Bones and Joints PDF

Bones & Joints Learning objectives Appreciate that disorders to the bones, cartilage and joints of the musculoskeletal system are an important cause of suffering affecting all ages. Appreciate that they are a major clinical & socio-econ...

Bones & Joints Learning objectives Appreciate that disorders to the bones, cartilage and joints of the musculoskeletal system are an important cause of suffering affecting all ages. Appreciate that they are a major clinical & socio-economic problem which will increase significantly as the population ages and becomes more obese. Understand what is meant by ‘connective tissues’ and how they are classified. Describe the cells of connective tissues. Describe the components of the extracellular matrix (ECM) State the functions of the cells and the components of the extracellular matrix and how they act together to form functional connective tissues. Disorders of the bones, cartilage and joints of the musculoskeletal system. Rheumatic diseases: broad spectrum affect connective tissues, bones and joints. ‘Arthritis’ inflammation of the joint BUT often used to include all joint disorders ‘Rheumatism’ – imprecise term often used to describe pain in muscles, bones or joints. The suffix ‘-itis’ means inflammation BUT not all diseases of the joints are inflammatory. ‘-osis’ often used to described a general functional disorder, but the constructed words are more specific – e.g. osteoporosis. Disorders of bones and joints affect all stages of life: Young – growth disorders Middle aged – injury/trauma Old age – osteoarthritis (OA); rheumatoid arthritis (RA); OP (osteoporosis) Bones & Joints 1 Bones & Joints 2 Bones & Joints 3  Problems from long-term drug treatment for disorders of the bones and joints. Many of the disorders of the bones and joints cannot be ‘cured’ – only their symptoms treated so long-term drug use is common. For example use of NSAIDs – non-steroidal anti-inflammatories (reduce inflammation, pain) – e.g. VIOXX (Merck) fewer GI problems, but could cause heart attacks, strokes. Evidence that long-term NSAIDs and corticosteroid treatment leads to accelerated bone loss, reduced fracture healing and compromised treatment of osteoporosis using bisphosphonates. Bones & Joints 4  The Coming Epidemic of Arthritis. Population ageing is unprecedented: without parallel in human history—and the 21st century will witness even more rapid ageing than the previous century. Population ageing is pervasive: a global phenomenon affecting every man, woman and child – BUT the pace of change differs greatly between countries. Countries that started the process later will have less time to adjust. Population ageing is enduring: we will never return to the young populations that our ancestors knew. Population ageing has profound implications for many facets of human life. In the U.K., half of those born after 2007 can expect to live to >100 yrs. Between 2010 and 2030 the number of people aged >65yrs will increase by 51%. The number of people aged over 85yrs will double during this period. Britain ‘woefully’ under-prepared for the dramatic increase in the elderly population (Guardian, 2021) Bones & Joints 5 Bones & Joints 6  Co-morbidity and Multimorbidity Comorbidity is the presence of one or more additional conditions often co- occurring with a primary condition Multimorbidities are co-occurring diseases eg. a person could have diabetes and heart disease and high blood pressure. increasingly common Musculoskeletal conditions are very common in multi-morbidity – often living with additional chronic conditions. Nearly four in ten people with multi-morbidity are living with a physical and a mental health condition. Globally, musculoskeletal conditions are the second most common cause of healthy years lost to morbidity with adverse impacts on quality of life. Correlation between walking disability from OA, and risk of premature death. Long-term chronic pain and lack of mobility cause diseases involving the immune, respiratory and cardiovascular systems (ischaemic heart disease, hypertension, heart failure) Pain – particularly chronic pain - incites depression. Living with daily pain is physically exhausting and emotionally stressful. Any form of arthritis – e.g. osteoarthritis (OA), rheumatoid arthritis (RA), psoriatic arthritis (PsA), lupus, ankylosing spondylitis, gout or fibromyalgia – can have a negative effect on mental health. This commonly manifests as depression or anxiety. It works the other way around, too. Depression makes pain worse. Mental health problems / depression can worsen arthritis symptoms / pain and affect mood, thinking and behaviour. Osteoarthritis (OA) – the scale of the problem. Bones & Joints 7  Direct costs: Indirect costs: Intangible costs: Surgery Loss of Multi-morbidity productivity, Hospital resources pain/suffering absence Pharm/Non-pharm decreased QoL Premature treatment mortality Depression / anxiety Disability Bones & Joints 8 Bones & Joints 9 Bones & Joints 10 Bones & Joints 11  Leg length discrepancy in a child Bones & Joints 12  Epiphyseodesis - one method of treatment Bones & Joints 13  Harris growth arrest lines Lines of increased bone density represent the position of the growth plate at the time of insult and formed on long bones due to growth arrest. Only visible by radiograph or in cross-section. The age at which the lines were formed can be estimated from a radiograph. Harris lines are often considered the result of juvenile malnutrition, disease or trauma. Other studies suggest Harris lines a result of normal growth and growth spurts, rather than a pure outcome of nutritional or pathologic stress Bones & Joints 14 Bones & Joints 15 Bones & Joints 16  Locomotor disorders are more common in the lderly Osteoporosis Bones & Joints 17  Osteoporosis Osteoporosis affects >3M people in the UK. 0.5M people receive hospital treatment for fragility fractures (fractures that occur from standing height or less) every year as a result of osteoporosis Primary causes bone resorption >> deposition – due to age, menopause (loss of oestrogen – increased osteoclast recruitment, decreased Ca absorption) Secondary causes endocrine, malnutrition, immobilisation. Osteoarthritis/osteoarthrosis (OA). 