The classification and monitoring of individuals with early knee osteoarthritis (OA) are important considerations for the design and evaluation of therapeutic interventions and require the identification of appropriate outcome measures. Potential outcome domains to assess for early OA include patient-reported outcomes (such as pain, function and quality of life), features of clinical examination (such as joint line tenderness and crepitus), objective measures of physical function, levels of physical activity, features of imaging modalities (such as of magnetic resonance imaging) and biochemical markers in body fluid. Patient characteristics such as adiposity and biomechanics of the knee could also have relevance to the assessment of early OA. Importantly, research is needed to enable the selection of outcome measures that are feasible, reliable and validated in individuals at risk of knee OA or with early knee OA. In this Perspectives article, potential outcome measures for early symptomatic knee OA are discussed, including those measures that could be of use in clinical practice and/or the research setting.
Subscribe to Journal
Get full journal access for 1 year
only $17.75 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Suri, P., Morgenroth, D. C. & Hunter, D. J. Epidemiology of osteoarthritis and associated comorbidities. PM R 4, S10–S19 (2012).
Murray, C. J. et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380, 2197–2223 (2013).
Bombardier, C., Hawker, G. & Mosher, D. The Impact of Arthritis in Canada: Today and Over the Next 30 Years (Arthritis Alliance of Canada, 2011).
Wright, E. A. et al. Impact of knee osteoarthritis on health care resource utilization in a US population-based national sample. Med. Care. 48, 785–791 (2010).
Losina, E. et al. Impact of obesity and knee osteoarthritis on morbidity and mortality in older Americans. Ann. Intern. Med. 154, 217–226 (2011).
Whittaker, J. L. et al. Association between MRI-defined osteoarthritis, pain, function and strength 3–10 years following knee joint injury in youth sport. Br. J. Sports Med. 52, 934–939 (2018).
Centre for Metabolic Bone Diseases, University of Sheffield. FRAX® Fracture Risk Assessment Tool. FRAX https://www.shef.ac.uk/FRAX/tool.jsp (2008).
Hippisley-Cox, J. & Coupland, C. Derivation and validation of updated QFracture algorithm to predict risk of osteoporotic fracture in primary care in the United Kingdom: prospective open cohort study. BMJ 344, e3427 (2012).
Viswanathan, M. et al. Screening to prevent osteoporotic fractures: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 319, 2532–2551 (2018).
Kerkhof, H. et al. Prediction model for knee osteoarthritis incidence, including clinical, genetic and biochemical risk factors. Ann. Rheum. Dis. 73, 2116–2121 (2014).
Roemer, F. W., Kwoh, C. K., Hayashi, D., Felson, D. T. & Guermazi, A. The role of radiography and MRI for eligibility assessment in DMOAD trials of knee OA. Nat. Rev. Rheumatol. 14, 372–380 (2018).
Luyten, F. et al. Toward classification criteria for early osteoarthritis of the knee. Semin. Arthritis Rheum. 47, 457–463 (2017).
Collins, N. J., Misra, D., Felson, D. T., Crossley, K. M. & Roos, E. M. Measures of knee function: International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form, Knee Injury and Osteoarthritis Outcome Score (KOOS), Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS), Knee Outcome Survey Activities of Daily Living Scale (KOS-ADL), Lysholm Knee Scoring Scale, Oxford Knee Score (OKS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Activity Rating Scale (ARS), and Tegner Activity Score (TAS). Arthritis Care Res. 63, S208–S228 (2011).
Collins, N. et al. Knee Injury and Osteoarthritis Outcome Score (KOOS): systematic review and meta-analysis of measurement properties. Osteoarthr. Cartil. 24, 1317–1329 (2016).
Broderick, J. E., Schneider, S., Junghaenel, D. U., Schwartz, J. E. & Stone, A. A. Validity and reliability of patient-reported outcomes measurement information system instruments in osteoarthritis. Arthritis Care Res. 65, 1625–1633 (2013).
Hawker, G. A., Mian, S., Kendzerska, T. & French, M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care Res. 63, S240–S252 (2011).
Dworkin, R. H. et al. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain 113, 9–19 (2005).
Gooberman-Hill, R. et al. Assessing chronic joint pain: lessons from a focus group study. Arthritis Care Res. 57, 666–671 (2007).
Hawker, G. et al. Understanding the pain experience in hip and knee osteoarthritis — an OARSI/OMERACT initiative. Osteoarthr. Cartil. 16, 415–422 (2008).
Maly, M. R. & Cott, C. A. Being careful: a grounded theory of emergent chronic knee problems. Arthritis Care Res. 61, 937–943 (2009).
Hensor, E., Dube, B., Kingsbury, S. R., Tennant, A. & Conaghan, P. G. Toward a clinical definition of early osteoarthritis: onset of patient-reported knee pain begins on stairs. Data from the Osteoarthritis Initiative. Arthritis Care Res. 67, 40–47 (2015).
Hawker, G. et al. Development and preliminary psychometric testing of a new OA pain measure — an OARSI/OMERACT initiative. Osteoarthr. Cartil. 16, 409–414 (2008).
Roos, E. M., Roos, H. P., Lohmander, L. S., Ekdahl, C. & Beynnon, B. D. Knee Injury and Osteoarthritis Outcome Score (KOOS) — development of a self-administered outcome measure. J. Orthop. Sports Phys. Ther. 28, 88–96 (1998).
