Alexander Oldroyd

The prevalence of osteoporosis in an older population with very high body mass index: evidence for an association

Studies have demonstrated the beneficial effect of normal and high body mass index (BMI) upon risk of osteoporosis (OP). No study has investigated the prevalence of OP in an older population with a very high BMI (higher than 40 kg/m2).

Frailty and bone health in European men

Abstract Background frailty is associated with an increased risk of fragility fractures. Less is known, however, about the association between frailty and bone health. Methods men aged 40–79 years were recruited from population registers in eight European centres for participation in the European Male Aging Study. Subjects completed a comprehensive assessment which included quantitative ultrasound (QUS) scan of the heel (Hologic-SAHARA) and in two centres, dual-energy bone densitometry (dual-energy x-ray absorptiometry, DXA). Frailty was defined based on an adaptation of Frieds phenotype criteria and a frailty index (FI) was constructed. The association between frailty and the QUS and DXA parameters was determined using linear regression, with adjustments for age, body mass index and centre. Results in total, 3,231 subjects contributed data to the analysis. Using the Fried categorisation of frailty, pre-frail and frail men had significantly lower speed of sound (SOS), broadband ultrasound attenuation (BUA) and quantitative ultrasound index (QUI) compared to robust men (P< 0.05). Similar results were seen using the FI after categorisation into ‘high’, ‘medium’ and ‘low’ levels of frailty. Using the Fried categorisation, frail men had lower femoral neck bone mineral density (BMD) compared to robust men (P < 0.05), but not lower lumbar spine BMD. Using the FI categorisation, a ‘high’ level of frailty (FI > 0.35) was associated with lower lumbar spine BMD (P < 0.05) when compared to those with low (FI < 0.2), but not lower femoral neck BMD. When analysed as a continuous variable, higher FI was linked with lower SOS, BUA and QUI (P < 0.05). Conclusions optimisation of bone health as well as prevention of falls should be considered as strategies to reduce fractures in frail older people.

Idiopathic inflammatory myopathies - a guide to subtypes, diagnostic approach and treatment

ABSTRACT The idiopathic inflammatory myopathies are a group of conditions characterised by inflammation of muscles (myositis) and other body systems. The diagnosis can be challenging because of the many potential clinical features and extra-muscular manifestations, which may be seemingly unrelated. An accurate diagnosis requires up-to-date understanding of the clinical manifestations, different clinical subtypes and appropriate interpretation of investigations, including newly described serological subtypes. This review will detail the approach to the diagnosis of an idiopathic inflammatory myopathy, based on up-to-date knowledge. The recently updated classification criteria and treatment options will also be described.

Increasing incidence of adult idiopathic inflammatory myopathies in the City of Salford, UK: a ten-year epidemiological study

Abstract Objectives The aim was to identify and characterize all incident adult cases of idiopathic inflammatory myopathies (IIM) between 1 January 2007 and 31 December 2016 in the City of Salford, UK. Methods Adults first diagnosed with IIM within the study period were identified by: a Salford Royal NHS Foundation Trust (SRFT) inpatient episode IIM-specific ICD-10 coding search; all new patient appointments to SRFT neuromuscular outpatient clinics; and all Salford residents enrolled within the UKMYONET study. All patients with definite IIM by the 2017 EULAR/ACR classification criteria were included, as were probable cases if consensus expert opinion agreed. Cases were excluded if <18 years of age at disease onset, if they did not meet probable criteria or when probable but expert opinion concluded a non-IIM diagnosis. Results The multimodal case ascertainment identified 1156 cases which, after review and application of exclusion criteria, resulted in 32 incident cases during the study period. Twenty-three of 32 were female, with a mean age of 58.1 years. The mean incidence of adult IIM was 17.6/1 000 000 person years, and higher for females than for males (25.2 vs 10.0/1 000 000 person years, respectively). A significant incidence increase over time was apparent (13.6 vs 21.4/1 000 000 person years; P = 0.032). Using EULAR/ACR classification criteria, the largest IIM subtype (21/32) was PM, followed by DM (8/32), IBM (2/32) and amyopathic DM (1/32). Expert opinion subtype differed from EULAR/ACR classification criteria in 19/32 cases. Conclusion The incidence of adult IIM in Salford is 17.6/1 000 000 person years, higher in females, and is increasing over time. Disagreement exists between EULAR/ACR-derived and expert opinion-derived IIM subtype assignments.

