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108. Genome-wide association and functional studies identify a role for matrix Gla protein in osteoarthritis of the hand

Author

Hollander, W. (Wouter) den, Boer, C.G. (Cindy G.), Hart, D.J. (Deborah), Yau, M.S. (Michelle S.), Ramos, Y.F.M. (Yolande F.M.), Metrustry, S. (Sarah), Broer, L. (Linda), Deelen, J. (Joris), Cupples, L.A. (Adrienne), Rivadeneira, F. (Fernando), Kloppenburg, M. (Margreet), Peters, M.A.D. (Marjolein), Spector, T.D. (Timothy), Hofman, A. (Albert), Slagboom, P.E. (Eline), Nelissen, R.G.H.H. (Rob), Uitterlinden, A.G. (André), Felson, D., Valdes, A.M. (Ana Maria), Meulenbelt, I. (Ingrid), Van Meurs, J.J.B. (Joyce J. B.), Hollander, W. (Wouter) den, Boer, C.G. (Cindy G.), Hart, D.J. (Deborah), Yau, M.S. (Michelle S.), Ramos, Y.F.M. (Yolande F.M.), Metrustry, S. (Sarah), Broer, L. (Linda), Deelen, J. (Joris), Cupples, L.A. (Adrienne), Rivadeneira, F. (Fernando), Kloppenburg, M. (Margreet), Peters, M.A.D. (Marjolein), Spector, T.D. (Timothy), Hofman, A. (Albert), Slagboom, P.E. (Eline), Nelissen, R.G.H.H. (Rob), Uitterlinden, A.G. (André), Felson, D., Valdes, A.M. (Ana Maria), Meulenbelt, I. (Ingrid), and Van Meurs, J.J.B. (Joyce J. B.)

Abstract

Objective Osteoarthritis (OA) is the most common form of arthritis and the leading cause of disability in the elderly. Of all the joints, genetic predisposition is strongest for OA of the hand; however, only few genetic risk loci for hand OA have been identified. Our aim was to identify novel genes associated with hand OA and examine the underlying mechanism. Methods We performed a genome-wide association study of a quantitative measure of hand OA in 12 784 individuals (discovery: 8743, replication: 4011). Genome-wide significant signals were followed up by analysing gene and allele-specific expression in a RNA sequencing dataset (n=96) of human articular cartilage. Results We found two significantly associated loci in the discovery set: at chr12 (p=3.5 × 10 -10) near the matrix Gla protein (MGP) gene and at chr12 (p=6.1×10 -9) near the CCDC91 gene. The DNA variant near t

Published
2017
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109. A knee brace alters patella position in patellofemoral osteoarthritis: a study using weight bearing magnetic resonance imaging:a study using weight bearing magnetic resonance imaging

Author

Callaghan, M J, Guney, H, Reeves, N D, Bailey, D, Doslikova, K, Maganaris, C N, Hodgson, R, and Felson, D T

Subjects
musculoskeletal diseases, musculoskeletal system, human activities
Abstract

Objective: To assess using weight bearing magnetic resonance imaging (MRIs), whether a patellar brace altered patellar position and alignment in patellofemoral joint (PFJ) osteoarthritis (OA). Design: Subjects age 40e70 years old with symptomatic and a radiographic KellgreneLawrence (KeL) evidence of PFJOA. Weight bearing knee MRIs with and without a patellar brace were obtained using an upright open 0.25 T scanner (G-Scan, Easote Biomedica, Italy). Five aspects of patellar position were measured: mediolateral alignment by the bisect offset index, angulation by patellar tilt, patellar height by patellar height ratio (patellar length/patellar tendon length), lateral patellofemoral (PF) contact area and finally a measurement of PF bony separation of the lateral patellar facet and the adjacent surface on the femoral trochlea (Fig. 1). Results: Thirty participants were recruited (mean age 57 SD 27.8; body mass index (BMI) 27.8 SD 4.2); 17 were females. Four patients had non-usable data. Main analysis used paired t tests comparing within subject patellar position with and without brace. For bisect offset index, patellar tilt and patellar height ratio there were no significant differences between the brace and no brace conditions. However, the brace increased lateral facet contact area (P ¼ .04) and decreased lateral PF separation (P ¼ .03). Conclusion: A patellar brace alters patellar position and increases contact area between the patella and femoral trochlea. These changes would lower contact stress at the PFJ. Such changes in patella position in weight bearing provide a possible biomechanical explanation for the success of the PFJ brace in clinical trials on PFJOA.

Published
2016
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111. A PROPOSAL FOR STRUCTURED REPORTING OF RANDOMIZED CONTROLLED TRIALS

Author

Andrew, E, Anis, A, Chalmers, T, Cho, M, Clarke, M, Felson, D, Gotzsche, P, Greene, R, Jadad, A, Jonas, W, Klassen, T, Knipschild, P, Laupacis, A, Meinert, C, Moher, D, Nichol, G, Oxman, A, Penman, M, Pocock, S, Reisch, J, Sackett, D, Schulz, K, Snider, J, Tugwell, P, and Tyson, J

Published
2016

112. COMMON VARIANTS IN SKELETAL DYSPLASIA GENES ARE ASSOCIATED WITH OSTEOARTHRITIS

Author

Kerkhof, H, Panagiotou, O, Irving, M, Esko, T, Meulenbelt, I, Panoutsopoulou, K, Styrkarsdottir, U, Zhu, Y, Cupples, A, Felson, D, Kloppenburg, M, Arden, N, Albert, H, Slagboom, E, Frank, L, Metspalu, A, Ioannidis, J, Jonsdottir, I, Stefansson, K, Spector, T, Uitterlinden, A, Zeggini, E, Valdes, A, Evangelou, V, and van Meurs, J

Published
2016

114. A genome-wide association study identifies an osteoarthritis susceptibility locus on chromosome 7q22

Author

Kerkhof, H, Lories, R, Meulenbelt, I, Jonsdottir, I, Valdes, A, Arp, P, Ingvarsson, T, Jhamai, M, Jonsson, H, Stolk, L, Thorleifsson, G, Zhai, G, Zhang, F, Zhu, Y, van der Breggen, R, Carr, A, Doherty, M, Doherty, S, Felson, D, Gonzalez, A, Halldorsson, B, Hart, D, Hauksson, V, Hofman, A, and Ioannidis, J

Abstract

OBJECTIVE: To identify novel genes involved in osteoarthritis (OA), by means of a genome-wide association study. METHODS: We tested 500,510 single-nucleotide polymorphisms (SNPs) in 1,341 Dutch Caucasian OA cases and 3,496 Dutch Caucasian controls. SNPs associated with at least 2 OA phenotypes were analyzed in 14,938 OA cases and approximately 39,000 controls. Meta-analyses were performed using the program Comprehensive Meta-analysis, with P values

Published
2016

119. Knee osteoarthritis and the risk of premature mortality in the community: an international individual patient level meta-analysis in 9889 subjects

Author

Leyland, K.M., primary, Gates, L.S., additional, Sanchez-Santos, M.T., additional, Prieto Alhambra, D., additional, Judge, A., additional, Collins, G., additional, Cleveland, R., additional, Felson, D., additional, Jordon, J.M., additional, Callahan, L.F., additional, Nevitt, M., additional, Saberi Hosnijeh, F., additional, van Meurs, J.B., additional, Jones, G., additional, Newton, J., additional, Batt, M., additional, Altman, D., additional, Cooper, C., additional, Arden, N., additional, and Committee, P.-C., additional

Published
2017
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120. AUTOMATICALLY DETERMINED MINIMAL JOINT SPACE WIDTH IS LOWER IN SUBJECTS WITH RADIOGRAPHIC HIP OA BUT NOT SIGNIFICANTLY DIFFERENT IF HIP PAIN IS PRESENT: A MULTI-COHORT ANALYSIS

Author

van den Berg, M.A., Boel, F., Riedstra, N.S., van Buuren, M.M.A., Tang, J., Bierma-Zeinstra, S.M.A., Felson, D., Krijthe, J.H., Lynch, J.A., Nelson, A.E., Nevitt, M., Runhaar, J., and Agricola, R.

