Osteoarthritis and Osteochondrosis Lecture Notes PDF

Osteoarthritis and osteochondrosis Learning Outcomes By the end of this lecture students should be able to: Describe the pathological processes leading to osteochondrosis Give examples of arthritic diseases, symptoms, clinical consequences and risk factors Describe the pathophysiological...

Osteoarthritis and osteochondrosis Learning Outcomes By the end of this lecture students should be able to: Describe the pathological processes leading to osteochondrosis Give examples of arthritic diseases, symptoms, clinical consequences and risk factors Describe the pathophysiological mechanisms underlying osteoarthritis Know scoring methods for categorising cartilage damage and lameness/pain behaviour BIOS3100: Musculoskeletal Physiology Dr John Harris (Dec ’24)  Osteochondrosis Skeletal disease affecting bone growth in growing animals (i.e. developmental) Results from a non-infectious disturbance in endochondral ossification Common in many species including: ‒ Pigs ‒ Horses ‒ Dogs ‒ Cattle ‒ Sheep ‒ Poultry ‒ Humans  Bone Growth (Ossification Recap) 1 Proliferation of chondrocytes (cartilage cells) in outer edge of epiphyseal plates next to epiphysis As new chondrocytes added on outer epiphyseal border, old chondrocytes on diphyseal border enlarge  Bone Growth (Ossification Recap) 2 Leads to temporary widening of epiphyseal plate i.e. epiphysis moves further from diaphysis Matrix around enlarged old chondrocytes becomes calcified and die due to lack of oxygen and nutrients  Bone Growth (Ossification Recap) 3 Osteoclasts remove dead chondrocytes/calcified matrix Osteoblasts from diaphysis invade space and produce new bone and capillary blood supply Epiphyseal plate (new chondrocytes) at original thickness  Cartilage Canals Epiphyseal growth cartilage Articular cartilage Ytrehus et al. (2007)  Osteochondrosis 1 A: Healthy cartilage in young animals is highly vascularised via cartilage canals B+C: Blood supply disruption causes ischemic necrosis of surrounding cartilage (osteochondrosis latens) D+F: A small defect may resolve when it reaches the advancing ossification front Ytrehus et al. (2007)  Osteochondrosis 2 E: Larger defects are unable to resolve, resulting in a cone of necrotic cartilage, which the ossification front advances around (osteochondrosis manifesta) G: These lesions may be surrounded by bone as the ossification front advances H: Or the overlying cartilage can rupture or detach causing osteochondrosis Ytrehus et al. (2007) dissecans  Some Arthritic Diseases Rheumatoid arthritis – autoimmune disease which targets joints but also other organs e.g. heart, lungs Septic arthritis – infection in a joint causing inflammation Psoriatic arthritis – consequence of psoriasis, an autoimmune disease causing red, scaly patches of skin Ankylosing spondylitis – autoimmune inflammation of the joints between vertebrae Juvenile idiopathic arthritis – autoimmune arthritis of unknown cause occurring in under 16s Gout – build up of uric acid in joints (often big toe) leading to inflammation Osteoarthritis – consequence of progressive breakdown of articular cartilage  Symptoms/Consequences Pain Swelling Redness Warmth Stiffness/Immobility/Decreased range of motion (ROM) Limping/Lameness Abnormal posture Reduced activity Muscle atrophy Change in temperament  Assessing Pain (Behaviour; Pigs) Numerical Rating Scale (NRS) Score Vocalisation 1 Low volume, occasional cries 2 Low volume, continuous cry 3 High volume, quite frequent cries 4 Screaming that lasts a long time Visual Analogue Scale (VAS) None Squealing while Squealing while touched or moved undisturbed or at rest Simple Descriptive Scale Score Vocalisation Normal Normal grunting/squealing when interacting Mild Squealing when moved or touched Moderate Squealing when standing or walking Severe Squealing when undisturbed  Assessing Lameness e.g. conformation assessments for pig leg weakness traits in the hind limbs Varus malalignment (a.k.a. o-shaped or bow-legged) - indicates dysfunction in the medial joint aspect Valgus malalignment (a.k.a. x-shaped or cow-hocked) - indicates dysfunction in the lateral joint aspect Conformational changes indicating