Introduction to module

1. Introduction to module • This module will consider the fundamental elements of osteoarthritis, rheumatoid arthritis and the spondyloarthropathies as impact on the rehabilitation process. It will also consider strategies that contribute to successful rehabilitation with preservation of function and quality of life.

2. Module goals and objectives • Identify epidemiological and risk factors for arthritis and disability related to the disease • Understand the normal physiology of joints and the pathophysiology of inflammatory and non-inflammatory arthropathies • Appreciate the clinical, imaging and laboratory features that contribute to the diagnosis of arthropathy. • Outline medical treatment options available for the treatment of primary rheumatological disease • Describe appropriate rehabilitation prescriptions for each disease/disability discussed.

3. Module outline • Joint Structure and Function • Ostearthritis • Rheumatoid Arthritis • Seronegative Spondylarthropathies

5. Types of Joints Diarthrodial: includes most of the mobile joints of the body (synovial joints) • Have a synovial membrane • They are surrounded by a joint capsule which varies from an inapparent membrane to a strong ligamentous band. • Joint capsules can be reinforced by ligaments, tendons and muscle crossing the joints. • Capsules ligaments and tendons are mainly formed by type 1 collagen. • The synovium lines the surfaces of all intracapsular structures. • These synovial lining cells are embedded in a matrix rich in collagen fibrils and proteoglycans. • The synovial membrane is supported by a a bed of fenestrated microvessels.

7. Types of Joints Types of Joints: • Synarthrosis: eg suture lines where the bones are connected by fibrous tissue. • Amphiarthrosis: eg symphysis pubis and part of the SI joint. The two bones are joined by a flexible fibrocartilage which allows a minor rotatory movement. • Intervertebral disc has developed to allow more movement.

8. Articular Cartilage Articular cartilage • Is a specialized connective tissue covering the weight bearing surface of diarthrodial joints. • Principal function of cartilage is to absorb shock and reduce friction associated with locomotion. • Articular cartilage is bathed in synovial fluid which lubricates and provides a source of nutrition to the articular cartilage. • More than 70% of the articular cartilage is water. • Dry components of the articular cartilage are mainly type2 collagen and proteoglycan aggregan. • Collagen type 2 provides the tensile strength of the articular cartilage. • The proteoglycans are responsible for the hydration and swelling of the cartilage. • There are several minor collagens and proteoglycans which play a role in the cartilage organization.

9. Articular Cartilage • The physical properties of the articular cartilage are determined by the fibrillar collagen network and the interdispersed proteoglycans that provide tensile strength and resilience. • Proteoglycans are associated with large quantities of water. • The capacity to resist compressive forces depends on the ability to extrude H2O. • Once the force subsides the proteoglycans reabsorb water and solutes into the matrix by osmosis. The articular cartilage thus returns to its original dimensions. • Articular cartilage is translucent and avascular nourished by diffusion from the subchondral bone and to a lesser degree from the synovial fluid.

10. Articular Cartilage • Different Zones of cartilage:

11. Articular Cartilage Chondrocytes: • Chondrocytes occupy as little as 2% of total cartilage volume. • They have limited capacity to replace collagen in mature articular cartilage. • Proteoglycans seem to be synthesized continuously. • Adult chondrocytes have limited repair capacity and may replace damaged or aging articular cartilage with Type 1 collagen containing fibrous tissue.

12. The Synovium • The synovium is formed by the splitting apart of adjacent musculoskeletal structures rather than infolding of extraembryonic spaces. • The fluid filled gap within the synovial structures rarely exceed 50 micrometers. • The synovium is multilayered and any number of those layers can appear or disappear as one follows the surface. • It is composed of an intima which is composed of a matrix and fibroblasts and macrophages. • The matrix has very small pores allowing the retension of synovial fluid. • A subintima has similar cells as the intima. • A superficial vascular plexus exists below the intima and is derived from the arterioles and venules of the subintima.

13. The Synovium Function: • Allows the disconnection between adjacent moving structures. • Fatty areas of the subintima provide deformable areas packing the spaces between incongruent cartilage surfaces. • Synovial villi which provide deformability during movement increase with age and may compensate for the inelasticity and increasingly fibrous character of the subintima. • Provides nutrition of the chondrocytes and controls the volume and composition of the synovial fluid.

