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Efficacy of bisphosphonates in specific knee osteoarthritis subpopulations: protocol for an OA Trial Bank systematic review and individual patient data meta-analysis.

ABSTRACT: INTRODUCTION:Randomised clinical trials to date investigating the efficacy of bisphosphonates in knee osteoarthritis (OA) have found divergent results, with a recent meta-analysis finding no superiority of these drugs over placebo. Whether particular patient subgroups are more likely to benefit from this therapy than others is still unclear. We aim to investigate the effects of bisphosphonates compared with a control group (placebo, no treatment, another active treatment) on clinical and structural outcomes in specific knee OA subpopulations with possible distinct rates of subchondral bone turnover. METHODS AND ANALYSIS:Medline, Embase, Scopus, Web of Sciences and Cochrane Central Register of Controlled Trials will be searched from inception to February 2018. Randomised clinical trials will be eligible if they reported at least one potential treatment effect modifier at baseline: gender, menopausal status, age, body mass index, radiographic stage, knee pain severity, presence of bone marrow lesions, levels of biochemical markers of bone turnover (serum and/or urinary) and systemic bone mineral density status. Authors of original trials will be contacted to obtain individual patient data from each study. Risk of bias will be assessed using the Cochrane Collaboration's tool. The primary outcomes will include pain and radiographic joint space width loss. Studies using other MRI-based assessment of disease progression will also be eligible. Outcomes will be grouped into short-term (?3 months), intermediate-term (>3 months; ?12 months) and long-term (>12 months). Regression models will be used, adding an interaction term for each subgroup of interest to determine possible subgroup effects. There was no source of funding for this study. ETHICS AND DISSEMINATION:Dissemination of our findings is planned to occur through conference presentations, publication in peer-reviewed journals and social media. No formal ethics approval is generally required as no new data collection will be undertaken. PROSPERO REGISTRATION NUMBER:CRD42018093327.

SUBMITTER: Deveza LA

PROVIDER: S-EPMC6303587 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Efficacy of bisphosphonates in specific knee osteoarthritis subpopulations: protocol for an OA Trial Bank systematic review and individual patient data meta-analysis.

Deveza Leticia A LA Bierma-Zeinstra Sita M A SMA van Spil Willem Evert WE Oo Win Min WM Saragiotto Bruno T BT Neogi Tuhina T van Middelkoop Marienke M Hunter David J DJ

BMJ open 20181219 12

<h4>Introduction</h4>Randomised clinical trials to date investigating the efficacy of bisphosphonates in knee osteoarthritis (OA) have found divergent results, with a recent meta-analysis finding no superiority of these drugs over placebo. Whether particular patient subgroups are more likely to benefit from this therapy than others is still unclear. We aim to investigate the effects of bisphosphonates compared with a control group (placebo, no treatment, another active treatment) on clinical and ...[more]

PMID: 30573485

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Project description:IntroductionObservational data suggest that vitamin D deficiency is associated with the onset and progression of knee osteoarthritis (OA). However, randomised controlled trials (RCTs) to date investigating the efficacy of vitamin D supplementation in knee OA have reported conflicting results. Further research is needed to clarify the effects of vitamin D on patient-reported outcomes and determine whether there are patient subgroups who may benefit from the supplementation. The aim of this individual patient data (IPD) meta-analysis is to identify patient-level predictors of treatment response to vitamin D supplementation on pain and physical function.Methods and analysisA systematic literature search will be conducted for RCTs of vitamin D supplementation on knee OA. Authors of original RCTs will be contacted to obtain the IPD. The primary outcomes will include long-term (≥12 months) pain and physical function. Secondary outcomes will include medium-term (≥6 months and <12 months) and short-term (<6 months) pain and physical function, as well as patient global assessment, quality of life and adverse events. Potential treatment effect modifiers to be examined in the subgroup analyses include age, gender, body mass index, baseline knee pain severity and physical function, baseline vitamin D level, radiographic stage, presence of bone marrow lesions on MRI, presence of clinical signs of local inflammation and concomitant depressive symptoms. Both one-step and two-step modelling methods will be used to determine the possible modifiable effect of each subgroup of interest.Ethics and disseminationResearch ethical or governance approval is exempt for this study as no new data are being collected. This study will be the first IPD meta-analysis to clarify the effect of vitamin D supplementation on clinical symptoms in different subgroups of patients with knee OA. The findings will be disseminated through peer-review publications and conference presentations.Prospero registration numberCRD42018107740.

