Knee osteoarthritis (OA) is one of the main health problems worldwide due to its high prevalence and associated costs. The available knowledge shows that the inflammatory component is fundamental in the development of this condition, abandoning the concept that OA is a purely degenerative disease. In this paper we will review, based on the available literature, the epidemiology and the risk factors involved, the new physiopathological knowledge, the clinical confrontation and the available medical and surgical treatments of this condition.
Introduction
Osteoarthritis is one of the main health problems worldwide due to its high prevalence, being considered the most common cause of permanent disability in people over 65 years of age in the countries in which it has been studied. greater frequency of this disease at the level of the knees 1-3 . OA was classically defined as an articular degenerative condition characterized by progressive loss of articular cartilage, marginal bone hypertrophy (osteophytes) and changes in the synovial membrane 2,4,5 , however today it is recognized that in this disease there is a gene pattern and proteomic inflammatory characteristics similar to that found in diseases as diverse as rheumatoid arthritis or metabolic syndrome 6-10 , so that currently recognizes the inflammatory component as a fundamental part. In this paper we will review the current confrontation of knee OA based on the reports available in the literature.
Glucosamine Chondroitin, Msm - 900 (3x300) Capsules
Epidemiology and risk factors
In order to determine the exact prevalence of knee OA, the definition of the disease used, the diagnosis method (clinical and / or imaging) and the affected joint are fundamental, and therefore the available data are diverse. Despite this, it is described that more than 50% of the population over 65 years of age presents some type of OA, with the knee joint being the most affected, with an incidence of 240 / 100,000 people / year.
Given that OA develops progressively over time, and that in 50% of patients the symptoms do not correlate with radiological alterations, it is essential to know which risk factors are associated with this condition and which are not. Among the recognized risk factors are age and female sex, while the genetic component has a low association with knee OA, unlike what occurs in other joints, such as the hip or hands 12 . Alterations in weight have been consistently related to knee OA, describing a relative risk of 2 for overweight people and 2.96 for obese people 13 . New systemic risk factors have been recognized in recent years highlighting the metabolic syndrome; the presence of 2 of its components causes a risk of knee OA of 2.3 times, while with 3 or more components the risk rises to 9.8 times 6 .
While physical activity has not been identified as a risk factor for the onset or progression of knee OA, 14 prior articular injuries are recognized as capable of conditioning the development of joint degenerative phenomenon. Special emphasis should be given to menisectomy greater than 30% and rupture of the anterior cruciate ligament (ACL), which condition a relative risk of the order of 7 14 and 5 times 15 respectively, producing an early posttraumatic OA (between 10-15 years of the original lesion); This is especially relevant in ACL injuries, since the surgical reconstruction of this does not reduce the risk of OA.
Pathophysiology of osteoarthritis
Without a doubt this is one of the issues that has generated a high number of research in recent years, because the final understanding of the phenomena involved would generate prevention strategies for the development of OA.
Classically, knee OA has been considered as a purely mechanical condition, with capital importance given to joint overloads associated with shaft alterations (mainly knees), traumatic injuries and multiligamentary instabilities. However, OA is currently recognized as a multifactorial disease where several noxious individuals are able to generate and perpetuate the damage to the articular cartilage, with the subsequent response of the synovial membrane and subchondral bone 11 . In this way, when the extracellular condral matrix (MEC) is compromised, a decrease in the water retention capacity is generated, losing the tissue resistance, resilience and elasticity against compression 16,17 , increasing the damage of the surrounding tissue. Due to the low rate of cell turnover and the poor reparative capacity of the cartilage, it can not compensate for the damage suffered, eventually generating the phenomenon of OA.
Regardless of the original cause of the damage, the fibroblasts of the synovial membrane respond by secreting various cytokines and inflammatory factors (IL-1, TNF-α, TGF-β, IL-8, GRO-α, among others). These inflammatory factors remain present in the joint, independent of the corrective treatment of the original cause of chondral damage (ligament stabilization, reduction of fractures, correction of axes, etc.), being able to maintain the progression of joint damage 9,18-21 . The inadequate response of the subchondral bone replaces the hyaline cartilage with fibrocartilage constituted mainly by type I collagen, which gives it a lower mechanical capacity 4,22,23 at the same time as a process of hypertrophy of the subchondral bone, characterized by angiogenesis with penetration of the neovessels in the deep layer of articular cartilage and chondral apoptosis followed by mineralization of the MEC 18,24 , which is clinically appreciated with the formation of osteophytes, geodes and decreased joint space.