14. Synovial Fluid • The water in the synovial fluid is a dialysate of the plasma. • The intimal fibroblasts secrete the high molecular weight polysaccharide hyalurinan. • The synovial intima is leakier than a basement membrane and allows small sized particles to filter through but hyaluronan cannot so this facilitates water retention.

15. Joint Function Stress distribution: • Substantial loading occurs across joints. • To avoid joint failure the normal joints are able to distribute their forces. • The greatest share of loading energy is taken up by the muscles and tendons crossing the joints. • The loading stress not absorbed by these structures impacts directly the opposing articular cartilage and the underlying bone. • Articular cartilage has viscoelastic properties that allow it to serve as a hydraulic shock absorber. • Underneath the articular cartialge is a plate of subchondral bone.

16. Joint Function Stability: • Depends on the shape of the component parts. • Ligaments guide and align normal joints through their range of motion( the collateral ligaments in the interphalangeal joints) • Muscles and tendons surrounding the joint(eg rotator cuff) • Synovial fluid acts as an adhesive seal that allows sliding motions between the cartilage but prevents distracting forces. • Intrarticular pressure is subatmospheric compared to the surrounding structures. • Pathological effusions act as a destabilizing factor as they increase the intrarticular pressure thus reducing this adhesiveness.

17. Joint Function Lubrication: • Normal joints have remarkable coefficients of friction • This is maintained by the constant renewal and restoration that occurs in living articular tissues. • Artificial joints therefore cannot parallel the function of a living joint. • Lubrication is facilitated by lubricin which coats the surface of the articular cartilage. • Hyaluronan makes the synovial fluid viscous thus retarding the outflow of the load bearing fluid.

18. Osteoarthritis • Definition of osteoarthritis • Epidemiology • Risk factors • Pathophysiology • Clinical picture • Laboratory findings • Radiological findings • Treatment

19. Osteoarthritis • It is the most common form of arthritis. • It is a leading cause of disability due to hip and knee involvement. • Rotterdam study conducted 1997 on 1040 patients between ages 55-65 found that only135 were free of radiographic OA in hips, knees, hands or spine. • Cause of disability in at least 10% of the population > 60years. • Current treatment of OA may improve the symptoms but does not alter the progression of the disease.

20. Osteoarthritis:Definition • Results from a series of mechanical and biological events that that interfere with the normal balance between degradation and synthesis occurring in articular cartilage chondrocytes, extracellular matrix and subchondral bone. • Manifested by fibrillation , ulceration and loss of articular cartilage. • Subchondral bone undergoes sclerosis and eburnation, osteophyte and subchondral cyst formation.

21. Osteoarthritis:Definition • Clinically manifests as joint pain tenderness, limitation of movement, occasional effusion and variable degrees of inflammation without systemic effects.

22. Classification of Osteoarthritis Primary osteoarthritis: . Affects the peripheral joints eg first CMC joint, hallux valgus, hallux rigidus, knees patello-femoral compartment, and tibio-femoral medial and lateral compartment, hips. • Spine : apophyseal joints and intervertebral joints. • Less commonly wrists, AC joints, shoulder joints

23. Classification of Osteoarthritis Secondary osteoarthritis: • Trauma • Underlying fracture • Septic arthritis • Rheumatoid arthritis • Crystal arthropathy : gout, and pseudogout. • Neuropathic disorders eg Charcot joint, tabes dorsalis. • Metabolic diseases eg hemochromatosis, Wilson’s disease • Congenital, eg congenital hip dislocation.

24. Osteoarthritis:Epidemiology Incidence: • Knee OA in the Framingham Study: • 2% of women per year developed radiographic OA. • 1% were symptomatic. • Versus 1.4% and 0.7% respectively in males. • Similar findings in a Dutch population based study.

25. Osteoarthritis:Epidemiology Incidence of hip OA : • Reported by Olivera et al to be 88 per 100,000. • Reported by Wilson et al to be 47.3 per 100, 000.

26. Osteoarthritis:Epidemiology Prevelance: • In women radiographic knee OA rises from 1-4% in ages 24-45 to 53-55% in women of age 80 years or older. • In men rises from 1-6% in those 45 years or younger to 22-33% in those 80 years and older.

