Glenn Haugeberg

Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: Results from 394 patients in the Oslo County rheumatoid arthritis register

OBJECTIVE To examine the bone mineral density (BMD), frequency of osteoporosis, and risk factors for BMD reduction in a representative population of female rheumatoid arthritis (RA) patients ages 20-70 years. METHODS BMD in the femoral neck, total hip, and spine L2-4 (anterior-posterior view) was measured in 394 RA patients recruited from a validated county RA register (completeness 85%) comprising 721 women ages 20-70 years. BMD was measured with dual-energy x-ray absorptiometry, and age-specific values were compared with pooled values from a European/US population of healthy subjects free from earlier fractures, chronic diseases, and medications influencing bone metabolism. A multiple linear regression model was used to determine individual predictors of BMD. RESULTS No statistically significant differences were found in demographic, disease activity, disease severity, or health status parameters between the RA register patients in whom BMD was measured and the remaining register patients. Femoral neck BMD was significantly reduced by 4.2% in the age group 50-59 years, and by 5.0% in those ages 60-70 years. For BMD in the total hip, the significant reductions were 3.7%, 6.0%, and 8.5% in the age groups 40-49 years, 50-59 years, and 60-70 years, respectively. No significant reduction in spine L2-4 BMD was found. A 2-fold increased frequency of osteoporosis was observed in all 4 age groups of RA patients compared with the reference population, ranging from 0% to 28.6% in the femoral neck, 0% to 29.9% in the total hip, and 1.8% to 31.5% in the spine. Predictors of reduced BMD were as follows: at the femoral neck, older age, low body weight, current use of corticosteroids, greater physical disability (as measured by the modified Health Assessment Questionnaire [M-HAQ]), and presence of rheumatoid factor; at the total hip, older age, low weight, current use of corticosteroids, and higher M-HAQ disability score; and at the lumbar spine, older age, low weight, and current use of corticosteroids. CONCLUSION Register-based prevalence data on BMD reduction in female RA patients ages 20-70 years are presented for the first time in this report, which demonstrates a 2-fold increase in osteoporosis in this representative population.

EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis

Objective To develop evidence-based recommendations on the use of imaging of the joints in the clinical management of rheumatoid arthritis (RA). Methods The task force comprised an expert group of rheumatologists, radiologists, methodologists and experienced rheumatology practitioners from 13 countries. Thirteen key questions on the role of imaging in RA were generated using a process of discussion and consensus. Imaging modalities included were conventional radiography, ultrasound, MRI, CT, dual-emission x-ray absorptiometry, digital x-ray radiogrammetry, scintigraphy and positron emission tomography. Research evidence was searched systematically for each question using MEDLINE, EMBASE and Cochrane CENTRAL. The experts used the evidence obtained from the relevant studies to develop a set of 10 recommendations. The strength of recommendation was assessed using a visual analogue scale. Results A total of 6888 references was identified from the search process, from which 199 studies were included in the systematic review. Ten recommendations were produced encompassing the role of imaging in making a diagnosis of RA, detecting inflammation and damage, predicting outcome and response to treatment, monitoring disease activity, progression and remission. The strength of recommendation for each proposition varied according to both the research evidence and expert opinion. Conclusions Ten key recommendations for the role of imaging in the management of RA were developed using research-based evidence and expert opinion.

Work disability remains a major problem in rheumatoid arthritis in the 2000s: Data from 32 countries in the QUEST-RA Study

IntroductionWork disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries.MethodsThe Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working in high-GDP versus low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses.ResultsAt the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had begun during the 2000s, the probabilities of continuing to work were 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working versus stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant identifier of work disability in all subgroups was Health Assessment Questionnaire (HAQ) functional disability score.ConclusionsWork disability rates remain high among people with RA during this millennium. In low-GDP countries, people remain working with high levels of disability and disease activity. Cultural and economic differences between societies affect work disability as an outcome measure for RA.

Cortical hand bone loss after 1 year in early rheumatoid arthritis predicts radiographic hand joint damage at 5-year and 10-year follow-up

Objective: To examine 1-year hand bone loss in early rheumatoid arthritis (RA) as a predictor of radiographic damage at 5-year and 10-year follow-up Methods: A total of 136 patients with RA (disease duration 0–4 years) were followed for 10 years with clinical data and hand radiographs. Joint damage was scored according to the van der Heijde modification of the Sharp method (vdH Sharp score) and hand bone mineral density (BMD) was measured by digital x ray radiogrammetry (DXR). Group comparisons, correlation analyses and multivariate analyses were performed to evaluate the relationship between hand bone loss and radiographic joint damage. Results: Patients with hand BMD loss at 1 year had a higher median increase in vdH Sharp score compared to patients without loss at 5 years (12 vs 2, p = 0.001) and 10 years (22 vs 4, p = 0.002). In a linear regression model adjusting for age, gender, baseline C-reactive protein (CRP), anti-cyclic citrullinated peptide (CCP), IgM rheumatoid factor (RF) and radiographic damage, absolute hand DXR-BMD loss at 1 year was an independent predictor of radiographic outcome at 5 years (p<0.01) and 10 years (p = 0.02). In a logistic regression model the odds ratio (95% CI) for radiographic progression among patients with hand BMD loss was 3.5 (1.4 to 8.8) and 3.5 (1.4 to 8.4) at 5 and 10 years, respectively. Conclusion: Early hand bone loss measured by DXR-BMD is an independent predictor of subsequent radiographic damage. Our findings support that quantitative hand bone loss in RA precedes radiographic joint damage and may be used as a tool for assessment of bone involvement in RA.

