Osteoarthritis

Osteoarthritis: It covers all the aspects of Osteoarthritis such as definition, etiology, pathophysiology, management such as pharmacotherapy, and non-pharmacological treatment.

1. OSTEOARTHRITIS BY DR.ZEEL NAIK

2. DEFINITION Osteoarthritis is a disease characterized by degeneration of cartilage and its underlying bone within a joint as well as bony overgrowth. The breakdown of these tissues eventually leads to pain and joint stiffness. The joints most commonly affected are the knees, hips, and those in the hands and spine. Osteoarthritis is also known as degenerative arthritis or hypertrophic arthritis or osteoarthrosis .

3. DEFINITION OA is common, slowly progressive disorder affecting primarily the weight baring diarthrodial (synovial) joints of the peripheral and axial skeleton. It is characterized by progressive deterioration and loss of articular cartilage, resulting in osteophyte (Bone Spur) formation, pain and limitation of motion, deformity and progressive diability in about 80% of people with osteoarthritis. Inflammation may or may not be present in the affected joints. It is most common form of arthritis or musculoskeletal condition in older people.

4. EPIDEMIOLOGY The prevalence rate for OA is 25%. It is estimated that 80% of the population have radiographic evidence of osteoarthritis by age 65, although 60% of those will have symptoms. It is the most common musculoskeletal condition. Around one-third of people aged 45 years and older have sought treatment for OA. It is more common in women than men and the prevalence increases steeply with age. The knee is most common site in the body to have OA. The other common site of OA is Hip OA and Hand and Wrist OA(DIP and PIP and base of Thumb)

5. EPIDEMIOLOGY Prevalence Overall OA affects 13.9% of adults aged 25 and older and 33.6% (12.4 million) of those 65+ Among the over 100 different types of arthritis conditions, osteoarthritis is the most common, affecting over 27 million people in the United States Incidence Before age 45, osteoarthritis occurs more frequently in males. After age 55 years, it occurs more frequently in females. Men have 45% lower incident risk of knee OA and 36% reduced risk of hip OA than women. A higher incidence of osteoarthritis exists in the Japanese population, while South African blacks, East Indians, and Southern Chinese have lower rates.

6. EPIDEMIOLOGY Mortality About 0.2 to 0.3 deaths per 100,000 population due to OA OA accounts for ~6% of all arthritis-related deaths. ~ 500 deaths per year attributed to OA; numbers increased during the past 10 years. Hospitalizations OA accounts for 55% of all arthritis-related hospitalizations; 409,000 hospitalizations for OA as principal diagnosis. Knee and hip joint replacement procedures accounted for 35% of total arthritis-related procedures during hospitalization.

7. RISK FACTORS Genetic Predisposition/Hereditary Factors Age(Older than 50 Years) Mechanical Injury/ Joint Trauma Gender( Female Sex) Obesity( BODY MASS INDEX >25) Bone Density Joint Disease( RA, SLE and Gout) Congenital Hip Dysplasia Occupation Over Use/Physical Workload High Intensity Sports activities Previous injury Muscle weakness Acromegaly ( disorder in which pituitary gland produces too much Growth Hormone) Calcium crystal deposition disease

8. CLASSIFICATION Most cases of osteoarthritis have no known cause and are referred to as Idiopathic or primary osteoarthritis. 1.Localized OA : involving one or two sites 2.Generalized OA : affecting three or four sites 3. Erosive OA : is used to describe the presence of erosion and marked proliferation in the proximal and distal interphalangeal joints. When the cause of the osteoarthritis is known, the condition is referred to as secondary osteoarthritis .

9. JOINT AND ITS PARTS A joint is the point where two or more bones are connected. joints are designed to allow movement between the bones and to absorb shock from movements like walking or repetitive motions. These movable joints are made up of the following parts: Cartilage is a protein substance that serves as a "cushion" between the bones of the joints. Joint capsule.  A tough membrane sac that encloses all the bones and other joint parts. Synovium .  A thin membrane inside the joint capsule that secretes synovial fluid. Synovial fluid.  A fluid that lubricates the joint and keeps the cartilage smooth and healthy. Ligaments, tendons, and muscles. Tissues that surround the bones and joints, and allow the joints to bend and move. Ligaments are tough, cord-like tissues that connect one bone to another. Tendons. Tough, fibrous cords that connect muscles to bones. Muscles are bundles of specialized cells that, when stimulated by nerves, either relax or contract to produce movement.