27. Osteoarthritis:Epidemiology Prevalence • Prevalence of hip OA increases with age particularly in women. • There is racial predisposition, less in Chinese, Asian Indians, Jamaicans than the European population. • Hand OA was similarly found to increase with age particularly in women

28. Osteoarthritis: Risk Factors Body Weight: • In the Framingham study, the median age was 37. their body weight predicted presence of knee OA 36 years later. • The relative risk was 2.07 of the heaviest quintile compared to the lightest in females and 1.5 in males. • A subsequent Framingham study ( mean age was 70 ) revealed that the higher the BMI the increased risk of OA.OR 1.5. These findings were mainly in women. • Obesity was linked to bilateral rather than unilateral OA of the knees. • The relationship between hip OA and obesity is less clear, but it seems obesity is more related to bilateral than unilateral hip OA. • Some studies have shown a relationship between obesity and hand OA, but others have failed.

29. Osteoarthritis: Risk Factors Age Body weight Gender Occupational activity Non occupational activity Bone mineral density Post menopausal hormone therapy Injury Genetic factors Congenital anomalies

30. Osteoarthritis:Risk Factors Age: • Aged cartilage has an altered chondrocyte function and properties, and responds differently to cytokines. • Join protective neural and mechanical factors may become altered with age ( eg joint laxity, decreased muscle strength, decreased proprioceptive sensation) • Most studies for the relationship between age and knee OA show an increased risk for OA with age. • Higher prevalence of knee OA in the older population has also been demonstrated. • Hip OA and hand OA show a clear relationship to age

31. Osteoarthritis: Risk Factors Gender: • Is thought to influence the prevalence of OA through: • Hormonal effects on chondrocytes • Injury risk • Mechanical environment around the knee eg varus and valgus deformity,muscle strength). • Knee osteoarthritis is more prevalent in women adjusting for age BMI, injury, nad physical activity. • Hip OA may be more prevalent in women, but the difference is less well pronounced. • Hand OA is more prevalent in women (risk 2.6).

32. Osteoarthritis: Risk Factors Occupational activity: • Health of the cartilage depends on regular loading. • Extreme loading results in OA development. • The Framingham study revealed that in males the risk of OA was more in those who held jobs 20 years earlier that required excessive knee bending.(OR=2.2) • These finding were supported by numerous studies. • In hip OA there a weak but persistent relationship with > 10 years of farming. • Hand OA is prevalent in certain occupations eg textile workers, dentists.

33. Osteoarthritis:Risk Factors Non occupational activity: • Elite athletes were studied in numerous studies and did show an increased risk for tibiofemoral and patellofemoral OA. (unclear if related to joint injury) • Recreational runners did not appear to have an increased risk of knee OA. • No association was found between leisure activities eg cycling ,walking, gardening • High intensity non-occupational activity may be linked to Hip OA.

34. Osteoarthritis:Risk Factors Bone Mineral Density: • Framingham, Rotterdam and Chingford studies have revealed that the risk of OA was more in those with a higher BMD. • The participants with Knee OA had a 5-10% higher BMD than those without OA. • Similar findings in Hip OA

35. Osteoarthritis: Risk Factors Postmenopausal Hormone replacement Therapy: • Estrogen replacement therapy may protect against knee OA though the studies do not reach statistical significance. • MRI studies show that women using estrogen replacement therapy may have greater articular cartilage volume than non users. • Similar findings for hip OA. • Current use had a better protective effect than non use. • Having taken estrogen replacement therapy in the past was protective as compared to their controls.

36. Osteoarthritis:Risk Factors Injury: • OA may result from direct injury to the articular cartilage, or damage to the weight attenuating structures surrounding the joints eg muscles and ligaments. • Knee injury is more related to unilateral OA rather than bilateral OA. • Knee injury was a stronger predictor than obesity for unilateral OA. • Involves both tibiofemoral and patellofemoral joints. • Hip trauma was associated with unilateral OA in males, not females.

37. Osteoarthritis: Risk Factors Genetic factors: • Multiple studies showed a genetic predisposition, in siblings, twins, some genetic loci and some HLA types. Congenital anomalies: • Congenital hip dislocation, acetabular dysplasia, Legg -Perthes disease Meniscectomy: • Increases the risk of OA . • Prevalence 21 years after meniscectomy of knee OA was 48% versus 7% in normal controls in one study. • This was worse in those with a higher BMI. • Supported by numerous studies.

