| Abstract|| |
Sixty patients suffering from primary osteoarthritis of the knee were selected for treatment with intraarticular Sodium Hyaluronate regimen of three injections at weekly intervals. One year follow up of these patients revealed a satisfactory reduction of pain on a Visual Analogue Score (VAS) on an average of 8 to 3. Range of movement also improved significantly to improve activities of daily living. Four of the patients had pre-injection arthroscopies and two so far have had post-injection arthroscopies. It has been found that there was some evidence of chondroprotection. This treatment modality has the potential to become an important option in our armamentarium for osteoarthritis given that lesser operative procedures (arthroscopy, HTO) do not achieve long symptom free intervals.
Keywords: Viscosupplementation- Sodium Hyaluronate- Arthritic Knee- Chondroprotection
|How to cite this article:|
Rao G S, Malviya A. Viscosupplementation in degenerative joint disease. Indian J Orthop 2002;36:7
| Introduction|| |
Osteoarthritis is one of the commonest diseases presenting to the orthopaedic department. It is primarily a disease of the elderly making its appearance after the age of 40 yrs and is more common in females. It has been estimated that after the age of 65 more than 40% of the people have osteoarthritis and the commonest joint to be affected is the knee.
It is not merely a static degenerative pathology but a dynamic one in which the process of degeneration is accompanied by reactive regeneration, of course with the degenerative process predominating. Primary osteoarthritis is an active process with enhanced metabolic activity in the joint. Articular cartilage involvement is the earliest pathology. Available disease modifying drugs aim to not only arrest this process but also help in regeneration of the articular cartilage. It is difficult to predict how far these so called nutritional supplements will go in modifying the course of the disease.
Synovial fluid acts as a lubricant of the joint when the joint motion is slow and as a shock absorber when the motion is fast. In addition, the quality of the synovial fluid dictates the nutrition available to the articular cartilage. In osteoarthritis the viscosity of synovial fluid is decreased thus exposing the joint to increased loads, which are poorly distributed. The viscosity is dependent on the hyaluronic acid content of the synovial fluid. Viscosupplementation is an endeavour to improve the quality and viscosity of the synovial fluid by intrarticular injection of hyaluronic acid. This viscous supplement also has anti-inflammatory properties and stimulates the endogenous synthesis of hyaluronic acid. It can delay the need of joint replacement surgery or make the patient comfortable until the joint replacement surgery becomes a viable option.
Based on the literature published it has been found that the viscosupplementation with hyaluronic acid does seem to modulate the painful symptoms of osteoarthritis in addition to improving the function of the degenerate joints especially in mild to moderate osteoarthritis. The positive clinical results are based on both the direct and indirect effects of viscosupplementation, which normalises the rheological properties of the synovial fluid, decreases inflammation and endcoating of the nociceptors of the osteoarthritic joints.
| Material and Methods|| |
Efficacy of hyaluronic acid injections in 60 patients of osteoarthritis and rheumatoid arthritis of the knee was studied. The exact indications for viscosupplementation are still evolving, but in our series the following patients were considered -
- Mild to moderate OA and RA not responding to traditional pharmacological and non- pharmacological treatment.
- Patients who are intolerant to traditional treatment due to gastrointestinal problems related to anti-inflammatory treatment.
- Severe OA and RA when any surgical intervention is not contemplated due to associated medical problem or due to financial or other constraints.
Cases with following contraindication to the injection were excluded
- Patients with known hypersensitivity to hyaluronate preparation and allergy to feathers, eggs, poultry or avian proteins
- Cases of infection or skin diseases in the area of the injection site
- Large effusion, infected joint
- Venous stasis
Three injections of 20 mg hyaluronic acid (Synject - Gland Pharma Ltd.) were given intra-articularly at weekly intervals. Routine strict aseptic technique was adhered to during the administration of the injections into the joint. After giving the injections patients were advised to avoid excessive weight bearing and strenuous or prolonged (>1hr) exercises for the next 48 hrs. They were also informed that they might develop transient pain or swelling after the injection.
The patients were followed up at intervals of 4 weeks for three months and then at intervals of three months up to one year. Our average follow-up was 24 weeks. Preoperative arthroscopy was done in four patients and post-operative arthroscopy was done in two patients six months after full course of injection.
