Comorbidities in Osteoarthritis: a systematic review and meta-analysis of observational studies

ObjectivesOsteoarthritis (OA) is a common chronic condition in older people but its association with other chronic conditions is largely unknown. This study aimed to systematically review the literature on comorbidities in people with OA compared to those without.MethodsWe searched four databases for observational studies on comorbidities in people with OA. Studies of OA only or in comparison with non‐OA controls were included. Risk of bias and study quality was assessed using the Newcastle‐Ottawa Scale (NOS). The prevalence of comorbidities in the OA group and prevalence ratio (PR) and 95% confidence interval (CI) between OA and non‐OA groups were calculated.ResultsForty‐two studies from 16 countries (27 case‐only and 15 comparative studies) met the inclusion criteria. Mean age of participants varied from 51 to 76 years. Pooled prevalence of any comorbidity was 67% (95%CI: 57%‐74%) in people with OA versus 56% (95%CI: 44%‐68%) in people without OA. The pooled PR for any comorbidity was 1.21 (95%CI: 1.02‐1.45). The PR increased from 0.73 (95%CI: 0.43‐1.25) for one comorbidity, to 1.58 (95%CI: 1.03‐2.42) for two, and 1.94 (95%CI 1.45‐ 2.59) for three or more comorbidities. The key comorbidities associated with OA were stroke (PR 2.61; 95%CI: 2.13‐3.21), peptic ulcer (PR 2.36; 95%CI: 1.71‐3.27) and metabolic syndrome (PR 1.94; 95%CI 1.21‐3.12).ConclusionsPeople with OA are more likely to have other chronic conditions. The association is dose‐dependent in terms of the number of comorbidities, suggesting multimorbidities. Further studies on the causality of this association and clinical implications are needed

Comment on: Conventional and biologic disease-modifying anti-rheumatic drugs for osteoarthritis: a meta-analysis of randomized controlled trials: Reply

MD reports a grant from AstraZeneca funding a non-drug PI-led study in Nottingham (Sons of Gout study) and honoraria for Advisory boards on osteoarthritis and gout for AstraZeneca, Grunenthal, Mallinckrodt, and Roche, outside the submitted work. WZ reports honoraria for Grunenthal and speaker fees for Bioiberica and Hisun, outside the submitted work. All other authors have declared no conflicts of interest

Proportion of contextual effects in the treatment of fibromyalgia - a meta-analysis of randomised controlled trials

Objectives: To examine the proportion of the total treatment effect that is attributable to contextual effects in randomised controlled trials (RCTs) of treatments for fibromyalgia. Methods: A systematic literature search was undertaken in Medline, Web of Science, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Allied and Complementary Medicine in September 2015. The proportion of contextualeffect (PCE) was calculated by dividing the improvement in the placebo arm by the improvement in the treatment arm. The measure was log-transformed for each trial and the random effects model was used to pool data. The primary outcome was pain. Secondary outcomes were fibromyalgia impact questionnaire (FIQ) total and fatigue. Heterogeneity was quantified using I2. Publication bias was assessed using a funnel plot and Egger's test. Subgroup analysis was undertaken to explore heterogeneity and potential determinants of the PCE. Results: 51 eligible trials (9599 participants) were identified. The PCE was 0.60 (95% CI0·56 to 0·64) for pain, 0·57 (95% CI 0·53 to 0·61) for FIQ total, and 0·63 (95% CI 0·59 to 0·68) for fatigue. The I2 was 99.4% for pain, 99.2% for FIQ total, and 97.6% for fatigue. Conclusion: More than half of the treatment effect in fibromyalgia RCTs results from non-specific contextual factors. Reporting the total treatment effect and the proportion of contextual effect in trials may help to better translate research evidence into clinical practice

Conventional and biologic disease-modifying anti-rheumatic drugs for osteoarthritis:a meta-analysis of randomized controlled trials

