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Osteogenesis imperfecta Osteopetrosis Osteochondroma Achondroplaisa AchondroplasiaOsteogenesis Imperfecta (Brittle Bones, Fragilitas Ossium)Osteopetrosis (Marble Bone Disease, Osteosclerosis) Hereditary Multiple Exotosis (Osteochondromatosis)Enchondromatosis (Ollier's Disease]Pyogenic osteomyelitis [Hematogenous (Pyogenic) Osteomyelitis]Tuberculosis Osteomyelitis from a Contiguous InfectionOsteomyelitis from an Introduced InfectionBone TuberculosisBone SyphilisFungus Infections of BoneOsteoporosis Osteoporosis Osteoporosis Tensynovitis Scurvy Paget's Disease [Paget's Disease of Bone (Osteitis Deformans]Rickets and OsteomalaciaBone Changes in Hyperparathyroidism (Generalized Osteitis Fibrosa Cystica, Von Recklinghausen's Disease of Bone) Renal OsteodystrophyHypertrophic Osteoarthropathy Fibrous Lesions Cysts Plasma Cell Myeloma Metastatic Disease Osteogenic Lesions -- Benign Cartilaginous TumorsBone-Forming TumorsTumors of Unknown HistogenesisMiscellaneous Tumors and Tumor-like Lesions of BoneFibrous Dysplasia of BoneFibrous Cortical Defect and Nonossifying FibromaSolitary Bone Cyst (Unicameral Bone Cyst)Aneurysmal Bone CystEosinophilic Granuloma of BoneBone Lesions of Gaucher's Disease
Diseases of Growth
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Repair of Connective Tissuse
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Infection
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Circulatory Disease
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Metabolic Bone Disease
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Achondroplasia Osteogenesis Imperfecta Osteopetrosis Epiphysiolysis (Slipped Capital Femoral Epiphysis) Epiphyseal Separation Congenital Pseudarthrosis  · Osteopoikilosis |
Fracture Repair  Fracture Repair Non-union Myositis Ossificans · Cartilage Repair |
Osteomyelitis, Pyogenic Osteomyelitis, Tuberculous Osteomyelitis, Fungal Arthritis, Pyogenic Arthritis, Tuberculous · Syphilis |
Avascular Necrosis, Secondary to Trauma Avascular Necrosis, Nontraumatic Osteochondroses Osteochondritis Dissecans · Sickle Cell Disease
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Normal Bone Metabolism Osteoporosis Osteomalacia/Rickets Hyperparathyroidism · Hypophosphatasia
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Arthritis
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Synovial Disease
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Skeletal Disease
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| Arthritis, Degenerative Arthritis, Inflammatory Gout Pseudogout |
Synovitis, Non-Specific Ganglion Pigmented Villonodular Synovitis Giant Cell Tumor of Tendon Sheath Synovial Chondromatosis |
Fibrous Dysplasia Ossifying Fibroma Paget's Disease Simple Bone Cyst Reticuloendothelioses |
Benign Skeletal Lesions
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Benign Cartilaginous Lesions
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Benign Osseous Lesions
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Malignant Lesions of Bone
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Benign Lesions of Soft Tissue
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Malignant Lesions of Soft Tissue
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| Non-Ossifying Fibroma Desmoplastic Fibroma Aneurysmal Bone Cyst Giant Cell Tumor |
Exostosis Periosteal Chondroma Enchondroma Chondroblastoma Chondromyxoid Fibroma |
Enostosis (Bone Island) Osteoma Osteoid Osteoma Osteoblastoma |
Myeloma Lymphoma Ewing's Sarcoma Metastatic Carcinoma Chondrosarcoma Chondrosarcoma, Clear Cell Chondrosarcoma, Dedifferentiated Chondrosarcoma, Juxtacortical Chondrosarcoma, Mesenchymal Chondrosarcoma, Secondary to Enchondroma Chondrosarcoma, Secondary to Exostosis Osteosarcoma Osteosarcoma, Low-Grade Intramedullary Osteosarcoma in Paget's Disease Osteosarcoma, Parosteal Osteosarcoma, Periosteal Osteosarcoma, Small Cell Osteosarcoma, Soft Parts Osteosarcoma, Telangiectatic Chordoma Adamantinoma |
Angiolipoma Lipoma Fibromatosis Hemangioma Neurilemoma Neurofibroma |
Soft Tissue Sarcoma Fibrosarcoma Liposarcoma Leiomyosarcoma Malignant Fibrous Histiocytoma Neurosarcoma Rhabdomyosarcoma Synovial Sarcoma Vascular Sarcoma |
Diseases of Growth
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Repair of Connective Tissuse
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Infection
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Circulatory Disease
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Metabolic Bone Disease
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Achondroplasia congenital and often hereditary (autosomal dominant) skeletal disorder characterized by a unique form of dwarfism and bone deformity resulting in a disproportinate shortness of the extremities relative to the trunk. caused by a failure of proliferation and column formation of epiphysial cartilage cells, that is, by a defect in endochondral bone formation which impairs the longitudinal growth of the tubular bones. Point mutations in the FGR3 gene (encoding fibroblast growth receptors) on human chromosome 4 p segregate with disease in achondroplasia families various degrees of expression. The severest cases result in fetal or neonatal death, and milder cases survive and comprise the commonest type of adult dwarfism. The adult height in achondroplasia is usually less than four feet. The extremities (legs, arms, fingers, toes) are very short (micromelia) relative to the trunk which is only slightly shortened. Intramembraneous ossification is not affected. The head (cranial vault) is large. The root of the nose is depressed. The skeletal deformities just noted along with normal intelligence and sexual development distinguish achondroplasia from dwarfism resulting from endocrine and nutritional deficiencies and other causes. The microscopic changes in achondroplasia are best shown by a section of the epiphysis of a long bone during the neonatal period. The epiphysial growth plate is thin. There are few cells in the zone of proliferating cartilage. The hypertrophic cartilage cells form extremely irregular columns, if any, and as a result the zone of provisionally calcified cartilage is small and does not provide an adequate scaffolding for bone matrix deposition by metaphysial osteoblasts. Periosteal new-bone formation by osteoblasts is not impaired. 
Osteogenesis imperfecta (OI) is a rare heritable and often congenital disorder of skeletal development .characterized by bone fragility which predisposes to fractures and deformity and by connective-tissue .abnormalities which may involve the eyes (blue sclerae), ears, teeth, joints, and skin. The underlying cellular defect lies in abnormal collagen synthesis by osteoblasts and fibroblasts. (Collagens are the major protein constituents of connective tissue, and type I collagen is the main collagen of bone, tendon, and skin.) Molecular studies indicate that the primary biochemical defect in OI is defective synthesis and secretion of collagen I caused by mutations (deletions, insertions, substitutions) in the two structural genes which encode the alpha1- and alpha 2- peptides of this triple helix molecule. Many, if not all, of the OI phenotypes are mutants of the two collagen 1 structural genes. Inheritance may be dominant, recessive, or sporadic. OI is divisible into two main clinical groups based upon the age of onset and the clinical severity: OI congenita with multiple fractures usually present at or before birth and often fatal. OI tarda in which disease expression is less severe and often not apparent at birth. There is a broad range of disease expression within each group. The chief clinical features are: fragility of bones, multiple fractures (of long bones), bone deformities, (caused by fracture healing with poor alignment and weak callus): and shortness of stature or dwarfism (in the congenita group). The bones of the extremities are shorter, smaller, and thinner than normal. A general decrease in bone mass (osteopenia/osteoporosis) is seen radiographically. The teeth may be fragile and discolored as a result of dentin imperfection (dentinogenesis imperfecta). A striking feature is the presence of blue sclerae caused by a thin or defective fibrous layer which is translucent to the underlying choroid and vitreous. Ligamentous laxity of joints and thin fragile skin also reflect a defective fibrous structure. Progressive impairment of hearing, more common in the tarda group, is caused by otosclerosis. The typical microscopic changes of OI can be seen in a section of a long bone of a severely affected child. The bone cortex is thin and porous. The bone trabeculae are thin, delicate, and widely separated. Many osteoblasts and osteocytes are present, but the formation and organization of osteoid is deficient. There is less bone tissue than normal and most of it is woven or non-lamellar bone with collagen fibers of small size and random distribution. The woven bone has an increase in basophilic ground substance (shown by blue staining in H.&E. sections): Replacement of immature by mature bone with circumferential lamellae and Haversian systems is delayed or incomplete. The woven bone in OI may persist into adolescence, whereas in normal children woven bone usually occurs only in the embryo or early childhood ( or in fracture repair). The proliferation of epiphysial cartilage cells is normal, but the formation of osteoid by osteoblasts is impaired and delays the process of endochondral bone formation. rare hereditary, usually congenital, disorder of skeletal development characterized by massive but fragile bones, with marked thickening of cortical and medullary bone and concomitant reduction of the marrow space, and resulting in some cases in severe, even fatal, anemia and in blindness and deafness. The cause of osteopetrosis is unknown but the pathogenesis appears to be related to a defect in the function of osteoclasts in bone resorption and remodeling. There are two different genetic and clinical forms of the disease. The autosomal recessive form runs a "malignant" course and is fatal in utero, infancy or young adult life as a result of bone marrow obliteration, profound anemia, or other hemopoietic abnormalities. The autosomal dominant form has a more benign course marked by repeated fractures on slight trauma, a near normal normal life expectancy, and the absence of hemopoietic abnormalities. Radiographically and pathologically, all bones are affected, but the most significant changes in osteopetrosis occur in the bones which are preformed in cartilage. The long bones of the extremities, vertebrae, pelvic bones, and base of the skull show a great increase in the density and thickness of the cortex, an increase in the number and size of bony trabeculae, marked reduction or obliteration of the marrow spaces and haversian systems. The reduction in the total amount of bone marrow leads to anemia and extramedullary hemopoiesis, resulting in enlargement of the spleen, liver, and lymph nodes. 
