Chapter 21 Bones, Joints-1 10.11-2023.pdf

BASIC STRUCTURE AND FUNCTION OF BONE The functions of bone include: a) b) c) d) e) Mechanical support, protection of visceral organs. Transmission of forces generated by muscle Mineral homeostasis Production of blood cells (erythrocytes, lymphocytes and platellets). Supplies an environment to bot...

BASIC STRUCTURE AND FUNCTION OF BONE The functions of bone include: a) b) c) d) e) Mechanical support, protection of visceral organs. Transmission of forces generated by muscle Mineral homeostasis Production of blood cells (erythrocytes, lymphocytes and platellets). Supplies an environment to both hematopoietic and mesenchymal stem cell. BASIC STRUCTURE AND FUNCTION OF BONE The constituents of bone include an extracellular matrix and specialized cells 1) Bone matrix is composed of an organic component osteoid (35%) and a mineral component (65%). **The inorganic mineral component consists mainly of calcium hydroxyapatite [Ca10(PO4)6(OH)2]. 2) Specialized cells The bone-forming cells include osteoblasts and osteocytes, osteoclast precursor cells and mature osteoclasts BONE TYPES MICRO-STRUCTURE OF CANCELLOUS BONE MICRO-STRUCTURE OF CORTICAL BONE All bones, except the joint surfaces, are covered with a thin layer of fibrous tissue called PERIOSTEUM. It is extremely rich in blood vessels and nerves irritation results in extreme pain sensation. It has a two-layer structure. 1. Stratum fibrosum; is the outer layer. It continues with the joint capsule. 2. Stratum cambium; It is also called stratum osteogenicum due to the osteoblasts in its structure. In case of bone fractures, osteoblasts in this layer are activated and accelerate healing. BONE ANATOMY YELLOW MARROW AND RED MARROW • At birth, all bones in the body have red bone marrow marrow hematopoietic produce all types of blood cells. • Around age 5 – 7 years, yellow bone marrow rich in adipocytes. • Begins to appear in the distal bones of the extremities. • In adult life, only the skull bones, vertebrae, sternum, ribs, clavicle, scapula, pelvis, femur and humeral heads contain red bone marrow. YELLOW MARROW RED MARROW Bone marrow cells Adipocytes Trabecular lamellar bone ●Your logo here COMPACT=CORTICAL BONE AND CANCELLOUS=TRABECULAR BONE • • • COMPACT=CORTICAL BONE AND The bone formation-destruction process: CANCELLOUS=TRABECULAR In addition to systemic hormonal effects, BONE It is under the control of locally produced (paracrine) substances. • • • Osteoclastic activity stimulates resorption (bone destruction). It stimulates osteoblastic activity (bone production). This relationship is called coupling. CELLS OF BONE CELLS OF BONE A: Osteoblast B: Ostecyte C: Osteoid matrix D: Cement E: Bone OSTEOBLASTS • Located on the surface of the bone matrix. • Synthesize, transport and assemble bone matrix. • Regulate bone mineralization. OSTEOCLASTS • Located on the bone surface • Specialized multinucleated cells • Responsible for bone resorption. • Located within the bone • Interconnected by a network of cytoplasmic processes • Through tunnels known as canaliculi. OSTEOCYTES WOWEN BONE AND LAMELLAR BONE The bone matrix is synthesized in one of two histologic forms, wowen and lamellar Woven bone is produced rapidly, (during fetal development or fracture repair). The haphazard arrangement of collagen fibers result in less structural integrity than the parallel collagen fibers in slowly produced lamellar bone. In an adult, the presence of woven bone is always abnormal, but it is not specific for any particular bone disease. LAMELLAR BONE • Mature bone found in the adult skeleton: • • (Normal cortical and trabecular bone is lamellar bone). Formation is slow. • Lamellar bone is durable. • Has few osteocytes WOVEN BONE • • Immature bone Produced in a faster manner. • Healing fractures, fetal growth, bone producing tumors Has more osteocytes than lamellar bone. • Has irregular collagen fibers • not durable. Lamellar bone Wowen bone Wowen bone ENCHONDRAL OSSIFICATION During embryogenesis, long bones develop from a cartilage