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EULAR evidence-based recommendations for the diagnosis of hand osteoarthritis: report of a task force of ESCISIT.
OBJECTIVES: To develop evidence-based recommendations for the diagnosis of hand osteoarthritis (OA). METHODS: The multidisciplinary guideline development group, representing 15 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched for systematically. Whenever possible, the sensitivity, specificity and likelihood ratio (LR) were calculated; relative risk and odds ratios were estimated for risk factors for hand OA. Quality of evidence was categorised using the European League Against Rheumatism (EULAR) hierarchy, and strength of recommendation was assessed by the EULAR visual analogue scale. RESULTS: Diagnostic topics included clinical manifestations, radiographic features, subgroups, differential diagnosis, laboratory tests, risk factors and comorbidities. The sensitivity, specificity and LR varied between tests depending upon the cut-off level, gold standard and controls. Overall, no single test could be used to define hand OA on its own (LR <10) but a composite of the tests greatly increased the chance of the diagnosis. The probability of a subject having hand OA was 20% when Heberden nodes alone were present, but this increased to 88% when in addition the subject was over 40 years old, had a family history of nodes and had joint space narrowing in any finger joint. CONCLUSION: Ten key recommendations for diagnosis of hand OA were developed using research evidence and expert consensus. Diagnosis of hand OA should be based on assessment of a composite of features.
Evidence-based recommendations for the role of exercise in the management of osteoarthritis of the hip or knee--the MOVE consensus.
OBJECTIVES: Exercise is an effective and commonly prescribed intervention for lower limb osteoarthritis (OA). Many unanswered questions remain, however, concerning the practical delivery of exercise therapy. We have produced evidence-based recommendations to guide health-care practitioners. METHODS: A multidisciplinary guideline development group was formed from representatives of professional bodies to which OA is of relevance and other interested parties. Each participant contributed up to 10 propositions describing key clinical points regarding exercise therapy for OA of the hip or knee. Ten final recommendations were agreed by the Delphi technique. The research evidence for each was determined. A literature search was undertaken in the Medline, PubMed, EMBASE, PEDro, CINAHL and Cochrane databases. The methodological quality of each retrieved publication was assessed. Outcome data were abstracted and effect sizes calculated. The evidence for each recommendation was assessed and expert consensus highlighted by the allocation of two categories: (1) strength of evidence and (2) strength of recommendation. RESULTS: The first round of the Delphi process produced 123 propositions. This was reduced to 10 after four rounds. These related to aerobic and strengthening exercise, group versus home exercise, adherence, contraindications and predictors of response. The literature search identified 910 articles; 57 intervention trials relating to knee OA, 9 to hip OA and 73 to adherence. The evidence to support each proposition is presented. CONCLUSION: These are the first recommendations for exercise in hip and knee OA to clearly differentiate research evidence and expert opinion. Gaps in the literature are identified and issues requiring further study highlighted.
Genetic influence on bone turnover in postmenopausal twins.
