Lesson 3 -Bone and Cartilage Physiopathology PDF

BONE AND CARTILAGE PHYSIOPATHOLOGY HISTOLOGICAL CLASSIFICATION OF THE BONE Talking about the bone, one must first consider the histological classification: Lamellar bone: Normal adult bone. Its particular structure is made of collagen fibers parallel one to the other, smaller cellular density, smal...

BONE AND CARTILAGE PHYSIOPATHOLOGY HISTOLOGICAL CLASSIFICATION OF THE BONE Talking about the bone, one must first consider the histological classification: Lamellar bone: Normal adult bone. Its particular structure is made of collagen fibers parallel one to the other, smaller cellular density, smaller osteocytic lacunae, greater mineral content. There are different types of lamellar bone that will be described in detail later on. Immature Bone (non – lamellar or woven) Bundles of collagen fibers run in various directions through the matrix, not organised, has a greater cellular density and a smaller mineral content. In adults it is present in the process of fracture healing and remodelling, at the level of the osteo-tendineal and osteo-ligamentous junctions, in the alveolar sockets and in pathological conditions (Paget’s disease). Therefore, there is basically only one type of bone prevailing in the body, because the mature skeleton in the body is composed mostly of lamellar bone. BONE COMPOSITION When considering bone composition, there are different parts that can be identified: a cellular component and an extracellular matrix. Cells 3 types of cells, and basically two are more advanced stages of the development of the original cell type, which is a mesenchymal osteoprogenitor cell. 1. Osteocytes 2. Osteoblasts 3. Osteoclasts Extracellular matrix - the major component. In bones, cartilage and tendons, the extracellular matrix is actually the major tissue component. These tissues have a much smaller cellular density with respect to other tissues, as muscle tissue and mesenchymal tissue, in which there is a greater amount of cells with respect to extracellular tissue. In bone and cartilage, the prevalence of the matrix is what gives them their peculiar characteristics, and when the cellular component is increased there is a pathological change, whether it is related to a healing process after a fracture or to a tissue specific pathology. The matrix is itself subdivided into: -Organic (35%) Collagen (type I) 90% Osteocalcin, osteonectin, proteoglycans, glycosaminoglycans, lipids (ground substance) -Inorganic (65%) Primarily hydroxyapatite Ca5(PO4)3(OH) - this is the only properly calcified tissue in our bone. Pag. 1 a 14 TYPES OF LAMELLAR BONE: -Cortical or compact bone Organised in units called osteons built around a Haversian canal, in which the vessels and nerves pass and where osteoblasts and perivascular cells are. Osteocytes are interconnected by canaliculi while osteons communicate with the medullary cavity through Volkmann’s canals (horizontal). Image: the Haversian canal is visible and the cylinder of bone tissue (extracellular matrix) in which osteocytes are embedded and interconnected by the horizontal Volkmann’s canals. This is the basis of all long bones. 🡪 -Trabecular or spongy bone On the other hand, short bones or flat bones, are mostly composed by trabecular bone. It is also present in the epiphysis and partially the metaphysis of long bones. In this case the trabeculae are oriented along force lines and lines of load distribution, not organised with the Haversian system: they follow Wolff's law1, which states that the trabeculae start forming along the force lines. By cutting the trabecular wall, one can see a strong circular organisation that follows the force lines applied to the bone as it develops. THE CELLULAR COMPONENT - Osteoblasts: They are the main cells of the bone and are in charge of forming new bone. They retain the ability to divide and secrete collagen and matrix proteins, constituting the osteoid or unmineralised bone. They are also responsible for the mineralisation of the matrix. In cortical bone they often found close to the periosteum and to the vessels, explaining why old osteoblasts can be referred to as lining cells. They are also found on the surface of new bone, secreting osteoid. Osteoblasts derive directly from mesenchymal stem cells, which nowadays are used also in bone, cartilage, joint reconstruction and in regenerative medicine. Mesenchymal stem cells are the progenitors of the osteoblast and in the adult human body they are found in