Abstract

Current epidemiological research on management and prevention of hip OA faces challenges due to the lack of a uniform OA definition. Automated detection of radiographic features on x-ray images across studies such as the minimal JSW (mJSW) could be a solution. However, having radiographic evidence of hip OA does not always imply having symptoms or disability and vice-versa. In order to create an automated hip OA definition, we need to improve our understanding of the interplay between the mJSW and clinical and radiographic factors in a large and diverse population.

Published
2024
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121. THE PRESENCE OF HIP PAIN DOES NOT MODIFY THE ASSOCIATION BETWEEN HIP MORPHOLOGY AND INCIDENT RADIOGRAPHIC HIP OA WITHIN 5-8 YEARS

Author

Boel, F., van den Berg, M.A., Riedstra, N.S., van Buuren, M.M.A., Tang, J., Bierma-Zeinstra, S.M.A., Felson, D., Lynch, J.A., Nelson, A.E., Nevitt, M., Runhaar, J., and Agricola, R.

Abstract

Different hip morphologies have been shown to be risk factors for hip OA. However, the associations found differ in size and are sometimes even contradictory. Different follow-up times, radiographic hip OA (RHOA) definitions, and quantification of hip morphology might explain these conflicting results. Additionally, previous studies have shown that hip pain in combination with a different hip morphology might alter the association with incident RHOA.

Published
2024
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122. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015