Postmenopausal bone mass is determined by both peak bone mass and subsequent bone loss. Previous studies have shown that peak bone mass is under genetic influence mediated partly by factors affecting bone formation. The rate of bone loss increases markedly after the menopause, but is highly variable from subject to subject. The aims of this study were to determine whether postmenopausal bone turnover was under genetic control, which should be linked to the genetic influence on the rate of postmenopausal bone loss. A classical twin study was performed that compared the intraclass correlations in monozygotic (MZ) twins with those in dizygotic (DZ) twins, with any difference assumed to be due to genetic factors. Markers of bone formation and resorption were measured in 240 untreated postmenopausal twins, aged 45-69 yr, on the average 12.3 yr (SD, 6.0) postmenopause, including 61 MZ pairs and 59 DZ pairs. The intraclass correlation coefficient of MZ twin pairs, rMZ (95% confidence interval), for 2 specific markers of bone formation, serum osteocalcin and bone-specific alkaline phosphatase, were higher than the corresponding rDZ [0.67 (range, 0.59-0.75) vs. 0.48 (range, 0.35-0.61; P = 0.06) for osteocalcin and 0.53 (range, 0.41-0.65) vs. 0.21 (range, 0.01-0.41; P = 0.02) for bone-specific alkaline phosphatase]. For serum propeptide of type I collagen, a type I collagen synthesis marker that exhibits only a slight increase after menopause, a high proportion of its variance was explained by genetic factors [rMZ = 0.82 (0.77-0.87), rDZ = 0.33 (0.16-0.50); P < 0.001]. The correlations for bone resorption measured by three distinct urinary markers, total deoxypyridinoline and two cross-linked type I collagen peptides (CrossLaps and NTX), that increase markedly after menopause were higher in MZ than in DZ pairs, but the difference reached significance only for NTX (P = 0.03). For urinary free dexoypyridinoline, a marker reflecting bone collagen degradation that increases moderately after menopause, the proportion of the variance explained by genetic factors was highly significant (P = 0.002). In conclusion, our data indicate that a proportion of the variance in postmenopausal levels of both bone formation and resorption markers are explained by genetic factors, but this contribution was clearly significant only for markers that do not change markedly at the menopause. These data suggest that the contribution of genetic factors to overall postmenopausal bone turnover and possibly bone loss is likely to be small.
The incidence and characteristics of accelerated knee osteoarthritis among women: the Chingford cohort.
BACKGROUND: Prior research on accelerated knee osteoarthritis (AKOA) was primarily confined to the Osteoarthritis Initiative, which was enriched with people with risk factors for knee osteoarthritis (KOA). It is unclear how often AKOA develops in a community-based cohort and whether we can replicate prior findings from the Osteoarthritis Initiative in another cohort. Hence, we determined the incidence and characteristics of AKOA among women in the Chingford Study, which is a prospective community-based cohort. METHODS: The Chingford Study had 1003 women with quinquennial knee radiographs over 15 years. We divided the 15-year observation period into three consecutive 5-year phases. Within each 5-year phase, we selected 3 groups of participants among women who started a phase without KOA (Kellgren-Lawrence [KL] 1 in 7 women with incident KOA had AKOA. Like the Osteoarthritis Initiative, people with AKOA were more likely to have greater age and BMI.
Rugby Health and Well-Being Study: protocol for a UK-wide survey with health data cross-validation.
INTRODUCTION: Rugby football (Union and League) provides physical activity (PA) with related physical and mental health benefits. However, as a collision sport, rugby research and media coverage predominantly focus on injuries in elite players while the overall impact on health and well-being remains unclear. This study aims to provide a greater understanding of the risks and benefits of rugby participation in a diverse sample of men and women, current and former rugby Union and League players from recreational to the elite level of play. We will explore: (1) joint-specific injuries and concussion; (2) joint pain and osteoarthritis (OA); (3) medical and mental health conditions; (4) PA and sedentary behaviour and (5) well-being (quality of life, flourishing and resilience). METHODS AND ANALYSIS: The Rugby Health and Well-being Study is designed in two phases: (1) a UK-wide cross-sectional survey and (2) cross-validation using health register data from Scotland. Participants will be at least 16 years old, current or former rugby players who have played rugby for at least one season. We will report standardised, level of play-, sex- and age-stratified prevalence of joint injury, concussion, medical conditions and PA. We will describe injury/concussion prevention expectations and protective equipment use. Rugby-related factors associated with injury, pain, OA, PA, health and well-being will be explored in regression models. We will compare joint pain intensity and duration, elements of pain perception and well-being between recreational and elite players and further investigate these associations in regression models while controlling for confounding variables. In the second phase, we will validate self-reported with health register data, and provide further information on healthcare use. ETHICS AND DISSEMINATION: The Yorkshire and the Humber-Leeds East Research Ethics Committee (REC reference: 19/HY/0377) has approved this study (IRAS project ID 269424). The results will be disseminated through scientific publications, conferences and social media.