Bone overgrowth at the base of the cranium causes narrowing of the optic foramina and pressure on the optic nerves, resulting in primary optic atrophy and blindness. Other cranial nerves, such as the auditory nerves, are similarly involved. In addition to the increased density and mass of the long bones, the most characteristic microscopic change in medullary and cortical bone is the presence and persistence into adult life of spicules of calcified cartilage which normally would have been resorbed, replaced, and remodeled preparatory to endochondral ossification. These changes apparently reflect a basic defect in the function of osteoclasts in the resorption and remodeling of mineralized epiphysial cartilage. Osteoclasts and active osteoblasts are few in number. The bone tissue formed is largely woven bone, and very little of it is remodeled and replaced by lamellar bone. Although massive, the bone structure is of poor structure and easily fractured. This is an hereditary developmental disorder of the skeleton in which multiple cartilage-capped bony outgrowths (exostoses/osteochondromas) protrude from the bone cortex in the metaphysial region of bones preformed in cartilage, such as the long bones of the extremities particularly in the region of the knee, ankle, or shoulderThe exostoses tend to have a bilateral and symmetrical distribution. The scapulae, ribs, inominate bones, vertebrae, and metacarpal and metatarsal bones may also be involved. Although not common, hereditary multiple exostosis is the most frequently seen systemic disorder of skeletal development. It is apparently inherited as an autosomal dominant, but there is an unexplained 3:1 preponderance of affected males compared to females. The precise origin of the cartilage-capped lesions is uncertain. The usual explanation is that the exostoses arise from foci of misplaced or misdirected epiphysial cartilage which grows outwardly rather than longitudionally, abetted by a lack of normal restraint from the covering perichondrium. The exostoses grow by endochondral ossification of the cartilage cap, and growth of the exostoses ceases at or prior to the skeletal maturation of the individual. Pathologically and radiographically, the exostoses are seen as sessile or stalked bony protuberances, with various shapes (knobby, hemispherical, conical) and sizes (1-10 cm. in diameter), protruding from the metaphysial region of the involved bones The exostoses of long bones characteristically point away from the joint because the epiphysial site of origin of the exostoses lags behind the advancing epiphysial growth plate as the long bones increase in length. Grossly, the exostoses are covered with periosteum and capped with a thin layer of cartilage In some ( 3-5%) cases of hereditary multiple exostosis, the cartilage cap or remnants of it undergoes malignant transformation to a sarcoma, most often a peripheral chondrosarcoma. Malignant transformation is less often seen in solitary exostosis which, although microscopically similar and much more common than multiple exostosis, does not have an hereditary basis and is not a systemic disorder of skeletal development. rare disorder of skeletal development characterized by the presence of multiple circumscribed foci or masses of cartilage in the interior of bones preformed in cartilage, particularly the long and short tubular bones of the extremities. The disorder does not appear to be hereditary. Clinical manifestations of the condition may first appear in early childhood. Swellings of the fingers and toes, bone deformities, leg length discrepancies, and pathological fractures may be caused by the presence of the enchondromasSkeletal involvement tends to be greater on one side of the body than the other. Multiple hemangiotama of the soft tissues and muscles is sometimes associated with enchondromatosis (Maffucci syndrome). multiple, central, well circumscribed areas of radiolucency, often striped with calcification, located in the short or long tubular bones, and frequently causing thinning and bulging of the cortex. of lobules of cartilage cells of benign but richly cellular appearance forming a hyaline matrix. The morphological appearance is similar to that of solitary enchondroma, a benign cartilage growth that involves only a single bone in an individual ( discussed under Bone Tumors). Acute hematogenous osteomyelitis occurs predominately in children and before the age of epiphysial closure (<21 yrs), typically originates in the metaphysis of long bones in the region of most rapid growth and greatest vascularity, and involves, in order of frequency, the lower end of the femur, the upper end of the tibia and humerus, and the radius. Hematogenous osteomyelitis of children sometimes results from the blood-borne spread to bone of an extraskeletal focus of infection (skin, ear, pharynx) , but most often such a source of infection is not clinically demonstrable. In that event it is generally assumed that transient "trivial" bacteremia arising from "trivial" trauma, such as ordinary cuts and bruises of the skin, is the original source of infection. Hematogeneous osteomyelitis of children is most often caused by S. aureus which accounts for 60-90% of cases. Osteomyelitis of neonates is also frequently caused by group B streptococci and E. coli. Children with sickle cell disease are prone to acquire Salmonella infections and to develop Salmonella osteomyelitis. Osteomyelitis of children usually begins in the metaphysis of long bones. The blood-borne bacteria are carried to the marrow space by way of the nutrient artery. The initial site of infection within a particular bone is determined by the vascular anatomy as related to the epiphysial growth plate. In children of more than 1 year of age (who account for most cases, about 80%, of hematogenous osteomyelitis), the metaphysial branches of the nutrient artery do not penetrate the growth plate. The vessels turn back upon themselves just proximal to the plate and enter venous sinusoids in the marrow space of the metaphysis. The venous sinusoids are much larger than the arteries feeding them, have a slower blood flow, and provide a medium favorable for bacterial growth. Hematogenous osteomyelitis in adults rarely involves the long bones but usually occurs in the vertebrae which are generally highly vascular. The hematogenous spread of infection can occur by way of the nutrient branches of the spinal artery or by flow from the pelvic veins to the lumbar veins and, under conditions of increased abdominal pressure, retrograde flow through the paravertebral venous plexus of Batson. The vertebral infection is usually secondary to a primary bacteremia caused by genitourinary tract infection, soft tissue and respiratory infections, and those contracted by i.v. drug abusers. S. aureus accounts for about 55% of adult bone infections, and Gram-negative bacteria and streptococci for much of the remainder. The complications of vertebral osteomyelitis include extension of the infection to the adjacent disk space and extension to retropharyngeal, mediastinal, peritoneal, and meningeal sites depending on the vertebrae involved. 
Pathology The bacterial infection causes a fulminant acute inflammation of the marrow space and an exudation of polymorphonuclear leukocytes. The presence of an inflammatory exudate within the rigid limits of the marrow space causes an increase in intramedullary pressure, reduced blood flow, local vascular occlusion, and thrombosis. Local ischemic injury and cell necrosis of marrow and osseous tissue occur, and the bacteria, pus cells, and necrotic debris comprise a septic focus of purulent inflammation. At the early stage of the infection, no specific bone changes are seen by radiography. The infection may then spread rapidly by way of vascular channels through the medullary cavity and the bone cortex which is thin in the region of the metaphysis and provides easy access to the periosteum. The purulent material may elevate the periosteum and form abscesses beneath it or penetrate the periosteum as sinus tracts which drain into the soft tissue or extend to the skin surface. The stripping away of the periosteum further impairs the blood supply to the cortical and medullary bone, and larger areas of ischemic bone tissue become necrotic. The areas of bone destruction may be seen in the radiograph as patchy areas of radiolucency. After several days a sizeable portion of the necrotic bone tissue may separate from the viable bone as an avascular bone fragment termed a sequestrum, which may be seen in the radiograph as a radioopaque sequestrumWith continuation of the bone infection, chronic inflammatory cells (lymphocytes, histiocytes, plasma cells), proliferating fibroblasts, and reactive new bone formation contribute to the microscopic picture of chronic osteomyelitisThe elevated periosteum is stimulated to form new bone which surrounds the underlying infected and inflammed bone with a bony envelope termed an involucrum. Clinical Course The onset of hematogenous osteomyelitis is usually sudden in children (but often insidious in adults). The early symptoms of childhood osteomyelitis are those of infection and inflammation: fever, bone pain often throbbing and severe and referred to the metaphysis, tenderness to pressure, limitation of movement which in the extreme may render the limb immobile ("pseudoparalysis"), local erythema, swelling, and heat. Blood cultures are positive in about 50% of pediatric cases . The clinical diagnosis of early osteomyelitis can be supported by a bone scan ( with technicium diphosphonate): increased tracer uptake reflects the inflammatory process in the bone lesion. Plain radiographs usually do not reveal changes until about 10 or more days after the onset of symptoms, because a substantial (30-50%) reduction in bone calcium content is required for the demonstration of an osteolytic destructive lesion. The course of acute hematogenous osteomyelitis is age-dependent. In neonates (< 3 months of age), bone infections are often fulminant but rarely necrotizing, because the spongy bone and thin cortex adapt to increased intraosseous pressure without compromising the blood supply. In infants (3-12 months) and adults, capillaries extend from the metaphysis to the epiphysis and can spread the infection to the adjacent joint, causing suppurative arthritis and septic joint effusion. In children (>1 yr.) who have an intact epiphysial plate without capillary penetration, a sterile "sympathetic" effusion may occur, indicating a barrier between the infection and the joint space. The pathological picture in hematogenous osteomyelitis may occasionally differ from the spreading and destructive pattern previously described. The initial focus of bone infection may become circumscribed by a fibrous capsule and bone sclerosis to form a localized abscess (Brodie's abscess) which may undergo sterilization or become a chronic focus of infection. Rarely, in other circumstances, exuberant periosteal new-bone formation dominates the pathological picture, resulting in a non-purulent sclerosing osteomyelitis (Garre's sclerosing osteomyelitis). A prompt clinical diagnosis and the institution of a potent and protracted regimen of antibiotic therapy have greatly decreased the mortality rate of osteomyelitis which reached as high as 20-40% of cases in the pre-antibiotic era. Nevertheless, even now a sizeable number of bone infections may be undiagnosed or inadequately treated. In chronic osteomyelitis, the avascular dead tissue, pus and bacteria may remain isolated within an area of bone fibrosis and sclerosis and give rise to recurrent episodes of acute osteomyelitis. The treatment of chronic bone infections usually requires , in addition to antimicrobial therapy, surgical intervention to drain abscesses and remove necrotic tissue. Burns, sinus disease, peridontal infection, soft tissue infection, and skin ulcers caused by peripheral vascular disease (arteriosclerosis, diabetes, vasculitis) are among the adjoining sites of microbial infection that may spread to bone. The onset is often insidious, and the symptoms are those of infection and inflammation of the involved bone. The pathological and radiological changes are similar to those seen in chronic hematogenous osteomyelitis. The treatment usually requires surgical intervention (debridement of necrotic tissue, drainage of abscesses, etc.) combined with bacteriological cultures and appropriate antimicrobial therapy. Blood cultures are positive in about 10% of cases. Tuberculous osteomyelitis is almost always caused by the hematogenous spread of organisms from an active focus