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Summary Objectives To describe whether body mass index (BMI) is a clinically meaningful predictor of patient reported outcomes following primary total hip replacement (THR) surgery. Design Combined data from prospective cohort studies. We obtained information from four cohorts of patients receiving primary THR for osteoarthritis: Exeter Primary Outcomes Study (EPOS) ( n = 1431); EUROHIP ( n = 1327); Elective Orthopaedic Centre ( n = 2832); and St. Helier ( n = 787). The exposure of interest was pre-operative BMI. Confounding variables included: age, sex, SF-36 mental health, comorbidities, fixed flexion, analgesic use, college education, OA in other joints, expectation of less pain, radiographic K&L grade, ASA grade, years of hip pain. The primary outcome was the Oxford Hip Score (OHS). Regression models describe the association of BMI on outcome adjusting for all confounders. Results For a 5-unit increase in BMI, the attained 12-month OHS decreases by 0.78 points 95%CI (0.27–1.28), P -value 0.001. Compared to people of normal BMI (20–25), those in the obese class II (BMI 35–40) would have a 12-month OHS that is 2.34 points lower. Although statistically significant this effect is small and not clinically meaningful in contrast to the substantial change in OHS seen across all BMI groupings. In obese class II patients achieved a 22.2 point change in OHS following surgery. Conclusions Patients achieved substantial change in OHS after THR across all BMI categories, which greatly outweighs the small difference in attained post-operative score. The findings suggest BMI should not present a barrier to access THR in terms of PROMs.

Objective:Genetic factors and abnormalities of joint morphology are important in the aetiology of hip osteoarthritis (OA). The extent to which genetic influences are manifest through joint morphology has undergone limited investigation. Using a cohort with an hereditary predisposition to end-stage hip OA and a control group with no inherited risk, we aimed to identify associations with abnormal joint morphology and clinical features.Design:One hundred and twenty-three individuals (mean age 52 years) with a family history of total hip arthroplasty (THA) (termed ‘sibkids’) were compared with 80 spouse controls. Morphology was assessed using standardised radiographs and cam, dysplasia, and pincer deformities defined. Regression modelling described the association of cohort with abnormal joint morphology, adjusting for confounders [age, gender, body mass index (BMI), OA, and osteophyte].Results:Sibkids had an odds ratio of 2.1 [95%confidence interval (CI) 1.3–3.5] for cam deformity. There were no differences in the prevalence of dysplasia or pincer deformities. In both groups, hips with cam deformities or dysplasia were more likely to have clinical features than normal hips [odds ratio (OR) 4.46 (1.8–11.3), and 4.40 (1.4–14.3) respectively]. Pincer deformity was associated with positive signs in the sibkids but not in the controls (OR 3.0; 1.1–8.2).Discussion:After adjustment for confounders that cause secondary morphological change, individuals with an hereditary predisposition to end-stage hip OA had a higher prevalence of morphological abnormalities associated with hip OA. Sibkids were more likely to demonstrate clinical features in the presence of pincer deformity, suggesting that the genes are acting not only through abnormal morphology but also through other factors that influence the prevalence of pain.

