Rheumatoid Arthritis: Ørstavik RE

Haugeberg G, Ørstavik RE, Kvien TK. · Oslo City Department of Rheumatology, Diakonhjemmet Hospital, Norway. · Curr Opin Rheumatol. · Pubmed #12819477 No free full text.

Abstract: 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)-kappabeta/receptor activator of NF-kappabeta ligand signaling system. Based on an improved understanding of this biology, new treatment opportunities exist.

Haugeberg G, Lodder MC, Lems WF, Uhlig T, Ørstavik RE, Dijkmans BA, Kvien TK, Woolf AD. · Department of Rheumatology, Sørlandet Hospital, N-4604 Kristiansand S, Norway. · Ann Rheum Dis. · Pubmed #15361395 links to  free full text

Abstract: OBJECTIVE: To investigate the relationship between hand bone mineral density (BMD) and radiographic joint damage, and between hand BMD and fractures in 50-70 year old women with longstanding RA. METHODS: Demographic, clinical data, and imaging data on hand radiographs and Genants vertebral deformity score on spine radiographs were collected from 135 women with RA of > or =5 years, recruited from three European rheumatology clinics. Metacarpal hand BMD was measured by digital hand x ray radiogrammetry (DXR), and hip and lumbar spine BMD by dual x ray absorptiometry (DXA). Multiple regression analyses were used to examine associations between hand BMD and radiographic joint damage, and hand BMD and fractures. RESULTS: Hand BMD was strongly and independently associated with radiographic hand joint damage in a linear regression model adjusted for age, centre, BMI, disease duration, RF, 18 deformed joint count, ESR, and femoral neck BMD. In a multivariate logistic regression model adjusted for relevant variables, hand BMD and femoral neck BMD, but not spine BMD, were independently associated with vertebral deformities and with non-vertebral fractures. CONCLUSION: BMD measured by DXR on conventional hand radiographs in patients with RA may potentially be used as an indicator of joint damage and of vertebral and non-vertebral fracture risk.

Ørstavik RE, Haugeberg G, Uhlig T, Mowinckel P, Kvien TK, Falch JA, Halse JI. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Ann Rheum Dis. · Pubmed #15249321 links to  free full text

Abstract: BACKGROUND: Quantitative ultrasound (QUS) is a reliable tool for discriminating between subjects with and without vertebral deformities in postmenopausal osteoporosis. Less is known about osteoporosis caused by inflammatory diseases or corticosteroid use. OBJECTIVES: (1). To compare in patients with rheumatoid arthritis the ability of QUS and dual energy x ray absorptiometry (DXA) to discriminate between those with and without vertebral deformities; (2). to explore whether the results are similar in population based controls. METHODS: Standardised lateral radiographs of the spine were obtained from 210 patients with rheumatoid arthritis aged over 50 years and 210 individually matched controls. Vertebral deformities were assessed morphometrically and semiquantitatively. All participants underwent bone measurements by DXA (Lunar Expert) and QUS (Lunar Achilles+). Receiver operating curve (ROC) analysis was used to compare the discriminating ability of BMD and QUS measurements in patients and controls with and without vertebral deformities. Analyses were repeated in patients stratified according to corticosteroid use. RESULTS: For all bone measurements except lumbar spine in the rheumatoid arthritis group, BMD discriminated significantly between the patients with and without vertebral deformities, and the results were similar to those obtained in controls. Among current corticosteroid users, neither QUS nor DXA could discriminate between subjects with and without vertebral deformities. CONCLUSIONS: These findings support QUS as an alternative tool for identifying patients at risk of having vertebral deformities in rheumatoid arthritis, although results should be interpreted with caution in current users of corticosteroids.

Ørstavik RE, Haugeberg G, Mowinckel P, Høiseth A, Uhlig T, Falch JA, Halse JI, McCloskey E, Kvien TK. · Oslo City Department of Rheumatology, Oslo, Norway. · Arch Intern Med. · Pubmed #14980993 links to  free full text

