Cardiovascular risk factors associated with polymyalgia rheumatica and giant cell arteritis in a prospective cohort: EPIC-Norfolk Study.

OBJECTIVES: PMR and GCA are associated with increased risk of vascular disease. However, it remains unclear whether this relationship is causal or reflects a common underlying propensity. The aim of this study was to identify whether known cardiovascular risk factors increase the risk of PMR and GCA. METHODS: Clinical records were examined using key word searches to identify cases of PMR and GCA, applying current classification criteria in a population-based cohort. Associations between cardiovascular risk factors and incident PMR and GCA were analysed using Cox proportional hazards. RESULTS: In 315 022 person years of follow-up, there were 395 incident diagnoses of PMR and 118 incident diagnoses of GCA that met the clinical definition. Raised diastolic blood pressure (>90 mmHg) at baseline/recruitment was associated with subsequent incident PMR [hazard ratio=1.35 (95% CI 1.01, 1.80) P=0.045], and ever-smoking was associated with incident GCA [hazard ratio=2.01 (95% CI 1.26, 3.20) P=0.003]. Estimates were similar when the analysis was restricted to individuals whose diagnoses satisfied the current classification criteria sets. CONCLUSION: PMR and GCA shares common risk factors with vascular disease onset, suggesting a common underlying propensity. This may indicate a potential for disease prevention strategies through modifying cardiovascular risk.

The association of vascular risk factors with visual loss in giant cell arteritis.

Objective: Blindness is a recognized complication of GCA; however, the frequency of and risk factors for this complication have not been firmly established. The aim of this study was to examine the incidence and determinants of blindness in patients with GCA, using a large international cohort. Methods: The analysis was conducted among subjects recruited into the Diagnosis and Classification Criteria in Vasculitis Study. The study captures consecutive patients presenting to clinic-based physicians. New-onset blindness was assessed 6 months after diagnosis by completion of the Vasculitis Damage Index. Logistic regression analysis was used to assess the association between blindness and clinical variables. Results: Of 433 patients with GCA from 26 countries, 7.9% presented with blindness in at least one eye at 6 months. Risk factors identified at baseline for blindness at 6 months were identified and included prevalent stroke [odds ratio (OR) = 4.47, 95% CI: 1.30, 15.41] and peripheral vascular disease (OR = 10.44, 95% CI: 2.94, 37.03). Conclusion: This is the largest study to date of subjects with incident GCA and confirms that blindness remains a common complication of disease and is associated with established vascular disease.Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov , NCT01066208.

Predictors and outcomes of sustained, intermittent or never achieving remission in patients with recent onset inflammatory polyarthritis: results from the Norfolk Arthritis Register.

OBJECTIVES: Early remission is the current treatment strategy for patients with inflammatory polyarthritis (IP) and RA. Our objective was to identify baseline factors associated with achieving remission: sustained (SR), intermittent (IR) or never (NR) over a 5-year period in patients with early IP. METHODS: Clinical and demographic data of patients with IP recruited to the Norfolk Arthritis Register (NOAR) were obtained at baseline and years 1, 2, 3 and 5. Remission was defined as no tender or swollen joints (out of 51). Patients were classified as NR or PR, respectively, if they were in remission at: no assessment or ⩾3 consecutive assessments after baseline, and IR otherwise. Ordinal regression and a random effects model, respectively, were used to examine the association between baseline factors, remission group and HAQ scores over time. RESULTS: A total of 868 patients (66% female) were included. Of these, 54%, 34% and 12% achieved NR, IR and SR, respectively. In multivariate analysis, female sex (odds ratio, OR 0.47, 95% CI: 0.35, 0.63), higher tender joint count (OR = 0.94, 95% CI: 0.93, 0.96), higher HAQ (OR = 0.59, 95% CI: 0.48, 0.74), being obese (OR = 0.70, 95% CI: 0.50, 0.99), hypertensive (OR = 0.67, 95% CI: 0.50, 0.90) or depressed (OR = 0.74, 95% CI: 0.55, 1.00) at baseline were independent predictors of being in a lower remission group. IR and SR were associated with lower HAQ scores over time and lower DAS28 at year 5. CONCLUSION: Women with higher tender joint count and disability at baseline, depression, obesity and hypertension were less likely to achieve remission. This information could help when stratifying patients for more aggressive therapy.