10. PATHOPHYSIOLOGY

11. PATHOPHYSIOLOGY In OA, the whole joint is involved in pathogenesis. In healthy joints , two bones articulate with one another, and the surface of each bone within the joint is covered by shock-absorbing cartilage. Both the bone and cartilage are important in dissipating the load placed through joints everyday. When the bone or cartilage is damaged as a consequence of large loads to the joint or some other form of impacts, numerous repair mechanisms attempt to restore normal function within the damaged joint to ensure the joint continues to dissipate the load correctly. This includes cell-mediating remodeling within the architecture of the cartilage and subchondral bone tissues. When the rate of damage exceeds the rate of repair, degeneration of the bone and cartilage ensues and the joint fails to effectively dissipate the load. This then results in a cycle of biomechanical and biochemical degeneration where the shock absorbing cartilage is progressively destroyed, thus exposing the bone to a greater load with subsequent bone damage(bone marrow lesions).

12. PATHOPHYSIOLOGY This then leads to further loss of cartilage, bone overgrowth with the formation of bony spurs( osteophytes ) and narrowing the joint space. The joint degeneration results in painful and tender inflammation of the synovial lining of the joint( synovitis ) and swelling of the joint(effusion). Synovitis may be present in early cartilage changes to the joint, and there is cellular infiltration with macrophages, activated T and B cells, and accompanying vasuclar proliferation. Inflammatory cytokine levels may also be elevated within the joint, but to much lesser extent than seen with RA.

13. PATHOPHYSIOLOGY

14. PATHOPHYSIOLOGY NORMAL CARTILAGE Articular cartilage is a unique substance with viscoelastic properties that provide lubrication with motion, shock absorbency during rapid movements, and load support. In synovial joints, articular cartilage is found between the synovial cavity on one side, and a narrow layer of calcified tissue overlying subchondral bone, on the other side.

15. PATHOPHYSIOLOGY Cartilage is comprised of a complex, hydrophillic , extracellular matrix. It is approximately 75%-85% water, 2%-5% chondrocytes ( the only cells in cartilage), and contains collagen proteins, smaller amounts of several other proteins, proteoglycans , and long hyaluronic acid molecules to form larger complexes, which are located within a meshwork of collagen fibrers . 5 types of collagen are located in cartilage, approximately 95% being type II collagen. The adult articular cartilage is avascular , with chondrocytes nourished by syanovial fluid. With movement and cyclic loading and unloading of joints, nutrients flow into the cartilage, whereas immobilization reduces nutrient supply. This one of the reasons that normal physical activity beneficial for joint health.

16. OSTEOARTHRITIC CARTILAGE OA commonly begins with damage articular cartilage. Damage to it dramatically increases the metabolic activity of chodrocytes . This leads to increased synthesis of matrix constituents, with swelling of cartilage. This hypertrophic response however, does not restore the cartilage to normal, but instead is the first step in a process ultimately leading to further loss of cartilage. Following the hypertrophic phase, there is increased collagen synthesis and destruction., but with destruction outpacing formation, with net loss of cartilage. Key players in this destruction are the matrix metalloproteinases (MMPs). In normal cartilage, activities of the enzymes are blocked tissue inhibitors of MMPs. In OA cartilage, there increased expression and synthesis of MMPs, resulting in proteolysis. In addition, chondrocytes contribute to loss, secreting MMPs in response to inflamatory mediators present in OA ( IN-1, TNF- alpha).

17. PATHOPHYSIOLOGY Also, chondrocytes in OA cartilage undergo apoptosis. Likely as a result of induction of nitric oxide synthase and production of toxic metabolites. This leaves fewer chondrocytes to synthesize matrix components. In addition OA chondrocytes are hyporesponsive to the anabolic stimulus transforming growth factor- beta. The net result of all this process is that there is a progressive cycle of cartilage destruction and loss of chondrocytes . In OA, subchondral bone releases vasoactive peptides and MMPs. Neovascularisation and subsequent increased permeability of adjacent cartilage also occurs and contributes further to cartilage loss.