Long-term persistence with rituximab in patients with rheumatoid arthritis

Abstract Objectives To investigate the long term persistence of rituximab (RTX) in a large observational RA cohort, investigate persistence of RTX when used as a first or second line biologic DMARD (bDMARD), to characterize subsequent bDMARD treatment following RTX. Methods Patients with RA starting treatment with RTX (MabThera) between 2008 and 2011 were recruited into the British Society for Rheumatology Biologics Register for RA. Duration of RTX treatment over the first 4 years after initiation was estimated via Kaplan-Meier estimates and the reason for discontinuation was ascertained. Subsequent bDMARD use following RTX discontinuation was characterised. Treatment survival in bDMARD-naïve (first line RTX use) and experienced (second line RTX use) cohorts was described. Results One thousand six hundred and twenty-nine patients were recruited (1371 bDMARD-experienced and 258 bDMARD-naïve). Sixty percent of the whole cohort remained on RTX after 4 years. Ineffectiveness (46%) and death (24%) were the most common reason for RTX discontinuation. RTX discontinuation was associated with RF negativity for the bDMARD-experienced cohort. Of those that discontinued RTX, 46% initiated treatment with another bDMARD, with tocilizumab being the most common. Conclusion This large study of patients initiating RTX treatment for severe RA found that 60% persisted with treatment after 4 years. This study also identified that RTX is tolerated well when used as a first or second line bDMARD.

OP0148 A validation of the 2017 eular/acr idiopathic inflammatory myopathies classification criteria in an expert-defined single-centre ten year incident cohort

Background The recently published 2017 European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups reflect a long-appreciated need for more accurate case definition in ongoing research in these complex and heterogenous diseases.1 However a number of issues remain unresolved. There was a high frequency of missing data in both the derivation and validation samples, only one of the now numerous myositis specific autoantibodies is included, and certain well recognised IIM subtypes are not specifically classified despite their well phenotyped and differing natural histories, clinical features and treatment modalities.2 3 Objectives To perform an external validation of the EULAR/ACR classification criteria in an incident IIM cohort and examine how classification criteria-assigned IIM subtype correlates with expert opinion. Methods Adults with newly diagnosed IIM attending Salford Royal NHS Foundation Trust Neuromuscular services were identified. A retrospective review of all putative cases was performed, and cases fulfilling a consensus expert-opinion diagnosis of definite IIM included. A broad range of clinical, serological and histological data were collected and each case assigned a single IIM subtype by expert opinion. The EULAR/ACR classification criteria were applied and sensitivity, specificity, positive and negative predictive value calculated, presented with 95% confidence intervals (CI). Results A total of 922 cases were screened with 255 expert opinion definite IIM identified. The sensitivity to diagnose an IIM was 99.6% (97.2–100) and 80.9% (76.0–85.8) for the classification criteria cut-points of ‘probable’ and ‘definite’ respectively. The sensitivity for ‘definite’ IIM improved to 90.2% (86.5–93.8) when biopsy data for 24/34 initially missed cases were excluded. In 94/255 cases the IIM subtype differed between expert opinion and classification criteria, most strikingly in the group subtyped ‘polymyositis’ using the EULAR/ACR criteria, where there was discrepancy in the majority (87/161).Abstract OP0148 – Table 1 PM, polymyositis; DM, dermatomyositis; IBM, inclusion body myositis; ADM, amyopathic dermatomyositis; IMNM, immune-mediated necrotizing myopathy; ASS, anti-synthetase syndrome; OM, overlap myositis. Conclusions The criteria performed with high sensitivity in identifying IIM in an external cohort of IIM patients. However, substantial disagreement exists in subtype assignment, especially resulting in a larger proportion of cases of ‘polymyositis’ with heterogeneous features, important to consider in the application of these criteria to subsequent research. References [1] Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, Visser M De, et al. EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis2017;76:1955–64. [2] Betteridge Z, McHugh N. Myositis-specific autoantibodies: An important tool to support diagnosis of myositis. J Intern Med2016;280:8–23. [3] Longo DL, Dalakas MC. Inflammatory muscle diseases. N Engl J Med2015;372:1734–47. Disclosure of Interest None declared

FRI0455 Increasing incidence of adult idiopathic inflammatory myopathies: a ten-year uk epidemiological study

