CC BY
0PREVENTION OF POST-TRAUMATIC ARTHROSIS OF THE KNEE
JOINT Djalilov F.R.
Djalilov Farkhodbek Rustamovich - Assistant, ANDIJAN STATE MEDICAL INSTITUTE, ANDIJAN, REPUBLIC OF UZBEKISTAN
Abstract: arthritis of the knee joint is a serious, painful disease that gets worse with age. Osteoarthritis is the most common type, and you can get it in one or both knees. The most common symptoms are pain, swelling and stiffness of the knee joint. There are many treatments that might help with the symptoms. Keywords: knee arthritis, symptoms, disease process, injury, pathogenic molecular.
UDC 617.616
Arthritis is inflammation of one or more of your joints. Pain, swelling, and stiffness are the primary symptoms of arthritis. Any joint in the body may be affected by the disease, but it is particularly common in the knee.
Knee arthritis can make it hard to do many everyday activities, such as walking or climbing stairs. It is a major cause of lost work time and a serious disability for many people.
The most common types of arthritis are osteoarthritis and rheumatoid arthritis, but there are more than 100 different forms. While arthritis is mainly an adult disease, some forms affect children.
Although there is no cure for arthritis, there are many treatment options available to help manage pain and keep people staying active.
Osteoarthritis (OA) is a painful and disabling disease caused by the breakdown of the cartilage lining between two bones within a joint. While OA may be viewed by some as an inevitable consequence of aging, arthritis continues to be one of the leading causes of disability among U.S. adults between the ages of 18-64 (Theis et al., 2018). In fact, almost all common joint injuries have been shown to progress into post-traumatic OA (PTOA) within 210 years after an acute injury. Joint injury leads to local inflammation that quickly damages the surrounding heathy joint tissues. Animal studies show that limiting the initial joint inflammation after an injury can prevent PTOA. However, current clinical treatments do not address early inflammation after an injury and, therefore, do not protect healthy tissues from being further damaged and prevent PTOA. Instead, treatments focus only on reducing pain and disability after OA has developed. Therefore, targeting the window of time immediately after an injury is essential to reducing the disability associated with
arthritis that can result in pain, a decline in mobility, and reduced quality of life, especially for military personnel for whom joint injuries are common. This overview of progress made in preventing post-traumatic osteoarthritis (PTOA) was delivered in a workshop at the Orthopaedics Research Society Annual Conference in 2019. As joint trauma is a major risk factor for OA, defining the molecular changes within the joint at the time of injury may enable the targeting of biological processes to prevent later disease. Animal models have been used to test therapeutic targets to prevent PTOA. A review of drug treatments for PTOA in rodents and rabbits between 2016 and 2018 revealed 11 systemic interventions, 5 repeated intra-articular or topical interventions, and 5 short-term intra-articular interventions, which reduced total Osteoarthritis Research Society International scores by 30%-50%, 20%-70%, and 0%-40%, respectively. Standardized study design, reporting of effect size, and quality metrics, alongside a "whole joint" approach to assessing efficacy, would improve the translation of promising new drugs. A roadblock to translating preclinical discoveries has been the lack of guidelines on the design and conduct of human trials to prevent PTOA. An international workshop addressing this in 2016 considered inclusion criteria and study design, and advocated the use of experimental medicine studies to triage candidate treatments and the development of early biological and imaging biomarkers. Human trials for the prevention of PTOA have tested anakinra after anterior cruciate ligament rupture and dexamethasone after radiocarpal injury. PTOA offers a unique opportunity for defining early mechanisms of OA to target therapeutically. Progress in trial design and high-quality preclinical research, and allegiance with patients, regulatory bodies, and the pharmaceutical industry, will advance this field. Osteoarthritis (OA) is a highly prevalent disease and an increasing burden to public health worldwide. Aging and obesity are established risk factors for OA, but joint trauma is another major contributor to the disease. For example, observational studies link knee injury in young adults to a four to sevenfold increased risk for knee OA by middle age. The resulting phenotype of OA following such known joint injury is often referred to as post-traumatic OA (PTOA), that is, assuming that the OA is caused by joint trauma. Typical knee injuries that increase the risk of knee OA include intra-articular ligament rupture, such as anterior cruciate ligament (ACL) rupture, an acute meniscal tear in the young and intra-articular fractures; the most frequent clinically significant injuries are thought to be in the ACL, the menisci, and/or the hyaline cartilage. Epidemiological studies estimate the prevalence of major acute knee trauma at 77/10,000 persons per year. ACL tears have an incidence of 8/10,000 persons per year and are associated with early subchondral bone changes after injury. Thus, there is a potential to observe the onset of PTOA relatively rapidly after trauma in injured patients, offering a unique opportunity to study early disease
mechanisms, with the aim of slowing or even halting the cascade of molecular events that occur during its early development.
