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2. Clinical and molecular associations with outcomes at two years after acute knee injury: a longitudinal study in the Knee Injury Cohort at the Kennedy (KICK)

Author

Garriga, C, Goff, M, Paterson, E, Hrusecka, R, Hamid, B, Alderson, J, Leyland, K, Honeyfield, L, Greenshields, L, Satchithananda, K, Lim, A, Arden, NK, Judge, A, Williams, A, Vincent, TL, and Watt, FE

Subjects
MODEL, Science & Technology, SYNOVIAL-FLUID, Rheumatology, RUPTURE, MARKERS, CARTILAGE, MURINE OSTEOARTHRITIS, ARTHRITIS, Life Sciences & Biomedicine, ANTERIOR CRUCIATE LIGAMENT, GENE-EXPRESSION, INFLAMMATORY CYTOKINES
Abstract

Background: Joint Injury is a major risk factor for osteoarthritis (OA) and an opportunity to prospectively examine its early processes. We investigated whether predefined baseline factors including demographic, clinical factors and protein analytes in knee synovial fluid (sf/SF) and in plasma/serum were associated with clinically relevant outcomes at two years after knee injury. Methods: This was a longitudinal cohort study (REC10/H0805/39;NCT02667756) with 150 individuals aged 16-50 recruited within 8 weeks of a clinically significant acute knee injury (effusion and structural injury on MRI), which was typically being treated surgically. Twelve SF and four plasma/serum biomarkers were measured by immunoassay as the exposures of interest. Primary outcome was “Knee Injury and Osteoarthritis Outcome Score” (KOOS)4. X-ray/3T-MRI knees were taken at baseline and two years. Linear and logistic regression models adjusting for predefined covariates assessed associations with 2year KOOS4 and secondary endpoints including new symptomatic (regular knee symptoms), tibio-femoral radiographic OA (TFROA, Kellgren Lawrence Grade 2 or more on an X-ray) respectively. Findings: Baseline KOOS4, medium/large knee effusion and moderate/severe SF blood staining and their interaction significantly predicted 2year KOOS4 (Coeff. -20·5 [95% confidence interval -34·8, -6·18]. Of the predefined markers, only sfMCP-1 and sfIL-6 -showed independent associations with 2year KOOS4 (-0.015[0.027,-0.004] and -0.0005[-0.0009,-0.0001] per change in 1 pg/ml units respectively), jointly with the interaction of effusion and blood staining accounting for 39% of outcome variability. New TFROA at two years was associated with baseline meniscal tear (OR5·7[1·25,25·92]). 13/22(59·1%) with new TFROA had no NHANES frequent knee symptoms. Only 3month medium/large effusion was associated with new symptomatic TFROA at two years (OR14·0[1·86,105·27]). No sf/blood markers were associated with predefined structural/symptomatic outcomes. Interpretation: Effusion-haemarthrosis was strongly associated with symptomatic outcomes after acute knee injury. The SF molecular protein response to acute knee injury (best represented by MCP-1 and IL-6) was independently associated with symptomatic but not with structural outcomes, with the biomarkers overall playing a minor role relative to clinical predictors. The relationship between symptoms and structure after acute knee injury and their apparent dissociation early in this process needs to be better understood to make clinical progress.

Published
2021

6. Predictive factors for patient reported symptoms and radiographic structural change at 2 years after acute knee injury

Author

Garriga, C., primary, Goff, M., additional, Leyland, K., additional, Paterson, E., additional, Hrusecka, R., additional, Hamid, B., additional, Honeyfield, L., additional, Satchithananda, K., additional, Lim, A., additional, Arden, N.K., additional, Judge, A., additional, Williams, A., additional, Vincent, T.L., additional, and Watt, F.E., additional

Published
2020
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8. The prevalence of hand and wrist osteoarthritis in elite former cricket and rugby union players

Author

Jones, M, Davies, M, Shah, K, Kemp, S, Peirce, N, Leyland, K, Stokes, K, Judge, A, Newton, J, Furniss, D, and Arden, N

Subjects
Aging, Athlete, Epidemiology, Prevalence, Injury, human activities
Abstract

Objectives: This study aimed to determine the prevalence of hand and wrist osteoarthritis in former elite cricket and rugby union players, by sport and playing position, and to define the prevalence of severe hand injury, and its association with hand osteoarthritis.Design: Cross-sectionalMethods: Data from cross-sectional studies of former elite male cricket and rugby players were used to determine the prevalence of hand pain, physician-diagnosed osteoarthritis, and previous severe injury. Multivariable logistic regression was used to determine the association of previous injury with pain and osteoarthritis.Results: Data from 200 cricketers and 229 rugby players were available. Complete case analysis resulted in 127 cricketers and 140 rugby players. Hand pain was more prevalent amongst cricketers (19.7%) than rugby players (10.0%). The prevalence did not differ between cricket and rugby players for hand osteoarthritis (2.4% and 3.6%), wrist osteoarthritis (1.6% and 2.1%), or previous severe hand injury (36.2% and 31.4%). No significant association between previous hand injury and pain or osteoarthritis was identified in either sport. Conclusions: Former elite cricketers reported more hand pain than rugby players. No significant association was found between self-reported severe injury and hand osteoarthritis in either cohort, potentially indicating that risk factors aside from injury may be more prominent in the development of hand osteoarthritis.

