Rheumatoid Arthritis: Haugeberg G

Haugeberg G, Emery P. · Department of Rheumatology, Sørlandet Hospital, Kristiansand, Norway. · Rheum Dis Clin North Am. · Pubmed #16287593 No free full text.

Abstract: New research has revealed common pathophysiologic and cellular mechanisms behind the development of osteoporosis and joint damage in rheumatoid arthritis (RA). Because osteoporosis is a direct consequence of the inflammatory disease process, bone mass measurements in principle could be an outcome marker of inflammation, of damage, and of response to therapeutic intervention. Several devices have been developed for quantitative bone mass assessment including dual energy x-ray absorptiometry (DXA), which is considered the reference standard. This article based on current data and understanding discusses the use of DXA as a diagnostic and assessment tool especially in early RA.

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, Andrup O, Lilleaas FG. · No affiliation provided · Tidsskr Nor Laegeforen. · Pubmed #10644226 No free full text.

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Vis M, Havaardsholm EA, Haugeberg G, Uhlig T, Voskuyl AE, van de Stadt RJ, Dijkmans BA, Woolf AD, Kvien TK, Lems WF. · Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands. · Ann Rheum Dis. · Pubmed #16606653 No free full text.

Abstract: OBJECTIVES: To examine whether treatment with anti-tumour necrosis factor (TNF) alpha prevents loss of bone mineral density (BMD) at the spine and hip (generalised) and in the hands (local) of patients with rheumatoid arthritis, and to study the changes in markers of bone metabolism, including receptor activator of the NFkappaB ligand (RANKL) and osteoprotegerin (OPG), during anti-TNF treatment. PATIENTS AND METHODS: 102 patients with active rheumatoid arthritis, who were treated with infliximab during 1 year, were included in this open cohort study. The BMD of the spine and hip (dual x ray absorptiometry) and hands dual x ray radiogrammetry was measured before the start of treatment and after 1 year. Changes in osteocalcin formation, beta-isomerised carboxy terminal telopeptide of type 1 collagen (beta-CTx, resorption), RANKL and OPG were determined at 0, 14, 30 and 46 weeks. RESULTS: The BMD of the spine and hip was unchanged during treatment with infliximab, whereas BMD of the hand decreased significantly by 0.8% (p<0.01). The BMD of the hip in patients with a good European League Against Rheumatism response showed a favourable change compared with patients not achieving such a response. Serum beta-CTx and RANKL were both considerably decreased compared with baseline at all time points. The decrease in beta-CTx was associated with the decrease in Disease Activity Score of 28 joints and C reactive protein during the 0-14 weeks interval. CONCLUSION: In patients with rheumatoid arthritis treated with infliximab, spine and hip bone loss is arrested, whereas metacarpal cortical hand bone loss is not stopped. The outcome of the study also supports a relationship between clinical response, in terms of reduced inflammatory activity, and changes in bone loss of the spine, hip and hands.

Haugeberg G, Strand A, Kvien TK, Kirwan JR. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Arch Intern Med. · Pubmed #15956010 links to  free full text

Abstract: BACKGROUND: Bone damage in rheumatoid arthritis presents as osteoporosis and joint erosions. Prednisolone has been shown to reduce the rate of hand joint destruction as seen on radiography but has not been shown to reduce the rate of hand bone loss. METHODS: In a double-blind study comparing oral prednisolone (7.5 mg/d for 2 years) with placebo, hand bone density assessed with digital x-ray radiogrammetry was examined in 95 patients with rheumatoid arthritis with disease duration of less than 2 years. RESULTS: The mean loss of hand bone density was less in prednisolone-treated patients compared with placebo-treated patients at the 1-year follow-up (-0.011 vs -0.022 g/cm(2)) (P = .005) and at the 2-year follow-up (-0.026 vs -0.039 g/cm(2)) (P = .03). The mean percentage group difference in loss of hand bone density was 2.8% (P = .004) at the 1-year follow-up and 3.5% (P = .01) at the 2-year follow-up. In the first year, C-reactive protein, a marker of inflammation, was strongly correlated with hand bone loss in placebo-treated patients but not in prednisolone-treated patients, suggesting that prednisolone breaks the link between bone loss and inflammation. CONCLUSIONS: To our knowledge, this is the first double-blind randomized study to show that disease-related loss of hand bone density in rheumatoid arthritis can be decelerated by prednisolone. This finding suggests that the deleterious effect of prednisolone on bone may be counteracted by its anti-inflammatory effect.