of tuberculosis elsewhere in the body, usually the lung and occasionally some other site (mediastinal or aortic lymph nodes, kidney, bowel, etc.). The bone infection may occur at any age but is most commonly seen in children. The vertebrae and the long bones of the extremities are most frequently involved. In many cases the infection also spreads to contiguous joints such as the hip, knee, and intervertebral joints. The bones and joints of the hands, feet, shoulder, elbow, and ribs are also sometimes involved. In some patients, it may be impossible to determine whether the infection originated within the cancellous bone of the metaphysis or the joint. The onset of tuberculous osteomyelitis is usually insidious. The infection is unrelenting, necrotizing, and destructive of bone, cartilage, and soft tissue. The tuberculous exudation and the inflammatory necrosis may extend through the medullary and cortical bone, penetrate through the periosteum, and progress through the epiphysial and articular cartilage (radiographic joint space). Tunneling sinuses may extend into the adjoining soft tissue and drain to the skin surface. Sequestration and the formation of an involucrum are uncommon. Tuberculosis of the spine (Pott's disease) most commonly involves the thoracic and lumbar vertebrae and usually comprises both tuberculous osteomyelitis and tuberculous arthritis. Tuberculosis of spine (Pott's disease) with vertebral collapse and acute kyphotic angulation. The infection often begins in the anterior part of the vertebral body and extends into the intervertebral disc: The tuberculous destruction and collapse of the vertebral bodies and discs result in serious deformities (kyphosis and kyphoscoliosis) of the spine. The kyphotic angulation along with the inflammation and edema of the dura caused by vertebral collapse may compress the spinal cord and nerve roots, resulting in pain, muscle spasm and weakness, and paralysis. The tuberculous exudate emerging from a bone or joint may spread through sinuses in the soft tissue or dissect along fascial planes and muscle sheaths and present at a more remote site as a "cold" abscess, socalled because there is a milder degree of heat compared to a pyogenic abscess and few, if any, acute inflammatory cells. In this way, tuberculous exudation from the thoracolumbar spine may spread along paravertebral muscles and the psoas muscle sheath and localize in the inguinal region (psoas abscess). Microscopically, tuberculosis of bone and joint is characterized, as are all tuberculous lesions, by the presence of epithelioid granulomas (tubercles) with central caseous necrosis and Langhans' multinucleate giant cells: For a definitive diagnosis, tubercle bacilli must be demonstrated microscopically in the lesions or cultured from bone, joint, or synovial fluid. Tubercle-like (tuberculoid) granulomas may be seen in some other inflammatory diseases of bone such as coccidioidomycosis and Boeck's sarcoid, which is characterized by granulomas that rarely, if ever, caseate or calcify. The two chief bone lesions of congenital syphilis are osteochondritis and periostitis. Syphilitic osteochondritis involves the metaphysial-epiphysial junctions of long bones and the costo-chondral junctions. Microscopically, the lesions reveal little evidence of osteoblast activity or endochondral bone formation, the epiphysial zone of provisional calcification is widened (as also shown radiologically), and syphilitic inflammatory granulation tissue extends across the metaphysis. The connection between the metaphysis and epiphysis may be loosened and result in epiphysial separation. The inflammatory granulation tissue permeating the metaphysis contains an abundance of proliferating capillaries and a prominent perivascular infiltrate of mononuclear inflammatory cells, with large numbers of plasma cells. In florid cases, spirochetes may be demonstrated in the lesions by silver stains. Syphilitic periostitis is usually seen in early childhood and is characterized by the infiltration of inflammatory granulation tissue between the periosteum and the bone cortex and by subperiosteal new-bone formation. The tibia is most often affected. The deposition of new bone along the anterior cortical surface produces a forward bowing and sharpening of the tibia, the "saber shin" deformity of congenital syphilis. Acquired syphilis of bone occurs in the tertiary stage of the disease and involves the long tubular bones, the skull, and the vertebrae. The lesions include syphilitic osteochondritis, periostitis with extensive subperiosteal new-bone formation, and osteomyelitis, usually caused by the formation of gummas in the medullary cavity. Arthritis
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Synovial Disease
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Skeletal Disease
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Benign Skeletal Lesions
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Benign Cartilaginous Lesions
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Benign Osseous Lesions
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Malignant Lesions of Bone
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Benign Lesions of Soft Tissue
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Malignant Lesions of Soft Tissue
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PROFILE
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BODY HABITUS
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DIETARY
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LIFE STYLE
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Caucasian
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Low weight
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Low calcium intake
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Inactivity
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Nulliparity
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Small frame
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High protein intake
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Smoking
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Scoliosis
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Leanness
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High phosphorus intake
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High alcohol intake
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Positive family history
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Lactase deficiency
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OTHER
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Low bone mass at skeletal maturity
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Early or surgically induced menopause
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Steroid or anticonvulsant medication
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Female sexAge > 70 yearsCaucasian or Asian raceEarly onset of menopauseLonger postmenopausal intervalInactivity, especially lack of weight bearing exerciseMetabolic bone disease, such as hyperparathyroidismNeoplasia, as with multiple myeloma or metastatic carcinomaMalnutritionDrug therapy, as with corticosteroidsProlonged immobilizationWeightlessness with space travelSmokingAlcohol abuseExcessive caffeine consumptionExcessive dietary protein consumptionLack of dietary calciumLack of sunlight exposure (to generate endogenous vitamin D)Radiographic measurement of bone densityLaboratory biochemical markersBone biopsy with pathologic assessmentAlkaline phosphatase, which reflects osteoclast activity in bone, is measured in serum, but it lacks sensitivity and specificity for osteoporosis, because it can be elevated or decreased with many diseases. It is increased with aging. Fractionating alkaline phosphatase for the fraction more specific to bone doesn't increase usefulness that much.Osteocalcin, also known as bone gamma-carboxyglutamate. It is synthesized by osteoblasts and incorporated into the extracellular matrix of bone, but a small amount is released into the circulation, where it can be measured in serum. The levels of circulating osteocalcin correlate with bone mineralization, but are influenced by age, sex, and seasonal variation. Laboratory methods also vary.Urinary calcium can give some estimate of resorbtion (loss of) bone, but there are many variables that affect this measurement. Thus, it is more specific for osteoporosis when measured following overnight fasting.Urinary hydroxyproline is derived from degradation of collagen, which forms extracellular bone matrix. However, hydroxyproline measurement is not specific for bone, because half of the body's collagen is outside the bony skeleton. It is also influenced by many diseases, as well as diet.Hip (femoral head and neck)WristVertebraeHip fractures that occur, even with minor falls, can be disabling and confine an elderly person to a wheelchair. It is also possible to surgically put in a prosthetic hip joint. Wrist fractures are common with falls forward with arms extended to break the fall, but the wrist bones break too. Vertebral fractures are of the compressed variety and may be more subtle. Vertebral fractures may result in back pain. Another consequence is shortening or kyphosis (bending over) of the spine. This can lead to the appearance of a "hunched over" appearance that, if severe enough, can even compromise respiratory function because the thorax is reduced in size.Persons suffering fractures are at greater risk for death, not directly from the fracture, but from the complications that come from hospitalization with immobilization, such as pulmonary thromboembolism and pneumonia.Osteoporosis is so common that, on average, about 1 in 2 elderly Caucasian women will have had a fracture. In contrast, only about 1 in 40 men of similar age will have had a fracture. Men start out with a greater bone mass to begin with, so they have a greater reserve against loss.Prevention StrategiesThe best long-term approach to osteoporosis is prevention. If children and young adults, particularly women, have a good diet (with enough calcium and vitamin D) and get plenty of exercise, then they will build up and maintain bone mass. This will provide a good reserve against bone loss later in life. Exercise places stress on bones that builds up bone mass, particularly skeletal loading from muscle contraction with weight training exercises. However, any exercise of any type is better than none at all, and exercise also provides benefits for prevention of cardiovascular diseases that are more common in the elderly. Athletes tend to have greater bone mass than non-athletes. Exercise in later life will help to retard the rate of bone loss.TreatmentPersons with osteoporosis may benefit from an improved diet, including supplementation with vitamin D and calcium, and moderate exercise to help slow further bone loss.Most drug therapies work by decreasing bone resorbtion. At any given time, there is bone that has been resorbed but not replaced, and this accounts for about 5 to 10% of bone mass. By decreasing resorbtion of bone, a gain in bone density of 5 to 10% is possible, taking about 2 to 3 years. However, no drug therapy will restore bone mass to normal. Women past menopause with accelerated bone loss may benefit from hormonal therapy using estrogen with progesterone. The estrogen retards bone resorption and thus diminishes bone loss. This effect is most prominent in the first years after menopause.One of the more common non-estrogen therapies is the use of alendronate, a biphosphonate that acts an an inhibitor of osteoclastic activity. Alendronate may be beneficial, particularly in women who cannot tolerate estrogen therapy. Alendronate is effective in inhibiting bone loss after menopause.Raloxifene is a selective estrogen receptor modulator that may also replace estrogen therapy. Raloxifene can act in concert with estrogen in bone to inhibit resorbtion and decrease the risk for fractures. Though raloxifene inhibits bone resorbtion, it does not have an anabolic effect. Additional potential benefits from raloxifene therapy include decreased risk for breast cancer, because raloxifene acts antagonistically to estrogen on the uterus. Conversely, raloxifene acts in concert with estrogen to protect against and reduce atherogenesis.Other drug therapies are less commonly employed. Calcitonin, a hormone that decreases bone resorbtion, may be taken by injection or by nasal spray. Sodium fluoride can increase the measured bone density in vertebra, but seems to have no overall effectiveness in reducing vertebral fracture. Fluoride helps reduce tooth decay.
