Osteoarthritis, osteoarthrosis and osteoarthropathy – what is the difference?

Osteoarthritis, osteoarthrosis and osteoarthropathy are diseases which doctors encounter daily in their practice. The use of all three terms is customary, often without a clear justification as to why a particular term is used for a particular case. In the past several decades, doctors mainly differentiated among these diseases based on clinical presentation and radiography. In the past several years, however, significant progress has been made in the field of biochemical, immunological and cytohistological research, which has provided explanations for the pathogenesis of these conditions, enabled defining differences amongst them, and facilitated the use of appropriate terms for each one of these diseases. The term arthritis (osteoarthritis) should be used exclusively for primarily inflammatory joint diseases – rheumatoid arthritis, juvenile arthritis, reactive arthritis (Reiter’s syndrome). If the etiology is infectious, this must also be emphasized – septic (purulent) arthritis, tuberculous arthritis. Arthrosis (osteoarthrosis) relates to changes in the joints occurring due to pathological processes within the joint itself, but which, in their basis, are not inflammatory. Arthropathy is a term for joint disease stemming from another diseased organ or system of organs.

INTRODUCTION

Osteoarthritis (or just arthritis), osteoarthrosis (arthrosis) and osteoarthropathy (arthropathy) are very common conditions which most orthopedic surgeons, rheumatologists and doctors of other specialties encounter daily in their practice. The use of all three terms is customary, often without a clear justification as to why a particular term is used for a particular case. This often makes communication amongst doctors more difficult, especially in the collaboration of doctors from different countries. Problems become even more pronounced in the domain of medical publications, rendering the search for the desired topic as well as the understanding of the material written more difficult [1],[2].

This situation probably stems from several decades ago, when clinical presentation and native radiography were the main methods defining and naming these diseases. Indeed, a great majority of joint diseases are, in this respect, very similar to each other – different degrees of pain, swelling, and limitation of movement can be found in all of the conditions [3]. The radiographic images are also similar – joint space narrowing, more, or less pronounced subchondral sclerosis, osteophytes, and subchondral cysts [4]. It is only a small number of parameters, such as pronounced redness of skin, suppuration, or significantly altered basic laboratory parameters, that can help in defining a particular state as inflammation, a metabolic, or an endocrinological disorder, though, even then, not with absolute certainty. Detailed diagnostics is necessary for establishing a precise diagnosis [5].

In the last 25 - 30 years, significant progress has been made in the field of biochemical, immunological and cytohistological research, which has provided explanations for the pathogenesis of these conditions, enabled defining differences amongst them, and facilitated the use of appropriate terms for each one of these diseases.

ORIGIN

The established rule in medical tradition is to name inflammations with terms that end in –itis. The names in everyday use that are well known, even outside the medical sphere, are terms such as: appendicitis, prostatitis, encephalitis, etc. There are exceptions to this rule, such as pneumonia – inflammation of the lungs, phlegmon – inflammation of the subcutaneous tissue. What is definite, however, is that –itis refers to inflammation [6]. This is why the term arthritis refers to different types of joint inflammation. If the inflammation is infectious, then the situation is clear – purulent (septic) arthritis, tuberculous arthritis, luetic arthritis. The problem arises with a large group of rheumatoid diseases (rheumatoid arthritis, juvenile arthritis, ankylosing spondylitis, Reiter’s syndrome, SLE, etc.) where inflammation exists, but, for a long time, the way it develops and whether it is the cause or result of damage to the joint had remained unknown [7].

A particular issue is a very common state of joint deterioration which has been noted to occur as a part of the ageing process, but also in middle age, without a clear cause, as well as in young individuals, as the result of previous damage to the joint caused by some other process [8]. There is no inflammation in such cases, or if it does occur, it develops later and is not pronounced. This is why this condition could not merely have been named arthritis; therefore, in order to differentiate it from other conditions, it was named osteoarthritis. Later, due to numerous dilemmas regarding the existence and the influence of inflammation in this condition, some authors strayed away from this term and started to use the term degenerative joint disease (DJD), while others, especially in Europe, started to use the term arthrosis.

The third term – arthropathy, could, based on general medical understanding, refer to overall joint pathology. The suffix -pathy is used for every pathological state, and, in medical practice, it is used in terms denoting a group of conditions or in terms naming incompletely defined conditions – coagulopathy, hemoglobinopathy, radiculopathy, myelopathy, encephalopathy, etc. [6]. In the same way, in orthopedics, the term arthropathy has become customary for all conditions of unclear origin and development, which, based on the clinical finding, do not significantly differ from inflammation and degeneration.

