About Author:
Nishith Sheth
M.Sc in Clinical Research
Cranfield university
sheth10687@gmail.com
Abstract
Osteoarthritis is one type of degenerative joint disease and also known as chronic musculoskeletal disease and it occurs mainly in elderly patients with the severe cause of disability. There are approximately 30 million persons affected with severe osteoarthritis and about 26 million persons are affected with severe osteoarthritis in United States only. The approximate annual cost to the public society in medical care is expected to reach 100 billion dollars by the end of 2020. From this much of cost, most of the cost is spent only in finding out the new diagnosis and treatment for this severe disease and also for the prevention of side effects. Today till 2010, 50% of the persons with the age over 75 suffer from the knee osteoarthritis. 80% of the aged persons with knee osteoarthritis feel difficulty in daily routine activities, while 20 % of the aged persons with mild osteoarthritis feel no difficulty in their daily routine activities.
In this disorder, the joint loses the slippery cartilage those results from ‘wear and tear’ on a joint. Thus the joint becomes large, thick and painful. Thus the bone near the cartilage tries to change and produce overgrowth of the bone. That’s why the tissue near the bone becomes inflamed and ligaments lose and joint muscle becomes weak. So the people with osteoarthritis feel pain when they are doing their normal routine activities.
REFERENCE ID: PHARMATUTOR-ART-1757
There are amounts medical and non-medical treatments obtainable for the disease and the goal behind this is to reduce the side effects and to minimize the severe disability. Non-pharmacological treatments like exercise and some beneficial nutrition, also vitamin C, D and E are used while as pharmacological management NSAIDs, glucosamine and chondritin sulfate is used. Also hyaluronic acid injection is used in severe condition.
The 30- 35 subjects within the age of greater than 40, with a mild to severe knee, hand, hip osteoarthritis pain with different sex, ethnicity and different genetic characteristics are participated. The inclusion criteria for the volunteers include suitable age, no any chronic medical conditions like severe liver and kidney disease, the agreement for the subjects regarding not start any new medication during the study. At first visit, the verbal and detailed description of the trial was provide to the subject and they have to sign the permission from regarding the participation in the study without any force and clears all doubts of the subjects regarding the participation in the study. The signed form is given to the subject. The patient was provided the questionnaire with the permission of the respective physician. They have to fill all details given in the questionnaires on their own. If any worries occur during the filling of questionnaires, then the doubts will be cleared by the respective personnel present there and the physician. Depending on the filling of the details in the questionnaire, the data will be collected and assessed for the study or for biochemical analysis.
After the 2 months of the study, various data were collected regarding the osteoarthritis patients. The data regarding the QOL before treatment and after treatment were also collected. The data like treatments used by the patients in severe condition of osteoarthritis, their pain function, their normal regular activities and the data regarding the QOL of the patients were also collected and presented on the graph individually and finally the QOL score was calculated to know the QOL of the patients.
Finally it was accomplished that the QOL of the subjects were comparatively good before the occurrence of the disease or the treatment, but when the disease precedes fast, the QOL of the patients become very severe and no treatment is available for them and they also lose their interest in any other daily routine activities.
INTRODUCTION
Osteoarthritis is one type of degenerative joint disease and also known as chronic musculoskeletal disease and it occurs mainly in elderly patients with the severe cause of disability. There are approximately 30 million persons affected with severe osteoarthritis and about 26 million persons are affected with severe osteoarthritis in United States only. The approximate annual cost to the public society in medical care is expected to reach 100 billion dollars by the end of 2020. From this much of cost, most of the cost is spent only in finding out the new diagnosis and treatment for this severe disease and also for the prevention of side effects. Today till 2010, 50% of the persons with the age over 75 suffer from the knee osteoarthritis. 80% of the aged persons with knee osteoarthritis feel difficulty in daily routine activities, while 20 % of the aged persons with mild osteoarthritis feel no difficulty in their daily routine activities.
In this disorder, the joint loses the slippery cartilage those results from ‘wear and tear’ on a joint. Thus the joint becomes large, thick and painful. Thus the bone near the cartilage tries to change and produce overgrowth of the bone. That’s why the tissue near the bone becomes inflamed and ligaments lose and joint muscle becomes weak. So the people with osteoarthritis feel pain when they are doing their normal routine activities.
Many risk factors are responsible for the development of severe osteoarthritis. Obesity, age, genetic predisposition, joint laxity, female sex and mechanical load on the body work as a vital function for its growth. Role of subchondral bone, cytokine and proteinases also works a vital function in the pathophysiology of the disease. Assessment of the severe osteoarthritis is done with the help of biomarkers and newly diagnostic procedures like sonography technique and MRI and also other new biomedical instruments and also most reliable way by using questionnaire on person’s Quality of Life.
There are number of medical and non-medical treatments available for the disease and the goal behind this is to reduce the side effects and to minimize the severe disability. Non-pharmacological treatments like exercise and some beneficial nutrition, also vitamin C, D and E are used while as pharmacological management NSAIDs, glucosamine and chondritin sulfate is used. Also hyaluronic acid injection is used in severe condition.
