Hertz Bone Cartilage Flashcards
woven vs lamellar bone
lamellar is stronger, more dark pink on histology
osteoclasts come from what?
macrophages. They eat up bone
Bachydactyly types D and E what is the deficiency
Hox D13- short, broad terminal phalanges of the first digits. (transcription factor)
Achondroplasia - what is the deficiency
FGFR3 Receptor defect
short stature, rhizomatic shortening of limbs, frontal bossing, midface deficiency
= most common disease of the growth plate and is a major cause of dwarfism.
Osteogenesis imperfecta types 1-4 deficiency
COLA1, COL A2
type 1 collagen
Bone fragility
osteogenesis imperfecta- why is the sclera blue?
missing type 1 collagen– now just looking straigth through the choroid
Osteogenesis imperfecta (OI),
or brittle bone disease, is a phenotypically diverse disorder caused by deficiencies in the synthesis of type I collagen.
The fundamental abnormality in OI is too little bone, resulting in extreme skeletal fragility
Types of osteogenesis imperfecta
Type 1- autosomal dominant- most commonly seen. Compatible with survival. (postnatal fractures, blue sclera, normal stature, skeletal fragility, dentinogenesis imperfecta, hearing impairment, joint laxity, blue sclerae
Type 2- die in utero
Type 3- progressive, deforming.
Type 4- shot pro-alpha2 chain, unstable triple helix
Osteopetrosis
= marble bone disease and Albers-Schönberg disease,: group of rare genetic diseases that are characterized by reduced bone resorption and diffuse symmetric skeletal sclerosis due to impaired formation or function of osteoclasts
See Erlenmeyer Flastk * on x-ray
bone marrow is missing- die of infections/ * leukopenia
get extramedullary hematopoiesis
Clinical Features of osteopetrosis
Severe infantile osteopetrosis is autosomal recessive and usually becomes evident in utero or soon after birth. Fracture, anemia, and hydrocephaly are often seen, resulting in postpartum mortality.
Affected individuals who survive into their infancy have cranial nerve defects (optic atrophy, deafness, and facial paralysis) and repeated—often fatal—infections because of leukopenia, despite extensive extramedullary hematopoiesis that can lead to prominent hepatosplenomegaly.
The mild autosomal dominant form may not be detected until adolescence or adulthood, when it is discovered on x-ray studies performed because of repeated fractures. These individuals may also have mild cranial nerve deficits and anemia
Robbins key concepts- bone and cartilage
abnormalities in a single bone or a localized group of bones- dysostoses. Arise from defects in the migration and condensation of mesenchyme. Manifest as absent, supernuerary or abnormally fused bones. Global disoranization of bone and/or cartilage is called dysplasia. Developmental abnormalities can be categorized by the associated genetic defect:
- transcription factors- HOX–> brachydactyly syndromes
- Hormones/ signal transduction molecules: FGFR3 mutations –> achondroplasia/ thanatophoric dysplasia –> dwarfism
- structural proteins (type I collagen)–> osteogenesis imperfecta - brittle bone disease. Defective bone formation and skeletal fragility
- metabolic enzymes and transporters. Mutations in CA2–> osteopetrosis (marble bone disease- bones are hard but brittle) and renal tubular acidosis
Osteopenia and Osteoporosis
The term osteopenia refers to decreased bone mass, and osteoporosis is defined as osteopenia that is severe enough to significantly increase the risk of fracture.
The most common forms of osteoporosis are
the senile and postmenopausal types
Age-related changes Reduced physical activity Genetic factors Calcium nutritional state Hormonal influences
Clinical Course
of osteoporosis
depend on which bones are involved.
- Vertebral fractures that frequently occur in the thoracic and lumbar regions are painful, and, when multiple, can cause significant loss of height and various deformities, including lumbar lordosis and kyphoscoliosis.
Complications of fractures of the femoral neck, pelvis, or spine, such as pulmonary embolism and pneumonia, are frequent and result in 40,000 to 50,000 deaths per year
Paget Disease (Osteitis Deformans)
Paget disease is a disorder of increased, but disordered and structurally unsound, bone mass
feels warm due to increased vascularity
Clinical Course
of paget’s
Clinical findings are extremely variable and depend on the extent and site of the disease. * Most cases are asymptomatic and are discovered as an incidental radiographic finding.
