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Cartilage Bone Osteoarthritis

Loss of articular cartilage, sclerosis and eburnation of sub-chondral bone, osteophytes and sub-chondral cysts (Keuttner and Goldberg 1995). Osteoarthritis (OA) is the most common disorder of the musculoskeletal system and is a consequence of mechanical and biological events that destabilize tissue homeostasis in articular joints. Osteoarthritis (OA) is currently defined by the American College of Rheumatology as a “heterogeneous group of conditions that leads to joint symptoms and signs which are associated with defective integrity of articular cartilage, in addition to related changes in the underlying bone at the joint margins.”

The etiology of OA is multi factorial, with inflammatory, metabolic, and mechanical causes. A number of environmental risk factors, such as obesity, occupation, and trauma, may initiate various pathological pathways. OA indicates the degeneration of articular cartilage together with changes in sub-chondral bone and mild intra-articular inflammation. Osteoarthritis (OA) has a very high prevalence among middle-aged and elderly people and the disease is responsible for substantial direct and indirect socioeconomic costs and the treatment options are few and unsatisfactory.

The principal treatment objectives are to control pain adequately, improve function, and reduce disability. Acetaminophen is frequently used for symptomatic OA with mild to moderate pain. Non-steroidal anti, or manual therapy. The value of interventions aimed at improving function and maximizing independence (occupational therapy, walking aids, and workplace adaptation) is also unclear. The disease course and patient's requirements often change over time, thus requiring a periodic review and readjustment of therapy rather than the rigid continuation of a single treatment.

The knee is one of the most commonly affected joints and patients present with a combination of pain, deformity, inflammation, stiffness and muscle atrophy. The essay reviews the electro magnetic therapy for treating knee osteoarthritis, analyzing the underlying principle of what it is and how it works. The research literature on the subject has been thoroughly reviewed to draw a meaningful conclusion about the effectiveness of the method.

ELECTRO MAGNETIC THERAPY

Electro magnetic therapy is a form of alternative medicine in which the disease is treated by applying electro magnetic energy to the body. Electro magnetic therapy is found to be successful in treating various forms of physical pain. The various electro magnetic devices, including magnets are used worldwide to laminate pain, to heal broken bones, to relieve many forms of stress, and to relieve symptoms involving the skeleton and the joints of the body. The human body produces very subtle electro magnetic fields, which have been generated in the body through chemical reaction within cells and ionic currents passing through the nervous system. In recent years scientists have been discovering more and more ways that electro magnetic fields influence the body's functioning both in a positive as well as a negative manner. These observations and other has led to the development of electro magnetic therapy. Osteoarthritis, which is also known as Degenerative Arthritis, is one of the most common types of arthritis. It involves the degeneration of the cartilage located in the joints. Osteoarthritis occurs due to loss of cartilage and electro magnetic therapy is believed to stimulate cartilage growth. This has led to the use of electro magnetic therapy in treating knee osteoarthritis.

CRITICAL REVIEW

Some researchers reported the successful management of osteoarthritis through controlled chondrocyte death and apoptosis, manipulation of response to anabolic and catabolic stimuli and matrix synthesis or degradation and inflammation (Fini et al., 2005). This comes under potential chondroprotective treatment. This treatment is considered to be the better approach relativAlthough many drugs o to medicine treatment as the majority of them relieve pain and increase function, but do not modify the complex pathological processes that occur in these tissues. Contrary to this pulsed electromagnetic fields (PEMFs) certainly show significant physiological effects on cells and tissues by the upregulation of gene expression of members of the transforming growth factor beta super family. This treatment also has advantage over the traditional medicines as it increases glycosaminoglycan levels, and an anti-inflammatory action. Hence there is a strong rationale for the use of electro magnetic therapy in treatment of osteoarthritis as it involves the vivo use of biophysical stimulation with PEMFs.

Liu et al., (1996) noticed the positive role of Pulsed electromagnetic fields (PEMF) as they influence the extracellular matrix metabolism of a diverse range of skeletal tissues. The positive effect of PEMF on the composition and molecular structure of cartilage proteoglycans was well established which can be considered as strong rationale for this therapy. One thing was made clear that PEMF treatment wouldn't affect the DNA content of explants. However its role in stimulated elevation of glycosaminoglycan content in the explant and conservation of the tissue's histological integrity was well documented. Moreover it was revealed that the PEMF treatment significantly suppressed both the degradation of pre-existing glycosaminoglycans biosynthetically labeled in ovo and the synthesis of new [35S]-sulfated glycosaminoglycans. Most notable finding emerged out of this study is that the exposure of embryonic chick cartilage explants to PEMF for 3 h/day maintained a balanced proteoglycan composition by down-regulating its turnover without affecting either molecular structure or function.