In osteoarthritis patients, Quality of Life related to health and routine in daily living activities is negatively affected. Quality of Life questionnaire is used to assess the Quality of Life in patients suffering from osteoarthritis. This questionnaire shows the person’s satisfaction and current functioning in daily living activities which include physical, mental, social functioning. After the complete filled questionnaire, score is calculated based on the criteria that classify the person’s different class of the disease.
Several clinical trials were carried out in the past on patients with osteoarthritis using several drugs like NSAIDs and some COX-2 inhibitors. The results had shown that the COX-2 inhibitor Rofecoxib is more effective than the high doses of NSAIDs in osteoarthritis. But this drug may lead to severe GI events, thus the patients discontinue the treatment to improve the tolerability.
HYPOTHESIS AND OBJECTIVES:
The main hypothesis behind this thesis investigate application is to assess the health related Quality of Life in patients with osteoarthritis in Gujarat using questionnaire.
Objectives:
1) To evaluate the health related Quality of Life in osteoarthritis patients in above 40 years of ages of patients in Gujarat.
2) To determine the risk factors associated with the disease.
3) To evaluate the Quality of Life of the patients with osteoarthritis before the treatment and after the treatment.
4) To compare the rate of occurrence of the disease in both male and female patients.
LITERATURE REVIEW
EPIDEMIOLOGY AND PREVALENCE:
The most widespread form of arthritis is osteoarthritis and it is the main leading cause of chronic disability and mainly occurs due to involvement of hip and knee. All osteoarthritis is not symptomatic but the WHO estimates that osteoarthritis mainly occurs in ages above 60 years with major severe chronic disability in 20% of the total population. The prevalence of osteoarthritis is higher in American countries and it affects about 30 million people with severe chronic disability. The percentage of osteoarthritis of the knee is higher in those countries than the other severe heart and lung disorders. Current treatments for osteoarthritis can reduce the symptoms but not completely cure the disease and also not decrease the development of the disease. In severe knee osteoarthritis and hip osteoarthritis patients, the only treatment available is joint and hip replacement surgery. The surgery may take higher cost than the other treatments, so most of the patients do not take part in this type of costly surgery. [1]
The osteoarthritis of the knee and hip increases with the ages with severe symptoms. In United States, the prevalence of osteoarthritis in patients was 40 million in 1995 and it may rise to 60 million in next 25 years with severe symptoms in 2020. [1]
The knee osteoarthritis and hip osteoarthritis ranks in the top 3 wellbeing care disorders in the developing world because it takes large amount of the cost for the treatment and is also not completely curable. The osteoarthritis prevalence is not same across the individuals of different genders means it is mainly found higher in women than men. Before age of 45-50, it occurs higher. But today the trend is totally changed. The rate of prevalence of osteoarthritis is higher after age 50 and it mainly affects women than men. The highest numbers of women is suffered from hip and knee osteoarthritis as compared to men who mainly have higher rate of hip osteoarthritis. The osteoarthritis epidemiology includes symptoms, severe disability and changes in the structure associated with the bone in it. [2]
The disease is known by the failure of cartilage in the involved joints. For the diagnosis, only radiography is available to see the inflammation between the involved joints and this radiography examination show narrowing joint space and osteophyte production around the joint surface and bone reformation whether available or not. Kellgren-Lawrence grading system is used to check the severity of the radiograph. This system shows the osteophyte production in the range of 0-4 degree but it does not help to narrow the space between the joint and bone formation. [3]
There is less literature available on the prevalence and incidence of osteoarthritis. Symptomatic osteoarthritis mainly occurs in more than 60 years of age persons which include 18% women and 9.6% men. Knee osteoarthritis is forth most common disease that causes disability in females and eighth in males.
In England, 1.80 million people are suffering from symptomatic osteoarthritis that mainly includes knee and hip. In German and Canadian countries, 4 million people are suffering from some kind of autoimmune diseases that mainly affects joints.
In USA, the age of the patients suffering from knee osteoarthritis is 60-65 years and the occurrence of the symptoms lasts for 7- 8 years. The frequency of osteoarthritis is superior in white persons than the black persons. In the year of 1999, more than 4, 50, 000 patients had taken the visits of the physicians for the osteoarthritis and they have to stay for 5-7 days there. After the release, they have to go to the nursing home for further treatments for severe osteoarthritis. In that year, more than 25% of the patients with knee osteoarthritis have undergone to the major surgery like total joint replacement. [4]
ETIOLOGY AND RISK FACTORS FOR OSTEOARTHRITIS:
Several risk factors are responsible for occurring of osteoarthritis. Some of them are explained below with information. Exact etiology for this condition is unknown but multiple risk factors are responsible for this condition.