almost all the tissues: the most modern concept of stem cells is that they are pericytes 2 and they are located close to small vessels. As one ages, the number of stem cells in the body 1 [Wolff's law, developed by the German anatomist and surgeon Julius Wolff in the 19th century, states that bone in a healthy person or animal will adapt to the loads under which it is placed. If loading on a particular bone increases, the bone will remodel itself over time to become stronger to resist that sort of loading. The internal architecture of the trabeculae undergoes adaptive changes, followed by secondary changes to the external cortical portion of the bone, perhaps becoming thicker as a result. The inverse is true as well: if the loading on a bone decreases, the bone will become less dense and weaker due to the lack of the stimulus required for continued remodeling.] 2 Pericytes are multipotent cells that are heterogeneous in their origin, function, morphology and surface markers. Similar to other types of stem cells, pericytes act as a repair system in response to injury by maintaining the structural integrity of blood vessels. Pag. 2 a 14 decreases, with the highest concentration of stem cells being found in bone marrow and adipose tissue. Osteoblasts align along bone surface and produce osteoid and thus they model the bone. -Osteocytes: They are the mature, fully differentiated osteoblasts that have become embedded in the secreted matrix. They will produce matrix only if stimulated and otherwise remain quiescent. Therefore, they do not produce osteoid as much as osteoblasts do. Despite their function remaining partially unclear, they regulate bone metabolism in response to chemical and physical stress. An osteoblast becomes an osteocyte once it becomes embedded in the matrix lacunae which are connected by canaliculi. When the bone is loaded, osteocytes sense oscillating fluid flow in the canaliculi. Osteocytes also perceive tensile strains during normal activities. Sclerostin is downregulated upon physiologic mechanical loading and, as a result of loss of inhibition, osteoblastic bone formation increases. The osteocytes are interconnected by cellular expansions that project into the canaliculi and this network is responsible for the response to chemical and physical stimuli. The bone is thus a dynamic tissue continuously remodelling, whose cells continuously die and develop, changing the bone by reabsorbing and depositing new matrix. -Osteoclasts: They are catabolic cells that derive from haematopoietic stem cells. They are multinucleated cells in charge of bone reabsorption. Therefore, a dysregulated osteoclastic activity is important in the pathogenesis of diseases such as primary and secondary osteoporosis. Their activity is stimulated by the activation of PTH receptor on osteoblasts, so they are strongly connected to the hormonal response. That is why diseases (vitamin A deficiency, rickets, malnutrition) leading to a primary or secondary dysfunction of the parathyroids will also lead to pathologic bone remodelling mediated by the osteoclasts. Osteoclasts do not have receptors for PTH but instead PTH exerts only an indirect effect on osteoclasts via receptors located on osteoblasts and osteocytes. In the picture ( 🡪) on can see the haversian system and the Volkmann’s canals and the typical structure of cortical bone. The osteocytes are all interconnected and all communicating through the extracellular matrix. 3 Surrounding the cortical bone is the periosteum . TISSUES INVOLVED IN BONE HEALING Different tissues are involved in this process: 3 Periosteum, dense fibrous membrane covering the surfaces of bones, consisting of an outer fibrous layer and an inner cellular layer (cambium). The outer layer is composed mostly of collagen and contains nerve fibers that cause pain when the tissue is damaged. It also contains many blood vessels, branches of which penetrate the bone to supply the osteocytes, or bone cells. These perpendicular branches pass into the bone along channels known as Volkmann canals to the vessels in the haversian canals, which run the length of the bone. Fibers from the inner layer also penetrate the underlying bone, serving with the blood vessels to bind the periosteum to the bone as Sharpey fibres. Not found on articular cartilage. Pag. 3 a 14 - Cortical bone - Periosteum - Bone marrow - Soft tissues For bone healing, there are two main requirements: - ADEQUATE BLOOD SUPPLY - ADEQUATE MECHANICAL STABILITY The