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ObjectiveThe effect of physical activity on the risk of developing knee osteoarthritis (OA) is unclear. We undertook this study to examine the relationship between recreational physical activity and incident knee OA outcomes using comparable physical activity and OA definitions.MethodsData were acquired from 6 global, community-based cohorts of participants with and those without knee OA. Eligible participants had no evidence of knee OA or rheumatoid arthritis at baseline. Participants were followed up for 5-12 years for incident outcomes including the following: 1) radiographic knee OA (Kellgren-Lawrence [K/L] grade ≥2), 2) painful radiographic knee OA (radiographic OA with knee pain), and 3) OA-related knee pain. Self-reported recreational physical activity included sports and walking/cycling activities and was quantified at baseline as metabolic equivalents of task (METs) in days per week. Risk ratios (RRs) were calculated and pooled using individual participant data meta-analysis. Secondary analysis assessed the association between physical activity, defined as time (hours per week) spent in recreational physical activity and incident knee OA outcomes.ResultsBased on a total of 5,065 participants, pooled RR estimates for the association of MET days per week with painful radiographic OA (RR 1.02 [95% confidence interval (95% CI) 0.93-1.12]), radiographic OA (RR 1.00 [95% CI 0.94-1.07]), and OA-related knee pain (RR 1.00 [95% CI 0.96-1.04]) were not significant. Similarly, the analysis of hours per week spent in physical activity also showed no significant associations with all outcomes.ConclusionOur findings suggest that whole-body, physiologic energy expenditure during recreational activities and time spent in physical activity were not associated with incident knee OA outcomes.

BackgroundOsteoarthritis (OA) is a chronic joint disease, with increasing global burden of disability and healthcare utilisation. Recent meta-analyses have shown a range of effects of OA on mortality, reflecting different OA definitions and study methods. We seek to overcome limitations introduced when using aggregate results by gathering individual participant-level data (IPD) from international observational studies and standardising methods to determine the association of knee OA with mortality in the general population.MethodsSeven community-based cohorts were identified containing knee OA-related pain, radiographs, and time-to-mortality, six of which were available for analysis. A two-stage IPD meta-analysis framework was applied: (1) Cox proportional hazard models assessed time-to-mortality of participants with radiographic OA (ROA), OA-related pain (POA), and a combination of pain and ROA (PROA) against pain and ROA-free participants; (2) hazard ratios (HR) were then pooled using the Hartung-Knapp modification for random-effects meta-analysis.Findings10,723 participants in six cohorts from four countries were included in the analyses. Multivariable models (adjusting for age, sex, race, BMI, smoking, alcohol consumption, cardiovascular disease, and diabetes) showed a pooled HR, compared to pain and ROA-free participants, of 1.03 (0.83, 1.28) for ROA, 1.35 (1.12, 1.63) for POA, and 1.37 (1.22, 1.54) for PROA.DiscussionParticipants with POA or PROA had a 35-37% increased association with reduced time-to-mortality, independent of confounders. ROA showed no association with mortality, suggesting that OA-related knee pain may be driving the association with time-to-mortality.FundingVersus Arthritis Centre for Sport, Exercise and Osteoarthritis and Osteoarthritis Research Society International.

ObjectivesTo examine whether foot and/or ankle pain increases the risk of knee OA.DesignWe utilised longitudinal data from the Multicentre Osteoarthritis Study (MOST); a community-based cohort of risk factors for knee OA. Participants without frequent knee pain (clinic visit only) and radiographic knee OA (RKOA) at baseline and, with no evidence of inflammatory musculoskeletal disease and a history of knee-related surgery were followed for up to 84-months for incident outcomes; i) RKOA (Kellgren-Lawrence (KL) ≥2), ii) symptomatic RKOA (RKOA and frequent pain in the same knee) and iii) frequent knee pain only. At baseline, ankle and foot symptoms were assessed, with knee radiographs and symptoms also assessed at 30, 60 and 84-months. Our exposures included baseline ankle, foot, and ankle and foot pain (participant-level). Associations between foot and/or ankle pain and incident outcomes were assessed using multiple logistic regression, with adjustment for participant characteristics and ankle/foot pain.ResultsNo statistically significant associations were observed between ankle, foot and, ankle and foot pain and incident RKOA, respectively. Ankle pain with (2.30, 95% CI 1.13 to 4.66) and without foot pain (OR: 2.53, 95% CI 1.34 to 4.80) were associated with increased odds of incident symptomatic RKOA and frequent knee pain. No statistically significant associations were observed between foot pain and these outcomes.ConclusionsAnkle pain should be a focus point, more so than foot pain, in the management of knee OA. Future studies should include additional ankle joint-specific symptom questions to better elucidate the knee OA biomechanical pathway.