Abstract: BACKGROUND: Previous studies have shown an increased prevalence of osteoporosis in rheumatoid arthritis (RA), but the extent of osteoporotic fractures is not clarified. The aim of this study was to compare the prevalence of vertebral deformities in a representative, population-based cohort of female patients with RA with that in matched controls, and to examine the relationship between deformities and RA, bone mineral density (BMD), and corticosteroid use. METHODS: Female patients (mean age, 63.0 years; range, 50.7-73.6 years) were recruited from a county register of patients with RA. Population controls were matched for age, sex, and residential area. Participants had thoracolumbar radiographs taken according to a standardized procedure, and BMD was measured at the hip and spine (L2-L4). RESULTS: The overall number of vertebral deformities was substantially higher in the RA group compared with controls (147 vs 51, applying the morphometric criteria), with a highly significant difference between patients and controls regarding the presence of multiple deformities measured morphometrically (11.2% vs 4.8%; odds ratio, 2.60; 95% confidence interval, 1.21-6.04) and moderate or severe deformities measured semiquantitatively (17.3% vs 10.0%; odds ratio, 2.00; 95% confidence interval, 1.11-3.74). In Poisson regression analysis, vertebral deformities were independently associated with RA, BMD, and long-term corticosteroid use. CONCLUSIONS: Vertebral deformities are markedly increased in patients with RA compared with controls, especially regarding severe and multiple deformities. A diagnosis of RA was associated with vertebral deformities independently of BMD and long-term corticosteroid use. These findings have important implications for prevention of established osteoporosis in RA.

Ørstavik RE, Haugeberg G, Uhlig T, Mowinckel P, Falch JA, Halse JI, Kvien TK. · Oslo City Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Ann Rheum Dis. · Pubmed #14722207 links to  free full text

Abstract: 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.

Ørstavik RE, Haugeberg G, Uhlig T, Falch JA, Halse JI, Høiseth A, Lilleås F, Kvien TK. · Oslo City Department of Rheumatology, Oslo, Norway. · Arthritis Rheum. · Pubmed #12794791 links to  free full text

Abstract: OBJECTIVE: To examine the occurrence of vertebral deformities in female patients with rheumatoid arthritis (RA), and the relationship between vertebral deformities and bone mineral density (BMD) and between vertebral deformities and clinical variables. METHODS: Lateral radiographs of the spine were obtained in 229 female patients with RA (mean age 63.4 years, range 51.4-73.6 years) recruited from a county RA register. Vertebral deformities were measured semiquantitatively by an experienced radiologist. A clinical examination including core measurements of disease activity and severity was performed, and BMD was measured at the spine (L2-L4) and hip. RESULTS: According to the statistical analysis, 49 patients were considered to have relevant vertebral deformities. The occurrence of vertebral deformities was independently associated with age, long-term corticosteroid use, and previous nonvertebral fracture, as well as reduced BMD. Our results failed to show any independent relationship between vertebral deformities and the activity or severity of disease. CONCLUSION: Corticosteroid use is an important marker of established osteoporosis in patients with RA. Additionally, there seems to be a consistent relationship between BMD and vertebral deformities in this patient group.

Haugeberg G, Ørstavik RE, Uhlig T, Falch JA, Halse JI, Kvien TK. · Oslo City Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Osteoporos Int. · Pubmed #12730749 No free full text.

Abstract: To compare quantitative ultrasound (QUS) and dual-energy X-ray absorptiometry (DXA) bone measurements in female rheumatoid arthritis (RA) patients and controls were randomly selected from the population; secondly, to examine disease and demographic factors associated with these bone measurements. In a total of 115 RA patients (mean age 63.0 years) and 115 age- and gender-matched controls demographic and clinical variables were collected and heel QUS parameters [speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness index (SI)] as well as DXA bone mineral density (BMD) at spine and hip were measured. The differences in QUS and DXA measurements between RA patients and controls were tested both on a group and on an individual level. Univariate and multivariate statistical tests were applied to explore for associations to the bone measurements. In the RA patients mean disease duration was 16.6 years, erythrocyte sedimentation rate 23.6 mm/h, M-HAQ 1.68, 28-swollen joint count 7.7, 18-deformed joint count 4.5, 50.0% were rheumatoid factor (RF) positive and 44.2% were current users of prednisolone. All bone measurements were reduced in RA patients compared with controls (SOS 1.9%, BUA 9.4%, SI 19.5%, femoral neck BMD 7.4%, total hip BMD 7.5%, spine L2-L4 BMD -3.0%). Only at spine was the BMD reduction not statistically significant ( P=0.21). In the subgroup of never users of prednisolone SOS was decreased by 1.4%, BUA by 3.7%, SI by 11.0, femoral neck BMD by 2.7%, and total hip BMD by 0.6%, whereas for spine L2-L4 BMD was increased by 4.3% and only for SOS and SI was the decrease statistically significant. The QUS discriminated better than DXA between patients and controls on a group level, but this difference in favor of QUS disappeared on an individual level when the measurement errors were taken into account. Age, BMI, RF and deformed joint count, but not corticosteroids, were independently associated with at least one of the QUS and one of the DXA measures; however, the association between disease-related variables was stronger with the QUS bone measures than with the DXA bone measures. The results for the quantitative QUS bone measures seem to mainly reflect bone mass. Disease-related variables in multivariate analysis remained independently associated with all QUS measures even when adjusting for DXA bone measures. Further studies are needed to examine if QUS may reflect other aspects than bone mass and be a potential better predictor for fracture risk in RA and corticosteroid-induced osteoporosis.

