What is Arthiritis

INTRODUCTION:

The word “arthritis” is derived from two Greek words – “arthron” meaning a joint & “it is” meaning inflammation. Arthritis is a condition in which joints are painful, stiff and inflamed. The most common types of arthritis are Osteoarthritis & Rheumatoid Arthritis.

EPIDEMIOLOGY:

Osteoarthritis (OA) is the most common form of arthritis & is a chronic degenerative disorder of multifactorial etiology. OA is characterized by loss of articular cartilage, hypertrophy of bone at the margins, subchondral sclerosis & a range of biochemical and morphological alterations of the synovial membrane and joint capsule.

It is also known as degenerative arthritis & commonly affects hands, feet, spine & larger weight-bearing joints, such as hips & knees.

STRUCTURE OF NORMAL JOINT VS OSTEOARTHRITIC JOINT:

PREVALENCE:

Osteoarthritis has a prevalence of 22% to 39% in India. Some studies also reported even a higher prevalence in the range of 50% to 60.6% in India.

SIGN & SYMPTOMS:

  • Joint Pain
  • Joint Stiffness
  • Muscle Weakness
  • Joint Inflammation

RISK FACTORS:

STAGE 1:

Proteolytic breakdown of cartilage matrix occurs. Chondrocyte metabolism is affected leading to an increased production of enzymes. These include Matrix Metallo Proteinases (MMP’s - Collagenase, Stromelysin) that destroy the cartilage matrix.

Chondrocytes also produce protease inhibitors, including tissue inhibitors of MMP’s but in amounts insufficient to counteract the proteolytic effect.

Symptoms:

  • A person with Stage 1 OA does not experience any pain or discomfort; as a result of very minor wear on the components of the joint.
  • Shows very minor bone spur growth.
  • Diagnosed only through X-ray.

STAGE 2:

Stage 2 involves the fibrillation & erosion of the cartilage surface; with a subsequent release of proteoglycan and collagen fragments into the synovial fluid.

Symptoms:

  • Pain developed after walking or any physical activity.
  • Greater stiffness in the joint when not used for several hours; tenderness when kneeling or bending.

STAGE 3:

Stage 3 involves the breakdown products of cartilage induce a chronic inflammatory response in the synovium. Synovial macrophage production of MMP, as well as cytokines such as Interleukin (IL-1), Tumor Necrosis Factor (TNF-alpha) occurs. These can diffuse back into the cartilage and directly destroy tissue or stimulate chondrocytes to produce more MMP’s. Other pro-inflammatory molecules (Example: Nitric Oxide

[NO] - An inorganic free radical, may also be a factor in Stage 3.

Symptoms:

  • The cartilage damages.
  • Space between the bones is narrowing.
  • Frequent pain when walking, running, bending or kneeling.
  • Joint stiffness.

STAGE 4:

Eventually, the above events alter the joint architecture & compensatory bone overgrowth occurs in an attempt to stabilize the joint. As the joint architecture is changed, further mechanical & inflammatory stress occurs on the articular surfaces.

Symptoms:

  • Great pain and discomfort when walking
  • Joint space between bones is dramatically reduced.
  • The cartilage is almost completely gone, leaving the joint stiff.
  • The synovial fluid is dramatically decreased.

SYNOVITIS & OSTEOARTHRITIS:

The synovial membrane (also known as synovium) is a specialized connective tissue that lines the inner surface of capsules of synovial joints and tendon sheath. It makes direct contact with the fibrous membrane on the outside surface and with the synovial fluid lubricant on the inside surface.

The synovial membrane is an important source of synovial fluid. The primary component is hyaluronic acid which is essential for normal cartilage and joint function. Synovial membrane abnormalities are reported in

50% of OA patients. In OA patients, synovial inflammation & hyperplasia, reduction in hyaluronic acid and increase in catabolic factors are seen. Synovitis is commonly reported and strongly correlated in both early and late stage of OA.

MUSCLE WEAKNESS/ATROPHY & OSTEOARTHRITIS:

Synovial muscle weakness is commonly found in OA affected joints. Both, knee extensor & knee flexor strengths are lost with the progress of knee OA. The quadriceps muscle weakness may precede knee OA.

Muscle impairment in patients with knee OA are not limited to quadriceps but also involve hamstring muscles.

CURRENT TREATMENT OPTIONS:

There's no known cure for osteoarthritis, but treatments can help to reduce pain & maintain joint movement.

INITIAL TREATMENT OPTIONS FOR MILD OSTEOARTHRITIS:

For mild osteoarthritis, pain is bothersome. Current treatment options include:

  • Rest
  • Exercise
  • Weight loss
  • Use of heat & cold therapy to manage pain
  • Physical therapist advice
  • Avoidance of stress to joints

TREATMENT OPTIONS FOR MODERATE OSTEOARTHRITIS:

Osteoarthritis pain that persists despite initial treatment may require medications in addition to initial treatment options. Medications that may be useful for moderate arthritis include: NSAIDs, etc.

TREATMENT OPTIONS FOR SEVERE OSTEOARTHRITIS:

  • Stronger painkillers
  • Cortisone injections
  • Visco-supplementation
  • Surgery is generally reserved as last option for those not responding to other treatments

MAJOR LIMITATIONS OF CURRENT PHARMACOLOGICAL TREATMENT OPTIONS FOR OSTEOARTHRITIS:

NSAIDs/ Analgesics/ Disease Modifying Drugs:

  • Lack of effect on immune mediated OA progression
  • Lack of selective 5-LOX inhibition
  • No effect on muscle strengthening
  • No comprehensive cartilage protection
  • Lack of evidence of long-term safety

NEED OF A NOVEL THERAPY FOR OSTEOARTHRITIS MANAGEMENT:

Considering the multifactorial nature of OA, comprehensive approach is required to address multiple factors.

Thus, a comprehensive approach should be able to:

  • Control the immune mediated pathway of cartilage degradation
  • Control pain and inflammation of joint
  • Lubricate the joint by stimulating hyaluronic acid production
  • Strengthen the muscles