Genetics:
As from the results of the previous studies, it was found that genetic factors are responsible for almost 30- 70% of patients with osteoarthritis. The genetic form of osteoarthritis occurs due to defects of collagen like structural protein, receptor of vitamin D, oligomeric protein of cartilage. These proteins are only attached on the chromosome, so it was found in very major cases of osteoarthritis. Sometimes mutation of the gene is also responsible for occurrence of osteoarthritis.[5]
Metabolism:
Hyperglycemia is the major risk factor in majority of cases in patients with osteoarthritis. In patients with osteoarthritis, mean fasting plasma glucose level is high than the normal patients. in patients with osteoarthritis with diabetes, they have higher sedimentation rate with pain in the rest condition. These all conditions occur due to changes in the structure of macromolecule of matrix. Sometimes in patients with osteoarthritis, high serum level of cholesterol is also mainly in knee osteoarthritis. [5]
Age:
Sometimes the disease occurs in the age of 20 years, but as the age proceeds it becomes serious condition and also difficult to treat. [6]
Sex:
The occurrence of osteoarthritis is superior in females than the men found in previous studies. In female, the rate of knee, hand and hip osteoarthritis is higher than the men due to involvement of more joint. Also the risk is higher after the menopause in female suffering from osteoarthritis. [6]
Obesity:
The most severe risk factor for osteoarthritis is obesity. Also for the knee osteoarthritis, sometimes overweight is also responsible for this condition. The case is also higher in women than in men. Sometimes due to overweight, bilateral hip osteoarthritis occurs rapidly in females. 2 mechanisms are responsible for this factor. In one mechanism, due to overload on the joint, disruption of the cartilage occur. Because the patients with osteoarthritis with overweight have higher bone mass, so it may grow the thickness of the subchondral bone, as a result, the breakdown of the cartilage occurs. In second mechanism, the systemic factors like growth factor are also responsible. [5]
Bone density:
There is an opposite correlation between osteoporosis and osteoarthritis. The increase in the bone density of the subchondral bone leads to cartilage breakdown that result in osteoarthritis. [5]
Sex hormones and gynecological factors:
The incident of knee osteoarthritis in female occurs after the menopause condition. But for this, very fewer cases are found.
Occupational factors:
Knee bending is severe factor in this class for the occurrence of osteoarthritis and is mainly found in carpenters and floor washers. High weight lifting is also responsible for this. [5]
Physical activity at leisure:
Some of the activities are harmful for some of the useful joints or in patients with osteoarthritis like jogging. Professional athletes are at higher risk of knee osteoarthritis while marathon athletes are at higher risk for hip osteoarthritis. [5]
Injuries:
Limb fractures are the major cause for the occurrence of secondary osteoarthritis.
Others:
Chondrocalcinosis, crystals in cartilage, continuous immobilization, and instability of the joints, diabetic conditions and some of the occupational factors are also responsible for the occurrence of osteoarthritis. [6]
COMPOSITION AND STRUCTURE OF ARTICULAR CARTILAGE:
Composition:
Articular cartilages are mainly living materials which are mainly composed of number of small cells. These cells are known as ‘chondrocytes’. These cells are surrounded by matrix which has more than one component in their structure. In human body, the main composition of water is about 70- 85% and the remaining are proteogycan and collagen. Proteogycan contains core of the protein to which glucosaminoglycan are attached and finally forms a tooth brush like structure. The proteogycan binds to the one of the site of the hyaluronic acid and it finally results to the formation of one of the macromolecule having weight of 200 million. [7]
Now, the concentration of the proteoglycan and water content varies according to the length of the tissue. Beneath the surface, there is low concentration and high water content. In the end region, the content of water is lower and the concentration is higher in the tissue. Another composition of cartilage is collagen which makes around 60- 70% of the tissue weight. [7]
The normal color of the articular cartilage is white with smooth surface. The whole joint is connected with a capsule of the fibrous tissue whose inner surface is coated with membrane of the synovium and it produces fluid known as ‘synovial fluid’. The cartilage totally works as a mechanical worker and it provides posture shell with minimum resistance and for the reason that of its observance, it provides better lubrication between the arthritic joints. [7]
Structure:
The structure of articular cartilage is divided into the four zones namely,
1) ‘Among the articular cartilage and the subchondral bone’
2) ‘The superficial tangential zone’
3) ‘The middle zone’
4) ‘The deep and calcified zone’
The calcified cartilage is the border line of the cartilage and the subchondral bone. The boundary between the deep zone and cartilage of the calcified tissue is called ‘tidemark’. Various microscopical methods are used to see the structure of the articular cartilage that includes electron and optical microscopy. [8] The performance of the articular cartilage is mainly calculated by the relations of the main parts of the collagen, proteoglycan and interstitial liquid of the articular cartilage. [10]
The articular cartilage is composed of charged solid matrix that contains charged proteoglycan macromolecules, fibers of collagen, the ion phase and the interstitial fluid phase. The articular cartilage supports and distributes loads and also provides lubrication to the arthritic joints. [8]
Cartilage metabolism:
It is one type of active process that involves each and individual component of the cartilage. Chondrocytes serves as a very important role in the metabolism of the cartilage because of their degradative properties. The chondrocytes gets the nutrition from the synovial fluid which gets diffused by the double barrier, first in the synovial tissue and then in the matrix of the cartilage.