45-day mortality after 467,779 knee replacements for osteoarthritis from the National Joint Registry for England and Wales: an observational study.

BACKGROUND: Understanding the risk factors for early death after knee replacement could help to reduce the risk of mortality after this procedure. We assessed secular trends in death within 45 days of knee replacement for osteoarthritis in England and Wales, with the aim of investigating whether any change that we recorded could be explained by alterations in modifiable perioperative factors. METHODS: We took data for knee replacements done for osteoarthritis in England and Wales between April 1, 2003, and Dec 31, 2011, from the National Joint Registry for England and Wales. Patient identifiers were used to link these data to the national mortality database and the Hospital Episode Statistics database to obtain details of death, sociodemographics, and comorbidity. We assessed mortality within 45 days by Kaplan-Meier analysis and assessed the role of patient and treatment factors by Cox proportional hazards models. FINDINGS: 467,779 primary knee replacements were done to treat osteoarthritis during 9 years. 1183 patients died within 45 days of surgery, with a substantial secular decrease in mortality from 0·37% in 2003 to 0·20% in 2011, even after adjustment for age, sex, and comorbidity. The use of unicompartmental knee replacement was associated with substantially lower mortality than was total knee replacement (hazard ratio [HR] 0·32, 95% CI 0·19­0·54, p<0·0005). Several comorbidities were associated with increased mortality: myocardial infarction (HR 3·46, 95% CI 2·81­4·14, p<0·0005), cerebrovascular disease (3·35, 2·7­4·14, p<0·0005), moderate/severe liver disease (7·2, 3·93­13·21, p<0·0005), and renal disease (2·18, 1·76­2·69, p<0·0005). Modifiable perioperative risk factors, including surgical approach and thromboprophylaxis were not associated with mortality. INTERPRETATION: Postoperative mortality after knee replacement has fallen substantially between 2003 and 2011. Efforts to further reduce mortality should concentrate more on older patients, those who are male and those with specific comorbidities, such as myocardial infarction, cerebrovascular disease, liver disease, and renal disease. FUNDING: National Joint Registry for England and Wales.

HLA allele variation as a potential explanation for the geographical distribution of granulomatosis with polyangiitis.

OBJECTIVE: Granulomatosis with polyangiitis (GPA) is a rare autoimmune systemic vasculitis considered to result from the interaction of environmental factors with a genetically predisposed host. The HLA-DPB1*0401 allele, the PI*Z allele of the gene encoding α1-antitrypsin (SERPINA1) and the proteinase 3 (PRTN3) gene have been associated with GPA. The incidence of GPA is lower in non-Caucasian populations and has been associated with higher latitude. Our aim was to determine whether variation in population carrier frequency of the HLA-DPB1*0401 and PI*Z alleles could explain in part the variation in GPA incidence between countries. METHODS: We systematically identified published reports on the incidence of GPA and used previously published data on the frequency of HLA-DBP1*0401 and PI*Z alleles. The relationship between GPA incidence, latitude and population HLA-DPB1*0401 and PI*Z allele frequencies was assessed by linear regression. RESULTS: On multivariate analysis GPA incidence was associated with HLA-DPB1*0401 allele frequency (P = 0.001) but not with PI*Z allele frequency or latitude. CONCLUSION: HLA-DPB1*0401 is a GPA susceptibility allele and HLA-DPB1*0401 population allele frequencies may help explain variations in GPA incidence described in the literature.

Genetic and Environmental Factors in Age-Related Hearing Impairment.

