Objective To study the association between metacarpal bone mineral density (BMD) loss and progressive hand osteoarthritis (OA) over 2 years. Methods Using the Kellgren-Lawrence (KL) grading scale... Show moreObjective To study the association between metacarpal bone mineral density (BMD) loss and progressive hand osteoarthritis (OA) over 2 years. Methods Using the Kellgren-Lawrence (KL) grading scale and the Osteoarthritis Research Society International Atlas, standardised hand radiographs of 181 patients with primary OA at multiple sites (mean age 60 years, 80% women, mean body mass index 27 kg/m(2)) were assessed for hand OA at baseline (KL >= 2 in two or more hand joints) and progressive hand OA over 2 years (>= 1 point increase in total osteophyte and joint space narrowing score in patients with hand OA at baseline). Changes in BMD were measured over 2 years in metacarpals 2-4 by digital x-ray radiogrammetry. Accelerated BMD loss was defined as loss of >3 mg/cm(2)/year. Logistic regression analyses were performed to assess the associations between BMD loss and progressive hand OA. Results The baseline prevalence of hand OA was 68% and, after 2 years, 32% of these patients had progressive hand OA. Accelerated BMD loss was present in 79% of the patients with progressive hand OA compared with 60% and 57% of the patients with non-progressive hand OA and no hand OA, respectively. BMD loss was independently associated with progressive hand OA compared with non-progressive hand OA with a RR (95% CI) of 2.1 (1.1 to 4.3). Conclusion Accelerated metacarpal BMD loss is associated with progressive hand OA over a period of 2 years; knowledge of common mechanisms may lead to development of therapeutic interventions for hand OA. Show less
Guler-Yuksel, M.; Bijsterbosch, J.; Allaart, C.F.; Meulenbelt, I.; Kroon, H.M.; Watt, I.; ... ; Kloppenburg, M. 2011
OBJECTIVE To study the association between metacarpal bone mineral density (BMD) loss and progressive hand osteoarthritis (OA) over 2 years. METHODS Using the Kellgren-Lawrence (KL) grading scale... Show moreOBJECTIVE To study the association between metacarpal bone mineral density (BMD) loss and progressive hand osteoarthritis (OA) over 2 years. METHODS Using the Kellgren-Lawrence (KL) grading scale and the Osteoarthritis Research Society International Atlas, standardised hand radiographs of 181 patients with primary OA at multiple sites (mean age 60 years, 80% women, mean body mass index 27 kg/m(2)) were assessed for hand OA at baseline (KL ≥ 2 in two or more hand joints) and progressive hand OA over 2 years (≥ 1 point increase in total osteophyte and joint space narrowing score in patients with hand OA at baseline). Changes in BMD were measured over 2 years in metacarpals 2-4 by digital x-ray radiogrammetry. Accelerated BMD loss was defined as loss of >3 mg/cm(2)/year. Logistic regression analyses were performed to assess the associations between BMD loss and progressive hand OA. RESULTS The baseline prevalence of hand OA was 68% and, after 2 years, 32% of these patients had progressive hand OA. Accelerated BMD loss was present in 79% of the patients with progressive hand OA compared with 60% and 57% of the patients with non-progressive hand OA and no hand OA, respectively. BMD loss was independently associated with progressive hand OA compared with non-progressive hand OA with a RR (95% CI) of 2.1 (1.1 to 4.3). CONCLUSION Accelerated metacarpal BMD loss is associated with progressive hand OA over a period of 2 years; knowledge of common mechanisms may lead to development of therapeutic interventions for hand OA. Show less
Objective To compare the reliability, sensitivity to change and feasibility of three radiographic scoring methods for hand osteoarthritis (OA). Methods Baseline, 2-year and 6-year hand radiographs... Show moreObjective To compare the reliability, sensitivity to change and feasibility of three radiographic scoring methods for hand osteoarthritis (OA). Methods Baseline, 2-year and 6-year hand radiographs of 90 patients with hand OA were read in triplicate in chronological order by three readers from different European centres using the OARSI atlas (OARSI), Kellgren-Lawrence grading scale (KL) and Verbruggen-Veys anatomical phase score (VV). Reliability was determined using intraclass correlation coefficients and smallest detectable change (SDC). Sensitivity to change was assessed by the proportion of progression above the SDC. Feasibility was reflected by the mean performance time. Results Intra-and inter-reader reliability was similar across methods. Inter-reader SDCs (% maximum score) for KL, OARSI and VV were 2.9 (3.2), 4.1 (2.9) and 2.7 (1.8) over 2 years and 3.8 (4.1), 4.6 (3.3) and 4.0 (2.5) over 6 years, respectively. KL detected a slightly higher proportion of progression. There were differences between readers, despite methods to enhance consistency. The mean performance time (SD, minutes) for KL, OARSI and VV was 4.3 (2.5), 9.3 (6.0) and 2.8 (1.5), respectively. Conclusion Methods had comparable reliability and sensitivity to change. Global methods were fastest to perform. For multicentre trials use of a central reading centre and multiple readers may minimise inter-reader variation. Show less
