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PURPOSE: Hip osteoarthritis (OA) is a major cause of pain and disability worldwide. Lack of effective therapies may reflect poor knowledge on its aetiology and risk factors, and result in the management of end-stage hip OA with costly joint replacement. The Worldwide Collaboration on OsteoArthritis prediCtion for the Hip (World COACH) consortium was established to pool and harmonise individual participant data from prospective cohort studies. The consortium aims to better understand determinants and risk factors for the development and progression of hip OA, to optimise and automate methods for (imaging) analysis, and to develop a personalised prediction model for hip OA. PARTICIPANTS: World COACH aimed to include participants of prospective cohort studies with ≥200 participants, that have hip imaging data available from at least 2 time points at least 4 years apart. All individual participant data, including clinical data, imaging (data), biochemical markers, questionnaires and genetic data, were collected and pooled into a single, individual-level database. FINDINGS TO DATE: World COACH currently consists of 9 cohorts, with 38 021 participants aged 18-80 years at baseline. Overall, 71% of the participants were women and mean baseline age was 65.3±8.6 years. Over 34 000 participants had baseline pelvic radiographs available, and over 22 000 had an additional pelvic radiograph after 8-12 years of follow-up. Even longer radiographic follow-up (15-25 years) is available for over 6000 of these participants. FUTURE PLANS: The World COACH consortium offers unique opportunities for studies on the relationship between determinants/risk factors and the development or progression of hip OA, by using harmonised data on clinical findings, imaging, biomarkers, genetics and lifestyle. This provides a unique opportunity to develop a personalised hip OA risk prediction model and to optimise methods for imaging analysis of the hip.

ObjectiveWith adults working to older ages, occupation is an important, yet less modifiable domain of physical activity to consider in the risk of knee osteoarthritis (OA). This study aimed to investigate the association between predominant lifetime occupation and prevalent knee OA.DesignParticipant-level data were used from five international community-based cohorts: Johnston County Osteoarthritis Project, the Hertfordshire Cohort Study, the Multicenter Osteoarthritis Study, the Tasmanian Cohort Study and Framingham Osteoarthritis Study. Self-reported predominant occupation was categorized into sedentary, light, light manual and heavy manual levels. Cross-sectional associations between predominant lifetime occupation and knee OA outcomes including prevalence of radiographic knee OA (RKOA), symptomatic RKOA and knee pain, were assessed using logistic regression, accounting for cohort clustering.ResultsData for 7391 participants were included. 24.7% reported sedentary lifetime occupation, 30.0% light, 35.9% light manual and 9.4% heavy manual. 43.3% presented with RKOA, 52.1% with knee pain and 29.0% with symptomatic RKOA. There was over a two-fold increase in the odds of having RKOA, knee pain and symptomatic RKOA in those whose with heavy manual compared to sedentary occupations ((odds ratio (OR): 2.14; 95% confidence interval (CI): 1.79, 2.58), (OR: 2.19; 95% CI: 1.78, 2.70), (OR: 2.41; 95% CI: 1.94, 2.99) respectively).ConclusionThis large international multi-cohort study demonstrated an association of heavy manual work with RKOA, symptomatic RKOA and knee pain. Measures that protect workers and are designed to reduce heavy manual related activities remain a priority to reduce the risk of knee OA.

ObjectivesOsteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects.MethodsWe performed a two-stage meta-analysis on more than 78,000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used.ResultsWe accumulated 11,277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9×10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p=5.6×10(-8)) and follow-up studies (p=7.3×10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9×10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2×10(-6), OR=1.27 in male specific analysis).ConclusionsNovel genetic loci for hip OA were found in this meta-analysis of GWAS.

Objectives: To investigate the rates of return to work and workability among working-age people following total hip arthroplasty (THA).Methods: Participants from the Geneva Arthroplasty Registry and the Clinical Outcomes for Arthroplasty Study aged 18-64 years when they had primary THA and with at least 5 years' follow-up were mailed a questionnaire 2017-2019. Information was collected about preoperative and post-THA employment along with exposure to physically demanding activities at work or in leisure. Patterns of change of job were explored. Survival analyses using Cox proportional hazard models were created to explore risk factors for having to stop work because of difficulties with the replaced hip.Results: In total, 825 returned a questionnaire (response 58%), 392 (48%) men, mean age 58 years, median follow-up 7.5 years post-THA. The majority (93%) of those who worked preoperatively returned to work, mostly in the same sector but higher rates of non-return (36%-41%) were seen among process, plant and machine operatives and workers in elementary occupations. 7% reported subsequently leaving work because of their replaced hip and the risk of this was strongly associated with: standing >4 hours/day (HR 3.81, 95% CI 1.62 to 8.96); kneeling/squatting (HR 3.32, 95% CI 1.46 to 7.55) and/or carrying/lifting ≥10 kg (HR 5.43, 95% CI 2.29 to 12.88).Conclusions: It may be more difficult to return to some (particularly physically demanding) jobs post-THA than others. Rehabilitation may need to be targeted to these types of workers or it may be that redeployment or job change counselling are required. [ABSTRACT FROM AUTHOR]