CURRENT CONSIDERATIONS

Biochemical and immunological research in the field of the pathogenesis of rheumatic diseases has brought about the current understanding that this is a group of, so called, autoimmune diseases - the immune system of the patient reacts against its own cells. In the different types of rheumatoid arthritis, the main target cells for the immune system are in the synovia of the joints. Therefore, the main pathological process occurring in the joint is inflammation [9]. Inflammation is accompanied by angiogenesis, the formation of pannus – which secrets enzymes (collagenase), and a change in the composition of the synovial fluid – where the expression of the interleukin-17 (IL-17), the main activator of mastocytes, has been registered [10].

As the second step within this complex immunological process, accompanied by biochemical and histological changes, the damage to the joint cartilage occurs [11]. Cartilage, which is avascular tissue, receives its nutrients from the synovial fluid, and is therefore very sensitive to any change in the composition of this fluid. When the effect of proteolytic enzymes and inflammatory cells is added to this, it is clear why cartilage becomes damaged and deteriorates very quickly.

Degeneration is a process that develops with ageing. In fact, one could say that degeneration is ageing. Ageing, characterized by progressive loss of tissue and organ function over time, is the most prominent individual risk factor for osteoarthrosis [12].

Various genetic mechanisms drive this process [13]. It has long been known that the main change within it is the reduction of anabolic processes. In the joints, this refers to the reduction in the synthesis of synovial fluid, which provides nutrients for the cartilage, as well as the reduction of the processes of synthesis within the cartilage itself – primarily reduced synthesis of proteoglycans and glycoproteins – which results in loss of water from the matrix, thinning of the cartilage, loss of elasticity and plasticity, and finally, in fibrillation, fragmentation and erosion of the cartilage [14],[15]. Based on this, it can be concluded that the main process is the pathological process within the cartilage and that this process is not inflammation [16]. The exact pathogenetic mechanisms of osteoarthrosis remain unknown, despite the modern-day developments in analysis and diagnosis [17].

After several decades of research, it has been confirmed that inflammation in the form of synovitis is present within the process of degeneration. The latest research in this field have shown that this is partially the result of the process of chondrocyte ageing, whereby antioxidative processes are slowed down and the secretion of several inflammatory and prodegenerative mediators is increased, which is triggered by oxidative stress [18]. However, the most important factors of inflammation are the fragments of cartilage which come away from the surface of the joint and directly, mechanically, irritate the synovia, as well as proinflammatory cytokines and MMP (matrix metalloproteinases), which are released from these fragments directly onto the synovia [19],[20]. Furthermore, as in rheumatic diseases, the inflamed synovia damages the cartilage, thus completing a vicious cycle of mutual injury. This clearly demonstrates that, although it does exist, inflammation occurs as a secondary process, i.e., as the result of a different process within the joint [21].

There is a large number of cases where joint damage occurs in young and middle-aged individuals. This process is very similar to degeneration, however, as it has been stated that degeneration is, indeed, ageing, the question arises as to why one or a few joints should age more quickly than other organs or systems of organs. Again, the answer lies in pathogenesis. Namely, joints get “worn” during use. This deterioration is accelerated by increased use as well as by increased mechanical stress – overuse and overweight. Increased mechanical stress is most frequently the result of excess body weight. However, activity (sports and work related), as well as inappropriate biomechanics (acetabular dysplasia, femoroacetabular impingement, Perthes’ disease, epiphysiolysis, varus knee, state after fracture, etc.) result in joint damage [8].

Osteoarthritis is the most frequent joint disease and one of the main public health issues of the century [22]. Due to increased life expectancy, especially in developed countries, its global prevalence is rapidly rising, making it a disease linked to a very high economic burden [22],[23].

The fundamental pathological change in these cases occurs in the subchondral bone. One of the most important roles of this bone is to be the basis for the joint cartilage and to facilitate its role in receiving, buffering and transferring the forces acting in the joint. If this role is disrupted – through thickening and deforming under increased pressure caused by body weight, through change in shape caused by fracture or other disease, or due to microfractures – this directly reflects on the cartilage, which, just like in the degenerative process, deteriorates leading to synovial inflammation, and the aforementioned vicious cycle is formed again. However, in this process, inflammation is again not the main trigger, but merely one of the components of the chain without which the process would definitely still occur, but probably somewhat more slowly.

Finally, there is a large group of diseases affecting different organs and systems of organs, which in their clinical presentation also include joint damage. The most significant amongst them are the following: diabetes mellitus, hemophilia, different neuropathies (tabes dorsalis, syringomyelia, paralyses, etc.), and numerous metabolic diseases (gout, pseudogout, alkaptonuria, hemosiderosis). A typical example of arthropathy is Charcot joint (most commonly as neuropathy or diabetic arthropathy) [24]. A common feature for all of these diseases is that the main pathological process occurs outside the joints and that the damage to the joints occurs as a secondary outcome. The mechanisms of damage vary. In neuropathies it is the inadequate action of the muscular forces, i.e., mechanic damage is at the basis of the disease [25]. In diabetes mellitus, it is a combination of neuropathy and ischemia. In hemophilia it is repeated bleeding in the joint, which leads to a disruption in the nourishment of the cartilage as well as the release of proinflammatory factors resulting from the breakdown of blood cells [26]. In metabolic diseases it is the accumulation of certain substances in the joints, which leads to direct cartilage damage and synovial inflammation [27]. Therefore, in these processes, the damage is the result of multiple mechanisms, including inflammation.