BackgroundOsteoarthritis (OA) is a chronic joint disease, with increasing global burden of disability and healthcare utilisation. Recent meta-analyses have shown a range of effects of OA on mortality, reflecting different OA definitions and study methods. We seek to overcome limitations introduced when using aggregate results by gathering individual participant-level data (IPD) from international observational studies and standardising methods to determine the association of knee OA with mortality in the general population.MethodsSeven community-based cohorts were identified containing knee OA-related pain, radiographs, and time-to-mortality, six of which were available for analysis. A two-stage IPD meta-analysis framework was applied: (1) Cox proportional hazard models assessed time-to-mortality of participants with radiographic OA (ROA), OA-related pain (POA), and a combination of pain and ROA (PROA) against pain and ROA-free participants; (2) hazard ratios (HR) were then pooled using the Hartung-Knapp modification for random-effects meta-analysis.Findings10,723 participants in six cohorts from four countries were included in the analyses. Multivariable models (adjusting for age, sex, race, BMI, smoking, alcohol consumption, cardiovascular disease, and diabetes) showed a pooled HR, compared to pain and ROA-free participants, of 1.03 (0.83, 1.28) for ROA, 1.35 (1.12, 1.63) for POA, and 1.37 (1.22, 1.54) for PROA.DiscussionParticipants with POA or PROA had a 35-37% increased association with reduced time-to-mortality, independent of confounders. ROA showed no association with mortality, suggesting that OA-related knee pain may be driving the association with time-to-mortality.FundingVersus Arthritis Centre for Sport, Exercise and Osteoarthritis and Osteoarthritis Research Society International.

ObjectivesTo examine whether foot and/or ankle pain increases the risk of knee OA.DesignWe utilised longitudinal data from the Multicentre Osteoarthritis Study (MOST); a community-based cohort of risk factors for knee OA. Participants without frequent knee pain (clinic visit only) and radiographic knee OA (RKOA) at baseline and, with no evidence of inflammatory musculoskeletal disease and a history of knee-related surgery were followed for up to 84-months for incident outcomes; i) RKOA (Kellgren-Lawrence (KL) ≥2), ii) symptomatic RKOA (RKOA and frequent pain in the same knee) and iii) frequent knee pain only. At baseline, ankle and foot symptoms were assessed, with knee radiographs and symptoms also assessed at 30, 60 and 84-months. Our exposures included baseline ankle, foot, and ankle and foot pain (participant-level). Associations between foot and/or ankle pain and incident outcomes were assessed using multiple logistic regression, with adjustment for participant characteristics and ankle/foot pain.ResultsNo statistically significant associations were observed between ankle, foot and, ankle and foot pain and incident RKOA, respectively. Ankle pain with (2.30, 95% CI 1.13 to 4.66) and without foot pain (OR: 2.53, 95% CI 1.34 to 4.80) were associated with increased odds of incident symptomatic RKOA and frequent knee pain. No statistically significant associations were observed between foot pain and these outcomes.ConclusionsAnkle pain should be a focus point, more so than foot pain, in the management of knee OA. Future studies should include additional ankle joint-specific symptom questions to better elucidate the knee OA biomechanical pathway.

ObjectivesTo examine the effect of occupation on knee osteoarthritis (OA) and total knee replacement (TKR) in working-aged adults.MethodsWe used longitudinal data from the Chingford, Osteoarthritis Initiative (OAI) and Multicentre Osteoarthritis (MOST) studies. Participants with musculoskeletal disorders and/or a history of knee-related surgery were excluded. Participants were followed for up to 19-years (Chingford), 96-months (OAI) and 60-months (MOST) for incident outcomes including radiographic knee OA (RKOA), symptomatic RKOA and TKR. In those with baseline RKOA, progression was defined as the time from RKOA incidence to primary TKR. Occupational job categories and work-place physical activities were assigned to levels of workload. Logistic regression was used to examine the relationship between workload and incident outcomes with survival analyses used to assess progression (reference group: sedentary occupations).ResultsHeavy manual occupations were associated with a 2-fold increased risk (OR: 2.07, 95% CI 1.03 to 4.15) of incident RKOA in the OAI only. Men working in heavy manual occupations in MOST (2.7, 95% CI 1.17 to 6.26) and light manual occupations in OAI (2.00, 95% CI 1.09 to 3.68) had a 2-fold increased risk of incident RKOA. No association was observed among women. Increasing workload was associated with an increased risk of symptomatic RKOA in the OAI and MOST. Light work may be associated with a decreased risk of incident TKR and disease progression.ConclusionHeavy manual work carries an increased risk of incident knee OA; particularly among men. Workload may influence the occurrence of TKR and disease progression.

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.