bone is highly vascularised and this allows it to heal efficiently. That is why any vessel injury during a fracture can compromise bone healing. Furthermore, the bone should not move while it is healing. To understand how the bone heals one must first study the mechanisms involved in bone formation. MECHANISMS OF BONE FORMATION Three4 mechanisms: 1. “CUTTING CONES” (BONE REMODELLING) 2. PERIOSTEAL OSSIFICATION 3. ENDOCHONDRAL OSSIFICATION 1. Cutting cones: this is the mechanism responsible for bone remodelling: it basically is a progressive substitution in one precise direction, generally determined by mechanical stimuli, of other tissue with bone tissue. One can think of this mechanism as similar to the advancement of a Legion of the ancient Roman Army: Osteoclasts destroy the old tissue (necrotic bone, old bone) and make up the head of the cutting cone; then they are followed by capillaries which develop to provide a supply for the main cells. Osteoblasts follow and lay down the osteoid to fill the cutting cone. This mechanism is a function of mechanical stimuli which direct the substitution. 2. Periosteal ossification: Mechanism by which the bone grows in thickness (appositional growth). Osteoblasts differentiate directly from periosteal pre-osteoblasts, and stem cells found close to the vessels, and lay down osteoid. Osteoblasts remain embedded in the osteoid they themselves produce and become osteocytes, as they continue to produce osteoid. There is NO intermediate cartilage 3. Endochondral Ossification: Most common mechanism of fracture repair, but also the main mechanism through which the bone grows in length. Humans stop growing around 16-18 years of age and the growth plates are the endochondral ossification points that allow bones to 4 A fourth mechanism, intramembranous ossification, also exists, but it was not mentioned. Pag. 4 a 14 grow in length. During development, the metaphysis of long bones are not constituted by mineralised matrix, but mostly by cartilage. The cartilage, which is a tissue with very little vascularization, works as an intermediate: the hypertrophy of chondrocytes determines degeneration (due to tissue hypoxia, easily occurring due to the poor vascularisation of the cartilage tissue, which seems to be the main mechanism starting the degeneration) and then calcification with vascular invasion and bone production by osteoblasts. All these processes will take place to heal a bone fracture. Most often however, the process of endochondral ossification, and to a lesser extent of direct (intramembranous) ossification, are the first ones to occur in order to heal the bone. Cutting cones is a process of remodelling that follows the initial healing and formation of new bone tissue. VASCULARISATION OF THE BONE The bone is a highly vascularized tissue, and the blood supply is essential for its function. Long bones have three sources of blood supply: Intramedullary nutrient artery: it pierces the cortical bone and enters the intramedullary cavity. Normally it supplies the majority of blood to the diaphyseal bone (80-85%). It enters the bone through a foramen (visible in cadaver bones) and gives off many collaterals along the bone shaft. Periosteal vessels Derive from the periosteum which is also highly vascularized. They are responsible for 15-20% of total blood supply to the cortical part. In case of damage to the intramedullary nutritional system they increase the blood supply of the damaged site and allow a compensation that is responsible for healing. Metaphyseal vessels Derive from periarticular vascular structures. Penetrate at the level of metaphyseal cortical and anastomose with the intra-medullary system. FRACTURE Def: Fracture = solution of continuity of a bone segment due to a mechanical cause (trauma). Two possible aetiologies, and the difference is on the application of the destructive force: - DIRECT TRAUMA Causes a fracture directly in the point of the bone where acting forces are applied. e.g. Car crash - INDIRECT TRAUMA Causes a fracture far away from the point where the acting forces are applied. Muchmore common that direct trauma. e.g. Joint traumas especially, for instance falling while skiing and rotating the knee. The acting force (developed during trauma) must be intense enough to overcome the limits of mechanical resistance and elasticity of the affected bone segment. This is obviously easier when the bone structure is already weak. Pag. 5 a 14 VASCULAR RESPONSE IN FRACTURE HEALING