Objectives To develop evidence-based recommendations for management of calcium pyrophosphate deposition (CPPD). Methods A multidisciplinary guideline development group of 15 experts, representing... Show moreObjectives To develop evidence-based recommendations for management of calcium pyrophosphate deposition (CPPD). Methods A multidisciplinary guideline development group of 15 experts, representing 10 European countries, generated key propositions for management of CPPD using a Delphi consensus approach. For each recommendation research evidence was searched systematically. Whenever possible, the effect size and number needed to treat for efficacy and RR or OR for side effects were calculated for individual treatment modalities. Strength of recommendation was assessed by the European League Against Rheumatism visual analogue scale. Results Nine key recommendations were generated, including topics for general management, treatment of acute attacks, prophylaxis against recurrent acute attacks and management of chronic symptoms. It was recommended that optimal treatment requires both non-pharmacological and pharmacological treatments. For acute CPP crystal arthritis, cool packs, temporary rest and joint aspiration combined with steroid injection are often sufficient. For prophylaxis or chronic inflammatory arthritis with CPPD, oral non-steroidal anti-inflammatory drugs with gastroprotective treatment and/or low-dose colchicine 0.5-1.0 mg daily may be used. Other recommendations included parenteral or oral corticosteroid for acute CPP arthritis in those unresponsive or unsuited to other measures, and low-dose corticosteroid, methotrexate or hydroxychloroquine for chronic inflammatory arthritis with CPPD. Asymptomatic CPPD requires no treatment. Strength of recommendations varies from 79% to 95%. Conclusion Nine key recommendations for management of CPP crystal associated arthritis were developed using both research evidence and expert consensus. Strength of recommendations was provided to assist the application of these recommendations. Show less
OBJECTIVE In order to gain insight in the pathogenesis of erosive hand osteoarthritis (OA), the evolution of erosions in hand OA and risk factors involved were investigated. METHODS The 6-year... Show moreOBJECTIVE In order to gain insight in the pathogenesis of erosive hand osteoarthritis (OA), the evolution of erosions in hand OA and risk factors involved were investigated. METHODS The 6-year evolution in radiographic Verbruggen-Veys anatomical phase was assessed in interphalangeal joints of 236 patients with hand OA (mean age 59 years, 83% women) from the GARP (for 'Genetics ARthrosis and Progression') sibling pair study. Erosive evolution comprised phase transitions from non-erosive to erosive phases and from active erosions to remodelling. Clustering of erosive evolution within patients was assessed using the χ² test. Familial aggregation was evaluated in sibling pairs by estimating ORs for siblings and probands sharing erosive evolution. Local baseline determinants and the effect of high sensitivity C reactive protein were assessed using generalised estimating equations. RESULTS Erosive evolution took place in 181 of 4120 interphalangeal joints at risk (4.4%), corresponding to 60 patients (25.4% of study sample). Erosive evolution was found more often in multiple interphalangeal joints in one patient than would be expected by chance (χ² 373.0, p < 0.001). The adjusted OR (95% CI) for a sibling having erosive evolution if the proband had erosive evolution was 4.7 (1.4 to 15.8). Systemic inflammation was not associated with erosive activity. Independent local determinants were joint space narrowing (OR (95% CI) 8.9 (4.8 to 16.4)) and self-reported pain (OR (95%CI) 2.3 (1.1 to 4.7)). CONCLUSIONS rosive evolution was clustered within patients and families. Local factors were also involved in the evolution. This increase in insight in the pathogenesis of erosive hand OA will contribute to the development of new treatments. Show less
