Significance of osteoarthritis (OA) in the global society
OA is a degenerative joint disease that causes joint dysfunction due to pain and restricted range of motion, that could result in lowering physical activity and the quality of life. Physical inactivity caused by OA is one of the global leading health risks of non-communicable diseases (NCDs) (1,2). Although many joints such as shoulder, elbow, wrist, spine, hip, knee, and ankle can be affected by OA, the knee joint is one of the most common and vulnerable joints among them.
The prevalence of knee OA increases with age and becomes prevalent within older adults. Roentgenographic knee OA of Kellgren-Lawrence II or higher in Japan is 35.2% for male and 57.1% for women at 60–69 years old, 48.2% for male and 71.9% for female at 70–79 years old, and 61.6% for male and 80.7% for female at the age of 80 or older (3). Although OA is considered one of the most common musculoskeletal disorders worldwide in recent years, the prevalence of OA was historically as low as 0.8% in male and 5.2% in female in the 1700–1800s, and it increased by 2.1 times in the mid-1900s (3). The reason for the increase in OA prevalence is not apparent since this phenomenon was even observed in the adjusted age and BMI (4).
In addition to the decrease of physical activity, it is known that 42% of OA patients are depressed and has relations to mental disabilities (5). Approximately one out of ten OA workers were absent from work, and approximately seven had presenteeism with the depressive symptoms being more severe (6). OA is thus known to cause not only physical disabilities but also mental and social dysfunction and has a significant effect on the global burden of disease (7,8).
Significance of defining early knee osteoarthritis
The American College of Rheumatology (ACR) has developed criteria for the classification of OA of the knee and hip, mainly in order to promote uniformity in reporting OA in epidemiological and intervention studies. These criteria were developed using combinations of clinical, laboratory, and radiographic criteria (9,10). These criteria were developed primarily for epidemiological purposes rather than for clinical use and are presumably mainly diagnostic for evident late-stage OA.
Since there have been no disease-modifying OA drugs (DMOADs) that can alter the development or pathology of OA, pharmaceutical therapy for symptomatic OA is being conducted not for joint disorders and consequent biomechanical changes, but the reduction of pain. Since long-lasting pain has been known to cause pain sensitization, which may make it difficult to treat pain effectively, early diagnosis and treatment are considered as a key. The effect of an exercise intervention on OA has been demonstrated (11,12), and patient education and weight control are also recommended for effective treatment (12). Since OA develops and deteriorates over time, it means that there is a wide window of opportunity to alter its developing course potentially. OA progression may be prevented (secondary prevention) or can be delayed through diagnosis at an early stage before the joint is irreversibly destroyed. When OA is treated appropriately at an early stage in which pathology of OA is still reversible, therapeutic or exercise treatment may be valid to stop progression or even heal OA. From the prevention and treatment aspects, a clear definition of early OA is paramount for diagnosis.
Thus, in order to discover and bring new OA treatment into practical use, further researches to demonstrate the usefulness of new drugs, medical devices, regenerative medicine, exercise intervention, and patient education for secondary prevention before reaching severe OA are vital. It is important to diagnose early OA additionally for the development of new OA treatment technology as well.
Definition of early knee joint OA
As described above, the early diagnosis of OA in the knee joint is critical for effective treatment before facing severe irreversible pathology, and to develop new OA treatment techniques. Therefore, discussion on defining early OA has become more globally active (13-18), and this paper will introduce two recent ones of them.
Definition of early OA advocated by the Italian Rheumatology Association International Initiative (17)
A systematic review and three focus groups (6 expert clinicians of rheumatology, 5 female OA patients, 6 OA basic researchers), two discussion groups which consisted of 29 international experts in rheumatology, internal medicine, physical medicine, epidemiology from Albania, Belarus, Bulgaria, Croatia, France, Italy, Portugal, Romania, Russia, Serbia, Spain, Turkey, followed by a Delphi survey, ending in face-to-face workshop method were conducted in 2014 in Milan. Early symptomatic knee OA (ESKOA) was defined in the presence of (I) two mandatory symptoms (knee pain in the absence of any recent trauma or injury and very short joint stiffness, lasting for less than 10 min at the start of movement) even in the absence of risk factors, or (II) knee pain, and 1 or 2 risk factors or (III) three or more risk factors in the presence of at least one mandatory symptom, with symptoms lasting less than 6 months without active inflammatory arthritis, generalized pain, Kellgren-Lawrence grade >0, any recent knee trauma or injury, and less than 40 years of age.