s / Osteoarthritis and Cartilage 22 (2014) S57–S489 S209 Purpose: Non-steroidal anti-inflammatory agents (NSAIDs) are commonly used to manage symptoms in patients with knee osteoarthritis (OA). While randomized controlled trials have demonstrated efficacy, real world effectiveness of these agents in long term studies is lacking. This study sought to estimate the effectiveness of NSAIDs on symptom management over 4 years among persons with radiographically confirmed OA. Marginal structural models, which take into consideration the likely dual role of indices of disease severity as confounders and intermediary variables, were compared to standard repeated-measure analyses. Methods: We identified NSAID naive participants with radiographic knee OA in the Osteoarthritis Initiative. Participants were evaluated over 4 years. NSAID users included those reporting any use of prescription medication use (i.e., either regular use or as-needed use) at each assessment. Outcome measures included WOMAC Pain, Stiffness and Physical Function. Beta coefficients derived from marginal structural models and generalized estimating equation models represented the average change in outcomemeasures attributed to long term NSAID use. Minimally important clinical differences were a priori set as at least 1.2 for pain, 0.5 for stiffness, and 4.1 for function. Results: Persons with radiographically confirmed OA with long term reports of prescription NSAIDS use experienced improvements in WOMAC Pain: -0.99 (95% Confidence Interval (CI): -2.38 to 0.4); WOMAC Stiffness: -0.64 (95% CI: -1.52 to 0.24); and WOMAC Function: -5.29 (95% CI: -9.7 to -0.89). In contrast, the analysis with generalized estimating equations yields an estimate of -0.03, -0.08 and 0.07 for difference in Pain, Stiffness and Function, respectively. Conclusions: When evaluated using marginal structural models, long term use of NSAIDs showed a modest trend towards relieving symptoms and a clinically significant improvement in function in patients with radiographically confirmed OA, whereas a standard regression models didn’t show such benefits. Studies on the treatment of OA using non-experimental data should consider using marginal structural models when evaluating the overall treatment effect from a timevarying treatment. 366 PATIENT REPORTED OUTCOMES FOLLOWING PRIMARY HIP REPLACEMENT SURGERY: DEVELOPMENT AND INTERNAL VALIDATION OF A PROGNOSTIC TOOL A. Judge yz, R.N. Batra y, D. Murray y, P.A. Dieppe x, M.T. Sanchez-Santos y, G. Thomas y, D. Beard y, M.K. Javaid yz, K. Dreinh€ ofer k{, K. Peter-G€ unther#, C. Cooper yz, N.K. Arden yz. yNIHR Musculoskeletal BioMed. Res. Unit, Univ. of Oxford, Oxford, United Kingdom; zMRC Lifecourse Epidemiology Unit, Univ. of Southampton, Southampton, United Kingdom; x Peninsula Coll. of Med. and Dentistry, Univ. of Plymouth, Plymouth, United Kingdom; k Inst. for Muskuloskeletal Rehabilitation, Charit e Univ.smedizin Berlin, Berlin, Germany; {Dept. of Orthopaedics, Traumatology and Sports Med., Med. Park Berlin Humboldtm€ uhle, Berlin, Germany; Dept. of Orthopaedic Surgery, Univ. Hosp. Carl Gustav Carus, Med. Faculty of the Technical Univ. of Dresden, Dresden, Germany Purpose: Although Total Hip Replacement (THR) is a successful surgical intervention, there are a minority of patients who do not achieve clinically meaningful improvement or whose symptoms get worse following surgery. The aim of this study was to develop a clinical risk prediction tool to predict patient reported outcomes following primary hip replacement surgery. Methods: We obtained data on two prospective cohorts of patients receiving primary THR for osteoarthritis: Exeter Primary Outcomes Study (n 1⁄4 1247); EUROHIP (n 1⁄4 845). The primary outcome was the Oxford Hip Score (OHS). Combining data from two large prospective cohort studies allowed us to take account of a wide and comprehensive range of both traditional and novel risk factors, including patient, radiographic and surgical predictors. Linear regression modelling was used to identify predictors of outcome. For internal validationwe used a combination of multiple imputation