Örtqvist, M., Roos, E. M., Broström, E. W., Janarv, P.-M. & Iversen, M. D. Development of the knee injury and osteoarthritis outcome score for children (KOOS-Child) comprehensibility and content validity. Acta Orthop. 83, 666–673 (2012).
Roos, E. M. & Toksvig-Larsen, S. Knee injury and Osteoarthritis Outcome Score (KOOS) — validation and comparison to the WOMAC in total knee replacement. Health Qual. Life Outcomes 1, 17 (2003).
Roos, E. M., Roos, H., Ekdahl, C. & Lohmander, L. Knee injury and Osteoarthritis Outcome Score (KOOS) — validation of a Swedish version. Scand. J. Med. Sci. Sports 8, 439–448 (1998).
Paradowski, P. T., Bergman, S., Sundén-Lundius, A., Lohmander, L. S. & Roos, E. M. Knee complaints vary with age and gender in the adult population. Population-based reference data for the Knee injury and Osteoarthritis Outcome Score (KOOS). BMC Musculoskelet. Disord. 7, 38 (2006).
Williamson, T., Sikka, R., Tompkins, M. & Nelson, B. J. Use of the Knee Injury and Osteoarthritis Outcome Score in a healthy United States population. Am. J. Sports Med. 44, 440–446 (2015).
Gignac, M. A., Cott, C. & Badley, E. M. Adaptation to disability: applying selective optimization with compensation to the behaviors of older adults with osteoarthritis. Psychol. Aging 17, 520–524 (2002).
Morden, A., Jinks, C. & Ong, B. N. Lay models of self-management: how do people manage knee osteoarthritis in context? Chronic Illn. 7, 185–200 (2011).
Clark, J. M., Chesworth, B. M., Speechley, M., Petrella, R. J. & Maly, M. R. Questionnaire to identify knee symptoms: development of a tool to identify early experiences consistent with knee osteoarthritis. Phys. Ther. 94, 111–120 (2014).
Bastick, A. et al. Defining knee pain trajectories in early symptomatic knee osteoarthritis in primary care: 5-year results from a nationwide prospective cohort study (CHECK). Br. J. Gen. Pract. 66, e32–e39 (2016).
Wesseling, J. et al. CHECK (Cohort Hip and Cohort Knee): similarities and differences with the Osteoarthritis Initiative. Ann. Rheum. Dis. 68, 1413–1419 (2009).
Kastelein, M. Traumatic and Non-traumatic Knee Complaints in General Practice. Thesis, Erasmus Univ., Rotterdam (2013).
Schiphof, D., Waarsing, E., Oei, E. & Bierma-Zeinstra, S. Crepitus, joint line tenderness and the feeling of giving way are predictive signs for early knee osteoarthritis. Osteoarthr. Cartil. 23, A330 (2015).
Schiphof, D. et al. Crepitus is a first indication of patellofemoral osteoarthritis (and not of tibiofemoral osteoarthritis). Osteoarthr. Cartil. 22, 631–638 (2014).
Maricar, N. et al. Interobserver and intraobserver reliability of clinical assessments in knee osteoarthritis. J. Rheumatol. 43, 2171–2178 (2016).
Andriacchi, T. P. et al. A framework for the in vivo pathomechanics of osteoarthritis at the knee. Ann. Biomed. Eng. 32, 447–457 (2004).
World Health Organization. International Classification of Functioning, Disability and Health: ICF (WHO, 2001).
Dobson, F. et al. Measurement properties of performance-based measures to assess physical function in hip and knee osteoarthritis: a systematic review. Osteoarthr. Cartil. 20, 1548–1562 (2012).
Dobson, F. et al. OARSI recommended performance-based tests to assess physical function in people diagnosed with hip or knee osteoarthritis. Osteoarthr. Cartil. 21, 1042–1052 (2013).
Kroman, S. L., Roos, E. M., Bennell, K. L., Hinman, R. S. & Dobson, F. Measurement properties of performance-based outcome measures to assess physical function in young and middle-aged people known to be at high risk of hip and/or knee osteoarthritis: a systematic review. Osteoarthr. Cartil. 22, 26–39 (2014).
Whittaker, J., Woodhouse, L., Nettel-Aguirre, A. & Emery, C. Outcomes associated with early post-traumatic osteoarthritis and other negative health consequences 3–10 years following knee joint injury in youth sport. Osteoarthr. Cartil. 23, 1122–1129 (2015).
Baltich, J. et al. The impact of previous knee injury on force plate and field-based measures of balance. Clin. Biomech. 30, 832–838 (2015).
Whittaker, J. et al. Health-related outcomes following a youth sport-related knee injury. Med. Sci. Sports Exerc. 51, 255–263 (2018).
Moksnes, H., Engebretsen, L., Eitzen, I. & Risberg, M. A. Functional outcomes following a non-operative treatment algorithm for anterior cruciate ligament injuries in skeletally immature children 12 years and younger. A prospective cohort with 2 years follow-up. Br. J. Sports Med. 47, 488–494 (2013).
Moksnes, H. & Risberg, M. A. Performance-based functional evaluation of non-operative and operative treatment after anterior cruciate ligament injury. Scand. J. Med. Sci. Sports 19, 345–355 (2009).