Background Humeral torsion is an important osseous adaptation in throwing athletes that can contribute to arm injuries. Currently there are no cheap and easy to use clinical tools to measure humeral torsion, inhibiting clinical assessment. Models with low error and "good" calibration slope may be helpful for prediction. Hypothesis/Purpose To develop prediction models using a range of machine learning methods to predict humeral torsion in professional baseball pitchers and compare these models to a previously developed regression-based prediction model. Study Design Prospective cohort Methods An eleven-year professional baseball cohort was recruited from 2009-2019. Age, arm dominance, injury history, and continent of origin were collected as well as preseason shoulder external and internal rotation, horizontal adduction passive range of motion, and humeral torsion were collected each season. Regression and machine learning models were developed to predict humeral torsion followed by internal validation with 10-fold cross validation. Root mean square error (RMSE), which is reported in degrees (°) and calibration slope (agreement of predicted and actual outcome; best = 1.00) were assessed. Results Four hundred and seven pitchers (Age: 23.2 +/-2.4 years, body mass index: 25.1 +/-2.3 km/m², Left-Handed: 17%) participated. Regression model RMSE was 12° and calibration was 1.00 (95% CI: 0.94, 1.06). Random Forest RMSE was 9° and calibration was 1.33 (95% CI: 1.29, 1.37). Gradient boosting machine RMSE was 9° and calibration was 1.09 (95% CI: 1.04, 1.14). Support vector machine RMSE was 10° and calibration was 1.13 (95% CI: 1.08, 1.18). Artificial neural network RMSE was 15° and calibration was 1.03 (95% CI: 0.97, 1.09). Conclusion This is the first study to show that machine learning models do not improve baseball humeral torsion prediction compared to a traditional regression model. While machine learning models demonstrated improved RMSE compared to the regression, the machine learning models displayed poorer calibration compared to regression. Based on these results it is recommended to use a simple equation from a statistical model which can be quickly and efficiently integrated within a clinical setting. [ABSTRACT FROM AUTHOR]

Objective: To assess the association between occupational exposures and knee osteoarthritis (OA).Methods: We systematically searched for observational studies that examined the relationship between occupational exposures and knee OA and total knee replacement. Four databases were searched up to October 1, 2019. Two reviewers independently assessed study quality using the Newcastle-Ottawa Scale and evidence quality using the Grading of Recommendations Assessment, Development and Evaluation approach. Subgroup meta-analyses were conducted for important study characteristics and each type of occupational exposure. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated for the meta-analysis using random-effects models.Results: Eighty eligible studies were identified including 25 case-control (n = 20,505 total participants), 36 cross-sectional (n = 139,463 total participants), and 19 cohort studies (n = 16,824,492 total participants). A synthesis of 71 studies suggested increased odds of knee OA (OR 1.52 [95% CI 1.37-1.69]) by combining different physically demanding jobs and occupational activities as compared to sedentary occupations and/or low-exposure groups. Odds of knee OA were greater in males and in industry-based studies and studies assessing lifetime occupational exposures. There were 9 specific job titles that were associated with knee OA, including farmer, builder, metal worker, and floor layer. Occupational lifting, kneeling, climbing, squatting, and standing were all associated with higher odds of knee OA as compared to the odds of knee OA in sedentary workers.Conclusion: Strenuous, physically demanding occupations and occupational activities were associated with increased odds of knee OA as supported by moderate-quality evidence. Specifically, agricultural and construction sectors, which typically involve heavy lifting, frequent climbing, prolonged kneeling, squatting, and standing, carried increased odds of knee OA. [ABSTRACT FROM AUTHOR]

