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1. Statistical shape modeling of the hip and the association with hip osteoarthritis: a systematic review

Author

van Buuren, M.M.A. (M. M.A.), Arden, N.K. (Nigel), Bierma-Zeinstra, S.M. (Sita), Bramer, W.M. (Wichor), Casartelli, N.C. (N. C.), Felson, D., Jones, G. (G.), Lane, N.E., Lindner, C. (C.), Maffiuletti, N.A. (N. A.), van Meurs, J.B.J. (J. B.J.), Nelson, A.E. (A. E.), Nevitt, M.C. (Michael), Valenzuela, P.L. (P. L.), Verhaar, J.A.N. (J. A.N.), Weinans, H.H. (Harrie), Agricola, R. (Rintje), van Buuren, M.M.A. (M. M.A.), Arden, N.K. (Nigel), Bierma-Zeinstra, S.M. (Sita), Bramer, W.M. (Wichor), Casartelli, N.C. (N. C.), Felson, D., Jones, G. (G.), Lane, N.E., Lindner, C. (C.), Maffiuletti, N.A. (N. A.), van Meurs, J.B.J. (J. B.J.), Nelson, A.E. (A. E.), Nevitt, M.C. (Michael), Valenzuela, P.L. (P. L.), Verhaar, J.A.N. (J. A.N.), Weinans, H.H. (Harrie), and Agricola, R. (Rintje)

Abstract

Objective: To summarize available evidence on the association between hip shape as quantified by statistical shape modeling (SSM) and the incidence or progression of hip osteoarthritis. Design: We conducted a systematic search of five electronic databases, based on a registered protocol (available: PROSPERO CRD42020145411). Articles presenting original data on the longitudinal relationship between radiographic hip shape (quantified by SSM) and hip OA were eligible. Quantitative meta-analysis was precluded because of the use of different SSM models across studies. We used the Newcastle–Ottawa Scale (NOS) for risk of bias assessment. Results: Nine studies (6,483 hips analyzed with SSM) were included in this review. The SSM models used to describe hip shape ranged from 16 points on the femoral head to 85 points on the proximal femur and hemipelvis. Multiple hip shape features and combinations thereof were associated with incident or progressive hip OA. Shape variants that seemed to be consistently associated with hip OA across studies were acetabular dysplasia, cam morphology, and deviations in acetabular version (either excessive anteversion or retroversion). Conclusions: Various radiographic, SSM-defined hip shape features are associated with hip OA. Some hip shape features only seem to increase the risk for hip OA when combined together. The heterogeneity of the used SSM models across studies precludes the estimation of pooled effect sizes. Further studies using the same SSM model and definition of hip OA are needed to allow for the comparison of outcomes across studies, and to validate the found associations.

Published
2021
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2. A consensus-based framework for conducting and reporting osteoarthritis phenotype research

Author

Spil, W.E. (Willem) van, Bierma-Zeinstra, S.M. (Sita), Deveza, L.A. (L. A.), Arden, N.K. (Nigel), Bay-Jensen, A.C. (Anne), Kraus, V.B. (V. Byers), Carlesso, L. (L.), Christensen, R. (Robin), Esch, M. (Martin) van der, Kent, P. (P.), Knoop, J. (Jesper), Ladel, C. (C.), Little, C.B. (C. B.), Loeser, R.F. (R. F.), Losina, E. (E.), Mills, K. (K.), Mobasheri, A. (Ali), Nelson, A.E. (A. E.), Neogi, T. (T.), Peat, G., Rat, A.-C. (A. C.), Steultjens, M.P.M. (Martijn), Thomas, M.J. (M. J.), Valdes, A.M. (Ana Maria), Hunter, D.J. (D. J.), Spil, W.E. (Willem) van, Bierma-Zeinstra, S.M. (Sita), Deveza, L.A. (L. A.), Arden, N.K. (Nigel), Bay-Jensen, A.C. (Anne), Kraus, V.B. (V. Byers), Carlesso, L. (L.), Christensen, R. (Robin), Esch, M. (Martin) van der, Kent, P. (P.), Knoop, J. (Jesper), Ladel, C. (C.), Little, C.B. (C. B.), Loeser, R.F. (R. F.), Losina, E. (E.), Mills, K. (K.), Mobasheri, A. (Ali), Nelson, A.E. (A. E.), Neogi, T. (T.), Peat, G., Rat, A.-C. (A. C.), Steultjens, M.P.M. (Martijn), Thomas, M.J. (M. J.), Valdes, A.M. (Ana Maria), and Hunter, D.J. (D. J.)