and bootstrapping with backward selection. Performance of the predictive model was assessed in terms of calibration and discrimination. Results: Of the radiographic variables pattern of OA was an important determinant of outcome. Those with superomedial, medial or concentric disease had worse outcomes than patients with a superolateral pattern of OA or no reduction in joint space. Arthritis in other joints, and previous surgery on other joints, were associated with worse outcomes. For surgical variables, a posterior surgical approach, and larger femoral component offset had better outcomes. For patient factors, worse preoperative pain/function, increasing age when over age 75, increasing BMI, lower levels of educational attainment and those with worse preoperative SF36 mental health scores, also had worse outcomes. These factors were operationalized into a clinical risk prediction tool. Calibration of the predicted 12-month post-operative OHS, and absolute change in OHS was good. The model showed good discriminatory ability with a bias corrected R-squared of 23.1%. We tested the ability of the model to identify patients with the worst possible outcomes following THR (defined as a change in OHS < 5-points of whom 89 (4.25%) patients met this criterion). Performance of the tool to identify patients with the worst outcomes was good (C-statistic 0.77 95%CI (0.72 to 0.82)). Conclusions: We have developed a clinical risk prediction tool that would provide information on the likely outcomes of hip replacement surgery. Following hip replacement the majority of patients do very well, and only a minority will not achieve clinically meaningful symptomatic change in OHS. The clinical tool performed well in terms of its calibration and discriminatory ability, and identification of those patients with the worst possible outcomes was good. The tool provides individualised risk prediction and allows patients to understand their expected outcomes of surgery – it has the potential to guide patientclinician decision-making. It will now undergo external validation in a new prospective cohort of patients. 367 COURSE OF PHYSICAL FUNCTIONING AND PAIN IN OSTEOARTHRITIS OF THE KNEE OR HIP: A SYSTEMATIC REVIEW M. de Rooij y, M. van der Leeden yz, A. H€ akkinen#x, W.F. Lems ky, L.D. Roorda y, C. Veenhof{, H.C. de Vet #, J. Dekker yy. yAmsterdam Rehabilitation Res. Ctr. j Reade, Amsterdam, Netherlands; zVU Univ. Med. Ctr., Dept. of Rehabilitation Med., Amsterdam, Netherlands; xDept. of Hlth. Sci., Univ. of Jyv€ askyl€ a and Jyv€ askyl€ a Central Hosp., Jyv€ askyl€ a, Finland; kVU Univ. Med. Ctr., Dept. of Rheumatology, Amsterdam, Netherlands; {Netherlands Inst. for Hlth. Services Res., Utrecht, Netherlands; VU Univ. Med. Ctr. EMGO Inst. for Hlth. and Care Res., Dept. of Epidemiology and Biostatistics, Amsterdam, Netherlands; yyVU Univ. Med. Ctr., Dept. of Psychiatry, Dept. of Rehabilitation Med., EMGO Inst., Amsterdam, Netherlands Purpose: (1) The aim of the study was to systematically summarize the literature from March 2005 to January 2013 on the course of physical functioning and pain in patients with OA of the knee or hip and (2) to provide an overview of prognostic factors of physical functioning and future pain for these patients. Methods: A search was conducted in PubMed, CINAHL, Embase and Psych-INFO in January 2013. Eligible studies were prospective cohort studies (minimum follow up was 6 months) that included participants with knee or hip OA diagnosed with radiographically and/or

