Influence of inflammatory polyarthritis on quantitative heel ultrasound measurements.

BACKGROUND: There are few data concerning the impact of inflammatory polyarthritis (IP) on quantitative heel ultrasound (QUS) measurements. The aims of this analysis were i) to determine the influence of IP on QUS measurements at the heel and, ii) among those with IP to determine the influence of disease related factors on these measurements. METHODS: Men and women aged 16 years and over with recent onset IP were recruited to the Norfolk Arthritis Register (NOAR). Individuals with an onset of joint symptoms between 1989 and 1999 were included in this analysis. At the baseline visit subjects underwent a standardised interview and clinical examination with blood taken for rheumatoid factor. A population-based prospective study of chronic disease (EPIC-Norfolk) independently recruited men and women aged 40 to 79 years from the same geographic area between 1993 and 1997. At a follow up assessment between 1998 and 2000 subjects in EPIC-Norfolk were invited to have quantitative ultrasound measurements of the heel (CUBA-Clinical) performed. We compared speed of sound (SOS) and broadband ultrasound attenuation (BUA), in those subjects recruited to NOAR who had ultrasound measurements performed (as part of EPIC-Norfolk) subsequent to the onset of joint symptoms with a group of age and sex matched non-IP controls who had participated in EPIC-Norfolk. Fixed effect linear regression was used to explore the influence of IP on the heel ultrasound parameters (SOS and BUA) so the association could be quantified as the mean difference in BUA and SOS between cases and controls. In those with IP, linear regression was used to examine the association between these parameters and disease related factors. RESULTS: 139 men and women with IP and 278 controls (mean age 63.2 years) were studied. Among those with IP, mean BUA was 76.3 dB/MHz and SOS 1621.8 m/s. SOS was lower among those with IP than the controls (difference = -10.0; 95% confidence interval (CI) -17.4, -2.6) though BUA was similar (difference = -1.2; 95% CI -4.5, +2.1). The difference in SOS persisted after adjusting for body mass index and steroid use. Among those with IP, disease activity as determined by the number of swollen joints at baseline, was associated with a lower SOS. In addition SOS was lower in the subgroup that satisfied the 1987 ACR criteria. By contrast, disease duration, steroid use and HAQ score were not associated with either BUA or SOS. CONCLUSIONS: In this general population derived cohort of individuals with inflammatory polyarthritis there is evidence from ultrasound of a potentially adverse effect on the skeleton. The effect appears more marked in those with active disease.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Abandoned Acid? Understanding Adherence to Bisphosphonate Medications for the Prevention of Osteoporosis among Older Women: A Qualitative Longitudinal Study

Background There is significant morbidity and mortality caused by the complications of osteoporosis, for which ageing is the greatest epidemiological risk factor. Preventive medications to delay osteoporosis are available, but little is known about motivators to adhere to these in the context of a symptomless condition with evidence based on screening results. Aim To describe key perceptions that influence older women's adherence and persistence with prescribed medication when identified to be at a higher than average risk of fracture. Design of Study A longitudinal qualitative study embedded within a multi-centre trial exploring the effectiveness of screening for prevention of fractures. Setting Primary care, Norfolk. United Kingdom Methods Thirty older women aged 70–85 years of age who were offered preventive medication for osteoporosis and agreed to undertake two interviews at 6 and 24 months post-first prescription. Results There were no overall predictors of adherence which varied markedly over time. Participants' perceptions and motivations to persist with medication were influenced by six core themes: understanding adherence and non-adherence, motivations and self-care, appraising and prioritising risk, anticipating and managing side effects, problems of understanding, and decision making around medication. Those engaged with supportive professionals could better tolerate and overcome barriers such as side-effects. Conclusions Many issues are raised following screening in a cohort of women who have not previously sought advice about their bone health. Adherence to preventive medication for osteoporosis is complex and multifaceted. Individual participant understanding, choice, risk and perceived need all interact to produce unpredictable patterns of usage and acceptability. There are clear implications for practice and health professionals should not assume adherence in any older women prescribed medication for the prevention of osteoporosis. The beliefs and motivations of participants and their healthcare providers regarding the need to establish acceptable medication regimes is key to promoting and sustaining adherence