Musculoskeletal ultrasound imaging of the plantar forefoot in patients with rheumatoid arthritis: inter-observer agreement between a podiatrist and a radiologist.
BACKGROUND: The use of musculoskeletal ultrasound (MSUS) in the diagnosis and management of foot and ankle musculoskeletal pathology is increasing. Due to the wide use of MSUS and the depth and breadth of training required new proposals advocate tailored learning of the technique to discrete fields of practice. The aims of the study were to evaluate the inter-observer agreement between a MSUS radiologist and a podiatrist, who had completed basic skills training in MSUS, in the MSUS assessment of the forefoot of patients with Rheumatoid Arthritis. METHODS: A consecutive sample of thirty-two patients with rheumatoid arthritis was assessed for presence of synovitis, erosions and bursitis within the forefoot using MSUS. All MSUS assessments were performed independently on the same day by a podiatrist and one of two Consultant Radiologists experienced in MSUS. RESULTS: Moderate agreement on image acquisition and interpretation was achieved for bursitis (kappa 0.522; p < 0.01) and erosions (kappa 0.636; p < 0.01) and fair agreement for synovitis (kappa 0.216; p < 0.05) during the primary assessments. Following a further training session, substantial agreement (kappa 0.702) between the two investigators was recorded. The sensitivity of the podiatrist using MSUS was 82.4% for detection of bursitis, 83.0% for detection of erosion and 84.0% for detection of synovitis. Specificity of the podiatrist using MSUS was 88.9% for detection of bursitis, 80.7% for detection of erosion and 35.9% for detection of synovitis. CONCLUSION: This study demonstrated good inter-observer agreement between a podiatrist and radiologist on MSUS assessment of the forefoot, particularly for bursitis and erosions, in patients with rheumatoid arthritis. There is scope to further evaluate and consider the role of podiatrists in the MSUS imaging of the foot following appropriate training and also in the development of reliable protocols for MSUS assessment of the foot.
Influence of vitamin D receptor genotype on bone mineral density in postmenopausal women: a twin study in Britain.
OBJECTIVES: To investigate the possible association between vitamin D receptor genotype and bone mineral density in a large group of postmenopausal twins. DESIGN: Cross sectional twin study. SETTING: Twin population based in Britain. SUBJECTS: 95 dizygotic (non-identical) pairs of twins and 87 monozygotic (identical) pairs of twins aged 50-69 years, postmenopausal, and free of diseases affecting bone, recruited from a national register of twins and with a media campaign. MAIN OUTCOME MEASURES: Bone mineral density measured at the hip, lumbar spine, forearm, and for the whole body by dual energy x ray absorptiometry in relation to differences in the vitamin D receptor genotype. RESULTS: At all sites the values of bone density among dizygotic twins were more similar in those of the same vitamin D receptor genotype than in those of differing genotype, and the values in the former were closer to the correlations seen in monozygotic twins. Women with the genotype that made them at risk of osteoporotic fracture had an adjusted bone mineral density that was significantly lower by SD 0.5 to 0.6 at the hip, lumbar spine, and for the whole body. The results could not be explained by differences in age, weight, years since menopause, or use of hormone replacement therapy. CONCLUSIONS: The findings that in postmenopausal women in Britain bone density-particularly at the hip and spine-is genetically linked and specifically associated with the vitamin D receptor genotypes should lead to novel approaches to the prevention and treatment of osteoporosis.
Common attributes in retired professional cricketers that may enhance or hinder quality of life after retirement: a qualitative study.