Author

Vos, T., Allen, C., Arora, M., Barber, R., Bhutta, Z., Brown, A., Carter, A., Casey, D., Charlson, F., Chen, A., Coggeshall, M., Cornaby, L., Dandona, L., Dicker, D., Dilegge, T., Erskine, H., Ferrari, A., Fitzmaurice, C., Fleming, T., Forouzanfar, M., Fullman, N., Gething, P., Goldberg, E., Graetz, N., Haagsma, J., Johnson, C., Kassebaum, N., Kawashima, T., Kemmer, L., Khalil, I., Kinfu, Y., Kyu, H., Leung, J., Liang, X., Lim, S., Lopez, A., Lozano, R., Marczak, L., Mensah, G., Mokdad, A., Naghavi, M., Nguyen, G., Nsoesie, E., Olsen, H., Pigott, D., Pinho, C., Rankin, Z., Reinig, N., Salomon, J., Sandar, L., Smith, A., Stanaway, J., Steiner, C., Teeple, S., Thomas, B., Troeger, C., Wagner, J., Wang, H., Wanga, V., Whiteford, H., Zoeckler, L., Abajobir, A., Abate, K., Abbafati, C., Abbas, K., Abd-Allah, F., Abraham, B., Abubakar, I., Abu-Raddad, L., Abu-Rmeileh, N., Ackerman, I., Adebiyi, A., Ademi, Z., Adou, A., Afanvi, K., Agardh, E., Agarwal, A., Kiadaliri, A., Ahmadieh, H., Ajala, O., Akinyemi, R., Akseer, N., Al-Aly, Z., Alam, K., Alam, N., Aldhahri, S., Alegretti, M., Alemu, Z., Alexander, L., Alhabib, S., Ali, R., Alkerwi, A., Alla, F., Allebeck, P., Al-Raddadi, R., Alsharif, U., Altirkawi, K., Alvis-Guzman, N., Amare, A., Amberbir, A., Amini, H., Ammar, W., Amrock, S., Andersen, H., Anderson, G., Anderson, B., Antonio, C., Aregay, A., Arnlov, J., Al, A., Asayesh, H., Assadi, R., Atique, S., Avokpaho, E., Awasthi, A., Quintanilla, B., Azzopardi, P., Bacha, U., Badawi, A., Balakrishnan, K., Banerjee, A., Barac, A., Barker-Collo, S., Barnighausen, T., Barregard, L., Barrero, L., Basu, A., Bazargan-Hejazi, S., Bell, B., Bell, M., Bennett, D., Bensenor, I., Benzian, H., Berhane, A., Bernabe, E., Betsu, B., Beyene, A., Bhala, N., Bhatt, S., Biadgilign, S., Bienhofff, K., Bikbov, B., Biryukov, S., Bisanzio, D., Bjertness, E., Blore, J., Borschmann, R., Boufous, S., Brainin, M., Brazinova, A., Breitborde, N., Brown, J., Buchbinder, R., Buckle, G., Butt, Z., Calabria, B., Ricardo Campos-Nonato, I., Cesar Campuzano, J., Carabin, H., Cardenas, R., Carpenter, D., Carrero, J., Castaneda-Orjuela, C., Castillo Rivas, J., Catala-Lopez, F., Chang, J., Chiang, P., Chibueze, C., Chisumpa, V., Choi, J., Chowdhury, R., Christensen, H., Christopher, D., Ciobanu, L., Cirillo, M., Coates, M., Colquhoun, S., Cooper, C., Cortinovis, M., Crump, J., Damtew, S., Dandona, R., Daoud, F., Dargan, P., das Neves, J., Davey, G., Davis, A., De Leo, D., Degenhardt, L., Del Gobbo, L., Dellavalle, R., Deribe, K., Deribew, A., Derrett, S., Des Jarlais, D., Dharmaratne, S., Dhillon, P., Diaz-Torne, C., Ding, E., Driscoll, T., Duan, L., Dubey, M., Duncan, B., Ebrahimi, H., Ellenbogen, R., Elyazar, I., Endres, M., Endries, A., Ermakov, S., Eshrati, B., Estep, K., Farid, T., Sofia e Sa Farinha, C., Faro, A., Farvid, M., Farzadfar, F., Feigin, V., Felson, D., Fereshtehnejad, S., Fernandes, J., Fischer, F., Fitchett, J., Foreman, K., Fowkes, G., Fox, J., Franklin, R., Friedman, J., Frostad, J., Furst, T., Futran, N., Gabbe, B., Ganguly, P., Gankpe, F., Gebre, T., Gebrehiwot, T., Gebremedhin, A., Geleijnse, J., Gessner, B., Gibney, K., Ginawi, I., Giref, A., Giroud, M., Gishu, M., Glaser, E., Godwin, W., Gomez-Dantes, H., Gona, P., Goodridge, A., Gopalani, S., Gotay, C., Goto, A., Gouda, H., Grainger, R., Greaves, F., Guillemin, F., Guo, Y., Gupta, R., Gupta, V., Gutierrez, R., Haile, D., Hailu, A., Hailu, G., Halasa, Y., Hamadeh, R., Hamidi, S., Hammami, M., Hancock, J., Handal, A., Hankey, G., Hao, Y., Harb, H., Harikrishnan, S., Maria Haro, J., Havmoeller, R., Hay, R., Beatriz Heredia-Pi, I., Heydarpour, P., Hoek, H., Horino, M., Horita, N., Hosgood, H., Hoy, D., Htet, A., Huang, H., Huang, J., Huynh, C., Iannarone, M., Iburg, K., Innos, K., Inoue, M., Iyer, V., Jacobsen, K., Jahanmehr, N., Jakovljevic, M., Javanbakht, M., Jayatilleke, A., Jee, S., Jeemon, P., Jensen, P., Jiang, Y., Jibat, T., Jimenez-Corona, A., Jin, Y., Jonas, J., Kabir, Z., Kalkonde, Y., Kamal, R., Kan, H., Karch, A., Karema, C., Karimkhani, C., Kasaeian, A., Kaul, A., Kawakami, N., Keiyoro, P., Kemp, A., Keren, A., Kesavachandran, C., Khader, Y., Khaiff, A., Khaiff, E., Khang, Y., Khera, S., Khoja, T., Khubchandani, J., Kieling, C., Kim, P., Kim, C., Kim, D., Kim, Y., Kissoon, N., Knibbs, L., Knudsen, A., Kokubo, Y., Kolte, D., Kopec, J., Kosen, S., Kotsakis, G., Koul, P., Koyanagi, A., Kravchenko, M., Defo, B., Bicer, B., Kudom, A., Kuipers, E., Kumar, G., Kutz, M., Kwan, G., Lal, A., Lalloo, R., Lallukka, T., Lam, H., Lam, J., Langan, S., Larsson, A., Lavados, P., Leasher, J., Leigh, J., Leung, R., Levi, M., Li, Y., Liang, J., Liu, S., Liu, Y., Lloyd, B., Lo, W., Logroscino, G., Looker, K., Lotufo, P., Lunevicius, R., Lyons, R., Mackay, M., Abd El Razek, M., Mahdavi, M., Majdan, M., Majeed, A., Malekzadeh, R., Marcenes, W., Margolis, D., Martinez-Raga, J., Masiye, F., Massano, J., McGarvey, S., McGrath, J., McKee, M., McMahon, B., Meaney, P., Mehari, A., Meija-Rodriguez, F., Mekonnen, A., Melaku, Y., Memiah, P., Memish, Z., Mendoza, W., Meretoja, A., Meretoja, T., Mhimbira, F., Miller, Ted, Mills, E., Mirarefin, M., Mitchell, P., Mock, C., Mohammadi, A., Mohammed, S., Monasta, L., Montanez Hernandez, J., Montico, M., Mooney, M., Moradi-Lakeh, M., Morawska, L., Mueller, U., Mullany, E., Mumford, J., Murdoch, M., Nachega, J., Nagel, G., Naheed, A., Naldi, L., Nangia, V., Newton, J., Ng, M., Ngalesoni, F., Quyen, L., Nisar, M., Nkamedjie Pete, P., Nona, J., Norheim, O., Norman, R., Norrving, B., Nunes, B., Ogbo, F., Oh, I., Ohkubo, T., Olivares, P., Olusanya, B., Olusanya, J., Ortiz, A., Osman, M., Ota, E., Mahesh, P., Park, E., Parsaeian, M., de Azeredo Passos, V., Paternina Caicedo, A., Patten, S., Patton, G., Pereira, D., Perez-Padilla, R., Perico, N., Pesudovs, K., Petzold, M., Phillips, M., Piel, F., Pillay, J., Pishgar, F., Plass, D., Platts-Mills, J., Polinder, S., Pond, C., Popova, S., Poulton, R., Pourmalek, F., Prabhakaran, D., Prasad, N., Qorbani, M., Rabiee, R., Radfar, A., Rafay, A., Rahimi, K., Rahimi-Movaghar, V., Rahman, M., Rahman, S., Rai, R., Rajsic, S., Ram, U., Rao, P., Refaat, A., Reitsma, M., Remuzzi, G., Resnikofff, S., Reynolds, A., Ribeiro, A., Rios Blancas, M., Rolm, H., Rojas-Rueda, D., Ronfani, L., Roshandel, G., Roth, G., Rothenbacher, D., Roy, A., Sagar, R., Sahathevan, R., Sanabria, J., Dolores Sanchez-Nino, M., Santos, I., Santos, J., Sarmiento-Suarez, R., Sartorius, B., Satpathy, M., Savic, M., Sawhney, M., Schaub, M., Schmidt, M., Schneider, I., Schottker, B., Schwebel, D., Scott, J., Seedat, S., Sepanlou, S., Servan-Mori, E., Shackelford, K., Shaheen, A., Shaikh, M., Sharma, R., Sharma, U., Shen, J., Shepard, D., Sheth, K., Shibuya, K., Shin, M., Shiri, R., Shiue, I., Shrime, M., Sigfusdottir, I., Silva, D., Alves Silveira, D., Singh, A., Singh, J., Singh, O., Singh, P., Sivonda, A., Skirbekk, V., Skogen, J., Sligar, A., Silwa, K., Soljak, M., Soreide, K., Soriano, J., Sposato, L., Sreeramareddy, C., Stathopoulou, V., Steel, N., Stein, D., Steiner, T., Steinke, S., Stovner, L., Stroumpoulis, K., Sunguya, B., Sur, P., Swaminathan, S., Sykes, B., Szoeke, C., Tabares-Seisdedos, R., Takala, J., Landon, N., Tanne, D., Tavakkoli, M., Taye, B., Taylor, H., Te Ao, B., Tedla, B., Terkawi, A., Thomson, A., Thorne-Lyman, A., Thrift, A., Thurston, G., Tobe-Gai, R., Tonelli, M., Topor-Madry, R., Topouzis, F., Tran, B., Dimbuene, Z., Tsilimbaris, M., Tura, A., Tuzcu, E., Tyrovolas, S., Ukwaja, K., Undurraga, E., Uneke, C., Uthman, O., van