Background Studying the epidemiology of rare conditions such as the idiopathic inflammatory myopathies (IIM) can assist in the identification of risk factors, disease associations and temporal trends. Interrogation of differing geographically and genetically diverse populations can help to construct a more complete picture of underlying disease patterns. A number of UK centres have contributed to national and international IIM research collaborations, but to date there has been no published report detailing the incidence or prevalence of adult IIM in the UK, or to establish the relative proportion of the varying clinical subtypes. Moreover, previous international studies have focussed on specific IIM subtypes, such as inclusion body myositis (IBM) or immune-mediated necrotising myopathy (IMNM), are historic, were undertaken before recent developments in our understanding of the range of IIM subtypes, and utilised widely varying methodologies and case acquisition strategies. The recently published combined European League Against Rheumatism and American College of Rheumatology (EULAR/ACR) classification criteria for adult and juvenile IIM represent potential progress in identifying IIM, as well as various disease subtypes1. We present here the first epidemiological study to utilise these new criteria as part of disease verification. Objectives Identify and characterise all incident adult cases of IIM between Jan 1 st 2007 and Dec 31 st 2016 in the City of Salford, UK. Methods Adults first diagnosed with IIM within the study period were identified by: i) a Salford Royal NHS Foundation Trust (SRFT)inpatient episode IIM-specific ICD-10 coding search; ii) all new patient appointments to SRFT neuromuscular outpatient clinics; iii) all Salford residents enrolled within the UKMYONET study. All patients with ‘definite’ IIM by the 2017 EULAR/ACR classification criteria were included, as were ‘probable’ cases if expert opinion agreed. Cases were excluded if <18 years at disease onset, if they did not meet ‘probable’ criteria, or when ‘probable’ but expert opinion concluded a non-IIM diagnosis. Results The case ascertainment procedures identified 1156 cases which, after review and application of exclusion criteria, resulted in 32 incident cases during the study period. 23/32 were female with a mean age of 58.1 years. The mean incidence of adult IIM was 17.6/1,000,000 person years (py), higher for females than for males (25.2 versus 10.0/1,000,000py respectively). A significant incidence increase over time was apparent (13.6 versus 21.4/1,000,000py; p=0.032). Using EULAR/ACR classification criteria, the largest IIM subtype (21/32) was polymyositis, followed by dermatomyositis (8/32), inclusion body myositis (2/32) and amyopathic dermatomyositis (1/32). Expert opinion subtype differed from EULAR/ACR Classification criteria in 19/32 cases. Conclusions The incidence of adult IIM in Salford is 17.6/1,000,000py, higher in females and is increasing over time. Disagreement exists between EULAR/ACR-derived and expert opinion-derived IIM subtype assignments. References [1] Lundberg IE, Tjärnlund A, Bottai M, et al. EULAR/ACR Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies and their Major Subgroups. Ann Rheum Dis. 2017;76:1955–64. Disclosure of Interest None declared

OP0279 The Standardised Mortality Rate in UK Adult-Onset Myositis Patients is Seven Times Higher than the UK General Population

Background The idiopathic inflammatory myopathies (IIM) are a group of autoimmune mediated disorders characterised by skeletal muscle inflammation. Identification of factors associated with mortality may allow future interventional measures to reduce mortality. Objectives To compare mortality rates in a large UK IIM population with those in the general population and to identify clinical, serological and demographic factors associated with mortality. Methods IIM patients were identified through the UKMYONET study from 84 UK centres. Patients with adult-onset probable or definite polymyositis (PM) or dermatomyositis (DM), or defined inclusion body myositis (IBM) as per accepted criteria (Bohan/Peter, Griggs, MRC) were recruited. Data included demographics, smoking status, cancer diagnosis, clinical features and presence of myositis-specific/associated antibodies (MSA/MAA). Date and cause of death was collated from the UK Health and Social Care Information Service. Age-standardised mortality rates (ASR) per 100,000 persons were calculated for each gender and IIM subtype. Mortality was compared between IIM subtypes (PM as a reference), clinical features and MSA/MAA subsets using calculated hazard ratios (HRs), adjusted for age, sex and smoking. Results 724 IIM patients were recruited (62.2% female, 34% smoked, mean age of disease onset 52.4 years [SD 14.9]). Mean symptom onset to diagnosis time was 1.3 years (SD 2.5). 72 (10%) had died at time of analysis. Median time from diagnosis to death for the whole cohort was 12 years (1st quartile 4 years, 3rd quartile 17 years), 8 years for the cancer-associated myositis (CAM) cohort and 16 years for the non-CAM cohort. Mortality risk did not vary between men and women: 10.2% vs 9.8%, p=0.9. 31 deaths were due to pneumonia, 2 interstitial lung disease (ILD), 1 pulmonary embolism, 16 cardiac causes (myocardial infarction, cardiac failure), 11 malignancy, 8 sepsis, 2 IIM and 1 spontaneous haemothorax. Increasing age at onset and smoking history were associated with mortality: HR 1.1 (95% CI 1.1, 1.2) and 2.3 (1.4, 3.8) respectively. Cardiovascular pathology was associated with higher mortality: HR 3.5 (1.2, 10.4). Periorbital oedema was associated with higher mortality in the DM group: HR 6.7 (1.5, 31.5). Table 1 shows that ASRs per 100,000 persons were more than seven times higher than those in the general UK population: ASR 7559 vs 987/100,000 persons respectively. IBM ASR was significantly lower than DM and PM for females only. CAM was significantly associated with mortality in men only: HR 5.7 (95% CI 2.5, 13.1). No other IIM subtype, clinical feature (including ILD) or MSA/MAA subsets (including Jo-1) were associated with mortality.Table 1. ASRs for UK IIM population Female ASR/100,000 95% CI Male ASR/100,000 95% CI Total 7154 5016, 9293 7498 4721, 10276 DM 8101 4001, 12201 7522 1949, 13094 PM 8825 4359, 13291 9830 3737, 15924 IBM 1944 38, 3850 3609 1108, 6110 CAM 10900 4144, 17655 20166 7667, 32666 Non-CAM 5561 363, 7458 4642 2497, 6787 Conclusions This is the first study to investigate factors associated with increased mortality in a large UK IIM population with a verified IIM diagnosis. Mortality rates in IIM are higher than those of the general UK population mainly due to cardiovascular pathology and cancer, with pneumonia being the leading cause of death. Disclosure of Interest None declared