Grindem, H., Eitzen, I., Moksnes, H., Snyder-Mackler, L. & Risberg, M. A. A. Pair-matched comparison of return to pivoting sports at 1 year in anterior cruciate ligament-injured patients after a nonoperative versus an operative treatment course. Am. J. Sports Med. 40, 2509–2516 (2012).
Logerstedt, D. et al. Single-legged hop tests as predictors of self-reported knee function after anterior cruciate ligament reconstruction the Delaware-Oslo ACL Cohort study. Am. J. Sports Med. 40, 2348–2356 (2012).
Kanko, L. E. et al. The star excursion balance test is a reliable and valid outcome measure for patients with knee osteoarthritis. Osteoarthr. Cartil. 27, 580–585 (2019).
Gribble, P. A., Hertel, J. & Plisky, P. Using the star excursion balance test to assess dynamic postural-control deficits and outcomes in lower extremity injury: a literature and systematic review. J. Athl. Train. 47, 339–357 (2012).
Plisky, P. J., Rauh, M. J., Kaminski, T. W. & Underwood, F. B. Star excursion balance test as a predictor of lower extremity injury in high school basketball players. J. Orthop. Sports Phys. Ther. 36, 911–919 (2006).
Herrington, L., Hatcher, J., Hatcher, A. & McNicholas, M. A comparison of star excursion balance test reach distances between ACL deficient patients and asymptomatic controls. Knee 16, 149–152 (2009).
Shaffer, S. W. et al. Y-balance test: a reliability study involving multiple raters. Mil. Med. 178, 1264–1270 (2013).
Hegedus, E. J., McDonough, S. M., Bleakley, C., Baxter, D. & Cook, C. E. Clinician-friendly lower extremity physical performance tests in athletes: a systematic review of measurement properties and correlation with injury. Part 2 — the tests for the hip, thigh, foot and ankle including the star excursion balance test. Br. J. Sports Med. 49, 649–656 (2015).
Jones, C. J. & Rikli, R. E. Measuring functional fitness of older adults. J. Active Aging 1, 24–30 (2002).
Jones, C. J., Rikli, R. E. & Beam, W. C. A. 30-s chair-stand test as a measure of lower body strength in community-residing older adults. Res. Q. Exerc. Sport 70, 113–119 (1999).
Rikli, R. E. & Jones, C. J. Functional fitness normative scores for community-residing older adults, ages 60–94. J. Aging Phys. Act. 7, 162–181 (1999).
Ekegren, C. L., Miller, W. C., Celebrini, R. G., Eng, J. J. & Macintyre, D. L. Reliability and validity of observational risk screening in evaluating dynamic knee valgus. J. Orthop. Sports Phys. Ther. 39, 665–674 (2009).
Weeks, B. K., Carty, C. P. & Horan, S. A. Kinematic predictors of single-leg squat performance: a comparison of experienced physiotherapists and student physiotherapists. BMC Musculoskelet. Disord. 13, 207 (2012).
Crossley, K. M., Zhang, W.-J., Schache, A. G., Bryant, A. & Cowan, S. M. Performance on the single-leg squat task indicates hip abductor muscle function. Am. J. Sports Med. 39, 866–873 (2011).
Lorenzen, K. et al. Kinetics and kinematics of the knee during a single leg squat 3–10 years after AN intra-articular knee injury sustained while participating in youth sports. Osteoarthr. Cartil. 23, A104 (2015).
Emery, C. A., Cassidy, J. D., Klassen, T. P., Rosychuk, R. J. & Rowe, B. H. Development of a clinical static and dynamic standing balance measurement tool appropriate for use in adolescents. Phys. Ther. 85, 502–514 (2005).
Aandstad, A., Holme, I., Berntsen, S. & Anderssen, S. A. Validity and reliability of the 20 meter shuttle run test in military personnel. Mil. Med. 176, 513–518 (2011).
Øiestad, B. E., Juhl, C. B., Eitzen, I. & Thorlund, J. B. Knee extensor muscle weakness is a risk factor for development of knee osteoarthritis. A systematic review and meta-analysis. Osteoarthr. Cartil. 23, 171–177 (2015).
Chang, A. H. et al. Hip muscle strength and protection against structural worsening and poor function and disability outcomes in knee osteoarthritis. Osteoarthr. Cartil. https://doi.org/10.1016/j.joca.2019.02.795 (2019).
Wang, X., Hunter, D., Xu, J. & Ding, C. Metabolic triggered inflammation in osteoarthritis. Osteoarthr. Cartil. 23, 22–30 (2015).
Chu, C. R., Williams, A. A., Coyle, C. H. & Bowers, M. E. Early diagnosis to enable early treatment of pre-osteoarthritis. Arthritis Res. Ther. 14, 212 (2012).
Richmond, S. A. et al. Are joint injury, sport activity, physical activity, obesity, or occupational activities predictors for osteoarthritis? A systematic review. J. Orthop. Sports Phys. Ther. 43, B515–B519 (2013).
Mezhov, V. et al. Does obesity affect knee cartilage? A systematic review of magnetic resonance imaging data. Obes. Rev. 15, 143–157 (2014).
Lim, Y. Z. et al. Association of obesity and systemic factors with bone marrow lesions at the knee: a systematic review. Semin. Arthritis Rheum. 43, 600–612 (2014).