Gool, C., Varakin, Y., Vasankari, T., Venketasubramanian, N., Verma, R., Violante, F., Vladimirov, S., Vlassov, V., Vollset, S., Wagner, G., Waller, S., Wang, L., Watkins, D., Weichenthal, S., Weiderpass, E., Weintraub, R., Werdecker, A., Westerman, R., White, R., Williams, H., Wiysonge, C., Wolfe, C., Won, S., Woodbrook, R., Wubshet, M., Xavier, D., Xu, G., Yadav, A., Yan, L., Yano, Y., Yaseri, M., Ye, P., Yebyo, H., Yip, P., Yonemoto, N., Yoon, S., Younis, M., Yu, C., Zaidi, Z., Zaki, M., Zeeb, H., Zhou, M., Zodpey, S., Zuhlke, L., Murray, C., Vos, T., Allen, C., Arora, M., Barber, R., Bhutta, Z., Brown, A., Carter, A., Casey, D., Charlson, F., Chen, A., Coggeshall, M., Cornaby, L., Dandona, L., Dicker, D., Dilegge, T., Erskine, H., Ferrari, A., Fitzmaurice, C., Fleming, T., Forouzanfar, M., Fullman, N., Gething, P., Goldberg, E., Graetz, N., Haagsma, J., Johnson, C., Kassebaum, N., Kawashima, T., Kemmer, L., Khalil, I., Kinfu, Y., Kyu, H., Leung, J., Liang, X., Lim, S., Lopez, A., Lozano, R., Marczak, L., Mensah, G., Mokdad, A., Naghavi, M., Nguyen, G., Nsoesie, E., Olsen, H., Pigott, D., Pinho, C., Rankin, Z., Reinig, N., Salomon, J., Sandar, L., Smith, A., Stanaway, J., Steiner, C., Teeple, S., Thomas, B., Troeger, C., Wagner, J., Wang, H., Wanga, V., Whiteford, H., Zoeckler, L., Abajobir, A., Abate, K., Abbafati, C., Abbas, K., Abd-Allah, F., Abraham, B., Abubakar, I., Abu-Raddad, L., Abu-Rmeileh, N., Ackerman, I., Adebiyi, A., Ademi, Z., Adou, A., Afanvi, K., Agardh, E., Agarwal, A., Kiadaliri, A., Ahmadieh, H., Ajala, O., Akinyemi, R., Akseer, N., Al-Aly, Z., Alam, K., Alam, N., Aldhahri, S., Alegretti, M., Alemu, Z., Alexander, L., Alhabib, S., Ali, R., Alkerwi, A., Alla, F., Allebeck, P., Al-Raddadi, R., Alsharif, U., Altirkawi, K., Alvis-Guzman, N., Amare, A., Amberbir, A., Amini, H., Ammar, W., Amrock, S., Andersen, H., Anderson, G., Anderson, B., Antonio, C., Aregay, A., Arnlov, J., Al, A., Asayesh, H., Assadi, R., Atique, S., Avokpaho, E., Awasthi, A., Quintanilla, B., Azzopardi, P., Bacha, U., Badawi, A., Balakrishnan, K., Banerjee, A., Barac, A., Barker-Collo, S., Barnighausen, T., Barregard, L., Barrero, L., Basu, A., Bazargan-Hejazi, S., Bell, B., Bell, M., Bennett, D., Bensenor, I., Benzian, H., Berhane, A., Bernabe, E., Betsu, B., Beyene, A., Bhala, N., Bhatt, S., Biadgilign, S., Bienhofff, K., Bikbov, B., Biryukov, S., Bisanzio, D., Bjertness, E., Blore, J., Borschmann, R., Boufous, S., Brainin, M., Brazinova, A., Breitborde, N., Brown, J., Buchbinder, R., Buckle, G., Butt, Z., Calabria, B., Ricardo Campos-Nonato, I., Cesar Campuzano, J., Carabin, H., Cardenas, R., Carpenter, D., Carrero, J., Castaneda-Orjuela, C., Castillo Rivas, J., Catala-Lopez, F., Chang, J., Chiang, P., Chibueze, C., Chisumpa, V., Choi, J., Chowdhury, R., Christensen, H., Christopher, D., Ciobanu, L., Cirillo, M., Coates, M., Colquhoun, S., Cooper, C., Cortinovis, M., Crump, J., Damtew, S., Dandona, R., Daoud, F., Dargan, P., das Neves, J., Davey, G., Davis, A., De Leo, D., Degenhardt, L., Del Gobbo, L., Dellavalle, R., Deribe, K., Deribew, A., Derrett, S., Des Jarlais, D., Dharmaratne, S., Dhillon, P., Diaz-Torne, C., Ding, E., Driscoll, T., Duan, L., Dubey, M., Duncan, B., Ebrahimi, H., Ellenbogen, R., Elyazar, I., Endres, M., Endries, A., Ermakov, S., Eshrati, B., Estep, K., Farid, T., Sofia e Sa Farinha, C., Faro, A., Farvid, M., Farzadfar, F., Feigin, V., Felson, D., Fereshtehnejad, S., Fernandes, J., Fischer, F., Fitchett, J., Foreman, K., Fowkes, G., Fox, J., Franklin, R., Friedman, J., Frostad, J., Furst, T., Futran, N., Gabbe, B., Ganguly, P., Gankpe, F., Gebre, T., Gebrehiwot, T., Gebremedhin, A., Geleijnse, J., Gessner, B., Gibney, K., Ginawi, I., Giref, A., Giroud, M., Gishu, M., Glaser, E., Godwin, W., Gomez-Dantes, H., Gona, P., Goodridge, A., Gopalani, S., Gotay, C., Goto, A., Gouda, H., Grainger, R., Greaves, F., Guillemin, F., Guo, Y., Gupta, R., Gupta, V., Gutierrez, R., Haile, D., Hailu, A., Hailu, G., Halasa, Y., Hamadeh, R., Hamidi, S., Hammami, M., Hancock, J., Handal, A., Hankey, G., Hao, Y., Harb, H., Harikrishnan, S., Maria Haro, J., Havmoeller, R., Hay, R., Beatriz Heredia-Pi, I., Heydarpour, P., Hoek, H., Horino, M., Horita, N., Hosgood, H., Hoy, D., Htet, A., Huang, H., Huang, J., Huynh, C., Iannarone, M., Iburg, K., Innos, K., Inoue, M., Iyer, V., Jacobsen, K., Jahanmehr, N., Jakovljevic, M., Javanbakht, M., Jayatilleke, A., Jee, S., Jeemon, P., Jensen, P., Jiang, Y., Jibat, T., Jimenez-Corona, A., Jin, Y., Jonas, J., Kabir, Z., Kalkonde, Y., Kamal, R., Kan, H., Karch, A., Karema, C., Karimkhani, C., Kasaeian, A., Kaul, A., Kawakami, N., Keiyoro, P., Kemp, A., Keren, A., Kesavachandran, C., Khader, Y., Khaiff, A., Khaiff, E., Khang, Y., Khera, S., Khoja, T., Khubchandani, J., Kieling, C., Kim, P., Kim, C., Kim, D., Kim, Y., Kissoon, N., Knibbs, L., Knudsen, A., Kokubo, Y., Kolte, D., Kopec, J., Kosen, S., Kotsakis, G., Koul, P., Koyanagi, A., Kravchenko, M., Defo, B., Bicer, B., Kudom, A., Kuipers, E., Kumar, G., Kutz, M., Kwan, G., Lal, A., Lalloo, R., Lallukka, T., Lam, H., Lam, J., Langan, S., Larsson, A., Lavados, P., Leasher, J., Leigh, J., Leung, R., Levi, M., Li, Y., Liang, J., Liu, S., Liu, Y., Lloyd, B., Lo, W., Logroscino, G., Looker, K., Lotufo, P., Lunevicius, R., Lyons, R., Mackay, M., Abd El Razek, M., Mahdavi, M., Majdan, M., Majeed, A., Malekzadeh, R., Marcenes, W., Margolis, D., Martinez-Raga, J., Masiye, F., Massano, J., McGarvey, S., McGrath, J., McKee, M., McMahon, B., Meaney, P., Mehari, A., Meija-Rodriguez, F., Mekonnen, A., Melaku, Y., Memiah, P., Memish, Z., Mendoza, W., Meretoja, A., Meretoja, T., Mhimbira, F., Miller, Ted, Mills, E., Mirarefin, M., Mitchell, P., Mock, C., Mohammadi, A., Mohammed, S., Monasta, L., Montanez Hernandez, J., Montico, M., Mooney, M., Moradi-Lakeh, M., Morawska, L., Mueller, U., Mullany, E., Mumford, J., Murdoch, M., Nachega, J., Nagel, G., Naheed, A., Naldi, L., Nangia, V., Newton, J., Ng, M., Ngalesoni, F., Quyen, L., Nisar, M., Nkamedjie Pete, P., Nona, J., Norheim, O., Norman, R., Norrving, B., Nunes, B., Ogbo, F., Oh, I., Ohkubo, T., Olivares, P., Olusanya, B., Olusanya, J., Ortiz, A., Osman, M., Ota, E., Mahesh, P., Park, E., Parsaeian, M., de Azeredo Passos, V., Paternina Caicedo, A., Patten, S., Patton, G., Pereira, D., Perez-Padilla, R., Perico, N., Pesudovs, K., Petzold, M., Phillips, M., Piel, F., Pillay, J., Pishgar, F., Plass, D., Platts-Mills, J., Polinder, S., Pond, C., Popova, S., Poulton, R., Pourmalek, F., Prabhakaran, D., Prasad, N., Qorbani, M., Rabiee, R., Radfar, A., Rafay, A., Rahimi, K., Rahimi-Movaghar, V., Rahman, M., Rahman, S., Rai, R., Rajsic, S., Ram, U., Rao, P., Refaat, A., Reitsma, M., Remuzzi, G., Resnikofff, S., Reynolds, A., Ribeiro, A., Rios Blancas, M., Rolm, H., Rojas-Rueda, D., Ronfani, L., Roshandel, G., Roth, G., Rothenbacher, D., Roy, A., Sagar, R., Sahathevan, R., Sanabria, J., Dolores Sanchez-Nino, M., Santos, I., Santos, J., Sarmiento-Suarez, R., Sartorius, B., Satpathy, M., Savic, M., Sawhney, M., Schaub, M., Schmidt, M., Schneider, I., Schottker, B., Schwebel, D., Scott, J., Seedat, S., Sepanlou, S., Servan-Mori, E., Shackelford, K., Shaheen, A., Shaikh, M., Sharma, R., Sharma, U., Shen, J., Shepard, D., Sheth, K., Shibuya, K., Shin, M., Shiri, R., Shiue, I., Shrime, M., Sigfusdottir, I., Silva, D., Alves Silveira, D., Singh, A., Singh, J., Singh, O., Singh, P., Sivonda, A., Skirbekk, V., Skogen, J., Sligar, A., Silwa, K., Soljak, M., Soreide, K., Soriano, J., Sposato, L., Sreeramareddy, C., Stathopoulou, V., Steel, N., Stein, D., Steiner, T., Steinke, S., Stovner, L., Stroumpoulis, K., Sunguya, B., Sur, P., Swaminathan, S., Sykes, B., Szoeke, C., Tabares-Seisdedos, R., Takala, J., Landon, N., Tanne, D., Tavakkoli, M., Taye, B., Taylor, H., Te Ao, B., Tedla, B., Terkawi, A., Thomson, A., Thorne-Lyman, A., Thrift, A., Thurston, G., Tobe-Gai, R., Tonelli, M., Topor-Madry, R., Topouzis, F., Tran, B., Dimbuene, Z., Tsilimbaris, M., Tura, A., Tuzcu, E., Tyrovolas, S., Ukwaja, K., Undurraga, E., Uneke, C., Uthman, O., van Gool, C., Varakin, Y., Vasankari, T., Venketasubramanian, N., Verma, R., Violante, F., Vladimirov, S., Vlassov, V., Vollset, S., Wagner, G., Waller, S., Wang, L., Watkins, D., Weichenthal, S., Weiderpass, E., Weintraub, R., Werdecker, A., Westerman, R., White, R., Williams, H., Wiysonge, C., Wolfe, C., Won, S., Woodbrook, R., Wubshet, M., Xavier, D., Xu, G., Yadav, A., Yan, L., Yano, Y., Yaseri, M., Ye, P., Yebyo, H., Yip, P., Yonemoto, N., Yoon, S., Younis, M., Yu, C., Zaidi, Z., Zaki, M., Zeeb, H., Zhou, M., Zodpey, S., Zuhlke, L., and Murray, C.