Age-related hearing impairment (ARHI) is a common condition with complex etiology but a recognized genetic component. Heritability estimates for pure tone audiogram-determined hearing ability lie in the range 26-75%. The speech-in-noise (SIN) auditory test, however, may be better at encapsulating ARHI symptoms, particularly the diminished ability to segregate environmental sounds into comprehendible auditory streams. As heritability of SIN has not previously been reported, we explored the genetic and environmental contributions to ARHI determined by SIN in 2,076 twins (87.8% female) aged 18-87 (mean age 54.4). SIN was found to be significantly heritable (A, unadjusted for age=40%; 95% confidence intervals, CI=32%-47%). With age adjustment, heritability fell (A=25%; 95% CI=16-33%), and a relatively strong influence of environmental exposure unshared within twin siblings was identified (E=75%). To explore the environmental aspects further, we assessed the influence of diet (through the Food Frequency Questionnaire, FFQ), smoking (through self-report and cotinine metabolite levels) and alcohol intake (through the FFQ). A negative influence of high cholesterol diet was observed after adjustment (p=.037). A protective effect of raised serum high-density lipoprotein (HDL) cholesterol levels was observed after adjustment (p=.004). This study is the first assessment of the genetic and environmental influence on SIN perception. The findings suggest SIN is less heritable than pure tone audiogram (PTA) ability and highly influenced by the environment unique to each twin. Furthermore, a possible role of dietary fat in the etiology of ARHI is highlighted.

Low back and common widespread pain share common genetic determinants.

Low back (LBP) and chronic widespread musculoskeletal pain (CWP) both have a significant genetic component and are associated with increased body mass index (BMI). We examined whether LBP and CWP share common genetic factors, and to what extent this correlation is modified by the genetic factors influencing BMI. Genetic analysis of binary traits such as pain is not simple, particularly if their risk is associated with age or other quantitative traits. Implementing Falconer's polygenic threshold concept for dichotomous traits inheritance, we developed new software to examine the extent of the genetic influence on LBP and CWP under age and BMI dependence. The analysis was conducted on 3266 and 2256 UK female twins, assessed for LBP and CWP, respectively. Analysis of the liability scores with threshold to LBP and CWP established substantial contribution of genetic factors to their variation (h(2) > 0.60, p<0.004-0.0003) and covariation (p=3.1E-08). Some 39% of the CWP and 70% of the LBP heritability estimates were attributable to genetic effects shared by both phenotypes, and 40% and 67% of the residual variation is caused by environmental factors simultaneously affecting both pain syndromes. However, contribution of BMI to variation/covariation of both pain phenotypes-although statistically highly significant (p∼10-7)-was not determinative.

90-day mortality after 409,096 total hip replacements for osteoarthritis, from the National Joint Registry for England and Wales: a retrospective analysis.

BACKGROUND: Death within 90 days after total hip replacement is rare but might be avoidable dependent on patient and treatment factors. We assessed whether a secular decrease in death caused by hip replacement has occurred in England and Wales and whether modifiable perioperative factors exist that could reduce deaths. METHODS: We took data about hip replacements done in England and Wales between April, 2003, and December, 2011, from the National Joint Registry for England and Wales. Patient identifiers were used to link these data to the national mortality database and the Hospital Episode Statistics database to obtain details of death, sociodemographics, and comorbidity. We assessed mortality within 90 days of operation by Kaplan-Meier analysis and assessed the role of patient and treatment factors by Cox proportional hazards model. FINDINGS: 409,096 primary hip replacements were done to treat osteoarthritis. 1743 patients died within 90 days of surgery during 8 years, with a substantial secular decrease in mortality, from 0·56% in 2003 to 0·29% in 2011, even after adjustment for age, sex, and comorbidity. Several modifiable clinical factors were associated with decreased mortality according to an adjusted model: posterior surgical approach (hazard ratio [HR] 0·82, 95% CI 0·73-0·92; p=0·001), mechanical thromboprophylaxis (0·85, 0·74-0·99; p=0·036), chemical thromboprophylaxis with heparin with or without aspirin (0·79, 0·66-0·93; p=0·005), and spinal versus general anaesthetic (0·85, 0·74-0·97; p=0·019). Type of prosthesis was unrelated to mortality. Being overweight was associated with lower mortality (0·76, 0·62-0·92; p=0·006). INTERPRETATION: Postoperative mortality after hip joint replacement has fallen substantially. Widespread adoption of four simple clinical management strategies (posterior surgical approach, mechanical and chemical prophylaxis, and spinal anaesthesia) could, if causally related, reduce mortality further. FUNDING: National Joint Registry for England and Wales.