Haugeberg G, Ørstavik RE, Uhlig T, Falch JA, Halse JI, Kvien TK. · Oslo City Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Ann Rheum Dis. · Pubmed #12429540 links to  free full text

Abstract: BACKGROUND: Preliminary clinical criteria based on age, inflammation, and immobility have been proposed to identify which patients with rheumatoid arthritis (RA) should be examined by dual energy x ray absorptiometry (DXA) to diagnose osteoporosis. The three item criteria have not been evaluated in male patients with RA or in the entire female RA population. OBJECTIVES: (1) To test the proposed criteria in a cohort of men and women thought to be representative of the entire underlying RA population. (2) To develop clinical decision rules, which could be applied to all patients with RA irrespective of corticosteroid use. METHODS: Clinical and demographic data were collected from a total of 287 representative patients with RA (235 (82%) women, 52 (18%) men, age range 25.3-73.1 years) from the Oslo RA register (completeness 85%). Bone mineral density (BMD) was measured in spine L2-4 (anterior-posterior view) and femoral neck by DXA. The criteria were applied and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: Mean age (SD) for the women and men with RA was 56.8 (11.0) years and 61.5 (10.2) years; disease duration was 15.5 (9.5) years and 14.7 (8.6) years. Of the women 163 (69%) were postmenopausal. One hundred and seventeen (50%) women and 28 (54%) men fulfilled the three item criteria. For the diagnosis of osteoporosis (T score <or=-2.5) using the original three item criteria sensitivity in women and men was 74% and 67%, specificity 57% and 50%, PPV 32% and 29% and NPV 89% and 83%, and including weight and ever use of corticosteroids in a five item criteria sensitivity increased to 82% and 83%, specificity decreased to 45% and 45%, PPV was 29% and 31%, and NPV was 90% and 90% respectively. CONCLUSION: The novel five item criteria (age, weight, inflammation, immobility, and ever use of corticosteroids) are a more accurate tool to identify patients with RA and osteoporosis than the original three item criteria (age, inflammation, and immobility). The clinical decision rules have an acceptable sensitivity and provide a practical tool for the doctor to identify patients with RA who should have a DXA measurement performed.

Haugeberg G, Ørstavik RE, Uhlig T, Falch JA, Halse JI, Kvien TK. · Diakonhjemmet Hospital, Oslo, Norway. · Arthritis Rheum. · Pubmed #12124854 links to  free full text

Abstract: OBJECTIVE: To evaluate the extent of and risk factors for bone loss in a population-based cohort of patients with rheumatoid arthritis (RA) receiving conventional health care. METHODS: In a longitudinal study, clinical data were collected and bone mineral density (BMD) measurements were performed at baseline and after 2 years. Dual-energy x-ray absorptiometry was used for hip and spine BMD measurements. At baseline, patients received advice about lifestyle adjustments and calcium and vitamin D supplementation; during the followup period they were treated with antirheumatic and bone-sparing drugs, according to clinical judgment. RESULTS: After a mean +/- SD of 2.2 +/- 0.2 years, 366 (298 women, 68 men) of the 488 patients who were examined at baseline were reexamined. At that time, 47.9% were current users of corticosteroids and 37.0% were using antiresorptive drugs (hormone replacement therapy, bisphosphonates, or calcitonin). The mean BMD reduction was -0.64% in the femoral neck, -0.77% in the total hip, and -0.29% in the spine at L2-4. BMD was increased at all measurement sites in current users of antiresorptive drugs (0.16-1.64%) but was decreased in patients using calcium and vitamin D alone (-1.99% to -1.39%) and in patients not using any osteoporosis treatment (-1.20% to -0.43%). Current use of corticosteroids was independently associated with increased risk for BMD loss in the total hip (odds ratio [OR] 2.63, 95% confidence interval [95% CI] 1.38-5.00) and spine at L2-4 (OR 2.70, 95% CI 1.30-5.63), whereas current use of antiresorptive drugs was associated with decreased risk for bone loss in the total hip (OR 0.43, 95% CI 0.20-0.89). CONCLUSION: Results of this population-based, 2-year followup study indicate that adequate management of patients with RA, addressing both the rheumatic disease and osteoporosis, protects against bone loss.