OBJECTIVES: Retired professional cricketers shared unique experiences and may possess specific psychological attributes with potential to influence quality of life (QOL). Additionally, pain and osteoarthritis can be common in retired athletes which may negatively impact QOL. However, QOL in retired athletes is poorly understood. This study explores the following questions from the personal perspective of retired cricketers: How do retired cricketers perceive and experience musculoskeletal pain and function in daily life? Are there any psychological attributes that might enhance or hinder retired cricketers' QOL? DESIGN: A qualitative study using semistructured interviews, which were subject to inductive, thematic analysis. A data-driven, iterative approach to data coding was employed. SETTING: All participants had lived and played professional cricket in the UK and were living in the UK or abroad at the time of interview. PARTICIPANTS: Eighteen male participants, aged a mean 57±11 (range 34-77) years had played professional cricket for a mean 12±7 seasons and had been retired from professional cricket on average 23±9 years. RESULTS: Fifteen participants reported pain or joint difficulties and all but one was satisfied with their QOL. Most retired cricketers reflected on experiences during their cricket career that may be associated with the psychological attributes that these individuals shared, including resilience and a positive attitude. Additional attributes included a high sense of body awareness, an ability to self-manage pain and adapt lifestyle choices to accommodate physical limitations. Participants felt fortunate and proud to have played professional cricket, which may have further contributed to the high QOL in this group of retired cricketers. CONCLUSIONS: Most retired cricketers in this study were living with pain or joint difficulties. Despite this, all but one was satisfied or very satisfied with their QOL. This may be partly explained by the positive psychological attributes that these retired cricketers shared.
Epidurals and sciatica
Sciatica is a common musculoskeletal condition associated with considerable pain in the acute stages, but which carries a good long term prognosis. Epidural corticosteroid injections have been used for almost 50 years in this condition, however the evidence from randomised controlled trials is far from conclusive. Although epidural corticosteroid injections may offer some short term pain relief, they offer no medium or long term benefits, either in terms pain, return to work or need for surgery. Their exact role in the place in the management of sciatica in uncertain. But they should certainly not be used until the patient has received a suitable course of simple measures such as analgesia and physiotherapy.
Effect of vitamin D supplementation on pain and physical function in patients with knee osteoarthritis (OA): an OA Trial Bank protocol for a systematic review and individual patient data (IPD) meta-analysis.
INTRODUCTION: Observational 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 ANALYSIS: A 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 DISSEMINATION: Research 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 NUMBER: CRD42018107740.
The Osteoarthritis Thumb Therapy (OTTER) II Trial: a study protocol for a three-arm multi-centre randomised placebo controlled trial of the clinical effectiveness and efficacy and cost-effectiveness of splints for symptomatic thumb base osteoarthritis.
INTRODUCTION: The economic cost of osteoarthritis (OA) is high. At least 4.4 million people have hand OA in the UK. Symptomatic thumb base OA affects 20% of people over 55 years, causing more pain, work and functional disability than OA elsewhere in the hand. Most evidence-based guidelines recommend splinting for hand OA. Splints that support or immobilise the thumb base are routinely used despite there being limited evidence on their effectiveness. The potential effects of placebo interventions in OA are acknowledged, but few studies investigate the clinical efficacy of rehabilitation interventions nor the impact of any placebo effects associated with splints. METHODS AND ANALYSIS: Participants aged 30 years and over with symptomatic thumb base OA will be recruited into the trial from secondary care occupational therapy and physiotherapy centres. Following informed consent, participants will complete a baseline questionnaire and then be randomised into one of three treatment arms: a self-management programme, a self-management programme plus a verum thumb splint or a self-management programme plus a placebo thumb splint. The primary outcome is the Australian Canadian Osteoarthritis Hand Index (AUSCAN) hand pain scale. The study endpoint is 8 weeks after baseline. Baseline assessments will be carried out prior to randomisation and outcomes collected at 4, 8 and 12 weeks. Cost-effectiveness analysis will be conducted and individual qualitative interviews conducted with up to 40 participants after 8 weeks to explore perceptions and outcome expectations of verum and placebo splints and exercise. ETHICS AND DISSEMINATION: South Central-Oxford C Research Ethics Committee approved this study (16/SC/0188). The findings will be disseminated to health professional conferences, journals and lay publications for patient organisations. The research will contribute to improving the management of thumb base OA and help clinicians and patients make informed decisions about the value of different interventions. TRIAL REGISTRATION NUMBER: ISRCTN54744256.