Fractures stimulate the release of growth factors that promote vasodilation and angiogenesis. Initially there will be bleeding, but once the release of GFs starts, it promotes the strong increase in blood flow at the level of fracture sites. The peak of increase is two weeks after the fracture. MECHANICAL STABILITY Early stability favours re-vascularization. A bone that does not have this sort of stability will never heal because proper healing depends on a balance between micromovements, mechanical load and the response of the bone: for bone callus formation, the mechanical forces determine the direction of new bone formation. In summary, the bone growth is stimulated by the loading, and one must take this into account when considering the positioning of a fractured bone. After the 1st month, the load and the micromotility among the fragments promote the formation of bone callus. Mechanical load and micro movements at the site of fracture stimulate healing. - Inadequate stabilisation can lead to mechanical deformations that prevent formation of enough bone. (soft callus5) - Excessive stabilisation instead reduces the formation of both soft and hard callus from the periosteum. The bone must therefore be both stable and dynamic. MECHANISM OF BONE HEALING There are two mechanisms of bone healing: 1. Direct or primary (no callus, no cartilage formation) 2. Indirect or secondary (intermediate step of callus formation) 1. Direct mechanism When there is no movement between the bone ends: absolute stability is required. The formation of a bone callus is not necessary. This only happens when the fracture is reduced and held absolutely rigidly following internal fixation and fracture compression. Osteoblasts have origin from perivascular endothelial cells and promote the direct formation of osteons that seal the fracture site and give stability to it. This process is very similar to the normal bone remodelling, with cutting cones. 2. Indirect mechanism Minimal movements between the bone ends are present and this prevents direct bone healing. There is formation of a periosteal reaction and a medullary callus, which later undergoes endochondral and partially intramembranous ossification. This is a rapid process, while the direct mechanism takes years. PHASES OF BONE CALLOUS FORMATION A. Phase of inflammation and hematoma around the fracture site (first 20 days). The 5 cardinal signs of inflammation are present. B. Formation of a first conjunction soft callus (from day 20 to 30), which connects the bones (bridging callus). 5 By callus we mean the structure made of several tissues that forms at the fracture site and around it during the various phases of healing. Pag. 6 a 14 C. Afterwards, calcification of bone callus, which becomes hard, is very different depending on the bone type and shape and the area of the bone which is involved. The type of bone tissue is woven or non-lamellar bone. Once the bridging woven bone has completely united the fracture ends, the fracture is consolidated. D. Finally the remodelling phase of the bone callus that substitutes non-lamellar with lamellar bone and adjusts it according to the force lines. In children, the prominent callus bump shrinks and radiographs can return to normal. In adults this process is rarely complete A. STAGE 1: Hematoma – Inflammatory reaction (1° to 20° day) Every fracture site is invaded by a haematoma, which is the main mechanism that starts the healing process. Within the hematoma there are a lot of growth factors which stimulate vessel growth and cell migration towards the fracture site. This is also promoted by the necrosis of the areas that were vascularised by the injured vessels.The hematoma is not a complication of the fracture, but rather part of the healing process, however it can become a complication if it keeps bleeding longer than necessary. This haematoma evolves rapidly and organises itself with the vessels coming from healthy surrounding tissues. The hematoma is slowly substituted by vascularised fibrous tissue and in the meantime cellular proliferation is already intense 24 hours after the trauma. Bone stumps are devitalised for several millimetres (up to 1 cm). The inflammatory phase comes next: all the periosteal reaction due to the hematoma and all the necrosis of the bone and vessel damage attracts a lot of proliferating cells. Usually these cells are mostly leukocytes, macrophages and fibroblasts and create a physiological inflammation area. Remember: FML