The radiograph of the pelvic region is shown above, with an intertrochanteric fracture located in the right femur of an elderly woman with osteoporosis. Below is the postoperative radiograph following surgical repair.Osteoporosis may be reasonably suspected in an elderly patient with a relatively atraumatic fracture of the hip or a postmenopausal woman complaining of back pain, recent or gradual loss of height, and progressive thoracic kyphosis, in the presence of risk factors and the absence of other causes of osteopenia previously noted. Of the approximately 1 million fractures (of hip, spine, wrist) occurring annually in the U.S. in women over the age of 50, a large majority is related to osteoporosis. Further, many elderly patients die within a few months after hip fracture although prosthetic joint replacement and early ambulation have decreased the mortality from this condition. Plain clinical x-rays do not detect osteopenia until it is considerably advanced and approximates a 30-50% loss of bone mass. Other noninvasive scanning techniques for the evaluation of osteoporosis ( applicable to distal radius, femoral neck, and lumbar vertebrae) include: single and dual photon absorptiometry and quantitative computed tomography (CT). Routine laboratory tests of blood (serum calcium, phosphate, alkaline phosphatase) and urine are usually normal in the typical osteoporotic patient, except for severe acute fracture with an associated increase in serum alkaline phosphatase activity. Urinary markers of increased bone resorption after menopause include measurements of urinary cross-linked peptides derived from type I collagen. Osteoporosis is a common condition and thus may coexist with other primary bone disorders of the aging, such as osteomalacia and Paget's disease of bone. In addition to supplemental calcium and vitamin D, therapeutic protocols that mainly decrease resorptive bone loss in postmenopausal osteoporosis include: estrogen replacement therapy, calcitonin, and the biphosphanate, alendronate. Raloxifene (a member of a new class of drugs called selective 'estrogen-receptor modulators') displays estrogen-like (agonistic) effects on bone and antiestrogen (antagonistic) effects on breast and uterus and was recently approved for the prevention of osteoporosis in postmenopausal women. The diseases resulting from vitamin D deficiency are rickets in infants and growing children and osteomalacia in adult life. The bone changes in both conditions are characterized by inadequate mineralization, resulting in a deficient amount of the mineral phase of bone and an excess of unmineralized osteoid. The osteoid excess is caused by a failure of the process of mineralization to keep up with the new formation of osteoid during bone formation and remodeling. In rickets, which mainly affects children between the ages of 6-30 months, inadequate mineralization occurs not only in bone but also in epiphysial cartilage at sites of endochondral ossification, resulting in growth disturbances, skeletal deformities, and susceptibility to fractures. Presenting symptoms of osteomalacia ("softness of bone") include diffuse skeletal pain, bone tenderness, and muscular weakness. Rickets and osteomalacia may be caused by: a deficiency or abnormal metabolism of vitamin D; a deficiency or abnormal utilization/excretion of inorganic phosphate (Pi). A deficiency of vitamin D may be due to:a dietary lack of the vitamin; insufficient ultraviolet exposure to form endogenous vitamin D; and, most commonly, malabsorption interfering with the intestinal absorption of fats and fat-soluble vitamin D. An abnormal metabolism of vitamin D commonly occurs in chronic renal failure. Vitamin D3 is photosynthesized in the skin by ultraviolet radiation of 7-dehydrocholesterol. Vitamins D2 and D3, both of which are biologically inactive, are also absorbed in the intestines from dietary sources. Vitamins D2 and D3 are enzymatically hydroxylated in the liver to 25-hydroxyvitamin D, which is transported to the kidney and converted to 1,25- and 24,25-dihydroxyvitamin D. 1,25-dihydroxyvitamin D, termed calcitriol or vitamin D hormone, is the most active metabolite of vitamin D. The main function of vitamin D is to maintain a normal serum balance of calcium and phosphate (Pi) through action of the active metabolites on target organs: the intestine, bone, and parathyroid gland. 1,25-dihydroxyvitamin D increases the intestinal absorption of calcium and Pi, thus bringing the concentration of serum calcium and Pi to a critical level required for the mineralization of newly formed osteoid. Conversely, if there is an inadequate amount of 1,25- dihydroxyvitamin D, the intestinal absorption of calcium decreases, and the serum calcium level falls, calling forth PTH secretion to support the calcium level .(Serum calcium has a negative feedback on PTH secretion by parathyroid chief cells: a low serum calcium level increases PTH secretion, and a high serum calcium level decreases PTH secretion.) The increased PTH secretion tends to restore the serum calcium level but also stimulates increased renal Pi clearance, resulting in lower serum Pi levels. If the concentrations of serum calcium and Pi fall below a critical level, mineralization of osteoid cannot take place, resulting in osteomalacia (and rickets). An inadequate dietary intake of vitamin D sufficient to cause rickets or osteomalacia is rare in developed countries which utilize foods supplemented with vitamin D. There are exceptions: premature infants; the economically underprivileged; elderly people; dietary idiosyncrasy. . As to the historical role of limited exposure to ultraviolet radiation, rickets was described long ago as a common disease of "smokey cities and cloudy skies". The most common cause of osteomalacia today is intestinal malabsorption of fats and fat-soluble vitamin D resulting from: hepatic disease (biliary tract obstruction, primary biliary cirrhosis, alcoholic liver disease), chronic pancreatitis, intestinal diseases ( regional ileitis, sprue), and surgical operations (gastrectomy, resection of portions of the small intestine). Osteomalacia is often a component of renal osteodystrophy, the collection of bone disorders that occur in varying degrees of severity in almost all patients with chronic renal failure (CRF). The development of osteomalacia and rickets ("renal rickets") in CRF is due to the loss of renal parenchyma accompanied by: a decreased renal enzymatic capacity to convert 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, resulting in impaired intestinal absorption of calcium and hypocalcemia; and a decreased renal excretion of Pi, resulting in hyperphosphatemia and a reciprocal decrease in serum calcium to a level below that required for the mineralization of osteoid. ( This stimulates the increased secretion and synthesis of PTH and secondary hyperplasia of the parathyroid gland, resulting in the superimposed bone changes of osteitis fibrosa.) Drug-induced rickets and osteomalacia may occur in association with the use of the anticonvulsive drug phenytoin and is attributed to phenytoin's interference with vitamin D metabolism in the liver. Rickets and osteomalacia are also associated with hypophosphatemia. An induced deficiency of serum Pi may occur in peptic ulcer patients receiving long-term treatment with antacids containing aluminum hydroxide, which forms insoluble complexes with Pi in the intestine and blocks its absorption. Rickets and osteomalacia may also accompany renal tubular disorders in which there is an impaired renal resorption of Pi, resulting in hypophosphatemia and hyperphosphaturia, or metabolic acidosis which also affects the metabolism of vitamin D, calcium, and Pi. These hypophosphatemic disorders include: renal tubular acidosis (RTA) of which there are several types; the Fanconi syndrome of sporadic or familial origin; and two hereditary forms of hypophosphatemia, namely, x-linked hypophosphatemia (also termed vitamin D-resistant rickets), which is the most common cause of rickets in the U.S. today, and vitamin D-dependent rickets (autosomal recessive), in which there is a defect in the synthesis or cellular utilization of 1,25-dihydroxyvitamin D.. Rickets is also seen in children with hypophosphatasia, a rare heritable enzyme deficiency which is characterized by extremely low levels of alkaline phosphatase in the blood and tissues. The morphological characteristics of rickets, in the order of their development, are as follows: failure of mineralization of the epiphysial provisional zone of mineralization, resulting in disordered endochondral ossification; failure of mineralization of newly formed osteoid, resulting in an excess of osteoid (hyperosteoidosis) as shown by wide osteoid seams; and skeletal deformities caused by interference with endochondral ossification or by bending of the osteomalacic (softened) bones. Of these changes, hyperosteoidosis caused by a failure of mineralization is common to both osteomalacia and rickets. The widened osteoid seams contain prominent osteoblasts. Osteoclasts are rare (unmineralized osteoid does not stimulate an osteoclastic reaction). Hyperosteoidosis also occurs in other skeletal disorders, such as Paget's disease of bone and osteitis fibrosa caused by hyperparathyroidism. In these conditions , in contrast to osteomalacia and rickets, there is a high rate of bone turnover and no failure or delay of bone mineralization. Bone biopsy is the definitive method of establishing the diagnosis of osteomalacia. Undecalcified bone sections stained with the von Kossa technique allow a clear distinction to be made between osteoid and mineralized boneA biopsy of severe osteomalacia shows that virtually all (~100%) bone surfaces are covered by osteoid (whereas in normal bone, surface osteoid is <20%). Mineralization dynamics can be evaluated if two single 10 day-spaced doses of tetracycline (which binds to the mineralization front and is autofluorescent) are given to the patient before the bone biopsy is performed. A biopsy of normal bone shows two discrete and separated layers of fluorescent label uptake marking successive mineralization fronts. Whereas osteomalacic bone has a smudgy appearance of label uptake (or in some cases no uptake at all), indicating defective and delayed mineralizationGrossly, long-standing osteomalacia may produce fractures and deformities of the softened bones. The main deformities are kyphosis, bowing of the long bones, and narrowing of the pelvis. A child with severe rickets may have: a prominent forehead ("frontal bossing") due to osteoid excess; beading of the ribs at the costochondral junctions ("rachitic rosary") caused by overgrowth of cartilage and osteoid; curved limb bones; lateral flattening of the rib cage with forward displacement of the sternum ("pigeon breast"); and a depression ("Harrison's grove") at the lower margin of the rib cage produced by muscle contraction of the diaphragm. Blood Chemistry
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Increased
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Decreased
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Serum calcium
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Multiple myeloma
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Vitamin D deficiency states:
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Primary hyperparathyroidism
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Malabsorption
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Metastatic cancer
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Dietary deficiency
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Hyperthyroidism
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Anticonvulsant drugs
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Hypervitaminosis D
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Vitamin D dependent rickets
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Immobilization
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Calcium deficiency
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Renal osteodystrophy
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Serum phosphate
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Renal osteodystrophy
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Hypophosphatemic rickets
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Metastatic cancer
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Vitamin D deficiency states
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Immobilization
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Primary hyperparathyroidism
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Hypervitaminosis D
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Serum alkaline phosphatase
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Paget's disease of bone
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Hypophosphatasia
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Renal osteodystrophy
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Primary hyperparathyroidism
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Vitamin D deficiency
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Hypophosphatemic rickets
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Metastatic cancer
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24 hour urinary calcium
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Hypercalcemia
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Renal osteodystrophy
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Hyperthyroidism
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Hypophosphatemic rickets
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Hypercortisolism
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Vitamin D deficiency states:
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Immobilization
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Calcium deficiency
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Hypophosphatasia
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Lactose intolerance
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Renal tubular acidosis
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Dietary