90% of OA cases are idiopathic (no known cause) also called Primary OA (female: male 2:1) 10% post-traumatic osteoarthritis (PTOA) also called Secondary OA Pain & stiffness of joints episodic initially then continuous Primary OA not due to passive ‘wear-and-tear’ Bones & Joints 18  Strong evidence for a biological basis, probably involving a long-term low grade inflammation Initiating factors unknown – correlation with age & obesity OA leads to cartilage loss and re-modelling of bone & progressive joint degeneration. No effective treatment - pain relief / reduced inflammation and pain key approach Development of disease-modifying osteoarthritis drugs (DMOADs) Treatment for OA. Treatment options to maintain functionality for as long as possible. Knee/hip arthroplasty a very successful procedure Rheumatoid Arthritis RA is a long term condition that causes pain, swelling and stiffness of joints. An inflammatory autoimmune disease – immune system attacks synovial cells – increased levels of inflammatory mediators – cartilage & bone destruction. Can affect anyone at any age - genetic & environmental factors Rheumatoid factor (RF – an autoantibody) has systemic effects on other tissues e.g. inflammation around lung & heart Pain medications, steroids, and NSAIDs frequently prescribed. Disease-modifying antirheumatic drugs (DMARDs), e.g. hydroxychloroquine and methotrexate, may be used to try to slow disease progression Bones & Joints 19 Bones & Joints 20  Why is repair of connective tissue so poor / non-existent? Poor vascular supply Limited supply of nutrients Very low synthesis rates of some tissue components Loss of cell-matrix interactions – leads to irreversible loss of phenotype Integration of repair tissue very poor Mechanical properties of repair tissue inferior/weak Components of Connective Tissues (CT). Bones & Joints 21  (a) Cells Resident cell Chondrocytes in cartilage, fibroblasts in most CTs, tenocytes (fibroblast-like cells) in tendon – cell type depends on mechanical role of the CT – cells control the mechanical stability of tissues by synthesis/degradation of the ECM In bone, osteoblasts (build NEW bone), osteoclasts (remove bone), osteocytes (maintains bone matrix/assist bone repair) Cells are very sensitive to their physico-chemical environment linked to the ECM by integrins# – role in mechanical signalling (i.e. mechanotransduction) Immigrant cells - i.e. macrophages, lymphocytes, neutrophils (defence), mast cells Integrins are transmembrane receptors that facilitate cell-cell and cell- extracellular matrix (ECM) adhesion and physical signalling (mechanotransduction). Chondrocytes in cartilage Exclusively responsible for synthesis / breakdown of ECM components. Can synthesise the full range of ECM proteins (collagens/ proteoglycans, degradative enzymes and inhibitors of enzymes etc.). Highly specialised cells. Normally synthesise cartilage-specific ECM components (collagen type II – basket-weave network; aggrecan). Cell metabolism highly sensitive to the physico-chemical environment. Specialised matrix surrounds cells (lacuna or chondron) Chondrocyte shape distinctive (rounded/elliptical) but phenotypically# unstable can de-differentiate to fibroblasts No cell division in healthy tissue – life-span years/decades? Fibroblasts in connective tissue Fibroblasts - activated connective tissue cells - abundant rough endoplasmic reticulum and synthesis of fibrous matrix proteins, particularly collagens (type Bones & Joints 22  I collagen). Forms rope-like network. Fibroblasts (metabolically activated state) Fibrocyte (relatively inactive) Cell metabolism is highly sensitive to the physico-chemical environment. Tissue damage stimulates production of fibroblasts. Critical role in wound healing. Fibroblasts only live for months. "-blast" denote a stem cell or a cell in an activated state of metabolism. (b) Extracellular matrix (ECM) - collagens & proteoglycans Collagens fibrillar proteins resist tensile stresses – like ‘rope’ Bones & Joints 23  Proteoglycans composed of negatively-charged glycosaminoglycans (GAGs) which attract cations and SWELL like partially inflated ‘balloons’ and resist compressive forces (c) Interstitial fluid Complex composition – influenced by the negatively charged GAGs. ECM turnover (synthesis/degradation) by cells throughout life Bones & Joints 24  In summary. Disorders, diseases and injuries of musculoskeletal systems cause considerable human suffering for all age groups and are a major growing clinical, sociological and economic problem for all Societies. Many disorders of the musculoskeletal system cannot be ‘cured’ and much of the ‘treatment’ is the management of chronic pain and slowing the inevitable progression of the disease. An understanding of the properties of the connective tissues which comprise the musculoskeletal system is central to identifying new treatments. The Locomotor Module will be an introduction to fundamental biomedical and clinical aspects of the musculoskeletal system and its treatment in diseases/disorders. Bones & Joints 25