B. STAGE 2: conjunction callus ( 20° to 30° day) The fracture site slowly gains stability thanks to the development of the fibrous callus. Motility decreases, collagen fibers are substituted by mineral salts that deposit. Fibro-vascular tissue undergoes a cartilage metaplasia that defines the primary callus. Then, the vascular supply increases oxygen tension responsible for substitution of peripheral chondrocytes with osteoblasts and the ossification starts. Moreover, osteoclasts, derived from the macrophages, start reabsorption of the devitalised bone stumps. Pag. 7 a 14 C. STAGE 3- Calcification and Repairing A periosteal callus develops peripherally to the fracture site (periosteal ossification6) An intramedullary callus develops at the centre of the fracture site (endochondral7 ossification in the area of the haematoma formation.) Mechanical and chemical factors stimulate callus formation and its development. Type II collagen produced by chondrocytes initially predominates in thecallus. As cartilage is transformed to woven bone by osteoblasts, the amount of type I collagen is increased In the radiological picture one can see a fracture of the tibia and fibula and then both the formation of the callus and the end result of the healing process can be seen. A LITTLE MORE CLARITY ON BONE HEALING8… ● Fracture healing involves a complex and sequential set of events to restore injured bone to pre-fracture condition o stem cells are crucial to the fracture repair process ▪ the periosteum and endosteum are the two major sources ● Fracture stability dictates the type of healing that will occur o the mechanical stability governs the mechanical strain o when the strain is below 2%, primary bone healing will occur o when the strain is between 2% and 10%, secondary bone healing will occur ● Modes of bone healing o primary bone healing (strain is < 2%) ▪ Bone heals directly with bone by the same mechanisms by which mature or woven bone remodel themselves ▪ occurs via Haversian remodelling ▪ occurs with absolute stability constructs o secondary bone healing (strain is between 2%-10%) ▪ involves responses in the periosteum and external soft tissues. ▪ endochondral healing (mostly) ▪ occurs with non-rigid fixation, as fracture braces, external fixation, bridge plating, intramedullary nailing, etc. o bone healing may occur as a combination of the above two process depending on the stability throughout the construct TIME FOR CALCIFICATION OF BONE CALLUS The inflammatory and hematoma phases are more or less the same for all types of bones. On the other hand, the phases of callus formation and remodelling are very different. In the ribs, clavicles, scapula, pelvic bones and sternum, the process of callus formation and remodelling is almost complete after just 30 days. In long bones, such as the femur, the process can take about 90 days and for malleolar fractures it may take up to 120 days for healing. 6 But with non-lamellar bone In some instances, medullary mesenchymal cells differentiate into osteoblasts during the inflammation and fibro-vascular callus formation, thus contributing with intramembranous ossification. 8 https://www.orthobullets.com/basic-science/9009/fracture-healing I also suggest reading the following: pages 17-18 from “McRae’s Orthopaedic Trauma” and pages 225-227 from “Manuale di ortopedia e traumatologia”. 7 Pag. 8 a 14 Humeral fractures take about 70 days to heal, while radius and ulna fractures take up to 90 days. The scaphoid in the metacarpal region will require more than 4 months to heal and 2 months of complete cast to have a complete immobilization. The different times for healing depend on the blood supply to the bones. ▪ Bone callus may develop also in case of displacement, but only if it is a mild displacement between the two stumps of bone, otherwise the healing will not occur efficiently. REMODELLING Immature bone gradually gets substituted by lamellar bone and reconstruction of the medullary cavity follows. The orientation of lamellar bone deposition is in relation with mechanical stimuli (stress and strain) according to the above-cited Wolff’s law. This phase occurs after the bony callus has formed to give the bone the correct shape and profile. In this phase there is formation of the normal lamellar bone and the process may take years to complete. FACTORS INVOLVED IN LOCAL REGULATION OF BONE HEALING ▪ Growth factors and growth factors antagonists - Transforming growth factor (TGF) is the main one - Bone morphogenetic