Project description:IntroductionKnee and hip osteoarthritis (OA) is a leading cause of disability worldwide. Therapeutic exercise is a recommended core treatment for people with knee and hip OA, however, the observed effect sizes for reducing pain and improving physical function are small to moderate. This may be due to insufficient targeting of exercise to subgroups of people who are most likely to respond and/or suboptimal content of exercise programmes. This study aims to identify: (1) subgroups of people with knee and hip OA that do/do not respond to therapeutic exercise and to different types of exercise and (2) mediators of the effect of therapeutic exercise for reducing pain and improving physical function. This will enable optimal targeting and refining the content of future exercise interventions.Methods and analysisSystematic review and individual participant data meta-analyses. A previous comprehensive systematic review will be updated to identify randomised controlled trials that compare the effects of therapeutic exercise for people with knee and hip OA on pain and physical function to a non-exercise control. Lead authors of eligible trials will be invited to share individual participant data. Trial-level and participant-level characteristics (for baseline variables and outcomes) of included studies will be summarised. Meta-analyses will use a two-stage approach, where effect estimates are obtained for each trial and then synthesised using a random effects model (to account for heterogeneity). All analyses will be on an intention-to-treat principle and all summary meta-analysis estimates will be reported as standardised mean differences with 95% CI.Ethics and disseminationResearch ethical or governance approval is exempt as no new data are being collected and no identifiable participant information will be shared. Findings will be disseminated via national and international conferences, publication in peer-reviewed journals and summaries posted on websites accessed by the public and clinicians.Prospero registration numberCRD42017054049.

Project description:BACKGROUND:Physical activity (PA) reduces pain and improves functioning in people with knee osteoarthritis (OA), but few people with the condition meet recommended PA guidelines. Successful intervention strategies to increase PA include goal setting, action planning, self-monitoring, and follow-up feedback from a healthcare professional. Recently developed consumer wearable activity trackers allow users to set activity goals, self-monitor daily goal-progress, and provide feedback on goal attainment. It is hypothesized that a multi-component physiotherapist-led intervention that includes a short (40-min) education module, guided goal-setting and action planning, the use of a wristband activity tracker, and weekly follow-up phone calls will lead to increased PA outcomes. METHODS/DESIGN:Thirty-six participants will be recruited from the community for a two-group pilot randomized controlled trial with a stepped-wedge design using an intention-to-treat analysis. Computer-generated block randomization will be performed using varying block sizes and a 1:1 allocation ratio. The 4-week intervention will be delivered immediately (immediate-intervention group) or after a 5-week delay (delayed-intervention group). Outcome measures of pain and disability (Knee Injury and OA Outcome Score), disease self-management ability (Partners in Health Scale), and objective bouted moderate-to-vigorous PA and sedentary time (BodyMedia SenseWear Mini Armband) will be collected at baseline (week 0) and two follow-ups (weeks 5 and 10), for a total study duration of 11 weeks. Feasibility data relating to process, resource, management, and scientific elements of the trial will be collected. Outcome measure and feasibility data will be summarized, and an estimate of intervention efficacy will be obtained by regression model with planned comparisons. The trial began recruiting in February 2015. To date, 34 subjects have been recruited. DISCUSSION:This study will evaluate the feasibility and preliminary efficacy of a novel intervention to promote PA in people living with knee OA. The results will provide valuable information to inform a larger randomized trial to assess intervention effectiveness. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02313506 (registration date 8 December 2014). First participant randomized 20 February 2015.

Project description:BackgroundSynovitis occurring frequently in osteoarthritis (OA) may be a targeted outcome. There are no data examining whether synovitis changes following intra-articular intervention.MethodsPersons aged 40 years and older with painful knee OA participated in an open label trial of intra-articular steroid therapy. At all time points they completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. They had a contrast-enhanced (CE) MRI immediately prior to an intra-articular steroid injection with a repeat scan within 20 days. Response status was assessed using the Osteoarthritis Research Society International (OARSI) response criteria. OARSI responders were followed until their pain relapsed either within 20% of baseline or 6 months, shortly after which a third MRI was performed. Synovial tissue volume (STV) was measured on postcontrast knee images. We looked at changes in the STV and in pain, and their association.Results120 subjects with preinjection and postinjection CE MRI were followed. Their mean age was 62.3 years (SD=10.3) and 62 (52%) were women. The median time between injection and follow-up scan was 8 days (IQR 7-14 days). 85/120 (71%) were OARSI responders. Pain decreased (mean change in KOOS=+23.9; 95% CI 20.1 to 27.8, p<0.001) following steroid injection, as did mean STV (mean change=-1071 mm(3); 95% CI -1839 mm(3) to -303 mm(3), p=0.01). Of the 80 who returned for a third MRI, pain relapsed in 57, and in the 48 of those with MRI data, STV increased between follow-up and final visit (+1220 mm(3); 95% CI 25 mm(3) to 2414 mm(3), p=0.05). 23 were persistent responders at 6 months and, in these, STV did not increase (mean change=-202 mm(3); 95% CI -2008 mm(3) to 1604 mm(3), p=0.83). Controlling for variation over time, there was a significant association between synovitis volume and KOOS pain (b coefficient-change in KOOS pain score per 1000 mm(3) change in STV=-1.13; 95% CI -1.87 to -0.39, p=0.003), although STV accounted for only a small proportion of the variance in change in pain.ConclusionsSynovial tissue volume in knee OA shrinks following steroid therapy, and rebounds in those whose pain relapses. It can be considered a treatment target in symptomatic knee OA.Trial registration numberISRCTN07329370.