The relationship between benign joint hypermobility syndrome and psychological distress: a systematic review and meta-analysis.

OBJECTIVE: This study examines the reported evidence of an association between benign joint hypermobility syndrome (BJHS) and psychological symptoms. METHODS: A systematic review of published (AMED, CINAHL, MEDLINE, EMBASE, PubMed, Cochrane Library) and unpublished research databases (OpenGrey, the World Health Organization (WHO) International Clinical Trials Registry Platform, Current Controlled Trials, the UK National Research Register Archive) was performed from their inception to January 2013. Studies assessing the prevalence and incidence of psychological conditions for people diagnosed with BJHS were included. Meta-analysis assessing the odds ratio (OR) and standardized mean difference in severity of psychological conditions was performed. Methodological quality was assessed using the Critical Appraisal Skills Programme (CASP) appraisal tools. RESULTS: Fourteen papers including 3957 participants, 1006 people with and 2951 controls without BJHS were eligible. The overall methodological quality was moderate. The results indicated that people with BJHS experience significantly greater perceptions of fear and more intense fear (P < 0.05) and have a higher probability of demonstrating agoraphobia (P < 0.05), anxiety (OR 4.39, 95% CI 1.92, 10.40), depression (OR 4.10, 95% CI 1.79, 9.41) and panic disorders (OR 6.72, 95% CI 2.22, 20.35) than those without BJHS (P ≤ 0.005). Neither anxiety nor depression have been assessed in childhood populations. CONCLUSION: People with BJHS commonly exhibit a range of symptoms related to anxiety and depression. Considerable emotional symptoms accompany BJHS. Further study is warranted to explore how these results relate to non-Mediterranean populations and children. However, the data suggest that targeting psychological symptoms could be an important approach to managing the range of symptoms reported in these patients.

Dietary fat and fatty acid profile are associated with indices of skeletal muscle mass in women aged 18-79 years.

Age-related loss of skeletal muscle mass results in a reduction in metabolically active tissue and has been related to the onset of obesity and sarcopenia. Although the causes of muscle loss are poorly understood, dietary fat has been postulated to have a role in determining protein turnover through an influence on both inflammation and insulin resistance. This study was designed to investigate the cross-sectional relation between dietary fat intake, as dietary percentage of fat energy (PFE) and fatty acid profile, with indices of skeletal muscle mass in the population setting. Body composition [fat-free mass (FFM; in kg)] and the fat-free mass index (FFMI; kg FFM/m(2)) was measured by using dual-energy X-ray absorptiometry in 2689 women aged 18-79 y from the TwinsUK Study and calculated according to quintile of dietary fat (by food-frequency questionnaire) after multivariate adjustment. Positive associations were found between the polyunsaturated-to-saturated fatty acid (SFA) ratio and indices of FFM, and inverse associations were found with PFE, SFAs, monounsaturated fatty acids (MUFAs), and trans fatty acids (TFAs) (all as % of energy). Extreme quintile dietary differences for PFE were -0.6 kg for FFM and -0.28 kg/m(2) for FFMI; for SFAs, MUFAs, and TFAs, these were -0.5 to -0.8 kg for FFM and -0.26 to -0.38 kg/m(2) for FFMI. These associations were of a similar magnitude to the expected decline in muscle mass that occurs over 10 y. To our knowledge, this is the first population-based study to demonstrate an association between a comprehensive range of dietary fat intake and FFM. These findings indicate that a dietary fat profile already associated with cardiovascular disease protection may also be beneficial for conservation of skeletal muscle mass.