Abstract

Background: The concept of osteoarthritis (OA) heterogeneity is evolving and gaining renewed interest. According to this concept, distinct subtypes of OA need to be defined that will likely require recognition in research design and different approaches to clinical management. Although seemingly plausible, a wide range of views exist on how best to operationalize this concept. The current project aimed to provide consensus-based definitions and recommendations that together create a framework for conducting and reporting OA phenotype research. Methods: A panel of 25 members with expertise in OA phenotype research was composed. First, panel members participated in an online Delphi exercise to provide a number of basic definitions and statements relating to OA phenotypes and OA phenotype research. Second, panel members provided input on a set of recommendations for reporting on OA phenotype studies. Results: Four Delphi rounds were required to achieve sufficient agreement on 11 definitions and statements. OA phenotypes were defined as subtypes of OA that share distinct underlying pathobiological and pain mechanisms and their structural and functional consequences. Reporting recommendations pertaining to the study characteristics, study population, data collection, statistical analysis, and appraisal of OA phenotype studies were provided. Conclusions: This study provides a number of consensus-based definitions and recommendations relating to OA phenotypes. The resulting framework is intended to facilitate research on OA phenotypes and increase combined efforts to develop effective OA phenotype classification. Success in this endeavor will hopefully translate into more effective, differentiated OA management that will benefit a multitude of OA patients.

Published
2020
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3. The OA Trial Bank: Meta-analysis of individual patient data from knee and hip osteoarthritis trials show that patients with severe pain exhibit greater benefit from intra-articular glucocorticoids

Author

Middelkoop, M. (Marienke) van, Arden, N.K. (Nigel), Atchia, I., Birrell, F. (Fraser), Chao, J., Rezende, M.U., Lambert, R.G.W., Ravaud, P. (Philippe), Bijlsma, J.W.J. (Hans), Doherty, M. (Michael), Dziedzic, K. (Krysia), Lohmander, L.S. (Stefan), McAlindon, T.E. (Timothy), Zhang, W. (Weiya), Bierma-Zeinstra, S.M. (Sita), Middelkoop, M. (Marienke) van, Arden, N.K. (Nigel), Atchia, I., Birrell, F. (Fraser), Chao, J., Rezende, M.U., Lambert, R.G.W., Ravaud, P. (Philippe), Bijlsma, J.W.J. (Hans), Doherty, M. (Michael), Dziedzic, K. (Krysia), Lohmander, L.S. (Stefan), McAlindon, T.E. (Timothy), Zhang, W. (Weiya), and Bierma-Zeinstra, S.M. (Sita)

Abstract

Objective: To evaluate the efficacy of intra-articular (IA) glucocorticoids for knee or hip osteoarthritis (OA) in specific subgroups of patients with severe pain and inflammatory signs using individual patient data (IPD) from existing trials. Design: Randomized trials evaluating one or more IA glucocorticoid preparation in patients with knee or hip OA, published from 1995 up to June 2012 were selected from the literature. IPD obtained from original trials included patient and disease characteristics and outcomes measured. The primary outcome was pain severity at short-term follow-up (up to 4 weeks). The subgroup factors assessed included severe pain (≥70 points, 0-100 scale) and signs of inflammation (dichotomized in present or not) at baseline. Multilevel regression analyses were applied to estimate the magnitude of the effects in the subgroups with the individuals nested within each study. Results: Seven out of 43 published randomized clinical trials (n = 620) were included. Patients with severe baseline pain had a significantly larger reduction in short-term pain, but not in mid- and long-term pain, compared to those with less severe pain at baseline (Mean Difference 13.91; 95% Confidence Interval 1.50-26.31) when receiving IA glucocorticoid injection compared to placebo. No statistical significant interaction effects were found between inflammatory signs and IA glucocorticoid injections compared to placebo and to tidal irrigation at all follow-up points. Conclusions: This IPD meta-analysis demonstrates that patients with severe knee pain at baseline derive more benefit from IA glucocorticoid injection at short-term follow-up than those with less severe pain at baseline.

Published
2016
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4. Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis

Author

Castaño Betancourt, M.C. (Martha), Evans, D.S. (Daniel), Ramos, Y.F.M. (Yolande), Boer, C.G. (Cindy G.), Metrustry, S. (Sarah), Liu, Y. (Youfang), Hollander, W. (Wouter) den, Rooij, J.G.J. (Jeroen) van, Kraus, V.B. (Virginia B.), Yau, M.S. (Michelle S.), Mitchell, B.D. (Braxton), Muir, K. (Kenneth), Hofman, A. (Albert), Doherty, M. (Michael), Doherty, S. (Sally), Zhang, W. (Weiya), Kraaij, R. (Robert), Rivadeneira Ramirez, F. (Fernando), Barrett-Connor, E. (Elizabeth), MacIewicz, R.A. (Rose), Arden, N.K. (Nigel), Nelissen, R.G.H.H. (Rob), Kloppenburg, M. (Margreet), Jordan, J.M. (Joanne M.), Nevitt, M.C. (Michael), Slagboom, P.E. (Eline), Hart, D. (Deborah), Lafeber, F.P.J.G. (Floris), Styrkarsdottir, U. (Unnur), Zeggini, E. (Eleftheria), Evangelou, E. (Evangelos), Spector, T.D. (Timothy), Uitterlinden, A.G. (André), Lane, N.E., Meulenbelt, I. (Ingrid), Valdes, A.M. (Ana Maria), Meurs, J.B.J. (Joyce) van, Castaño Betancourt, M.C. (Martha), Evans, D.S. (Daniel), Ramos, Y.F.M. (Yolande), Boer, C.G. (Cindy G.), Metrustry, S. (Sarah), Liu, Y. (Youfang), Hollander, W. (Wouter) den, Rooij, J.G.J. (Jeroen) van, Kraus, V.B. (Virginia B.), Yau, M.S. (Michelle S.), Mitchell, B.D. (Braxton), Muir, K. (Kenneth), Hofman, A. (Albert), Doherty, M. (Michael), Doherty, S. (Sally), Zhang, W. (Weiya), Kraaij, R. (Robert), Rivadeneira Ramirez, F. (Fernando), Barrett-Connor, E. (Elizabeth), MacIewicz, R.A. (Rose), Arden, N.K. (Nigel), Nelissen, R.G.H.H. (Rob), Kloppenburg, M. (Margreet), Jordan, J.M. (Joanne M.), Nevitt, M.C. (Michael), Slagboom, P.E. (Eline), Hart, D. (Deborah), Lafeber, F.P.J.G. (Floris), Styrkarsdottir, U. (Unnur), Zeggini, E. (Eleftheria), Evangelou, E. (Evangelos), Spector, T.D. (Timothy), Uitterlinden, A.G. (André), Lane, N.E., Meulenbelt, I. (Ingrid), Valdes, A.M. (Ana Maria), and Meurs, J.B.J. (Joyce) van

Abstract

Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10−8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs496547

Published
2016
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5. Assessment of osteoarthritis candidate genes in a meta-analysis of nine genome-wide association studies

Author

Rodriguez-Fontenla, C. (Cristina), Calaza, M. (Manuel), Evangelou, E. (Evangelos), Valdes, A.M. (Ana Maria), Arden, N.K. (Nigel), Blanco, F.J., Carr, A.J. (Andrew Jonathan), Chapman, K. (Kay), Deloukas, P. (Panagiotis), Doherty, M. (Michael), Esko, T. (Tõnu), Garcés Aletá, C.M. (Carlos), Gomez-Reino Carnota, J.J. (Juan), Helgadottir, H.T. (Hafdis), Hofman, A. (Albert), Jonsdottir, I. (Ingileif), Kerkhof, J.M. (Hanneke), Kloppenburg, M. (Margreet), McCaskie, A. (Andrew), Ntzani, E.E. (Evangelia), Ollier, W.E.R. (William), Oreiro, N. (Natividad), Panoutsopoulou, K. (Kalliope), Ralston, S.H. (Stuart), Ramos, Y.F.M. (Yolande), Riancho, J.A. (José), Rivadeneira Ramirez, F. (Fernando), Slagboom, P.E. (Eline), Styrkarsdottir, U. (Unnur), Thorsteinsdottir, U. (Unnur), Thorleifsson, G. (Gudmar), Tsezou, A. (Aspasia), Uitterlinden, A.G. (André), Wallis, G.A. (Gillian), Wilkinson, J.M. (Mark), Zhai, G. (Guangju), Zhu, Y. (Yanyan), Felson, D., Ioannidis, J.P.A. (John), Loughlin, J. (John), Metspalu, A. (Andres), Meulenbelt, I. (Ingrid), Zwart, J-A. (John-Anker), Meurs, J.B.J. (Joyce) van, Zeggini, E. (Eleftheria), Spector, T.D. (Timothy), Gonzalez, A. (Antonio), Rodriguez-Fontenla, C. (Cristina), Calaza, M. (Manuel), Evangelou, E. (Evangelos), Valdes, A.M. (Ana Maria), Arden, N.K. (Nigel), Blanco, F.J., Carr, A.J. (Andrew Jonathan), Chapman, K. (Kay), Deloukas, P. (Panagiotis), Doherty, M. (Michael), Esko, T. (Tõnu), Garcés Aletá, C.M. (Carlos), Gomez-Reino Carnota, J.J. (Juan), Helgadottir, H.T. (Hafdis), Hofman, A. (Albert), Jonsdottir, I. (Ingileif), Kerkhof, J.M. (Hanneke), Kloppenburg, M. (Margreet), McCaskie, A. (Andrew), Ntzani, E.E. (Evangelia), Ollier, W.E.R. (William), Oreiro, N. (Natividad), Panoutsopoulou, K. (Kalliope), Ralston, S.H. (Stuart), Ramos, Y.F.M. (Yolande), Riancho, J.A. (José), Rivadeneira Ramirez, F. (Fernando), Slagboom, P.E. (Eline), Styrkarsdottir, U. (Unnur), Thorsteinsdottir, U. (Unnur), Thorleifsson, G. (Gudmar), Tsezou, A. (Aspasia), Uitterlinden, A.G. (André), Wallis, G.A. (Gillian), Wilkinson, J.M. (Mark), Zhai, G. (Guangju), Zhu, Y. (Yanyan), Felson, D., Ioannidis, J.P.A. (John), Loughlin, J. (John), Metspalu, A. (Andres), Meulenbelt, I. (Ingrid), Zwart, J-A. (John-Anker), Meurs, J.B.J. (Joyce) van, Zeggini, E. (Eleftheria), Spector, T.D. (Timothy), and Gonzalez, A. (Antonio)