Genome-wide association and functional studies identify the DOT1L gene to be involved in cartilage thickness and hip osteoarthritis.
Hip osteoarthritis (HOA) is one of the most disabling and common joint disorders with a large genetic component that is, however, still ill-defined. To date, genome-wide association studies (GWAS) in osteoarthritis (OA) and specifically in HOA have yielded only few loci, which is partly explained by heterogeneity in the OA definition. Therefore, we here focused on radiographically measured joint-space width (JSW), a proxy for cartilage thickness and an important underlying intermediate trait for HOA. In a GWAS of 6,523 individuals on hip-JSW, we identified the G allele of rs12982744 on chromosome 19p13.3 to be associated with a 5% larger JSW (P = 4.8 × 10(-10)). The association was replicated in 4,442 individuals from three United Kingdom cohorts with an overall meta-analysis P value of 1.1 × 10(-11). The SNP was also strongly associated with a 12% reduced risk for HOA (P = 1 × 10(-4)). The SNP is located in the DOT1L gene, which is an evolutionarily conserved histone methyltransferase, recently identified as a potentially dedicated enzyme for Wnt target-gene activation in leukemia. Immunohistochemical staining of the DOT1L protein in mouse limbs supports a role for DOT1L in chondrogenic differentiation and adult articular cartilage. DOT1L is also expressed in OA articular chondrocytes. Silencing of Dot1l inhibited chondrogenesis in vitro. Dot1l knockdown reduces proteoglycan and collagen content, and mineralization during chondrogenesis. In the ATDC5 chondrogenesis model system, DOT1L interacts with TCF and Wnt signaling. These data are a further step to better understand the role of Wnt-signaling during chondrogenesis and cartilage homeostasis. DOT1L may represent a therapeutic target for OA.
A consensus-based framework for conducting and reporting osteoarthritis phenotype research.
BACKGROUND: The concept of osteoarthritis (OA) heterogeneity is evolving and gaining renewed interest. According to this concept, distinct subtypes of OA need to be defined that will likely require recognition in research design and different approaches to clinical management. Although seemingly plausible, a wide range of views exist on how best to operationalize this concept. The current project aimed to provide consensus-based definitions and recommendations that together create a framework for conducting and reporting OA phenotype research. METHODS: A panel of 25 members with expertise in OA phenotype research was composed. First, panel members participated in an online Delphi exercise to provide a number of basic definitions and statements relating to OA phenotypes and OA phenotype research. Second, panel members provided input on a set of recommendations for reporting on OA phenotype studies. RESULTS: Four Delphi rounds were required to achieve sufficient agreement on 11 definitions and statements. OA phenotypes were defined as subtypes of OA that share distinct underlying pathobiological and pain mechanisms and their structural and functional consequences. Reporting recommendations pertaining to the study characteristics, study population, data collection, statistical analysis, and appraisal of OA phenotype studies were provided. CONCLUSIONS: This study provides a number of consensus-based definitions and recommendations relating to OA phenotypes. The resulting framework is intended to facilitate research on OA phenotypes and increase combined efforts to develop effective OA phenotype classification. Success in this endeavor will hopefully translate into more effective, differentiated OA management that will benefit a multitude of OA patients.
The epidemiology of osteoporotic fractures
Osteoporosis is a major public health issue affecting a large proportion of the population aged over fifty years. It leads to a huge burden through the increased morbidity and mortality associated with fragility fractures. Although the age-specific incidence of fractures has been increasing over the last 40 years in the West, this now seems to be plateauing. However, with the predicted increase in the world population, particularly the over 65's, over the next 40 years, the future burden of fractures will increase substantially. There is a large genetic component to peak bone mass, which is polygenic in origin. Increasingly it is recognised that environmental factors not only affect the rate of bone loss, but also affect peak bone mass gained. This has led to a new approach, based on the idea of "foetal programming". Patient assessment has, in the past, been based on bone mineral density and the relative risk of fracture. New approaches involve determining a patient's 5-10 year absolute risk of fracture, which will allow better targeting of today's more effective but expensive treatments.
