Recent Advances in the Management of Osteoarthritis

 

Col K  Narayanan, Senior Advisor ( Medicine & Rheumatology ) , Army Hospital

( Research & Referral), Delhi Cantt.

           

Osteoarthritis (OA) is the commonest disease affecting synovial joints and occurs in 40% of the population over 65 years.   Though hip, ankle, shoulder and small joints of hand and feet may be involved, the commonest joints to be affected are knee joints. Previously considered a wear and tear, boring degenerative disease that must be accepted as an inevitable consequence of trauma and ageing, OA is now seen as a dynamic, essentially reparative process with genetic predisposition and exciting prospects of medical intervention. It is now known as a disease of the synovial joint affecting subchondral bone,synovium,meniscus,ligaments and supporting neuromuscular apparatus as well as the cartilage.   As OA is primarily due to breakdown of articular cartilage with poor repair both mechanisms are targets of therapeutic maneuvers.

 

Pathophysiology of cartilage changes in OA

           

Articular cartilage is composed of proteoglycans,which are responsible for the compressive stiffness of the tissue and collagen which provides tensile strength and resistance to shear.   Cartilage also contains a family of matrix metalloproteinases (MMPs) which can degrade all the components of the extra cellular matrix at neutral pH. The turnover of normal cartilage is affected through a degradative cascade,intiated by interleukin 1 ( IL), a cytokine produced by mononuclear cells and chondrocytes.   The chondrocytes in OA carilage undergo active cell division are very active metabolically proor to cartilage loss and proteoglycan depletion.  This mechanism of repair may maintain the joint in a reasonably functional state for years (Compensated OA).

 

Management

           

OA has a variable progression with some patients rapidly progressing to disability, whereas others may continue to have mild symptoms for long term. Treatment should be tailored to fit the clinical severity of the disease.    The principal goals of management are:-

 

♦ Education of the patient about OA

♦ Pain relief

♦ Achieving and maintaining optimal joint and limb function

♦ Reducing adverse factors to beneficially modify the osteoarthritis process and its outcome.

 

Non pharmacological management

 

Activities that cause excessive loading of involved joint should be avoided. Among obese weight loss can significantly reduce the risk of acquiring the disease.   Patient education, lower extremity strengthening exercises for 20-30 minutes daily, gait training, use of canes, walker, mechanical aids in the form of shock absorbing footwear with good mediolateral support, arch support and calcanial cushion are effective in reducing pain and disability. Lateral heel wedges in OA of medial tibiofemoral compartment and patellar tapping for patellofemoral OA are useful. Application of heat like hot water bath and trans cutaneous nerve stimulation (TENS) may also reduce pain and stiffness of the joints.

 

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Pharmacological Management

 

Medicine used in OA can be classified as  :-

 

  1. Symptom modifying drugs which reduces pain over short periods. (NSAIDS, Paracetamol, Capsaicin cream)
  2. Symptomatic slow acting drugs for OA (SYSDOA).  This include Hyaluronic acid (Viscosupplementation) and Neutraceuticals (Glucosamine sulphate and Chondroitin Sulphate)
  3. Structure modifying OA drugs/ Chondroprotectives (Polysulfated Glycosaminoglycans, Doxycycline, Minocycline)- Still under clinical trials.

 

Viscosupplementation :    This refers to intra articular injection of Hyaluronic acid into the joints of patients with OA. Hyaluronic acid is a polysacchride comprised of repeating disaccharide units of glucoronic acid and N-acetyl glucosamine. Viscosupplementation is based on the premise that the synovial fluid in OA is less viscous due to reduced concentration of hyaluronan and decrease in its chain length and molecular weight.  (Normal molecular weight 6-7 x 106   Da, concentration 2-4 mg/ml) Intra articular injections of hyaluronan have the potential to restore the rheological properties of synovial fluid in the osteoarthritic joint and stimulate the endogenous synthesis of a higher molecular weight and more functional hyaluronan.   It is hoped that this will clinically translate into improved mobility and decreased pain.

 

Three to five intra articular injections given at weekly intervals provide long-term symptomatic relief in moderately severe OA knee.   The potential disease-modifying role of this treatment requires confirmation by further studies. It should not be used in patients with allergy to avian products since it is derived from rooster comb.   Side effects are generally mild and transient, comprise local reactions at injection site with pain, tenderness and erythema.