Objective In order to gain insight in the pathogenesis of erosive hand osteoarthritis (OA), the evolution of erosions in hand OA and risk factors involved were investigated. Methods The 6-year... Show moreObjective In order to gain insight in the pathogenesis of erosive hand osteoarthritis (OA), the evolution of erosions in hand OA and risk factors involved were investigated. Methods The 6-year evolution in radiographic Verbruggen-Veys anatomical phase was assessed in interphalangeal joints of 236 patients with hand OA (mean age 59 years, 83% women) from the GARP (for 'Genetics ARthrosis and Progression') sibling pair study. Erosive evolution comprised phase transitions from non-erosive to erosive phases and from active erosions to remodelling. Clustering of erosive evolution within patients was assessed using the chi(2) test. Familial aggregation was evaluated in sibling pairs by estimating ORs for siblings and probands sharing erosive evolution. Local baseline determinants and the effect of high sensitivity C reactive protein were assessed using generalised estimating equations. Results Erosive evolution took place in 181 of 4120 interphalangeal joints at risk (4.4%), corresponding to 60 patients (25.4% of study sample). Erosive evolution was found more often in multiple interphalangeal joints in one patient than would be expected by chance (chi(2) 373.0, p < 0.001). The adjusted OR (95% CI) for a sibling having erosive evolution if the proband had erosive evolution was 4.7 (1.4 to 15.8). Systemic inflammation was not associated with erosive activity. Independent local determinants were joint space narrowing (OR (95% CI) 8.9 (4.8 to 16.4)) and self-reported pain (OR (95% CI) 2.3 (1.1 to 4.7)). Conclusions Erosive evolution was clustered within patients and families. Local factors were also involved in the evolution. This increase in insight in the pathogenesis of erosive hand OA will contribute to the development of new treatments. Show less
Huetink, K.; ' t Klooster, R. van; Kaptein, B.L.; Watt, I.; Kloppenburg, M.; Nelissen, R.G.H.H.; ... ; Stoel, B.C. 2011
OBJECTIVE: To validate a newly developed quantification method that automatically detects and quantifies the joint space width (JSW) in hand radiographs. Repeatability, accuracy and sensitivity to... Show moreOBJECTIVE: To validate a newly developed quantification method that automatically detects and quantifies the joint space width (JSW) in hand radiographs. Repeatability, accuracy and sensitivity to changes in JSW were determined. The influence of joint location and joint shape on the measurements was tested. METHODS: A mechanical micrometer set-up was developed to define and adjust the true JSW in an acrylic phantom joint and in human cadaver-derived phalangeal joints. Radiographic measurements of the JSW were compared to the true JSW. Repeatability, systematic error (accuracy) and sensitivity (defined as the smallest detectable difference (SDD)) were determined. The influence of joint position on the JSW measurement was assessed by varying the location of the acrylic phantom on the X-ray detector with respect to the X-ray beam and the influence of joint shape was determined by using morphologically different human cadaver joints. RESULTS: The mean systematic error was 0.052 mm in the phantom joint and 0.210 mm in the cadaver experiment. In the phantom experiments, the repeatability was high (SDD = 0.028 mm), but differed slightly between joint locations (p = 0.046), and a change in JSW of 0.037 mm could be detected. Dependent of the joint shape in the cadaver hand, a change in JSW between 0.018 and 0.047 mm could be detected. CONCLUSIONS: The automatic quantification method is sensitive to small changes in JSW. Considering the published data of JSW decline in the normal and osteoarthritic population, the first signs of OA progression with this method can be detected within 1 or 2 years. Show less
Objective To investigate the long-term clinical and radiographic disease course of hand osteoarthritis (OA) and determinants of outcome. Methods Clinical and radiographic measures were obtained at... Show moreObjective To investigate the long-term clinical and radiographic disease course of hand osteoarthritis (OA) and determinants of outcome. Methods Clinical and radiographic measures were obtained at baseline and after 6 years in 289 patients with hand OA (mean age 59.5 years, 83.0% women). Clinical outcomes were self-reported pain and functional limitations assessed with the Australian/Canadian Osteoarthritis Hand Index (AUSCAN). Poor clinical outcome was defined as a follow-up score not fulfilling the Patient Acceptable Symptom State. Radiographic outcome was assessed by osteophytes and joint space narrowing (JSN) on standardised hand radiographs using the