Project description:IntroductionSymptomatic treatments for osteoarthritis (OA) provide only small-to-moderate efficacy over placebo in randomised controlled trials (RCTs). Treatment guidelines therefore have emphasised the need to identify predictors of treatment response through subgroup and multiple regression analysis. Individual participant data (IPD) meta-analysis is recommended as an efficient approach for this purpose. To our knowledge, this has not been undertaken for oral non-steroidal anti-inflammatory drugs (NSAIDs), including paracetamol, in OA. In this IPD meta-analysis, we aim to identify RCTs with specific mechanistic features related to OA pain, such as joint inflammation. We hypothesise that NSAIDs may work better for participants with joint inflammation, whereas paracetamol may not.Methods and analysisA comprehensive literature search will be conducted on the databases of Web of Science, Embase, Medline, CINAHL, AMED and the Cochrane Library from 1 January 1998 to 1 December 2020. All RCTs related to oral NSAIDs or paracetamol including placebo-controlled trials in people with OA that have evaluated pain-related peripheral risk factors (eg, clinically detected knee effusion, synovial hypertrophy or effusion on imaging, knee morning stiffness, elevated serum C-reactive protein (CRP) level) and/or central pain risk factors (eg, pain elsewhere, depression, anxiety, sleep disturbance) will be retrieved. The outcome will be change in pain from baseline. Change in function and patient global assessment will also be included as outcomes if available. Investigators of all eligible trials will be contacted for IPD. Multilevel regression models will be used to identify predictors for the specific (active-placebo) and the overall treatment effect (change from baseline in active group).Ethics and disseminationNo identifiable data will be included in this study and no formal ethics approval is required as no new data collection will be processed. Results of this hypothesis-driven IPD meta-analysis will be disseminated through conference presentations and publication in peer-reviewed journals.Prospero registration numberCRD42020165098.

Project description:INTRODUCTION:Knee osteoarthritis (OA) is the most common joint disease worldwide. As of today, there are no disease-modifying drugs, but there is evidence that muscle strengthening exercises can substantially reduce pain and improve function in this disorder, and one very well tested physiotherapy protocol is the 'Better Management of Patients with Osteoarthritis' developed in Sweden. Given the high prevalence of knee OA, a potentially cost-effective, digitally delivered approach to treat knee OA should be trialled. This study aims to explore the benefits of iBEAT-OA (Internet-Based Exercise programme Aimed at Treating knee Osteoarthritis) in modulating pain, function and other health-related outcomes in individuals with knee OA. METHODS AND ANALYSIS:A randomised controlled trial was designed to evaluate the efficacy of a web-based exercise programme in a population with knee OA compared with standard community care provided by general practitioners (GPs) in the UK. We anticipate recruiting participants into equal groups. The intervention group (n=67) will exercise for 20-30?min daily for six consecutive weeks, whereas the control group (n=67) will follow GP-recommended routine care. The participants will be assessed using a Numerical Rating Scale, the Western Ontario and McMaster Universities Osteoarthritis Index, the Arthritis Research UK Musculoskeletal Health Questionnaire, the Pittsburgh Sleep Quality Index, 30?s sit to stand test, timed up and go test, quantitative sensory testing, musculoskeletal ultrasound scan, muscle thickness assessment of the vastus lateralis, and quadriceps muscles force generation during an isokinetic maximum voluntary contraction (MVC). Samples of urine, blood, faeces and synovial fluid will be collected to establish biomarkers associated with changes in pain and sleep patterns in individuals affected with knee OA. Standard parametric regression methods will be used for statistical analysis. ETHICS AND DISSEMINATION:Ethical approval was obtained from the Research Ethics Committee (ref: 18/EM/0154) and the Health Research Authority (protocol no: 18021). The study was registered in June 2018. The results of the trial will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER:NCT03545048.

Dataset Information

Efficacy of bisphosphonates in specific knee osteoarthritis subpopulations: protocol for an OA Trial Bank systematic review and individual patient data meta-analysis.

Publications

Efficacy of bisphosphonates in specific knee osteoarthritis subpopulations: protocol for an OA Trial Bank systematic review and individual patient data meta-analysis.

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