Oral bisphosphonates (oBPs) have been associated with reduced fractures and mortality. However, their risks and benefits are unclear in patients with moderate–severe CKD. This study examined the association between oBPs and all‐cause mortality in G3B‐5D CKD. This is a population‐based cohort study including all subjects with an estimated glomerular filtration rate (eGFR) <45/mL/min/1.73 m2 (G3B: eGFR <45/mL/min/1.73 m2 G4: eGFR 15–29/mL/min/1.73 m2 G5: eGFR <15/mL/min/1.73 m2 G5D: hemodialysis) aged 40+ years from the UK Clinical Practice Research Datalink (CPRD) and the Catalan Information System for Research in Primary Care (SIDIAP). Previous and current users of other anti‐osteoporosis drugs were excluded. oBP use was modeled as a time‐varying exposure to avoid immortal time bias. Treatment episodes in oBP users were created by concatenating prescriptions until patients switched or stopped therapy or were censored or died. A washout period of 180 days was added to (date of last prescription +180 days). Propensity scores (PSs) were calculated using prespecified predictors of mortality including age, gender, baseline eGFR, socioeconomic status, comorbidities, previous fracture, co‐medications, and number of hospital admissions in the previous year. Cox models were used for PS adjustment before and after PS trimming (the first and last quintiles). In the CPRD, of 19,351 oBP users and 210,954 non‐oBP users, 5234 (27%) and 85,105 (40%) deaths were recorded over 45,690 and 915,867 person‐years of follow‐up, respectively. oBP users had 8% lower mortality risk compared to non‐oBP users (hazard ratio [HR] 0.92; 95% CI, 0.89 to 0.95). Following PS trimming, this became nonsignificant (HR 0.98; 95% CI, 0.94 to 1.04). In the SIDIAP, of 4146 oBP users and 86,127 non‐oBP users, 1330 (32%) and 36,513 (42%) died, respectively. oBPs were not associated with mortality in PS adjustment and trimming (HR 1.04; 95% CI, 0.99 to 1.1 and HR 0.95; 95% CI, 0.89 to 1.01). In this observational, patient‐based cohort study, oBPs were not associated with increased mortality among patients with moderate–severe CKD. However, further studies are needed on other effects of oBPs in CKD patients. © 2020 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Objective To estimate the lifetime risk of knee and hip replacement following a diagnosis of RA. Methods The analysis was undertaken using routinely collected data from the English NHS. Diagnosis of RA was identified using primary care records, with knee and hip replacement observed in linked hospital records. Parametric survival models were fitted for up to 15 years of follow-up, with age, sex, Charlson comorbidity score, socioeconomic status, BMI and smoking status included as explanatory variables. A decision model was used to combine and extrapolate survival models to estimate lifetime risk. Results The number of individuals with a diagnosis of RA and included in the study was 13 961. Lifetime risk of knee replacement and hip replacement was estimated to be 22% (95% CI: 16, 29%) and 17% (95% CI: 11, 26%) following a diagnosis of RA for the average patient profile (non-smoking women aged 64 with no other comorbidities, BMI of 27 and in the top socioeconomic quintile). Risks were higher for younger patients. Conclusion The lifetime risk of knee and hip replacement for individuals with a diagnosis of RA is approximately double that of the general population. These findings allow for a better understanding of long-term prognosis and healthcare resource use, and highlight the importance of timely diagnosis and effective treatment. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis is a substantial cause of disability. Joint replacement prevalence relates to the burden of severe osteoarthritis, and identifying risk factors for end-stage disease may indicate intervention opportunities. American football has high youth and elite participation, and determining risk factors for severe osteoarthritis may support future morbidity prevention. Purpose: To (1) determine the prevalence of hip and knee replacement in retired National Football League (NFL) athletes, (2) examine risk factors for replacement, and (3) identify the association between knee injuries and knee replacement. Study Design: Case-control study; Level of evidence, 3. Methods: Retired NFL athletes who participated in a general health survey were included. This historical cohort included those playing between 1929 and 2001. The association between self-reported playing or injury history, and replacement after retirement, was assessed with prevalence ratios (PRs). Models were adjusted for potential confounders of age and weight. Results: Data for 2432 retired male NFL players (69.3% response rate) who had participated in football for a mean 15.2 years were included, in which 277 players reported replacement after retirement (11.4%). More participants reported knee replacement (7.7%) than hip replacement (4.6%). The majority of participants reported previous severe knee injury (53%), and the most prevalent was meniscal tear (32.2%). In multivariable models, age (10-year increase, PR, 2.23; 95% CI, 1.99-2.51), current weight (PR, 1.10; 95% CI, 1.06-1.14), and reporting 1 (PR, 1.78; 95% CI, 1.14-2.77), 2 (PR, 1.91; 95% CI, 1.16-3.15), or ≥3 knee injuries (PR, 3.44; 95% CI, 2.33-5.09) were associated with knee replacement. Age (10-year increase, PR, 1.86; 95% CI, 1.59-2.18), linemen (PR, 1.62; 95% CI, 1.03-2.55), and reporting 1 (PR, 1.72; 95% CI, 1.05-2.80), 2 (PR, 2.77 95% CI, 1.58-4.84), or ≥3 (PR, 2.44; 95% CI, 1.52-3.91) hip injuries were associated with hip replacement. Each reported knee injury type was cross-sectionally associated with replacement after retirement (P <.05). Conclusion: Knee replacement was more prevalent than hip replacement. Risk factors differed between the hip and the knee, with age and severe joint injury associated with hip and knee replacement, weight with knee replacement, and playing position associated with hip replacement. Joint injury and weight management may be prevention opportunities to reduce morbidity and end-stage osteoarthritis in this population. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine the prevalence of hand and wrist osteoarthritis in former elite cricket and rugby union players, by sport and playing position, and to define the prevalence of severe hand injury, and its association with hand osteoarthritis.Design: Cross-sectional.Methods: Data from cross-sectional studies of former elite male cricket and rugby players were used to determine the prevalence of hand pain, physician-diagnosed osteoarthritis, and previous severe injury. Multivariable logistic regression was used to determine the association of previous injury with pain and osteoarthritis.Results: Data from 200 cricketers and 229 rugby players were available. Complete case analysis resulted in 127 cricketers and 140 rugby players. Hand pain was more prevalent amongst cricketers (19.7%) than rugby players (10.0%). The prevalence did not differ between cricket and rugby players for hand osteoarthritis (2.4% and 3.6%), wrist osteoarthritis (1.6% and 2.1%), or previous severe hand injury (36.2% and 31.4%). No significant association between previous hand injury and pain or osteoarthritis was identified in either sport.Conclusions: Former elite cricketers reported more hand pain than rugby players. No significant association was found between self-reported severe injury and hand osteoarthritis in either cohort, potentially indicating that risk factors aside from injury may be more prominent in the development of hand osteoarthritis. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated how tumor necrosis factor inhibitor (TNFi) therapy influenced need for total hip and total knee replacement procedures in patients with rheumatoid arthritis (RA). Topics explored include the clinical characteristics, progression, and risk factors for RA, comparison of outcomes from TNFi and conventional synthetic disease-modifying antirheumatic drugs (DMARD) administration, and the reduction in total hip replacement in older patients.