Osteoarthritis Research Society International (OARSI) atlas. Radiographic progression was defined as a change in osteophytes or JSN, above the smallest detectable change. Change in outcome measures was calculated and baseline determinants for poor clinical outcome and radiographic progression were assessed using logistic regression analysis. Results Clinical change showed great variation, with half of the population reporting deterioration. Poor outcome in pain was related to high levels of functional limitations and a high number of painful joints at baseline. Poor outcome on functional limitations was related to high baseline pain levels. Radiographic progression was present in 52.5% of patients and associated with high baseline levels of pain, nodes, osteophytes and the presence of erosive OA and nodal OA. Clinical change and radiographic progression were not related. Conclusions This study gives insight in the clinical and radiographic course of hand OA as well as determinants of outcome. These findings enable better patient information on prognosis. The relationship between clinical and radiographic outcome needs further investigation. Show less
OBJECTIVE To systematically evaluate the association between MRI findings (cartilage defects, bone marrow lesions (BML), osteophytes, meniscal lesion, effusion/synovitis, ligamentous abnormalities,... Show moreOBJECTIVE To systematically evaluate the association between MRI findings (cartilage defects, bone marrow lesions (BML), osteophytes, meniscal lesion, effusion/synovitis, ligamentous abnormalities, subchondral cysts and bone attrition) and pain in patients with knee osteoarthritis (OA) in order to establish the relevance of such findings when assessing an individual patient. METHODS The Medline, Web of Science, Embase and Cumulative Index to Nursing & Allied Health Literature (CINAHL) databases up to March 2010 were searched without language restriction to find publications with data on the association between MRI findings of knee OA (exposure of interest) and knee pain (outcome). The quality of included papers was scored using a predefined criteria set. The levels of evidence were determined qualitatively using best evidence synthesis (based on guidelines on systematic review from the Cochrane Collaboration Back Review Group). Five levels of evidence were used: strong, moderate, limited, conflicting and no evidence. RESULTS A total of 22 papers were included; 5 had longitudinal and 17 cross-sectional data. In all, 13 reported a single MRI finding and 9 multiple MRI findings. Moderate levels of evidence were found for BML and effusion/synovitis. The OR for BML ranged from 2.0 (no CI was given) to 5.0 (2.4 to 10.5). The OR of having pain when effusion/synovitis was present ranged between 3.2 (1.04 to 5.3) and 10.0 (1.1 to 149). The level of evidences between other MRI findings and pain were limited or conflicting. CONCLUSIONS Knee pain in OA is associated with BML and effusion/synovitis suggesting that these features may indicate the origin of pain in knee OA. However, due to the moderate level of evidence these features need to be explored further. Show less
Objective To systematically evaluate the association between MRI findings (cartilage defects, bone marrow lesions (BML), osteophytes, meniscal lesion, effusion/synovitis, ligamentous abnormalities,... Show moreObjective To systematically evaluate the association between MRI findings (cartilage defects, bone marrow lesions (BML), osteophytes, meniscal lesion, effusion/synovitis, ligamentous abnormalities, subchondral cysts and bone attrition) and pain in patients with knee osteoarthritis (OA) in order to establish the relevance of such findings when assessing an individual patient. Methods The Medline, Web of Science, Embase and Cumulative Index to Nursing & Allied Health Literature (CINAHL) databases up to March 2010 were searched without language restriction to find publications with data on the association between MRI findings of knee OA (exposure of interest) and knee pain (outcome). The quality of included papers was scored using a predefined criteria set. The levels of evidence were determined qualitatively using best evidence synthesis (based on guidelines on systematic review from the Cochrane Collaboration Back Review Group). Five levels of evidence were used: strong, moderate, limited, conflicting and no evidence. Results A total of 22 papers were included; 5 had longitudinal and 17 cross-sectional data. In all, 13 reported a single MRI finding and 9 multiple MRI findings. Moderate levels of evidence were found for BML and effusion/synovitis. The OR for BML ranged from 2.0 (no CI was given) to 5.0 (2.4 to 10.5). The OR of having pain when effusion/synovitis was present ranged between 3.2 (1.04 to 5.3) and 10.0 (1.1 to 149). The level of evidences between other MRI findings and pain were limited or conflicting. Conclusions Knee pain in OA is associated with BML and effusion/synovitis suggesting that these features may indicate the origin of pain in knee OA. However, due to the moderate level of evidence these features need to be explored further. Show less