Published
2019
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10. Novel Approach to Estimate Osteoarthritis Progression: Use of the Reliable Change Index in the Evaluation of Joint Space Loss

Author

Parsons, C.M., Judge, A., Leyland, K., Bruyere, O., Dop, F. Petit, Chapurlat, R., Reginster, J.Y., Edwards, M.H., Dennison, E.M., Riel, P.L.C.M. van, Cooper, C., Inskip, H., Parsons, C.M., Judge, A., Leyland, K., Bruyere, O., Dop, F. Petit, Chapurlat, R., Reginster, J.Y., Edwards, M.H., Dennison, E.M., Riel, P.L.C.M. van, Cooper, C., and Inskip, H.

Abstract

Contains fulltext : 202254.pdf (publisher's version ) (Closed access), OBJECTIVE: Osteoarthritis-related changes in joint space measurements over time are small and sensitive to measurement error. The Reliable Change Index (RCI) determines whether the magnitude of change observed in an individual can be attributed to true change. This study aimed to examine the RCI as a novel approach to estimating osteoarthritis progression. METHODS: Data were from 167 men and 392 women with knee osteoarthritis (diagnosed using the American College of Rheumatology criteria) randomized to the placebo arm of the 3-year Strontium Ranelate Efficacy in Knee Osteoarthritis trial (SEKOIA) and assessed annually. The RCI was used to determine whether the magnitude of change in joint space width (JSW) on radiographs between study years was likely to be true or due to measurement error. RESULTS: Between consecutive years, 57-69% of participants had an apparent decrease (change <0) in JSW, while 31-43% of participants had annual changes indicating improvement in JSW. The RCI identified JSW decreases in only 6.0% of patients between baseline and year 1, and in 4.5% of patients between the remaining study years. The apparent increases in JSW were almost eliminated between baseline and year 1, and between years 1 and 2 only 1.3% of patients had a significant increase, dropping to 0.9% between years 2 and 3. CONCLUSION: The RCI provides a method to identify change in JSW, removing many apparent changes that are likely to be due to measurement error. This method appears to be useful for assessing change in JSW from radiographs in clinical and research settings.

Published
2019

12. The association of knee osteoarthritis and premature mortality in the community: an international individual patient level meta-analysis in six prospective cohorts

Author

Leyland, K, Gates, L, Sanchez-Santos, M, Prieto-Alhambra, D, Judge, A, Collins, G, Cleveland, R, Felson, D, Jordan, J, Callahan, L, Nevitt, M, Hosnijeh, F, Van Meurs, J, Jones, G, Newton, J, Batt, M, Altman, D, Cooper, C, and Arden, N

Abstract

To combine individual participant data (IPD) from major international population-based cohorts, using harmonised OA data, to assess whether subjects with knee OA have an increased association with premature mortality.

Published
2018

14. The association between radiographic knee osteoarthritis and pain: an epidemiological analysis of a twenty-year community-based cohort

Author

Leyland, K, Arden, N, Javaid, M, Judge, A, Arden, N, Javaid, M, and Judge, A

Subjects
Musculoskeletal system--Diseases--Epidemiology
Abstract

Background: Knee osteoarthritis (OA) is one of the leading musculoskeletal burdens in the world, causing both structural damage and pain to the joint. Radiographs are the most common imaging method for diagnosing OA, however the relationship between radiographic changes (ROA) and symptoms is not well understood. This thesis will establish the natural history of twenty-year ROA, compare diagnostic methods of ROA assessment, evaluate the cross-sectional relationship between ROA and pain, and will determine the long-term predictive validity of features of ROA with future knee replacements (TKRs). Methods: Data from the Chingford women's study, a twenty-year prospective UK-based cohort was used for the analysis. Risk factors included atlas-based ROA scoring methods and quantitative joint space width (JSW), which were analysed against pain and TKR outcome measures. A novel method for assessing joint space on low-contrast x-rays was developed which had high reproducibility and validity. Results: The twenty-year natural history of ROA showed relatively low levels of annual incidence (3.8%), progression (3.6%), and worsening (4.5%), and emphasised the involvement of both medial and lateral osteophytes. Severe joint space narrowing (JSN) had the best construct validity with pain, while any size of lateral tibial osteophyte had good construct validity. Medial quantitative JSW had good construct validity, but no predictive validity with future TKRs. Lateral JSN and osteophytes had the best predictive validity for future TKR. Conclusion: This research demonstrates that radiographic scoring methods have strong construct and predictive validity with symptomatic knee OA. These results support the use of x-rays to identify early disease changes which indicate future joint failure.