Influence of arthritis and non-arthritis related factors on areal bone mineral density (BMDa) in women with longstanding inflammatory polyarthritis: a primary care based inception cohort

<p>Abstract</p> <p>Background</p> <p>The aim of this analysis was to determine the relative influence of disease and non-disease factors on areal bone mineral density (BMD_a) in a primary care based cohort of women with inflammatory polyarthritis.</p> <p>Methods</p> <p>Women aged 16 years and over with recent onset inflammatory polyarthritis were recruited to the Norfolk Arthritis Register (NOAR) between 1990 and 1993. Subjects were examined at both baseline and follow up for the presence of tender, swollen and deformed joints. At the 10^thanniversary visit, a sub-sample of women were invited to complete a bone health questionnaire and attend for BMD_a(Hologic, QDR 4000). Linear regression was used to examine the association between BMD_awith both (i) arthritis-related factors assessed at baseline and the 10^thanniversary visit and (ii) standard risk factors for osteoporosis. Adjustments were made for age.</p> <p>Results</p> <p>108 women, mean age 58.0 years were studied. Older age, decreasing weight and BMI at follow up were all associated with lower BMD_aat both the spine and femoral neck. None of the lifestyle factors were linked. Indices of joint damage including 10^thanniversary deformed joint count and erosive joint count were the arthritis-related variables linked with a reduction in BMD_aat the femoral neck. By contrast, disease activity as determined by the number of tender and or swollen joints assessed both at baseline and follow up was not linked with BMD_aat either site.</p> <p>Conclusion</p> <p>Cumulative disease damage was the strongest predictor of reduced femoral bone density. Other disease and lifestyle factors have only a modest influence.</p

Screening in the community to reduce fractures in older women (SCOOP): a randomised controlled trial

Background Despite effective assessment methods and medications targeting osteoporosis and related fractures, screening for fracture risk is not currently advocated in the UK. We tested whether a community-based screening intervention could reduce fractures in older women. Methods We did a two-arm randomised controlled trial in women aged 70–85 years to compare a screening programme using the Fracture Risk Assessment Tool (FRAX) with usual management. Women were recruited from 100 general practitioner (GP) practices in seven regions of the UK: Birmingham, Bristol, Manchester, Norwich, Sheffield, Southampton, and York. We excluded women who were currently on prescription anti-osteoporotic drugs and any individuals deemed to be unsuitable to enter a research study (eg, known dementia, terminally ill, or recently bereaved). The primary outcome was the proportion of individuals who had one or more osteoporosis-related fractures over a 5-year period. In the screening group, treatment was recommended in women identified to be at high risk of hip fracture, according to the FRAX 10-year hip fracture probability. Prespecified secondary outcomes were the proportions of participants who had at least one hip fracture, any clinical fracture, or mortality; and the effect of screening on anxiety and health-related quality of life. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN 55814835. Findings 12 483 eligible women were identified and participated in the trial, and 6233 women randomly assigned to the screening group between April 15, 2008, and July 2, 2009. Treatment was recommended in 898 (14%) of 6233 women. Use of osteoporosis medication was higher at the end of year 1 in the screening group compared with controls (15% vs 4%), with uptake particularly high (78% at 6 months) in the screening high-risk subgroup. Screening did not reduce the primary outcome of incidence of all osteoporosis-related fractures (hazard ratio [HR] 0·94, 95% CI 0·85–1·03, p=0·178), nor the overall incidence of all clinical fractures (0·94, 0·86–1·03, p=0·183), but screening reduced the incidence of hip fractures (0·72, 0·59–0·89, p=0·002). There was no evidence of differences in mortality, anxiety levels, or quality of life. Interpretation Systematic, community-based screening programme of fracture risk in older women in the UK is feasible, and could be effective in reducing hip fractures. Funding Arthritis Research UK and Medical Research Council