mold by the process of endochondral ossification. The central portion is resorbed, creating the medullary canal. Simultaneously, at midshaft (diaphysis): Osteoblasts begin to deposit the cortex beneath the periosteum Producing the primary center of ossification and growing the bone radially. PRIMARY AND SECONDARY OSSIFICATION CENTERS • • • Simultaneously, at midshaft (diaphysis): Osteoblasts begin to deposit the cortex beneath the periosteum Producing the primary center of ossification and growing the bone radially. ENCHONDRAL OSSIFICATION • • • Growing cartilage at the epiphyseal plates is provisionally mineralized and then Progressively resorbed and replaced by osteoid matrix Which undergoes mineralization to create bone FORMATON OF EPIPHYSEAL PLATE FORMATION OF EPIPHYSEAL PLATE Eventually, a plate of the cartilage becomes entrapped between the two expanding centers of ossification, forming the physis or growth plate. Active growth plate with ongoing endochondral ossification: 1: Reserve zone. 2: Prolipheration zone. 3: Hypertrophy zone. 4: Mineralization zone. 5: Primary spongiose bone. ENCHONDRAL OSSIFICATION The chondrocytes within the growth plate undergo sequential proliferation, hypertrophy, and apoptosis. In the region of apoptosis the matrix mineralizes and is invaded by capillaries. This process produces longitudinal bone growth. Intramembranous ossification, by contrast, is responsible for the development of flat bones Bones of the cranium are formed by osteoblasts directly from a fibrous layer of tissue, without cartilage. The enlargement of flat bones is achieved by deposition of new bone on a pre-existing mesenchymal surface. INTRAMEMBRANOUS OSSIFICATION INTRAMEMBRANOUS OSSIFICATION HOMEOSTASIS AND REMODELING • • The adult skeleton is constantly turning over in a tightly regulated process known as remodeling. An important signaling pathway involves three factors: (1) The transmembrane receptor activator of NF-κB (RANK), which is expressed on osteoclast precursors; (2) RANK ligand (RANKL), which is expressed on osteoblasts and marrow stromal cells; (3) Osteoprotegerin (OPG), a receptor made by osteoblasts that can block RANK interaction with RANKL. PARACRINE MECHANISMS REGULATING OSTEOCLASTS Osteoblast/stromal cell membrane associated RANKL binds to its receptor RANK located on the cell surface of osteoclast precursors. This interaction in the background of macrophage M-CSF causes the precursor cells to produce functional osteoclasts. Stromal cells/Osteoblast also secrete osteoprotegrin (OPG), which acts as a “decoy” receptor for RANKL, preventing it from binding the RANK receptor on osteoclast precursors. Consequently, OPG prevents bone resorption by inhibiting osteoclast differentiation. PARACRINE MECHANISMS REGULATING OSTEOCLASTS/OSTEOBLASTS Bone resorption or bone formation is associated with RANK-OPG ratio. ***Factors that affect this balance: Parathyroid hormone, estrogen, testosterone hormones, vitamin D, inflammatory cytokines (IL-1), and growth factors. The parathyroid hormone, IL-1, and glucocorticoids promote osteoclast differentiation and bone turnover. ***In contrast, BMPs (bone morphogenic proteins) and sex hormones (estrogen, testosterone) block osteoclast activity by favoring OPG expression. BONE DEVELOPMENT SET POINT Peak bone mass is achieved in early adulthood after the cessation of skeletal growth. This set point is determined by many factors, including polymorphisms in the vitamin D and LRP5/6 receptors, nutrition, and physical activity. Beginning in the fourth decade, resorption exceeds formation, resulting in a decline in skeletal mass. *The LRP5/ and 6 receptors on osteoblasts trigger the production of OPG. CONGENITAL BONE DISEASES CONGENITAL DISORDERS OF BONE 1) DYSOSTOSIS: Localized abnormalities in the migration and condensation of mesenchyme affecting ossification abnormal bone development. - APLASIA: congenital absence of a digit or a rib. - EXTRA BONE FORMATION: supernumerary digits or ribs. - ABNORMAL FUSION OF BONES: - Fusion of two or more digits together: SYNDACTYLY. - Premature closure of the cranial sutures: CRANIOSYNOSTOSIS. 