ObjectivesThe role of inflammation in OA is controversial and it is unclear whether suppressing inflammation with conventional or biologic DMARDs is effective. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to compare DMARDs with placebo in participants with symptomatic OA.MethodsDatabases (Medline, Embase, Allied and Complementary Medicine Database, Web of Science and Cochrane Library), conference abstracts and ClinicalTrials.gov were searched to end of November 2017 for placebo-controlled RCTs of DMARDs, including biologics, in symptomatic OA. Pain data at treatment peak time point were extracted and combined using a random-effects meta-analysis. Markers of inflammation and adverse events were extracted and reviewed. Risk of bias assessment was conducted using Cochrane’s tool.ResultsEleven RCTs (1205 participants) were meta-analysed, including six for conventional DMARDs (757 participants) and five for biologics (448 participants). Overall, DMARDs were statistically superior to placebo [effect size (ES) = 0.18, 95% CI: 0.03, 0.34], although the difference was not clinically significant (0.5 ES threshold). Furthermore, no statistically significant differences were observed in sub-analysis of high-quality trials (ES = 0.11, 95% CI : −0.06, 0.28), biologics (ES = 0.16, 95% CI: −0.02, 0.34) or conventional DMARDs (ES = 0.24, 95% CI: −0.05, 0.54). No difference was found between erosive vs non-erosive hand OA, hand vs knee OA or anti-IL1 vs anti-TNF biologics.ConclusionDMARDs did not offer clinically significant pain relief above placebo in OA. This poor efficacy indicates that inflammation may not be a prime driver for OA pain

Comment on: Conventional and biologic disease-modifying anti-rheumatic drugs for osteoarthritis: a meta-analysis of randomized controlled trials: Reply

MD reports a grant from AstraZeneca funding a non-drug PI-led study in Nottingham (Sons of Gout study) and honoraria for Advisory boards on osteoarthritis and gout for AstraZeneca, Grunenthal, Mallinckrodt, and Roche, outside the submitted work. WZ reports honoraria for Grunenthal and speaker fees for Bioiberica and Hisun, outside the submitted work. All other authors have declared no conflicts of interest

Prediction of persistent knee pain by pressure pain detection thresholds: results from the Knee Pain In the Community cohort (KPIC)

Background: Knee pain results from a combination of nociceptive input from the joint, and processing by the central nervous system. Pressure pain detection thresholds (PPTs) are lower and pain is more severe in people with greater central sensitisation. Objective: We hypothesised that lower PPTs predicted worse pain prognosis in people with knee pain. Methods: KPIC participants were people aged >40 years recruited from Nottingham, UK. Participants were mailed questionnaires at baseline and 1 year. This study reports a sample of responders who attended baseline and 1 year clinical assessment, had self-reported knee pain (within the last 4 weeks) and underwent PPT. PPTs were measured at the knee, anterior tibia and the sternum. Radiographic knee OA was classified using an atlas. Questionnaires measured ICOAP (constant and intermittent knee pain), painDETECT (neuropathic-like) and average knee pain severity over 4 weeks (0-10). The presence of pain at baseline and 1 year (persistent pain), or pain severity were predicted from baseline anterior tibia PPT. Additional analyses adjusted for baseline pain score, age, sex, BMI, or for radiographic knee OA. Pain persistence (Yes/No) was analysed using t tests, odds ratios (OR) and logistic regression. Pain severity was analysed using linear regression. Results: The sample for this study contained n=419 people at baseline, and n=182 people reported knee pain persistent over both time points. The mean (SD) values were age 61 (9) years, BMI 30.1 (5.8) kg m-2, 59% female, and 36% fulfilled radiographic OA criteria at the index knee, for those with persistent knee pain at 1 year. In univariate analysis, persistent knee pain was associated with a lower PPT at baseline (461 vs 424 kPa; OR (95% CI) 0.58 (0.34-0.97) p=0.020). Adjustments for age, sex and BMI removed the significance from the association (adjusted OR (95% CI) 0.64 (0.36-1.13) p=0.120). In those with persistent pain, worse 1 year ICOAP-constant, ICOAP-intermittent, painDETECT and knee pain severity were correlated with lower baseline anterior tibia PPT ( r= -0.28 to -0.24; p<0.004). After adjustment for baseline pain, 1 year ICOAP-constant pain scale was significantly predicted by baseline PPT (B (95% CI), -1.05 (-1.91 to -0.20) p=0.016). Linear regression with adjustments for age, sex and BMI also indicated that baseline PPT predicted worse ICOAP-constant pain (B (95% CI)-0.99 (-1.94 to -0.04) p=0.041). The presence of radiographic OA at baseline was not significantly associated with PPT at baseline. Adjustment for baseline radiographic OA did not remove the association between baseline PPT and ICOAP-constant at 1 year (anterior tibia PPT -1.04 (-1.89 to -0.18) p=0.018). PPT at joint lines or sternum displayed similar patterns of association with 1 year pain as did PPT at the anterior tibia. Conclusions: Pressure pain detection thresholds suggestive of central sensitisation at baseline were associated with knee pain prognosis at 1 year, in particular with constant knee pain. The presence of radiographic OA also predicted 1 year pain prognosis, independent of PPT