Lohmander, L. S., de Verdier, M. G., Rollof, J., Nilsson, P. M. & Engström, G. Incidence of severe knee and hip osteoarthritis in relation to different measures of body mass: a population-based prospective cohort study. Ann. Rheum. Dis. 68, 490–496 (2009).
Cibere, J. et al. Association of clinical findings with pre-radiographic and radiographic knee osteoarthritis in a population-based study. Arthritis Care Res. 62, 1691–1698 (2010).
Wang, Y. et al. Body composition and knee cartilage properties in healthy, community-based adults. Ann. Rheum. Dis. 66, 1244–1248 (2007).
Myer, G. D. et al. Injury initiates unfavourable weight gain and obesity markers in youth. Br. J. Sports Med. 48, 1477–1481 (2014).
Onat, A., Uğur, M., Can, G., Yüksel, H. & Hergenç, G. Visceral adipose tissue and body fat mass: predictive values for and role of gender in cardiometabolic risk among Turks. Nutrition 26, 382–389 (2010).
Toomey, C. M. et al. Higher fat mass is associated with a history of knee injury in youth sport. J. Orthop. Sports Phys. Ther. 47, 80–87 (2017).
Fox, C. S. et al. Abdominal visceral and subcutaneous adipose tissue compartments. Circulation 116, 39–48 (2007).
Berry, P. et al. The relationship between body composition and structural changes at the knee. Rheumatology 49, 2362–2369 (2010).
Visser, A. et al. The role of fat mass and skeletal muscle mass in knee osteoarthritis is different for men and women: the NEO study. Osteoarthr. Cartil. 22, 197–202 (2014).
Ding, C., Stannus, O., Cicuttini, F., Antony, B. & Jones, G. Body fat is associated with increased and lean mass with decreased knee cartilage loss in older adults: a prospective cohort study. Int. J. Obes. 37, 822–827 (2013).
Visser, A. W. et al. Adiposity and hand osteoarthritis: the Netherlands Epidemiology of Obesity study. Arthritis Res. Ther. 16, R19 (2014).
Teichtahl, A. J. et al. The longitudinal relationship between body composition and patella cartilage in healthy adults. Obesity 16, 421–427 (2008).
Miller, M. E., Rejeski, W. J., Reboussin, B. A., Have, T. R. & Ettinger, W. H. Physical activity, functional limitations, and disability in older adults. J. Am. Geriatr. Soc. 48, 1264–1272 (2000).
Vignon, É. et al. Osteoarthritis of the knee and hip and activity: a systematic international review and synthesis (OASIS). Joint Bone Spine 73, 442–455 (2006).
Chmelo, E. et al. Physical activity and physical function in older adults with knee osteoarthritis. J. Phys. Act. Health 10, 777–783 (2013).
Rejeski, W. J., Ettinger, W. H. Jr, Martin, K. & Morgan, T. Treating disability in knee osteoarthritis with exercise therapy: a central role for self-efficacy and pain. Arthritis Care Res. 11, 94–101 (1998).
Hovis, K. K. et al. Physical activity is associated with magnetic resonance imaging-based knee cartilage T2 measurements in asymptomatic subjects with and those without osteoarthritis risk factors. Arthritis Rheum. 63, 2248–2256 (2011).
Lin, W. et al. Physical activity in relation to knee cartilage T2 progression measured with 3 T MRI over a period of 4 years: data from the Osteoarthritis Initiative. Osteoarthr. Cartil. 21, 1558–1566 (2013).
Dunlop, D. D. et al. Relation of physical activity time to incident disability in community dwelling adults with or at risk of knee arthritis: prospective cohort study. BMJ 348, g2472 (2014).
Santos-Lozano, A. et al. Actigraph GT3X: validation and determination of physical activity intensity cut points. Int. J. Sports Med. 34, 975–982 (2013).
Strath, S. J. et al. Guide to the assessment of physical activity: clinical and research applications: a scientific statement from the American Heart Association. Circulation 128, 2259–2279 (2013).
Butte, N. F., Ekelund, U. & Westerterp, K. R. Assessing physical activity using wearable monitors: measures of physical activity. Med. Sci. Sports Exerc. 44, S5–S12 (2012).
Ahn, G. E. et al. Relationship of objective to self-reported physical activity measures among adults in the osteoarthritis initiative [abstract 242]. Arthritis Rheum. 64, S104–S105 (2012).
Christensen, R., Astrup, A. & Bliddal, H. Weight loss: the treatment of choice for knee osteoarthritis? A randomized trial. Osteoarthr. Cartil. 13, 20–27 (2005).
Bartels, E. et al. Effect of a 16 weeks weight loss program on osteoarthritis biomarkers in obese patients with knee osteoarthritis: a prospective cohort study. Osteoarthr. Cartil. 22, 1817–1825 (2014).
Zheng, H. & Chen, C. Body mass index and risk of knee osteoarthritis: systematic review and meta-analysis of prospective studies. BMJ Open 5, e007568 (2015).
Christensen, R., Bartels, E. M., Astrup, A. & Bliddal, H. Effect of weight reduction in obese patients diagnosed with knee osteoarthritis: a systematic review and meta-analysis. Ann. Rheum. Dis. 66, 433–439 (2007).