Abstract

Objective To assess candidate genes for association with osteoarthritis (OA) and identify promising genetic factors and, secondarily, to assess the candidate gene approach in OA. Methods A total of 199 candidate genes for association with OA were identified using Human Genome Epidemiology (HuGE) Navigator. All of their single-nucleotide polymorphisms (SNPs) with an allele frequency of >5% were assessed by fixed-effects meta-analysis of 9 genome-wide association studies (GWAS) that included 5,636 patients with knee OA and 16,972 control subjects and 4,349 patients with hip OA and 17,836 control subjects of European ancestry. An additional 5,921 individuals were genotyped for significantly associated SNPs in the meta-analysis. After correction for the number of independent tests, P values less than 1.58 × 10-5 were considered significant. Results SNPs at only 2 of the 199 candidate genes (COL11A1 and VEGF) were associated with OA in the meta-analysis. Two SNPs in COL11A1 showed association with hip OA in the combined analysis: rs4907986 (P = 1.29 × 10-5, odds ratio [OR] 1.12, 95% confidence interval [95% CI] 1.06-1.17) and rs1241164 (P = 1.47 × 10-5, OR 0.82, 95% CI 0.74-0.89). The sex-stratified analysis also showed association of COL11A1 SNP rs4908291 in women (P = 1.29 × 10-5, OR 0.87, 95% CI 0.82-0.92); this SNP showed linkage disequilibrium with rs4907986. A single SNP of VEGF, rs833058, showed association with hip OA in men (P = 1.35 × 10-5, OR 0.85, 95% CI 0.79-0.91). After additional samples were genotyped, association at one of the COL11A1 signals was reinforced, whereas association at VEGF was slightly weakened. Conclusion Two candidate genes, COL11A1 and VEGF, were significantly associated with OA in this focused meta-analysis. The remaining candidate genes were not associated. Copyright

Published
2014
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6. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip

Author

Evangelou, E. (Evangelos), Kerkhof, J.M. (Hanneke), Styrkarsdottir, U. (Unnur), Ntzani, E.E. (Evangelia), Bos, S.D. (Steffan), Esko, T. (Tõnu), Evans, D.S. (Daniel), Metrustry, S. (Sarah), Panoutsopoulou, K. (Kalliope), Ramos, Y.F.M. (Yolande), Thorleifsson, G. (Gudmar), Tsilidis, K.K. (Konstantinos), Arden, N.K. (Nigel), Aslam, N. (Nadim), Bellamy, N. (Nicholas), Birrell, F. (Fraser), Blanco, F.J., Carr, A.J. (Andrew Jonathan), Chapman, K. (Kay), Day-Williams, A.G. (Aaron), Deloukas, P. (Panagiotis), Doherty, M. (Michael), Engström, G., Helgadottir, H.T. (Hafdis), Hofman, A. (Albert), Ingvarsson, T. (Torvaldur), Jonsson, H. (Helgi), Keis, A. (Aime), Keurentjes, J.C. (J. Christiaan), Kloppenburg, M. (Margreet), Lind, P.A. (Penelope), McCaskie, A. (Andrew), Martin, N.G. (Nicholas), Milani, A.L. (Alfredo), Montgomery, G.W., Nelissen, R.G.H.H. (Rob), Nevitt, M.C. (Michael), Nilsson, P. (Peter), Ollier, W.E.R. (William), Parimi, N. (Neeta), Rai, A. (Ashok), Ralston, S.H., Reed, M.R. (Mike), Riancho, J.A. (José), Rivadeneira Ramirez, F. (Fernando), Rodriguez-Fontenla, C. (Cristina), Southam, L. (Lorraine), Thorsteinsdottir, U. (Unnur), Tsezou, A. (Aspasia), Wallis, G.A. (Gillian), Wilkinson, J.M. (Mark), Gonzalez, A. (Antonio), Lane, N.E., Lohmander, L.S. (Stefan), Loughlin, J. (John), Metspalu, A. (Andres), Uitterlinden, A.G. (André), Jonsdottir, I. (Ingileif), Zwart, J-A. (John-Anker), Slagboom, P.E. (Eline), Zeggini, E. (Eleftheria), Meulenbelt, I. (Ingrid), Ioannidis, J.P.A. (John), Spector, T.D. (Timothy), Meurs, J.B.J. (Joyce) van, Valdes, A.M. (Ana Maria), Evangelou, E. (Evangelos), Kerkhof, J.M. (Hanneke), Styrkarsdottir, U. (Unnur), Ntzani, E.E. (Evangelia), Bos, S.D. (Steffan), Esko, T. (Tõnu), Evans, D.S. (Daniel), Metrustry, S. (Sarah), Panoutsopoulou, K. (Kalliope), Ramos, Y.F.M. (Yolande), Thorleifsson, G. (Gudmar), Tsilidis, K.K. (Konstantinos), Arden, N.K. (Nigel), Aslam, N. (Nadim), Bellamy, N. (Nicholas), Birrell, F. (Fraser), Blanco, F.J., Carr, A.J. (Andrew Jonathan), Chapman, K. (Kay), Day-Williams, A.G. (Aaron), Deloukas, P. (Panagiotis), Doherty, M. (Michael), Engström, G., Helgadottir, H.T. (Hafdis), Hofman, A. (Albert), Ingvarsson, T. (Torvaldur), Jonsson, H. (Helgi), Keis, A. (Aime), Keurentjes, J.C. (J. Christiaan), Kloppenburg, M. (Margreet), Lind, P.A. (Penelope), McCaskie, A. (Andrew), Martin, N.G. (Nicholas), Milani, A.L. (Alfredo), Montgomery, G.W., Nelissen, R.G.H.H. (Rob), Nevitt, M.C. (Michael), Nilsson, P. (Peter), Ollier, W.E.R. (William), Parimi, N. (Neeta), Rai, A. (Ashok), Ralston, S.H., Reed, M.R. (Mike), Riancho, J.A. (José), Rivadeneira Ramirez, F. (Fernando), Rodriguez-Fontenla, C. (Cristina), Southam, L. (Lorraine), Thorsteinsdottir, U. (Unnur), Tsezou, A. (Aspasia), Wallis, G.A. (Gillian), Wilkinson, J.M. (Mark), Gonzalez, A. (Antonio), Lane, N.E., Lohmander, L.S. (Stefan), Loughlin, J. (John), Metspalu, A. (Andres), Uitterlinden, A.G. (André), Jonsdottir, I. (Ingileif), Zwart, J-A. (John-Anker), Slagboom, P.E. (Eline), Zeggini, E. (Eleftheria), Meulenbelt, I. (Ingrid), Ioannidis, J.P.A. (John), Spector, T.D. (Timothy), Meurs, J.B.J. (Joyce) van, and Valdes, A.M. (Ana Maria)

Abstract

Objectives: Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. Methods: We performed a two-stage meta-analysis on more than 78 000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. Results: We accumulated 11 277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9×10-9and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p=5.6×10-8) and follow-up studies (p=7.3×10-4). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9×10-7, OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2×10-6, OR=1.27 in male specific analysis). Conclusions: Novel genetic loci for hip OA were found in this meta-analysis of GWAS.

Published
2014
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7. A reference case for economic evaluations in osteoarthritis: An expert consensus article from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)

Author

Hiligsmann, M. (Mickael), Cooper, C. (Charles), Guillemin, F. (F.), Hochberg, M.C. (Marc), Tugwell, P. (Peter), Arden, N.K. (Nigel), Berenbaum, F. (Francis), Boers, M. (Maarten), Boonen, A. (Annelies), Branco, M.R. (Miguel), Maria-Luisa, B. (Brandi), Bruyère, F. (Françoise), Gasparik, A. (Andrea), Kanis, J.A. (John), Kvien, T.K. (Tore), Martel-Pelletier, J. (Johanne), Pelletier, J.-P. (Jean-Pierre), Pinedo-Villanueva, R. (Rafael), Pinto, D. (Daniel), Reiter-Niesert, S. (Susanne), Rizzoli, R., Rovati, L.C. (Lucio), Severens, J.L. (Hans), Silverman, S. (Stuart), Reginster, J-Y. (Jean-Yves), Hiligsmann, M. (Mickael), Cooper, C. (Charles), Guillemin, F. (F.), Hochberg, M.C. (Marc), Tugwell, P. (Peter), Arden, N.K. (Nigel), Berenbaum, F. (Francis), Boers, M. (Maarten), Boonen, A. (Annelies), Branco, M.R. (Miguel), Maria-Luisa, B. (Brandi), Bruyère, F. (Françoise), Gasparik, A. (Andrea), Kanis, J.A. (John), Kvien, T.K. (Tore), Martel-Pelletier, J. (Johanne), Pelletier, J.-P. (Jean-Pierre), Pinedo-Villanueva, R. (Rafael), Pinto, D. (Daniel), Reiter-Niesert, S. (Susanne), Rizzoli, R., Rovati, L.C. (Lucio), Severens, J.L. (Hans), Silverman, S. (Stuart), and Reginster, J-Y. (Jean-Yves)