Abstract

© 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY licenseBackground Non-fatal outcomes of disease and injury increasingly detract from the ability of the world's population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes affecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015. Methods We estimated incidence and prevalence by age, sex, cause, year, and geography with a wide range of updated and standardised analytical procedures. Improvements from GBD 2013 included the addition of new data sources, updates to literature reviews for 85 causes, and the identification and inclusion of additional studies published up to November, 2015, to expand the database used for estimation of non-fatal outcomes to 60?900 unique data sources. Prevalence and incidence by cause and sequelae were determined with DisMod-MR 2.1, an improved version of the DisMod-MR Bayesian meta-regression tool first developed for GBD 2010 and GBD 2013. For some causes, we used alternative modelling strategies where the complexity of the disease was not suited to DisMod-MR 2.1 or where incidence and prevalence needed to be determined from other data. For GBD 2015 we created a summary indicator that combines measures of income per capita, educational attainment, and fertility (the Socio-demographic Index [SDI]) and used it to compare observed patterns of health loss to the expected pattern for countries or locations with similar SDI scores. Findings We generated 9·3 billion estimates from the various combinations of prevalence, incidence, and YLDs for causes, sequelae, and impairments by age, sex, geography, and year.

Published
2016

123. Baseline trabecular bone and its relation to incident radiographic knee osteoarthritis and increase in joint space narrowing score: directional fractal signature analysis in the MOST study

Author

Podsiadlo, P., Nevitt, M., Wolski, Marcin, Stachowiak, G., Lynch, J., Tolstykh, I., Felson, D., Segal, N., Lewis, C., Englund, M., Podsiadlo, P., Nevitt, M., Wolski, Marcin, Stachowiak, G., Lynch, J., Tolstykh, I., Felson, D., Segal, N., Lewis, C., and Englund, M.

