Abstract
Introduction: Bone phenotype, such as osteoarthritis (OA) pattern and development of osteolysis or heterotopic ossification (HO) after THA, may be governed by genetic and environmental factors. We investigated whether single nucleotide polymorphisms within the gene encoding secreted-Frizzled Related Protein-3, FRZB Arg200Trp and FRZB Arg324Gly influence bone phenotype.
Methods: Genomic DNA was extracted from 609 subjects at a mean of 11 years following cemented THA for idiopathic osteoarthritis. Pre-operative OA was defined using The American College of Rheumatology criteria and post operative HO after primary THA was assessed using Brooker’s classification
Results: For FRZB Arg200Trp, minor allele carriage (MAC) was greater in subjects with pre-operative pelvic osteophytes (n=267) versus those without osteophytes (n=34) (MAC 27.9% versus 6.3%, Fisher’s exact test p=0.037). There were no associations with other radiographic criteria of OA. MAC was also higher in HO+ve subjects (n=291) versus HO-ve subjects (n=341), (MAC 21.7% versus 12.0%, χ2 test p=0.063). Finally MAC was 14.2% in osteolysis +ve subjects (n=268) and 21.7% in osteolysis –ve subjects (n=341) (χ2 test p=0.041).
The adjusted odds ratios for pelvic osteophytes and HO with carriage of the rare FRZB 200 variant were 4.34 (1.01–18.7 p=0.048) and 1.64 (1.05 to 2.54, p=0.028) respectively. The adjusted odds ratio for osteolysis was 0.62 (0.38 to 0.99 p=0.049).
There were no bone phenotype associations with the FRZB Arg324Gly variants.
Discussion: Carriage of the FRZB 200Trp allele is positively associated with osteophyte and HO formation and negatively associated with osteolysis, suggesting this locus may be a marker for pro-osteoblastic activity.
Correspondence should be addressed to Mr John Hodgkinson, BHS, c/o BOA, The Royal College of Surgeons, 35–43 Lincoln’s Inn Fields, London WC2A 3PE.