2) DYSPLASIA: Diffuse disorganization of bone/cartilage. ACHONDROPLASIA • Achondroplasia is the most common form of dwarfism. • It is caused by activating point mutations in *** fibroblast growth factor receptor 3 (FGFR3) ***. • FGFR3 inhibits the proliferation of chondrocytes on the growth plate. • The length of long bones is severely stunted. • The disorder is inherited in autosomal dominant fashion, • But many cases arise from new spontaneous mutations. • Which activating mutation causes achondroplasia? • • Achondroplasia affects all bones that develop by enchondral ossification. The cartilage of the growth plates is disorganized and hypoplastic. The most conspicuous changes include: - short stature, - bowing of the legs, disproportionate shortening of the proximal extremities, frontal bossing with midface hypoplasia. ACHONDROPLASIA FEATURES THANATOPHORIC DYSPLASIA ➢ Thanatophoric= deathbearing dwarfism is a lethal variant of dwarfism. ➢ (1/20,000 live births (thanatophoric: “Greek: death-loving”). ➢ This disease is caused by missense or point mutations of the extracellular domains of FGFR3. ➢ Affected heterozygotes exhibit extreme shortening of the limbs, frontal bossing of the skull, and an extremely small thorax, which is the cause of fatal respiratory failure in the perinatal period. TYPE I COLLAGEN DISEASES (OSTEOGENESIS IMPERFECTA) Osteogenesis imperfecta, also known as “brittle (gevrek) bone disease,” is a group of genetic disorders caused by defective synthesis of ***type I collagen. **Because type I collagen is a major component of extracellular matrix in other parts of the body, there are also numerous extraskeletal manifestations (affecting skin, joints, teeth, and eyes). **The mutations underlying OI characteristically involve the coding sequences for α1 or α2 chains of type I collagen. TYPE I COLLAGEN DISEASES (OSTEOGENESIS IMPERFECTA) Any primary defect in a collagen chain tends to disrupt the entire structure and results in its premature degradation. As a consequence, OI may be associated with severe malformations. ***The fundamental abnormality in all forms of OI is too little bone, resulting in extreme skeletal fragility. OSTEOGENESIS IMPERFECTA ➢ The type I collagen disease: ptnts have a normal lifespan, with only a modestly increased tendency for fractures during childhood (decreasing in frequency after puberty). resulting in bone deformities. ➢ The type II variant: is uniformly fatal in utero or immediately postpartum as a consequence of multiple fractures. ➢ The classic finding of ***blue sclerae is attributable to decreased scleral collagen content; this deficit causes a relative transparency that allows the underlying choroid to be seen. ➢ ➢ Hearing loss can be related to conduction defects in the ear bones. Small, misshapen teeth are a result of dentin deficiency. OI- PROGRESSIVE BONE DEFORMITIES OSTEOPETROSIS: ALBERS SHÖNBERG DISEASE **Osteopetrosis is a group of rare genetic disorders characterized by defective osteoclast-mediated bone resorption. “Stone bone/marble bone disorder” is an appropriate name, since the bones are **dense, solid, and stonelike. **Because turnover is decreased, the persisting bone tissue becomes weak over time and predisposed to fractures like a piece of chalk. Several variants are known, the two most common being an 1) Autosomal dominant adult form with mild clinical manifestations, 2) Autosomal recessive infantile, with a severe/lethal phenotype.