Abstract

Background: General recommendations for a reference case for economic studies in rheumatic diseases were published in 2002 in an initiative to improve the comparability of cost-effectiveness studies in the field. Since then, economic evaluations in osteoarthritis (OA) continue to show considerable heterogeneity in methodological approach. Objectives: To develop a reference case specific for economic studies in OA, including the standard optimal care, with which to judge new pharmacologic and non-pharmacologic interventions. Methods: Four subgroups of an ESCEO expert working group on economic assessments (13 experts representing diverse aspects of clinical research and/or economic evaluations) were charged with producing lists of recommendations that would potentially improve the comparability of economic analyses in OA: outcome measures, comparators, costs and methodology. These proposals were discussed and refined during a face-to-face meeting in 2013. They are presented here in the format of the recommendations of the recently published Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement, so that an initiative on economic analysis methodology might be consolidated with an initiative on reporting standards. Results: Overall, three distinct reference cases are proposed, one for each hand, knee and hip OA; with diagnostic variations in the first two, giving rise to different treatment options: interphalangeal or thumb-based disease for hand OA and the presence or absence of joint malalignment for knee OA. A set of management strategies is proposed, which should be further evaluated to help establish a consensus on the "standard optimal care" in each proposed reference case. The recommendations on outcome measures, cost itemisation and methodological approaches are also provided. Conclusions: The ESCEO group proposes a set of disease-specific recommendations on the conduct and reporting of economic evaluations in OA that could help the stand

Published
2014
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8. Health economics in the field of osteoarthritis: An Expert's consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)

Author

Hiligsmann, M. (Mickael), Cooper, C. (Charles), Arden, N.K. (Nigel), Boers, M. (Maarten), Branco, M.R. (Miguel), Luisa Brandi, M. (Maria), Bruyère, F. (Françoise), Guillemin, F. (Francis), Hochberg, M.C. (Marc), Hunter, D.J. (David), Kanis, J.A. (John), Kvien, T.K. (Tore), Laslop, A. (Andrea), Pelletier, C. (Cory), Pinto, D. (Duane), Reiter-Niesert, S. (Susanne), Rizzoli, R., Rovati, L.C. (Lucio), Severens, J.L. (Hans), Silverman, S. (Stuart), Tsouderos, Y. (Yannis), Tugwell, P. (Peter), Reginster, J-Y. (Jean-Yves), Hiligsmann, M. (Mickael), Cooper, C. (Charles), Arden, N.K. (Nigel), Boers, M. (Maarten), Branco, M.R. (Miguel), Luisa Brandi, M. (Maria), Bruyère, F. (Françoise), Guillemin, F. (Francis), Hochberg, M.C. (Marc), Hunter, D.J. (David), Kanis, J.A. (John), Kvien, T.K. (Tore), Laslop, A. (Andrea), Pelletier, C. (Cory), Pinto, D. (Duane), Reiter-Niesert, S. (Susanne), Rizzoli, R., Rovati, L.C. (Lucio), Severens, J.L. (Hans), Silverman, S. (Stuart), Tsouderos, Y. (Yannis), Tugwell, P. (Peter), and Reginster, J-Y. (Jean-Yves)

Abstract

Objectives: There is an important need to evaluate therapeutic approaches for osteoarthritis (OA) in terms of cost-effectiveness as well as

Published
2013
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9. Genome-wide association study meta-analysis of chronic widespread pain: Evidence for involvement of the 5p15.2 region