Abstract

Purpose: To explore the association of baseline trabecular bone structure with incident tibiofemoral (TF) osteoarthritis (OA) and with increase in joint space narrowing (JSN) score. Methods: The Multicenter Osteoarthritis Study (MOST) includes subjects with or at risk for knee OA. Knee radiographs were scored for Kellgren–Lawrence (KL) grade and JSN at baseline, 30, 60 and 84 months. Knees (KL = 1) at baseline were assessed for incident OA (KL = 2) and increases in JSN score. For each knee image at baseline, a variance orientation transform method (VOT) was applied to subchondral tibial bone regions of medial and lateral compartments. Seventeen fractal parameters were calculated per region. Associations of each parameter with OA incidence and with medial and lateral JSN increases were explored using logistic regression. Analyses were stratified by digitized film (DF) vs computer radiography (CR) and adjusted for confounders. Results: Of 894 knees with CR and 1158 knees with DF, 195 (22%) and 303 (26%) developed incident OA. Higher medial bone roughness was associated with increased odds of OA incidence at 60 and 84 months and also, medial and lateral JSN increases (primarily vertical). Lower medial and lateral anisotropy was associated with increased odds of medial and lateral JSN increase. Compared to DF, CR had more associations and also, similar results at overlapping scales. Conclusion: Baseline trabecular bone texture was associated with incident radiographic OA and increase of JSN scores independently of risk factors for knee OA. Higher roughness and lower anisotropy were associated with increased odds for radiographic OA change.

Published
2016

124. Genome Scan for Hand Osteoarthritis: The Framingham Study

Author

Demissie, S., Cupples, L.A., Myers, R.H., Aliabadi, P., and Felson, D.

Subjects
Framingham, Massachusetts -- Health aspects, Osteoarthritis -- Genetic aspects, Genetic disorders -- Research, Biological sciences
Published
2001

128. Measuring the variation between self-reported osteoarthritis pain assessments

Author

Leyland, K.M., primary, Gates, L.S., additional, Nevitt, M., additional, Felson, D., additional, Ambrose, K., additional, Bierma-Zeinstra, S.M., additional, Conaghan, P.G., additional, Engebretsen, L., additional, Hochberg, M., additional, Hunter, D.J., additional, Jones, G., additional, Jordan, J.M., additional, Judge, A., additional, Lohmander, S., additional, Roos, E.M., additional, Sanchez-Santos, M.T., additional, Sheard, S., additional, Yoshimura, N., additional, van Meurs, J.J., additional, Batt, M.E., additional, Newton, J., additional, Cooper, C., additional, and Arden, N.K., additional

Published
2016
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131. Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region

Author

Peters, M.J., Broer, L., Willemen, H.L.D.M., Eiriksdottir, G., Hocking, L.J., Holliday, K.L., Horan, M.A., Meulenbelt, I., Neogi, T., Popham, M., Schmidt, C.O., Soni, A., Valdes, A.M., Amin, N., Dennison, E.M., Eijkelkamp, N., Harris, T.B., Hart, D.J., Hofman, A., Huygen, F.J.P.M., Jameson, K.A., Jones, G.T., Launer, L.J., Kerkhof, H.J.M., Kruijf, M. de, McBeth, J., Kloppenburg, M., Ollier, W.E., Oostra, B., Payton, A., Rivadeneira, F., Smith, B.H., Smith, A.V., Stolk, L., Teumer, A., Thomson, W., Uitterlinden, A.G., Wang, K., Wingerden, S.H. van, Arden, N.K., Cooper, C., Felson, D., Gudnason, V., Macfarlane, G.J., Pendleton, N., Slagboom, P.E., Spector, T.D., Volzke, H., Kavelaars, A., Duijn, C.M. van, Williams, F.M.K., and Meurs, J.B.J. van

Published
2013

132. Use of Diagnostic Performance of Clinical Examination Measures and Pain Presentation to Identify Patellofemoral Joint Osteoarthritis.

Author

Stefanik, J. J., Duncan, R., Felson, D. T., and Peat, G.

Subjects
OSTEOARTHRITIS diagnosis, COMPARATIVE studies, DIFFERENTIAL diagnosis, KINEMATICS, KNEE, KNEE diseases, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, OSTEOARTHRITIS, RESEARCH, SOUND, WALKING, EVALUATION research, PAIN measurement, PREDICTIVE tests, PLICA syndrome, SEVERITY of illness index, JOINT pain, DIAGNOSIS
Abstract

Objective: To assess the diagnostic performance of a comprehensive set of tests and measures to discriminate patellofemoral (PF) from tibiofemoral (TF) osteoarthritis (OA).Methods: The Clinical Assessment of the Knee Study is a study of knee pain in the general population. The presence of PF crepitus and pain with PF compression were assessed. Anterior knee pain was determined using a knee pain map. Pain with climbing/descending stairs and walking on level ground were assessed with the Western Ontario and McMaster Universities Osteoarthritis Index. Radiographs were used to define the compartment(s) of the knee affected by OA (no OA, isolated/predominant PF joint OA, and isolated/predominant TF joint OA). In knees with mixed OA, knees with more severe PF joint OA were included in the isolated/predominant PF group (the same was done for TF joint OA). We determined the sensitivity, specificity, positive predictive value (PPV), negative predictive value, and positive likelihood ratio (LR+) for each test and measure individually, and the combination of these measures, in distinguishing knees with PF joint OA from knees with TF joint OA or no OA.Results: There were 745 knees included in the study. No measure had high sensitivity and specificity. Pain with climbing/descending stairs had the greatest sensitivity (90%) but poor specificity (15%). The combination of definite crepitus with no pain on walking had the greatest specificity (96%), PPV (53%), and LR+ (1.8), but poor sensitivity (7%).Conclusion: Typical clinical examination findings and knee pain patterns commonly thought to represent underlying PF joint pathology do not discriminate knees with PF joint OA from knees without OA or TF joint OA. [ABSTRACT FROM AUTHOR]

Published
2018
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133. Individual MRI and radiographic features of knee OA in subjects with unilateral knee pain: Health ABC study

Author

Javaid, MK, Kiran, A, Guermazi, A, Kwoh, K, Zaim, S, Carbone, L, Harris, T., McCulloch, C.E., Arden, NK, Lane, NE, Felson, D, and Nevitt, M

Subjects
musculoskeletal diseases, Cartilage, Articular, Male, Aging, Knee Joint, Pain, Osteoarthritis, Knee, musculoskeletal system, Magnetic Resonance Imaging, Severity of Illness Index, Article, respiratory tract diseases, Radiography, Body Composition, Humans, Female, Knee, human activities, Aged, Pain Measurement
Abstract

Strong associations between radiographic features of knee osteoarthritis (OA) and pain have been demonstrated in persons with unilateral knee symptoms. This study was undertaken to compare radiographic and magnetic resonance imaging (MRI) features of knee OA and assess their ability to discriminate between painful and nonpainful knees in persons with unilateral symptoms.The study population included 283 individuals ages 70-79 years with unilateral knee pain who were enrolled in the Health, Aging, and Body Composition Study, a study of weight-related diseases and mobility. Radiographs of both knees were read for Kellgren/Lawrence (K/L) grade and individual radiographic features, and 1.5T MRIs were assessed using the Whole-Organ Magnetic Resonance Imaging Score. The association between structural features and pain was assessed using a within-person case-control design and conditional logistic regression. Receiver operating characteristic (ROC) analysis was then used to test the discriminatory performance of structural features.In conditional logistic analyses, knee pain was significantly associated with both radiographic features (any joint space narrowing grade ≥ 1) (odds ratio 3.20 [95% confidence interval 1.79-5.71]) and MRI features (any cartilage defect scored ≥ 2) (odds ratio 3.67 [95% confidence interval 1.49-9.04]). However, in most subjects, MRI revealed osteophytes and cartilage and bone marrow lesions in both knees, and using ROC analysis, no individual structural feature discriminated well between painful and nonpainful knees. The best-performing MRI feature (synovitis/effusion) was not significantly more informative than K/L grade ≥ 2 (P = 0.42).In persons with unilateral knee pain, MRI and radiographic features were associated with knee pain, confirming that structural abnormalities in the knee have an important role in the etiology of pain. However, no single MRI or radiographic finding performed well in discriminating between painful and nonpainful knees. Further work is needed to examine how structural and nonstructural factors influence knee pain.

