Osteoarthritis Overview: Risk factors, causes and how it affects the human body
Osteoarthritis is an inflammatory disease
The first step in understanding Osteoarthritis is to acknowledge that it as an inflammatory disease. Which means that inflammation is not exclusive to Rheumatoid Arthritis and other classical inflammatory arthritis.
Although Osteoarthritis has been largely overshadowed by Rheumatoid Arthritis due to the most severe histological and biochemical abnormalities, there have been studies since 1959 that have found that elevated levels of inflammatory plasma proteins can be found both in the bloodstream and synovial fluid in patients with Osteoarthritis.
The researchers suggested that "The type of change in permeability in the synovial tissue is similar for both diseases, although this change becomes more apparent in rheumatoid arthritis." These "standard" studies have changed the way we perceive Osteoarthritis from "weariness" disease, in an inflammatory process.
The community of rheumatology often considers Osteoarthritis as a condition manifested by significant cartilage loss and mesangia stenosis. In fact, however, according to the American Society of Rheumatology, the current classification criteria for Osteoarthritis require the presence of radiological lesions with bone enlargement or osteophyte formation.
It is now clear that inflammation is present in joints with Osteoarthritis long before the development of significant X-ray changes. In addition, a combination of sensitive imaging methods has shown that, in early stages, that is, before visible cartilage degeneration occurs, Osteoarthritis is already an inflammatory disease.
Research Data & Studies
Studies involving serial arthroscopy on the knee revealed a clear correlation between the presence of synovitis and the future development of cartilage loss. Similarly, other studies using magnetic resonance imaging (MRI) as a method suggested that there was a connection between synovitis and the progression of Osteoarthritis.
Several additional meta-analyzes of studies suggested that inflammation was observed from the very first stages of disease progression. While in a study of these, although the synovial tissue exhibited a series of radiographic Osteoarthritis, severe articular inflammation was observed in only 41% of patients. It is noteworthy that in many individuals who presented a small degree of X-ray findings of Osteoarthritis, synovial inflammation was already present.
Other studies have found that increased penetration of mononuclear cells and overexpression of inflammatory mediators are mainly presented in the early stages of the disease.
Finally, in a series of patients who did not show radiographic evidence of Osteoarthritis and who underwent arthroscopic meniscectomy to repair traumatic meniscal injury, syphilis was observed in 43% of patients, which was associated with more severe pre-operative pain and difficulty in joint functioning. These studies show that the typical signs of articular inflammation from the early Osteoarthritis are the appropriate opportunity for targeting inflammatory processes to be more effective in preventing and treating the disease. The synovial membrane is not the only tissue involved in Osteoarthritis and associated with inflammation, but it is an important area of undetectable and microscopic inflammatory change. It usually consists of 2 to 3 cell layers thick and a remarkable lack of inflammatory cells.
The regulation of inflammation is often characterized by sympathetic hyperplasia and infiltration of inflammatory cells, mainly composed of macrophages, but also by a smaller number of T and B cells, mast cells and natural killer cells. It is worth noting that the degree of evaluation is extremely heterogeneous. For example, some patients suffer from inflammation similar to that seen in rheumatoid arthritis, while others may have predominantly degenerative histopathology with minimal inflammation.
Yemenitis & Chondropathies
It should be noted that the critical role of synovitis does not in any way exclude the involvement of cartilage and chondrocytes in pathogenesis, either in the initial or subsequent progression of osteoarthritis.
Cartilage degradation products in synovial fluid, as well as micro-cracks in articular cartilage, exist long before any mark is depicted using current MRI technology or any arthroscopic visualization. Early cartilage degradation may in fact play an important role in the development of inflammation within the joint, and in particular in the synovium.
Data demostrate that in a large proportion of patients suffering from osteoarthritis, low-grade chronic inflammation is a major driving force for systemic degeneration of the joints.
Chronic Inflammation & Disease
Many of the physiological illnesses that occur in the body by the aging process are implicitly related to the chronic low-level systemic inflammation.
1. In atherosclerosis, chronic inflammation is perpetuated and extended into the atherosclerotic plaque, resulting in a possible rupture of atherosclerotic plaque and acute vascular events, such as myocardial infarction or stroke.