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The skeletal changes in hyperparathyroidism are characterized by diffuse or focal resorptive loss and fibrous replacement of bone due to an excess of osteoclastic over osteoblastic activity and caused by an over-production of parathormone (PTH) in primary or secondary hyperparathyroidism. Primary hyperparathyroidism is a metabolic disorder in which parathyroid cells, either neoplastic or hyperplastic and in the absence of any known stimulus, secrete excessive amounts of PTH. Primary hyperparathyroidism is usually caused by a functioning adenoma of a single parathyroid gland, less commonly by diffuse hyperplasia of all four parathyroid glands, and rarely by primary parathyroid carcinoma or multiple parathyroid adenomas. Secondary hyperparathyroidism is associated with many conditions that lead to hypocalcemia and most often occurs as a consequence of the hyperphosphatemia and hypocalcemia of chronic renal failure. The complex bone changes in chronic renal failure are called renal osteodystrophy and include osteomalacia, rickets ("renal rickets"), osteitis fibrosa and other bone changes of hyperparathyroidism. Some non-parathyroid carcinomas (arising in lung, kidney,or elsewhere and without bony metastases) may produce a PTH-like hormone associated with a syndrome resembling hyperparathyroidism. This syndrome is called pseudohyperparathyroidism or ectopic hyperparathyroidism and may be reversed by removal of the functioning tumor. Primary hyperparathyroidism most frequently occurs in adults, has a peak incidence between the third and fifth decades and a female to male ratio of two or three to one, and is rarely seen in children under 10 years of age. Primary hyperparathyroidism, in the absence of renal disease, is characterized biochemically by hypercalcemia, hypophosphatemia, hypercalciuria, elevated serum alkaline phosphatase activity (in the presence of bone disease), and increased levels of PTH measured by radioimmunoassays. The symptoms of primary hyperparathyroidism may be minimal for many years, depending upon the extent of the metabolic disorder. The clinical presentations are divisible into three categories: most commonly, manifestations of hypercalcemia, such as neuromuscular weakness, fatigue, gastrointestinal symptoms, and, rarely, coma in severe hypercalcemic crisis; renal stones (often bilateral); calcification of the kidneys (nephrocalcinosis); and metastatic calcification of other tissues; bone resorption and fibrous replacement resulting in diffuse osteopenia (which may be difficult to distinguish radiologically from common osteoporosis); in some cases, "cystic" or tumor-like lesions of bone ("brown tumors"); pathological fractures; and, rarely seen today, widespread alterations and deformities affecting the demineralized and softened bones of the entire skeleton (generalized osteitis fibrosa cystica).Osteolytic tumors (metastatic cancer, multiple myeloma, leukemia) Hyperparathyroidism Tumors that produce ectopic PTH (pseudohyperparathyroidism) Vitamin D excess Hyperthyroidism Excess calcium (milk) intake Immobilization Sarcoidosis Addisonian crisis The causes of primary hyperparathyroidism are: single parathyroid adenoma (~80% of cases), diffuse hyperplasia of all four parathyroid glands (15%), primary parathyroid carcinoma and/or multiple parathyroid adenomas (the remainder). Parathyroid adenoma usually arises in one of the inferior glands and may be difficult to locate if in some aberrant location, such as behind the mediastinum or elsewhere. Parathyroid adenomas are generally small (~0.4-4 cm in diameter), encapsulated, and colored variously yellow, tan, or red. Microscopically, the adenomas comprise pure or mixed cell types. Adenomas composed largely of chief cells are the more common while water-clear cell adenomas are seen less often. Parathyroid carcinoma is rare and distinguishable from adenoma on the basis of capsular and blood vessel invasion and biological behaviour, such as recurrence after local excision and metastases to regional lymph nodes or elsewhere. Primary hyperplasia usually involves all four parathyroid glands although not always symmetricallyThe superior glands, normally smaller, are often more enlarged by hyperplasia than the inferior pair. Chief cell hyperplasia is the more common lesion, but water-clear cell hyperplasia generally produces greater enlargement of the glands which may attain a total weight of 10-500 times that of all four normal glands (~0.05-0.3 g). The pathological changes of the skeleton in hyperparathyroidism comprise: diffuse bone loss resulting from osteoclastic resorption and fibrous replacement of bone (osteitis fibrosa); foci of cystic lesions (osteitis fibrosa cystica) or tumor-like lesions of bone ("brown tumors"); pathological fractures; and, rarely, profound alterations of the demineralized and softened bones of the entire skeleton. The osteoclastic and fibrous reaction (osteitis fibrosa) may involve bones throughout the skeleton, including the skull, vertebrae, shaft of long bones, and small bones, such as phalanges. Resorptions of the medial cortex of the phalanges and the tips of the distal phalanges of the hand are characteristic early radiographic findings. Microscopically, the earliest changes of osteitis fibrosa are resorptive loss and fibrous replacement of bone brought about by an excess of osteoclastic over osteoblastic activity and by fibroblast proliferation in the marrow space. Characteristically, numerous osteoclasts in Howship's lacunae are seen on bone surfaces undergoing resorption, beginning in the cancellous bone and tunneling through Haversian canals in the cortexThe marrow space is displaced and replaced by fibrocellular tissue and bone cells. Many osteoclasts may be seen on one surface of resorbing bone with active osteoblasts producing osteoid on the opposite surface, reflecting a high rate of bone turnover. The osteoid seams may be wide, but there is a normal rate of mineralization. The bone formed is often of an immature ( woven bone) type. (These histopathological changes may be difficult to distinguish from those of active Paget's disease of bone). The focal cystic lesions (osteitis fibrosa cystica) are often multiple; usually develop in the shaft of long bones, the jaw, and skull; are osteolytic and expansive; may form a tumor-like mass of brown, yellow, or hemorrhagic tissue ("brown tumor"); and evoke a weak response of bone regeneration in the adjacent bulging and thinning cortex. The foci of bone destruction are rarefied and thus "cystic" in a radiological sense. The bone lesions are not neoplastic. 1084 Anteroposterior (AP) and lateral views show focal osteolytic lesions of the tibia in primary hyperparathyroidism. Microscopically, the "brown tumors" of hyperparathyroidism are composed of proliferated osteoclasts and fibroblasts in a fibrous stroma, often located in a region of hemorrhage, and characteristically associated with hemosiderin deposition (which imparts a brown color). These focal lesions are sometimes referred to as reparative giant cell granulomas. The brown tumors of hyperparathyroidism must be distinguished from true giant cell tumors of bone, which they resemble histologically and radiographically. Giant cell tumors are true neoplasms, solitary, and arise spontaneously, usually in the epiphysis of long bones, commonly near the knee, and after epiphysial closure. The brown tumors of hyperparathyroidism are not neoplastic, usually occur in the diaphysis of long bones, the jaw, and the skull, and may be multiple. The chief clinical manifestations of primary hyperparathyroidism are hypercalcemia, renal stones, and bone changes. Virtually all patients with primary hyperparathyroidism have hypercalcemia and increased levels of serum PTH measured by radioimmunoassays. Among the many conditions included in the differential diagnosis of hypercalcemia, the most frequently encountered is "malignant" hypercalcemia caused by the presence in bone of metastatic osteolytic carcinoma (of breast, lung, kidney, thyroid) or multiple myeloma. The measurement and interpretation of serum PTH levels as determined by conventional radioimmunoassays are complex because not all of the immunoreactive fragments of PTH are biologically active. Recently developed radioimmunoassays for circulating intact PTH, the main biologically active form of the hormone, may become the future standard for clinical evaluations of hyperparathyroidism. Many disorders characterized by hypercalcemia and hypercalciuria may result in the formation of calcium-containing stones in the kidney (nephrolithiasis), bladder, or some other site in the urinary tract. Primary hyperparathyroidism accounts for about 5% of all cases of calcium renal stones. The diffuse and focal bone lesions of hyperparathyroidism must be distinguished from other skeletal disorders. The diffuse osteopenia caused by resorptive bone loss in hyperparathyroidism may be difficult to differentiate radiologically from common types of osteoporosis. The focal cystlike lesions and brown tumors of hyperparathyroidism must be distinguished from other radiolucent "bubbly" lesions of bone, among them: Fibrous dysplasia Giant cell tumor Simple bone cyst Aneurysmal bone cyst Fibrous cortical defect Enchondroma Eosinophilic granuloma Renal osteodystrophy (or uremic bone disease) is the term for a complex group of bone disorders that occur in patients with chronic renal failure (CRF). The bone disorders in renal osteodystrophy include: osteomalacia of adults and rickets of children (so-called "renal rickets"); osteitis fibrosa and other bone changes of secondary hyperparathyroidism; osteopenia; and osteosclerosis. Renal osteodystrophy occurs more often in children than in adults and particularly in the presence of congenital renal anomalies, such as renal hypoplasia and polycystic kidneys, that are associated with the development of slowly progressive renal insufficiency. The loss of functioning renal parenchyma in CRF is central to the pathogenesis of renal osteodystrophy. The bone changes are brought about by the abnormal metabolism of vitamin D, the overproduction of parathyroid hormone (PTH), and chronic metabolic acidosis. The diminished renal mass in CRF leads to a decreased renal conversion of 25-hydroxyvitamin D into 1,25-dihydroxyvitamin D, the active metabolite of vitamin D, resulting in diminished intestinal absorption of calcium, hypocalcemia, and defective bone mineralization characterized by the presence of wide osteoid seams, osteomalacia in adults, and rickets in children. The renal retention of phosphate in CRF causes hyperphosphatemia and further hypocalcemia, resulting in an increased synthesis and secretion of PTH, secondary hyperplasia of the parathyroid glands, and osteitis fibrosa and other bone changes of hyperparathyroidism, characterized by increased osteoclastic resorption and fibrous replacement of bone, increased osteoblastic activity, woven bone, and reparative giant-cell granulomas ("brown tumors"). The rapid remodeling and reorganization of bone in secondary hyperparathyroidism may result in osteosclerosis (increased amount of mineralized bone per unit volume). The metabolic acidosis occurring in CRF also inhibits the conversion of 25-hydroxyvitamin D into 1,25-dihydroxyvitamin D and increases the solubility of bone mineral, contributing further to the osteopenia resulting from osteitis fibrosa and/or osteomalacia. The bone changes of renal osteodystrophy as seen in an individual patient may reflect one or more of these metabolic abnormalities. In children, osteitis fibrosa and rickets occur separately or combined. In adults, a mixed pattern of osteomalacia, osteitis fibrosa, and osteosclerosis may be seen. Complications of renal osteodystrophy, such as spontaneous fractures, avascular necrosis (of the femoral head), and metastatic calcification of soft tissues may occur. Clinical symptoms of musculoskeletal disease occur in a small proportion of patients with renal osteodystrophy and may include bone pain, muscle weakness, deformities and growth retardation in children, and complicating pathological fractures. Skeletal abnormalities are found by radiography in about one third of patients with advanced renal failure and include: deformities and growth retardation similar to that seen in children with nutritional rickets; bone changes of secondary hyperparathyroidism typically showing resorptions and erosions of the tips of the distal phalanges and clavicles; and osteosclerosis as often noted radiographically by alternating bands of increased and normal or low density of the vertebrae (so-called "rugger jersey spine"). The laboratory findings in renal osteodystrophy include hyperphosphatemia, hypocalcemia, elevated alkaline phosphatase activity (reflecting increased osteoblastic activity), and increased PTH levels, particularly when assayed for C-terminal PTH which is an immunoreactive but biologically inactive fragment normally excreted only by the kidney. The management of patients with renal osteodystrophy includes: treatment of hyperphosphatemia by reduction of the dietary intake and absorption of phosphate through the use of intestinal phosphate binders (aluminum hydroxide); and dietary supplementation with 1,25-dihydroxyvitamin D to treat osteomalacia and osteitis fibrosa. Microscopically, the mixed phase of Paget's disease may resemble the bone changes of hyperparathyroidism. Radiologically, the advancing regions of osteolysis are followed by adjoining regions of increased density where new bone is formed. In the final stage of Paget's disease as resorptive activity wanes, sclerotic bone is formed (sclerotic phase) with a characteristic "mosaic" pattern of histologic structureNote the "mosaic" pattern of cement lines outlining irregular patches of sclerotic lamellar bone. The sclerotic bone is composed of patches of lamellar bone which are outlined by a mosaic pattern of cement lines, reflecting previous waves of bone resorption and reformation. The bone trabeculae become thick and prominent, particularly along the lines of stress.The bone width may be increased and the surface roughened by periosteal new-bone formation. Although often rocklike because of a lack of remodeling, the sclerotic bone is poorly organized, structurally weak, and predisposed to transverse fractureThe osteosclerotic phase is the most characteristic radiographic stage of Paget's diseaseThe presence of normal serum calcium and Pi, elevated serum alkaline phosphatase activity, and characteristic radiographic findings help to distinguish Paget's disease from other metabolic bone diseases. The majority of patients with Paget's disease of bone are asymptomatic. Their disease is usually monostotic and discovered fortuitously by radiographic findings or laboratory tests showing an elevated serum alkaline phosphatase activity. Symptomatic patients usually have polyostotic Paget's disease which most commonly involves the pelvic bones, followed in order of frequency by femur, tibia, skull, lumbosacral and thoracic spine, clavicles, and ribs. Pain is the most common presenting symptom and may result from microfractures, bony impingement on nerves, or other causes. Additional symptoms include bone enlargement or deformity, gait disturbance, overt pathological fracture or some other disease complication. In advanced cases, femurs and tibias may be bowed and the hips deformed; the vertebral bodies may be compressed, resulting in kyphosis or scoliosis; and some bones, such as the skull, may be enlarged. One of Paget's original patients, an elderly man, had to increase the size of his hat almost yearly, a rare but distinctive feature. Hearing loss is common in advanced Paget's disease and is caused by pagetic bone impingement on the auditory nerve at the nerve foramen or by ossicle involvement and otosclerosis. Severe Paget's disease may be complicated by: pathological fracture of affected bones; hemodynamic changes caused by bone hypervascularity, resulting in high-output left ventricular failure; and, in about 1% of patients, neoplastic transformation of pagetic bone into bone sarcoma: most commonly, osteogenic sarcoma; less often, fibrosarcoma; and, rarely, giant cell tumor. The radiographic findings in Paget's disease reflect the pathological changes and the disease activity at the site of the examination. Different skeletal areas may show different phases of the pagetic process. The osteolytic and combined osteolytic and osteoblastic lesions are clinically active, with skeletal pain as the most common symptom. Radioisotopic bone scans may be useful in revealing areas of disease activity not detectable by conventional radiographs. The osteosclerotic lesions are usually asymptomatic as well as the most characteristic radiologic stage of Paget's disease. Nevertheless, osteosclerotic bone lesions recognized by radiography may be found in many clinical conditions, among them: Metastatic osteoblastic carcinoma (of breast, prostate) Paget's disease of bone Osteopetrosis Myelosclerosis Osteochondroma Osteogenic sarcoma Osteoid osteoma Callus formation Greenstick fracture:
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the bone is cracked, but not broken in two pieces.