Rheumatoid arthritis - clinical aspects: 134. Predictors of Joint Damage in South Africans with Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) causes progressive joint damage and functional disability. Studies on factors affecting joint damage as clinical outcome are lacking in Africa. The aim of the present study was to identify predictors of joint damage in adult South Africans with established RA. Methods: A cross-sectional study of 100 black patients with RA of >5 years were assessed for joint damage using a validated clinical method, the RA articular damage (RAAD) score. Potential predictors of joint damage that were documented included socio-demographics, smoking, body mass index (BMI), disease duration, delay in disease modifying antirheumatic drug (DMARD) initiation, global disease activity as measured by the disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and autoantibody status. The predictive value of variables was assessed by univariate and stepwise multivariate regression analyses. A p value <0.05 was considered significant. Results: The mean (SD) age was 56 (9.8) years, disease duration 17.5 (8.5) years, educational level 7.5 (3.5) years and DMARD lag was 9 (8.8) years. Female to male ratio was 10:1. The mean (SD) DAS28 was 4.9 (1.5) and total RAAD score was 28.3 (12.8). The mean (SD) BMI was 27.2 kg/m2 (6.2) and 93% of patients were rheumatoid factor (RF) positive. More than 90% of patients received between 2 to 3 DMARDs. Significant univariate predictors of a poor RAAD score were increasing age (p = 0.001), lower education level (p = 0.019), longer disease duration (p < 0.001), longer DMARD lag (p = 0.014), lower BMI (p = 0.025), high RF titre (p < 0.001) and high ESR (p = 0.008). The multivariate regression analysis showed that the only independent significant predictors of a higher mean RAAD score were older age at disease onset (p = 0.04), disease duration (p < 0.001) and RF titre (p < 0.001). There was also a negative association between BMI and the mean total RAAD score (p = 0.049). Conclusions: Patients with longstanding established RA have more severe irreversible joint damage as measured by the clinical RAAD score, contrary to other studies in Africa. This is largely reflected by a delay in the initiation of early effective treatment. Independent of disease duration, older age at disease onset and a higher RF titre are strongly associated with more joint damage. The inverse association between BMI and articular damage in RA has been observed in several studies using radiographic damage scores. The mechanisms underlying this paradoxical association are still widely unknown but adipokines have recently been suggested to play a role. Disclosure statement: C.I. has received a research grant from the Connective Tissue Diseases Research Fund, University of the Witwatersrand. All other authors have declared no conflicts of interes

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

A Multicenter, Randomized, Placebo‐Controlled Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients With Rheumatoid Arthritis

Objective: Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVEs in RA patients. Methods: A randomized, double‐blind, placebo‐controlled trial was designed to detect a 32% CVE risk reduction based on an estimated 1.6% per annum event rate with 80% power at P 50 years or with a disease duration of >10 years who did not have clinical atherosclerosis, diabetes, or myopathy received atorvastatin 40 mg daily or matching placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary and tertiary end points included plasma lipids and safety. Results: A total of 3,002 patients (mean age 61 years; 74% female) were followed up for a median of 2.51 years (interquartile range [IQR] 1.90, 3.49 years) (7,827 patient‐years). The study was terminated early due to a lower than expected event rate (0.70% per annum). Of the 1,504 patients receiving atorvastatin, 24 (1.6%) experienced a primary end point, compared with 36 (2.4%) of the 1,498 receiving placebo (hazard ratio [HR] 0.66 [95% confidence interval (95% CI) 0.39, 1.11]; P = 0.115 and adjusted HR 0.60 [95% CI 0.32, 1.15]; P = 0.127). At trial end, patients receiving atorvastatin had a mean ± SD low‐density lipoprotein (LDL) cholesterol level 0.77 ± 0.04 mmoles/liter lower than those receiving placebo (P < 0.0001). C‐reactive protein level was also significantly lower in the atorvastatin group than the placebo group (median 2.59 mg/liter [IQR 0.94, 6.08] versus 3.60 mg/liter [IQR 1.47, 7.49]; P < 0.0001). CVE risk reduction per mmole/liter reduction in LDL cholesterol was 42% (95% CI −14%, 70%). The rates of adverse events in the atorvastatin group (n = 298 [19.8%]) and placebo group (n = 292 [19.5%]) were similar. Conclusion: Atorvastatin 40 mg daily is safe and results in a significantly greater reduction of LDL cholesterol level than placebo in patients with RA. The 34% CVE risk reduction is consistent with the Cholesterol Treatment Trialists’ Collaboration meta‐analysis of statin effects in other populations