18. PATHOPHYSIOLOGY Substantial loss of cartilage causes joint space narrowing and leads to painful, deformed joint. As cartilage is destroyed and the adjacent subchondral bone undergoes pathologic changes, cartilage is eroded completely leaving denuded subchondral bone which becomes dense, smooth and glistening Accompanying the changes in cartilage and subchondral bone local inflammatory changes and pathologic changes can occur in the joint capsule and synovium . This includes increased levels of IN-1,PG E-2,TNF- alpha and NO in synovial fluid. The pain of OA is not related to destruction of cartilage but arises from activation of nociceptive nerve endings within the joint by mechanical and chemical irritants.

19. Clinical Manifestations/Signs and Symptoms Pain and stiffness are the most common symptoms. The pain is often worse after exercise and when you put weight or pressure on the joint. The person with OA notice a rubbing, grating or crackling sound when the person move the joint. During the day, the pain may get worse when the person is active and feel better when at rest. Pain may even wake the person up at the night. Some people might not have symptoms even though x-rays show the changes of OA. The stiffness in OA is of shorter duration compared to RA. Joint deformity is another common finding in OA, especially as disease advances. Herberden’s nodes(DIP) and Bouchard’ nodes(PIP) commonly seen in OA.

20. ClLINICAL MANIFESTATIONS/SIGNS AND SYMPTOMS SYMPTOMS Nearly all patients have pain in affected joints, with the hands, hips, knees being the most common locations. Pain in most common cases is associated with motion, but pain in late disease can occur with rest. Joint stiffness resolves with motion, recurs with rest. SIGNS Joint stiffness with or without enlargement. Crepitus , a crackling sound heard with joint movement that is caused by irregularity of joint surfaces may be present. Limited range of motion that may be accompanied by joint instability Late- stage disease is associated with joint deformity.

21. HERBERDEN’S NODE AND BOUCHARD’S NODE

22. DIAGNOSIS When diagnosing OA, many factors must be considered, including careful evaluation of the patient’s history, physical examination of affected joints and radiographic findings. A complete evaluation of a patient with OA would include classification of the disease, identification of the joints involved, radiological and clinical staging and assessment of the patient’s functional capacity. A good history should include questions about the duration and severity of symptoms and the patient’s ability to perform simple daily tasks. The American College of Rheumatology(ACR) has developed criteria that review clinical, laboratory and radiographic findings seen in OA, as well as location of joint involvement.

23. DIAGNOSIS-PHYSICAL EXAMINATION CREPITUS(AUDIBLE). LOCAL INFLAMMATION. HERBERDEN AND BOUCHARD NODES. DECREASE RANGE OF MOTION. BONY PROJECTION.

24. ACR CLASSIFICATION CRITERIA FOR OA OF THE HIP

25. ACR CLASSIFICATION CRITERIA FOR OA OF THE KNEE

26. DIAGNOSIS The diagnosis of OA is made through history, physical examination, characteristic radiographic findings, and laboratory testing. (a) For hip OA, a patient must have pain in the hip and at least two of the following three: an erythrocyte sedimentation rate <20 mm/h, femoral or acetabular osteophytes on radiography, or joint space narrowing on radiography. This provides a sensitivity of 89% and a specificity of 91%. (b) For knee OA, a patient must have pain at the knee and osteophytes on radiography plus one of the following: age older than 50 years, morning stiffness no more than 30 minutes, crepitus on motion, bony enlargement, bony tenderness, or palpable warmth. This provides a sensitivity of 95% and a specificity of 69%. The addition of laboratory or radiographic data further improves accuracy of diagnosis.

27. DIAGNOSIS Arthrocentesis is often performed in the doctor's office. During arthrocentesis , a sterile needle is used to remove joint fluid for analysis. Joint fluid analysis is useful in excluding gout, infection, and other causes of arthritis. Removal of joint fluid and injection of corticosteroids into the joints during arthrocentesis can help relieve pain, swelling, and inflammation. Arthroscopy is a surgical technique whereby a doctor inserts a viewing tube into the joint space. Abnormalities of and damage to the cartilage and ligaments can be detected and sometimes repaired through the arthroscope . If successful, patients can recover from the arthroscopic surgery much more quickly than from open joint surgery.