** OSTEOPETROSIS ***Besides fractures, Patients with osteopetrosis frequently have *a) Cranial nerve palsies (due to compression of nerves within shrunken cranial foramina), *b) Recurrent infections because of reduced marrow size and activity *c) Hepatosplenomegaly caused by extramedullary hematopoiesis *** Mutations in CA2, TCIRG1. Morphologically, the primary spongiosa, which normally is removed during growth, persists, filling the medullary cavity, and bone is deposited in increased amounts woven bone. ACQUIRED DISEASES OF BONE METABOLIC DISORDERS OF BONE Many nutritional, endocrine, and systemic disorders affect the development of the skeletal system. Deficiencies of: *Vitamin C (involved in collagen cross-linking; **causes scurvy) *Vitamin D (involved in calcium uptake; deficiency causes **rickets and **osteomalacia). Primary and secondary forms of hyperparathyroidism also cause significant skeletal changes! Many of these disorders are characterized by inadequate osteoid, also called **osteopenia; The most important clinically significant osteopenia is osteoporosis. OSTEOPENIA AND OSTEOPOROSIS Osteopenia refers to decreased bone mass. Osteoporosis is defined as osteopenia that is severe enough to significantly increase the risk of fracture. Osteoporosis is characterized by reduced bone mass, leading to bone fragility and susceptibility to fractures. Generalized osteoporosis may be primary secondary to a large variety of insults, including metabolic diseases, vitamin deficiencies, and drug exposures. OSTEOPOROSIS ●Your logo here OSTEOPOROSIS • • • • Primary forms of osteoporosis are most common and may be associated with aging (senile osteoporosis) or the postmenopausal osteoporotic state in women. The decrease in estrogen following menopause tends to exacerbate the loss of bone. **The risk of osteoporosis with aging is related to the peak bone mass earlier in life, which is influenced by genetic, nutritional, and environmental factors. The progressive loss of bone mass is clinically significant because of the resultant increase in the risk of fractures. (the vertebrae and the hips) PATHOGENESIS OF OSTEOPOROSIS • Age-related changes (senile osteoporosis) • Reduced physical activity. • Genetic factors. (e.g., LRP5 mutations) • Decreased calcium nutritional state • Hormonal influences. *** OSTEOPOROSIS CLINICAL COURSE The clinical outcome with osteoporosis depends on which bones are involved. Thoracic and lumbar vertebral fractures are extremely common, (kyphoscoliosis), which can compromise respiratory function. Pulmonary embolism and pneumonia are common complications of fractures of the femoral neck, pelvis, or spine and result in deaths. OSTEOPOROSIS CLINICAL COURSE • • • • Osteoporosis is difficult to diagnose because it is asymptomatic until a fracture. Moreover, **it cannot be reliably detected in plain radiographs until to 40% of bone mass has already disappeared. Serum levels of calcium, phosphorus, and alkaline phosphatase are notoriously insensitive. Current state-of the-art methods for bone loss estimation consist of specialized radiographic techniques to assess bone mineral density, such as **dual-energy absorptiometry and **quantitative computed tomography. **Osteoporosis prevention and treatment begin with adequate dietary calcium intake, vitamin D supplementation, and a regular exercise regimen—starting before the age of 30—to maximize the peak bone mass. Pharmacologic treatments include use of antiresorptive and osteoanabolic agents. The antiresorptive agents, such as bisphosphonates, calcitonin, estrogen, and denosumab, decrease bone resorption by osteoclasts. The main anabolic agent is parathyroid hormone or an analogue, given in amounts that stimulate osteoblastic activity. RICKETS AND OSTEOMALASIA **Both rickets and osteomalacia are manifestations of vitamin D deficiency or its abnormal metabolism. **The fundamental defect is an impairment of mineralization and a resultant accumulation of unmineralized matrix. **This contrasts with osteoporosis, in which the mineral content of the bone is normal and the total bone mass is decreased. **Rickets refers to the disorder in children, in which it interferes with the deposition of bone in the growth plates. **Osteomalacia is the adult counterpart, in which bone formed during remodeling is under mineralized. • Deficiency of vitamin D tends to cause hypocalcemia. This in turn stimulates PTH production, which (1) activates renal α1-hydroxylase, increasing the amount of active vitamin D and calcium absorption; (2) mobilizes calcium