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Background/Aims Radiographic hip osteoarthritis (rHOA) is traditionally defined on hip x-rays, using subjective methods such as Kellgren-Lawrence scoring. Associations between subjective rHOA measures and symptoms are inconsistent. Applying digital tools to high-resolution dual-energy X-ray absorptiometry (DXA) scans, we aimed to develop a novel semi-automated classifier for rHOA and evaluate the face validity of the classifier based on relationships with hip pain, hospital diagnosed OA (HES OA), and risk of total hip replacement (THR). Methods Using hip DXAs in UK Biobank, osteophyte grades 0-3 were assigned based on manually measured osteophyte area. Minimum joint space width (mJSW) was automatically measured using outline points placed by a machine learning-based algorithm and then used to categorise individuals into joint space narrowing (JSN) grades 0-3. Osteophyte and JSN grades were combined, using a novel system giving greater to weight to osteophytes, to categorise individuals into rHOA grades 0-4. Logistic regression giving odds ratios (OR) was used to examine associations between rHOA grade and hip pain, and HES OA. Cox proportional hazard models giving hazard ratios (HR) were used to examine associations between rHOA grade and subsequent THR. Our adjusted model included age, sex, height and weight as covariates. Results 40,340 individuals were included in the study (mean age 63.7 [range 44-82], 19294/21046 male/female). 32758 (81.2%) had rHOA grade 0, 4565 (11.3%) grade 1, 2317 (5.7%) grade 2, 543 (1.3%) grade 3, 157 (0.4%) grade 4, with all features of rHOA being more common in males than females. rHOA grades ≥2 were associated with all three clinical outcomes in both unadjusted and adjusted models, a clear dose-response relationship was seen with each increase in grade showing a large rise in OR/HRs (Table 1). Grade 4 rHOA was strongly predictive of THR (HR 57.70 [95%CI 38.08-87.44]). Conclusion We successfully applied a novel semi-automated classifier to over 40,000 individuals from UKB. The validity of our classifier was supported by the strong and progressive relationships observed between rHOA and hip pain, and HES OA and risk of THR. We conclude that hip DXAs provide a promising means of defining rHOA, with potential screening applications in the clinic. Disclosure B.G. Faber: None. R. Ebsim: None. F.R. Saunders: None. M. Frysz: None. C. Lindner: None. J.S. Gregory: None. R.M. Aspden: None. N.C. Harvey: None. G. Davey Smith: None. T. Cootes: None. J.H. Tobias: None.

Objectives Responsive biomarkers are needed to assess the progression of OA and their lack has hampered previous clinical trials. Statistical shape modelling (SSM) from radiographic images identifies those at greatest risk of fast-progression or joint replacement, but its sensitivity to change has not previously been measured. This study evaluates the responsiveness of SSM in knee OA in a 12-month observational study. Methods A total of 109 people were recruited who had undergone knee radiographs in the previous 12 months, and were grouped based on severity of radiographic OA (Kellgren–Lawrence grading). An SSM was built from three dual-energy X-ray absorptiometry scans at 6-month intervals. Change-over-time and OA were assessed using generalized estimating equations, standardized response means (SRM) and reliable change indices Results Mode 1 showed typical features of radiographic OA and had a strong link with Kellgren–Lawrence grading but did not change significantly during the study. Mode 3 showed asymmetrical changes consistent with medial cartilage loss, osteophytes and joint malalignment, and was responsive to change, with a 12-month SRM of 0.63. The greatest change was observed in the moderate radiographic OA group (SRM 0.92) compared with the controls (SRM 0.21), and the reliable change index identified 14% of this group whose progression was clinically significant. Conclusion Shape changes linked the progression of osteophytosis with increasing malalignment within the joint. Modelling of the whole joint enabled quantification of change beyond the point where bone-to-bone contact has been made. The knee SSM is, therefore, a responsive biomarker for radiographic change in knees over 12 months.

Objective. Previously, active shape modelling (ASM) of the proximal femur was shown to identify those individuals at highest risk of developing radiographic OA. Here we determine whether ASM predicts the need for total hip replacement (THR) independent of KellgrenLawrence grade (KLG) and other known risk factors. Methods. A retrospective cohort study of 141 subjects consulting primary care with new hip pain was conducted. Pelvic radiographs taken on recruitment were assessed for KLG, centre-edge angle, acetabular depth and femoral head migration. Clinical factors (duration of pain, use of a stick and physical function) were collected by self-completed questionnaires. ASM differences between shape mode scores at baseline for individuals who underwent THR during the 5-year follow-up (n = 27) and those whose OA did not progress radiographically (n = 75) were compared. Results. A1 S.D. reduction in baseline ASM mode 2 score was associated with an 81% reduction in odds of THR (OR = 0.19, 95% CI 0.52, 0.70) after adjustment for KLG, radiographic and clinical factors. A similar reduction in odds of THR was associated with a 1 S.D. reduction in mode 3 (OR = 0.45, 95% CI 0.28, 0.71) and a 1 S.D. increase in mode 4 score (OR = 2.8, 95% CI 1.7, 4.7), although these associations were no longer significant after adjustment for KLG and clinical factors. Conclusion. ASM of the hip joint is a reliable early biomarker of radiographic OA severity, which can improve the ability to identify patients at higher risk of rapid progression and poor outcome even when KLG and clinical risk factors are taken into account.

The traditional view of OA is that it is primarily a disease of articular cartilage that results, by altering the biomechanics of the joint, in secondary changes to the subchondral bone and, through secondary inflammation, other joint tissues. This focus on cartilage tends to ignore other musculoskeletal changes reported, especially those remote from affected joints. It has been proposed instead that generalized OA is a systemic musculoskeletal disorder with a metabolic component. Evidence for this position will be presented by summarizing changes identified in all the major musculoskeletal tissues. This will endeavour to show the links between these tissues, most of which have a common mesenchymal origin. Dysregulated tissue turnover, with the balance in favour of growth, will be seen to be a common thread underlying many of the changes described. It is proposed that the production of new tissue in the midst of existing tissue, in the wrong place and at the wrong time, could result in the changes observed and that reversion of cellular behaviour to an earlier, developmental-like, phenotype may provide a mechanism that could drive the disease process. New therapies may arise both from recognizing this whole musculoskeletal disease phenotype and by exploring what might be the factors underlying this cellular reversion.