Pease CT, Haugeberg G, Montague B, Hensor EM, Bhakta BB, Thomson W, Ollier WE, Morgan AW. · Department of Rheumatology, Chapel Allerton Hospital, Chapeltown Road, Leeds LS74SA, UK. · Rheumatology (Oxford). · Pubmed #18980958 No free full text.

Abstract: 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.

Hoff M, Kvien TK, Kälvesten J, Elden A, Haugeberg G. · Department of Rheumatology, St Olav's Hospital, Trondheim, Norway. · Ann Rheum Dis. · Pubmed #18801760 links to  free full text

Abstract: 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.

Haugeberg G. · Division of Rheumatology at Norwegian University of Science and Technology, and Department of Rheumatology, Sørlandet Hospital, Norway. · Nat Clin Pract Rheumatol. · Pubmed #18594493 No free full text.

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Hoff M, Haugeberg G, Odegård S, Syversen S, Landewé R, van der Heijde D, Kvien TK. · Department of Rheumatology, St. Olav's Hospital, University Hospital in Trondheim, Trondheim, Norway. · Ann Rheum Dis. · Pubmed #18339664 No free full text.

Abstract: 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.

Sokka T, Haugeberg G, Pincus T. · Jyväskylä Central Hospital, Jyväskylä, Finland. · Clin Exp Rheumatol. · Pubmed #18021512 No free full text.

Abstract: Quality of care of many diseases, such as diabetes, hypertension, hyperlipidemia, and osteoporosis, can be assessed effectively from information in usual medical records concerning blood tests, blood pressure, bone density, etc. However, quality of care of rheumatoid arthritis (RA), as well as most rheumatic diseases, cannot be assessed from usual medical records. The primary basis for this problem involves limitations of laboratory tests and the absence of a single "gold standard" measure in RA Therefore, indices which include laboratory tests, joint counts, and patient questionnaires have been developed. These indices are collected in all RA clinical trials and other clinical research, but not in usual clinical care, a phenomenon which may limit severely possible assessment and improvement of quality and patient outcomes. Patient questionnaires and joint counts, rather than laboratory tests or radiographs in a medical record, are the best measures to assess and monitor RA patient status. Patient questionnaires are the most significant clinical prognostic markers for severe long-term RA outcomes, such as work disability, costs and premature mortality, and are more cost-effective and easily-collected than formal quantitative joint counts in busy clinical settings. The value of patient questionnaires and joint counts in RA is reviewed in three examples from the authors' research concerning premature mortality in RA, changes in patient clinical status between 1985 and 2000, and a QUEST-RA global perspective, to better evaluate the structure, processes, and outcomes of RA care.

Hoff M, Haugeberg G, Kvien TK. · Norwegian University of Science and Technology, MTFS, Department of Neuroscience, Division of Rheumatology, NO-7489 Trondheim, Norway. · Arthritis Res Ther. · Pubmed #17705865 links to  free full text

Abstract: The aim of this 2-year longitudinal observational study was to explore hand bone loss as a disease outcome measure in established rheumatoid arthritis (RA). A cohort of 215 patients with RA (170 women and 45 men, aged 20-70 years) were recruited from the Oslo RA registry and studied for changes in hand bone mass during a 2-year follow-up. Digital X-ray radiogrammetry (DXR) was used to measure cortical hand bone mineral density (BMD) and metacarpal cortical index, whereas dual-energy X-ray absorptiometry (DXA) was used to assess whole hand BMD, which measures total cortical and trabecular bone. DXA-BMD total hip and spine and informative data for disease and therapy were also collected. Hand bone loss could be revealed over a 2-year follow-up measured by DXR-BMD (-0.90%, P < 0.01), but not by DXA-BMD (0.00%, P = 0.87). DXA-BMD hand bone loss was only observed in patients with disease duration < or = 3 years and not in patients with longer disease duration (-0.96% versus 0.24%, P < 0.01), whereas loss of DXR-BMD was independent of disease duration. Disease activity (measured by the disease activity score including 28 joints) independently predicted loss of DXR-BMD but not changes in the DXA-BMD hand in the multivariate analysis. The change in DXR metacarpal cortical index was highly correlated to DXR-BMD (r = 0.94, P < 0.001).These data suggest that DXR-BMD may be a more appropriate technique to identify RA-related bone involvement in hands compared with DXA-BMD measurement, but further studies are needed to explore this hypothesis.

Haugeberg G, Green MJ, Conaghan PG, Quinn M, Wakefield R, Proudman SM, Stewart S, Hensor E, Emery P. · Department of Rheumatology Sørlandet Hospital, Kristiansand, Norway. · Ann Rheum Dis. · Pubmed #17491097 No free full text.