Novel genetic variants associated with lumbar disc degeneration in northern Europeans: a meta-analysis of 4600 subjects.

OBJECTIVE: Lumbar disc degeneration (LDD) is an important cause of low back pain, which is a common and costly problem. LDD is characterised by disc space narrowing and osteophyte growth at the circumference of the disc. To date, the agnostic search of the genome by genome-wide association (GWA) to identify common variants associated with LDD has not been fruitful. This study is the first GWA meta-analysis of LDD. METHODS: We have developed a continuous trait based on disc space narrowing and osteophytes growth which is measurable on all forms of imaging (plain radiograph, CT scan and MRI) and performed a meta-analysis of five cohorts of Northern European extraction each having GWA data imputed to HapMap V.2. RESULTS: This study of 4600 individuals identified four single nucleotide polymorphisms with p<5×10(-8), the threshold set for genome-wide significance. We identified a variant in the PARK2 gene (p=2.8×10(-8)) associated with LDD. Differential methylation at one CpG island of the PARK2 promoter was observed in a small subset of subjects (ß=8.74×10(-4), p=0.006). CONCLUSIONS: LDD accounts for a considerable proportion of low back pain and the pathogenesis of LDD is poorly understood. This work provides evidence of association of the PARK2 gene and suggests that methylation of the PARK2 promoter may influence degeneration of the intervertebral disc. This gene has not previously been considered a candidate in LDD and further functional work is needed on this hitherto unsuspected pathway.

Do people with benign joint hypermobility syndrome (BJHS) have reduced joint proprioception? A systematic review and meta-analysis.

Joint proprioceptive deficit is documented in a variety of musculoskeletal conditions including osteoarthritis, ligament and meniscal injuries, and individuals with increased joint hypermobility, such as those with Ehlers-Danlos. No systematic reviews have assessed joint proprioception in people with benign joint hypermobility syndrome (BJHS). This study addresses this to determine whether people with BJHS exhibit reduced joint proprioception, and, if so, whether this is evident in all age groups. The search strategy was conducted on 31st January 2013. The published literature was assessed using the databases: AMED, CINAHL, MEDLINE, EMBASE, PubMed and the Cochrane Library. Unpublished literature and trial registries were assessed including: OpenGrey, the WHO International Clinical Trials Registry Platform, Current Controlled Trials, the UK National Research Register Archive. All studies comparing the proprioceptive capability of people with and without BJHS were included. Study methodological quality was assessed using the CASP appraisal tool. Meta-analysis techniques were used when study homogeneity permitted. Five studies including 254 people were identified. People with BJHS demonstrated statistically significantly poorer lower limb joint position sense (JPS) (p < 0.001) and threshold detection to movement (p < 0.001) than those without BJHS. The evidence for upper limb proprioceptive difference was less clear, with no statistically significant difference between the cohorts for shoulder JPS (p = 0.10), but a statistically significant difference in finger JPS (p < 0.001). One study which assessed childhood BJHS reported reduced knee proprioceptive capability in those with BJHS (p < 0.001). To conclude, lower limb joint proprioception is reduced in those with BJHS compared to non-BJHS cohorts, whilst unclear in the upper limb.

The contrasting epidemiology of granulomatosis with polyangiitis (Wegener's) and microscopic polyangiitis.