Published
2016

15. Obesity and the relative risk of replacement surgery in knee osteoarthritis patients: A prospective cohort study

Author

Leyland, K, Judge, A, Diez-Perez, A, Carr, A, Cooper, C, Arden, N, Prieto-Alhambra, D, and Javaid, M

Abstract

Objective: It is unclear what the impact of obesity has on the progression of knee osteoarthritis (KOA), from diagnosis to knee replacement (KR) surgery. This research examines the relative risk of KR surgery in overweight/obese patients with newly diagnosed knee osteoarthritis in a community population. Methods: Subjects were selected from the SIDIAP database, which compiles comprehensive clinical information collected by healthcare professionals for 80% of the population of Catalonia, Spain (>5.5 million people). Patients newly diagnosed with KOA in primary care between 2006 and 2011 were included. KR was ascertained using ICD-9-CM codes from linked hospital admissions data. Multivariable Cox regression models were fitted for KR according to BMI, and were adjusted for relevant confounders. Population proportional attributable risk was calculated. Results: 105,189 participants were followed up for a median (inter-quartile range) of 2.6 (1.3-4.2) years. 7,512 (7.1%) patients underwent KR. Adjusted HRs for KR were: 1.41 (95% CI 1.27 to 1.57) for overweight, 1.97 (1.78 to 2.18) for obese I, 2.39 (2.15 to 2.67) for obese II, and 2.67 (2.34 to 3.04) for obese III compared to normal-weight. The effect of BMI on risk of KR was stronger amongst younger participants. The population attributable risk of obesity for KOA-related KR is 31.0%. Conclusion: Overweight and obese patients are at over 40% and 100% increased risk of KR surgery compared to normal-weight respectively. This association is even stronger in younger patients. Weight reduction strategies could potentially reduce the need for KR surgery by 31% amongst KOA patients. This article is protected by copyright. All rights reserved.

Published
2015

20. Basic Science * 208. Stem Cell Factor Expression is Increased in the Skin of Patients with Systemic Sclerosis and Promotes Proliferation and Migration of Fibroblasts in vitro