proteins (BMP): these have recently been used as drugs in bone healing to speed up the process of recovery - Fibroblast growth factors (FGF) - Platelet-derived growth factors (PDGF) - Insulin-like growth factors (IGF) ▪ Cytokines: they can be either anabolic or catabolic for the bone formation and the balance between these two actions is what determines the end result in bone healing ▪ Prostaglandins/leukotrienes o Have species-dependent effects: ▪ Prostaglandin E (PGE): ● Stimulate bone neoformation ● Inhibit osteoclastic activity ● Leukotrienes: o Globally stimulate the deposition of bone matrix o Stimulate also selective bone reabsorption Pag. 9 a 14 ▪ Hormones - Oestrogens (stimulate fractures healing with a mechanism of receptors) - Thyroid hormones - Glucocorticoids - PTH - GH (stimulate maturation of bone callus) All the alterations of PTH and GH have an effect on bone homeostasis. HISTOLOGICAL CLASSIFICATION OF CARTILAGE Glycosaminoglycans Hyaline -Characterised by matrix containing type 2 collagen, GAGs and proteoglycans and mostly found at the level of articular surfaces, nose, trachea, bronchi, epiphyseal growth plates. Elastic -Characterised by elastic fibres and elastic lamellae and is found in the ear pavilion and part of the epiglottis Fibrocartilage -Characterised by abundant type 1 collagen as well as the matrix of hyaline cartilage. It is found in part of the larynx, the pubic symphysis, articular discs of the temporomandibular and sternoclavicular joints, menisci and intervertebral discs. The articular cartilage is a unique tissue (a specialised form of hyaline cartilage9) that is also very different from the bone. With respect to the bone tissue, cartilage is characterised by: - No blood supply - No lymphatic drainage - No neural elements - Chondrocytes are shielded from immunological recognition. They are immune-privileged cells because they are embedded in the matrix. - 60 – 80% of human cartilage is water. - Limited healing capacity. ARTICULAR CARTILAGE and MATRIX ORGANISATION: This type of cartilage covers the articular surface of movable joints. It is a very sophisticated tissue and from the mechanical point of view it works as the main shock absorber of the joint. Together with the bone it constitutes the osteochondral unit.10 Histologically, it looks completely different from the bone: in adults, the articular cartilage is 5mm thick and four layers can be identified: 9 With respect to hyaline cartilage, the articular cartilage lacks a perichondrium , it is organised in 4 layers (described later) and it is a remnant of the hyaline cartilage that served as a template for bone formation. 10 The articular cartilage is anchored to the subchondral bone through an interface of calcified cartilage, which as a whole makes up the osteochondral unit. This unit functions primarily by transferring load-bearing weight over the joint to allow for normal joint articulation and movement. Unfortunately, irreversible damage and degeneration of the osteochondral unit can severely limit joint function (e.g. in osteoarthritis) Pag. 10 a 14 - - - Superficial (tangential) zone: a pressure-resistant zone closest to the articular surface. Chondrocytes are horizontal and flattened, organised in lamellae, rather than in columns as in deeper layers and allow the gliding of the articular cartilage surface. Collagen fibrils are organised parallel to the surface. The most superficial layer of the articular cartilage is also called the lamina Splendens11. Intermediate (transitional) zone: it lies just below the tangential zone and it contains chondrocytes that start to organise in columns. Deep (radial) zone: chondrocytes are organised in columns perpendicular to the articular surface. Collagen fibril are in between columns and parallel to them. Calcified zone: a calcified matrix separated from the layers above by the tidemark line. Above this layer interstitial growth takes place. Just below is the subchondral bone. This structure is perfect to sustain loads and to allow a sliding surface. These morphologic, biochemical and functional differences between zones of the articular cartilage based on the depth from the articular surface allow to resist shearing forces on the surface and compression on the deepest layers. CHONDROCYTES Chondrocytes are the "cellular manufacturing sites" of cartilage and are responsible for the production and maintenance of the surrounding matrix. Like osteocytes, they are embedded in the matrix they themselves produce. Unlike osteocytes, however, they are much more isolated than osteocytes as they are not connected by canaliculi. Chondrocytes can be connected indirectly by hormonal regulation. SYNOVIOCYTES These cells line the internal surface (intima) of the synovial membrane of joint capsules and have a role in the homeostasis of synovial fluid. Two types of synoviocytes have been identified: ▪ Macrophagic cells (type A cells): blood-derived cells, can be considered as tissue macrophages. They are similar to osteoclasts and their role is to phagocytose cellular debris and wastes in the joint cavity. They also have antigen presenting activity. 