Whether the resulting PTOA phenotype is similar or different from nontraumatic OA remains controversial, but the ability to relate OA development temporally to a risk event is certainly unique to PTOA. It is also important to remember that, even without joint injury, some of these individuals would have developed OA anyway and also that micro injury-related pathways may also be relevant in those with other OA, for example, cases associated with malalignment or obesity. Thus, the distinction between the classification of PTOA and "primary OA" is far from clear. In such individuals, one hypothesis is that a joint injury may accelerate the pathogenesis or just move it earlier as compared with someone with no joint injury exposure.
In trying to understand the etiology of PTOA, one could classify the consequences of joint injury into two main heavily inter-related pathogenic processes: (1) potentially adverse acute and chronic effects on molecular homeostasis, for example, inflammatory pathway activation within joint tissues by acute tissue injury (contusion or tears), chronic instability (abnormal joint loading), and/or the acute and chronic molecular effects of intra-articular bleeding (hemarthrosis) and (2) acute and chronic consequences of unfavorably altered biomechanical loading patterns and instability due to joint structural damage and associated muscle weakness. Although we know from preclinical models that many of the critical molecular pathways are mechanosensitive, we still know very little about the relative contribution of these inflammatory and biomechanical pathways in the initiation, resolution, or progression of human disease and importantly, about any interactions between the two in the etiology and pathogenesis of PTOA. Such knowledge is essential because it is plausible that both these processes may need to be considered and targeted to reduce the risk of OA following joint injury. Indeed, restoration of joint stability alone post injury does not appear to reduce the risk of future OA, implying that a deeper and multidisciplinary understanding of disease mechanisms is needed for progress in this area. It is tempting to speculate that one might define the pathogenic molecular response within the joint tissues at the time of the injury, including those inflammatory signaling pathways associated with joint pain, dysfunction, and later structural change, and the relevant biomechanical adverse factors (or those which bring about repair). This would then enable the targeting of key biological processes in this early window after the joint injury to ameliorate later disease. Current interventions at the time of acute knee injury, including rehabilitation and surgical interventions, such as ligament reconstruction, aim to improve knee pain and instability, and restore function as rapidly as possible. There has been much controversy about the relative benefits and risks of different types and timings of interventions in the posttraumatic period, particularly surgical, and whether certain surgical approaches could in
some circumstances exacerbate an injury response or delay recovery. The knee-injury "model" of OA in humans is a highly attractive model for PTOA research: acute knee trauma is common and relevant injuries well-defined and the onset of PTOA of the knee is relatively rapid. The extent of injury necessary to "cause" OA and the relative importance of different types of injury could be better understood. There are accepted imaging protocols and scoring systems for MRI of this joint in the context of injury and knee X-ray outcomes (albeit with its limitations, discussed elsewhere). The synovial fluid analysis provides a window on the joint at this time and is relatively straight forward in large joints such as the knee. Assessment of the presence of hemarthrosis is also possible via this invasive monitoring, which may represent an important prognostic factor at the time of joint injury. Following those at the time of knee injury thus offers a unique opportunity to prevent joint degeneration by measuring and modulating molecular and structural events arising from the trauma.
References
1. Gelber A.C. Joint injury in young adults and risk for subsequent knee and hip osteoarthritis. Ann Intern Med. 2000;133:321-328.
2. Wilder F. V., Hall B.J., Barrett J.P., Lemrow N.B. History of acute knee injury and osteoarthritis of the knee: a prospective epidemiological assessment. The Clearwater Osteoarthritis Study. Osteoarthritis Cartilage. 2002;10:611-616.