Author

Karrar, S., primary, Shiwen, X., additional, Nikotorowicz-Buniak, J., additional, Abraham, D. J., additional, Denton, C., additional, Stratton, R., additional, Bayley, R., additional, Kite, K. A., additional, Clay, E., additional, Smith, J. P., additional, Kitas, G. D., additional, Buckley, C., additional, Young, S. P., additional, Ye, L., additional, Zhang, L., additional, Goodall, J., additional, Gaston, H., additional, Xu, H., additional, Lutalo, P. M., additional, Zhao, Y., additional, Meng Choong, L., additional, Sangle, S., additional, Spencer, J., additional, D'Cruz, D., additional, Rysnik, O. J., additional, McHugh, K., additional, Bowness, P., additional, Rump-Goodrich, L., additional, Mattey, D., additional, Kehoe, O., additional, Middleton, J., additional, Cartwright, A., additional, Schmutz, C., additional, Askari, A., additional, Gardner, D. H., additional, Jeffery, L. E., additional, Raza, K., additional, Sansom, D. M., additional, Fitzpatrick, M., additional, Wallace, G., additional, Young, S., additional, Shaw, J., additional, Hatano, H., additional, Cauli, A., additional, Giles, J. L., additional, Mathieu, A., additional, Kollnberger, S., additional, Webster, S., additional, Ellis, L., additional, O'Brien, L. M., additional, Fitzmaurice, T. J., additional, Nazeer Moideen, A., additional, Evans, L., additional, Osgood, L., additional, Williams, A., additional, Jones, S., additional, Thomas, C., additional, O'Donnell, V., additional, Nowell, M., additional, Ouboussad, L., additional, Savic, S., additional, Dickie, L. J., additional, Hintze, J., additional, Wong, C. H., additional, Cook, G. P., additional, Buch, M., additional, Emery, P., additional, McDermott, M. F., additional, Hardcastle, S. A., additional, Gregson, C. L., additional, Deere, K., additional, Davey Smith, G., additional, Dieppe, P., additional, Tobias, J. H., additional, Dennison, E., additional, Edwards, M., additional, Bennett, J., additional, Coggon, D., additional, Palmer, K., additional, Cooper, C., additional, McWilliams, D., additional, Young, A., additional, Kiely, P. D., additional, Walsh, D., additional, Taylor, H. J., additional, Harding, I., additional, Hutchinson, J., additional, Nelson, I., additional, Blom, A., additional, Tobias, J., additional, Clark, E., additional, Parker, J., additional, Bukhari, M., additional, Jayakumar, K., additional, Kiely, P., additional, Diffin, J., additional, Lunt, M., additional, Marshall, T., additional, Chipping, J., additional, Symmons, D., additional, Verstappen, S., additional, Bluett, J., additional, Bowes, J., additional, Ho, P., additional, McHugh, N., additional, Buden, D., additional, Fitzgerald, O., additional, Barton, A., additional, Glossop, J. R., additional, Nixon, N. B., additional, Emes, R. D., additional, Dawes, P. T., additional, Farrell, W. E., additional, Mattey, D. L., additional, Scott, I. C., additional, Steer, S., additional, Seegobin, S., additional, Hinks, A. M., additional, Eyre, S., additional, Morgan, A., additional, Wilson, A. G., additional, Hocking, L., additional, Wordsworth, P., additional, Worthington, J., additional, Cope, A., additional, Lewis, C. M., additional, Guerra, S., additional, Ahmed, B. A., additional, Abraham, D., additional, Fonseca, C., additional, Robinson, J., additional, Taylor, J., additional, Haroon Rashid, L., additional, Flynn, E., additional, Isaacs, J., additional, Barrett, J. H., additional, Kingston, B., additional, Ahmed, M., additional, Kirwan, J. R., additional, Marshall, R., additional, Chapman, K., additional, Pearson, R., additional, Heycock, C., additional, Kelly, C., additional, Rynne, M., additional, Saravanan, V., additional, Hamilton, J., additional, Saeed, A., additional, Coughlan, R., additional, Carey, J. J., additional, Farah, Z., additional, Matthews, W., additional, Bell, C., additional, Petford, S., additional, Tibbetts, L.-M., additional, Douglas, K. M. J., additional, Holden, W., additional, Ledingham, J., additional, Fletcher, M., additional, Winfield, R., additional, Price, Z., additional, Mackay, K., additional, Dixon, C., additional, Oppong, R., additional, Jowett, S., additional, Nicholls, E., additional, Whitehurst, D., additional, Hill, S., additional, Hammond, A., additional, Hay, E., additional, Dziedzic, K., additional, Righetti, C., additional, Lebmeier, M., additional, Manning, V. L., additional, Hurley, M., additional, Scott, D. L., additional, Choy, E., additional, Bearne, L., additional, Nikiphorou, E., additional, Morris, S., additional, James, D., additional, Wong, E. C., additional, Long, J., additional, Fletcher, A., additional, Holmes, S., additional, Hockey, P., additional, Abbas, M., additional, Chattopadhyay, C., additional, Flint, J., additional, Gayed, M., additional, Schreiber, K., additional, Arthanari, S., additional, Nisar, M., additional, Khamashta, M., additional, Gordon, C., additional, Giles, I., additional, Robson, J., additional, Kiran, A., additional, Maskell, J., additional, Arden, N., additional, Hutchings, A., additional, Emin, A., additional, Culliford, D., additional, Dasgupta, B., additional, Hamilton, W., additional, Luqmani, R., additional, Jethwa, H., additional, Rowczenio, D., additional, Trojer, H., additional, Russell, T., additional, Loeffler, J., additional, Hawkins, P., additional, Lachmann, H., additional, Verma, I., additional, Syngle, A., additional, Krishan, P., additional, Garg, N., additional, McGowan, S. P., additional, Gerrard, D. T., additional, Chinoy, H., additional, Ollier, W. E., additional, Cooper, R. G., additional, Lamb, J. A., additional, Taborda, L., additional, Correia Azevedo, P., additional, Isenberg, D., additional, Leyland, K. M., additional, Judge, A., additional, Hunter, D., additional, Hart, D., additional, Javaid, M. K., additional, Edwards, M. H., additional, Litwic, A. E., additional, Jameson, K. A., additional, Deeg, D., additional, Cushnaghan, J., additional, Aihie