11 The uppermost layer of hyaline articular cartilage is called Lamina Splendens. This film-like layer is seldom seen arthroscopically. The Lamina Splendens has extremely important articular function as it provides a very low friction lubrication surface and contains collagen fibrils which run parallel to the surface of articulation. This surface zone layer is likely to play a key role in maintaining the mechanical response of articular cartilage to load. It is the first region of cartilage to degrade in osteoarthritis and yet there is no evidence that it is regenerated when articular cartilage is repaired, not even with autologous chondrocytes Pag. 11 a 14 ▪ Fibroblast-like cells (type B cells): real synoviocytes, involved in the production of synovial fluid. Responsible for swollen joints due to excess production of synovial fluid. EXTRACELLULAR MATRIX - Collagen: The major matrix protein made by macromolecules that contain characteristic helical amino acid chains. Provide with tensile strength and morphology of cartilage. They allow cartilage to be more elastic and more resistant than the bone. Proteoglycans are attached to the collagen framework. In cartilage, the most abundant type is type 2. -Proteoglycans They consist of a core protein, aggrecan, to which glycosaminoglycan side chains of chondroitin sulphate and keratan sulphate are bound. These are then bound to a large hyaluronan molecule. These charged side chains account for the hydration and resistance to compression of the cartilage matrix. A lack of proteoglycans will result in cartilage destruction as they allow to maintain the tissue hydrated. Water constitutes at least 70% of cartilage, so the absence of the framework that keeps water in the tissue will cause it to lose structural integrity. -Multi-adhesive non-collagenous, non-proteoglycan-linked glycoproteins Articular cartilage is the main tissue affected by Osteoarthritis (OA) Sometimes called wear and tear arthritis, osteoarthritis (OA) is the most common type of arthritis. When the smooth cushion between bones (cartilage) breaks down, joints can get painful, swollen and hard to move. OA can affect any joint, but it occurs most often in hands, knees, hips, lower back and neck. OA can happen at any age, but it commonly starts in the 50s and affects women more often than men. This disease starts gradually and worsens over time, but there are ways to manage OA to prevent or minimise pain and preserve motility. -OA results in: - Increased tissue swelling - Change in colour - Cartilage fibrillation - Cartilage erosion down to the subchondral bone Nowadays OA is considered a disease of the whole joint. With time, synovial fluid is overproduced and the joint swells causing further damage once the fluid leaks into the cracks on the bone surface (possibly forming subchondral bone cysts). At the end of the process, OA will produce a completely different tissue with respect to healthy bone and articular cartilage. These Pag. 12 a 14 effects can be seen in the pictures on the right. CAUSES12 Osteoarthritis was long believed to be caused by the wearing down of joints over time. Scientists now see it as a disease of the joint. Here are some things that may contribute to OA: ● Age. The risk of developing OA increases someone gets older because bones, muscles and joints are also aging. ● Joint injury. A break or tear, can lead to OA after years. ● Overuse. Using the same joints over and over in a job or sport can result in OA. ● Obesity. Extra weight puts more stress on a joint and fats cells promote inflammation. ● Weak muscles. Joints can get out of the right position when there’s not enough support. ● Genes. People with family members who have OA are more likely to develop OA. ● Sex. Women are more likely to develop OA than men. SYMPTOMS Symptoms tend to build over time