s / Osteoarthritis and Cartilage 20 (2012) S54–S296 S152 study ,using the cell culturing technology, was to observe what different results would come out from the MTTassay of the ATDC5 cell proliferation, whick had been cultured with different concentration E2. Methods: The 17-bestradiol we use was ordered from Sigma co. and the ATDC5 cell line was form the Riken cell bank. We culture the ATDC5 24 hours in the media with different concentration 17-bestradiol, then we test the OD value of the different cells in MTT assay to assume the proliferation of the ATDC5. Results: After culturing 24 hours in the media with different concentration 17-bestradiol, the proliferation of the ATDC5 in different concentration 17-bestradiol were different significantly, the higher of the concentration, the higher of the proliferation, as follows: beside the 10-11M against 0 M, the 10-10,10-9,10-8 and 10-7 M have significant difference in stimulating the proliferation of ATDC5 against 0 M. between the different concentration groups, only 10-8 M has significant difference against 10-11,10-10 M. Conclusions: First, 17-bestradiol has stimulation on the proliferation of ATDC5. Second, 10-8 M concentration of 17-bestradiol has the strongest stimulating effect than the other concentration of 17-bestradiol. Clinical Aspects / Outcomes 302 PRE-OPERATIVE BMI AS A PREDICTOR OF PATIENT REPORTED OUTCOMES OF PRIMARY HIP REPLACEMENT SURGERY: A COMBINED ANALYSIS OF 4 PROSPECTIVE COHORT STUDIES R.N. Batra , A. Judge , M.K. Javaid , G.E. Thomas , D. Beard , D. Murray , P. Dieppe , K. Drienhoefer , K. Peter-Geunther , R. Field , C. Cooper , N.K. Arden . NIHR BioMed. Res. Unit, Univ. of Oxford, Oxford, United Kingdom; MRC Lifecourse Epidemiology Unit, Univ. of Southampton, Southampton, United Kingdom; 3 Peninsula Coll. of Med. and Dentistry, Plymouth, United Kingdom; Charite Univ.smedizin Berlin, Dept. of Orthop., Traumatology and Sports Med., Berlin, Germany; Univ. Hosp. Carl Gustav Carus, Technical Univ. of Dresden, Dresden, Germany; 6 Elective Orthop. Ctr., Epsom, United Kingdom Purpose: Total hip replacement (THR) is a successful surgical intervention, providing relief from pain, increasingmobility and improving quality of life for majority of patients. Within the literature some, but not all studies, have found that obesity is associated with worse patient reported outcomes (PROMs) of THR, and there is increasing concern that obesity may be used as a barrier to accessing surgery. Methods: We obtained information from 4 prospective cohort studies of patients receiving primary THR for osteoarthritis (OA): Exeter Primary Outcomes Study (EPOS) (n1⁄41589); EUROHIP (n1⁄4908); South West London Elective Orthopaedic Centre (SWLEOC) (n1⁄41523); and St. Helier (n1⁄4799). The primary outcome was the 12 month Oxford Hip Score (OHS) which is used to assess pain and function.For the EUROHIP study, we imputed the OHS from WOMAC scores using truncated regression. Confounding variables included: age, sex, SF-36 mental health, comorbidities, fixed flexion, analgesic use, college education, OA in other joints, expectation of less pain, radiographic KL only age and sex were available in all 4 cohorts. Linear regression (ANCOVA) is used to describe the association of BMI on the 12 month OHS, adjusting for the pre-operative OHS. Multiple imputation methods were used to handle missing data. In order to combine data across the 4 studies we used two methodological approaches: a) Meta-Analysis For each study, separate models are built to describe the association of BMI on outcome. Models are adjusted only for age and sex in order to construct related hypotheses in each study. Fixed effects metaanalysis is used to combine the results; b) Combining studies Data from all 4 studies are combined using multiple imputation methods to impute data on missing confounders, allowing the association of BMI on outcome to be adjusted for all potential confounders. Results: a) Meta-Analysis Adjusting for age and sex, for a 5 unit increase in BMI, the 12 month OHS decreases by 0.81 95%CI (0.55 1.08) units (Figure 1); Ă b) Combining Studies Adjusting for age and sex alone, for a 5 unit increase in BMI, the 12 month OHS decreases by 0.72 (0.46 0.99) units. Adjusting for all potential confounders, the effect is attenuated to 0.51 (0.09 0.92). Hence, for each 5 unit increase in BMI, the difference in post-op OHS becomes larger and more important. For example, compared to people with a normal BMI (20 25), those in the morbidly obese group (BMI 35 40) would have a post-op OHS that is 1.53 units lower. However, there is a substantial improvement in OHS after THR across all BMI groups, which greatly outweighs any difference in post-op score (Figure 2).