OUR PERSPECTIVE

From all that has been stated, it is clear that there is a great similarity among the above-described processes. Inflammation always exists as a more or less pronounced factor. Certain studies are aimed at demonstrating that it is the main factor in all of the diseases. Cytokines and MMP, secreted by chondrocytes have already been mentioned, as well as IL-17 secreted by the synovia. Also, there are the IL-15 [28] and the system of complements, whose values are elevated in the synovial fluid, even in degenerative damage [29]. Crystals of uric acid in gout as well as CPPD (Ca-pyrophosphate dihydrate) in pseudogout are also present in the degenerative process and react with NALP3 inflammasome, the intracellular protein complex, which activates IL-1ß i IL-18, also proinflammatory factors [30],[31]. The newest theory describes the so called “adipokines”, cytokines secreted by adipose tissue, which are considered to have influence on the development of inflammation in the process of joint damage in obese people [32],[33],[34].

However, the following must be noted: inflammation is one of the main pathological processes occurring on a daily basis in the human body. Many processes are accompanied by inflammation. It occurs directly after bone fracture. Consequently, should the term fracture be changed to fracturitis? Every skin wound is followed by inflammation. Vulneritis? Is this, however, crucial from the clinical point of view? We think that it is not. The main pathogenetic process and the resulting therapeutic procedures are what a disease should be based on. Rheumatoid arthritis is a disease of inflammatory pathogenesis. It can successfully be treated over a number of years with anti-inflammatory drugs. This is why it is termed arthritis, just like juvenile arthritis, ankylosing spondyloarthritis, etc.

Diabetes mellitus, hemophilia, gout, and pseudogout can be treated, each disease in its own way. In some of these, anti-inflammatory drugs have an important role, since the inflammatory factor is strong, however, the main therapy is something else – the treatment that affects the main pathogenetic mechanism.

Finally, numerous therapeutic attempts to treat the process of arthrosis with anti-inflammatory drugs, even with the most up-to-date anti-IL-1 and anti-TNF medicaments, have been completely unsuccessful [35],[36]. This, of course, is not a reason for anti-inflammatory drugs to not be used at all, but, their role is in symptomatic treatment, and not in achieving an effect on the course of the disease [37].

CONCLUSION

Based on all that above-stated, we make the following suggestions:

◆ The term arthritis (osteoarthritis) should be used exclusively for primarily inflammatory diseases of the joints – rheumatoid arthritis, juvenile arthritis, reactive arthritis (Reiter’s syndrome). If there is an infectious etiology, this also needs to be stated – septic (purulent) arthritis, tuberculous arthritis.

◆ Arthrosis (the established acronym OA can remain but should refer to the term osteoarthrosis) relates to changes occurring in the joint as the result of pathological processes within the joint itself, which are not, in their essence, inflammatory. There, also, one must be precise:
1. Primary arthrosis – develops on a previously unchanged joint:
a) degenerative – occurs during the ageing process;
b) idiopathic – occurs more quickly than the natural ageing process, but without a clear cause.
2. Secondary arthrosis – occurs at the site of a pathological process within the joint itself. The most frequent causes are trauma, Perthes’ disease, epiphysiolysis, avascular necrosis, osteochondral defect.

Arthropathy is a term for joint disease which has developed as the result of the disease of another organ or system of organs. There are: neuroarthropathy, ischemic arthropathy, hemophilic arthropathy, diabetic arthropathy, metabolic arthropathies (gout, pseudogout, ochronosis – alkaptonuria, hemosiderosis).

This nomenclature has been in everyday use in our hospital for a number of years and from everyday practice we can say that any unclarity or uncertainty as to diagnosis is avoided in this way.

Research in this area should be continued, especially in the direction of studying the link between mechanical stress and inflammation. There are indications that abnormal mechanical stress can be transformed into intracellular signals which result in increased production of inflammation mediators [38],[39]. Further research of anti-inflammatory drugs is necessary because, even though they cannot stop the illness, these drugs are very important in lessening the symptoms. However, until a revolutionary breakthrough occurs, we propose that in everyday clinical practice we should adhere to terms that will enable more efficient and more precise diagnostics and facilitate communication amongst doctors, as well as communication between doctors and patients, to whom it will be much more easy to explain their state and answer the question as to why their neighbor has been managing joint disease successfully with medication for years while they have to undergo a surgical procedure.