Radiographic endophenotyping in hip osteoarthritis improves the precision of genetic association analysis.

OBJECTIVE: Osteoarthritis (OA) has a strong genetic component but the success of previous genome-wide association studies (GWAS) has been restricted due to insufficient sample sizes and phenotype heterogeneity. Our aim was to examine the effect of clinically relevant endophenotyping according to site of maximal joint space narrowing (maxJSN) and bone remodelling response on GWAS signal detection in hip OA. METHODS: A stratified GWAS meta-analysis was conducted in 2118 radiographically defined hip OA cases and 6500 population-based controls. Signals were followed up by analysing differential expression of proximal genes for bone remodelling endophenotypes in 33 pairs of macroscopically intact and OA-affected cartilage. RESULTS: We report suggestive evidence (p<5×10-6) of association at 6 variants with OA endophenotypes that would have been missed by using presence of hip OA as the disease end point. For example, in the analysis of hip OA cases with superior maxJSN versus cases with non-superior maxJSN we detected association with a variant in the LRCH1 gene (rs754106, p=1.49×10-7, OR (95% CIs) 0.70 (0.61 to 0.80)). In the comparison of hypertrophic with non-hypertrophic OA the most significant variant was located between STT3B and GADL1 (rs6766414, p=3.13×10-6, OR (95% CIs) 1.45 (1.24 to 1.69)). Both of these associations were fully attenuated in non-stratified analyses of all hip OA cases versus population controls (p>0.05). STT3B was significantly upregulated in OA-affected versus intact cartilage, particularly in the analysis of hypertrophic and normotrophic compared with atrophic bone remodelling pattern (p=4.2×10-4). CONCLUSIONS: Our findings demonstrate that stratification of OA cases into more homogeneous endophenotypes can identify genes of potential functional importance otherwise obscured by disease heterogeneity.

The management and mortality of patients undergoing hip fracture surgery following recent acute myocardial infarction.

Having major elective surgery within 6 months of an Acute Myocardial Infarction carries an increased risk of re-infarction and death. However delaying surgery in patients with proximal femoral neck fractures would most likely lead to complications secondary to prolonged immobilisation and also provide difficulties with regards to nursing care. The aim of this retrospective study was to assess the mortality of hip fracture patients with a recent myocardial infarction that have undergone surgery at our institution. During the period January 2005 to September 2007, twenty-five patients were identified with an Acute Myocardial Infarction around the time of admission but prior to surgical treatment. There were 20 female and 5 male patients with an average age of 88 years (range: 78 to 98). All patients underwent surgery between 1 and 12 days post Acute Myocardial Infarction. We report mortality rates of 28% and 40% at 1 and 6 months respectively, which is much higher than that of the overall proximal femoral neck fracture population. This group of patients can provide a major dilemma to surgeons and anaesthetists alike with respect to the type and timing of surgery. We hope that this data, the largest published series to date, can provide accurate and timely prognostic information to not only clinicians, but also patients and relatives at such a difficult time.

Is a periacetabular osteotomy as efficacious in retroversion as it is in dysplasia? : The role of femoral anteversion on outcome.