Objective To describe the clinical burden of erosive osteoarthritis (EOA) of the hand in terms of pain, functioning and health-related quality of life (HRQL) and its relationship to nodal... Show moreObjective To describe the clinical burden of erosive osteoarthritis (EOA) of the hand in terms of pain, functioning and health-related quality of life (HRQL) and its relationship to nodal osteoarthritis (OA). Methods Patients with EOA (n=42) and non-EOA (n=194) of the hand were compared. Pain was assessed with the Australian/Canadian Osteoarthritis Hand Index (AUSCAN), the Michigan Hand Outcome Questionnaire (MHQ) and pain intensity upon pressure. Functioning was evaluated with AUSCAN, MHQ, grip strength, pinch grip and hand mobility tests. HRQL was measured with the Short Form-36. Patient satisfaction with hand function and aesthetics were also evaluated. The presence of nodal OA as well as its extent (reflected by the number of nodes) was assessed. Mean differences between patient groups were estimated with linear mixed models. To determine whether differences were independent of the nodal character of the disease, adjustments were made for the number of nodes. Results Patients with EOA experienced more pain, more functional limitation, less satisfaction with hand function and aesthetics and worse hand mobility than patients with non-EOA. HRQL was similar for the two groups. Patients with EOA had more nodes. A higher number of nodes was associated with worse outcome. After correction for the number of nodes, only hand mobility and patient satisfaction remained different between the groups. Conclusion Patients with EOA have a higher clinical burden than those with non-erosive disease. This higher burden is only partly attributed to the erosive disease itself, but mainly to the nodal character of the disease. Show less
Guler-Yuksel, M.; Allaart, C.F.; Watt, I.; Goekoop-Ruiterman, Y.P.M.; Vries-Bouwstra, J.K. de; Schaardenburg, D. van; ... ; Kloppenburg, M. 2010
OBJECTIVES To investigate the association between systemic and local inflammation and incident and progressive radiographic secondary osteoarthritis (OA) in interphalangeal joints (IPJs) over 3... Show moreOBJECTIVES To investigate the association between systemic and local inflammation and incident and progressive radiographic secondary osteoarthritis (OA) in interphalangeal joints (IPJs) over 3 years in rheumatoid arthritis (RA) patients and the effect of tumor necrosis factor alpha (TNF-α) inhibitor infliximab on secondary OA in IPJs. METHODS In the present observational longitudinal study baseline and 3-year hand X-rays of 416 recent-onset RA patients were scored for osteophytes and erosions in IPJs, blinded for time, using Osteoarthritis Research Society International atlas and Sharp-van der Heijde score. The associations between inflammatory factors and incident and progressive secondary OA in distal IPJs (DIPJs) and proximal IPJs (PIPJs) and the effect of infliximab compared to disease-modifying anti-rheumatic drug treatment on secondary OA were analyzed by multivariable regression and generalised estimating equations analyses. RESULTS Sixty-seven percent of the patients were female with, at baseline, a mean age of 54 years and OA present in DIPJs and PIPJs in 37% and 13%. Three years later, new secondary OA in DIPJs and PIPJs was seen in 11% and 10%, and progressive secondary OA in 36% and 35%. High erythrocyte sedimentation rate over 3 years and progressive erosive damage were risk factors for incident secondary OA in DIPJs, but not in PIPJs. At joint level, progression of erosions was associated with both incident and progressive secondary OA, only in DIPJs. Infliximab treatment was associated with lower incident secondary OA in PIPJs [relative risk 0.5 (95% confidence interval 0.2, 1.0)], independent of decrease in inflammation. CONCLUSION Incident and progressive secondary OA in DIPJs over 3 years was associated with high inflammatory activity in RA. Infliximab treatment reduced incident secondary OA in PIPJs independent of decrease in inflammation, suggesting that anti-TNF-α therapy might be effective against secondary hand OA via other pathways than suppression of inflammation. Further studies in populations of primary hand OA are necessary to determine the role of anti-TNF-α in treatment of primary hand OA. Show less