Sayer, A., additional, Jagannath, D., additional, Parsons, C., additional, Stoppiello, L., additional, Mapp, P., additional, Ashraf, S., additional, Wilson, D., additional, Hill, R., additional, Scammell, B., additional, Wenham, C., additional, Shore, P., additional, Hodgson, R., additional, Grainger, A., additional, Aaron, J., additional, Hordon, L., additional, Conaghan, P., additional, Bar-Ziv, Y., additional, Beer, Y., additional, Ran, Y., additional, Benedict, S., additional, Halperin, N., additional, Drexler, M., additional, Mor, A., additional, Segal, G., additional, Lahad, A., additional, Haim, A., additional, Rath, U., additional, Morgensteren, D. M., additional, Salai, M., additional, Elbaz, A., additional, Vasishta, V. G., additional, Derrett-Smith, E., additional, Hoyles, R., additional, Khan, K., additional, Ezeonyeji, A., additional, Takhar, G., additional, Ong, V., additional, Loughrey, L., additional, Bissell, L.-A., additional, Hensor, E., additional, Abignano, G., additional, Redmond, A., additional, Del Galdo, F., additional, Hall, F. C., additional, Malaviya, A., additional, Baker, S., additional, Furlong, A., additional, Mitchell, A., additional, Godfrey, A. L., additional, Ruddlesden, M., additional, Hadjinicolaou, A., additional, Hughes, M., additional, Moore, T., additional, O'Leary, N., additional, Tracey, A., additional, Ennis, H., additional, Dinsdale, G., additional, Roberts, C., additional, Herrick, A., additional, Denton, C. P., additional, Guillevin, L., additional, Hunsche, E., additional, Rosenberg, D., additional, Schwierin, B., additional, Scott, M., additional, Krieg, T., additional, Anderson, M., additional, Matucci-Cerinic, M., additional, Alade, R., additional, Xu, S., additional, Nihtyanova, S., additional, Clark, K. E., additional, Tam, F. W. K., additional, Unwin, R., additional, Stratton, R. J., additional, Schreiber, B., additional, Seng Edwin Lim, C., additional, Corsiero, E., additional, Sutcliffe, N., additional, Wardemann, H., additional, Pitzalis, C., additional, Bombardieri, M., additional, Tahir, H., additional, Donnelly, S., additional, Greenwood, M., additional, Smith, T. O., additional, Easton, V., additional, Bacon, H., additional, Jerman, E., additional, Armon, K., additional, Poland, F., additional, Macgregor, A., additional, van der Heijde, D., additional, Sieper, J., additional, Elewaut, D., additional, Pangan, A. L., additional, Nguyen, D., additional, Badenhorst, C., additional, Kirby, S., additional, White, D., additional, Harrison, A., additional, Garcia, J. A., additional, Stebbings, S., additional, MacKay, J. W., additional, Aboelmagd, S., additional, Gaffney, K., additional, Deodhar, A., additional, Braun, J., additional, Mack, M., additional, Hsu, B., additional, Gathany, T., additional, Han, C., additional, Inman, R. D., additional, Cooper-Moss, N., additional, Packham, J., additional, Strauss, V., additional, Freeston, J. E., additional, Coates, L., additional, Nam, J., additional, Moverley, A. R., additional, Helliwell, P., additional, Wakefield, R., additional, Mease, P., additional, Fleischmann, R., additional, Wollenhaupt, J., additional, Kielar, D., additional, Woltering, F., additional, Stach, C., additional, Hoepken, B., additional, Arledge, T., additional, Gladman, D., additional, Coteur, G., additional, Kavanaugh, A., additional, Purcaru, O., additional, McInnes, I., additional, Gottlieb, A. B., additional, Puig, L., additional, Rahman, P., additional, Ritchlin, C., additional, Li, S., additional, Wang, Y., additional, Mendelsohn, A., additional, Doyle, M., additional, Tillett, W., additional, Jadon, D., additional, Shaddick, G., additional, Cavill, C., additional, Robinson, G., additional, Sengupta, R., additional, Korendowych, E., additional, de Vries, C., additional, Thomas, R. C., additional, Shuto, T., additional, Busquets-Perez, N., additional, Marzo-Ortega, H., additional, McGonagle, D., additional, Richards, G., additional, Bingham, S., additional, John Hamlin, P., additional, Adshead, R., additional, Cambridge, S., additional, Suppiah, P., additional, Cullinan, M., additional, Nolan, A., additional, Thompson, W. M., additional, Mathieson, H. R., additional, Mackie, S. L., additional, Bryer, D., additional, Krutikov, M., additional, Gray, L., additional, Bruce, E., additional, Keat, A., additional, Innes, W., additional, Pandit, R., additional, Kay, L., additional, Lapshina, S., additional, Myasoutova, L., additional, Erdes, S., additional, Wallis, D., additional, Waldron, N., additional, Thorne, I., additional, Harris, C., additional, Vohra, K., additional, Khinchi, D., additional, Kaur, L., additional, Jones, A., additional, Harrison, N., additional, Harris, D., additional, Jones, T., additional, Rees, J., additional, Bennett, A., additional, Fazal, S., additional, Tugnet, N., additional, Barkham, N., additional, Basu, N., additional, McClean, A., additional, Harper, L., additional, Amft, E. N., additional, Dhaun, N., additional, Luqmani, R. A., additional, Little, M. A., additional, Jayne, D. R., additional, Flossmann, O., additional, McLaren, J., additional, Kumar, V., additional, Reid, D. M., additional, Macfarlane, G. J., additional, Jones, G., additional, Yates, M., additional, Watts, R. A., additional, Igali, L., additional, Mukhtyar, C., additional, Doll, H., additional, Yew, S., additional, Suppiah, R., additional, Hoglund, P., additional, Jayne, D., additional, Westman, K., additional, Win Maw, W., additional, Patil, P., additional, Williams, M., additional, Adizie, T., additional, Christidis, D., additional, Borg, F., additional, Robertson, A., additional, Croft, A. P., additional, Smith, S., additional, Carr, S., additional, Youssouf, S., additional, Salama, A., additional, Pusey, C., additional, and Morgan, M., additional