28. Diagnosis OTHER RADIOGRAPHIC TESTS- PLAIN RADIOGRAPHIC FILMS Joint space narrowing, appearance of osteophytes in moderate disease. Abnormal alignments of joints and joint effusion in later disease. Physical findings of joint enlargement of the knees.

29. Plain x-ray films of the knee demonstrating joint space narrowing.

30. RADIOGRAPHIC FINDINGS ASYMMETRICAL JOINT INVOLVEMENT. SUBCHONDROL SCLEROSIS(HARDENING). OSTEOPHYTES JOINT SPACE NARROWING BONE ENLARGEMENT EBURNATION.

31. GOALS OF THE TREATMENT Goals To educate the patient, caregivers, and relatives. To relieve pain and stiffness. To maintain or improve joint mobility. To limit functional impairment; and To maintain or improve quality of life. To educate patients and family members about OA and its therapies.

32. TREATMENT/MANAGEMENT The treatment is divided into 2 parts: ( i )Maintenance of Function Ambulatory assistive devices such as canes, crutches, walkers etc Physical Therapy, occupation therapy and weight loss if overweight. (ii)Palliation of symptoms Exercise Heat and Ice Shoe Insoles Topical NSAIDs Systemic NSAIDs

33. PHARMACOTHERAPY Pain relief is a primary indication for initiating drug therapy in patients with OA. Because there is no medications currently available that reverse or alter the structural and biochemical changes associated with OA, drug therapy is only given to control symptoms. Individualization of patient therapy is important when dealing with medications. Many patients with OA are older and have concurrent diseases. Careful selection of agents and evaluation are important to minimize ADR and maximize efficacy.

34. PHARMACOLOGICAL THERAPY FOR OA PATIENTS ORAL ACETAMINOPHEN 4G/DAY. COX-2 SPECIFIC INHIBITOR: CELECOXIB 200 MG/DAY. NON-SELECTIVE NSAID(IBUPROFEN 1600 mg/d, ARTHROTEC 150 mg/d, VOLTAREN 150 mg/d , NAPROXEN 750 mg/d, SULINDAC 200 mg/d) plus misoprostol or proton pump inhibitor. NON-ACETYLATED SALICYLATES . OTHER PURE ANALGESICS a. TRAMADOL 50 mg( upto 400 mg/day) b. Ultracet 37.5 mg( upto 300 mg/day) 6. OPIOIDS 7 . ALTERNATIVE THERAPY : GLUCOSAMINE 1500 mg/day (alone or in combination with chondroitin ) 8 . Intraarticular : Glucocorticoids , Hyaluronan 9. Topical: Capsaicin, Methyl Salicylate , Diclofenac .

35. NON-PHARMACOLOGICAL TREATMENT OF OA Patient Education. Self-management programs. Personalized social support through telephone contact. Weight loss if overweight. Aerobic exercise programs. Physical Therapy. Range of motion exercises. Muscle strengthening exercises. Assistive Devices for ambulation. Patellar taping. Appropriate footwear. Lateral-wedged insoles. Bracing. Occupational Therapy. Joint protection and energy conservation. Joint replacement therapy or ARTHROPLASTY.

36. TREATMENT OF OA OF THE HIP Non-pharmacological treatment and acetaminophen up to 1 gm qid. If response inadequate, use alternative strategies, low dose ibuprofen (up to 400 mg qid). If response inadequate, use full-dose NSAIDs with misoprostol if patient has risk factors for GI bleed or ulcer disease If response inadequate , consider joint surgery( osteotomy, total joint arthroplasty).

37. TREATMENT OF OA OF THE KNEE Non-pharmacological treatment. Acetaminophen( upto 1gm qid) for pain and symptom control. If necessary add topical capsaicin cream. If response inadequate, use alternative strategies, low dose ibuprofen (up to 400 mg qid) If response inadequate, use full-dose NSAIDs with misoprostol if patient has risk factors for GI bleed or ulcer disease . If response inadequate , consider joint surgery( osteotomy, total joint arthroplasty).

38. Acetaminophen It is recommended by the ACR as first line drug therapy for pain management of OA. The dose is 325 to 650 mg every 4-6 hrs on a scheduled basis( maximum 4g/day; maximum 2g/day if chronic alcohol intake or underlying liver disease). It is well tolerated, but potentially fatal hepatotoxicity with overdose can occur.