Abstract: OBJECTIVE: To examine the role of hand dual-energy x ray absorptiometry (DEXA) compared with radiography in the assessment of bone involvement in patients with early rheumatoid arthritis (RA) who have active disease. METHODS: The study population (n = 79) had RA of <12 months' duration and were selected for poor prognostic features. Clinical data and bone mineral density (BMD) data were collected at baseline, 24 and 48 weeks. Hand radiographs were performed at baseline and 48 weeks. Bone damage analyses were performed for the group and individuals using the smallest detectable change (SDC) method. RESULTS: At baseline, mean disease duration was 8.5 months, erythrocyte sedimentation rate was 34.3 mm/hour, C-reactive protein was 40.2 mg/l, Health Assessment Questionnaire score was 1.35 and 81% of patients were positive for rheumatoid factor. Mean (95% CI) hand BMD loss was 2.5% (-3.5 to -1.5) at 24 weeks and 2.6% (-3.8 to -1.5) at 48 weeks. Individual hand bone loss exceeding the SDC was seen in 46.8% at 24 weeks and in 58.2% at 48 weeks. In the subgroup of 58 patients who had undergone radiography, radiographic joint damage score evaluated by the Sharp-van der Heijde method increased from 4.8 to 10.6 (p = 0.001). Individual hand bone loss in this subgroup exceeding the SDC was seen in 50.0% at 24 weeks and in 56.9% at 48 weeks, whereas at 48 weeks only 22.4% had deteriorated in modified Sharp score. CONCLUSION: The study results indicate that hand DEXA is a more sensitive tool than radiology (radiographic joint-damage scores), for measuring disease-related bone damage in early RA.

Haugeberg G, Green MJ, Quinn MA, Marzo-Ortega H, Proudman S, Karim Z, Wakefield RJ, Conaghan PG, Stewart S, Emery P. · Academic Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, UK. · Ann Rheum Dis. · Pubmed #16284095 links to  free full text

Abstract: OBJECTIVES: (1) To examine the change in regional bone mineral density (BMD), including the hands, and assess its role as a predictor of outcome in patients presenting with an early undifferentiated inflammatory arthritis; (2) to examine for associations with the changes in hand BMD. METHODS: 74 patients with undifferentiated hand arthritis of less than 12 months' duration were examined at baseline and then at three, six, and 12 months follow up, including BMD measurement of the femoral neck, spine (L2-4), and the whole hands using dual energy absorptiometry (DXA). RESULTS: During the study, 13 patients were diagnosed as having rheumatoid arthritis, 19 as having inflammatory non-rheumatoid joint disorders, and 42 as having non-inflammatory joint disorders. At the femoral neck and lumbar spine no significant bone loss was seen in any of the three subgroups. At the 12 months follow up the mean (95% confidence interval) hand BMD loss in the patients with rheumatoid arthritis was -4.27% (-1.41 to -7.13); in the inflammatory non-rheumatoid group, -0.49% (-1.33 to +0.35); and in the non-inflammatory joint disorder group, -0.87% (-1.51 to -0.23). In a multivariate linear regression model (including age, rheumatoid factor, mean C reactive protein, mean HAQ score, and cumulative glucocorticoid dose), only mean C reactive protein (p<0.001) and rheumatoid factor (p = 0.04) were independently associated with change in hand BMD during follow up. CONCLUSIONS: Hand DXA provides a very sensitive tool for measuring bone loss in early rheumatoid arthritis and may be useful in identifying patients at high risk of developing progressive disease. Further studies are needed to evaluate the role of hand bone loss as a prognostic factor and outcome measure in rheumatoid arthritis.

Pease CT, Haugeberg G, Morgan AW, Montague B, Hensor EM, Bhakta BB. · Academic Unit of Musculoskeletal and Rehabilitation Medicine, University of Leeds, Leeds, UK. · J Rheumatol. · Pubmed #15940765 No free full text.

Abstract: OBJECTIVE:. To examine for demographic and clinical differences between late onset rheumatoid arthritis (LORA), polymyalgia rheumatica (PMR), and temporal arteritis (TA) patients presenting with polymyalgic symptoms (PMS) and to identify baseline clinical and laboratory features that would lead to a more accurate final diagnosis. METHODS: Three hundred forty-nine consecutive patients with new onset of symptoms suggestive of LORA, PMR, or TA presenting at or above age 60 years were enrolled in a prospective study. RESULTS: During followup, 9 patients diagnosed initially as PMR developed LORA (giving a final total of 145), 5 patients initially diagnosed as LORA changed diagnosis to PMR (final total 147), and 29 patients had PMS that predated TA symptoms (final total 57). The delay in diagnosis ranged from 1 to 30 months. DRB1*04 was associated with development of both LORA and TA. CONCLUSION: In about 10% of patients the correct diagnosis of LORA, PMR, and TA in those presenting with PMS may be delayed due to similarities in initial clinical presentation. Longterm followup is essential to establish correct diagnosis. Laboratory tests tend to be unhelpful, although a positive rheumatoid factor or persistently raised plasma viscosity despite steroids might indicate RA, and the presence of HLA-DRB1*04 may indicate underlying RA or TA.