Published
2013
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23. Differences between race and sex in measures of hip morphology: a population-based comparative study.

Author

Edwards K, Leyland KM, Sanchez-Santos MT, Arden CP, Spector TD, Nelson AE, Jordan JM, Nevitt M, Hunter DJ, and Arden NK

Subjects
Acetabulum anatomy & histology, Black or African American, Aged, Asian People, Female, Femur Head anatomy & histology, Femur Neck anatomy & histology, Hip Joint anatomy & histology, Humans, Male, Middle Aged, Osteoarthritis, Hip epidemiology, Radiography, Sex Factors, White People, Acetabulum diagnostic imaging, Femur Head diagnostic imaging, Femur Neck diagnostic imaging, Hip Joint diagnostic imaging, Osteoarthritis, Hip ethnology
Abstract

Objective: This paper aims to (i) identify differences in measures of hip morphology between four racial groups using anteroposterior (AP) hip x-rays, and (ii) examine whether these differences vary by sex., Methods: 912 hip x-rays (456 individuals) from four racial groups (European Caucasians, American Caucasians, African Americans and Chinese) were obtained. Males and females (45-75 years) with no radiographic hip OA (Kellgren and Lawrence < Grade 2 or Croft < Grade 1) were included. Eleven features of hip joint morphology were analysed. Linear regression with generalised estimating equations (GEE) was used to determine race and sex differences in hip morphology. Post-hoc Bonferroni procedure was used to adjust for multiple comparisons., Results: The final analysis included 875 hips. Chinese hips showed significant differences for the majority of measures to other racial groups. Chinese were characterised by more shallow and narrow acetabular sockets, reduced femoral head coverage, smaller femoral head diameter, and a lesser angle of alignment between the femoral neck and shaft. Variation was found between other racial groups, but with few statistically significant differences. The average of lateral centre edge angle, minimum neck width and neck length differed between race and sex (p-value for interaction < 0.05)., Conclusions: Significant differences were found in measures of morphology between Chinese hips compared to African Americans or Caucasian groups; these may explain variation in hip OA prevalence rates between these groups and the lower rate of hip OA in Chinese. Sex differences were also identified, which may further explain male-female prevalence differences for OA., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2020
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24. Novel Approach to Estimate Osteoarthritis Progression: Use of the Reliable Change Index in the Evaluation of Joint Space Loss.

Author

Parsons CM, Judge A, Leyland K, Bruyère O, Petit Dop F, Chapurlat R, Reginster JY, Edwards MH, Dennison EM, Cooper C, and Inskip H

Subjects
Aged, Female, Humans, Male, Middle Aged, Osteoarthritis, Knee drug therapy, Osteoarthritis, Knee epidemiology, Reproducibility of Results, Bone Density Conservation Agents therapeutic use, Disease Progression, Knee Joint diagnostic imaging, Osteoarthritis, Knee diagnostic imaging, Severity of Illness Index, Thiophenes therapeutic use
Abstract

Objective: Osteoarthritis-related changes in joint space measurements over time are small and sensitive to measurement error. The Reliable Change Index (RCI) determines whether the magnitude of change observed in an individual can be attributed to true change. This study aimed to examine the RCI as a novel approach to estimating osteoarthritis progression., Methods: Data were from 167 men and 392 women with knee osteoarthritis (diagnosed using the American College of Rheumatology criteria) randomized to the placebo arm of the 3-year Strontium Ranelate Efficacy in Knee Osteoarthritis trial (SEKOIA) and assessed annually. The RCI was used to determine whether the magnitude of change in joint space width (JSW) on radiographs between study years was likely to be true or due to measurement error., Results: Between consecutive years, 57-69% of participants had an apparent decrease (change <0) in JSW, while 31-43% of participants had annual changes indicating improvement in JSW. The RCI identified JSW decreases in only 6.0% of patients between baseline and year 1, and in 4.5% of patients between the remaining study years. The apparent increases in JSW were almost eliminated between baseline and year 1, and between years 1 and 2 only 1.3% of patients had a significant increase, dropping to 0.9% between years 2 and 3., Conclusion: The RCI provides a method to identify change in JSW, removing many apparent changes that are likely to be due to measurement error. This method appears to be useful for assessing change in JSW from radiographs in clinical and research settings., (© 2018, American College of Rheumatology.)

Published
2019
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25. Harmonising measures of knee and hip osteoarthritis in population-based cohort studies: an international study.