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Closed fracture:
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: the overlying tissues are intact
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Open fracture:
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: the bacteria have a route from the surface to the bone; bone may be sticking out the wound
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Comminuted fracture:
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: the bone is broken into several pieces
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Pathologic fracture:
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due to intrinsic disease of the bone; the force would not have broken normal bone
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Procallus:
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: fibrin/granulation tissue bump forming from the hematoma at the fracture site. “Provisional callus”
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Callus:
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granulation tissue bump at the fracture site that is starting to turn into fibrous tissue and cartilage, from which healed bone will arise. Eventually becomes bony callus and then
remodels to look more or less like the original bone
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Pseudarthrosis:
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the ends of the bone did not heal back together with bone. A “false joint” is created.
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http://edcenter.med.cornell.edu/CUMC_PathNotes/Skeletal/Bone_TOC.html
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Achondroplasia
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Osteogenesis Imperfecta (Brittle Bones, Fragilitas Ossium)
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Osteopetrosis (Marble Bone Disease, Osteosclerosis)
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Hereditary Multiple Exotosis (Osteochondromatosis)
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Enchondromatosis (Ollier's Disease)
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Fibrous dysplasia of bone is a non-neoplastic disorder of unknown etiology affecting one or several bones, thus divisible into monostotic and polyostotic forms, and characterized by the localized replacement of the bone interior by a distinctive fibro-osseous connective tissue and occasionally accompanied by abnormal skin pigmentation, endocrine dysfunction, or other extraskeletal manifestations. Although the pathogenesis and etiology are unknown, fibrous dysplasia apparently represents a peculiar developmental anomaly of the skeleton and the bone-forming mesenchyme. Fibrous dysplasia is a relatively common bone disorder and is usually first seen in children and young adults in the 2nd to 3rd decades and more frequently in males than females. The majority (~70-75%) of patients have a single bone lesion. Monostotic fibrous dysplasia frequently involves the rib (and is one of the commonest benign tumor-like lesions of ribs), femur, tibia, maxilla (the most frequently involved facial bone), calvarium, mandible, humerus, and ulna. Monostotic fibrous dysplasia is often asymptomatic. The clinical presentation may include: pain, tumor-like expansion and pathologic fracture of affected bones, and disfigurement by involvement of craniofacial bones. Extraskeletal changes aside from an occasional patch of skin hyperpigmentation are unusual in monostotic fibrous dysplasia. The monostotic disease does not appear to precede or to change into polyostotic fibrous dysplasia. Polyostotic fibrous dysplasia comprises the remaining 25-30% of cases. Several or many bones may be involved; the skeletal involvement tends to be unilateral; the craniofacial bones as well as the pelvic and shoulder girdles are often affected; and deformities and pathologic fractures occur in patients with extensive disease. The chief extraskeletal manifestations of polyostotic fibrous dysplasia are abnormal skin pigmentation, appearing as light or dark brown (melanin-containing) macules often located on the side of bony involvement, and endocrine (gonadal, thyroid, adrenal, pituitary) disorders which occur in about 3% of all patients with fibrous dysplasia. The clinical triad of fibrous dysplasia, skin pigmentation, and precocious puberty (in females) is known as Albright's syndrome. Grossly, the lesions of fibrous dysplasia are focal, expansive and tumor-like, usually located centrally and in the bone shaft, composed of rubbery or gritty, gray-red fibrous tissue with occasional areas of softening, and often bounded by a thin shell of cortical bone. Radiologically, the lesions are usually radiolucent and may have a "ground-glass" or "bubbly" appearance. Microscopically, the normal bone tissue is replaced by foci of cellular fibrous tissue with a whorled pattern of distribution and containing curlicues and trabeculae of newly formed woven boneThe connective-tissue cells are fibroblast-like in appearance but, unlike ordinary fibroblasts, produce woven bone and express high levels of alkaline phosphatase activity as shown histochemically. The woven bone trabeculae are not rimmed by osteoblasts. The fibrous or fibro-osseous lesions sometime contain islands of hyaline cartilage. Fibrous dysplasia is apparently a developmental anomaly of the skeleton, is usually first seen in childhood and young adults, and may be slowly progressive over many years. The clinical symptoms depend upon the site and extent of skeletal involvement. While many patients with monostotic lesions have little or no symptoms, the clinical presentation may include pain, limp, or local swelling. The skeletal involvement in patients with severe forms of the disease, which are commonly manifested in early childhood, may lead to serious deformities or disfigurement and repeated spontaneous fractures. The treatment of monostotic fibrous dysplasia usually includes curettage of the bone lesion and, if necessary, packing with bone chips. Polyostotic disease may require additional orthopedic procedures to stabilize fractures and correct or prevent deformities. Sarcomatous transformation of a bone lesion of fibrous dysplasia is a serious and rare complication occurring in a fraction of a percent (~0.5%) of all cases. Fibrous cortical defect is a common developmental anomaly occurring mainly in children over 2 years of age and characterized by the presence of one or more fibrous defects in the metaphysial cortex of the femur or other long bones of the lower limbs. Skeletal surveys show that between 30-40% of children, particularly those of younger age, develop one or more fibrous cortical defects which usually are small, asymptomatic, and gradually disappear, apparently by bony replacement and remodeling. Infrequently, a fibrous cortical defect may persist and enlarge by fibroblastic proliferation, extend into the medullary cavity, and become symptomatic, resulting in local pain and tenderness, bone swelling, and predisposition to fracture. This tumor-like lesion is commonly termed a nonossifying (or nonosteogenic) fibroma or sometimes, in keeping with its apparent developmental and non-neoplastic origin, a metaphysial fibrous defect. Fibrous cortical defect and nonossifying fibroma have essentially the same histological appearance and are thought to arise by the same basic process of periosteal fibroblastic proliferation. Nonossifying fibroma is much less common than fibrous cortical defect and occurs mainly in the age range of 10-20 years or sometimes beyond, with slight male predominance. Nonossifying fibroma characteristically occurs in the metaphysis of a long bone, most commonly in the lower part of the femur followed in frequency by tibia and fibula. The radiological features of the larger nonossifying fibroma (as well as the smaller fibrous cortical defect) are usually characteristic and diagnostic with a high degree of accuracy. Nonossifying fibroma is typically located in the metaphysis; in profile view is positioned eccentrically in the cortical wall; has a radiolucent multiloculated "soap bubble" appearance; is usually longer than it is wide; and commonly measures between 4 and 7 cm in greatest diameter. The lesion is outlined by a narrow margin of cortical or sclerotic bone. Grossly, a nonossifying fibroma is composed of firm fibrous-like tissue with gray, tan, or yellow color, sometimes with areas of hemorrhage, and surrounded by a thin shell of sclerotic bone. Histologically, the lesion consists of foci of interlacing or whorling bundles of spindle-shaped fibroblasts, along with infrequent small multinucleate giant cells and small or large collections of "foam" cells, which are thought to be lipid-laden fibroblasts and may be the predominant cell-type in some lesions. Focal hemorrhage and hemosiderin deposition may also be seen. , fibrous cortical defect is usually asymptomatic and spontaneously disappears over time. The radiological diagnosis of fibrous cortical defect or nonossifying fibroma with typical features is highly accurate. Fibrous cortical defect is rarely biopsied whereas nonossifying fibroma comprises a small but significant proportion of all benign bone biopsies. The cytological features of nonossifying fibroma may be a possible source of confusion to those unfamiliar with its appearance and may suggest a serious bone lesion, such as fibrosarcoma or giant cell tumor. A small, clinically silent fibrous cortical defect requires no treatment, whereas a large nonossifying fibroma with a predisposition to fracture is usually treated by curettage and packing with bone chips if necessary. Radiologically, a solitary bone cyst is characterized by a central, symmetrical, radiolucent lesion surrounded by a thin rim of bone and located in the metaphysis, usually of a long tubular bone of the extremities, near but not crossing the epiphysial plate and in later stages "moving" more shaftward as the epiphysial plate grows away from the lesion. Grossly, an intact bone cyst is a single expansive cavity bounded by a thin translucent bone cortex, lined by a thin smooth fibrous wall, and containing clear, straw-colored, or blood-tinged fluid. Following a fracture through the thinned cortex, the cyst fluid and lining may be grossly discolored by blood and contain organizing blood clots and yellow-brown "fatty" material. Histologically, the cyst wall is fibrous and lined by 2 or 3 layers of connective-tissue cells, intermixed with fibrin, disintegrating red cells, scattered hemosiderin-laden macrophages, infrequent chronic inflammatory cells, and a few small multinucleate giant cells, and bounded by reactive new bone tissue laid down by the periosteum. After a fracture through the cyst, more extensive repair tissue is produced and comprises woven bone, osteoid, and fibrous tissue which may contain numerous sharp-pointed cholesterol cleftsThe fibrous tissue may also contain lipid- and hemosiderin-laden macrophages and frequent small multinucleate giant cells, often clustered about an area of hemorrhage. The histological appearance in some cases of solitary bone cyst complicated by fracture may be confused with fibrous cortical defect, nonossifying fibroma, or even giant cell tumor. Aneurysmal bone cyst is a rare, solitary, expansive vascular lesion most often located in the long bones, vertebrae, or flat bones and most frequently seen between 5-20 years of age. The presenting symptoms are usually swelling or pain. The etiology and pathogenesis are unknown, but aneurysmal bone cyst is usually considered to be an arteriovenous or other vascular anomaly resulting from a local circulatory