Dai, Z., Niu, J., Zhang, Y., Jacques, P. & Felson, D. T. Dietary intake of fibre and risk of knee osteoarthritis in two US prospective cohorts. Ann. Rheum. Dis. 76, 1411–1419 (2017).
Ameye, L. G. & Chee, W. S. Osteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence. Arthritis Res. Ther. 8, R127 (2006).
Sanghi, D. et al. Elucidation of dietary risk factors in osteoarthritis knee — a case–control study. J. Am. Coll. Nutr. 34, 15–20 (2015).
Subar, A. F. et al. The Automated Self-Administered 24-hour dietary recall (ASA24): a resource for researchers, clinicians, and educators from the National Cancer Institute. J. Acad. Nutr. Diet. 112, 1134–1137 (2012).
Schröder, H. et al. A short screener is valid for assessing Mediterranean diet adherence among older Spanish men and women. J. Nutr. 141, 1140–1145 (2011).
Sturnieks, D. L. et al. Knee joint biomechanics following arthroscopic partial meniscectomy. J. Orthop. Res. 26, 1075–1080 (2008).
Gardinier, E. S., Manal, K., Buchanan, T. S. & Snyder-Mackler, L. Altered loading in the injured knee after ACL rupture. J. Orthop. Res. 31, 458–464 (2013).
Haughom, B. D., Souza, R., Schairer, W. W., Li, X. & Ma, C. B. Evaluating rotational kinematics of the knee in ACL-ruptured and healthy patients using 3.0 Tesla magnetic resonance imaging. Knee Surg. Sports Traumatol. Arthrosc. 20, 663–670 (2012).
Waite, J., Beard, D., Dodd, C., Murray, D. & Gill, H. In vivo kinematics of the ACL-deficient limb during running and cutting. Knee Surg. Sports Traumatol. Arthrosc. 13, 377–384 (2005).
Zhang, L.-Q., Shiavi, R. G., Limbird, T. J. & Minorik, J. M. Six degrees-of-freedom kinematics of ACL deficient knees during locomotion — compensatory mechanism. Gait Posture 17, 34–42 (2003).
Noyes, F. R., Schipplein, O. D., Andriacchi, T. P., Saddemi, S. R. & Weise, M. The anterior cruciate ligament-deficient knee with varus alignment. An analysis of gait adaptations and dynamic joint loadings. Am. J. Sports Med. 20, 707–716 (1992).
Hubley-Kozey, C., Deluzio, K., Landry, S., McNutt, J. & Stanish, W. Neuromuscular alterations during walking in persons with moderate knee osteoarthritis. J. Electromyogr. Kinesiol. 16, 365–378 (2006).
Heiden, T. L., Lloyd, D. G. & Ackland, T. R. Knee joint kinematics, kinetics and muscle co-contraction in knee osteoarthritis patient gait. Clin. Biomech. 24, 833–841 (2009).
Mündermann, A., Dyrby, C. O. & Andriacchi, T. P. Secondary gait changes in patients with medial compartment knee osteoarthritis: increased load at the ankle, knee, and hip during walking. Arthritis Rheum. 52, 2835–2844 (2005).
Rudolph, K. S., Schmitt, L. C. & Lewek, M. D. Age-related changes in strength, joint laxity, and walking patterns: are they related to knee osteoarthritis? Phys. Ther. 87, 1422–1432 (2007).
Hortobágyi, T. et al. Altered hamstring-quadriceps muscle balance in patients with knee osteoarthritis. Clin. Biomech. 20, 97–104 (2005).
Benedetti, M. et al. Muscle activation pattern and gait biomechanics after total knee replacement. Clin. Biomech. 18, 871–876 (2003).
Kuntze, G., von Tscharner, V., Hutchison, C. & Ronsky, J. L. Alterations in lower limb multimuscle activation patterns during stair climbing in female total knee arthroplasty patients. J. Neurophysiol. 114, 2718–2725 (2015).
Kuntze, G., von Tscharner, V., Hutchison, C. & Ronsky, J. Multi-muscle activation strategies during walking in female post-operative total joint replacement patients. J. Electromyogr. Kinesiol. 25, 715–721 (2015).
Cicuttini, F., Wluka, A., Hankin, J. & Wang, Y. Longitudinal study of the relationship between knee angle and tibiofemoral cartilage volume in subjects with knee osteoarthritis. Rheumatology 43, 321–324 (2004).
Sharma, L. et al. The role of knee alignment in disease progression and functional decline in knee osteoarthritis. JAMA 286, 188–195 (2001).
Wikstrom, E. A., Tillman, M. D., Chmielewski, T. L. & Borsa, P. A. Measurement and evaluation of dynamic joint stability of the knee and ankle after injury. Sports Med. 36, 393–410 (2006).
Riemann, B. L. & Lephart, S. M. The sensorimotor system, part II: the role of proprioception in motor control and functional joint stability. J. Athl. Train. 37, 80–84 (2002).
Williams, G. N., Buchanan, T. S., Barrance, P. J., Axe, M. J. & Snyder-Mackler, L. Quadriceps weakness, atrophy, and activation failure in predicted noncopers after anterior cruciate ligament injury. Am. J. Sports Med. 33, 402–407 (2005).
Suter, E. & Herzog, W. Does muscle inhibition after knee injury increase the risk of osteoarthritis? Exerc. Sport Sci. Rev. 28, 15–18 (2000).