Author

Peters, M.J. (Marjolein), Broer, L. (Linda), Willemen, H.L.D.M. (Hanneke), Eiriksdottir, G. (Gudny), Hocking, L.J. (Lynne), Holliday, K.L. (Kate), Horan, M. (Mike), Meulenbelt, I. (Ingrid), Neogi, T. (Tuhina), Popham, M. (Maria), Schmidt, C.O. (Carsten Oliver), Soni, B., Valdes, A.M. (Ana Maria), Amin, N. (Najaf), Dennison, E.M. (Elaine), Eijkelkamp, B. (Bart), Harris, T.B. (Tamara), Hart, D.J. (Deborah), Hofman, A. (Albert), Huygen, F.J.P.M. (Frank), Jameson, K. (Karen), Jones, G.T. (Gregory), Launer, L.J. (Lenore), Kerkhof, J.M. (Hanneke), Kruijf, M. (Marjolein) de, McBeth, J. (John), Kloppenburg, M. (Margreet), Ollier, W.E.R. (William), Oostra, B.A. (Ben), Payton, A. (Antony), Rivadeneira Ramirez, F. (Fernando), Smith, B.H. (Blair), Smith, A.V. (Davey), Stolk, L. (Lisette), Teumer, A. (Alexander), Thomson, W. (Wendy), Uitterlinden, A.G. (André), Wang, K. (Ke), Wingerden, S. (Sophie) van, Arden, N.K. (Nigel), Cooper, C. (Charles), Felson, D., Gudnason, V. (Vilmundur), Macfarlane, G.J. (Gary), Pendleton, N. (Neil), Slagboom, P.E. (Eline), Spector, T.D. (Timothy), Volzke, H. (Henry), Kavelaars, A. (Annemieke), Duijn, C.M. (Cornelia) van, Williams, F.M. (Frances), Meurs, J.B.J. (Joyce) van, Peters, M.J. (Marjolein), Broer, L. (Linda), Willemen, H.L.D.M. (Hanneke), Eiriksdottir, G. (Gudny), Hocking, L.J. (Lynne), Holliday, K.L. (Kate), Horan, M. (Mike), Meulenbelt, I. (Ingrid), Neogi, T. (Tuhina), Popham, M. (Maria), Schmidt, C.O. (Carsten Oliver), Soni, B., Valdes, A.M. (Ana Maria), Amin, N. (Najaf), Dennison, E.M. (Elaine), Eijkelkamp, B. (Bart), Harris, T.B. (Tamara), Hart, D.J. (Deborah), Hofman, A. (Albert), Huygen, F.J.P.M. (Frank), Jameson, K. (Karen), Jones, G.T. (Gregory), Launer, L.J. (Lenore), Kerkhof, J.M. (Hanneke), Kruijf, M. (Marjolein) de, McBeth, J. (John), Kloppenburg, M. (Margreet), Ollier, W.E.R. (William), Oostra, B.A. (Ben), Payton, A. (Antony), Rivadeneira Ramirez, F. (Fernando), Smith, B.H. (Blair), Smith, A.V. (Davey), Stolk, L. (Lisette), Teumer, A. (Alexander), Thomson, W. (Wendy), Uitterlinden, A.G. (André), Wang, K. (Ke), Wingerden, S. (Sophie) van, Arden, N.K. (Nigel), Cooper, C. (Charles), Felson, D., Gudnason, V. (Vilmundur), Macfarlane, G.J. (Gary), Pendleton, N. (Neil), Slagboom, P.E. (Eline), Spector, T.D. (Timothy), Volzke, H. (Henry), Kavelaars, A. (Annemieke), Duijn, C.M. (Cornelia) van, Williams, F.M. (Frances), and Meurs, J.B.J. (Joyce) van

Published
2013
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10. Genome-wide association and functional studies identify the DOT1L gene to be involved in cartilage thickness and hip osteoarthritis

Author

Castaño Betancourt, M.C. (Martha), Cailotto, F. (Frederic), Kerkhof, J.M. (Hanneke), Cornelis, F.M.F. (Frederique M.), Doherty, S. (Sally), Hart, D.J. (Deborah), Hofman, A. (Albert), Luyten, F.P. (Frank), Maciewicz, R.A. (Rose), Mangino, M. (Massimo), Metrustry, S. (Sarah), Muir, K.R. (Kenneth), Peters, M.J. (Marjolein), Rivadeneira Ramirez, F. (Fernando), Wheeler, M. (Margaret), Zhang, W. (Weiya), Arden, N.K. (Nigel), Spector, T.D. (Timothy), Uitterlinden, A.G. (André), Doherty, M. (Michael), Lories, R.J. (Rik), Valdes, A.M. (Ana Maria), Meurs, J.B.J. (Joyce) van, Castaño Betancourt, M.C. (Martha), Cailotto, F. (Frederic), Kerkhof, J.M. (Hanneke), Cornelis, F.M.F. (Frederique M.), Doherty, S. (Sally), Hart, D.J. (Deborah), Hofman, A. (Albert), Luyten, F.P. (Frank), Maciewicz, R.A. (Rose), Mangino, M. (Massimo), Metrustry, S. (Sarah), Muir, K.R. (Kenneth), Peters, M.J. (Marjolein), Rivadeneira Ramirez, F. (Fernando), Wheeler, M. (Margaret), Zhang, W. (Weiya), Arden, N.K. (Nigel), Spector, T.D. (Timothy), Uitterlinden, A.G. (André), Doherty, M. (Michael), Lories, R.J. (Rik), Valdes, A.M. (Ana Maria), and Meurs, J.B.J. (Joyce) van