from bone; (3) decreases renal calcium excretion; and (4) increases renal excretion of phosphate. Thus, the serum level of calcium is restored to near normal, but hypophosphatemia persists, so mineralization of bone is impaired or there is high bone turnover RICKETS HYPERPARATHYROIDISM • • Excess production and activity of PTH results in increased osteoclastic activity bone resorption osteopenia. Although the entire skeleton is affected, the osteopenia in some bones (e.g., phalanges) is more conspicuous radiographically. HYPERPARATHYROIDISM PTH plays a central role in calcium homeostasis: • Osteoclastic activation, increasing bone resorption, and mobilizes bone calcium (by increased RANKL expression on osteoblasts). • Increased resorption of calcium by the renal tubules. • Increased urinary excretion of phosphates. • Increased synthesis of active vitamin D by the kidneys Calcium absorption from the gut. HYPERPARATHYROIDISM The net result of the actions of PTH is an elevation in serum calcium which, under normal circumstances, inhibits PTH production. Excessive or inappropriate levels of PTH can result from: 1) 2) Autonomous parathyroid secretion (primary hyperparathyroidism/parathyroid adenoma) or In the setting of underlying renal disease (secondary hyperparathyroidism) Hyperparathyroidism leads to significant skeletal changes related to osteoclastic activity. SECONDARY HYPERPARATHYROIDISMCHRONIC RENAL FAILURE In chronic renal insufficiency there is inadequate 1,25-(OH)2-D synthesis, which affects gastrointestinal calcium absorption. As bone mass decreases, affected patients are increasingly susceptible to fractures, bone deformation, and joint problems. Fortunately, a reduction in PTH levels to normal can completely reverse the bone changes. **** BROWN TUMOR BROWN TUMOR PAGET DISEASE OF BONE (OSTEITIS DEFORMANS) Paget disease is a condition of increased, but disordered and structurally unsound bone. This unique skeletal disease can be divided into three sequential phases: (1) An initial osteolytic stage, (2) A mixed osteoclastic–osteoblastic stage, which ends with a predominance of osteoblastic activity and evolves into: (3) A final burned-out quiescent osteosclerotic stage. PAGET DISEASE OF BONE (OSTEITIS DEFORMANS) Paget disease usually presents in mid to late adulthood. Marked variation in prevalence has been reported in different populations: The disorder is rare in Scandinavia, China, Africa and relatively common in much of Europe, Australia, New Zealand, and the United States, affecting up to 2.5% of the adult populations. The incidence of Paget disease is decreasing. PAGET DISEASE OF BONE (OSTEITIS DEFORMANS) Both genetic and environmental. 50% of familial and 10% of sporadic. Mutations in the SQSTM1 gene. (Increase the activity of NFκB(RANK) which, in turn increases osteoclastic activity. Activating mutations in RANK and inactivating mutations in OPG account for some cases of juvenile Paget disease. In cell cultures: Infection of osteoclast precursors with viruses such as measles or other RNA viruses alters vitamin D sensitivity and IL-6 secretion, both of which can lead to increased bone resorption. PAGET DISEASE OF BONE (OSTEITIS DEFORMANS) Paget disease is monostotic (tibia, ilium, femur, skull, vertebrae, and humerus) in about 15% of cases; Polyostotic in 85% the axial skeleton or the proximal femur is involved in as many as 80% of cases. **Elevations in serum alkaline phosphatase and increased urinary excretion of hydroxyproline reflect exuberant bone turnover. In some patients, the early hypervascular bone lesions cause warmth of the overlying skin. PAGET DISEASE OF BONE (OSTEITIS DEFORMANS) ➢ With extensive polyostotic disease, hypervascularity can result in high-output congestive heart failure. ➢ In the proliferative phase of the disease involving the skull, common symptoms attributable to nerve impingement include headache and visual and auditory disturbances. ➢ Vertebral lesions cause back pain and may be associated with disabling fractures and nerve root compression. ➢ ➢ Affected long bones in the legs often are deformed. Brittle long bones in particular are subject to chalk stick fractures. PAGET DISEASE OF BONE (OSTEITIS DEFORMANS) The development of sarcoma in Paget’s: in 1% of the ptnts. The sarcomas usually are osteogenic (osteosarcoma). Paget disease usually follows a relatively benign course. Most patients have mild symptoms that are readily controlled with bisphosphonates, drugs that interfere with bone resorption. FRACTURES FRACTURES A fracture is loss of bone integrity resulting from mechanical injury and/or diminished bone strength. The following qualifiers describe fracture types: • Simple: the overlying skin is intact (closed fracture) • Compound: the bone communicates with the skin surface (open fracture). • Comminuted: the bone is fragmented (splintered). • Displaced: the ends of the bone at the fracture site are not aligned • Stress fracture: **A stress fracture develops slowly over time as a collection of microfractures associated with increased physical activity (subjected to repetitive loads). • A greenstick fracture occurs when a bone bends and cracks, instead of breaking completely into separate pieces. Common in infants when bones are softer. • Pathologic fracture: If the break occurs at the site of previous disease (a bone cyst, a malignant tumor, or a brown tumor associated with elevated PTH), it is termed a **pathologic fracture. • FRACTURE HEALING- BASIC PRINCIPLES Fracture repair involves regulated expression of a multitude of genes. • Fracture repair can be separated into overlapping stages with particular molecular, biochemical, histologic, and biomechanical features. FRACTURE HEALINGPHYSIOLOYGY 1) Bone progenitors in the periosteum and medullary cavity deposit a new focus of woven bone. 2) Activated mesenchymal cells at the fracture site differentiate into cartilage-synthesizing chondroblasts- . In uncomplicated fractures, this early repair process peaks within 2 to 3 weeks. The newly formed cartilage acts as a nidus for endochondral ossification. With ossification, the fractured ends are bridged by a bony callus. FRACTURE HEALING- STAGES • • • • 1- Formation of an organising hematoma and pro inflammatory state at the fracture site 2- Formation of a soft callus and woven bone 3- Formation of a hard callus 4- Remodelling After fracture, rupture of blood vessels results in a hematoma, which fills the fracture gap and surrounds the area of bone injury. The clotted blood provides a fibrin mesh, creating a scaffold for the influx of inflammatory cells and the ingrowth of fibroblasts and new capillaries. FRACTURE HEALING • • • Simultaneously, platelets and inflammatory cells and fibroblasts release: PDGF, TGF-β, FGF and other factors causing a proinflammatory state at the fracture site Activating osteoprogenitor cells in the periosteum, medullary cavity, and surrounding soft tissues and stimulate osteoclastic and osteoblastic activity. By the end of the first week: a mass of predominantly uncalcified tissue called soft callus provides anchorage (support) between the ends of the fractured bones. After approximately 2 weeks, the soft callus is transformed into a bony callus. The activated osteoprogenitor cells deposit woven bone. In some cases, the activated mesenchymal cells in the soft tissues and bone surrounding the fracture line Differentiate into chondrocytes that make fibrocartilage and hyaline cartilage. The newly formed cartilage undergoes endochondral ossification. The fractured ends are bridged in this fashion (see figure). FRACTURE HEALING • • • • As the callus matures and is subjected to weight bearing forces, portions that are not physically stressed are resorbed. This remodeling reduces the size of the callus Until the shape and outline of the fractured bone are reestablished as lamellar bone. The healing process is complete with restoration of the medullary cavity. The reaction to a fracture begins with an organizing hematoma. Within two weeks, the two ends of the bone are bridged by a fibrin meshwork in which