Purpose: Establishing a population-based estimate for the lifetime risk of total hip and knee replacement (THR/TKR) is an important epidemiological development which will assist health service planners in assessing the future burden of lower limb arthroplasty. Methods:We used data from the U.K. General Practice Research Database (GPRD) which contains all the computerised records of 6.25m patients, and is representative of the population of the U.K. We collected data on all THRs and TKRs performed between 1991 and 2006, a total of over 27,000 THRs and 24,000 TKRs. We calculated incidence rates for THR/TKR under a Poisson model and combined these rates with mortality rates from the U.K Office for National Statistics (ONS) using a life-table framework. These estimates were then aggregated to produce a simple lifetime risk of THR and TKR by gender for age 50 and above. We also calculated the temporal trend in lifetime risk at age 50 by single calendar year from 1991 to 2006. Results: We estimated that at age 50 the mortality-adjusted lifetime risk of THR was 7.80% for females and 5.05% for males (TKR: 6.66% and 5.04% respectively). The risks of THR for females aged 50 was 54% greater for than for males (32% greater for TKR). The risk percentage decreases with increasing age for both THR and TKR in males and females. At age 80 the gender gap in risk of THR remains in favour of females (53% higher) but in TKR it is two-thirds of that at age 50 (females 21% higher). Between 1991 and 2006, the lifetime risk of THR rose from 3.89% to 10.41% for females and for males from 3.43% to 6.34%. Over the same period, for TKR the risk for females increased from 2.78% to 10.02% and for males from 1.57% to 7.39%.

Summary Objective Femoroacetabular Impingement (FAI) and Acetabular Dysplasia are common deformities, which have been implicated as a major cause of hip osteoarthritis (OA). We examined whether these subtle deformities of the hip are associated with the development of radiographic OA and total hip replacement (THR) in women. Design A population-based, longitudinal cohort of 1003 women underwent pelvis radiographs at years 2 and 20. Alpha Angle, Triangular Index Height, Lateral Centre Edge (LCE) angle and Extrusion Index were measured. An alpha angle of greater than 65° was defined as Cam-type FAI. Radiographic OA and the presence of a THR were then determined at 20 years. Results Cam-type FAI was significantly associated with the development of radiographic OA. Each degree increase in alpha angle above 65° was associated with an increase in risk of 5% (Odds Ratio (OR) 1.05 [95% confidence interval (CI) 1.01–1.09]) for radiographic OA and 4% (OR 1.04 [95% CI 1.00–1.08]) for THR. For Acetabular Dysplasia, each degree reduction in LCE angle below 28° was associated with an increase in risk of 13.0% (OR 0.87 [95% CI 0.78–0.96]) for radiographic OA and 18% (OR 0.82 [95% CI 0.75–0.89]) for THR. Conclusions This study demonstrates that Cam-type FAI and mild Acetabular Dysplasia are predictive of subsequent OA and THR in a large female population cohort. These are independent of age, BMI and joint space and significantly improve current predictive models of hip OA development.