Effects of rheumatoid arthritis on bone

The effects of rheumatoid arthritis on bone include structural joint damage (erosions) and osteoporosis. The latter may lead to increased risk for fractures, which are associated with increased morbidity and mortality. Osteoporosis in rheumatoid arthritis is characterized by a complexity of risk factors, including primary osteoporosis risk factors in addition to inflammation, immobilization, and use of corticosteroids. Quantitative assessment of periarticular and generalized bone loss in rheumatoid arthritis may be reliable indicators of future disease course and potential response variables in intervention studies. The osteoclast cell in rheumatoid arthritis plays a crucial role in the development of erosions and periarticular and generalized osteoporosis, suggested to be mediated through the osteoprotegerin/receptor activator of Nuclear Factor (NF)-&kgr;&bgr;/receptor activator of NF-&kgr;&bgr; ligand signaling system. Based on an improved understanding of this biology, new treatment opportunities exist.

Reduced bone mineral density in male rheumatoid arthritis patients: Frequencies and associations with demographic and disease variables in ninety-four patients in the Oslo county rheumatoid arthritis register

OBJECTIVE To examine reductions in bone mineral density (BMD) and factors associated with reduced BMD in 94 male rheumatoid arthritis (RA) registry patients ages 20-70 years. METHODS Dual-energy x-ray absorptiometry was used to measure BMD in the anteroposterior lumbar spine at L2-LA, the femoral neck, and the total hip, and clinical data were collected. The patients were recruited from a validated county RA registry (completeness 85%) comprising 192 men ages 20-70 years. Age-specific BMD values were compared with a pooled healthy European/United States population. Bivariate and multivariate analyses were performed to determine demographic and disease-related associations with BMD and reduced bone mass (Z score of < or =1 SD below the mean value in controls). RESULTS A statistically significant BMD reduction was found only for the oldest age group (60-70 years): 5.2% reduction in the femoral neck and 6.9% in the total hip. No BMD reduction was found at L2-L4. The proportions (95% confidence intervals) of RA patients with Z scores of < or =1 SD below control (16% expected) were 30.9% (21.6-40.2) for L2-L4, 30.8% (95% CI 21.3-40.3) for the femoral neck, and 33.0% (95% CI 23.3-42.7) for the total hip. Disease activity and severity measures were, in general, not associated with BMD or reduced bone mass. CONCLUSION A 2-fold statistically significant increased frequency of patients with reduced bone mass (Z score of < or =1 SD below control; 16% expected) was found for both the spine and the hip. The only significant reduction in BMD by age group was for the hip in patients who were ages 60-70 years, with no reduction in L2-LA BMD. Multivariate analyses did not reveal consistent associations between reduced BMD and demographic or disease variables.

Adalimumab therapy reduces hand bone loss in early rheumatoid arthritis: Explorative analyses from the PREMIER study

Objective: The effect of adalimumab on hand osteoporosis was examined and related to radiographic joint damage in the three treatment arms of the PREMIER study: adalimumab plus methotrexate, adalimumab and methotrexate monotherapy. Predictors of hand bone loss were also searched for. Methods: 768 patients (537 fulfilled 2 years) with rheumatoid arthritis (RA) for less than 3 years, never treated with methotrexate, were included. Hand bone loss was assessed by digital x ray radiogrammetry (DXR) on the same hand radiographs scored with modified Sharp score at baseline, 26, 52 and 104 weeks. For DXR, metacarpal cortical index (MCI) was the primary bone measure. Results: At all time points the rate of percentage DXR–MCI loss was lowest in the combination group (−1.15; −2.16; −3.03) and greatest in the methotrexate monotherapy group (−1.42; −2.87; −4.62), with figures in between for the adalimumab monotherapy group (−1.33; −2.45; −4.03). Significant differences between the combination group and the methotrexate group were seen at 52 (p = 0.009) and 104 weeks (p<0.001). The order of hand bone loss across the three treatment arms was similar to the order of radiographic progression. Older age, elevated C-reactive protein and non-use of adalimumab were predictors of hand bone loss. Conclusion: This study supports a similar pathogenic mechanism for hand bone loss and erosions in RA. The combination of adalimumab and methotrexate seems to arrest hand bone loss less effectively than radiographic joint damage. Quantitative measures of osteoporosis may thus be a more sensitive tool for assessment of inflammatory bone involvement in RA.