osteoclasts, osteoblasts, and chondrocytes differentiate from precursors. These cells produce cartilage and bone matrix, Which, adequate mobilization following adequate immobilization, remodels the hard callus into normal lamellar bone. FACTORS DISRUPTING THE HEALING OF A FRACTURE 1) Displaced and comminuted fractures frequently result in some deformity Devitalized fragments of splintered bone require resorption This delays healing, enlarges the callus, requires inordinately long periods of remodeling and May never completely normalize. FACTORS DISRUPTING THE HEALING OF A FRACTURE 2) Inadequate immobilization permits constant movement at the fracture site, so that the normal constituents of callus do not form. The healing site is composed mainly of fibrous tissue and cartilage, Instable tissue and resulting in delayed union and non-union. FACTORS DISRUPTING THE HEALING OF A FRACTURE Inadequate immobilization: Too much motion along the fracture gap (as in nonunion) Causes the central portion of the callus cystic degeneration; The luminal surface of the cyst can be lined by synovial-type cells, creating a false joint= pseudarthrosis. Normal healing can be achieved only if the interposed soft tissues are removed and the fracture site is stabilized. FACTORS DISRUPTING THE HEALING OF A FRACTURE • 3) Infection (a risk in comminuted and open fractures) is a serious obstacle to fracture healing. • 4) Malnutrition and skeletal dysplasia. Bone repair obviously will be impaired in the setting of inadequate levels of calcium or phosphorus, vitamin deficiencies, systemic infection, diabetes, or vascular insufficiency. With uncomplicated fractures in children and young adults, practically perfect reconstitution is the norm. When fractures occur in older age groups or in abnormal bones (e.g., osteoporotic bone), repair frequently is less than optimal without orthopedic intervention. FRACTURE HEALING Granulation tissue Woven bone Lamellar bone FRACTURE REPAIR FRACTURE REPAIR OTHER BONE DISEASES OSTEONECROSIS (AVASCULAR NECROSIS OF BONE) Ischemic necrosis with resultant bone infarction occurs relatively frequently. Mechanisms contributing to bone ischemia include: • Vascular compression or disruption (e.g., after a fracture). • Steroid administration. • Thromboembolic disease (nitrogen bubbles in caisson disease) • Primary vessel disease (e.g., vasculitis) • Severe anemia (e.g.: sickle cell crisis). Most cases of bone necrosis are due to fracture or occur after corticosteroid use, but in many instances the etiology is unknown. OSTEONECROSIS (AVASCULAR NECROSIS OF BONE) • • • • • Symptoms depend on the size and location of injury. SUBCHONDRAL INFARCTS: initially present with pain during physical activity that becomes more persistent with time. MEDULLARY INFARCTS: usually are silent unless large in size (as may occur with caisson disease or sickle cell d.). Medullary infarcts usually are stable, but subchondral infarcts often collapse and may lead to severe osteoarthritis. OSTEOMYELITIS • • • • Inflammation of bone and marrow, due to infection. Osteomyelitis can be secondary to systemic infection but more frequently occurs as a primary isolated focus of disease. It can be an acute process or a chronic, debilitating illness. Although any microorganism can cause osteomyelitis, ***the most common etiologic agents are pyogenic bacteria and Mycobacterium tuberculosis. PYOGENIC OSTEOMYELITIS Most cases of acute osteomyelitis are caused by bacteria. **The offending organisms reach the bone by one of three routes: (1) Hematogenous dissemination (**most common); (2) Extension from an infection in adjacent joint or soft tissue. (3) Traumatic implantation after compound fractures. (4) After orthopedic procedures. PYOGENIC OSTEOMYELITIS • • • • • ***Staphylococcus aureus is the most frequent causative organism. Escherichia coli and group B streptococci are important causes of acute osteomyelitis in neonates. Salmonella is an especially common pathogen in persons with sickle cell disease. Mixed bacterial infections, including