Background: Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR). The validity of JADAS for all ILAR subtypes in the routine clinical setting is unknown. We investigated the construct validity of JADAS in the clinical setting in all subtypes of JIA through application to a prospective inception cohort of UK children presenting with new onset inflammatory arthritis. Methods: JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all subtypes. All correlations were calculated using Spearman's rank statistic. Results: 262/1238 visits had sufficient data for calculation of JADAS (1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%) ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and 64% were female. Correlation between JADAS 10, 27 and 71 approached 1 for all subtypes. Median JADAS 71 was 5.3 (IQR 2.2-10.1) with a significant difference between median JADAS scores between subtypes (p < 0.01). Correlation of JADAS 71 with each single marker of DA was moderate to high in the total cohort (see Table 1). Overall, correlation with AJC, PGA and PGE was moderate to high and correlation with ESR, limited JC, parental pain and CHAQ was low to moderate in the individual subtypes. Correlation coefficients in the extended oligoarticular, rheumatoid factor negative and enthesitis related subtypes were interpreted with caution in view of low numbers. Conclusions: This study adds to the body of evidence supporting the construct validity of JADAS. JADAS correlates with other measures of DA in all ILAR subtypes in the routine clinical setting. Given the high frequency of missing ESR data, it would be useful to assess the validity of JA

Knee arthroplasty (KA) has been considered to be a successful and cost-effective intervention for individuals with severe end stage Osteoarthritis (OA). A number of clinically important predictors of outcomes following KA have been established, however there are still other factors to be identified to improve our ability to recognise patients at risk of poor KA outcomes. Although the relationship between foot, ankle and knee kinematics has become widely accepted, it is not known whether foot and ankle status affect KA outcomes. This thesis therefore aims to determine whether clinical foot and ankle measures are useful in predicting patient reported outcomes following KA. A formal literature review was firstly undertaken to identify current methods of assessing musculoskeletal foot and ankle status. Findings of the review revealed an absence of a standardised assessment protocol and a lack of agreement and validity for many current clinical measures. In response to this an international expert consensus study was undertaken to produce an agreed set of objective clinical musculoskeletal foot and ankle assessment measures to form a new protocol. Two measures identified from the review, and agreed via expert consensus, as the most robust assessment methods- the Foot Posture Index (FPI) and ankle dorsiflexion, were introduced to a large prospective cohort of patients awaiting knee arthroplasty, in addition to foot pain questions. Results show that ankle dorsiflexion and foot posture were not associated with one year knee outcomes, however pre-operative foot pain was associated to outcome; the presence of foot pain increased the risk of a poor post-operative clinical outcome. Findings suggest that it would be beneficial to address foot pain prior to surgery to reduce the risks associated with a poor outcome. Further work would be beneficial to establish the sequential link between foot pain and knee OA in order to inform the most appropriate method of the conservative man

Knee arthroplasty (KA) has been considered to be a successful and cost-effective intervention for individuals with severe end stage Osteoarthritis (OA). A number of clinically important predictors of outcomes following KA have been established, however there are still other factors to be identified to improve our ability to recognise patients at risk of poor KA outcomes. Although the relationship between foot, ankle and knee kinematics has become widely accepted, it is not known whether foot and ankle status affect KA outcomes. This thesis therefore aims to determine whether clinical foot and ankle measures are useful in predicting patient reported outcomes following KA. A formal literature review was firstly undertaken to identify current methods of assessing musculoskeletal foot and ankle status. Findings of the review revealed an absence of a standardised assessment protocol and a lack of agreement and validity for many current clinical measures. In response to this an international expert consensus study was undertaken to produce an agreed set of objective clinical musculoskeletal foot and ankle assessment measures to form a new protocol. Two measures identified from the review, and agreed via expert consensus, as the most robust assessment methods- the Foot Posture Index (FPI) and ankle dorsiflexion, were introduced to a large prospective cohort of patients awaiting knee arthroplasty, in addition to foot pain questions. Results show that ankle dorsiflexion and foot posture were not associated with one year knee outcomes, however pre-operative foot pain was associated to outcome; the presence of foot pain increased the risk of a poor post-operative clinical outcome. Findings suggest that it would be beneficial to address foot pain prior to surgery to reduce the risks associated with a poor outcome. Further work would be beneficial to establish the sequential link between foot pain and knee OA in order to inform the most appropriate method of the conservative man

Background: Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR). The validity of JADAS for all ILAR subtypes in the routine clinical setting is unknown. We investigated the construct validity of JADAS in the clinical setting in all subtypes of JIA through application to a prospective inception cohort of UK children presenting with new onset inflammatory arthritis. Methods: JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all subtypes. All correlations were calculated using Spearman's rank statistic. Results: 262/1238 visits had sufficient data for calculation of JADAS (1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%) ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and 64% were female. Correlation between JADAS 10, 27 and 71 approached 1 for all subtypes. Median JADAS 71 was 5.3 (IQR 2.2-10.1) with a significant difference between median JADAS scores between subtypes (p < 0.01). Correlation of JADAS 71 with each single marker of DA was moderate to high in the total cohort (see Table 1). Overall, correlation with AJC, PGA and PGE was moderate to high and correlation with ESR, limited JC, parental pain and CHAQ was low to moderate in the individual subtypes. Correlation coefficients in the extended oligoarticular, rheumatoid factor negative and enthesitis related subtypes were interpreted with caution in view of low numbers. Conclusions: This study adds to the body of evidence supporting the construct validity of JADAS. JADAS correlates with other measures of DA in all ILAR subtypes in the routine clinical setting. Given the high frequency of missing ESR data, it would be useful to assess the validity of JA