2. Likewise, periodontitis is a chronic inflammatory process resulting not only in tooth loss but also in potentially elevated rates of atherosclerotic cardiovascular disease associated with local systemic inflammation
3. Two additional degenerative diseases common to the progression of age are associated with activation of the innate immune and low grade inflammation, age-related macular degeneration and Alzheimer's disease
Given its role in many chronic conditions, chronic inflammation should be considered as the main driving force of progressive degeneration of the joints of osteoarthritis.
A chronic and progressively evolving inflammation
The development of chronic inflammation in osteoarthritis by trauma or excessive use can be understood as a vicious, self-sustaining, cycle of local tissue damage, that is, inflammation that prevents joint repair, therefore osteoarthritis can be likened to a chronic and progressive evolving "sore". The initial damage resulting from an acute, subacute or chronic lesion causes a local pathological inflammatory reaction that results in further loss of cartilage and progressive joint injury over time.
BMI is of central importance for the development of OA since chronic damage from an initial mechanical disorder (such as a meniscus problem), from abuse, hyperactivity, or from anatomic misalignment can cause harm, which in turn will develop into a systemic inflammation. However, in current chronic inflammation, mechanical disorder is the inducing factor.
Scientific Analysis - How Does Osteoarthritis Evolve?
How mechanically induced processes can spread the inflammation? It seems unlikely that an individual injury, even with resulting chronic mechanical instability, could lead by itself to OA's characteristic chronic inflammatory processes. Thus, there must be perpetuation factors that can transfer mechanical events to inflammatory signals.
There is a list of molecules involved in the innate immune response within the damaged joint, potentially contributing to the chronic inflammation observed in OA. Such molecules include destructurized extracellular matrix (ECM) products containing fibronectin and hyaluronan, as well as known and new DAMPS (damaged plasma metalloproteinases) that are elevated in the synovial fluid secondary to vascular exudation.
Fiodonectin fragments cause the production of proinflammatory cytokines, including (TNFα) and IL-1β, as well as matrix metalloproteinases MMP1 and MMP3, mediators that are now known to be involved in cholestolysis [Homandberg and Hui, 1996].
The damage leads to ECM degradation, producing DAMPS capable of stimulating local inflammatory reactions resulting in further cholesterol and release of ECM degradation products. It is worth noting that several additional ECM cleavage products have been implicated as DAMPS in joint damage mediation, including tenascin C and hyaluronic acid.
Many inflammatory cytokines have the ability to induce cartilage catabolism but many can also promote OA progression by inhibiting critical anabolic processes that contribute to cartilage homeostasis. As an example, IL-1β has been shown to inhibit the production of ECM (cartilage component), including angrecan and collagen types II and IX. The role of adiponectin is less clear.
One study noted an increase in the levels of antibiotic in patients with corrosive disease compared to non-corrosive disease [Filkova et al. 2009], while others suggest a protective role of the antipodectin in OA.
In addition to traditional cytokines, a new class of soluble mediators known as lipophores has been associated with CA [Honda et al. 2011]. Mainly (if not exclusively) they are derived from adipose tissue, lipophores, including leptin [Ku et al. 2009], and have been correlated with the appearance and severity of OA.
Recent studies have highlighted the beneficial role of lipocins as regards the development of obesity related to inflammation and metabolic syndrome [Qatanani et al. 2009].
Thus, epidemiological studies demonstrate that more elevated lipophores in osteoarthritis may indicate a potential mechanism by which obesity increases the risk of OA [Felson et al. 1988].
Obesity: No1 cause for the origin of osteoarthritis
However, the relationship between obesity and knee OA can be confused with altered biomechanics, as the above kilos overload the joint, dragging it on a daily basis.
Thus, local fat deposits in the tissues within the hinge including the superabroader fat pad can provide an additional source of inflammatory mediators such as lipokines and neuropeptides, as well as the more classical soluble mediators of inflammation such as IL-1β, TNFα and IL-6.
Conclusions
To sum up, clinical osteoarthritis is not a disease, but a secondary pathway for many factors that have to do with predisposition, such as age, injuries, change in biomechanics and, of course, obesity.