Author

Leyland KM, Gates LS, Nevitt M, Felson D, Bierma-Zeinstra SM, Conaghan PG, Engebretsen L, Hochberg M, Hunter DJ, Jones G, Jordan JM, Judge A, Lohmander LS, Roos EM, Sanchez-Santos MT, Yoshimura N, van Meurs JBJ, Batt ME, Newton J, Cooper C, and Arden NK

Subjects
Aged, Canada, Cohort Studies, Consensus, Disability Evaluation, Disease Progression, Female, Follow-Up Studies, Humans, Internationality, Magnetic Resonance Imaging methods, Male, Middle Aged, Osteoarthritis, Hip pathology, Osteoarthritis, Knee diagnostic imaging, Osteoarthritis, Knee pathology, Severity of Illness Index, Time Factors, Tomography, X-Ray Computed methods, Osteoarthritis, Hip diagnostic imaging, Osteoarthritis, Hip physiopathology, Osteoarthritis, Knee physiopathology, Pain Measurement, Range of Motion, Articular physiology
Abstract

Objective: Population-based osteoarthritis (OA) cohorts provide vital data on risk factors and outcomes of OA, however the methods to define OA vary between cohorts. We aimed to provide recommendations for combining knee and hip OA data in extant and future population cohort studies, in order to facilitate informative individual participant level analyses., Method: International OA experts met to make recommendations on: 1) defining OA by X-ray and/or pain; 2) compare The National Health and Nutrition Examination Survey (NHANES)-type OA pain questions; 3) the comparability of the Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) scale to NHANES-type OA pain questions; 4) the best radiographic scoring method; 5) the usefulness of other OA outcome measures. Key issues were explored using new analyses in two population-based OA cohorts (Multicenter Osteoarthritis Study; MOST and Osteoarthritis Initiative OAI)., Results: OA should be defined by both symptoms and radiographs, with symptoms alone as a secondary definition. Kellgren and Lawrence (K/L) grade ≥2 should be used to define radiographic OA (ROA). The variable wording of pain questions can result in varying prevalence between 41.0% and 75.4%, however questions where the time anchor is similar have high sensitivity and specificity (91.2% and 89.9% respectively). A threshold of 3 on a 0-20 scale (95% CI 2.1, 3.9) in the WOMAC pain subscale demonstrated equivalence with the preferred NHANES-type question., Conclusion: This research provides recommendations, based on expert agreement, for harmonising and combining OA data in existing and future population-based cohorts., (Copyright © 2018. Published by Elsevier Ltd.)

Published
2018
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26. A comparison of radiographic anatomic axis knee alignment measurements and cross-sectional associations with knee osteoarthritis.

Author

Goulston LM, Sanchez-Santos MT, D'Angelo S, Leyland KM, Hart DJ, Spector TD, Cooper C, Dennison EM, Hunter D, and Arden NK

Subjects
Adult, Aged, Anatomic Landmarks pathology, Bone Malalignment diagnostic imaging, Bone Malalignment pathology, Female, Humans, Knee Joint diagnostic imaging, Middle Aged, Osteoarthritis, Knee diagnostic imaging, Osteoarthritis, Knee pathology, Pain etiology, Prospective Studies, Radiographic Image Interpretation, Computer-Assisted methods, Radiography methods, Reproducibility of Results, Bone Malalignment complications, Knee Joint pathology, Osteoarthritis, Knee etiology
Abstract

Objective: Malalignment is associated with knee osteoarthritis (KOA), however, the optimal anatomic axis (AA) knee alignment measurement on a standard limb radiograph (SLR) is unknown. This study compares one-point (1P) and two-point (2P) AA methods using three knee joint centre locations and examines cross-sectional associations with symptomatic radiographic knee osteoarthritis (SRKOA), radiographic knee osteoarthritis (RKOA) and knee pain., Methods: AA alignment was measured six different ways using the KneeMorf software on 1058 SLRs from 584 women in the Chingford Study. Cross-sectional associations with principal outcome SRKOA combined with greatest reproducibility determined the optimal 1P and 2P AA method. Appropriate varus/neutral/valgus alignment categories were established using logistic regression with generalised estimating equation models fitted with restricted cubic spline function., Results: The tibial plateau centre displayed greatest reproducibility and associations with SRKOA. As mean 1P and 2P values differed by >2°, new alignment categories were generated for 1P: varus <178°, neutral 178-182°, valgus >182° and for 2P methods: varus <180°, neutral 180-185°, valgus >185°. Varus vs neutral alignment was associated with a near 2-fold increase in SRKOA and RKOA, and valgus vs neutral for RKOA using 2P method. Nonsignificant associations were seen for 1P method for SRKOA, RKOA and knee pain., Conclusions: AA alignment was associated with SRKOA and the tibial plateau centre had the strongest association. Differences in AA alignment when 1P vs 2P methods were compared indicated bespoke alignment categories were necessary. Further replication and validation with mechanical axis alignment comparison is required., (Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.)

Published
2016
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27. Measures of hip morphology are related to development of worsening radiographic hip osteoarthritis over 6 to 13 year follow-up: the Johnston County Osteoarthritis Project.