Individual responses to topical ibuprofen gel or capsaicin cream for painful knee osteoarthritis: a series of n-of-1 trials

OBJECTIVES: To determine individual responses to ibuprofen gel or capsaicin cream for painful, radiographic knee OA using a series of n-of-1 trials. METHODS: Twenty-two participants were allocated 5% ibuprofen gel (A) and 0.025% capsaicin cream (B) in random sequence (AB or BA). Patients underwent up to 3 treatment cycles, each comprising one treatment for 4 weeks, an individualized washout period (maximum 4 weeks), then the other treatment for 4 weeks. Differential (ibuprofen or capsaicin) response was defined when change-from-baseline pain intensity scores (0-10 NRS) differed by ≥1 between treatments in ≥2 cycles within a participant. RESULTS: A total of 104 treatment periods were aggregated. Mean pain reduction was 1.2 (95% CI: 0.5, 1.8) on ibuprofen and 1.6 (95% CI: 0.9, 2.4) on capsaicin (P = 0.221). Of 22 participants, 4 (18%) had a greater response to ibuprofen, 9 (41%) to capsaicin, 4 (18%) had similar responses, and 5 (23%) were undetermined. CONCLUSION: Irrespective of equal efficacy overall, 59% of people displayed a greater response to one treatment over the other. Patients who do not benefit from one type of topical treatment should be offered to try another, which may be more effective. N-of-1 trials are useful to identify individual response to treatment. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov, NCT03146689

Contribution of central and peripheral risk factors to prevalence, incidence and progression of knee pain:a community-based cohort study

AimTo explore risk factors that may influence knee pain (KP) through central or peripheral mechanisms.MethodsA questionnaire-based prospective community cohort study with KP defined as pain in or around a knee on most days for at least a month. Baseline prevalence, and one year incidence and progression (KP worsening) were examined. Central (e.g., Pain Catastrophizing Scale (PCS)) and peripheral (e.g., significant injury) risk factors were examined. Adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated using logistic regression. Proportional risk contribution (PRC) was estimated using receiver-operator-characteristic (ROC) analysis.ResultsOf 9506 baseline participants, 4288 (45%) had KP (men 1826; women, 2462). KP incidence was 12% (men 11%, women 13%), and KP progression 19% (men 16%, women 21%) at one year. While both central and peripheral factors contributed to prevalence, central factors contributed more to progression, and peripheral factors more to incidence of KP. For example, although PCS (OR 2.06, 95% CI 1.88–2.25) and injury (5.62, 4.92–6.42) associated with KP prevalence, PCS associated with progression (2.27, 1.83–2.83) but not incidence (1.14, 0.86–1.52), whereas injury more strongly associated with incidence (69.27, 24.15–198.7) than progression (2.52, 1.48–4.30). The PRC of central and peripheral factors were 19% and 23% for prevalence, 14% and 29% for incidence, and 29% and 5% for progression, respectively.ConclusionsBoth central and peripheral risk factors influence KP but relative contributions may differ in terms of development (mainly peripheral) and progression (mainly central). Further study of such relative contributions may inform primary and secondary prevention strategies

Constitutional morphological features and risk of hip osteoarthritis: A case-control study using standard radiographs

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. Objectives: To evaluate the risk of association with hip osteoarthritis (OA) of 14 morphological features measured on standard antero-posterior pelvis radiographs. Methods: A case-control study of 566 symptomatic unilateral hip OA cases and 1108 controls without hip OA, using the Genetics of OA and Lifestyle database. Unaffected hips of cases were assumed to reflect pre-OA morphology of the contralateral affected hip. ORs with 95% CI adjusted for confounding factors were calculated using logistic regression. Hierarchical clustering on principal component method was used to identify clusters of morphological features. Proportional risk contribution (PRC) of these morphological features in the context of other risk factors of hip OA was estimated using receiver operating characteristic analysis. Results: All morphological features showed right-left symmetry in controls. Each feature was associated with hip OA after adjusting for age, gender and body mass index. Increased sourcil angle had the strongest association (OR: 6.93, 95% CI 5.16 to 9.32). Three clusters were identified. The PRC varied between individual features, as well as between clusters. It was 35% (95% CI 31% to 40%) for all 14 morphological features, compared to 21% (95% CI 19% to 24%) for all other well-established risk factors. Conclusions: Constitutional morphological variation strongly associates with hip OA development and may explain much of its heritability. Relevant morphological measures can be assessed readily on standard radiographs to help predict risk of hip OA. Prospective studies are required to provide further support for causality