Definition of early OA by the First International Early OA Workshop (18)
In November 2014, the first international early OA workshop was held in Tokyo. A research group with a total of 85 people that consisted of basic scientists, clinical scientists, rheumatologists, orthopedic surgeons and physiotherapists gathered, and early OA classification and draft standards were considered. In this workshop, after the introduction of related topics and discussion with the subcommittee, the following three classes of criteria were agreed upon: (I) pain, symptoms/signs, self-reported function, and quality of life using tools such as KOOS: scoring ≤85% in at least 2 out of these 4 categories; (II) clinical examination: at least 1 present out of joint line tenderness or crepitus; (III) knee radiographs: Kellgren & Lawrence (KL) grade of 0 or 1. Although there were discussions regarding MRI, it was not adopted as a criterion of early OA from the fact that there were no established consensus standards at that time. Biomarkers were also thought to be useful in the classification of this disease in the future, but the poor level of evidence made it so that it was decided not to be included in the criteria.
Future prospects for early OA
Several years have passed since the definition of early OA were started to be discussed globally, and several proposals have been put out. Definition of early OA with a combination of “symptoms” of joint pain, “signs” such as joint stiffness, tenderness, risk factors, and diagnostic imaging such as radiographs have been proposed. Knee osteoarthritis is a degenerative disorder of articular cartilage and includes the pathology of wide tissues such as the meniscus, synovial membrane, subchondral bone constituting the knee joint, ligament, joint capsule, tendon, and muscle. These integrated structural and qualitative abnormalities interfere with joint function, motor function, and physical activity. Furthermore, OA creates a burden both mentally and socially as well as physically and is recognized as a high global health risk causing NCD (19,20).
Consensus on a more detailed definition and classification of early OA is necessary to develop new treatment methods to suppress or prevent symptoms at an early stage before any progressive and irreversible change. Diagnostic imaging techniques such as MRI and ultrasound are superior compared to X-ray for visualization of soft tissues of joints, and quantitative evaluation of these two have been recently developed and become available. Japan has the highest number of MRI equipment adoption in the world, which makes an ideal clinical setting for evaluation of OA pathology. It also makes it possible to quantify physical activity directly as well. Recently developed wearable devices such as an accelerometer with a wireless reporting system can be used to measure physical activity quantitatively and will become a powerful tool to obtain joint biomechanics and physical activity in large scales to create big-data (21,22). Quantification of exercise and/or physical activity will be key for the evaluation and development of new treatment strategies for early stages of arthritis in the near future, due to the fact that the structural and qualitative abnormalities of joints directly affect physical activity, and improvement of that will be the primary outcome of treatment for osteoarthritis in society.
We acknowledge AMED (Japan Agency for Medical Research and Development) and Grant-in-Aid for Scientific Research (B) for K Nakata to support our research.