disturbance in the affected bone. In some cases, the condition is associated with some other, presumably antecedant lesion, among them, nonossifying fibroma, fibrous dysplasia, fracture, or a bone neoplasm, such as giant cell tumor. Pathology Radiographically, aneurysmal bone cyst of a long bone is a radiolucent lesion, usually eccentrically located in the metaphysis and often with a characteristic subperiosteal "blow out" appearance. Grossly, aneurysmal bone cyst is an irregular expansile lesion, usually delimited by a thin shell of cortical bone, composed of large and small vascular channels containing fresh, or sometimes clotted, blood, and traversed by fibrous septae or bone trabeculae. Histologically, the lesion consists of blood-filled channelsAneurysmal bone cyst, H&E, the lesion consists of blood-filled vascular channels which are bounded by fibrous walls and reactive new bone. which are bounded by septae and walls of fibrous tissue, reactive bone, and granulation tissue along with clusters of small multinucleate giant cells and a few chronic inflammatory cells. Cartilage is also occasionally present. Eosinophilic granuloma of bone is a rare, non-neoplastic but tumor-like disorder characterized by the presence of one or more destructive histiocytic lesions of bones, in the absence of extraskeletal involvement. Eosinophilic granuloma limited to bone is at the benign end of an apparent clinical "spectrum" of histiocytic proliferative disorders of unknown etiology and undetermined nature (termed "histiocytosis X" or Langerhans cell histiocytosis) which includes: eosinophilic granuloma of bone without extraskeletal involvement; eosinophilic granuloma with both bony and extraskeletal involvement and often fatal (also called Hand-Schuller-Christian disease); and generalized histiocytosis which is usually fatal (also called Letterer-Siwi disease). Eosinophilic granuloma of bone occurs mainly in children under 10 years of age and with male preponderance, usually produces a solitary lesion of a single bone or occasionally of multiple bones, and most often involves flat bones and long bones, such as the calvarium, ribs, femur, and vertebrae. The presenting symptom may be localized aching pain. Radiographically, eosinophilic granuloma of a long bone is characterized by the presence of a round or oval, radiolucent lesion located centrally in the diaphysis or near the metaphysis but rarely the epiphysis, and surrounded in the later phases of the disease by a border of reactive bone sclerosis. The radiographic features may resemble those of osteomyelitis. Histopathologically, the lesion is a granuloma composed of diffuse collections or masses of histiocytes intermixed with eosinophilic leukocytes in various proportions, with eosinophils predominating in some areasand histiocytes the predominant or equally abundant cell-type in other regions. Small multinucleate giant cells, lymphocytes, and plasma cells may also be present. The course of eosinophilic granuloma limited to bone is usually benign. A unifocal bone lesion is treated by curettage or, if indicated by size or location, radiotherapy. A solitary lesion may become multifocal in some cases. Gaucher's disease, an autosomal recessive genetic disorder, is a lysosomal storage disease caused by a deficiency of the enzyme glucocerebrosidase and an excessive accumulation of glucocerebrosides in distinctive large pale cells (Gaucher cells) derived from, and distributed throughout, the reticuloendothelial system and also in neurons of the central nervous system. Gaucher's disease has a higher racial incidence among persons of Hebrew descent and most particularly among Ashkenazi Jews. There are three clinical subtypes of Gaucher's disease: adult (type I), infantile (type II), and juvenile (type III) which is intermediate between I and II. In the adult form of disease, Gaucher cells containing glucocerebrosides accumulate in the spleen, liver, lymph nodes, and bone marrow, but not in neurons. The clinical course of the adult disease is chronic and characterized by enlargement of the spleen (commonly to ten or more times the normal size and weight), liver, and lymph nodes, hematologic abnormalities, and bone lesions caused by the infiltration of Gaucher cells. In the infantile form of disease, glucocerebrosides accumulate in neurons as well as in Gaucher cells. The clinical course is acute, rapidly fatal, and dominated by the involvement of the central nervous system. There are no gross bone lesions although the bone marrow may contain diagnostic Gaucher cells. The enlargement of spleen and liver resulting from a massive infiltration of Gaucher cells is the most common pathological finding in the adult form of Gaucher's disease. The splenic pulp is infiltrated with sheets of Gaucher cells which typically are large, pale, polyhedral shaped cells possessing a single, relatively small, eccentrically located nucleus. Bone lesions are also frequently seen by radiography, and these are often found in the femur, humerus, spine, pelvis, and ribs. Radiographically, a typical lesion of a long bone is radiolucent and diffuse and is characterized by a widened radiolucent medullary cacity, thin cortex, and expanded contourThe radiograph shows a diffuse radiolucent lesion which erodes the inner cortex and widens the medullary cavity of the lower end of the femur. The bone lesions are caused by a diffuse infiltration of Gaucher cells in the bone marrow and eroding the inner cortex. The affected bone may be the site of pathologic fracture or avascular necrosisThe gross section shows that the cancellous bone is diffusely infiltrated with pale yellow tissue distinguishable from fatty marrow (and histologically proven to be an infiltration of Gaucher cells). The Gaucher cell is a reticuloendothelial cell that is morphologically distinguishable from virtually any other cell-type. It is a large, polyhedral shaped, cell (~20-40 micrometer diameter) with a relatively small, often eccentrically located, nucleus and weakly eosinophilic cytoplasm containing delicate striations or wavy fibrils that impart a distinctive "wrinkled tissue paper" appearance. Gaucher cells are characterized as large, pale, polyhedral shaped cells possessing a single, relatively small, eccentric nucleus and weakly eosinophilic cytoplasm containing indistinct striations which impart a "wrinked tissue paper" appearance. H&E. The identification of Gaucher cells in smears or sections of a bone marrow biopsy establishes the pathological diagnosis of Gaucher's disease. |
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Focal Lesion
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Diffuse Lesion
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Central (Medullary)
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Eccentric (Cortical/Juxtacortical)
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Tumorlike Lesions
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Solitary bone cyst* (metaphysis)
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Nonossifying fibroma* (metaphysis)
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Osteoporosis
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Fibrous dysplasia* (shaft)
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Aneurysmal bone cyst* (metaphysis)
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Osteomalacia
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Eosinophilic granuloma* (shaft)
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Exuberant fracture callus
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Hyperparathyroidism
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Hyperparathyroidism ("brown tumors")
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Myositis ossificans (juxtacortical)
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Paget's disease of bone
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Gaucher's disease
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Benign Neoplasms
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Enchondroma (metaphysis)
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Osteochondroma (metaphysis)
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Osteoid osteoma & Osteoblastoma (metaphysis)
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Giant cell tumor (also malignant) (metaphysis/epiphysis)
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Chondroblastoma* (epiphysis)
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Malignant Neoplasms
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Central chondrosarcoma (diaphysis)
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Osteogenic sarcoma* (metaphysis)
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Osteogenic sarcoma* (osteolytic)
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Medullary fibrosarcoma
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Peripheral chondrosarcoma
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Multiple myeloma (diaphysis)
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Metastatic carcinoma
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Ewing's sarcoma* (diaphysis)
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Metastatic carcinoma
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* Predilection for children and teenagers
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Focal Lesion
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Diffuse Lesion
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Tumorlike Lesions
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Tumors
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"Bubbly" Lesions of Bone
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Nonossifying fibroma
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Enchondroma
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Fibrous dysplasia
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Central chondrosarcoma
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Solitary bone cyst
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Giant cell tumor
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Eosinophilic granuloma
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Metastatic carcinoma (thyroid, renal,etc.)
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"Brown tumor" of hyperparathyroidism
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Osteosclerotic (Osteoblastic) Lesions of Bone
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Bone island
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Osteochondroma
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Fracture callus
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Osteoid osteoma
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Paget's disease of bone (also lytic)
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Osteogenic sarcoma (also lytic)
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Chronic osteomyelitis
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Metastatic osteoblastic carcinoma (breast, prostate)
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Bone infarct
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Osteolytic Lesions of Bone
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Acute osteomyelitis
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Multiple myeloma
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Ewing's sarcoma
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Leukemia
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Osteogenic sarcoma (also sclerotic)
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Metastatic osteolytic carcinoma (breast, lung, etc.)