anaerobes, typically are responsible for osteomyelitis secondary to bone trauma. In as many as 50% of cases, no organisms can be isolated. • OSTEOMYELITISBacterial prolipheration MORPHOLOGY • Inducing an acute inflammatory reaction • Consequent cell death. • Entrapped central bone rapidly becomes necrotic. • This non-viable bone is called a sequestrum. OSTEOMYELITISMORPHOLOGY • Bacteria and inflammation can disseminate throughout the Haversian systems • Reach the periosteum. • In children, the periosteum is loosely attached to the cortex. • Subperiosteal abscesses can form and extend for long distances along the bone surface. OSTEOMYELITISMORPHOLOGY • • • • • • • Lifting of the periosteum further impairs the blood supply to the affected region. Both suppurative and ischemic injury can cause segmental bone necrosis. Rupture of the periosteum can lead to subperiosteal abscess formation in the surrounding soft tissue That may lead to a draining sinus. Sometimes epiphyseal infection can spread into the adjoining joint Producing suppurative arthritis. Sometimes ends with an extensive destruction of the articular cartilage and permanent disability. OSTEOMYELITISMORPHOLOGY • • • • An analogous process can involve vertebrae, with an infection destroying intervertebral discs and spreading into adjacent vertebrae. After the first week of infection, chronic inflammatory cells become more numerous. Leukocyte cytokine release Stimulates osteoclastic bone resorption, fibrous tissue ingrowth, and bone formation in the periphery. OSTEOMYELITISMORPHOLOGY • Reactive woven or lamellar bone is deposited. • This forms a shell of living tissue around a sequestrum, it is called an involucrum Viable organisms can persist in the sequestrum for years after the original infection. • OSTEOMYELITIS- CLINIC Osteomyelitis classically manifests as an acute systemic illness, with malaise, fever, leukocytosis, and throbbing (künt, zonklayan ağrı) pain over the affected region. Symptoms also can be subtle, with only unexplained fever, particularly in infants, or only localized pain in the adult. The diagnosis is suggested by characteristic radiologic findings: a destructive lytic focus surrounded by edema and a sclerotic rim. In many untreated cases, blood cultures are positive, but biopsy and bone cultures are usually required to identify the pathogen. OSTEOMYELITIS- CLINIC A combination of I.V. antibiotics and surgical drainage usually is curative. Up to 1/4 of cases do not resolve and persist as chronic infections. ***Chronicity may develop with delay in diagnosis, extensive bone necrosis, inadequate antibiotic therapy, inadequate surgical debridement, and/or weakened host defenses. ***Chronic osteomyelitis may be complicated by pathologic fracture, secondary amyloidosis, endocarditis, sepsis, development of squamous cell carcinoma if the infection creates a sinus tract, and rarely osteosarcoma. TUBERCULOUS OSTEOMYELITIS Mycobacterial infection of bone has long been a problem in developing countries; with the resurgence of tuberculosis. Due to immigration patterns, increasing numbers of immunocompromised persons it is becoming an important disease in other countries as well. 1% to 3% of cases of pulmonary tuberculosis osteomyelitis. With hematogenous spread Long bones and vertebrae are the favored sites. tuberculosis TUBERCULOUS OSTEOMYELITIS The lesions often are solitary but can be multifocal (in immunodeficient ptnts.) Because the Mycobateria is microaerophilic, the synovium, with its higher oxygen pressures, is a common site of initial infection. The infection then spreads to the adjacent epiphysis, where it elicits typical granulomatous inflammation with caseous necrosis and extensive bone destruction. Tuberculosis of the vertebra is a clinically serious form of OM. Infection at this site causes vertebral deformity, collapse, and posterior displacement (***Pott disease), leading to neurologic deficits. Extension of the infection to the adjacent soft tissues with the development of ***psoas muscle abscesses is fairly common.