Conflicts of Interest: The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
- Liu Q, Niu J, Huang J, et al. Knee osteoarthritis and all-cause mortality: the Wuchuan Osteoarthritis Study. Osteoarthritis Cartilage 2015;23:1154-7. [Crossref] [PubMed]
- Yoshimura N, Muraki S, Oka H, et al. Prevalence of knee osteoarthritis, lumbar spondylosis, and osteoporosis in Japanese men and women: the research on osteoarthritis/osteoporosis against disability study. J Bone Miner Metab 2009;27:620-8. [Crossref] [PubMed]
- Waldron HA. Prevalence and distribution of osteoarthritis in a population from Georgian and early Victorian London. Ann Rheum Dis 1991;50:301-7. [Crossref] [PubMed]
- Wallace IJ, Worthington S, Felson DT, et al. Knee osteoarthritis has doubled in prevalence since the mid-20th century. Proc Natl Acad Sci U S A 2017;114:9332-6. [Crossref] [PubMed]
- Shimura Y, Kurosawa H, Tsuchiya M, et al. Serum interleukin 6 levels are associated with depressive state of the patients with knee osteoarthritis irrespective of disease severity. Clin Rheumatol 2017;36:2781-7. [Crossref] [PubMed]
- Nakata K, Tsuji T, Vietri J, et al. Work impairment, osteoarthritis, and health-related quality of life among employees in Japan. Health Qual Life Outcomes 2018;16:64. [Crossref] [PubMed]
- Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2163-96. [Crossref] [PubMed]
- Cross M, Smith E, Hoy D, et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 2014;73:1323-30. [Crossref] [PubMed]
- Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum 1986;29:1039-49. [Crossref] [PubMed]
- Altman R, Alarcón G, Appelrouth D, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip. Arthritis Rheum 1991;34:505-14. [Crossref] [PubMed]
- Uthman OA, van der Windt DA, Jordan JL, et al. Exercise for lower limb osteoarthritis: systematic review incorporating trial sequential analysis and network meta-analysis. Br J Sports Med 2014;48:1579. [Crossref] [PubMed]
- Farr JN, Going SB, McKnight PE, et al. Progressive resistance training improves overall physical activity levels in patients with early osteoarthritis of the knee: a randomized controlled trial. Phys Ther 2010;90:356-66. [Crossref] [PubMed]
- Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis, part I: critical appraisal of existing treatment guidelines and systematic review of current research evidence. Osteoarthritis Cartilage 2007;15:981-1000. [Crossref] [PubMed]
- Zhang W, Doherty M, Peat G, et al. EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis. Ann Rheum Dis 2010;69:483-9. [Crossref] [PubMed]
- Luyten FP, Denti M, Filardo G, et al. Definition and classification of early osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc 2012;20:401-6. [Crossref] [PubMed]
- Qazi AA, Folkesson J, Pettersen PC, et al. Separation of healthy and early osteoarthritis by automatic quantification of cartilage homogeneity. Osteoarthritis Cartilage 2007;15:1199-206. [Crossref] [PubMed]
- Migliore A, Scirè CA, Carmona L, et al. The challenge of the definition of early symptomatic knee osteoarthritis: a proposal of criteria and red flags from an international initiative promoted by the Italian Society for Rheumatology. Rheumatol Int 2017;37:1227-36. [Crossref] [PubMed]
- Luyten FP, Bierma-Zeinstra S, Dell'Accio F, et al. Toward classification criteria for early osteoarthritis of the knee. Semin Arthritis Rheum 2018;47:457-63. [Crossref] [PubMed]
- Lee IM, Shiroma EJ, Lobelo F, et al. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet 2012;380:219-29. [Crossref] [PubMed]
- WHO 2009 Global Health Risks: Mortality and burden of disease attributable to selected major risks (Part. P1-16). Available online: https://www.who.int/healthinfo/global_burden_disease/GlobalHealthRisks_report_full.pdf
- Li LC, Sayre EC, Xie H, et al. A Community-Based Physical Activity Counselling Program for People With Knee Osteoarthritis: Feasibility and Preliminary Efficacy of the Track-OA Study. JMIR Mhealth Uhealth 2017;5:e86. [Crossref] [PubMed]
- Dijkhuis TB, Blaauw FJ, van Ittersum MW, et al. Personalized Physical Activity Coaching: A Machine Learning Approach. Sensors (Basel) 2018. [Crossref] [PubMed]
Cite this article as: Kanamoto T, Mae T, Yokoyama T, Tanaka H, Ebina K, Nakata K. Significance and definition of early knee osteoarthritis. Ann Joint 2020;5:4.