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Osteochondroma is the most common of the benign tumors or tumorlike lesions of bone, may occur in almost any bone preformed in cartilage, particularly long tubular bones, and presents as a solitary cartilage-capped bony outgrowth protruding from the bone surface near the metaphysis. Solitary osteochondroma most commonly occurs in children and shows no notable difference in sex incidence. An osteochondroma is quite as much an anomaly of skeletal development as a neoplasm. It grows by the aberrant proliferation of epiphysial cartilage cells and resulting endochondral ossification, and its growth ceases at, or prior to, the time of skeletal maturation. The most common location of an osteochondroma is in the region of the knee, particularly the lower metaphysis of the femur or the upper metaphysis of the tibia. An osteochondroma of a long bone characteristically points away from the joint because its epiphysial site of origin lags behind the advancing growth plate as the bone lengthens. Occasionally, an osteochondroma originates in a flat bone, such as a rib, clavicle, ilium, or vertebra. Anatomically, an osteochondroma is a sessile or stalked, cartilage-capped, bony protusion which extends from the metaphysial region of the affected bone. Microscopically, an osteochondroma has a cap of mature cartilage beneath which, if the lesion is actively growing, are proliferating cartilage cells growing in columns and undergoing endochondral ossification, much as seen in the epiphysial growth plate. The cortex and the medullary cavity of the stalk of an osteochondroma are composed of normal bone which merges with the bone of origin. In older individuals, the cartilage cap usually disappears although rarely the cap, or remants of it, undergoes malignant transformation to peripheral chondrosarcoma, which is a less frequent complication of solitary osteochondroma (<1% of all cases) than of osteochondromatosis (~20%) (refer to: Hereditary Multiple Exostosis). Solitary enchondroma of bone is a benign tumor which is composed of mature hyaline cartilage and develops in the medullary cavity of a single bone. This tumor usually occurs in the third to sixth decades of life, with the average age of occurence between 30 and 40 years. The most common location is in the bones of the hand: about one-third of all cases occur in the phalanges. The bones of the foot, a long tubular bone such as the humerus or femur, and the pelvic and shoulder girdles are sometimes involved. The typical x-ray picture of an enchondroma shows a central, or slightly eccentric, well-circumscribed or "bubbly" radiolucent lesion, finely or densely stippled with calcification, and located in the interior of a short or long tubular bone. Gross specimens of solitary enchondromas are usually received as surgical curettings of the lesion and consist of lobules of glistening, bluish white cartilage of firm consistency, intermixed with dull, yellow-grey, gritty or hard areas of calcification. Some portions of the tumor may be soft and sticky ("myxoid" change). A large enchondroma located in a long tubular bone or in the pelvic or shoulder girdles arouses strong suspicion of malignant transformation to chondrosarcoma, which many of them prove to be. Solitary enchondroma (of femur) composed of lobules of benign cartilage cells and hyaline matrix. H&E. The histopathological appearance of solitary enchondroma is similar to that of enchondromatosis, a developmental disorder of cartilage of bone (refer to: Enchondromatosis) which differs from the solitary lesion in involving multiple bones, being more cellular, and having slightly larger nuclei, more binucleate cells, and a greater frequency of malignant transformation to chondrosarcoma. Chondrosarcoma of bone is a malignant cartilaginous tumor in which the basic neoplastic component is cartilage, without tumor osteoid or bone being formed by the sarcomatous stroma. Occasionally, myxoid changes may be present. Chondrosarcoma usually occurs in the third to sixth decades of life (average age of 45 years) and is slightly more common in males than females. Chondrosarcoma may originate in the medullary cavity (central chondrosarcoma), arising de novo in about 75% of cases or by malignant transformation of a preexisting enchondroma particularly in patients with enchondromatosis, or originate in a juxtacortical location (peripheral chondrosarcoma) by sarcomatous change in the cartilage cap of an osteochondroma. Chondrosarcomas are symptomatic tumors, and pain, becoming severe and persistent, is a common presenting symptom. The size of the tumor is also clinically significant. While there are few, if any, small chondrosarcomas, a large bulky cartilaginous tumor is best regarded as a chondrosarcoma unless proved otherwise. Chondrosarcomas are most commonly located in the flat bones of the pelvis, the large limb bones, and the ribs.Approximately 25% of cases occur in the femur; the ribs and the humerus are the next most common sites. The typical radiograph of a central chondrosarcoma of a long bone, Central chondrosarcoma of femur. shows a large lesion in the interior of the diaphysis or metaphysis characterized by irregular or circular ( or "bubbly") radiolucencies, granular or lobular radioopaque areas of calcification, "fuzzy" or "scalloped" regions of destruction of the inner cortex, enlargement of bone contours, focal periosteal reaction, and, most ominously, penetration of the cortex and extension of the tumor into the soft tissue. Of course, the actual extent of a chondrosarcoma may exceed its apparent size as imaged in a standard clinical x-ray. Grossly, a central chondrosarcoma of a long bone is composed of confluent lobules of glistening white hyaline cartilage with dull grey gritty areas of calcification. The tumor infiltrates the medullary cavity, erodes and penetrates the cortex, and expands into the surrounding soft tissue. Microscopically, a chondrosarcoma usually retains a lobular cartilaginous architecture, is highly cellular, frequently shows more than one nucleated cell per lacuna, occasionally reveals tumor giant cells or clear cells, and, with increasing grades of malignancy, has marked variation in nuclear and cellular size and shapeCellular ClassificationEwing's Tumor of Bone (ETB) and Extraosseous Ewing's (EOE)Primitive Neuroectodermal Tumor (PNET)Stage InformationLocalized Tumors of the Ewing's Family 
TB is most common infection of pediatric spine paraspinal abscess +/- calcification nontuberculous spondylitis primary or metastatic neoplasm (rarely only at 1 level) histiocytosis (usually --> collapse {vert plana}) autosomal recessive dense, sclerotic bones [Cf: osteopetrosis (sporadic, not inherited)] open cranial sutures + fontanelles Wormian bones dolichocephaly sclerotic vertebrae fractured long bones short, stubby hands partial agenesis/aplasia of terminal phalanges [simulates acro-osteolysis] abnormally dense bones brittle, fracture easily "rugger jersey" spine may be cause of anemia (d/t obliterated marrow space) pyknodysostosis Camurati-Engelmann disease males a/w GC ?? polyarthritis feet (Launois deformity ??) SI joints knees / ankles (jt effusions) urethritis uveitis / conjunctivitis presents by 3-6 months, almost always < 2 yrs loss of zone of provisional calcification wide physis (> 1 mm)(increased osteoid) cupping, fraying + irregularity of metaphyses bowing of long bones decreased bone density rachitic rosary periosteal reaction age > 40y; M:F 2:1 skull osteoporosis circumscripta (outer table destroyed only) "cotton wool" appearance increased hat size! spine monostotic vertebral involvment usually pelvis affected in 2/3 cases consists of cortical thickening enlargement of pubis/ischium coarse trabecular pattern extremities "blade of grass" appearance elevation of alk phos (up to 20X), normal calcium, normal phosphorus complications: path fractures in 8% cases (usu. femur = "shepard's crook") malignant degeneration (usu. osteosarcoma-50%, fibrosarcoma-25%) site: junction of metaphysis + epiphysis types: pyogenic (Staph. aureus) TB syphilis Salmonella (hemoglobinopathy, Gaucher dz) 10 days --> periosteal reaction, loss of cortical margins sequestrum / involucrum chronic osteo: Brodie's abscess complications: amyloidosis squamous cell metaplasia of sinus tract --> squamous cell Ca or fibrosarcoma distal end of long bones well-defined, lytic +/- sclerotic rim tx: open abscess, curette, pack with bone chips prognosis: excellent after tx osteoid osteoma EG dietary deficiency of vitamin D3, lack of solar irradiation deficiency of metabolism of vitamin D chronic renal tubular disease phenobarbitol, diphenylhydantoin decreased absorption of vitamin D (malabsorption, gastrectomy) diphosphonates (decrease calcium deposition; rx. for Paget's) osteopenia bone softening/deformity: hourglass thorax, bowing of long bones increased fractures, biconcave vertebral bodies mottled skull pseudofractures multiple, small, circumscribed round or ovoid areas of increased bone density, widely distributed, caused by condensations of the spongiosa NO symptoms dermatofibrosis lenticularis disseminata scleroderma syndactyly dwarfism endocrine abnormalities melorrheostosis cleft palate demineralization, cortical thinning multiple fractures with pseudoarthrosis exuberant callus formation blue sclerae presenile deafness dentinogenisis imperfecta wide sutures + Wormian bones osteogenesis imperfecta cleidocranial dysostosis cretinism idiopathic Down syndrome hypophosphatasia Menkes kinky-hair syndrome progeria pyknodysostosisST swelling fragmented apophysis with irregularly increased density males (75-85%) age: 10-15 (boys), 8-13 (girls) 25% bilateral 
idiopathic avascular necrosis ("osteochondritis") of proximal femoral epiphysis probably 2' to acute or chronic trauma (Cf: AVN) MALES (90%) (converse of CDH) unilateral (90%) peak age: 4 - 8 yrs uncommon before 3 y/o except in CDH self-limited can progress to coxa plana 
Legg-Calve-Perthes disease (capital femoral epiphysis) Kohler disease (tarsal navicular) Osgood-Schlatter disease (tibial tuberosity) Scheuermann disease (vertebral ring epiphyses) Freiberg infraction (metatarsal head) Sever disease (apophysis of os calcis) medial femoral condyle close to fossa intercondylaris bilateral in 20-30%, rarely lateral mouse = osteochondrotic fragment mouse bed = sclerosed pit in articular surface rare multiple enchondromata 40 - 45% malignant transformation --> chondrosarcoma multiple cavernous hemangiomata may degenerate --> angiosarcoma lytic bone lesion can cross joint spaces + interosseous membranes vertebral body: vertical striations ("ivory") skull: "sunburst" or "sunrise" long bone: "soap bubble" or honeycomb, which may surround a joint age 0 - 1 yr worst prognosis (70% mortality) visceral involvement: hepatosplenomegaly purpura, anemia, lymphadenopathy bone: extensive lytic skull lesions, "raindrop" skull metastases , myeloma sclerotic mets or treated lytic mets preservation of disc space and vertebral body size Paget's disease usually single vertebral body expanded body with thickened cortex and coarsened trabeculation disc space preserved lymphoma preservation of disc space and vertebral body size infection (low grade)eg. TB end plate destruction disc space narrowing paraspinal soft tissue mass hemangioma renal osteodystrophy osteosarcoma osteoporosis with collapse flourosis sickle cell disease osteopetrosis most common primary malignant neoplasm of bone 50-70y; M:F 2:1 symptoms: vague bone pain of progressive severity, fever, anemic sxs complications: pathologic fractures solitary plasmacytoma: solitary osseous focus of MM (uncommon) loss of bone density - from diffuse marrow involvement "punched out" lesions - esp. skull, long bones diffuse bone destruction - esp. pelvis, sacrum invasion of soft tissues - often paraspinal, extrapleural mass osteosclerosis - very rare metastatic calcifications - particularly kidneys, occ. lungs Paget's disease osteoid osteoma fibrous dysplasia melorheostosis hyperparathyroidism hematologic disorders Paget disease (rare) fibrous dysplasia renal osteodystrophy 