Objective: To examine whether body mass index (BMI), menopausal status, and hormone therapy (HT) use modify the association between physical activity (PA) patterns throughout middle age and the incidence and prevalence of joint symptoms in women in later middle age.Methods: Data were from 6,661 participants (born 1946-1951) in the Australian Longitudinal Study on Women's Health. Surveys, with questions on joint pain and stiffness, PA, height and weight, menopausal symptoms, and HT use, were completed every 3 years from 1998 to 2010. PA patterns were defined as none or low, low or meeting guidelines, fluctuating, or meeting guidelines at all times (reference pattern). Logistic regression was used to examine the association between PA patterns and prevalent (in 2010) and cumulative incident (1998-2010) joint symptoms and effect modification by patterns in BMI, menopausal status, and HT.Results: The groups representing fluctuating PA (odds ratio [OR] 1.34 [99% confidence interval (99% CI) 1.04-1.72]) and no or low PA (OR 1.60 [99% CI 1.08-2.35]) had higher odds of incident joint symptoms than those described as meeting guidelines at all times. Stratification by BMI showed that this association was statistically significant in the obese group only. No evidence for effect modification by menopausal status or HT use was found. The findings were similar for prevalent joint symptoms.Conclusion: Maintaining at least low levels of PA throughout middle age was associated with a lower prevalence and incidence of joint symptoms later in life. This apparent protective effect of PA on joint symptoms was stronger in obese women than in under- or normal-weight women, and not related to menopause or HT status. [ABSTRACT FROM AUTHOR]