Cartilage is one type of tissue cells; hence it controls the transport of nutrients and other materials with the use of matrix. Also regulatory substances like hormones and peptides are also controlled by them. When this all process occurs, at the same time the other waste products are secreted by the cells into the matrix. After the all processes are over, the new macromolecules are synthesized by the cells into the matrix. [9]
PATHOPHYSIOLOGY OF OSTEOARTHRITIS:
In past years, osteoarthritis was occurred due to age or trauma. Since it occurs due to involvement of various bio-chemical, genetic and mechanical factors, its etiology is multiple and still not specific factor was found out for its development. The disease progression is divided mainly in three broad stages. [11]
1) Breakdown of matrix of cartilage through proteolytic enzymes.
2) Erosion of cartilage surface and fibrillation and in synovial fluid, release of breakdown products.
3) Synovial inflammation. This occurs when the synovial cells ingest breakdown products through phagocytosis and finally production of proteases and proinflammatory cytokines.
The main characteristics of osteoarthritis are cartilage loss with required bone changes that includes sclerosis, disintegration of subchondral bone, and development of cysts in the bone and production of osteophyte. The loss of cartilage in the bone starts as a lesion and then it progressively extends in the other bony area includes joint compartments and thus it induces alterations in articular cartilage and finally leads to loss and death of cartilage. [12]
Superficial fibrillation is characterized by loss of biglycan, decorin and large proteoglycan and they are mainly present at the surface of the articular cartilage. Thus it leads to breakdown of increased collagen II through collagenase and finally small proteoglycan degradation. The degradation of articular cartilage on the joint surface occurs due to increase in the proteolytic enzyme activity. The degradation of cartilage matrix occurs due to involvement of matrix metalloproteinase (MMP) that leads to degeneration of the cartilage. The aggrecans are groups of matrix metalloproteinase are involved in the breakdown of aggrecans, a newly founded group of enzymes. [12]
As the disease proceeds, the pH of the cartilage falls and then the Cathepsin B, L and K from the chondrocytes may participate for the further destruction of the cartilage. IL-1, TNF- alpha, Prostaglandins and leukotrienes are also implicated for the breakdown of the articular cartilage. [12]
The process of the osteoarthritis spreads in the five categories: [13]
1) Apoptosis,
2) Changes in artificial action
3) Deprivation (Degradation) changes
4) Phenotypic inflection of the chondrocytes present in the articular cartilage
5) Osteophyte formation.
The other reasons for developing osteoarthritis are: [14]
1) The properties of articular cartilage and subchondral bone are normal and they are biomaterial in nature. So the excessive loading on the bone cause the tissue to die or fail.
2) Sometimes the properties of the bone are inferior instead of the applied reasonable load. So it may lead to death of the tissue.
The wear is the main risk factor for the loss of the cartilage. It is stimulated by the IL-1 or other etiologic factors, MMPs, Cathepsin and plasmin are all available for breaking of the cartilage during the synthesis and secretion process. [14]
Nitric Oxide also plays a vital function for the breakdown of the articular cartilage as it absorbs matrix metalloproteinase of the chondrocytes. The chondrocytes in osteoarthritis patients undergoes the cell division process and produces very high amounts of DNA, RNA collagen and Prostaglandins. This may lead to an increased concentration of the prostaglandins and it is correlated with the thickening of the articular cartilage and it produces the compensated osteoarthritis with the homeostatic mechanism. These mechanisms maintain the tissue of the joint for a years and it does not undergo any mechanical stress. Sometimes the concentration of the prostaglandin falls, thus the synthesis of the prostaglandins reduced and finally end stage osteoarthritis develops. [14]
Osteoarthritis consists of every bony tissue that leads to the formation of the joints which consist of cartilage, synovium and the subchondral bone. It is the process runs dynamically in which the anabolic and catabolic process occurs simultaneously. The cartilage degradation, narrower space of the joint, stiffening of the joint tissue and production of the osteophyte are main characteristics for the development of osteoarthritis. [15]
The process again develops in three different steps. [15]
1) Interruption of the matrix cartilage by the injury, genetic or unknown risk factors.
2) Repair of the damaged cartilage by the chondrocytes. This stage proceeds through the production of energy and release of energy process which ultimately results to bone or erosion of the cartilage.
3) Reduction in the response of the chondrocytes which again leads to articular cartilage loss.
