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Khiloni Dodhia kd822@ic.ac.uk MSK: Cartilage biology & osteoarthritis, MSK emergencies & presentations A MedED LECTURE Osteoarthritis What is it? • Disease of the whole joint, involving articular cartilage loss • Affects bone, soft tissue too • Most common form of arthritis • Can lead to constant pain or functional limitations • Increasing due to: • ageing population • obesity • Incidence + prevalence increases with age • Affects F>M Articular cartilage: Arthroscopy Meniscus Normal Chondral defect • Can see 2 surface of the joints with • Ragged edges articular cartilage clearly • Can see the pink bone • Smooth • If prodded, will deform but bounce back • Very resilient and toughArticular cartilage: Microscopy Tide mark – important landmark, found at the junction between calcified and non-calcified cartilage Chondrocytes • <5% of tissue • Produce AND degrade cartilage matrix • High metabolic activity • Exist in relative hypoxia • Interacts with matrix: Growth factors, mechano- transduction • No cell division after adolescence (harder to heal/heals with fibrous tissue)Composition of healthy cartilage Key point: Under a high mechanical load, aggrecan able to give up water. When the mechanical load is relieved, aggrecans able to regain the water. Matrix molecules • Type 2 collagen is the main one in articular cartilage • Collagenases: • Matrix metalloproteinases – cleave collagen • Specific ones to remember for Type 2 collagen: MMP-1 • • MMP-8 • MMP-13 • MMP-3 (a stromelysin) • Non-specific collagenase – Cathepsin K Matrix molecules • Aggrecan = a type of proteoglycan • Keratin sulfate, chondroitin sulfate • Mucopolysaccharide chains • These are highly –vely charged • Makes them good at holding onto water • 2 types of aggrecanases – MMPs, aggrecanases • Key enzymes - ADAMTS-4, ADAMTS-5, MMP-3 Anabolic + anti-catabolic factors for articular cartila Intrinsic • Anti-catabolic - TIMPs 1-4 (tissue inhibitor of metalloproteinases) • Anabolic - Growth factors e.g. FGF-2 (fibroblast growth factor), IGF (insulin-like growth factor), TGF-beta (transforming growth factor), activin A Extrinisic • Hormones e.g. testosterone, oestrogen • Some drugs e.g. FGF-18 Why does matrix loss occur? Excessive degradation: Pathogenesis of osteoarthritis • Disease of the WHOLE joint (involves articular cartilage, bone, soft tissue) • 3 pain processes going on: • Inflammation • Repair re-modelling • Pain Pathology of OA: early vs established EARLY OA ESTABLISHED OA Note: loss of proteoglycan staining as you progress downwards Risk factors for OA • Age • Obesity Evidence for mechanical factors Destabilising joint injuries increase risk • Mechanical factors e.g. joint injury of OA • FHx – about 100 genetic variants associated Intra-articular fracture increases risk of OA • Chondrodysplasias e.g. Stickler syndrome Occupational examples e.g. ‘coal (Defect in Type 2 collagen) miners’ back’ • Other medical conditions e.g. Mal-aligned joints get OA e.g. varus haemochromatosis (excess Fe absorption) Paralysed joints usually protected from • Secondary joint damage due to inflammation OA e.g. Rheumatoid arthritis High-yield slide on OA OA – NOT just ‘wear and tear’. Diagnosis • Clinical diagnosis It is an ACTIVE biological process that is DEPENDENT on aggrecanases • Joint pain on ACTIVITY • Stiffness <30 mins (not prolonged morning stiffness) • Difficulty doing tasks (e.g. requiring fine Incidence and prevalence of OA increases motor movement) with: Age Greater in women Examination findings • Crepitus Sites most commonly affected: • Bony deformity • Knee (most common) • Joint line tenderness • Hands • Loss of normal range • Hip Load going through the knee is always greatest • X-ray + bloods NOT necessary for diagnosis through the medial compartment of the knee -> • Bloods – may want to rule out other causes e.g. rheumatoid arthritis, where you tend to see OA first haemochromatosis Key changes on radiographs Key X-Ray changes • Loss of joint space • Osteophytes • Subchondral sclerosis • Subchondral cystsHypothesis for OA Knee osteoarthritis • Most commonly affected site •Women have a lifetime risk of 45% of knee OA •Some require a total knee replacement Hand osteoarthritis • Very common (F>M) • Specific joints affected (in order of which is affected first): • Distal interphalangeal joint (DIPJ) • Proximal interphalangeal joint (PIPJ) • Base of thumb (carpometacarpal joint) • Often occurs around menopause • Get bony expansions of the joints sometimes: • DIPJ – Heberden’s nodes • PIPJ – Bouchard’s nodes Management of OA •Conservative management •Medical management •Surgical management Management of OA Conservative management • Exercise (disease modifier, strengthen muscle around the joints) • Weight management • Information and support (e.g. what they could do to prevent progression, tell them about misconceptions) Management of OA Medical management • Pharmacological therapies – topical NSAIDs for knee OA. • Offer oral NSAIDs if topical NSAIDs do not work (+ offer PPI alongside for gastroprotection) • DO NOT offer: • Long-term paracetamol or weak opioids routinely • If other treatments are ineffective: consider intra-articular corticosteroid injections for short-term relief Management of OA Surgical management • Total joint replacement (‘arthroplasty’) – for hip or knee •Very effective • Uni-compartmental replacement for the knee is possible • For OA affecting base of