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.

Orstavik RE, Haugeberg G, Uhlig T, Mowinckel P, Falch JA, Halse JI, Kvien TK. · Department of Rheumatology, Diakonhjemmet Hospital, Box 23, Vinderen, 0319, Oslo, Norway. · Osteoporos Int. · Pubmed #15197538 No free full text.

Abstract: To date, no studies have been published on incident deformities in patients with rheumatoid arthritis (RA). Morphometric X-ray absorptiometry (MXA) is an alternative to conventional X-rays for identifying vertebral deformities. The aim of the present study was to describe the incidence of vertebral deformities in 255 female RA patients measured by MXA, and the relationship between incident deformities and clinical and demographic variables. MXA is still under evaluation for its ability to identify deformities, so we explored four different cut-off thresholds including fixed percentage reduction and the principle of least significant change (LSC). MXA (T4-L4) and BMD (L2-L4 and total hip; Lunar Expert) were performed on 255 patients (mean age 54.3, range 29.2-70.8 years) at baseline and after a mean period of 2.3 years. MXA scans were analyzed pairwise by the same trained technician, and incident deformities calculated applying LSC with a 99.9% and 99.99% confidence limit, and a fixed reduction of 20% and 25% for anterior, middle or posterior heights. Long term precision (%CV) of height measurements for all vertebrae combined (T4-L4) were 4.8, 4.8 and 4.4, respectively. Frequency and distribution of incident deformities varied from 39 deformities in 33 patients (fixed 20% reduction) to 17 deformities in 15 patients (fixed 25% reduction), and quality control analyses revealed a high number of presumed false deformities. Incidence per 100 patient years varied from 2.9 to 6.7 deformities according to method, and was comparable to those obtained from intervention studies in corticosteroid-induced osteoporosis. Patients with incident deformities were significantly older, had lower BMD, higher disability and more often a previous non-vertebral fractures than those without incident deformities Incident deformities by MXA need further evaluation in secondary osteoporosis. It seems, however, that older patients with previous limb fractures and low BMD are especially prone to this complication.

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.

Lodder MC, Haugeberg G, Lems WF, Uhlig T, Orstavik RE, Kostense PJ, Dijkmans BA, Kvien TK, Woolf AD, Anonymous00341. · Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands. · Arthritis Rheum. · Pubmed #12687512 links to  free full text

Abstract: OBJECTIVE: To examine variables associated with bone mineral density (BMD) and vertebral deformities in women with rheumatoid arthritis (RA) from 3 northwest European countries. METHODS: Female patients were recruited from rheumatology clinics in Oslo, Norway; Truro, UK; and Amsterdam, The Netherlands (150 total, 50 per center, age 50-70 years, disease duration > or = 5 years). Demographic and clinical data were collected and BMD was measured by means of dual energy x-ray absorptiometry. Associations between demographic and clinical measures on the one hand and BMD and vertebral deformities on the other were investigated by single and multiple regression analyses. RESULTS: Body mass index (BMI), medication use, RA damage measures, and BMD differed significantly between the 3 centers. Overall, Norwegian patients had the lowest BMI, used more corticosteroids and anti-osteoporotic drugs, had lower joint damage measured by Larsen score, and lower BMD at both spine and hip. High age, low BMI, and high cumulative dose of corticosteroids (last 2 years) are related to low BMD. A high Larsen score was associated with low BMD at the hip. Larsen score was the independent determinant of vertebral deformities after correction for center, age, BMI, and BMD. CONCLUSION: Data from 3 countries on BMD and vertebral deformities in female patients aged 50-70 years with longstanding RA are presented, demonstrating an association between radiographic RA damage and low BMD and between radiographic RA damage and vertebral deformities.

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.

Haugeberg G, Uhlig T, Falch JA, Halse JI, Kvien TK. · Diakonhjemmet Hospital, Oslo, Norway. · Arthritis Rheum. · Pubmed #11145036 links to  free full text

Abstract: 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.