The subchondral bone undergoes the cell proliferation or cell division as the disease spreads and leads to the production of the dense bone. Then at the surface of the cartilage and margin of the joint, bone remodeling occurs which ultimately leads to the production of the osteophyte. Because of the production of the osteophyte, the avoidance between the joint occurs and also looses the motion. [15]
SIGNS AND SYMPTOMS OF OSTEOARTHRITIS:
Symptoms start with minor pain and it disappears at rest, but as the disease progresses, the severe pain occurs. Finally the joint gets severe pain and it disturbs the sleep of the patient. Sometimes stiffness also occurs after the long rest, but as the disease progresses, it will become very severe and also affect the normal regular activities. Crepitus (the sound obtained while doing normal regular activities) is most characteristic feature of the advanced osteoarthritis.
Swelling, warmth and cracking sound of the joint also occur in very severe condition. Sometimes but to the loss of the cartilage, there is less friction occur between the bones. Sometimes patients suffering from knee osteoarthritis develop a limp.
Other symptoms are severe joint pain, morning stiffness, formation of gel like structure on the joint, instability, loss of function,
The other developing signs of osteoarthritis are enlargement of the bone, Crepitus, tenderness when applying more pressure on the bone, joint effusion and joint deformity also occur in very severe cases.
BIOMARKERS FOR OSTEOARTHRITIS:
Biomarkers are one type of characteristic which is measured objectively and sometimes evaluated as normal pathologic, biologic and pharmacologic processes to intervention of the disease therapy. Some biomarkers directly detect multiple targets using various physiologic and pharmacologic conditions to detect the disease in very severe condition. They can also detect various drug targets and control the selection of various large molecular weight substances that directly act together with these achievements for further clinical research and development. Sometimes these biomarkers can also allow the faster growth of the molecules from the pharmacokinetic to therapeutic exploratory clinical studies to quantify the objective inflection relatively than accomplishment of the MTDs. They are also used to explain the pathological processes in the region of the space of the joint and also distinguish the exaggerated and non-exaggerated joint diagnostically. They are also used to differentiate the level of deprivation in the articular cartilage of the joint space. [16]
The markers directly released into the biological fluid and assist to reproduce the metabolism of the tissue joint of the bone. Their reflection provides accurate measurement of the metabolism of the diseased joint in individual. They are released in biological fluids through bone turn-over process. It has the advantage that change in the concentration of the bone marker seen very rapidly than the changes in the mineral density of the bone. The biomarkers are straight and tortuous indicators of the skeletal yield and it is used to provide important discussion about the anabolism and catabolism of the bone and also give information regarding the release of products in term of stress and joint damage. [16]
Various biomarkers for osteoarthritis to detect the disease are explained below.
1) Skeletal marker:
These markers provide information about the metabolism of the bone, synovium and cartilage and they can also detect osteoarthritis in very early stages. Various skeletal markers with useful information are explained below.
A) Synovium Turnover Markers:
Synovial membrane is a flexible tissue which is coating on the space of the joint. Glucosyl Galactosyl Pyridinoline is a one type of non-reducible connection of collagen which is only available in synovial tissue of human but not present in other soft tissue, bone and cartilage. Due to the absence of the link from other parts of the body, it acts as a biomarker for synovial turnover.
B) Bone Markers:
Bone mainly consists of type I collagen and other non-collagenous proteins such as osteocalcin and proteoglycan. Degradation of the type I collagen is simply detected by the quantity of Pyridinoline cross relations in the urine because during the secretion process their level is high in urine in osteoarthritis patients. Pyridinoline and deoxypyridinoline are markers for the resorption of bone and they are mainly seen in cartilage and type I collagen of the bone respectively.
For the formation of bone, a noncollagenous marker osteocalcin is used as a marker. The osteocalcin is mainly produced by the osteoblasts, so it mainly acts as a marker for the development of the bone tissue. The synthesis activity of osteocalcin is only measured in their serum concentration because it is mainly found higher in women than men.
C) Cartilage Marker:
The synthesis of collagen type II increases in the initial stages of osteoarthritis to repair the synthesis process which finally results to the formation of Procollagen Type II C Peptide (PIICP) concentration in cartilage of osteoarthritis than the normal cartilage. [17]
These markers are used as a formation marker for cartilage tissue. Chondrocytes becomes metabolically active in patients with osteoarthritis and thus it increase expression of the level of the proteolytic enzymes. Because of this degradation of the proteolytic enzymes, the concentration of collagen type II produces more which is a mainly detected using increased concentration of CTX-II. This marker is very useful for the measurement of the cartilage degradation. [18, 19]
The other marker for the degradation of the collagen is Type II Collagen Helical Peptide (HELIXII). Their levels are high in urine in patients with osteoarthritis than the normal.
The other marker for the degradation of the cartilage is the aggrecans which is mainly detected by using levels of chondritin and keratin sulfate in the tissue. [20]
The other marker for cartilage degradation is COMP. It mainly acts as a mixed marker i.e. used for both. It mainly regulates the assembly of fibril and also maintains the network of the collagen. The previous studies have shown that the on feet for 30 minutes can raise the levels of COMP.