Clinical confrontation, diagnosis and classification
OA of the knee is a condition whose diagnosis is eminently clinical based on the patient's signs and symptoms, the risk factors and the alterations present in the physical examination. The classic presentation of this condition is in patients over 50 years of age with chronic pain of mechanical characteristics, which is greater when initiating movements, and may subsequently decrease associated with joint stiffness greater than 30 min and joint deformity with loss of joint ranges, crepitus and effusion. However, there is a wide range of presentation of this table, not requiring all of it to make the diagnosis, so that clinical suspicion is essential, especially in patients who have the risk factors described. For the diagnosis of precision, specific criteria have been described, highlighting those of the American College of Rheumatology 25 ( Table 1 ). However, from the practical point of view these criteria are mainly used in the development of research studies.
Once diagnosed, the OA must be classified as primary or idiopathic (in balloon they correspond to 70% of knee OA) or secondary 11 , which is fundamental for the therapeutic approach in relation to the presence of other conditions susceptible to treating specifically . It is important to remember that there is no direct correlation between the degree of radiological joint deterioration and the clinical presentation of patients, 26 although it is advisable to have a basic study of rays in all patients. It is essential to obtain radiographs of good technical quality, recommending a basic study in anteroposterior, lateral, axial projection of the patella and Rosenberg ( Figure 1 ). It seems fundamental to emphasize the importance of this last projection, since it is the one that has the best correlation with the reduction of the thickness of the articular cartilage, especially in the medial compartment 27 . Radiologically, knee OA is classified in 5 grades as described by Kellgren-Lawrence ( Table 2 ) 28 , and there are other classifications described, such as Ahlback. Currently, in patients with arthritic joint pain and a negative or nonspecific radiological study, our challenge is to associate a second-line study such as magnetic resonance or arthro-CAT to adequately evaluate the characteristics of articular cartilage, soft structures periarticular and rule out other differential diagnoses (avascular necrosis). The techniques and sequences currently used in magnetic resonance imaging, such as T2 mapping, dGEMRIC or T1rho, allow to obtain quantitative information of the present chondral damage and to adequately differentiate generalized disorders of the joint (OA) with focal chondral or osteochondral lesions, which can be confronted in a specific way with highly satisfactory results 29 .
Conservative treatment alternatives
It is fundamental to understand that even today's knowledge there is no conservative treatment of OA demonstrated as capable of stopping or slowing the progression of its progression. There are a series of interventions that have been postulated as effective for the reduction of symptomatology and functional improvement, presenting solid evidence of its usefulness in weight reduction 30 and low-impact aerobic physical activity in water and floor associated with joint physiotherapy ( [TENS] exercises of joint ranges, open chain fortifications) 31 .
In relation to the available pharmacological treatments, it is essential to differentiate between those that have a clearly analgesic purpose and those that are proposed as chondroprotectors or modulators of the disease ( Figure 2 ). Within the first group of medicines we find:
- - Paracetamol (acetaminophen): analgesic without potent anti-inflammatory effects, it is considered as the 1st line drug in the treatment of knee OA, its safety being proven in long-term use 32 .
- - Non-steroidal anti-inflammatories (NSAIDs): drugs that, through the inhibition of COX enzymes, control the inflammatory process and the cascade of pain. They have been shown to be more effective than placebo and paracetamol in the treatment of pain, function and rigidity. The current recommendations are its use in patients who do not respond to paracetamol, since they have potential deleterious effects in its long-term use 33 .
- - Intra-articular corticosteroids (CIA): antiinflammatory agents historically used for OA due to its ability to reduce the inflammatory phenomenon, and through this decrease the symptomatology. Studies in animals have shown that low doses of CIA normalize the synthesis of proteoglycans and reduce chondral damage. However, when evaluating clinical use, the CIA have only shown a beneficial effect in the short term for pain relief (one week after treatment), compared to placebo, but in the long term it does not show beneficial effects and could even induce a increase in chondral damage and increase the risk of joint infection 34,35 . Our current confrontation does not recommend the use of these compounds in clinical practice, except in the cases of transient synovitis associated with joint effusion in patients diagnosed with previous OA.
Within the second group of drugs (postulated as chondroprotectors or disease modifiers) include:
- - Glucosamine (GA) and chondroitin sulfate (CS): compounds that participate in the formation of MEC proteoglycan synthesis. Both medications are administered orally. According to the available evidence, they may have a limited role in the symptomatic treatment of OA, but there are no studies that consistently demonstrate the modification of the progression of the disease 36,37 . Our current confrontation does not recommend the use of these compounds in clinical practice.
- - Unsaponifiable waste medicines: these drugs have demonstrated in vitro the ability to inhibit interleukin-1 and to stimulate the synthetic activity of articular chondrocytes. However, there are conflicting reports in relation to its usefulness in reducing or stopping the progression of the arthritic phenomenon 38 . Due to biological logic and basic science studies, our current approach includes its use with caution 39 .