Abstract

Hip osteoarthritis (HOA) is one of the most disabling and common joint disorders with a large genetic component that is, however, still ill-defined. To date, genome-wide association studies (GWAS) in osteoarthritis (OA) and specifically in HOA have yielded only few loci, which is partly explained by heterogeneity in the OA definition. Therefore, we here focused on radiographically measured joint-space width (JSW), a proxy for cartilage thickness and an important underlying intermediate trait for HOA. In a GWAS of 6,523 individuals on hip-JSW, we identified the G allele of rs12982744 on chromosome 19p13.3 to be associated with a 5% larger JSW (P = 4.8 × 10-10). The association was replicated in 4,442 individuals from three United Kingdom cohorts with an overall meta-analysis P value of 1.1 × 10-11. The SNP was also strongly associated with a 12% reduced risk for HOA (P = 1 × 10-4). The SNP is located in the DOT1L gene, which is an evolutionarily conserved histone methyltransferase, recently identified as a potentially dedicated enzyme for Wnt target-gene activation in leukemia. Immunohistochemical staining of the DOT1L prote

Published
2012
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11. Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: The TREAT-OA consortium

Author

Kerkhof, J.M. (Hanneke), Meulenbelt, I. (Ingrid), Akune, T. (Toru), Arden, N.K. (Nigel), Aromaa, A. (Arpo), Bierma-Zeinstra, S.M. (Sita), Cooper, C. (Charles), Dai, J., Doherty, M. (Michael), Doherty, S. (Sally), Felson, D., Gonzalez, A. (Antonio), Gordon, A., Harilainen, A. (Arsi), Hart, D.J., Hauksson, V.B. (Valdimar), Heliovaara, M. (Markku), Hofman, A. (Albert), Ikegawa, S., Ingvarsson, T. (Torvaldur), Jiang, Q., Jonsson, H., Jonsdottir, I. (Ingileif), Kawaguchi, H., Kloppenburg, M. (Margreet), Kujala, U.M. (Urho), Lane, N.E., Leino-Arjas, P. (Päivi I.), Lohmander, L.S. (Stefan), Luyten, F.P. (Frank), Malizos, K.N. (Konstantinos), Nakajima, M., Nevitt, M.C. (Michael), Pols, H.A.P. (Huib), Rivadeneira Ramirez, F. (Fernando), Shi, D., Slagboom, P.E. (Eline), Spector, T.D. (Timothy), Stefansson, K. (Kari), Sudo, A. (Akihiro), Tamm, A., Tamm, A.E. (Aile), Tsezou, A. (Aspasia), Uchida, A., Uitterlinden, A.G. (André), Wilkinson, J.M. (Mark), Yoshimura, N., Valdes, A.M. (Ana Maria), Meurs, J.B.J. (Joyce) van, Carr, A.J. (Andrew Jonathan), Kerkhof, J.M. (Hanneke), Meulenbelt, I. (Ingrid), Akune, T. (Toru), Arden, N.K. (Nigel), Aromaa, A. (Arpo), Bierma-Zeinstra, S.M. (Sita), Cooper, C. (Charles), Dai, J., Doherty, M. (Michael), Doherty, S. (Sally), Felson, D., Gonzalez, A. (Antonio), Gordon, A., Harilainen, A. (Arsi), Hart, D.J., Hauksson, V.B. (Valdimar), Heliovaara, M. (Markku), Hofman, A. (Albert), Ikegawa, S., Ingvarsson, T. (Torvaldur), Jiang, Q., Jonsson, H., Jonsdottir, I. (Ingileif), Kawaguchi, H., Kloppenburg, M. (Margreet), Kujala, U.M. (Urho), Lane, N.E., Leino-Arjas, P. (Päivi I.), Lohmander, L.S. (Stefan), Luyten, F.P. (Frank), Malizos, K.N. (Konstantinos), Nakajima, M., Nevitt, M.C. (Michael), Pols, H.A.P. (Huib), Rivadeneira Ramirez, F. (Fernando), Shi, D., Slagboom, P.E. (Eline), Spector, T.D. (Timothy), Stefansson, K. (Kari), Sudo, A. (Akihiro), Tamm, A., Tamm, A.E. (Aile), Tsezou, A. (Aspasia), Uchida, A., Uitterlinden, A.G. (André), Wilkinson, J.M. (Mark), Yoshimura, N., Valdes, A.M. (Ana Maria), Meurs, J.B.J. (Joyce) van, and Carr, A.J. (Andrew Jonathan)

Abstract

Objective: To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes. Methods: Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consortium were collected. We investigated whether different OA definitions result in different association results by creating various hip OA definitions in one large population based cohort (the Rotterdam Study I

Published
2011
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