2) Inflammatory Markers:
They are useful for detection of the targeted joints. C- reactive protein and ESR are not definite markers but they are useful in this type of severe conditions. YKL-40 is the inflammatory marker and it is a non-collagenous glycoprotein and is mainly produced by chondrocytes, cells of the synovium and other cells. It mainly induces T cell mediated immune response. [21, 22]
Another marker of synovial inflammation is Hyaluronic acid. It is mainly produced by fibroblasts and cell of the connective tissue. The level of Hyaluronic acid is high in patients with osteoarthritis that may lead to degradation of the cartilage.
Proteases are also act as a inflammatory marker for osteoarthritis.
The clinical advantage of the biomarkers for osteoarthritis is described by the BIPED approach.
Burden of Disease:
These markers are helped to detect the ruthlessness of the disease but not for the social or economical load of the disease.
e.g. - COMP, CTX-II, Hyaluronan
Investigative Marker:
These are the markers having inadequate information to take account of in the categories of the BIPED classification.
Prognostic Marker:
These markers are used to expect the commencement of the disease without the signs of the disease or for the existing disease in individuals at the baseline level.
E.g. MMPs, Osteocalcin, COMP
Efficacy of Intervention Marker:
These markers are used to evaluate the outcome of the treatment.
E.g. Collagenases, Stremolysin
Diagnostic Marker:
These markers are used to distinguish the unhealthy or healthy individuals.
E.g. COMP, CTX-II and Inflammatory markers.
MANAGEMENT OF OSTEOARTHRITIS:
Various different treatments are available for osteoarthritis. The goals are:
1) To reduce the severe pain,
2) Increase in functional capacity,
3) To reduce disability,
There should be individual treatment for osteoarthritis. Some severe conditions like cardiac, renal and gastric conditions and also patient’s life style and their needs and expectations must also be considered.
Non-pharmacologic management:
1) Patient Education:
Some health care professionals carry out the learning of the arthritis course to teach and learn about the disease, its process and how it spreads during severe conditions in individuals. These all activities are carried out through Quality of Life questionnaires and by other methods like health assessment questionnaires. Previous studies had shown good results by the use of telephonic contacts with the patients and it was found to be cost-effective. For this, regular contact is required with the patients. [23]
2) Exercise:
Recent studies have shown that regular exercise cannot increase the joint pain and also relief from the symptoms. The goal for this is to maintain the health, muscle strength. The patients suffering from knee osteoarthritis has to perform quadriceps-strengthening exercises regularly and have to encourage performing them on regular basis. Patients may also prefer to some aerobic exercise programs like fitness walking or swimming. These exercises show good results in their walking and also improve the symptoms and also decrease the depression and anxiety. [23]
3) Assistive Devices:
Many patients with severe hip and knee osteoarthritis are comfortable in wearing shock absorbing properties devices. The regular use of cane can decrease loading of hip by 20- 30%. Patients suffering from physical disability may get profit from some physical and occupational treatment. The physical counselor professional can instruct the patient about the use of therapeutic heat and massage. An occupational counselor professional can help the patient about the use of raised toilet and teach how to seat on it. Sometimes, splints are used to reduce the inflammation of the special joints. [23]
4) Weight Management:
The main risk factor for osteoarthritis is obesity and there is strong relation between them. So there is necessary to reduce the weight in overweight patients who are already suffered from knee osteoarthritis. [23]
Pharmacologic Management:
1) Simple Analgesics:
A wide number of treatments are available in the market and consumed by the patients suffering from the osteoarthritis. The first line treatment for the osteoarthritis is the use of paracetamol. One previous study had shown that the use of PCM in the dose of 4 gm per day can relieve the symptoms and also helps to improve the function. Opioids derivatives are used for short term therapies to reduce the severe pain. These agents are not regularly used because constipation and high chances of falling occur in elder patients. [23]
2) NSAIDS:
If NSAIDs are used as pain relievers in this type of condition, then there should be continuously monitor hepatic and renal function, because some NSAIDs may cause renal and hepatic toxicity to the older patients. Some health care professional prefer to carry out Hb, renal test before carrying out the NSAID therapy. When the pain is severe, the NSAID is given in combination with proton pump inhibitors or some prostaglandin analogs to prevent the GI symptoms. Sometimes H2 blockers are also prescribed to reduce the NSAID induced ulcer and acidity. The present all NSAIDs work through the inhibition of COX-1 and COX-2. [23]
They are mainly used as second line therapy for osteoarthritis. They are mainly used in lower doses and then the doses are increased as per the condition of the patient.
Newer Developments:
Celecoxib is the first COX-2 inhibitor approved by the USFDA for the osteoarthritis and Rheumatoid arthritis. The previous studies had shown that it may reduce the pain and inflammation and also has less GI side effects. These classes of drugs have equal potency and efficacy compared to NSAIDs, but the problem of duodenal ulcer is low with this. These classes of drugs cause loss of anti-platelet activity which results to severe cardiovascular adverse events.