39. NSAIDS NSAIDs at prescription strength are often prescribed for OA patients after the treatment with acetaminophen proves ineffective or patients with inflammatory OA. Analgesic effects begin within 1-2 hours, whereas anti-inflammatory benefits may require 2-3 weeks of continuous therapy. Selection of NSAID depends on prescriber experience, medication cost, patient preference, toxicities and adherence issue. An individual patient should be given a trial of one drug that is adequate in time (2-3 weeks) and dose. If the first NSAID fail, another agent in the same or another chemical class can be tried, this process may be repeated until an effective drug is found. Combining 2 NSAIDs increases ADR without providing additional benefit. Cyclooxygenase -2 (COX-2) selective inhibitors (e.g. celecoxib ) demonstrate analgesic benefits that are similar to traditional non-selective NSAIDs. Although COX-2 selective inhibition was designed to reduce NSAID induced gastropathy (e.g. ulcers, bleeding), concern about adverse cardiovascular events( e.g myocardial infarction, stroke) have led authorities to recommend their use only in selected patients who are at high risk for NSAID related GI effects.

40. NSAIDS GI complaints are the most common adverse effects of NSAIDs. Nausea, dyspepsia, anorexia, abdominal pain, flatulence and diarrhoea occur in 10%-60% of patients. NSAIDs should be taken with food or milk. For OA patients who need an NSAID but are at high risk for GI complications, the ACR recommendations include either a COX-2 selective inhibitor or a non-selective NSAID in combination with either a proton pump inhibitor or misoprostol. NSAIDs may cause kidney diseases, hepatitis, hypersensitivity reactions, rash and CNS complaints of drowsiness, dizziness, headaches, depression, confusion and tinnitus. Should be avoided in late pregnancy. The most potentially serious drug interactions include the concomitant use of NSAIDs with lithium, warfarin , oral hypoglycemic agents, methotrexate , antihypertensives , ACE inhibitors, Beta Blockers and diuretics.

41. TOPICAL THERAPIES Capsaicin, an extract of red peppers that cause release and ultimately depletion of substance P from nerve fibres , has been beneficial in providing pain relief in OA when applied topically over affected joints. It may be used alone or in combination with oral analgesics or NSAIDs. Topical Diclofenac is a dimethyl sulphoxide carrier is a safe and effective treatment for OA pain. Topical rubefacients containing Methly salicylate may have modest, short term efficacy for treating acute pain associated with OA.

42. GLUCOSAMINE AND CHONDROITIN Glucosamine and chondroitin are dietary supplements that were shown to stimulate proteoglycan synthesis from articular cartilage, Although their excellent safety profile makes them appealing for patient at high risk of adverse drug events. Dosing should be at least glucosamine sulphate 1500 mg/day and chondroitin sulphate 1,200 mg/day in divided doses. Glucosamine adverse effects are mild and include GI gas, bloating and cramps. It should not be used in patients with a shellfish allergies. The most common ADR of chondroitin is nausea.

43. CORTICOSTEROIDS Systemic corticosteroids therapy is not recommended in OA, given the lack of benefit and well-known adverse effects with long term use. Intra- articular corticosteroid injection can provide relief. Average doses for injection of large joints in adults are Methylprednisolone acetate 20-40 mg or triamcinolone hexacetonide 10 to 20 mg. Pain relief may occur in 24 to 72 hours, with peak relief occuring in about 1 week and lasting for 4-8 weeks. Therapy is limited to 3 or 4 injections per year because of potential systemic effects of the drugs and because the need for more frequent injections indicates poor response to therapy.

44. HYALURONATE INJECTIONS High molecular weight hyaluronic acid is a constituent of normal cartilage that provide lubrication with motion and shock absorbency during rapid movements. Because the concentration and molecular size of endogenous hyaluronic acid decreases in OA, exogenous administration has been studied to reconstitute synovial fluid and reduce symptoms. Hyaluronic acid injections temporarily and modestly increase synovial fluid viscosity and decrease pain. 4 intra- articular hyaluronic acid preparations are available for treating pain associated with OA of the knee: Sodium hyaluronate ( Hyalgan 20 mg/2 ml, supartz 25 mg/2.5 ml) Hylan Polymers( Synvisc 16 mg/ 2ml) Hyaluronan ( orthovisc 30 mg/2ml) Hyaluronate injections are very expensive.