Author

Nelson AE, Stiller JL, Shi XA, Leyland KM, Renner JB, Schwartz TA, Arden NK, and Jordan JM

Subjects
Black or African American statistics & numerical data, Aged, Case-Control Studies, Disease Progression, Female, Femoracetabular Impingement complications, Femoracetabular Impingement diagnostic imaging, Femoracetabular Impingement ethnology, Follow-Up Studies, Hip Joint diagnostic imaging, Humans, Male, Middle Aged, Osteoarthritis, Hip ethnology, Osteoarthritis, Hip etiology, Radiography methods, Severity of Illness Index, Sex Factors, White People statistics & numerical data, Femoracetabular Impingement pathology, Hip Joint pathology, Osteoarthritis, Hip diagnostic imaging, Osteoarthritis, Hip pathology
Abstract

Objectives: We sought to describe the effect of alterations in hip morphology with respect to worsening hip OA in a community-based sample including African American (AA) and white men and women., Methods: This nested case-control study defined case hips as Kellgren Lawrence grade (KLG) <3 on baseline supine pelvis radiographs and KLG ≥3 or THR for OA at the 1st or 2nd follow-up visit (mean 6 and 13 years, respectively); control hips had KLG <3 at both visits, with gender/race distribution similar to cases. Hip morphology was assessed using HipMorf software (Oxford, UK). Descriptive means and standard errors were obtained from generalized estimating equation (GEE) models. Sex-stratified GEE regression models (accounting for within-person correlation), adjusted for age, race, BMI, and side were then employed., Results: A total of 120 individuals (239 hips; 71 case/168 control) were included (25% male, 26% AA, mean age 62 years, BMI 30 kg/m(2)). Case hips tended to have greater baseline AP alpha angles, smaller minimum joint space width (mJSW) and more frequent triangular index signs. Adjusted results among men revealed that higher AP alpha angle, Gosvig ratio, and acetabular index were positively associated with case hips; coxa profunda was negatively associated. Among women, greater AP alpha angle, smaller mJSW, protrusio acetabuli, and triangular index sign were associated with case hips., Conclusions: We confirmed an increased risk of worsening hip OA due to baseline features of cam deformity among men and women, as well as protrusio acetabuli among women, and provide the first estimates of these measures in AAs., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Published
2016
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28. Associations between body mass index and foot joint pain in middle-aged and older women: a longitudinal population-based cohort study.

Author

Gay A, Culliford D, Leyland K, Arden NK, and Bowen CJ

Subjects
Aged, Cohort Studies, Female, Humans, Longitudinal Studies, Middle Aged, Arthralgia physiopathology, Body Mass Index, Foot Joints physiopathology
Abstract

Objective: To investigate the relationship between body mass index (BMI) and foot joint pain (FJP) over a 5-year period in a community-based cohort., Methods: We examined a subset of women from the Chingford Women's Study, a community cohort followed up for 20 years. From a baseline of 1,003 female participants, we reviewed data from 639 women (64%) for whom complete data sets for FJP and BMI were obtained over a 5-year period between year 10 (Y10) and year 15 (Y15). Descriptive statistics, binary regression modeling, and odds ratios (ORs) were used to examine the longitudinal relationship between BMI and FJP., Results: For Y10 and Y15, the median age was 61 years (interquartile range [IQR] 57-67) and 66 years (IQR 62-72), respectively, and the mean ± SD BMI was 26.7 ± 4.6 kg/m(2) and 27.2 ± 4.8 kg/m(2) , respectively. FJP prevalence was 21.6% at Y10 and 26.6% at Y15. Longitudinal analyses showed that both BMI and FJP increased significantly from Y10 to Y15 (P < 0.001). The odds of having FJP after a 5-year period increased by 4.9% for each BMI unit increase 5 years earlier (OR 1.049 [95% confidence interval (95% CI) 1.011-1.089], P = 0.012). This remained significant when adjusted for age, diabetes mellitus, and rheumatoid arthritis (OR 1.051 [95% CI 1.011-1.091], P = 0.012)., Conclusion: This is the first large longitudinal cohort study demonstrating that, in middle-aged women, a high BMI precedes and is predictive of FJP independent of age. Evidence from our findings can be used to identify those individuals at risk of developing FJP., (© 2014 The Authors. Arthritis Care & Research is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.)

Published
2014
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29. Osteoarthritis year 2013 in review: clinical.

Author

Arden NK and Leyland KM

Subjects
Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Arthroplasty, Replacement, Humans, Muscle Strength physiology, Obesity complications, Obesity epidemiology, Osteoarthritis etiology, Osteoarthritis therapy, Risk Factors, Treatment Outcome, Osteoarthritis epidemiology
Abstract

Some major themes over the past year in clinical research of osteoarthritis (OA) include obesity, muscle strength, pain mechanisms, novel disease modifying drugs, and risk factors for poor outcomes of joint replacement surgery. A systematic literature search was performed using PubMed from January 2012 to December 2012. The articles selected for this review represent topics the authors thought best highlight recent clinical OA research., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Published
2013
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