s / Osteoarthritis and Cartilage 22 (2014) S57–S489 S412 high sensitive C-reactive protein (hsCRP), matrix metalloproteinase (MMP) mediated degradation of CRP (CRPM) and MMP-mediated collagen type I, II, and III degradation (C1M, C2M, and C3M, respectively). Statistical analyses were performed in IBM SPSS Statistics, version 19. One-way ANOVA was used to compare serological biomarkers and PPT measures and Fisher’s Least Significant Difference (LSD) post hoc test was applied. Results: Group B (BLOKS 1⁄4 2,3) had decreased PPTs compared to controls (p< 0.05, figure 1) and increased levels of C1M (p1⁄4 0.001), C2M (p 1⁄4 0.001) and hsCRP (p 1⁄4 0.023), but a lower level of C3M (p 1⁄4 0.033) compared to controls (Figure 2). Group A had increased levels of C1M (p 1⁄4 0.039), C2M (p1⁄4 0.001) and CRPM (p1⁄4 0.028) and lower level of C3M (p 1⁄4 0.019), but no difference was found in PPTs compared to controls. Dividing Group A into BLOKS 1⁄4 0, (n 1⁄4 16) and BLOKS 1⁄4 1 (n 1⁄4 22) revealed that patients with BLOKS 1⁄4 0 had decreased PPTs compared to patients with BLOKS 1⁄4 1 (p < 0.05, Figure 1). Interestingly, the level of PPTs of the BLOKS1⁄4 0 group was at the level of the group with BLOKS 2. There was no significant difference in the biomarker level in the differentiated Group A in any of the investigated markers (Figure 2). Conclusions: Patients with widespread synovitis have decreased PPTs and significantly increased levels of bone and cartilage degradation and inflammation. However, these patients had a decrease in synovial membrane degradation compared to controls. Dividing patients with localized synovitis into two groups based on the synovitis score identified subgroups with significantly different PPTs, but the same level of the biomarkers studied. This study illustrate that patients with different levels of sensitization have different profiles of tissue turnover and each constitute a specific group of severe KOA patients. 741 A CLINICAL TOOL FOR THE PREDICTION OF PATIENT-REPORTED OUTCOMES AFTER KNEE REPLACEMENT SURGERY M.T. Sanchez-Santos y, A. Judge yz, R.N. Batra y, D. Murray y, A. Price y, A.D. Liddle y, M.K. Javaid yz, C. Cooper yz, N.K. Arden yz. yNIHR Musculoskeletal BioMed. Res. Unit, Nuffield Dept. of Orthopaedics, Rheumatology and Musculoskeletal Sci., Univ. of Oxford, Oxford, United Kingdom; zMRC Lifecourse Epidemiology Unit, Univ. of Southampton, Southampton Gen. Hosp., Southampton, United Kingdom Purpose: To develop a clinical risk prediction tool to predict patientreported outcomes after undergoing primary total knee replacement (TKR) surgery. Methods:We used data from 1,649 patients from the Knee Arthroplasty Trial (KAT) who received primary TKR across 34 centres in the United Kingdom between July 1999 and January 2003. The main outcome was Oxford Knee Score (OKS) 12-months after surgery. A wide range of preoperative predictor variables including patient characteristics, clinical and surgical factors, were considered. Bootstrap backward linear regression analysis was used to identify risk factors of outcome. Results: Presence of a fixed flexion deformity, presence of varus/valgus deformity (compared with no deformity), and an absent preoperative ACL (compared with intact ACL) were associated with better OKS at 12 months. The clinical factors associated with worse post-operative OKS were worse ASA grade, presence of other conditions affecting mobility and previous knee surgery. Lower pre-operative OKS, living in poor areas, high BMI and worse SF-12 mental health score were also associated with worse outcome. Discrimination and calibration statistics were good. Patients’ characteristics explained 16.6% of the variability in outcome, when clinical variables were included 18.9% of the variance of outcome was explained, reaching 20.2% when surgical variables were added. Conclusions: The clinical risk tool will help to inform patients and clinicians regarding expectations of the outcome after knee replacement surgery, and may also provide useful information to support shared decision-making. External validation of the tool, to confirm its performance and validity, will be undertaken in a new prospective cohort of patients. 742 ASSOCIATION BETWEEN SYNOVITIS AND DEPRESSION IN PATIENTS WITH KNEE OSTEOARTHRITIS: A CROSS-SECTIONAL STUDY Y. Shimura y, H. Kurosawa y, M. Tsuchiya y, H. Kaneko z, L. Liu z, R. Sadatsuki z, A. Yusup z, S. Hada z, M. Kinoshita z, Y. Makino y, M. Sawa y, Y. Iwase y, K. Kaneko z, M. Ishijima z. y Juntendo Tokyo Koto Geriatric Med. Ctr., Tokyo, Japan; z Juntendo Univ. Graduate Sch. of Med.