OBJECTIVES: Granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic polyangiitis (MPA) are uncommon and have unknown aetiology. The aim of the study was to investigate the epidemiology of GPA and MPA in a stable, well-defined population looking for differences in the pattern of occurrence, which might suggest a different aetiology. METHODS: Since 1988, we have maintained a prospective register of all patients with systemic vasculitis attending the Norfolk and Norwich University Hospital. Patients presenting with new-onset GPA and MPA as defined by the European Medicines Agency algorithm and registered with general practitioners in the former Norwich Health Authority area between 1988 and 2010 were identified. The population in 2008 was estimated to be 459 000 (221 000 males). RESULTS: One hundred and eleven GPA and 58 MPA incident cases were identified during 1988-2010. The overall annual incidence of GPA and MPA was 11.3/million and 5.9/million, respectively. There was evidence of a cyclical pattern of occurrence with a periodicity of 7.6 years for GPA with a peak incidence of 28.3/million in 2005 and the lowest in 2002 (2.2/million). Other lesser peaks occurred in 1990 and 1996. While the peak incidence of MPA was in 2008 (15.2/million), there was no convincing evidence of periodicity. The incidence of cANCA/PR3- or pANCA/MPO-positive vasculitis showed a similar pattern to GPA and MPA, respectively. CONCLUSION: This study lends support to the notion that the aetiology of GPA and MPA may be distinct conditions with different aetiologies. The cyclical incidence of GPA is possibly an indication for the influence of infection.

An evaluation of rheumatology practitioner outreach clinics: a qualitative study.

BACKGROUND: Services for Rheumatoid Arthritis (RA) have evolved with the development of independently led outreach Rheumatology Practitioner (RP) clinics in Primary Care (PC). Their clinical and cost effectiveness, compared with Secondary Care (SC) services, has not been assessed. The RECIPROCATE study aims to evaluate their clinical and cost effectiveness. This part of the study aimed to explore health professionals' opinions of rheumatology outreach service. METHODS: Using a qualitative design, semi-structured interviews were conducted with GPs, practice nurses, hospital doctors and RPs, from one hospital and seven PC practices in Norfolk, to elicit their opinions of the service. The interviews were analysed using thematic analysis. RESULTS: All participants agreed the service was supportive and valuable providing high quality personalised care, disease management, social, and educational support. Advantages identified included convenience, continuity of care and proximity of services to home. RPs helped bridge the communication gap between PC and SC. Some participants suggested having a doctor alongside RPs. The service was considered to be cost effective for patients but there was uncertainty about cost effectiveness for service providers. Few disadvantages were identified the most recurring being the lack of other onsite services when needed. It was noted that more services could be provided by RPs such as prescribing and joint injections as well as playing a more active role in knowledge transfer to PC. CONCLUSIONS: Professionals involved in the care of RA patients recognised the valuable role of the RP outreach clinics. This service can be further developed in rheumatology and the example can be replicated for other chronic conditions.

Lumbar disc degeneration and genetic factors are the main risk factors for low back pain in women: the UK Twin Spine Study.

OBJECTIVE: Low back pain (LBP) is a common musculoskeletal disorder, but it is still unclear which individuals develop it. The authors examined the contribution of genetic factors, lumbar disc degeneration (LDD) and other risk factors in a female sample of the general population. MATERIAL AND METHODS: A cross-sectional study was conducted among 2256 women (371 and 698 monozygotic and dizygotic twin pairs and 29 sibling pairs and 60 singletons) with a mean age of 50 years (18-84). A self-reported validated questionnaire was used to collect back pain data. Risk factors including body weight, smoking, occupation, physical exercise and MRI assessed LDD were measured. Data analysis included logistic regression and variance decomposition. RESULTS: The major factors associated with LBP included genetic background, with OR approximately 6 if the monozygotic co-twin had LBP, or 2.2 if she was a dizygotic co-twin. In addition, LDD and overweight were highly significantly (p<0.001) associated with non-specific LBP. The single most important risk factor was the amount of LDD. After adjustment for other risk factors, the individuals who exhibited advanced LDD (90% vs 10%) had 3.2 higher odds of manifesting LBP. The data also showed a significant (p<0.001) genetic correlation between the LBP and LDD measurements, suggesting that approximately 11-13% of the genetic effects are shared by LDD and LBP. CONCLUSIONS: The main risk factors for reported episodes of severe and disabling LBP in UK women include the degree of LDD as assessed by MRI, being overweight and genetic heritability.