Rofecoxib is also from the same class and used once only for osteoarthritis and for relief from the pain. [23]
Local Analgesics:
Capsaicin, a pepper plant derivative has shown to reduce the pain in osteoarthritis patients. Previous studies had shown that the use of capsaicin cream (4 times daily) has reduced the pain caused by osteoarthritis and the improvement of pain is measured by the use of visual analog scale. Its main side effect is burning sensation, so the patients have advised to apply cream with the use of gloves. [23]
3) Intra-articular Corticosteroid Injections:
Intra-articular injections of corticosteroid like methylprednisolone or triamcinolone are used in severe pain of osteoarthritis. The injections are not given more than 4 times in a year because repeated injections may cause the cartilage damage. [23]
Injections of triamcinolone and methylprednisolone give temporary benefits up to 4 weeks. But The American College of Rheumatology suggests that it should not be prescribed for more than 4 years. They are only used when severe joint effusion are present that inflammatory condition of the bone. Main side effects with these are atrophy of skin and skin pigmentation.
4) Intra-articular Injections of Hyaluronic Acid like Products:
Hyaluronic acid is a major non-structural component for the matrix cartilage of the bone. In patients with osteoarthritis, the molecular weight and concentration of the hyaluronic acid is decreased, thus viscosupplementation with these types of products are given in patients with osteoarthritis. Sodium Hyaluronate and Hylan GF-20 are these type of products and widely used for severe pain of osteoarthritis because of its lubricating properties. [23]
5) Surgery:
Patients who are not relieved from the medical treatment, they have to undergo with the surgery like arthroscopic debridement or joint lavage or arthroplasty. Total joint arthroplasty have great outcome and also have marked improved quality of life. [23]
There are 4 types of surgeries available:
a) Fusion:
It is also known as ‘Arthrodesis Surgical Fusion of the Joint’. In this procedure, the joint surfaces are removed and bone ends are connected. This gives relief from the pain, but the joint cannot bend. The main disadvantage for this is lack of mobility. This type of surgery is mainly performed in younger individuals who have only single joint involvement. [24]
b) Osteotomy:
This is the procedure in which the experienced surgeon cuts the bone below from the affected joint, then realigns it and resets in a better position. It provides relief from the pain and also leaves the joint mobile. This procedure is only performed in younger arthritis sufferers. [24]
c) Scoping the Joint:
In this, the joint is totally washed out. The examination of a joint is done through the use of tiny video camera. Then by means of arthroscopy, the physician can look for the damaged tissue in the joint. In this, a small incision is made through the skin, and then the small microsurgical tools are used to remove the areas of the cartilage or its fragments and thoroughly wash the joints. This procedure does not provide complete relief from the pain, but it may give relief for 1 to 6 months. [24]
d) Total Joint Replacement:
This involves complete removal of the affected joint. So the artificial joint can be placed over there using the combination of materials including Stainless steel, VitaminTM, Titanium and high density polyethylene plastics. This has shown good response in hip and knee arthritis. The joint replacements last for 10 to 20 years. [24]
6) Nutritional Supplements: (Nutripharmaceuticals)
Many of the over the counter supplements are in the market, but they are not used without the permission of the physician because of the counter effect. Glucosamine and Chondritin Sulfate are used to repair the matrix cartilage and have positive effect in osteoarthritis. The combination preparation of these two drugs, known as Cosamin DS, has found to reduce the pain and also improve the functional capacity of the bone. [26]
Glucosamine Sulfate and Chondritin Sulfate are widely marketed nutrisupplements and widely prescribed in USA and have beneficial effects on cartilage and also used in painful osteoarthritis. [25]
Glucosamine is naturally occurring substance that is found in the human body where it is acetylated and then converted into keratan sulfate, Heparan sulfate and Hyaluronan. These substances build the cartilaginous matrix and maintain the structural and functional integrity of the bone; therefore the cartilage absorbs pressure in the bone. Because of these effects, glucosamine is used to treat the disease. The proteoglycans stabilizes the membranes of the cell. Thus the glucosamine sulfate blocks the progression of the disease. It is mainly given in the dose of 500 mg 3 times daily orally for at least 6 weeks.
Chondritin sulfate mainly preserves the cartilage by providing the substrate for proteoglycan synthesis reduces the pain and decreases the overall mobility of the patients. It also stabilizes the medial femoro- tibial joint space and also alters the expression of markers of bone and cartilage metabolism. It is mainly given in the dosage of 400 mg twice daily.
Hyaluronic Acid serves as a lubricant and shock absorber for a synovial fluid. It is not absorbed orally, but intra-articularly found to be safe in the osteoarthritis in animals.It provides extra lubrication of the synovial membrane. It also controls permeability of the synovial membrane, therefore controls effusions. It directly blocks the inflammation by breaking of the free radicals. Because it is directly injected into the joint, its onset of action is rapid. It is very costly.
Chondritin Sulfate inhibits degradative enzymes that break down the matrix cartilage in the synovial fluid in osteoarthritis patients. It is also reserved for its anti-atherosclerotic effect.