Bone loss in patients with active early rheumatoid arthritis: infliximab and methotrexate compared with methotrexate treatment alone. Explorative analysis from a 12-month randomised, double-blind, placebo-controlled study

Objective: To examine the effect of infliximab plus methotrexate (MTX) compared with placebo plus MTX on bone loss in patients with early rheumatoid arthritis (RA) in a double-blind randomised study design. Further, to explore the associations between bone loss and markers of RA disease. Methods: All 20 patients with RA (10 patients in each treatment group) had active, early RA. Bone mineral density (BMD) was assessed at the hand, lumbar spine (L2–4) and hip by dual energy x-ray absorptiometry at baseline and 12 months’ follow-up. Clinical data were collected at regular visits. Results: BMD loss was significantly reduced in the infliximab group compared with the placebo group at the femoral neck (−0.35% vs −3.43%, p = 0.01) and total hip (−0.23% vs −2.62%, p = 0.03) but not at the hand (−2.09% vs −2.82%, p = 0.82) and spine (−0.75% vs −1.77%, p = 0.71). Measures of disease process and joint damage were found to be independently associated with bone loss. Conclusions: This study provides strong evidence of a causal link between inflammation and bone loss in RA. The anti-inflammatory effect of infliximab was potent enough to arrest inflammatory bone loss at the hip but not at the spine and hand.

Self reported non-vertebral fractures in rheumatoid arthritis and population based controls: incidence and relationship with bone mineral density and clinical variables

Objective: To compare the incidence of self reported non-vertebral fractures after RA diagnosis between female patients with RA and control subjects, and to explore possible associations between non-vertebral fractures and bone mineral density (BMD), disease, and demographic factors. Methods: 249 women (mean age 63.0 years) recruited from a county register of patients with RA and population controls (n = 249) randomly selected after matching for age, sex, and residential area were studied. Data on previous non-vertebral fractures were obtained from a detailed questionnaire, and BMD was measured at the hip and spine. Results: 53 (21.3%) patients with RA had had 67 fractures after RA diagnosis, the corresponding numbers for controls were 50 (20.1%) and 60 (odds ratio (OR) for paired variables for overall fracture history 1.09, 95% CI 0.67 to 1.77). The overall fracture rates per 100 patient-years were 1.62 and 1.45, respectively, but self reported hip fractures were increased in RA (10 v 2, OR 9.0, 95% CI 1.2 to 394.5). Patients with a positive fracture history had longer disease duration, were more likely to have at least one deformed joint, and had lower age and weight adjusted BMD than those with no fracture history. In logistic regression analysis, fracture history was independently related to BMD only. Conclusions: With the probable exception of hip fractures, non-vertebral fractures do not seem to be a substantial burden in RA. Similar independent relationships between levels of BMD and fracture history were found in patients with RA and in population based controls.

Polymyalgia rheumatica can be distinguished from late onset rheumatoid arthritis at baseline: results of a 5-yr prospective study

OBJECTIVE To describe the pattern of arthropathy and HLA-DRB1 alleles associated with PMR in order to develop a diagnostic algorithm that could help distinguish PMR and RF-negative (RF -ve) late-onset RA (LO-RA) at presentation. METHODS This was a prospective study of all patients presenting with PMR or LO-RA over a 10-yr period to one physician. Demographic, clinical and laboratory data were collected at presentation and during a minimum of 5 yrs of follow-up. The accuracy of the initial diagnosis was systematically reviewed. RESULTS One hundred and forty-two patients with LO-RA, 147 with PMR and 42 with PMR + TA were studied. Peripheral synovitis was observed in 23% of the PMR patients. In comparison with RF -ve LO-RA, PMR patients were younger (P < 0.001), myalgia more frequent [100 vs 16% (P < 0.001)] and arthritis of PIP, MCP and wrist were less frequent (P < 0.001). The combination of wrist + MCP/PIP or wrist + PIP + MCP were highly suggestive of RF -ve LO-RA (P < 0.001). HLA-DRB1*0101/0102 and *0401 were significantly increased in PMR patients compared with healthy controls. Plasma viscosity and arthritis in the wrist, in combination with at least one MCP or PIP joint at disease onset, were predictive of whether a non-erosive RF -ve patient would ultimately be diagnosed as having RF -ve LO-RA or PMR (+/-/arthritis). CONCLUSION Our longitudinal follow-up data were consistent with RF -ve LO-RA being a separate disease entity to PMR despite some phenotypic and immunogenetic similarities at disease onset. A diagnostic algorithm was derived using baseline clinical features to predict the final diagnosis of RF -ve, non-erosive patients.