problems in the stifle and hock include hind feet positioned under the abdomen (standing under) or behind the stifle joint (standing back)  Osteoarthritis Highest prevalence of all the arthritic diseases Typically affects weight-bearing joints e.g. dogs – elbow, hip, stifle, shoulder, back Degradation of the joint can begin a long time before OA becomes symptomatic No cure and no reversal of the disease process Risk factors include: ‒ Age ‒ Gender ‒ Prior joint trauma ‒ Obesity ‒ Sedentary lifestyle  Structure of Synovial Joint (Recap) Subchondral bone either side of joint e.g. femur and tibia in diarthroidal stifle/knee joint Bones ‘capped’ with hyaline cartilage Fibrocartilage menisci Joint capsule Outer fibrous membrane (collagen) Inner synovial membrane (synovium) Synovial fluid Ligaments Shapiro et al. (2014) Bursae  Pathology of OA Degeneration of cartilage ECM and cartilage thinning - can lead to full thickness erosion exposing subchondral bone Subchondral bone undergoes remodelling and sclerosis Osteophyte formation Synovial Shapiro et al. (2014) inflammation  OA Initiation Recent studies point to an inflammatory mechanism for the initial stages of OA in response to mechanical injury Trigger chondrocytes, osteoblasts, and synoviocytes to release: ‒ Cytokines, such as interleukin-1 (IL-1), IL-4, IL-9, IL-13, and TNFα ‒ Degradative enzymes such as a disintegrin and metalloproteinase thrombospondin-like motifs (ADAMTS) and collagenases/matrix metalloproteinases (MMPs) Activation of immune system OA Mechanisms Glyn-Jones et al. (2015  Cartilage Degeneration Healthy cartilage - chondrocytes have low metabolic activity (little cell division or death) Maintain anabolic/catabolic equilibrium - supports healthy ECM Biomechanical changes → upregulation of synthetic activities in early OA to attempt ECM repair → chondrocyte cloning, formation of clusters and hypertrophy, losing the ability to form new cartilage matrix Disruption of cartilage → increased inflammatory cytokines e.g. IL-1ß, IL-6 and TNFα and protease release e.g. ADAMTS-4, ADAMTS-5, MMP-13 Alters the ECM structure, particularly the content and organisation of type II collagen and proteoglycans → cartilage degradation/thinning, loss of elasticity, fibrillation/fissures Chondrocytes long-living → age-related changes including oxidative stress and apoptosis hence cartilage loss  Abnormal Bone Remodelling 1 Subchondral bone undergoes abnormal remodelling. Early OA - increased osteoclast activity causes subchondral (trabecular) bone loss Causes channels to extend from the subchondral bone and ultimately pass across the tidemark into the articular cartilage Vascular invasion (angiogenesis) into these channels promoted by vascular endothelial growth factor (VEGF) from chondrocytes Accompanied by extensions of sympathetic/sensory nerves from subchondral bone  Abnormal Bone Remodelling 2 In late OA, remodelling is dominated by osteoblast activity Produces higher bone density and volume leading to subchondral sclerosis Leads to the formation of subchondral cysts Osteophytes form on the outer joint edges These serve to correct the joint instability caused by the disease  Synovial Membrane The synovial membrane (synovium) produces synovial fluid (composed of lubricin and hyaluronic acid) Lubricates the joint and nourishes the articular cartilage The synovium is composed of two types of synoviocytes: ‒ Fibroblasts which produce the synovial fluid components ‒ Macrophages which are usually dormant but are activated during inflammation  Synovitis OA causes joint swelling due to synovial fluid effusion (excess fluid production) and thickening of the synovium because of intima layer hyperplasia Cartilage breakdown fragments within the synovial fluid contact the synovium, resulting in an inflammatory response intended to repair and protect the joint but instead contributes to chondrocyte dysfunction and further cartilage degradation The inflammation results in synovial cells and chondrocytes increasing production of cytokines and proteases, including MMPs and aggrecanases The inflammation also elicits synovial angiogenesis and increased synovial macrophages Synovial membrane progressively