Thamsborg et al., (2005) also investigated the effectiveness of pulsed electromagnetic fields (PEMF) in the treatment of osteoarthritis (OA) of the knee. The emphasis was mainly given to a randomized, double-blind, placebo-controlled clinical trial and.the Western Ontario and McMaster Universities (WOMAC) questionnaire. It was revealed that a significant improvement in ADL (Activities of daily learning), stiffness and pain was recorded with PEMF-treated groups. One of the weak points that emerged out of this study is that the improvement witnessed with PMEF is not significant with aged people. The rationale for this study is that the patients <65 years of age responded extremely well to PMEF treatment in terms of reduced pain caused by osteoarthritis.

No doubt, the positive role of electromagnetic therapy in pain reduction is well established. The mechanism in which this pain reduction occurs is as follows:

Pain signals are transmitted along nerve cells to pre-synaptic terminals. At these terminals, channels in the cell alter due to a movement of ions. The membrane potential changes, causing the release of a chemical transmitter from a synaptic vesicle contained within the membrane. The pain signal is chemically transferred across the synaptic gap to chemical receptors on the post-synaptic nerve cell. This all happens in about 1/2000th of a second, as the synaptic gap is only 20 to 50 nm wide. As the pain signal, in chemical form, approaches the post-synaptic cell, the membrane changes and the signal is transferred. If we look at the voltages across the synaptic membrane then, under no pain conditions, the level is about -70 mV. When the pain signal approaches the membrane potential increases to approximately +30 mV, it allows sodium flow. This in turn triggers the synaptic vesicle to release the chemical transmitter and so transfer the pain signal across the synaptic gap or cleft. After the transmission, the voltage reduces back to its normal quiescent level until the next pain signal arrives. The application of pulsed magnetism to painful sites causes the membrane to be lowered to a hyper-polarization level of about -90 mV. When a pain signal is detected, the voltage must now be raised to a relatively higher level in order to fire the synaptic vesicles. Since the average change of potential required to reach the trigger voltage of nearly +30 mV is +100 mV, the required change is too great and only +10 mV is attained. This voltage is generally too low to cause the synaptic vesicle to release the chemical transmitter and hence the pain signal is blocked. The most effective frequencies that have been observed from research in order to cause the above changes to membrane potentials are a base frequency of around 100Hz and pulse rate settings of between 5 and 25Hz”.

THE RATIONALE

Let us critically analyse the rationale behind the efficacy and application of electro magnetic therapy in treatment of osteoarthritis. The review of some most relevant research papers has been carried out to come to a valid conclusion.

The role of electro magnetic therapy in gene expression regulation was considered to be the main rationale (Aaron et al., 2004). This gene expression happens in connective tissue cells for structural extracellular matrix (ECM) proteins resulting in an increase in cartilage and bone production. It was also established that the electro magnetic therapy enhanced repair and a gain in mechanical properties of the repairing tissues. The weakness of the study is that the biophysical interactions of electric and electromagnetic fields at the cell membrane are not well understood and require considerable additional study. It was also noticed that the understanding physical interactions and transmembrane signaling will most likely be necessary to establish dosing paradigms and improve therapeutic efficacy. Most notably, considerable information has been generated on an intermediary mechanism of activity - growth factor stimulation. In short, electric and electromagnetic fields increase gene expression for, and synthesis of, growth factors and this may function to amplify field effects through autocrine and paracrine signaling. Electric and electromagnetic fields can produce a sustained upregulation of growth factors, which enhance, but do not disorganize endochondral bone formation.

Another important rationale for using electromagnetic therapy in treatment of osteoarthritis is that it plays crucial role in chondrogenic differentiation in endochondral ossification (Coimbor et al., 2002). But it has to be applied in extremely low frequency. The positive role of electro magnetic therapy was well established by the demineralized bone matrix (DBM)-induced endochondral ossification model. The electro magnetic therapy brought significant changes in [35S]-Sulfate and [3H]-thymidine incorporation and glycosaminoglycan (GAG) content. Bistolfi (2006) emphasized the importance of electro magnetic therapy in causing bioeffects at the bone and soft tissue level, and at the cellular level. It affects the functioning of osteoblasts, osteoclasts, keratinocytes, fibroblasts, chondrocytes, nerve cells and endothelial and muscle cells. The strong rationale behind the role of electro magnetic therapy lies in transduction phenomena occurring in living matter. The main drawback of this theory is that electromagnetic and mechanical signals are not always interchangeable, depending on their respective intensity.

One theory on efficacy of electromagnetic theory in reducing the pain caused due to osteoarthritis states that the aged animals may not respond well. However, it was proved wrong as some research investigations conducted on Guinea pigs revealed that the pulsed electromagnetic field (PEMF) stimulation has a chondro protective effect on osteoarthritis (OA) progression in the knee joints of aged guinea pigs. Even in the presence of severe OA lesions PEMFs maintained a significant efficacy in reducing lesion progression.