Hurley, M. V. The role of muscle weakness in the pathogenesis of osteoarthritis. Rheum. Dis. Clin. North Am. 25, 283–298 (1999).
Bennell, K. L., Hunt, M. A., Wrigley, T. V., Lim, B.-W. & Hinman, R. S. Role of muscle in the genesis and management of knee osteoarthritis. Rheum. Dis. Clin. North Am. 34, 731–754 (2008).
Roos, E. M., Herzog, W., Block, J. A. & Bennell, K. L. Muscle weakness, afferent sensory dysfunction and exercise in knee osteoarthritis. Nat. Rev. Rheumatol. 7, 57–63 (2011).
Van de Velde, S. K. et al. Increased tibiofemoral cartilage contact deformation in patients with anterior cruciate ligament deficiency. Arthritis Rheum. 60, 3693–3702 (2009).
Liu, F. et al. In vivo tibiofemoral cartilage deformation during the stance phase of gait. J. Biomech. 43, 658–665 (2010).
Gardinier, E. S., Di Stasi, S., Manal, K., Buchanan, T. S. & Snyder-Mackler, L. Knee contact force asymmetries in patients who failed return-to-sport readiness criteria 6 months after anterior cruciate ligament reconstruction. Am. J. Sports Med. 42, 2917–2925 (2014).
Gardinier, E. S., Manal, K., Buchanan, T. S. & Snyder-Mackler, L. Clinically-relevant measures associated with altered contact forces in patients with anterior cruciate ligament deficiency. Clin. Biomech. 29, 531–536 (2014).
Andriacchi, T. P., Favre, J., Erhart-Hledik, J. & Chu, C. R. A systems view of risk factors for knee osteoarthritis reveals insights into the pathogenesis of the disease. Ann. Biomed. Eng. 43, 376–387 (2015).
Gardiner, B. S. et al. Predicting knee osteoarthritis. Ann. Biomed. Eng. 44, 222–233 (2015).
Kobsar, D., Osis, S. T., Phinyomark, A., Boyd, J. E. & Ferber, R. Reliability of gait analysis using wearable sensors in patients with knee osteoarthritis. J. Biomech. 49, 3977–3982 (2016).
Kobsar, D., Osis, S. T., Boyd, J. E., Hettinga, B. A. & Ferber, R. Wearable sensors to predict improvement following an exercise intervention in patients with knee osteoarthritis. J. Neuroeng. Rehabil. 14, 94 (2017).
Tadano, S., Takeda, R., Sasaki, K., Fujisawa, T. & Tohyama, H. Gait characterization for osteoarthritis patients using wearable gait sensors (H-Gait systems). J. Biomech. 49, 684–690 (2016).
Sutter, E. G. et al. In vivo measurement of localized tibiofemoral cartilage strains in response to dynamic activity. Am. J. Sports Med. 43, 370–376 (2015).
Chehab, E. F., Favre, J., Erhart-Hledik, J. C. & Andriacchi, T. P. Baseline knee adduction and flexion moments during walking are both associated with 5 year cartilage changes in patients with medial knee osteoarthritis. Osteoarthr. Cartil. 22, 1833–1839 (2014).
Walter, J. P. et al. Muscle synergies may improve optimization prediction of knee contact forces during walking. J. Biomech. Eng. 136, 021031 (2014).
Gerus, P. et al. Subject-specific knee joint geometry improves predictions of medial tibiofemoral contact forces. J. Biomech. 46, 2778–2786 (2013).
Johnson, W. R., Alderson, J., Lloyd, D. G. & Mian, A. Predicting athlete ground reaction forces and moments from spatio-temporal driven CNN models. IEEE Trans. Biomed. Eng. 66, 689–694 (2019).
Long, M. J., Papi, E., Duffell, L. D. & McGregor, A. H. Predicting knee osteoarthritis risk in injured populations. Clin. Biomech. 47, 87–95 (2017).
Pfeiffer, S. et al. Associations between slower walking speed and T1ρ magnetic resonance imaging of femoral cartilage following anterior cruciate ligament reconstruction. Arthritis Care Res. 70, 1132–1140 (2018).
Chu, C. R. et al. Mechanically stimulated biomarkers signal cartilage changes over 5 years consistent with disease progression in medial knee osteoarthritis patients. J. Orthop. Res. 36, 891–897 (2018).
Pietrosimone, B. et al. Biochemical markers of cartilage metabolism are associated with walking biomechanics 6-months following anterior cruciate ligament reconstruction. J. Orthop. Res. 35, 2288–2297 (2017).
Favre, J., Erhart-Hledik, J., Chehab, E. & Andriacchi, T. Baseline ambulatory knee kinematics are associated with changes in cartilage thickness in osteoarthritic patients over 5 years. J. Biomech. 49, 1859–1864 (2016).
Erhart-Hledik, J. et al. A relationship between mechanically-induced changes in serum cartilage oligomeric matrix protein (COMP) and changes in cartilage thickness after 5 years. Osteoarthr. Cartil. 20, 1309–1315 (2012).
Hayashi, D., Roemer, F. & Guermazi, A. Recent advances in research imaging of osteoarthritis with focus on MRI, ultrasound and hybrid imaging. Clin. Exp. Rheumatol. 36 (Suppl. 114), 43–52 (2018).