ABSTRACT In January 2005, the National Institute for Health and Care Excellence (NICE) in England and Wales provided new guidance on the use of antiosteoporosis therapies for the secondary prevention of osteoporotic fractures. This was shortly followed in the same year by market authorization of a generic form of alendronic acid within the UK. We here set out to estimate the actual practice impact of these events among hip fracture patients in terms of antiosteoporosis medication prescribing and subsequent fracture incidence using primary care data (Clinical Practice Research Datalink) from 1999 to 2013. Changes in level and trend of prescribing and subsequent fracture following publication of NICE guidance and availability of generic alendronic acid were estimated using an interrupted time series analysis. Both events were considered in combination within a 1-year 'intervention period.' We identified 10,873 primary hip fracture patients between April 1999 and Sept 2012. Taking into account prior trend, the intervention period was associated with an immediate absolute increase of 14.9% (95% CI, 10.9 to 18.9) for incident antiosteoporosis prescriptions and a significant and clinically important reduction in subsequent major and subsequent hip fracture: -0.19% (95% CI, -0.28 to -0.09) and -0.17% (95% CI, -0.26 to -0.09) per 6 months, respectively. This equated to an approximate 14% (major) and 22% (hip) reduction at 3 years postintervention relative to expected values based solely on preintervention level and trend. We conclude that among hip fracture patients, publication of NICE guidance and availability of generic alendronic acid was temporally associated with increased prescribing and a significant decline in subsequent fractures. © 2016 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Oral bisphosphonates (BPs) are highly effective in preventing fractures and are recommended first-line therapies for patients with osteoporosis.We identified the incidence and predictors of oral BP treatment failure, defined as the incidence of two ormore fractures while on treatment (⩾2 FWOT) among users with high adherence. Fractures were considered from6 months after treatment initiation and up to 6 months after discontinuation. Data from computerized records and pharmacy invoices were obtained from Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primàaria (SIDIAP; Catalonia, Spain) and Danish Health Registries (Denmark) for all incident users of oral BPs in 2006-2007 and 2000-2001, respectively. Fine and Gray survival models using backwardstepwise selection (p-entry 0.049; p-exit 0.10) and accounting for the competing risk of therapy cessation were used to identify predictors of ⩾2 FWOT among patients having persisted with treatment ⩾6 months with overall medication possession ratio (MPR) ⩾80%. Incidence of ⩾2 FWOT was 2.4 (95% confidence interval [CI], 1.8 to 3.2) and 1.7 (95% CI, 1.2 to 2.2) per 1000 patient-years (PYs) within Catalonia and Denmark, respectively. Older age was predictive of ⩾2 FWOT in both Catalonian and Danish cohorts: subhazard ratio (SHR)=2.28 (95%CI, 1.11 to 4.68) and SHR=2.61 (95% CI, 0.98 to 6.95), respectively, for 65 to<80 years; and SHR=3.19 (95% CI, 1.33 to 7.69) and SHR=4.88 (95% CI, 1.74 to 13.7), respectively, for ⩾80 years. Further significant predictors of ⩾2 FWOT identified within only one cohort were dementia, SHR=4.46 (95% CI, 1.02 to 19.4) (SIDIAP); and history of recent or older fracture, SHR=3.40 (95%CI, 1.50 to 7.68) and SHR=2.08 (95%CI: 1.04-4.15), respectively (Denmark). Even among highly adherent users of oral BP therapy, a minority sustainmultiple fractures while on treatment. Older age was predictive of increased risk within both study populations, as was history of recent/old fracture and dementia within one but not both populations. Additional and/or alternative strategies should be investigated for these patients. [ABSTRACT FROM AUTHOR]

Objective. To assess whether publication of national treatment guidelines improved the management of early RA in the UK. Methods. Incident diagnoses of RA in persons aged over 18 years from 1995 to 2010 were identified from the Clinical Practice Research Datalink. Using a natural experimental study design, interrupted time series analysis was used to assess whether trends in the proportion of patients receiving DMARDs, within 3 and 12 months of diagnosis, changed following publication of British Society for Rheumatology guidelines in 2006. Results. Between 1995 and 2010, 11 772 incident cases of RA were identified. There was a progressive increase in the proportion of patients prescribed any DMARD within 12 months from 43.3% in 1995 to 78.5% in 2010. After publication of the British Society for Rheumatology guidelines, the proportion of patients prescribed any DMARD within 12 months increased by 4.2% (P = 0.053). Prior to the guidance, prescribing was increasing by 1.64% per year, compared with 3.55% per year after publication (P< 0.001). Conclusion. Guidelines published by a national body can improve the proportion of patients receiving DMARD treatment in the first year after diagnosis of RA. [ABSTRACT FROM AUTHOR]

Context and objective: We evaluated the predictive value of serum cartilage oligomeric matrix protein (sCOMP) levels over 20 years on the development of radiographic (RKOA) and painful knee osteoarthritis (KOA) in a longitudinal cohort of middle-aged women. Materials and methods: Five hundred and ninety-three women with no baseline KOA underwent 5-year knee radiographs over 20-years and were asked about knee pain a month before each assessment. A repeated measures logistic regression model was used where the outcomes were recorded at 5, 10, 15 and 20-years follow-up. Results: The highest quartile of sCOMP was associated with increased risk of RKOA with overall OR of 1.97 (95% CI: 1.33–2.91) over 20 years when compared with the lowest sCOMP quartile. The association with painful KOA was similar and also independent, but only when the fourth and third sCOMP quartiles were compared. Discussion and conclusion: This study demonstrates that sCOMP levels are predictive of subsequent structural changes and incidence of painful KOA, independently of age and BMI. [ABSTRACT FROM AUTHOR]