FRI0303 The Effect of Secondary Amenorrhoea on Bone Mineral Density

Background Bone mineral density (BMD) of the femoral neck is used as part of the FRAX Tool to calculate a patients 10 year probability of having a fragility fracture. Risk factors for a reduction in BMD include reduction in oestrogen in female patients. Amenorrhoea is a reliable clinical indicator of oestrogen deficiency as its occurrence coincides with a more rapid reduction in BMD (1). Patients with the onset of menopause before the age of 45 have previously been shown to be at risk of low BMD, but studies have not addressed whether a history of amenorrhoea was associated with a reduction in BMD. Objectives To investigate whether secondary amenorrhoea causes a reduction in BMD compared to normal healthy controls after adjustment for possible confounders. Methods Data of female individuals that underwent Dual-energy X-ray Absorptiometry scan at a District hospital in the North West of England between 1992 and 2010 were used. The age of patients was recorded as well as the BMD in femoral neck and lumbar spine. Other characteristics recorded included height and weight to calculate body mass index (BMI) and percentage body fat. Patients with secondary amenorrhoea or a history of amenorrhoea were compared to a female only control group with no identifiable risk factors for scanning. Initially, differences in age at scan, BMI and body fat were compared using a Students T test. Logistic regression modelling, adjusted for age, BMI and body fat was used to examine any reduction in BMD of the lumbar spine or femoral neck between patients and controls. Results 277 patients were identified that had secondary amenorrhoea or previous amenorrhoea. Median age was 44.2 years (IQR 34.9,50.75) compared to 4763 female controls median age 57.9 years (IQR 51.4,67.00). 53 (19.13%) of the patients had sustained a fracture. BMI in cases was significantly less than controls (23.4 kg/m2 vs 26.6 kg/m2 p<0.001). Body fat was also less in cases than controls (23.1% vs 29.1% p<0.001). The unadjusted odds ratio for a reduction of BMD of the lumbar spine was 0.36 (95% CI 0.18, 0.70) and in the femoral neck the odds were 3.52 (95% CI 1.19, 10.42). After adjusting for age, the odds ratio for a reduction in BMD of the lumbar spine was 0.05 (95% CI 0.02,0.11) and 0.08 (95% CI 0.01,0.33) for the femoral neck. Adjusting for age and BMI showed an OR of 0.09 (95%CI 0.04, 0.22) in the lumbar spine and OR 0.25 (95%CI 0.05,1.15) in the femoral neck. When adjusting for body fat and age at scan the odds were 0.15 (95%CI 0.05,0.46) in the lumbar spine and 0.13 (95%CI 0.03,0.56) in the femoral neck. Adjusting for both BMI and body fat gave odds of 0.21 (95%CI 0.07,0.68) and 0.21 (0.04,0.99) respectively. Conclusions After adjusting for age and BMI, secondary amenorrhoea appears to have a detrimental effect on the BMD of the lumbar spine and a trend of effect on the femoral neck. When adjusting for percentage body fat it shows a reduction in both sites. As the FRAX tool uses femoral neck BMD and BMI as a predictor for fracture, not using percent body fat could lead to an underestimation of the fracture risk in this group of patients. Further research is required to investigate the effects of secondary amenorrhoea on BMD and its longitudinal prediction. References Choktanasiri W, Rojanasakul A, Rajatanavin R. Bone mineral density in primary and secondary amenorrhoea. J Med Assoc Thai. 2000 Mar;83 (3):243-8. Disclosure of Interest None declared