Published
2012

134. Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region

Author

Peters, Marjolein, Broer, Linda, Willemen, HLDM, Eiriksdottir, G, Hocking, LJ, Holliday, KL, Horan, MA, Meulenbelt, I, Neogi, T, Popham, M, Schmidt, CO, Soni, A, Valdes, AM, Amin, Najaf, Dennison, EM, Eijkelkamp, N, Harris, TB, Hart, DJ, Hofman, Bert, Huygen, Frank, Jameson, KA, Jones, GT, Launer, LJ (Lenore), Kerkhof, HJM, Kruijf, Marjolein, McBeth, J, Kloppenburg, M, Ollier, WE, Oostra, Ben, Payton, A, Rivadeneira, Fernando, Smith, BH, Smith, AV, Stolk, Lisette, Teumer, A, Thomson, W, Uitterlinden, André, Wang, K, Wingerden, Sophie, Arden, NK, Cooper, C, Felson, D, Gudnason, V, Macfarlane, GJ, Pendleton, N, Slagboom, PE (Eline), Spector, TD, Volzke, H, Kavelaars, A, Duijn, Cornelia, Williams, FMK, van Meurs, Joyce, Internal Medicine, Epidemiology, Anesthesiology, and Clinical Genetics

Subjects
Genotype, Epidemiology, Fibromyalgis/Pain Syndromes, Polymorphism, Single Nucleotide, Disease Models, Animal, Mice, Gene Polymorphism, Animals, Chromosomes, Human, Pair 5, Humans, Female, Genetic Predisposition to Disease, Chronic Pain, Basic and Translational Research, Genome-Wide Association Study
Abstract

BACKGROUND AND OBJECTIVES: Chronic widespread pain (CWP) is a common disorder affecting ∼10% of the general population and has an estimated heritability of 48-52%. In the first large-scale genome-wide association study (GWAS) meta-analysis, we aimed to identify common genetic variants associated with CWP. METHODS: We conducted a GWAS meta-analysis in 1308 female CWP cases and 5791 controls of European descent, and replicated the effects of the genetic variants with suggestive evidence for association in 1480 CWP cases and 7989 controls. Subsequently, we studied gene expression levels of the nearest genes in two chronic inflammatory pain mouse models, and examined 92 genetic variants previously described associated with pain. RESULTS: The minor C-allele of rs13361160 on chromosome 5p15.2, located upstream of chaperonin-containing-TCP1-complex-5 gene (CCT5) and downstream of FAM173B, was found to be associated with a 30% higher risk of CWP (minor allele frequency=43%; OR=1.30, 95% CI 1.19 to 1.42, p=1.2×10(-8)). Combined with the replication, we observed a slightly attenuated OR of 1.17 (95% CI 1.10 to 1.24, p=4.7×10(-7)) with moderate heterogeneity (I2=28.4%). However, in a sensitivity analysis that only allowed studies with joint-specific pain, the combined association was genome-wide significant (OR=1.23, 95% CI 1.14 to 1.32, p=3.4×10(-8), I2=0%). Expression levels of Cct5 and Fam173b in mice with inflammatory pain were higher in the lumbar spinal cord, not in the lumbar dorsal root ganglions, compared to mice without pain. None of the 92 genetic variants previously described were significantly associated with pain (p>7.7×10(-4)). CONCLUSIONS: We identified a common genetic variant on chromosome 5p15.2 associated with joint-specific CWP in humans. This work suggests that CCT5 and FAM173B are promising targets in the regulation of pain.

Published
2012

135. COMMON VARIANTS IN SKELETAL DYSPLASIA GENES ARE ASSOCIATED WITH OSTEOARTHRITIS

Author

Kerkhof, H, Panagiotou, O, Irving, M, Esko, T, Meulenbelt, I, Panoutsopoulou, K, Styrkarsdottir, U, Zhu, Y, Cupples, A, Felson, D, Kloppenburg, M, Arden, N, Albert, H, Slagboom, E, Frank, L, Metspalu, A, Ioannidis, J, Jonsdottir, I, Stefansson, K, Spector, T, Uitterlinden, A, Zeggini, E, Valdes, A, Evangelou, V, van Meurs, J, and Consortium, A

Published
2011

136. Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22

Author

Evangelou, E., Valdes, A. M., Kerkhof, H. J. M., Styrkarsdottir, U., Zhu, Y. Y., Meulenbelt, I., Lories, R. J., Karassa, F. B., Tylzanowski, P., Bos, S. D., Akune, T., Arden, N. K., Carr, A., Chapman, K., Cupples, L. A., Dai, J., Deloukas, P., Doherty, M., Doherty, S., Engstrom, G., Gonzalez, A., Halldorsson, B. V., Hammond, C. L., Hart, D. J., Helgadottir, H., Hofman, A., Ikegawa, S., Ingvarsson, T., Jiang, Q., Jonsson, H., Kaprio, J., Kawaguchi, H., Kisand, K., Kloppenburg, M., Kujala, U. M., Lohmander, L. S., Loughlin, J., Luyten, F. P., Mabuchi, A., McCaskie, A., Nakajima, M., Nilsson, P. M., Nishida, N., Ollier, W. E. R., Panoutsopoulou, K., van de Putte, T., Ralston, S. H., Rivadeneira, F., Saarela, J., Schulte-Merker, S., Shi, D. Q., Slagboom, P. E., Sudo, A., Tamm, A., Thorleifsson, G., Thorsteinsdottir, U., Tsezou, A., Wallis, G. A., Wilkinson, J. M., Yoshimura, N., Zeggini, E., Zhai, G. J., Zhang, F., Jonsdottir, I., Uitterlinden, A. G., Felson, D. T., van Meurs, J. B., Stefansson, K., Ioannidis, J. P. A., Spector, T. D., ArcOGEN Consortium, and Translation Res Europe Appl

Subjects
obesity, hip, classification, joint, gdf5, cohorts, body-mass, heterogeneity, risk-factors, frzb
Abstract

Objectives Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. Methods A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. Results With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p = 9.2 x 10(-9)), thereby confirming its role as a susceptibility locus for OA. Conclusion The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment. Ann Rheum Dis

Published
2011

138. ACR Hybrid Analysis of Certolizumab Pegol Plus Methotrexate in Patients With Active Rheumatoid Arthritis: Data From the RAPID 1 Trial

Author

van Vollenhoven, R.F., Felson, D., Strand, V., Weinblatt, M.E., Luijtens, K., and Keystone, E. C.