Progression of lumbar disc degeneration over a decade: a heritability study.

OBJECTIVES: Lumbar disc degeneration (LDD) is prevalent, age-related and contributes to low back pain. Cross-sectional LDD as determined by MRI scan is known to be highly heritable. The authors postulated that the rate of progression might also be controlled by genetic factors. METHODS: A 10-year follow-up of MRI-determined LDD was performed in 234 pairs of twin volunteers in the UK and Australia, comprising 90 monozygotic pairs and 144 dizygotic same-sex twin pairs. Of the total sample, 95% were female. The mean age at baseline was 53.3 years (range 32.3-69.5). The rate of progression was calculated and, because the effect of age was non-linear, the sample was divided into age strata and heritability estimated for each trait's progression. RESULTS: All MRI-determined traits worsened significantly over the period of follow-up (p<0.0001 for each). Change in disc height was not heritable at any age while posterior disc bulge was heritable across all age categories (range 28-53%), with higher heritability in those over 60 years. Change in disc signal intensity and anterior osteophytes were found to be heritable only in those aged under 50 years at baseline (heritability estimates 76% (95% CI 44% to 100%) and 74% (42% to 100%), respectively). CONCLUSIONS: Longitudinal change in LDD traits is heritable for all traits except disc height, but there is a significant influence of age, which varies across traits. Future studies to define the genetic variants influencing LDD progression should examine MRI traits individually and in women should focus on those under 50 years of age.

Impact of COVID-19 pandemic social restriction measures on people with rheumatic and musculoskeletal diseases in the UK: a mixed-methods study.

OBJECTIVES: To determine the impact of COVID-19 pandemic social restriction measures on people with rheumatic and musculoskeletal diseases (RMDs) and to explore how people adapted to these measures over time. DESIGN: Mixed-methods investigation comprising a national online longitudinal survey and embedded qualitative study. SETTING: UK online survey and interviews with community-dwelling individuals in the East of England. PARTICIPANTS: People in the UK with RMDs were invited to participate in an online survey. A subsection of respondents were invited to participate in the embedded qualitative study. PRIMARY AND SECONDARY OUTCOME MEASURES: The online survey, completed fortnightly over 10 weeks from April 2020 to August 2020, investigated changes in symptoms, social isolation and loneliness, resilience and optimism. Qualitative interviews were undertaken assessing participant's perspectives on changes in symptoms, exercising, managing instrumental tasks such a shopping, medication and treatment regimens and how they experienced changes in their social networks. RESULTS: 703 people with RMDs completed the online survey. These people frequently reported a deterioration in symptoms as a result of COVID-19 pandemic social restrictions (52% reported increase vs 6% reported a decrease). This was significantly worse for those aged 18-60 years compared with older participants (p=0.017). The qualitative findings from 26 individuals with RMDs suggest that the greatest change in daily life was experienced by those in employment. Although some retired people reported reduced opportunity for exercise outside their homes, they did not face the many competing demands experienced by employed people and people with children at home. CONCLUSIONS: People with RMDs reported a deterioration in symptoms when COVID-19 pandemic social restriction measures were enforced. This was worse for working-aged people. Consideration of this at-risk group, specifically for the promotion of physical activity, changing home-working practices and awareness of healthcare provision is important, as social restrictions continue in the UK.

Evidence that bone mineral density plays a role in degenerative disc disease: the UK Twin Spine study.