becomes fibrotic over time  Macroscopic scoring of OA Grade Articular surface appearance Walsh et al. (2009) 0 Normal cartilage – smooth, unbroken surface and a homogenous white to off-white colour 1 Swelling and softening of the cartilage, a little brown homogenous colouration 2 Superficial fibrillation, lightly broken surface and white to off- white/light brown in colour 3 Deep fibrillation – coarsely broken cartilage surface, dark brown, grey or red in colour 4 Subchondral bone exposure – stifled white and dark brown/red in colour  OARSI Histological Scoring of OA Grade Osteoarthritic damage 0 Normal 0.5 Loss of Safranin-O without structural changes 1 Small fibrillations without loss of cartilage Vertical clefts down to the layer immediately below the superficial layer and some loss 2 of surface lamina Vertical clefts/erosion to the calcified cartilage extending to 75% of the articular surface Glasson et al. (2010  Grade 0 Normal articular cartilage. The cartilage surface is smooth. The matrix and chondrocytes are organized into superficial, mid and deep zones  Grade 1 The articular surface is uneven and can demonstrate superficial fibrillation. This may be accompanied by cell death or proliferation. The mid zone and deep zone are unaffected.  Grade 2 Focally fibrillation extends through the superficial zone to the superficial zone – mid zone portion ↓. This may be accompanied by cell proliferation, increased or decreased matrix staining and/or cell death in mid zone.  Grade 3 Matrix fibrillation extends vertically downward into the mid zone. As the OA becomes more extensive, the fissures may branch and extend into the deep zone. Cell death and all proliferation may be observed most prominently adjacent to fissures.  Grade 4 Cartilage matrix loss is observed which in earliest stage may be only delamination of superficial zone cartilage. More extensive erosion results illustrated in excavation, loss of matrix in fissured domains.  Grade 5 The unmineralized hyaline cartilage is completely eroded. The articular surface is mineralized cartilage or bone. Microfracture through the bone plate may result in reparative fibrocartilage occupying gaps in the surface.  Grade 6 The processes of microfracture, repair and bone remodelling change the contour of the articular surface. At the earliest phase, fibrocartilage has grown along the level of the previously eroded and denuded surface. Fibrocartilaginous articular surfaces, marginal and central osteophytes are processes associated with more extensive articular contour deformation.  Management/Treatment Weight management/control/maintenance (OA) Regular, moderate, controlled physical activity (OA) Joint supplements/neutraceuticals (OA) e.g. omega-3 fatty acids, glucosamine/chondroitin sulphate, polysulphated glycosaminoglycans (GAGs) - Injection Analgesics/anti-inflammatories e.g. NSAIDs, opioids e.g. tramadol (OA), steroids (RA) Disease-modifying anti-rheumatic drugs (DMARDs) (RA) e.g. hydroxychloroquine, methotrexate Surgery (OA, RA) Alternative treatments e.g. low-level laser treatment, acupuncture, hydrotherapy, shockwave treatment, stem cell therapy (OA)  Some Further Reading Ytrehus, B., Carlson, C.S. & Ekman, S. (2007) Etiology and Pathogenesis of Osteochondrosis, Veterinary Pathology, 44(4): 429-448. Pritzker, K.P.H. et al. (2006) Osteoarthritis cartilage histopathology: grading and staging, Osteoarthritis and Cartilage, 14: 13e29. Glasson, S.S., Chambers, M.G., Van Den Berg, W.B. & Little, C.B. (2010) The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the mouse, Osteoarthritis and Cartilage, 18: S17-S23. Yuan, X.L., Meng, H.Y., Wang, Y.C., Peng, J., Guo, Q.Y. & Lu, S.B. (2014) Bone–cartilage interface crosstalk in osteoarthritis: potential pathways and future therapeutic strategies, Osteoarthritis and Cartilage, 22: 1077- 1089. Shapiro, L.M., McWalter, E.J., Son, M., Levenston, M., Hargreaves, B.A. & Gold, G.E. (2014). Mechanisms of osteoarthritis in the knee: MR imaging appearance. Journal of Magnetic Resonance Imaging, 39(6): 1346-1356. Glyn-Jones, S., Palmer, A.J.R., Agricola, R., Price, A.J., Vincent, T.L., Weinans, H. & Carr, A.J. (2015) Osteoarthritis, Lancet, 386: 376–87.