Subjects
Adult, Male, Antibodies, Monoclonal, Humanized, Article, United States, Polyethylene Glycols, Arthritis, Rheumatoid, Immunoglobulin Fab Fragments, Methotrexate, Rheumatology, Certolizumab Pegol, Humans, Drug Therapy, Combination, Female, Societies, Medical
Abstract

The American College of Rheumatology (ACR) hybrid (a modified mean percent response to treatment) was officially recommended by the ACR as a revision to 20%, 50%, and 70% response criteria (ACR20/50/70) scores, but has not been tested in clinical trials. We performed a post hoc analysis of a phase III study of certolizumab pegol (Rheumatoid Arthritis Prevention of Structural Damage 1 [RAPID 1]) using the ACR hybrid.Patients with active rheumatoid arthritis were randomized to certolizumab pegol (200 mg or 400 mg every other week) plus methotrexate or placebo plus methotrexate. ACR hybrid scores were compared with ACR20/50/70 outcomes.Differences between active treatment and placebo were significant throughout the study using the ACR20 and ACR hybrid outcomes. In the certolizumab pegol 200 mg group, the median ACR hybrid score at week 52 (last observation carried forward) was 49.99. A total of 258 (65.8%) of 392 and 172 (43.9%) of 392 patients had ACR20 and ACR50 responses, respectively. An additional 55 patients (14.0%) and 59 patients (15.1%) had mean improvements in ACR core measures of ≥ 20% and ≥ 50%, respectively, and therefore had positive ACR hybrid scores, despite lacking ACR20 and ACR50 responses, respectively. In the placebo group, median ACR hybrid scores were10 at most time points; unlike other measures, the ACR hybrid measure indicated worsening scores for many patients.ACR hybrid analysis had greater sensitivity than traditional ACR20/50/70 criteria, demonstrating improvements in ACR20 nonresponders treated with certolizumab pegol. Negligible benefit was observed with placebo using ACR hybrid analysis.

Published
2011

139. Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: the TREAT-OA consortium

Author

Gordon, A, Harilainen, A, Hart, D J, Hauksson, V B, Heliovaara, M, Hofman, A, Ikegawa, S, Ingvarsson, T, Jiang, Q, Kerkhof HJ, Meulenbelt, I, Akune, T, Arden, N K, Aromaa, A, Bierma-Zeinstra, S M A, Carr, A, Cooper, C, Dai, J, Doherty, M, Doherty, S A, Felson, D, González Martínez-Pedrayo, Antonio, Jonsson, H, Jonsdottir, I, Kawaguchi, H, Kloppenburg, M, Kujala, U M, Lane, N E, Leino-Arjas, P, Lohmander, L S, Luyten, F P, Malizos, K N, Nakajima, M, Nevitt, M C, Pols, H A P, Rivadeneira, F, Shi, D, Slagboom, E, Spector, T D, Stefansson, K, Sudo, A, Tamm, A, Tamm, A E, Tsezou, A, Uchida, A, Uitterlinden, A G, Wilkinson, J M, Yoshimura, N, Valdes, A M, and van Meurs, J B J

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 (RSI)) and testing those for association with gender, age and body mass index using one-way ANOVA. For ROA, we standardized the hip-, knee- and hand ROA definitions and calculated prevalence's of ROA before and after standardization in nine cohort studies. This procedure could only be performed in cohort studies and standardization of SOA definitions was not feasible at this moment. RESULTS: In this consortium, all studies with SOA phenotypes (knee, hip and hand) used a different definition and/or assessment of OA status. For knee-, hip- and hand ROA five, four and seven different definitions were used, respectively. Different hip ROA definitions do lead to different association results. For example, we showed in the RSI that hip OA defined as "at least definite joint space narrowing (JSN) and one definite osteophyte" was not associated with gender (P =0.22), but defined as "at least one definite osteophyte" was significantly associated with gender (P=3x10(-9)). Therefore, a standardization process was undertaken for ROA definitions. Before standardization a wide range of ROA prevalence's was observed in the nine cohorts studied. After standardization the range in prevalence of knee- and hip ROA was small. CONCLUSION: Phenotype definitions influence the prevalence of OA and association with clinical variables. ROA phenotypes within the TREAT-OA consortium were standardized to reduce heterogeneity and improve power in future genetics studies.

Published
2011

140. Minimal clinically important difference module: summary, recommendations, and research agenda

Author

Wells, G., Anderson, J., Beaton, D., Bellamy, N., Boers, M., Bombardier, C., Breedveld, F., Carr, A., Cranney, A., Dougados, M., Felson, D., Kirwan, J., Schiff, M., Shea, B., Simon, L., Smolen, J., Strand, V., Tugwell, P., Riel, P., and Vivian Welch

Subjects
Pathogenese en behandeling [Chronische arthritis], Pathogenesis and treatment [Chronic arthritis]
Abstract

Item does not contain fulltext

Published
2001

141. THE arcOGEN CONSORTIUM: STAGE 1 OF A GENOME-WIDE ASSOCIATION SCAN FOR OSTEOARTHRITIS

Author

Panoutsopoulou, K., Southam, L., Rayner, W., Zhai, G., Beazley, C., Arden, N., Carr, A., Chapman, K., Deloukas, P., Doherty, M., McCaskie, A., Olher, W., Ralston, S., Spector, T., Valdes, A., Wallis, G., Wilkinson, M., Arden, E., Battley, K., Blackburn, H., Blanco, F., Bumpstead, S., Cupples, A., Day-Williams, A., Dixon, K., Dohertys, S., Elliott, K., Evangelou, E., Felson, D., Gomez-Reino, J., Gonzalez, A., Gordon, A., Gwilliam, R., Hofman, A., Hunt, S., Ioannidis, J., Jonsdottir, I., Keen, R., Kerkhof, H., Kloppenburg, M., Koller, N., Lakenberg, N., Lane, N., Lee, A., Meulenbelt, I., Nevitt, M., O'Neill, F., Parimi, N., Potter, S., Rego-Perez, I., Riancho, J., Sherburn, K., Slagboom, E., Styrkarsdottir, U., Sumillera, M., Swift, D., Tsezou, A., Uitterlinden, A., Meurs, J. van, Watkins, B., Wheeler, M., Mitchelle, S., Zhu, Y., Zmuda, J., Zeggini, E., Loughlin, J., and ArcOGEN Consortium

Abstract

Osteoarthritis and Cartilage

Published
2010

142. 361 RECOMMENDATIONS FOR STANDARDIZATION AND PHENOTYPE DEFINITIONS IN GENETIC STUDIES OF OSTEOARTHRITIS: THE TREAT-OA CONSORTIUM

Author

Kerkhof, H.J., Meulenbelt, I., Arden, N., Cooper, C., Doherty, M., Felson, D., Gonzalez, A., Ikegawa, S., Jiang, Q., Jonsdottir, I., Kujala, U., Lane, N., Leino-Arjas, P., Lohmander, S., Luyten, F., Nevitt, M., Slagboom, E., Spector, T., Stefansson, K., Tamm, A., Tsezou, A., Wilkinson, J., Yoshimura, N., Valdes, A., and van Meurs, J.

Subjects
Rheumatology, Biomedical Engineering, Orthopedics and Sports Medicine
Published
2010
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