Involving research users in setting priorities for research is essential to ensure research outcomes are patient-centred and to maximise research value and impact. The Musculoskeletal (MSK) Disorders Research Advisory Group Versus Arthritis led a research priority setting exercise across MSK disorders. The Child Health and Nutrition Research Initiative (CHRNI) method of setting research priorities with a range of stakeholders were utilised. The MSKD RAG identified, through consensus, four research Domains: Mechanisms of Disease; Diagnosis and Impact; Living Well with MSK disorders and Successful Translation. Following ethical approval, the research priority exercise involved four stages and two surveys, to: 1) gather research uncertainties; 2) consolidate these; 3) score uncertainties using agreed criteria of importance and impact on a score of 1–10; and 4) analyse scoring, for prioritisation.Background
Methods
This paper reports on a proof of concept project funded by the UK National Council for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), with the aim of developing an
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.
In-vitro evidence suggests that wear debris can alter osteoblast function resulting in decreased bone matrix production and negative remodelling balance. FRZB encodes for Secreted Frizzled-Related Protein 3 which may play a role in bone formation and osteoarthritis. This study was undertaken to investigate whether the recently described single nucleotide polymorphisms (SNPs) at positions [+6] and [+109] of the FRZB gene are associated with osteolysis after THA. Genomic DNA was extracted from 481 North European Caucasians at a mean of 12 years following cemented THA for idiopathic osteoarthritis. The control group consisted of 267 subjects and the osteolysis group 214 subjects. The [+6] and [+109] FRZB SNPs were genotyped using standard techniques. For the FRZB [+6] SNP, the rare T allele was significantly over-represented in control versus the osteolysis group (χ2 test for trend, p=0.02,). The odds ratio for osteolysis associated with carriage of the [+6] T-allele versus the [+6] C-allele was 0.58 (95%CI 0.36 to 0.94), p=0.03. The odds ratio for osteolysis associated with carriage of the [+109] G-allele versus the [+109] C-allele was 0.66 (0.38 to 1.12), p=0.15. A number of covariates have previously been described in this cohort and after adjustment for the effects of these covariates, the odds ratio for osteolysis with carriage of the [+6] T-allele was 0.69 (0.42–1.16). We found that the FRZB [+6] T-allele is less common in subjects with osteolysis after THA versus controls, suggesting that allelic variants of genes associated with bone formation pathways may have a role in modulating the risk of osteolysis. However its loss of significance after correction for other factors suggests an interaction between this allele and other risk factors in osteolysis.
From a prospective, cross-sectional survey of 402 patients who had a total hip (THR) or a total knee (TKR) replacement for idiopathic osteoarthritis (OA) at a major centre, we determined the prevalence of these replacements for idiopathic OA in their 1171 siblings and 376 spouses. Using spouses as controls, the relative risk of THR in siblings was 1.86 (95% CI 0.93 to 3.69). The relative risk for TKR in siblings The increased risks of joint replacement for severe, idiopathic OA which we found in siblings suggest that genetic influences are important in end-stage OA of the hip and knee.