rather than show up suddenly. They include: ● Pain or aching in the joint during activity, after long activity or at the end of the day. ● Joint stiffness usually occurs first thing in the morning or after resting. ● Limited range of motion that may go away after movement. ● Clicking or cracking sound when a joint bends. ● Swelling around a joint. ● Muscle weakness around the joint. ● Joint instability or buckling (knee gives out). Here are ways that OA may affect different parts of the body: ● Hips. Pain is felt in the groin area or buttocks and sometimes on the inside of the knee or thigh. ● Knees. A “grating” or “scraping” feeling when moving the knee. ● Fingers. Bony growths (spurs) at the edge of joints can cause fingers to become swollen, tender and red. There may be pain at the base of the thumb. ● Feet. The big toe feels painful and tender. Ankles or toes may swell. As OA gets worse, cartilage may get uneven edges and cracks. Bones may harden, change shape and get bumpy. Once cartilage breaks down, it doesn’t grow back on its own. HEALTH EFFECTS Pain, reduced mobility, side effects from medications and other factors associated with osteoarthritis can lead to negative health effects not directly related to the joint disease. Obesity, Diabetes and Heart Disease Knee or hip pain may make it harder to exercise. That can cause or worsen weight gain and lead to obesity. Being overweight or obese can lead to the development of high cholesterol, diabetes, heart disease and high blood pressure. Falls People with osteoarthritis experience as much as 30 percent more falls and have a 20 percent greater risk of facture than those without OA. Having OA can decrease function, weaken muscles and make it more likely that someone has a fall. Side effects from pain medications, such as dizziness, can also contribute to falls. DIAGNOSIS Medical history, a physical examination and lab tests help to make an OA diagnosis. A primary care doctor may be the first person you talk to about joint pain. The doctor will go over medical history information, symptoms, how the pain affects activities, as well as medical problems and medication use. The doctor will look at and move the joints. These tests help to make the diagnosis: ● Joint aspiration. After numbing the area, a needle is inserted into the joint to pull out fluid. This test will look for infection or crystals in the fluid . The results can help rule out other medical conditions or other forms of arthritis. ● X-ray. X-rays can show joint or bone damage or changes related to osteoarthritis. ● MRI. Magnetic resonance imaging (MRI) gives a better view of cartilage and other parts of the joint. Treatment 12 What follows from here was not explained in class and it was added to have a complete picture of OA. As it will probably be explained in the next lectures, feel free to skip this part. If this were not the case, then these two pages may turn out to be useful. Pag. 13 a 14 There is no cure for OA, but medication, nondrug methods and assistive devices can help to ease pain. As a last resort, a damaged joint can be surgically replaced with a metal, plastic or ceramic one. ▪ Medications Pain and anti-inflammatory medicines for osteoarthritis are available as pills, syrups, patches and creams, or they are injected into a joint. They include: Analgesics. These are pain relievers and include acetaminophen and opioids. Acetaminophen is available over-the-counter (OTC), and opioids must be prescribed by a doctor. Nonsteroidal anti-inflammatory drugs (NSAIDs). These are the most commonly used drugs to ease inflammation and pain. They include aspirin, ibuprofen, naproxen, celecoxib. They are available OTC or by prescription, but the OTC versions only help the pain. Counterirritants. These OTC products have ingredients like capsaicin, menthol and lidocaine. They irritate nerve endings, so the painful area feels cold, warm or itchy to take focus away from the actual pain. Corticosteroids –These prescription anti-inflammatory medicines work in a similar way to a hormone called cortisol. The medicine is taken by mouth or injected into the joint at a doctor’s office. Platelet-rich plasma (PRP). Available from a doctor by injection, this product has proteins that help ease pain and inflammation. Other drugs. The anti-depressant duloxetine (Cymbalta) and the anti-seizure drug pregabalin (Lyrica) are oral medicines that are FDA-approved to treat OA pain. ▪ Nondrug Therapies ▪ Exercise ▪ Weight loss Pag. 14 a 14