Hayashi, D., Roemer, F. W. & Guermazi, A. Imaging of osteoarthritis — recent research developments and future perspective. Br. J. Radiol. 91, 20170349 (2018).
Brandt, K. D., Fife, R. S., Braunstein, E. M. & Katz, B. Radiographic grading of the severity of knee osteoarthritis: relation of the Kellgren and Lawrence grade to a grade based on joint space narrowing, and correlation with arthroscopic evidence of articular cartilage degeneration. Arthritis Rheum. 34, 1381–1386 (1991).
Kellgren, J. H. & Lawrence, J. S. Radiological assessment of osteo-arthrosis. Ann. Rheum. Dis. 16, 494–502 (1957).
Wirth, W. et al. Direct comparison of fixed flexion, radiography and MRI in knee osteoarthritis: responsiveness data from the Osteoarthritis Initiative. Osteoarthr. Cartil. 21, 117–125 (2013).
Guermazi, A. et al. Prevalence of abnormalities in knees detected by MRI in adults without knee osteoarthritis: population based observational study (Framingham Osteoarthritis Study). BMJ 345, e5339 (2012).
Hunter, D. J. et al. Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI Osteoarthritis Knee Score). Osteoarthr. Cartil. 19, 990–1002 (2011).
Sharma, L. et al. Tissue lesions in osteoarthritis initiative participants with normal X-rays and risk factors for incident cartilage damage [abstract 2467]. Arthritis Rheum. 64 (Suppl. 10), S1039–S1040 (2012).
Su, F. et al. Cartilage morphology and T 1 and T 2 quantification in ACL-reconstructed knees: a 2-year follow-up. Osteoarthr. Cartil. 21, 1058–1067 (2013).
Van Ginckel, A., Verdonk, P. & Witvrouw, E. Cartilage adaptation after anterior cruciate ligament injury and reconstruction: implications for clinical management and research? A systematic review of longitudinal MRI studies. Osteoarthr. Cartil. 21, 1009–1024 (2013).
Hunter, D. J. et al. The effect of anterior cruciate ligament injury on bone curvature: exploratory analysis in the KANON trial. Osteoarthr. Cartil. 22, 959–968 (2014).
Neogi, T. & Felson, D. T. Osteoarthritis: bone as an imaging biomarker and treatment target in OA. Nat. Rev. Rheumatol. 12, 503–504 (2016).
Bowes, M. et al. Marked and rapid change of bone shape in acutely ACL injured knees — an exploratory analysis of the KANON trial. Osteoarthr. Cartil. 27, 638–645 (2019).
Hunter, D. J. et al. Definition of osteoarthritis on MRI: results of a Delphi exercise. Osteoarthr. Cartil. 19, 963–969 (2011).
Schiphof, D. et al. Sensitivity and associations with pain and body weight of an MRI definition of knee osteoarthritis compared with radiographic Kellgren and Lawrence criteria: a population-based study in middle-aged females. Osteoarthr. Cartil. 22, 440–446 (2014).
Culvenor, A. G. et al. Early knee osteoarthritis is evident one year following anterior cruciate ligament reconstruction: a magnetic resonance imaging evaluation. Arthritis Rheumatol. 67, 946–955 (2015).
Roemer, F. W. et al. Molecular and structural biomarkers of inflammation at two years after acute anterior cruciate ligament injury do not predict structural knee osteoarthritis at five years. Arthritis Rheumatol. 71, 238–243 (2019).
Roemer, F. W., Frobell, R., Lohmander, L. S., Niu, J. & Guermazi, A. Anterior Cruciate Ligament OsteoArthritis Score (ACLOAS): longitudinal MRI-based whole joint assessment of anterior cruciate ligament injury. Osteoarthr. Cartil. 22, 668–682 (2014).
Hunter, D. et al. OARSI Clinical Trials Recommendations: knee imaging in clinical trials in osteoarthritis. Osteoarthr. Cartil. 23, 698–715 (2015).
Guermazi, A. et al. Assessment of synovitis with contrast-enhanced MRI using a whole-joint semiquantitative scoring system in people with, or at high risk of, knee osteoarthritis: the MOST study. Ann. Rheum. Dis. 70, 805–811 (2011).
Magnusson, K., Kumm, J., Turkiewicz, A. & Englund, M. A naturally aging knee, or development of early knee osteoarthritis? Osteoarthr. Cartil. 26, 1447–1452 (2018).
Baert, I. A. et al. Weak associations between structural changes on MRI and symptoms, function and muscle strength in relation to knee osteoarthritis. Knee Surg. Sports Traumatol. Arthrosc. 22, 2013–2025 (2014).
Neogi, T. et al. Association between radiographic features of knee osteoarthritis and pain: results from two cohort studies. BMJ 339, b2844 (2009).
Kraus, V. B., Blanco, F. J., Englund, M., Karsdal, M. A. & Lohmander, L. S. Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use. Osteoarthr. Cartil. 23, 1233–1241 (2015).
Bruyère, O. et al. Longitudinal study of magnetic resonance imaging and standard X-rays to assess disease progression in osteoarthritis. Osteoarthr. Cartil. 15, 98–103 (2007).
Hayashi, D. et al. Pre-radiographic osteoarthritic changes are highly prevalent in the medial patella and medial posterior femur in older persons: Framingham OA study. Osteoarthr. Cartil. 22, 76–83 (2014).