38. Osteoarthritis: Pathology Articular Cartilage: • Articular cartilage is an avascular structure. • It responds to injury by fibrillation which is a vertically oriented vertical dehiscence of the extracellular matrix in early OA. • Many of these patterns of fibrillation do not progress to clinically significant OA. • Fibrillation that progresses is more deep, associated with the dissolution of matrix and the proliferation of chondrocytes. • Cartilage injury extending to the deep to zone of calcified cartilage are called cracking. • Cracking is associated with erosion of cartilage from weight bearing areas and is associated with progressive OA. • The original hyaline cartilage in OA is replaced by repair cartilage. • The repair cartilage has the characteristics of fibrocartilage with broad collagen fibers and less proteoglycans.

39. Osteoarthritis: Pathology Subchondral bone • Remodelling of the bone cartilage interface occurs early in the course of OA in the areas of fibrillated articular cartilage. • Proliferation of the bone in the subchondral areas leads to the remodeling of the bone calcified cartilage interface with vascular invasion into the articular cartilage. • Spikes of granulation tissue and fibrous tissue reach the joint surface. • Enchondral ossification and ossification of the fibrovascular tissue penetrating the cartilage results in thinning of the cartilage. • This results in eventual exposure of the bone on the articular surface called eburnation. • There is sclerosis of the subchondral bone. • The bone undergoes areas of osteonecrosis which results in the collapse of the articular cartilage.

40. Osteoarthritis: Pathology • Subchondral pseudocysts develop . • Osteochondral loose bodies are formed. • Their origin is from the disordered surface as there are corresponding defects left by their avulsion. • Enchondral bone formation is the characteristic of progressive OA, either at the base of the articular cartilage. Or at the margins of the joints.

41. Cattano NM, Barbe MF, Massicotte VS, Sitler MR, Balasubramanian E, Tierney R, Driban JB. Joint trauma initiates knee osteoarthritis through biochemical and biomechanical processes and interactions. OA Musculoskeletal Medicine 2013 Mar 01;1(1):3.

43. Osteoarthritis: Clinical Picture Pain: • Is the predominant symptom of OA. • Cartilage has no nerve supply so the pain comes from the surrounding structures eg the joint capsule , periosteum and subchondral bone microfractures. • OA pain increases with the use of the joint and is relieved by rest. Later also becomes at rest. • Many patients feel that OA pain is exacerbated by cold and damp weather.

44. Osteoarthritis: Clinical Picture Stiffness: • Morning stiffness may occur and is typically<30 mins. • Occurs in the area surrounding the affected joint, whereas RA pain morning stiffness is more diffuse. Limitation of joint function: • For recreational vocational and self care activities • May be due to pain, loss of joint space, or weakness of the surrounding muscles.

45. Osteoarthritis: Clinical Picture Distribution: • May be mono- or polyarticular. • Mostly involved sites include knees, hips, spine and hands. • Unusual sites such as wrists or elbows should raise suspicion of a systemic disease or trauma.

46. Osteoarthritis: Clinical Picture Exam: • Verify that the symptoms of the patient are from the joint and not an periarticular structure. • Which joints are involved. • Tenderness along the joint margin in superficial joints. • Joint enlargement due to joint effusion/osteophytes. • Joint warmth or erythema should alert to other possibilities eg crystal, septic or rheumatoid arthritis.

47. Osteoarthritis: Clinical Picture Exam (cont): • Crepitus • Limitation of movement, pain, effusions, loose bodies, and muscle spasms. • Misalignment eg varus or valgus deformities occurring in the knee

48. Osteoarthritis: laboratory investigations • No pathognomonic lab abnormalities. • Blood and urine tests are usually normal. • Blood and synovial fluid tests are mainly done to exclude other forms of arthritis. • ESR in OA is usually normal though there have been reports that transient increases of ESR may occur in exacerbations. • ESR >50 should alert to another diagnosis. • Elevated CRP have been observed in patients with severe disease but these studies did not correct for cardiac disease which can be a cause for elevated CRP

49. Osteoarthritis: laboratory investigations • Recently there has been an interest in measurement of various cartilalge turnover productsEg Keratan sulphate,, chondroitin sulphate epitopes, Type 2 collagen propeptide, and COMP protein, MMP -3, Fibulin 3-2 peptides,, Follistatin –like protein 1. • The purpose of trying to identify new markers is to identify early disease, to predict prognosis, monitor treatment. • These assays have not been adequately standardized or validated.

50. Osteoarthritis: laboratory investigations