OBJECTIVE: Osteoarthritis (OA) and osteoporosis are often considered to lie at opposite ends of a spectrum of bone phenotypes. Lumbar degenerative disc disease (LDD) may be associated with low back pain (LBP) and is similar in many ways to OA. LDD is reported in small studies to be associated with increased spine bone mineral density (BMD). The present work aimed to confirm this association in a large population sample using MRI and explore the relationship further, in particular to determine whether it is mediated genetically. METHODS: A population based sample (N = 908, age range 32-74 years) of UK female twins having MRI of the lumbar spine was used in this study. LDD traits and summary measures and their relationship with BMD at the lumbar spine and hip were examined using multivariate multiple regression and maximum likelihood based variance decomposition. RESULTS: There was a significant positive correlation between LDD and BMD at the lumbar spine and hip, which remained significant after adjustment for confounders. Both traits were highly heritable and the associations between them were mediated genetically. CONCLUSIONS: A clear, significant and independent association of BMD at hip and lumbar spine with LDD was found which is, in part, genetically mediated. The association with the non-axial site, the hip, is of particular interest and suggests a systemic bone effect. This should encourage the search for pleiotropic genes to help in the understanding of the bone-cartilage relationship. Moreover, genetic variants identified could provide novel therapeutic targets in the management of LBP.

Pain reporting at different body sites is explained by a single underlying genetic factor.

OBJECTIVES: Musculoskeletal pain is reported commonly; however, the extent to which pain in individual body areas reflects the severity of site-specific pathology or a more generalized propensity to feel pain is uncertain. We used a classical twin design to examine the pattern of pain reporting at different body sites among monozygotic (MZ) and dizygotic (DZ) twins to assess its heritability and to examine evidence for a common underlying propensity to report musculoskeletal pain. METHODS: A well-characterized sample of female twins (TwinsUK cohort) was sent a questionnaire to determine their experience of pain in the neck and back, elbow, knee, thigh, hands or feet. The genetic contribution to pain reporting was assessed through univariate and multivariate analyses. RESULTS: Pain was reported with a prevalence of 17-46%, depending on the anatomical site. Univariate analysis indicated an underlying heritability for pain reporting at all sites of 28-71%. Pain reporting at different sites was modestly but uniformly correlated; a single factor accounted for 95% of the overall variance in pain reporting. The correlation for scores on this factor was 0.46 in MZ twins and 0.23 in DZ twins, corresponding to a 'pain reporting factor' heritability of 46% (95% CI 40%, 52%). CONCLUSIONS: A single genetic factor underlies the propensity to report body pain at different musculoskeletal sites. These findings, which contrast with those for radiographic OA that is determined by genetic factors specific to each anatomical site, will inform the future search for therapeutic targets to treat pain in chronic degenerative diseases.

Dietary garlic and hip osteoarthritis: evidence of a protective effect and putative mechanism of action.

BACKGROUND: Patterns of food intake and prevalent osteoarthritis of the hand, hip, and knee were studied using the twin design to limit the effect of confounding factors. Compounds found in associated food groups were further studied in vitro. METHODS: Cross-sectional study conducted in a large population-based volunteer cohort of twins. Food intake was evaluated using the Food Frequency Questionnaire; OA was determined using plain radiographs. Analyses were adjusted for age, BMI and physical activity. Subsequent in vitro studies examined the effects of allium-derived compounds on the expression of matrix-degrading proteases in SW1353 chondrosarcoma cells. RESULTS: Data were available, depending on phenotype, for 654-1082 of 1086 female twins (median age 58.9 years; range 46-77). Trends in dietary analysis revealed a specific pattern of dietary intake, that high in fruit and vegetables, showed an inverse association with hip OA (p = 0.022). Consumption of 'non-citrus fruit' (p = 0.015) and 'alliums' (p = 0.029) had the strongest protective effect. Alliums contain diallyl disulphide which was shown to abrogate cytokine-induced matrix metalloproteinase expression. CONCLUSIONS: Studies of diet are notorious for their confounding by lifestyle effects. While taking account of BMI, the data show an independent effect of a diet high in fruit and vegetables, suggesting it to be protective against radiographic hip OA. Furthermore, diallyl disulphide, a compound found in garlic and other alliums, represses the expression of matrix-degrading proteases in chondrocyte-like cells, providing a potential mechanism of action.