The clinical and cost effectiveness of splints for thumb base osteoarthritis: a randomized controlled clinical trial.
OBJECTIVES: To investigate the clinical effectiveness, efficacy and cost effectiveness of splints (orthoses) in people with symptomatic basal thumb joint OA (BTOA). METHODS: A pragmatic, multicentre parallel group randomized controlled trial at 17 National Health Service (NHS) hospital departments recruited adults with symptomatic BTOA and at least moderate hand pain and dysfunction. We randomized participants (1:1:1) using a computer-based minimization system to one of three treatment groups: a therapist supported self-management programme (SSM), a therapist supported self-management programme plus a verum thumb splint (SSM+S), or a therapist supported self-management programme plus a placebo thumb splint (SSM+PS). Participants were blinded to group allocation, received 90 min therapy over 8 weeks and were followed up for 12 weeks from baseline. Australian/Canadian (AUSCAN) hand pain at 8 weeks was the primary outcome, using intention to treat analysis. We calculated costs of treatment. RESULTS: We randomized 349 participants to SSM (n = 116), SSM+S (n = 116) or SSM+PS (n = 117) and 292 (84%) provided AUSCAN Osteoarthritis Hand Index hand pain scores at the primary end point (8 weeks). All groups improved, with no mean treatment difference between groups: SSM+S vs SSM -0.5 (95% CI: -1.4, 0.4), P = 0.255; SSM+PS vs SSM -0.1 (95% CI: -1.0, 0.8), P = 0.829; and SSM+S vs SSM+PS -0.4 (95% CI: -1.4, 0.5), P = 0.378. The average 12-week costs were: SSM £586; SSM+S £738; and SSM+PS £685. CONCLUSION: There was no additional benefit of adding a thumb splint to a high-quality evidence-based, supported self-management programme for thumb OA delivered by therapists. TRIAL REGISTRATION: ISRCTN 54744256 (http://www.isrctn.com/ISRCTN54744256).
Physical activity in former elite cricketers and strategies for promoting physical activity after retirement from cricket: a qualitative study.
OBJECTIVES: The health benefits of professional sport dissipate after retirement unless an active lifestyle is adopted, yet reasons for adopting an active or inactive lifestyle after retirement from sport are poorly understood. Elite cricket is all-encompassing, requiring a high volume of activity and unique physical demands. We aimed to identify influences on physical activity behaviours in active and insufficiently active former elite cricketers and provide practical strategies for promoting physical activity after cricket retirement. DESIGN: 18 audio-recorded semistructured telephone interviews were performed. An inductive thematic approach was used and coding was iterative and data-driven facilitated by NVivo software. Themes were compared between sufficiently active and insufficiently active participants. SETTING: All participants formerly played professional cricket in the UK. PARTICIPANTS: Participants were male, mean age 57±11 (range 34-77) years, participated in professional cricket for 12±7 seasons and retired on average 23±9 years previously. Ten participants (56%) were classified as sufficiently active according to the UK Physical Activity Guidelines (moderate-intensity activity ≥150 min per week or vigorous-intensity activity ≥75 min per week). Eight participants did not meet these guidelines and were classified as insufficiently active. RESULTS: Key physical activity influences were time constraints, habit formation, intrinsic and extrinsic motivation, physical activity preferences, pain/physical impairment and cricket coaching. Recommendations for optimising physical activity across the lifespan after cricket retirement included; prioritise physical activity, establish a physical activity plan prior to cricket retirement and don't take a break from physical activity, evaluate sources of physical activity motivation and incorporate into a physical activity plan, find multiple forms of satisfying physical activity that can be adapted to accommodate fluctuations in physical capabilities across the lifespan and coach cricket. CONCLUSIONS: Physically active and less active retired cricketers shared contrasting attributes that informed recommendations for promoting a sustainable, physically active lifestyle after retirement from professional cricket.