- - Nutraceuticals: Among the "natural" therapeutic alternatives with possible antiarthritic effects, numerous nutraceutical compounds stand out, which share antioxidant capacities among their effects. In vitro studies have been reported in which interesting effects are shown in relation to improving the articular cartilage environment, mainly by the stimulation of anabolic metabolic pathways. Resveratrol and green tea, which have been evaluated in OA models. These polyphenols inhibit intracellular signaling pathways that stimulate proinflammatory effects capable of inducing chondral damage, a mechanism by which they could be useful 40 . They have not entered into our current therapeutic scheme due to the lack of better quality studies.
- - Hyaluronic acid (HA): unsulfated glycosaminoglycan found in large quantities in the MEC and the joint fluid. It is produced mainly by chondrocytes, synoviocytes and fibroblasts. Its function is to capture water molecules, giving it elasticity and thus contributing to the distribution function of the load of the joints. It has lubricating, mechanical barrier, anti-inflammatory, analgesic and chondroprotective effects demonstrated by in vitro and in vivo studies, promoting chondral proliferation and the synthesis of ECM components. The available evidence indicates that intra-articular HA is effective in approximately 60% of patients with knee OA in generating symptomatic improvement 41,42 . There are several treatment schemes (single injection versus repeated lower dose cycles), but it is accepted that the treatment can be repeated every 6 months. It is a good therapeutic alternative, its high cost being a limiting factor for its massive use.
- - Platelet rich plasma: natural source of cytokines obtained from platelets, which store more than 60 growth factors in their α-granules, which are subsequently released into the extracellular environment regulating different biological processes. In relation to knee OA, there is evidence that symptomatically it has better results than HA in patients with OA, 43,44 however its high cost complicates its use in current clinical practice.
Alternatives of surgical treatments
Surgical treatments for knee OA are recommended mainly in 2 clinical contexts: in those patients with unicompartmental OA and alteration of axis in which a surgical intervention (osteotomy or unicompartmental prosthesis) manage to improve the symptomatology and the anatomical alteration, being able to diminish the progression to a generalized degenerative joint phenomenon; The other group of patients with surgical indication are those with failure of conservative treatment, either due to pain progression or decreased joint function, mainly loss of range of motion ( Figure 2 ).
In relation to the non-prosthetic surgical techniques available for knee OA, arthroscopic grooming (associated with meniscal and / or chondral regularization techniques) and osteotomies are described. In the studies in which OA arthroscopy has been evaluated, limited symptomatic improvement and similar rates of arthroplasty have been demonstrated in medium-term follow-ups, 45 which is why in patients over 50 years of age we advise against this alternative and recommend treatment prosthetic. The osteotomies, whose objective lies in the correction of axes and in the discharge of the affected compartment, were widely used between 1970 and 1990 as a treatment for OA, with patients benefiting most from those with a unicompartmental commitment and considering themselves an alternative to prostheses. partial, with similar functional results according to the available evidence and recommended for those patients who wish to remain active from the sporting point of view, and with warning of the eventuality of progression of the arthritic phenomenon to the other compartments 46 .
Prosthetic alternatives are currently the most accepted solution in the international literature for knee OA. At the international level there is an increase of 170% in knee prostheses in the last decade, with a total knee prosthesis rate of 8.7 per 1,000 inhabitants, with a higher incidence in female patients (1, 5: 1). On the other hand, the duration of the prosthesis has improved considerably over the course of history, reaching revision rates of less than 10% in follow-ups at 15 years, a period with excellent functional results. 47 These epidemiological changes have begun to be seen in our country with a progressive increase in rates of knee arthroplasties in recent years. The main reported complications of these surgical interventions correspond to infection (< 1%) and aseptic loosening of the implant (< one%). There are different advances in recent years in prosthetic designs, among which it is convenient to point out the fixation of the components (cemented / uncemented), the improvement of the interface between these prosthetic components (high density polyethylene), specific designs by sex and even patient-specific, variations from surgical techniques with bone references to ligamentary references, etc., all of which have generated better results in the medium-term follow-up, with no long-term results to be recorded. The specific type of prosthesis to be used should be evaluated patient to patient to obtain the best functional result with the longest possible duration of in situ arthroplasty.
conclusion
OA of the knee is a highly prevalent disease, with great associated social and economic costs. Current knowledge indicates that this condition is multifactorial, abandoning the concept of pure degenerative disease and recognizing the importance of the inflammatory component. The confrontation is fundamentally clinical, with a basic image study. The currently available conservative treatments have not shown utility in decreasing the progression of the disease. Surgical alternatives are the treatment of choice for OA in definitive stages, being safe procedures, with low complication rates and a durability close to 90% in long-term follow-up.
Conflict of interests
The authors declare that they have no conflicts of interest.