45. OPIOID ANALGESIC Low dose opioid analgesic( e.g. oxycodone ) may be useful for patients who experience no relief with acetaminophen, NSAIDs, Intra- articular injections or topical therapy. ADRs: Constipation, nausea, sedation and pruritus.

46. TRAMADOL Tramadol with or without acetaminophen has modest analgesic effects in patients with OA. It may also be effective as addition therapy in patients taking NSAIDs or COX-2 inhibitors. Tramadol should be initiated at a lower dose(100 mg/ day in divided doses) and may be increased to a dose of 200 mg/day. ADRs: Nausea, vomiting, dizziness, contipation , head ache and somnolence(excessive sleepiness) are common.

47. DRUG THERAPY Acute pain ACETAMINOPHEN (Related toxicological information in ACETAMINOPHEN-ACUTE, ACETAMINOPHEN-REPEATED SUPRATHERAPEUTIC) Adults: 650 to 1000 mg orally every 4 to 6 hours as needed (maximum 4 g/day) IBUPROFEN (Related toxicological information in IBUPROFEN) Adults: 200 to 800 mg orally every 6 to 8 hours as needed (maximum 3.2 g/day) NAPROXEN (Related toxicological information in NAPROXEN) Adults: 250 to 500 mg orally every 12 hours as needed HYDROCODONE BITARTRATE/ACETAMINOPHEN Adults: Hydrocodone 5 to 20 mg/acetaminophen 325 to 1000 mg orally every 4 hours as needed (maximum 4 g acetaminophen/day) ACETAMINOPHEN/OXYCODONE HYDROCHLORIDE Adults: Oxycodone 5 to 20 mg/acetaminophen 325 to 1000 mg orally every 4 hours as needed (maximum 4 g acetaminophen/day) TRAMADOL HYDROCHLORIDE Adults (immediate release): Initial dose 25 mg orally every morning, titrated by 25 mg increments every 3 days until 100 mg daily (25 mg 4 times a day); may then titrate by 50 mg as tolerated to reach 200 mg/day (50 mg 4 times a day). After titration, may use 50 to 100 mg orally every 4 to 6 hours as needed (maximum 400 mg/day) [5]

48. Intra- articular steroid injection for osteoarthritis   TRIAMCINOLONE ACETONIDE (Related toxicological information in CORTICOSTEROIDS) Adults (large joint): Inject 5 to 40 mg intra- articularly initially; may repeat every 3 months for up to 2 years  Adults (medium joint): Inject 2.5 to 20 mg intra- articularly initially; may repeat every 3 months for up to 2 years  Adults (small joint): Inject 2.5 to 10 mg intra- articularly initially; may repeat every 3 months for up to 2 years METHYLPREDNISOLONE (Related toxicological information in CORTICOSTEROIDS) Adults (large joint): Inject 20 to 80 mg intra- articularly initially; may repeat every 3 months for up to 2 years Adults (medium joint): Inject 10 to 40 mg intra- articularly initially; may repeat every 3 months for up to 2 years Adults (small joint): Inject 4 to 10 mg intra- articularly initially; may repeat every 3 months for up to 2 years BETAMETHASONE (Related toxicological information in CORTICOSTEROIDS) Adult: Inject 3 to 12 mg intra- articularly , depending on the size of the joint Intra- articular hyaluronate injection for osteoarthritis  HYALURONATE SODIUM Adults: Inject 30 mg/2 mL intra- articularly into the knee once weekly for a total of 3 or 4 injections

49. PROCEDURAL THERAPY/ ARTHROPLASTY Surgical procedure: Patients should be referred for joint replacement surgery if they are not receiving adequate pain relief and functional gains with other nonpharmacological and pharmacological therapy.

50. PHYSICAL AND OCCUPATIONAL THERAPY Physical therapy—with heat or cold treatments and an exercise program—helps to maintain and restore joint range of motion and to reduce pain and muscle spasms. Warm baths or warm water soaks may decrease pain and stiffness. Heating pads should be used with caution, especially in the elderly. Patients should be warned not to fall asleep on the heat source or to lie on it for more than brief periods to avoid burns.

51. AMBULATORY ASSISTIVE DEVICE