the thumb (CMCJ) -> trapeziectomy (removal of the thumb bone) • Arthroscopy – NOT evidence-based treatment for OA Management of OA: Future New treatments: Aim Unmet clinical need of OA: Clinical trials • Symptom modifying OA • Finding the correct drug drugs targets (safety and efficacy) • Treat pain • Finding the right population – • Improve function find those who are most at • Disease modifying OA drugs risk of progression (DMOAD) • Right outcome measures e.g. • Slow down the progression look at imaging outcomes, or of OA patient reported outcomes? SBA 1 osteoarthritis?e following X-ray changes is not associated with A. Subchondral sclerosis B. Loss of joint space C. Peri-articular erosions D. Osteophytes SBA 1 osteoarthritis?e following X-ray changes is not associated with A. Subchondral sclerosis B. Loss of joint space C. Peri-articular erosions D. Osteophytes SBA 2 stiffness in her knee, lasting 10 minutes in the morning. She has also noticed pain in her knee when she walks far, however this is relieved when she rests. Her BMI is 32kg/m^2. A. Rheumatoid arthritis B. Osteoarthritis C. Septic arthritis D. Gout SBA 2 stiffness in her knee, lasting 10 minutes in the morning. She has also noticed pain when she walks a lot, however this is relieved with rests. Her BMI is 32kg/m^2. A. Rheumatoid arthritis B. Osteoarthritis C. Septic arthritis D. Gout SBA 2 Managing MSK emergencies Case 1 •54 M •2 day history of a hot, red, swollen left knee •He has not had a recent injury •PMHx – hypertension and diabetes Case 1 Top 5 differential diagnoses: • Septic arthritis • Gout • Pseudogout • Haemorrhage Bursitis • Case 1 Main test to rule in/out the differentials: JOINT ASPIRATION + send for MC&S and polarising light microscopyCase 2 – Investigations interpretation Effect of bacteria being present on: Joint aspiration • • Would look turbid and cloudy • Darker • Pus present • Increased viscosity • Increased volume Blood • • High WCC • High CRP (and maybe ESR)Case 1 – Treatment • Aspirate • Give antibiotics • If confirmed infection on aspirate: joint washout with keyhole arthroscopy • Continue antibiotics (to treat residual infection) Case 2 her left groin. She has a previous history of falls, with one 7 months ago, where sheain in sustained a wrist fracture. On physical examination – Left leg is shortened and externally rotated and any movement of the leg is painful. What is the most likely diagnosis? Case 2 her left groin. She has a previous history of falls, with one 7 months ago, where sheain in sustained a wrist fracture. On physical examination – Left leg is shortened and externally rotated and any movement of the leg is painful. What is the most likely diagnosis? Hip fracture Case 2 Intra-caspular fractures further subclassified: Types of hip fractures: Using the Garden classification • Intra-capsular • Extra-capsular Garden III and IV -> more displacement, therefore higher risk of damage to the femoral head blood supply Case 2 – Osteoporosis • Drugs Factors increasing the risk: • Glucocorticoids • Age • Anti-epileptics • Anti-coagulants (heparin in particular) • Female – increased risk as reduced oestrogen after • Endocrine disorders menopause • Hyperthyroidism • Oestrogen slows bone loss + • Cushing’s syndrome improves body’s absorption of Hypogonadism Ca2+ • • Previous low energy fracture • Medical disorders • Lifestyle: • Malnutrition or malabsorption • Excess alcohol • Anorexia nervosa • Inflammatory intestinal disease • Smoking • Rheumatoid arthritis (chronic inflammatory • Low BMI disease) • Physical inactivity Case 2 – Treatment options Extracapsular fractures – internal fixation (plates or screws) Intracapsular fractures – fix or replace -> more complex due to involvement of femoral head blood supply Intracapsular fracture management: Dependent on: • Location • Displacement • Age of patient If displaced: <55 -> reduce and fixation with screws >65 years -> replace (if fit and mobile -> total hip replacement, if not fit -> hemiarthroplasty) If undisplaced: Fixation with screws Case 2 – Management • Multidisciplinary approach: ED doctors • • Nurses • Orthopaedic surgeons • Orthogeriatricians • Physios • Radiographers • Ward clerk • Porters GP • • Occupational therapists • Holistic, patient-centred approach required Case 3 – Trauma 18 year old is involved in a car accident, where his right leg gets crushed. He is in extreme pain, despite painkillers and is barely able to move his leg or feet. What do you think is going on? Case 3 – Trauma 18 year old is involved in a car accident, where his right leg gets crushed. He is in extreme pain, despite painkillers and is barely able to move his leg or feet. What do you think is going on? Compartment syndrome How do this occur? • Muscles are arranged into compartments in your leg. • The muscle groups are surrounded by fascia. • Trauma occurring must have caused bleeding within the compartment (since it is an enclosed space, the blood has nowhere to go) • Increases the pressure in that compartment, compressing the surrounding arterial and venous blood supply to the leg -> leading to acute limb ischaemia Case 3 – Trauma Treatment of compartment syndrome: Must make an incision in the fascia + drain any blood, to reduce the pressure Consequences of not treating this -> acute limb ischaemia. Symptoms are: Cold • • Pulseless • Pale • Paralysis • Paraesthesia • PressureTHANKYOU FOR COMING! Email: kd822@ic.ac.uk PLEASE FILL IN THE FEEDBACK FORM!