.049) and for HO was 1.64 (1.05 to 2.54; p = 0.028), after adjustment for the effects of other risk factors associated with the development of osteolysis or HO. Variants in the FRZB 324 locus alone were not associated with osteolysis or HO. However, the most frequent haplotype (FRZB 200Arg:324Arg) was associated with osteolysis (OR 1.50, 95% CI 1.09 to 2.07; p = 0.014). Our data suggest that the FRZB Arg200Trp locus may be a marker for pro-osteoblastic activity after THA. Carriage of the FRZB 200Trp allele is associated with a "positive" bone balance phenotype (osteolysis -: HO+). (c) 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Publication metadata

Author(s): Gordon A, Southam L, Loughlin J, Wilson AG, Stockley I, Hamer AJ, Eastell R, Wilkinson JM

Publication type: Article

Publication status: Published

Journal: Journal of Orthopaedic Research

Year: 2007

Volume: 25

Issue: 12

Pages: 1665-1670

ISSN (print): 0736-0266

ISSN (electronic): 1554-527X

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/jor.20446


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