Englund, M. et al. Incidental meniscal findings on knee MRI in middle-aged and elderly persons. N. Engl. J. Med. 359, 1108–1115 (2008).
Felson, D. & Lohmander, L. Whither osteoarthritis biomarkers? Osteoarthr. Cartil. 17, 419–422 (2009).
Bay-Jensen, A. C., Thudium, C. S. & Mobasheri, A. Development and use of biochemical markers in osteoarthritis: current update. Curr. Opin. Rheumatol. 30, 121–128 (2017).
Ling, S. M. et al. Serum protein signatures detect early radiographic osteoarthritis. Osteoarthr. Cartil. 17, 43–48 (2009).
Golightly, Y. M. et al. 124 serum cartilage oligomeric matrix protein hyaluronan high-sensitivity C-reactive protein and keratan sulfate as predictors of incident radiographic knee osteoarthritis: differences by chronic knee symptoms. Osteoarthr. Cartil. 18, S62–S63 (2010).
Blumenfeld, O. et al. Association between cartilage and bone biomarkers and incidence of radiographic knee osteoarthritis (RKOA) in UK females: a prospective study. Osteoarthr. Cartil. 21, 923–929 (2013).
Sowers, M. et al. The associations of bone mineral density and bone turnover markers with osteoarthritis of the hand and knee in pre- and perimenopausal women. Arthritis Rheum. 42, 483–489 (1999).
Kosinska, M. K. et al. Sphingolipids in human synovial fluid: a lipidomic study. PLOS ONE 9, e91769 (2014).
Adams, S. et al. Global metabolic profiling of human osteoarthritic synovium. Osteoarthr. Cartil. 20, 64–67 (2012).
Bauer, D. et al. Classification of osteoarthritis biomarkers: a proposed approach. Osteoarthr. Cartil. 14, 723–727 (2006).
Kraus, V. B. et al. OARSI clinical trials recommendations: soluble biomarker assessments in clinical trials in osteoarthritis. Osteoarthr. Cartil. 23, 686–697 (2015).
Van Spil, W., DeGroot, J., Lems, W., Oostveen, J. & Lafeber, F. Serum and urinary biochemical markers for knee and hip-osteoarthritis: a systematic review applying the consensus BIPED criteria. Osteoarthr. Cartil. 18, 605–612 (2010).
FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource (National Institutes of Health, 2016).
van der Elst, K. et al. Unraveling patient-preferred health and treatment outcomes in early rheumatoid arthritis: a longitudinal qualitative study. Arthritis Care Res. 68, 1278–1287 (2016).
The authors acknowledge the support of Alberta Team Osteoarthritis (Alberta Innovates Health Solutions Collaborative Research and Innovation Opportunity Team), Arthritis Research UK and the Osteoarthritis Research Society International. The authors acknowledge the following consortium affiliations: 18D-BOARD Consortium, European Commission Framework 7 programme (S.B.-Z., J.R. and A.Mo.), Primary Care Versus Arthritis, UK (G.P.), the Centre for Sport, Exercise and Osteoarthritis Versus Arthritis, UK (A.Mo. and N.K.A.) and the APPROACH Consortium, European Commission Innovative Medicines Initiative (A.Mo.). The authors thank T. Childs (Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada) for administrative support.
Nature Reviews Rheumatology thanks J. Driban and other anonymous reviewer(s), for their contribution to the peer review of this work.
C.A.E., J.L.W., A. Ma., N.K.A., K.L.B., C.M.T., R.A.R., D.T., J.L.R., G.K., D.G.L., T.A., M.E., V.B.K., E.L., S.B.-Z., J.R., G.P., F.P.L., L.S.-M., M.A.R. and A. Mo. declare no competing interests. E.M.R. and L.S.L. declare that they contributed to the development of the KOOS. L.S.L. also declares that he contributed to the development of the ICOAP and the Anterior Cruciate Ligament Osteoarthritis Score (ACLOAS). A.G. is a consultant to AstraZeneca, Merck Serono, TissueGene and Pfizer, and he is a shareholder of Boston Imaging Core Lab, LCC. D.J.H. is a consultant to Merck Serono, Pfizer, TissueGene and TLCBio, and contributed to the development of the MRI Osteoarthritis Knee Score (MOAKS).
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
KOOS scoring instructions: http://www.koos.nu/
Osteoarthritis Initiative: https://nda.nih.gov/oai
Single leg hop for distance: https://www.sralab.org/rehabilitation-measures/single-limb-hop-tests
30-Second chair sit-to-stand test: https://vimeo.com/74649743
6-Minute walk test: https://vimeo.com/74649737
About this article
Cite this article
Emery, C.A., Whittaker, J.L., Mahmoudian, A. et al. Establishing outcome measures in early knee osteoarthritis. Nat Rev Rheumatol 15, 438–448 (2019). https://doi.org/10.1038/s41584-019-0237-3
Effect of total joint replacement in hip osteoarthritis on serum COMP and its correlation with mechanical-functional parameters of gait analysis
Osteoarthritis and Cartilage Open (2020)
Cross-cultural adaptation and validation of the Romanian International Knee Documentation Committee—subjective knee form
miR-20a regulates inflammatory in osteoarthritis by targeting the IκBβ and regulates NK-κB signaling pathway activation
Biochemical and Biophysical Research Communications (2019)