7) Role of Calcitonin:
The previous study shows that the Calcitonin given orally everyday to the post-menopausal women for 3 months, it was tolerated without any adverse effect. It decreases the subchondral bone’s turnover in osteoarthritis and also removes the cartilage lesions in severe cases of osteoarthritis. Thus it is mainly analgesic to bone and has superior activity than the other agents for reducing the pain. [27]
QUALITY OF LIFE AND OSTEOARTHRITIS:
Methods used to assess Quality of Life in osteoarthritis:
Various methods are used to evaluate the Quality of Life in patients with osteoarthritis.
1) Patient Self assessment:
This is very easy method to evaluate the Quality of Life. This method is very simple, also has less cost and also acceptable to the patients. This can be obtained by using simple questionnaires which are self- reported and interviewer administered. Finally the outcomes obtained are various clinical and psychological symptoms and various physical and social functions.
Pain Measurement:
The instruments used for the measurement of pain in osteoarthritis patients include scales and semantic questionnaires for evaluation of subjects, verbal evaluation scale, and visual analog scale are most commonly used. [28] The VTS (Verbal Transitional Scale) mainly evaluates the pain determination over a specific period of time means whether the pain is severe or improved. With VRS (Verbal Rating Scale) the patient is asked to describe the pain on a scale as mild, moderate, severe on a 0 (no pain) to 10 (severe pain). The Visual Analog Scale (VAS) is mainly a 10 cm line in which the left end is assigned to 0 (no pain) and right end is assigned to 100 (severe pain). These scales are widely used in the patients because it is simple to utilize and also accessible to the patients. The Faces Pain Scale is used to explain the emotional state of the pain and mainly used in illiterate patients or in children.
The McGill pain questionnaire is also used to evaluate the pain which consist of 78 descriptions of pain and divided into 20 subclasses. [29, 30]This method is slight difficult because it must be read by the patient by the interviewer to assess the outcome of the clinical results. Severe pain with emotional behavior is mainly assessed by the use of daily diary of the patients or interviewer asked questionnaires.
VARIOUS ISSUES IN OSTEOARTHRITIS:
1) Drug related issues:
Several issues occur during the clinical trials in the past using the several drugs like NSAIDs and some COX-2 inhibitors. Finally the results had shown that the COX-2 inhibitor is more effective than the high doses of NSAIDs. After sometimes, the patients discontinue the use of NSAIDs because the NSAIDs may lead to severe GI events to improve the tolerability. To avoid this type of event, COX-2 inhibitors were developed by inhibiting the COX-1. The safety of GI event is first supported by the use of endoscopy which shows the mucosal alterations in the stomach compared to NSAIDs. These all matters were confirmed in one large study of patients with severe episodes of rheumatoid arthritis. These study shows that the use of aspirin is not profitable. The patients especially the women with higher co-morbid conditions like hypertension and some cardiovascular events are at higher risk for osteoarthritis. These patients were treated with low dose of aspirin and some anti-hypertensive agents to prevent the co-morbid conditions. So the Rofecoxib produces lower GI events than the naproxen. Also the Study of Rofecoxib was carried out on medium level patients to check its effect on hypertension than the use of naproxen. The patients using Rofecoxib and NSAIDs had shown good reducing level in blood pressure than the use of naproxen. Finally some limitations were there. Both of the drugs Rofecoxib and naproxen are used for same condition with their analgesic and anti-inflammatory properties and its use in osteoarthritis, but these medications are less consistent due to the flare-up symptoms. [33]
The use of intra-articular hyaluronic acid does not have useful action on patients suffering from osteoarthritis who have pain at relax condition. It does not result to the development in the task of the normal joint but it may lead to severe adverse events than the use of placebo. Some experimental and animal studies had shown that the molecular mass of hyaluronic acid sometimes influence the pain and the known inflammatory mechanisms in osteoarthritis. So this type of treatment is not effective for severe painful osteoarthritis. [34]
One of the studies was carried out using Opioids analogs on more number of patients and from them 60% of the patients had shown the maximum side effects. [39]The European League against Rheumatism says that Opioids analogs in combination with or without paracetamol are the best treatments for the patients of osteoarthritis in which NSAIDs and other inhibitors are poorly contraindicated or poorly tolerated. [35, 36]
The American Pain Society and The American College of Rheumatology suggest same things for the utilization of Opioids in osteoarthritis and rheumatoid arthritis. The past results had shown that the utilization of Opioids can improve Quality of Life of the patients. In overdose, it can cause respiratory failure but does not lead to any organ toxicity. Nausea, vomiting and sedation also occur and thus the patients may develop tolerance on these. In one of the study, it was found out that dry mouth occur as side effect in 30% of the patients. Some patients had shown very serious side effects like difficulty in driving the car and thus the Quality of life of the patients becomes very poor. Opioids can reduce the pain in severe malignancy and the past clinical trials had shown the improved Quality of Life in the patients. [37, 38]
One past study shows that Hyaluronic acid is more effe
.png)