Objectives. To prospectively investigate whether hip shape variants at baseline are associated with the need for future total hip replacement (THR) in women and to validate the resulting associated shape variants of the Cohort Hip and Cohort Knee (CHECK) cohort and the Chingford cohort. Methods. Female participants from the CHECK cohort without radiographic OA (Kellgren-Lawrence score <2) at baseline were included (1100 hips); 22 hips had a THR within 5 years of follow-up. For the Chingford cohort, with only female participants, hips without radiographic OA at baseline were selected and a nested case-control design was used, with 19 THR cases within 19 years of follow-up and 95 controls matched 5 to 1 for age and BMI. Hip shape on baseline anteroposterior pelvic radiographs was assessed by statistical shape modelling (SSM) using the same model for both cohorts. Results. In the CHECK and Chingford cohorts, the respective mean age was 55.8 (S.D. 5.1) and 53.6 (S.D. 5.4) and the BMI was 26.14 (S.D. 4.3) and 25.7 (S.D. 3.3), respectively. Multiple shape variants of the hip were significantly (P<0.05) associated with future THR in both the CHECK (modes 4, 11, 15, 17 and 22) and Chingford (modes 2 and 17) cohorts. Mode 17 [odds ratio (OR) 0.51 (95% CI 0.33, 0.80) in the CHECK cohort], representing a flattened head-neck junction and flat greater trochanter, could be confirmed in the Chingford cohort [OR 0.41 (95% CI 0.23, 0.82)]. Modes 4 and 15 of the CHECK cohort also showed non-significant trends in the Chingford cohort. Conclusion. Several baseline shape variants are associated with the future need for THR within a cohort. Despite differences in participant characteristics, radiographic protocol and follow-up time, we could validate at least one shape variant, suggesting that SSM is reasonably transferable between cohorts. [ABSTRACT FROM AUTHOR]

The OHS/OKS are PROMs for assessing symptomatic pain and function following TJA. However, actual change in pre-operative/post-operative scores cannot distinguish patients of varying baseline symptom severity. The percentage of potential change (PoPC) is a simple method that accounts for this, expressing the actual change attained, as a percentage of the potential change possible. Measures are described using OHS/OKS at baseline and 6-months (1784 – TKA, 1523 – THA) from the Elective Orthopaedic Centre. Each method identified different proportions of patients as satisfied and importantly, the measures identified different patients. PoPC overcomes floor and ceiling effects and standardises measures to an easy to interpret − 100 to + 100 scale. In addition to actual change, we recommend using PoPC to assess the overall outcome of patients. [ABSTRACT FROM AUTHOR]

ABSTRACT The objective of this work was to study the associations between ankylosing spondylitis (AS) and clinical vertebral and nonvertebral fractures. Data from a large population-based public health database in Spain, Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària (SIDIAP), were used in this parallel cohort study. All participants registered in SIDIAP on January 1, 2006, were screened to identify those with a diagnosis of AS. Five age-matched, gender-matched, and general practice surgery-matched controls were selected for each patient with AS. All participants were followed until December 31, 2011, transfer out date, or death date. Fractures during this time were classified as vertebral or nonvertebral. Adjustment was made for potential confounders (tobacco smoking, alcohol consumption, body mass index, and use of oral steroids). Of 4,920,353 eligible patients in SIDIAP, 6474 AS patients with matched controls ( n = 32,346) were available. A higher proportion of patients with AS versus controls had clinical vertebral (0.86% versus 0.41%) and nonvertebral (3.4% versus 2.7%) fractures. Adjusted Cox regression models showed an increased risk of clinical vertebral (hazard ratio [HR] 1.93; 95% confidence interval [CI], 1.39 to 2.68; p < 0.001) and nonvertebral (HR 1.19; 95% CI, 1.02 to 1.39; p = 0.03) fractures among patients with AS. However, the observed increased risks were apparent only in those not on regular nonsteroidal anti-inflammatory drugs (NSAIDs). There were no interactions with inflammatory bowel disease, psoriasis, or previous back pain. Patients with AS are at increased risk of vertebral and nonvertebral clinical fractures, independently of various risk factors. Regular use of NSAIDs appears to eliminate the excess fracture risk related to AS, but the mechanisms involved are unknown. © 2014 American Society for Bone and Mineral Research [ABSTRACT FROM AUTHOR]