Articular cartilage is the joint structure most affected by osteo-arthritis. It is constituted by cells known as chondrocytes. These cells manufacture, secrete and maintain the organic component of the extracellular compartment, or cartilage matrix, composed of a dense collagen fibril network enmeshed in aconcentrated solution of proteoglycans and water. They determine the biomechanical behaviour of the tissue in response to dynamic loading (Mow et al, 1989; Mow and Wang, 1999). Their malfunction is often related to a decrease in proteoglycan concentration, in addition to underlying bone damage, bone necrosis, and bone remodelling, leading to disruption of the cartilage collagen-proteoglycan matrix, and a decreasing ability of cartilage and the surrounding joint tissues to absorb compressive stresses.

A number of animal studies have shown that when electric field is applied on articular cartilage an increase in its proteoglycan content (Aaron and Ciombor, 1993) can be found. This is indicated by an increase in its sulphate incorporation. The biological explanation for this outcome is not very clear, but may involve information transferred to the chondrocytes concerning the nature of their mechanical environment and the state of the extracellular matrix which modifies transcription and synthesis (Aaron and Ciombor, 1993).

Alternately, pulsed electro magnetic fields may interact with ligands on the chondrocyte cell surface membrane, and this interaction may lead to changes in internal calcium concentrations that trigger proteoglycan production (Granziana et al, 1990; Lee et al, 1993). The fields may also increase chondrocyte synthesis of proteoglycans directly themselves (Aaron and Ciombor, 1993). This response, which may be cell specific may depend upon the electro physical parameters of the applied pulsed electro magnetic fields, including: amplitude, duration and frequency, in addition to the density of the cells themselves, and, intermittent exposure of cartilage cells to pulsed electro magnetic fields may be superior to continuous exposure.

In terms of duration, Brighton et al(1984) found the incorporation of sulphate into artilage macromolecules was increased within five days of pulsed electro magnetic field application to chondrocyte cell cultures and that this increased even further, after 12 days. Furthermore, the cultures exposed to the electrical fields retained 95% of their newly formed proteoglycans compared to 70% of those assayed in control cultures (Aaron and Ciombor, 1993), hence suggesting catabolism was slower in the treated tissue cultures.

Similar findings have been reported by Smith and Nagel (1983) and although cartilage collagen content tends to remain unchanged during exposure to pulsed electro magnetic fields (Aaron and Ciombor, 1993), cartilage proteoglycan molecules that are synthesised in response to pulsed electro magnetic fields appear to be normal in size and composition. Pulsed electro magnetic field treatments might also help to preserve extracellular matrix integrity in early stages of osteoarthritis, where excessive proteoglycan is laid down, by down-regulating proteoglycan synthesis and degradation in aco-ordinated manner without affecting structural integrity, and by increasing the proliferation of available chondrocytes, and their DNA synthetic mechanisms.

The mechanical and functional properties of articular cartilage depend on the complex composition and organization of its extracellular matrix (ECM). The synthesis and degradation of ECM components is strictly regulated by articular chondrocytes, which maintain cartilage homeostasis in normal conditions. In pathological conditions, such as osteoarthritis (OA), alterations in the normal functional activities of chondrocytes contribute to the imbalance in turnover of ECM components with degradation exceeding synthesis resulting in gradual damage of the articular cartilage. The articular cartilage metabolism is controlled by insulin like growth factors which can be modulated by electro magnetic forces. Clinical and animal studies show the possibility that exposure to electro magnetic force can have a positive effect on treatment of osteoarthritis.

Studies indicate that PEMF can prevent cartilage degeneration through an adenosine receptor agonist effect that can control locally the inflammatory processes that are always associated with OA progression. Evidence for enhanced cell differentiation and extracellular matrix synthesis due to PEMF has been proved by a study published in the journal of orthopaedic research (2002). An important finding of this research was that, Proteoglycans (PG) are synthesized earlier and to a greater degree in EMF-exposed ossicles. The evidence for enhanced maturation in the exposed ossicles is further supported by a temporal acceleration and quantitative increase in the expression of mRNA for aggrecan and type II collagen compared to control ossicles on days 6 and 8 of development. Accelerated maturation of cartilagematrix by EMF is also observed morphologically and biochemically. Earlier chondrocyte hypertrophy and matrix calcification are evident. Collectively, these data suggest that chondrogenic differentiation occurs earlier,and that cartilage extracellular matrix is synthesized to a greater degree and matures faster in response to EMF exposure. The result suggests the occuring of chondrogenic differentiation and that, the exposure of various configurations of electro magnetic fields can help repair osteoarthritis.

CONCLUSION

Overall, the electro magnetic therapy has helped in clinical treatment of osteoarthritis by manipulating gene expression in repair tissues, positive effect on cartilage growth and several other bio-chemical changes at cellular level in living cells. Its effect was found to be significant even in aged patients. However, the effects of magnetic fields on body tissues are complex and appear to vary from tissue to tissue and from different intensities and duration of the magnetic field applied. Much work needs to be done to optimize such variables as signal configuration and duration of treatment before pulsating electro magnetic field therapy can be generally recommended. Several research investigations though confirmed the superiority of electromagnetic therapy, its extent of positive role on knee osteo arthritis has to be further studied before drawing valid conclusions (Hulme et al., 2002).

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