AIMS: Periacetabular osteotomy (PAO) is an established treatment for acetabular dysplasia. It has also been proposed as a treatment for patients with acetabular retroversion. By reviewing a large cohort, we aimed to test whether outcome is equivalent for both types of morphology and identify factors that influenced outcome. METHODS: A single-centre, retrospective cohort study was performed on patients with acetabular retroversion treated with PAO (n = 62 hips). Acetabular retroversion was diagnosed clinically and radiologically (presence of a crossover sign, posterior wall sign, lateral centre-edge angle (LCEA) between 20° and 35°). Outcomes were compared with a control group of patients undergoing PAO for dysplasia (LCEA < 20°; n = 86 hips). Femoral version was recorded. Patient-reported outcome measures (PROMs), complications, and reoperation rates were measured. RESULTS: The mean Non-Arthritic Hip Score (NAHS) preoperatively was 58.6 (SD 16.1) for the dysplastic hips and 52.5 (SD 12.7) for the retroverted hips (p = 0.145). Postoperatively, mean NAHS was 83.0 (SD 16.9) and 76.7 (SD 17.9) for dysplastic and retroverted hips respectively (p = 0.041). Difference between pre- and postoperative NAHS was slightly lower in the retroverted hips (18.3 (SD 22.1)) compared to the dysplastic hips (25.2 (SD 15.2); p = 0.230). At mean 3.5 years' follow-up (SD 1.9), one hip needed a revision PAO and no hips were converted to total hip arthroplasty (THA) in the retroversion group. In the control group, six hips (7.0%) were revised to THA. No differences in complications (p = 0.106) or in reoperation rate (p = 0.087) were seen. Negative predictors of outcome for patients undergoing surgery for retroversion were female sex, obesity, hypermobility, and severely decreased femoral anteversion. CONCLUSION: A PAO is an effective surgical intervention for acetabular retroversion and produces similar improvements when used to treat dysplasia. Femoral version should be routinely assessed in these patients and when extremely low (< 0°), as an additional procedure to address this abnormality may be necessary. Females with signs of hypermobility should also be consulted of the likely guarded improvement. Cite this article: Bone Jt Open 2021;2(9):757-764.

A minimally invasive periacetabular osteotomy technique: minimizing intraoperative risks.

The periacetabular osteotomy (PAO) is an extensive surgical procedure associated with potential risk to the adjacent neurovascular structures. A steep learning curve exists, with surgeon experience an important factor in outcome. Little detail exists of the osteotomies themselves, and how to make them safe and reproducible. This article describes our PAO technique with emphasis on specific safety steps. When performing the posterior column cut, migration of the osteotome beyond the lateral pelvis may lead to damage of the sciatic nerve. The safety features detailed include novel measurement of the posterior column width and the use of specific-width osteotomes to complete this osteotomy. To plan the cut, several computerized tomography-based measurements are taken starting just above the greater sciatic notch and continuing down to the inferior part of the acetabulum. The angle of this cut is determined by acetabular morphology and the width of the posterior column. These posterior column width measurements will determine the width of the osteotomes used to perform the cut with little risk that an osteotome will penetrate too far on the lateral side of the pelvis. To ensure the lateral cortex has been cut completely proximally, an osteotome with pre-measured depths may be used from a medial to a direct lateral trajectory. The senior author has been performing this modified approach since 2010 (n = 530 PAOs) and has witnessed no vascular injuries and no nerve injuries aside from minor lateral femoral cutaneous nerve issues. Utilization of these techniques has prevented any major nerve injury without the need for intraoperative electromyography.

Malreduction of tibial articular width in bicondylar tibial plateau fractures treated with circular external fixation is associated with post-traumatic osteoarthritis.

OBJECTIVES: We aimed to report outcomes of Bicondylar Tibial Plateau (BTP) fractures treated using Ilizarov fixation, and identify risk factors for developing post-traumatic radiographic osteoarthritis (ROA). METHODS: Retrospective study of 80 BTP fractures managed with Ilizarov fixation. RESULTS: All fractures united, with only 3 cases of deep infection. ROA was evident in 12.5% at average 13 months post-injury. Increased tibial articular-widening associated with risk of developing ROA (p = 0.02). CONCLUSION: Ilizarov fixation is safe and reliable in the management of BTP fractures. Restoration of tibial articular-width at fixation associated with reduced risk of developing radiographic OA.

Investigation of association between hip osteoarthritis susceptibility loci and radiographic proximal femur shape.