Guler-Yuksel, M.; Allaart, C.F.; Watt, I.; Goekoop-Ruiterman, Y.P.M.; Vries-Bouwstra, J.K. de; Schaardenburg, D. van; ... ; Kloppenburg, M. 2010
Objectives: To investigate the association between systemic and local inflammation and incident and progressive radiographic secondary osteoarthritis (OA) in interphalangeal joints (IPJs) over 3... Show moreObjectives: To investigate the association between systemic and local inflammation and incident and progressive radiographic secondary osteoarthritis (OA) in interphalangeal joints (IPJs) over 3 years in rheumatoid arthritis (RA) patients and the effect of tumor necrosis factor alpha (TNF-alpha) inhibitor infliximab on secondary OA in IPJs. Methods: In the present observational longitudinal study baseline and 3-year hand X-rays of 416 recent-onset RA patients were scored for osteophytes and erosions in IPJs, blinded for time, using Osteoarthritis Research Society International atlas and Sharp-van der Heijde score. The associations between inflammatory factors and incident and progressive secondary OA in distal IPJs (DIPJs) and proximal IPJs (PIPJs) and the effect of infliximab compared to disease-modifying anti-rheumatic drug treatment on secondary OA were analyzed by multivariable regression and generalised estimating equations analyses. Results: Sixty-seven percent of the patients were female with, at baseline, a mean age of 54 years and OA present in DIPJs and PIPJs in 37% and 13%. Three years later, new secondary OA in DIPJs and PIPJs was seen in 11% and 10%, and progressive secondary OA in 36% and 35%. High erythrocyte sedimentation rate over 3 years and progressive erosive damage were risk factors for incident secondary OA in DIPJs, but not in PIPJs. At joint level, progression of erosions was associated with both incident and progressive secondary OA, only in DIPJs. Infliximab treatment was associated with lower incident secondary OA in PIPJs [relative risk 0.5 (95% confidence interval 0.2, 1.0)], independent of decrease in inflammation. Conclusion: Incident and progressive secondary OA in DIPJs over 3 years was associated with high inflammatory activity in RA. Infliximab treatment reduced incident secondary OA in PIPJs independent of decrease in inflammation, suggesting that anti-TNF-alpha therapy might be effective against secondary hand OA via other pathways than suppression of inflammation. Further studies in populations of primary hand OA are necessary to determine the role of anti-TNF-alpha in treatment of primary hand OA. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. Show less
Purpose: To define localized development of knee osteoarthritis (OA) that arises from anterior cruciate ligament (ACL) and meniscal injuries identified at magnetic resonance (MR) imaging performed... Show morePurpose: To define localized development of knee osteoarthritis (OA) that arises from anterior cruciate ligament (ACL) and meniscal injuries identified at magnetic resonance (MR) imaging performed a decade ago and the subsequent management of those findings in patients with subacute knee symptoms. Materials and Methods: The present study was approved by local medical ethics review boards, and written informed consent was obtained. Three hundred twenty-six patients (mean age, 42 years; 108 female) from a previously reported series of 855 patients were followed up with regard to the effect of MR imaging-guided treatment for subacute knee problems. The mean follow-up period was 10 years. Initial findings and treatment were compared with the follow-up radiograph and 3.0-T MR image findings. Odds ratios (ORs), with corresponding 95% confidence intervals, were used to identify the effects between variables. Results: Patients with ACL ruptures had an increased risk of developing joint space narrowing (JSN), cartilaginous defects, osteophytes, bone marrow lesions, and subchondral cysts medially or laterally (OR, 2.4-9.8). Patients with medial meniscal tears had an increased risk of developing JSN, cartilaginous defects, osteophytes, and bone marrow lesions medially (OR, 2.0-15.3). Patients with lateral meniscal tears had an increased risk of developing JSN, cartilaginous defects, osteophytes, bone marrow lesions, and subchondral cysts laterally (OR, 2.1-10.5). Meniscectomy had no effect on the risk of developing OA. Conclusion: Localized knee OA developed from risk factors identified from the findings of MR imaging performed a decade ago in patients with subacute knee symptoms and did not depend on the surgical treatment of those findings. (C) RSNA, 2010 Show less