During the initial presentation and on follow-up the following parameters were noted down. Subjective Scoring of Pain - on Visual Analogue Score (VAS)
Objective findings - Knee Society Knee Score 
Pain - none, mild, moderate, severe
Range of motion
Stability - antero posterior, medio-lateral
Function - walking, stair climbing
Taking these criteria into consideration we assessed the improvement or deterioration of the disease. The results were graded into good / moderate / poor according to the improvement in scores.
| Results|| |
The study was conducted in 88 knees in 60 patients with bilateral affection in 28 patients. Thirty-four patients were females. Osteoarthritis accounted for 82 knees while six were cases of rheumatoid arthritis. The arthritis could be graded as mild, moderate or severe [Table 1]. Subjectively the average visual analogue score was 8 in preinjection group and 3 in postinjection group. Objective improvement in the Knee Society Knee Score was seen in 49 patients and 72 knees [Table 2],[Table 3]. No complication like septic arthritis, hypersensitivity or exacerbation was seen. Eleven patients had no or minimal improvement.
| Discussion|| |
Hyaluronic acid has been the subject of interest for centuries i.e from the time of Paracelsius who compared joint fluid with eggwhite to Virchow who isolated it from the vitreous humour. It was Mayer who coined the term hyaluronic acid in the 1930's. The first medical use of hyaluronic acid was as a vitreous replacement in ophthalmology. In the late 1960's animal studies were carried out for its use in osteoarthritis  following joint injuries in horses. Human trials ,, in the joint have shown its beneficial effects and it has been in clinical use since 1987 when it was first used in Japan and Italy.  The term Viscosupplementation was proposed in 1993. 
Hyaluronic acid is a copolymer of D-Glucuronic Acid & N-acetyl D-Glucosamine with repeating disaccharide units. It is a glycosaminoglycan made up of long unbranched polysaccharide chains with a high negative charge and viscosity. The concentration in the joint in young adults is about 3.8 mg/ml but it decreases with age and over 30 yrs the concentration drops to about 2.5 mg/ml.
The normal knee contains 1-2 ml of synovial fluid with about 2.5-8 mg of hyaluronic acid. It is continuously distributed within the joint space and tissues from the cartilage surface through the joint fluid to the intercellular matrix of the synovial tissue and the capsule. There are no barriers between these compartments. It is secreted by the beta synovial cells lining the synovial tissue and moves into the joint fluid and back through the synovial tissue. In the joint fuid hyaluronic acid molecules are crowded together and coiled in an entangled network.
Hyaluronic acid has been shown to have biological effect on injection into the joint. Intraarticular administration is said to stimulate the intrinsic hyaluronic acid synthesis, form a microlayer over the articular cartilage, increase the concentration and average molecular weight of hyaluroic acid of the synovial fluid, improve the viscoelasticity and shock absorbing ability of the joint and also has anti-inflammatory properties. Its beneficial effect has been proved by pre-injection and post-injection arthroscopic biopsy and histopathological examination in the form of macroscopic characteristics, cellularity and the number of vessels after treatment. In the deepest region of the synovial membrane it induces structural modifications typical of reparative processes, such as increase in the number of fibroblasts and in the amount of fibrosis and decrease in inflammatory cells.  Thus it has come as a valuable means to ameliorate the structural variables of the osteoarthritic synovial membrane at least in the medium term. Recent data has shown the positive effect of repeated intra-articular injections of hyaluronic acid in the human knee evaluated by X-ray joint space narrowing and arthroscopy. ,
Viscosupplementation restores visscoelastic properties of the synovial fluid. It is well tolerated and has few side effects. It is good for low deformation frequencies. It provides chondroprotection and its benefit has been proven arthroscopically. , It has shown to reduce synovial inflammation and helps in reconstitution of superficial amorphous layer of the cartilage and improves chondrocyte density.
Source of this preparation  has been both exogenous and endogenous. The main source has been rooster combs, which contain the polymer at a higher concentration with respect to other animal tissue. Another important source has been from the micro-organisms through a fermentation process. The endogenous source has been the aqueous and the vitreous humor of the eye.
In our series hyaluronic acid injections were found to be more effective in mild arthritis rather than moderate or severe arthritis. Poor results were seen in severe and moderate arthritis that were given these injections, as no other treatment modality was feasible. Even in these cases short-term improvement in pain was observed.
Two patients had postinjection arthroscopies after 6 months. Findings suggested some degree of chondroprotection. However this will have to be substantiated by further study and statistical analysis.
Cost is a major factor in more widespread use of these injections. Taking into account the falling prices and the long-term benefit in the form of postponing or doing away with the need for surgery, the viability of these injections cannot be denied. We believe that viscosupplementation is a useful mode of treatment in the spectrum of arthritis treatment from NSAIDs to total arthroplasty. Different trials have yielded varying degrees of efficacy, the majority of them favourable ,, and some showing lack of efficacy. ,
The progression in cartilage degeneration has made the corticosteroids injections unpopular in the recent times. Intraarticular hyaluronic acid is a viable alternative. However, intra-articular steroids are faster acting while the action of hyaluronan takes longer time. Studies have also demonstrated additive effect of hyaluronan with intra-articular corticosteroids.,
Since it is a small series with only one year follow-up we cannot really comment on long-term results. However they definitely seem to postpone an arthroscopic debridement of the joint and have come as a reasonable alternative to steroid injections, the long-term deleterious effects of which have been proven. Animal studies have shown the protective effect of intraarticular hyaluronic acid on preservation of the articular cartilage on long-term basis. We can hope for similar results in human beings.
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G S Rao
Medwin Hospital, Raghava Ratna Towers,Chirag Ali Lane, Hyderabad 500001
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3]