OBJECTIVE: To test whether previously reported hip morphology or osteoarthritis (OA) susceptibility loci are associated with proximal femur shape as represented by statistical shape model (SSM) modes and as univariate or multivariate quantitative traits. METHODS: We used pelvic radiographs and genotype data from 929 subjects with unilateral hip OA who had been recruited previously for the Arthritis Research UK Osteoarthritis Genetics Consortium genome-wide association study. We built 3 SSMs capturing the shape variation of the OA-unaffected proximal femur in the entire mixed-sex cohort and for male/female-stratified cohorts. We selected 41 candidate single-nucleotide polymorphisms (SNPs) previously reported as being associated with hip morphology (for replication analysis) or OA (for discovery analysis) and for which genotype data were available. We performed 2 types of analysis for genotype-phenotype associations between these SNPs and the modes of the SSMs: 1) a univariate analysis using individual SSM modes and 2) a multivariate analysis using combinations of SSM modes. RESULTS: The univariate analysis identified association between rs4836732 (within the ASTN2 gene) and mode 5 of the female SSM (P = 0.0016) and between rs6976 (within the GLT8D1 gene) and mode 7 of the mixed-sex SSM (P = 0.0003). The multivariate analysis identified association between rs5009270 (near the IFRD1 gene) and a combination of modes 3, 4, and 9 of the mixed-sex SSM (P = 0.0004). Evidence of associations remained significant following adjustment for multiple testing. All 3 SNPs had previously been associated with hip OA. CONCLUSION: These de novo findings suggest that rs4836732, rs6976, and rs5009270 may contribute to hip OA susceptibility by altering proximal femur shape.

Quantifying the characteristics of the acetabulum and proximal femur using a semi-automated hip morphology software programme (SHIPS).

BACKGROUND: Hip-joint shape is an important factor that affects an individual's risk of developing osteoarthritis (OA). However, validated tools to quantify these morphological characteristics on clinical plain radiographs are few. We developed a Matlab-based Semi-automated HIP Software programme (SHIPS) that measures 10 morphologic characteristics of the hip that are risk factors for OA using a plain digitised antero-posterior pelvic radiograph. In this study we validated the accuracy and repeatability of this freeware-tool. METHODS: Software accuracy was assessed using a test pelvic radiograph, and by repeated measurements of an AP-pelvic radiograph digitally recreated from pelvis computed-tomography images reformatted to create images rotated in 2-dimensions (2.5° increments, range -15° to +15°). Intra- and inter-observer repeatability was assessed using pelvic radiographs from 30 subjects analysed twice using the software by two readers, and expressed as coefficient of variation (CV). Clinical-repeatability was assessed by measuring sequential pelvic radiographs taken on the same day after re-positioning in 23 subjects. RESULTS: Software accuracy was within 0.1% for linear-ratios and 0.4° for angular-measurements. Changes in pelvic inclination and rotation of ±15° resulted in <14% change in linear-measurement ratios and <7° change in angular-measurements. The intra-observer CV was between 0.3 to 4.1%, and inter-observer CV 0.7 to 9.7% with the exception of horizontal-toit-externa (HTE, 14.6 and 24.2% respectively). Short-term clinical-repeatability varied from 0.4 to 6.1%, with the exception of HTE (37.4%). CONCLUSION: The software showed good accuracy and repeatability for measurement of most hip-joint morphologic risk factors for OA apart from HTE. This tool has particular value in studying large or retrospective datasets where cross-sectional imaging is not feasible or available.

Accurate bone segmentation in 2D radiographs using fully automatic shape model matching based on regression-voting.

Recent work has shown that using Random Forests (RFs) to vote for the optimal position of model feature points leads to robust and accurate shape model matching. This paper applies RF regression-voting as part of a fully automatic shape model matching (FASMM) system to three different radiograph segmentation problems: the proximal femur, the bones of the knee joint and the joints of the hand. We investigate why this approach works so well and demonstrate that the performance comes from a combination of three properties: (i) The integration of votes from multiple regions around the model point. (ii) The combination of multiple independent votes from each tree. (iii) The use of a coarse to fine strategy. We show that each property can improve performance, and that the best performance comes from using all three. We demonstrate that FASMM based on RF regression-voting generalises well across application areas, achieving state of the art performance in each of the three segmentation problems. This FASMM system provides an accurate and time-efficient way for the segmentation of bony structures in radiographs.