ABSTRACT Although oral bisphosphonates (BPs) are highly effective in preventing fractures, some patients will fracture while on treatment. We identified predictors of such fractures in a population-based cohort of incident users of oral BPs. We screened the Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària (SIDIAP) database to identify new users of oral BPs in 2006-2007. SIDIAP includes pharmacy invoice data and primary care electronic medical records for a representative 5 million people in Catalonia (Spain). Exclusion criteria were the following: Paget disease; <40 years of age; and any antiosteoporosis treatment in the previous year. A priori defined risk factors included age, gender, body mass index, vitamin D deficiency, smoking, alcohol drinking, preexisting comorbidities, and medications. Fractures were considered if they appeared at least 6 months after treatment initiation. 'Fractures while on treatment' were defined as those occurring among participants persisting for at least 6 months and with an overall high compliance (medication possession ratio ≥80%). Fine and Gray survival models accounting for competing risk with therapy discontinuation were fitted to identify key predictors. Only 7449 of 21,385 (34.8%) participants completed >6 months of therapy. Incidence of fracture while on treatment was 3.4/100 person-years (95% confidence interval [CI], 3.1-3.7). Predictors of these among patients persisting and adhering to treatment included: older age (subhazard ratio [SHR] for 60 to <80 years, 2.18 [95% CI, 1.70-2.80]; for ≥80 years, 2.5 [95% CI, 1.82-3.43]); previous fracture (1.75 [95% CI, 1.39-2.20] and 2.49 [95% CI, 1.98-3.13], in the last 6 months and longer, respectively); underweight, 2.11 (95% CI, 1.14-3.92); inflammatory arthritis, 1.46 (95% CI, 1.02-2.10); use of proton pump inhibitors (PPIs), 1.22 (95% CI, 1.02-1.46); and vitamin D deficiency, 2.69 (95% CI, 1.27-5.72). Even among high compliers, 3.4% of oral BP users will fracture every year. Older age, underweight, vitamin D deficiency, PPI use, previous fracture, and inflammatory arthritides increase risk. Monitoring strategies and/or alternative therapies should be considered for these patients. © 2014 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Objective. To identify pre-operative predictors of patient-reported outcomes of primary total knee replacement (TKR) surgery.Methods. The Elective Orthopaedic Centre database is a large prospective cohort of 1991 patients receiving primary TKR in south-west London from 2005 to 2008. The primary outcome is the 6-month post-operative Oxford Knee Score (OKS). To classify whether patients had a clinically important outcome, we calculated a patient acceptable symptom state (PASS) for the 6-month OKS related to satisfaction with surgery. Potential predictor variables were pre-operative OKS, age, sex, BMI, deprivation, surgical side, diagnosis, operation type, American Society of Anesthesiologists grade and EQ5D anxiety/depression. Regression modelling was used to identify predictors of outcome.Results. The strongest determinants of outcome include pre-operative pain/function—those with less severe pre-operative disease obtain the best outcomes; diagnosis in relation to pain outcome—patients with RA did better than those with OA; deprivation—those living in poorer areas had worse outcomes; and anxiety/depression—worse pre-operative anxiety/depression led to worse pain. Differences were observed between predictors of pain and functional outcomes. Diagnosis of RA and anxiety/depression were associated with pain, whereas age and gender were specifically associated with function. BMI was not a clinically important predictor of outcome.Conclusion. This study identified clinically important predictors of attained pain/function post-TKR. Predictors of pain were not necessarily the same as functional outcomes, which may be important in the context of a patient’s expectations of surgery. Other predictive factors need to be identified to improve our ability to recognize patients at risk of poor TKR outcomes. [ABSTRACT FROM PUBLISHER]

Objectives. To describe the incidence and prevalence of peripheral neuropathy in ANCA-associated vasculitis (AAV); to evaluate the correlation of neuropathy with other clinical manifestations; and to review the long-term outcome of treated neuropathy.Methods. Presence of neuropathy was determined using items from the BVAS and vasculitis damage index (VDI) during 5 years from enrolment into clinical trials conducted by the European Vasculitis Study Group (EUVAS).Results. Forty (8%) of 506 patients had vasculitic neuropathy at baseline. Incidence of vasculitic motor-involving neuropathy was identical between microscopic polyangiitis (MPA) [16 (7%) out of 237] and granulomatosis with polyangiitis (Wegener's) [19 (7%) out of 269], P = 0.94. Pure sensory neuropathy was reported in 5 (2%) out of 269 patients with granulomatosis with polyangiitis, but not in patients with MPA, P = 0.065. Vasculitic neuropathy at baseline was associated with systemic [odds ratio (OR) = 1.81], cutaneous (OR = 1.29), mucous membranes (OR = 1.21) and ENT (OR = 1.14) manifestations of vasculitis (P < 0.05 for all). There was no association between neuropathy and renal, chest, cardiovascular or abdominal vasculitis or with overall mortality. Of the 40 patients with vasculitic neuropathy at baseline, 35% had complete resolution within 6 months. The cumulative prevalence of chronic neuropathy at any time up to 5 years was 15% (75 of 506). Chronic neuropathy was associated with older age [hazard ratio (HR) = 1.03], higher BVAS (HR = 1.07) and lower baseline creatinine (HR = 0.82) (P < 0.01 for all).Conclusion. Peripheral neuropathy is an occasional accompaniment of AAV that typically remits in concert with non-neuropathic manifestations, usually involves motor nerves, often produces long-lasting symptoms and is not associated with life-threatening organ involvement. [ABSTRACT FROM PUBLISHER]