 

Neutraceuticals :    Glucosamine and Chondroitin sulfate have recently become popular for treatment of OA.They are sold as nutritional supplements in US and do not have USFDA approval.    Two randomized controlled double blind trials in Belgium and Czech Republic suggested that this drug (1.5 g daily) has a substantial symptom and structure modifying effect in patients with mild to moderate OA knee.

 

IL-1 Inhibition in Osteoarthritis

 

IL-1 has been shown to accelerate the degradation of cartilage matrix by inducing proteolytic enzymes,interfering with the activity of growth factors such as insulin-like growth factor or decreasing the synthesis of key matrix components such as aggrecan.   Diacerein is a slow acting drug which interferes with the post receptor pathways following IL-1 stimulation in chondocytes and inflammatory cells.It is to be given for not less than six months at a dose of 50 mg twice a day.

 

Intra-articular Corticosteroid injection can be given in cases of inflammatory OA or OA knee with effusion once in 4-6 month interval.

 

                       

 

 

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            Tidal irrigation of the knee using large bore needles may give comfort to those who do not respond attributable to placebo effect.

 

Surgery

 

            Osteotomy and joint preserving surgical procedures should be considered in young adults with symptomatic OA, especially in the presence of dysplasia or varus/valgus deformity.

 

            Joint replacement has to be considered in patients with radiographic evidence of hip/ knee OA who have refractory pain and disability.

 

Future Prospects

 

1.         Intra articular injection of Interleukin 1 receptor antagonist can slow the progression of disease. It has been found safe and well tolerated in clinical trials.

 

2.            Cartilage regeneration : Autologus chondrocyte transplantation and attempts at cartilage repair using mesenchymal stem cells and autologus osteochondral plugs are currently being used experimentally.

 

3.         Gene therapy : The underlying concept is to deliver OA genes that have products with antiarthritic properties.   Synovium and articular cartilage are two attractive sites for the delivery of anti-OA genes.

 

EULAR Recommendations 2003 for the management of knee osteoarthritis

           

            The propositions are ranked in the order of importance as debated by the expert opinion panel.

  1. The optimal management of knee OA requires a combination of non-pharmacological and pharmacological treatment modalities
  2. The treatment of knee OA should be tailored according to:-

 

    1. Knee risk factors (obesity, adverse mechanical factors, physical activity)
    2. General risk factors (age, co morbidity, polypharmacy)
    3. Level of pain intensity and disability
    4. Sign of inflammation—for example, effusion
    5. Location and degree of structural damage

 

  1. Non-pharmacological treatment of knee OA should include regular education, exercise, appliances (sticks, insoles, knee bracing), and weight reduction.
  2. Paracetamol is the oral analgesic to try first and, if successful, the preferred long term oral analgesic.
  3. Topical applications (NSAID, capsaicin) have clinical efficacy and are safe.
  4. NSAIDs should be considered in patients unresponsive to paracetamol. In patients with an increased gastrointestinal risk, non-selective NSAIDs and effective gastroprotective agents, or selective COX 2 inhibitors should be used.

 

 

 

 

 

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  1. Opioid analgesics, with or without paracetamol, are useful alternatives in patients in whom NSAIDs, including COX 2 selective inhibitors, are contraindicated, ineffective, and/or poorly tolerated.
  2. SYSADOA (glucosamine sulphate, chondroitin sulphate, diacerein, hyaluronic acid) have symptomatic effects and may modify structure.
  3. Intra-articular injection of long acting corticosteroid is indicated for flare of knee pain, especially if accompanied by effusion.
  4. Joint replacement has to be considered in patients with radiographic evidence of knee OA who have refractory pain and disability.

References

 

  1. Oxford text book of Rheumatology. Third Edition.2004.
  2. Rheumatic disease clinics of North America- Osteoarthritis. May 99;  25 : 2.
  3. Charles W, Philip B. Basic principles underlying the development of Viscosupplementation for the tratment of osteoarthritis.Journal of clinical Rheumatology:1999;5: 2.
  4. Jordan KM et al. EULAR Recommendations 2003: An evidence based approach to the management of knee osteoarthritis.Ann Rheu Dis 2003;62:1145-55.
  5. Kenneth D.Osteoarthritis.Harrison’s Principles of Internal Medicine 16th ed.2005.
  6. Chevalier X et al. Safety study of intraarticular injection of Interleukin 1 receptor antagonist in patients with painful knee osteoarthritis:A multicenter study.J Rheumatol 2005 Jul;32 (7):1317-23.