The article discusses the result of a study which investigated prenatal influences on bone health. The findings suggest that intrauterine growth may influence postnatal volumetric density and skeletal size and that the tracking of skeletal development originates in the prenatal period. It also indicates that the factors affecting late intrauterine growth may have lasting effects on postnatal skeletal development. It concludes that the velocity of femur growth from 19 to 34 weeks predicts childhood skeletal size at four years.

Background: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. Methods and findings: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each \(1 kg/m^{2}\) higher BMI was associated with 1.15% lower 25(OH)D \((p = 6.52×10^{−27})\). The BMI allele score was associated both with BMI \((p = 6.30×10^{−62})\) and 25(OH)D (−0.06% [95% CI −0.10 to −0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D \((p≤8.07×10^{−57}\) for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: −4.2 [95% CI −7.1 to −1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores). Conclusions: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency. Please see later in the article for the Editors' Summary.

Background: This study aimed at identifying preoperative predictors of patient-reported outcomes after total knee arthroplasty (TKA) and at investigating their association with the outcomes over time.Methods: We used data from 2080 patients from the Knee Arthroplasty Trial who received primary TKA in the United Kingdom between July 1999 and January 2003. The primary outcome measure was the Oxford knee score (OKS) collected annually over 10 years after TKA. Preoperative predictors included a range of patient characteristics and clinical conditions. Mixed-effects linear regression model analysis of repeated measurements was used to identify predictors of overall OKS, and pain and function subscale scores over 10 years, separately.Results: Worse preoperative OKS, worse mental well-being, body mass index greater than 35 kg/m2, living in the most deprived areas, higher American Society of Anesthesiologists grade, presence of comorbidities, and history of previous knee surgery were associated with worse overall OKS over 10 years after surgery. The same predictors were identified for pain and function subscale scores, and for both long-term (10 years) and short-to-medium-term outcomes (1 and 5 years). However, fitted models explained more variations in function and shorter-term outcomes than in pain and longer-term outcomes, respectively.Conclusion: The same predictors were identified for pain and functional outcomes over both short-to-medium term and long term after TKA. Within the factors identified, functional and shorter-term outcomes were more predictable than pain and longer-term outcomes, respectively. Regardless of their preoperative characteristics, on average, patients achieved substantial improvement in pain over time, although improvement for function was less prominent. [ABSTRACT FROM AUTHOR]

Abstract: The gold standard for measuring knee alignment is mechanical axis determined using full-limb radiographs (FLR). Measurement of joint alignment using antero-posterior (AP) knee radiographs is more accessible, economical and involves less radiation exposure to the patient compared with using full-limb radiographs. The aim of this study was to compare and assess the reproducibility of knee joint axial alignment on full-limb radiographs and conventional AP knee radiographs. Knee alignment was measured in 40 subjects (80 knees) from the TwinsUK registry. Measurement of mechanical knee alignment was from FLR, and anatomic knee alignment from weight-bearing AP knee radiographs. Reproducibility was assessed by intra-class correlation coefficients and kappa statistics. Reproducibility of knee alignment for both methods was good, with intra-observer ICC''s of 0.99 for both FLR and AP radiographs. The mean alignment angle on FLR was 178.9° (SD 2.1, range 173–183°), and 179.0° (SD 2.1, range 173–185°) on AP films. 58.8% of knees on FLR and 66.3% on AP films were of varus alignment. Good correlations were seen between results for FLR and AP radiographs, with ICC ranging from 0.87–0.92 for left and right knees, and kappa statistics of 0.65–0.74. Standard AP knee radiographs can be used to measure knee alignment with good reproducibility, and provide comparable results to those obtained from FLR. This will facilitate measurement of knee alignment in existing cohort studies to assess malalignment as a risk factor of incident OA, and in clinical practice. [Copyright &y& Elsevier]