Paget disease is * monostotic in about 15% of cases and * polyostotic in the remainder. The axial skeleton or proximal femur is involved in up to 80% of cases. Pain localized to the affected bone is common. It is caused by microfractures or by bone overgrowth that compresses spinal and cranial nerve roots. Enlargement of the craniofacial skeleton may produce leontiasis ossea (lion face) and a cranium so heavy that is difficult for the person to hold the head erect
A variety of tumor and tumor-like conditions develop in Pagetic bone
The benign lesions include giant cell tumor, giant cell reparative granuloma, and extra-osseous masses of hematopoietic tissue. The * most dreaded complication is sarcoma, which occurs in less than 1% of all individuals with Paget disease, and in 5% to 10% of those with severe polyostotic disease
Many affected individuals have * elevated serum alkaline phosphatase levels but normal serum calcium and phosphorus
saber bone
paget’s bowing
Rickets and Osteomalacia
Both rickets and osteomalacia are manifestations of vitamin D deficiency or its abnormal metabolism
Rickets refers to the disorder in children, in whom it interferes with the deposition of bone in the growth plates. Osteomalacia is the adult counterpart, in which bone formed during remodeling is undermineralized, resulting in predisposition to fractures
Hyperparathyroidism
Osteoclast activation, increasing bone resorption and calcium mobilization. PTH mediates the effect indirectly by increased RANKL expression on osteoblasts.
- Increased resorption of calcium by the renal tubules
- Increased urinary excretion of phosphates
- Increased synthesis of active vitamin D, 1,25(OH)2-D, by the kidneys, which in turn enhances calcium absorption from the gut and mobilizes bone calcium by inducing RANKL on osteoblasts
Renal Osteodystrophy
The term renal osteodystrophy describes collectively the skeletal changes that occur in chronic renal disease, including those associated with dialysis
Tubular dysfunction
Generalized renal failure
Decreased production of secreted factors
Robbins key concepts: bone and cartilage
osteopenia and osteoporosis- histologically normal bone, decreased quantity. -porosis –> fractures. Factors include peak bone mass, age, activity, genetics, nutrition, hormonal influences
Paget- locally increased but disordered bone. Asymptomatic, usually discovered incidentally. Mosaic pattern of mineralization - histologic hallmark at late stage of disease. Genetic/ possibly viral infectious etiologies.
Osteomalacia- insufficiently mineralized bone. Rickets in kids
Hyperparathyroidism- autonomous or compensatory hypersecretion of PTH –> osteoporosis, brown tumors, osteitis fibrosa cystica. (these rarely seen in developed countries)
Renal osteodystrophy- constellation of bone abnormalities (osteopenia, -malacia, hyperparathyroidism, and growth retardation) from chronic renal failure. Mechanisms are complex but stem from decreased tubular, glomerular, and hormonal functions of the kidney.
Fractures
Types
Simple: the overlying skin is intact.
Compound: the bone communicates with the skin surface.
Comminuted: the bone is fragmented.
Displaced: the ends of the bone at the fracture site are not aligned.
Stress: a slowly developing fracture that follows a period of increased physical activity in which the bone is subjected to repetitive loads
“Greenstick”: extending only partially through the bone, common in infants when bones are soft
Pathologic: involving bone weakened by an underlying disease process, such as a tumor
most common: femoral head fracture (old guy falls)
conditions associated with osteonecrosis
alcohol abuse bisphosphonate therapy (esp. jawbones) connective tissue disorders * corticosteroid administration chronic pancreatitis dysbarism (the "bends") Gaucher disease infection pregnancy radiation therapy sickle cell crisis Trauma Tumors
femoral head fracture: artery issue
obturator artery is single supply to head of the femur
Osteomyelitis
Osteomyelitis denotes inflammation of bone and marrow, virtually always secondary to infection
Pyogenic Osteomyelitis
(1) Hematogenous spread, (2) extension from a contiguous site, and (3) direct implantation
Staphylococcus aureus is responsible for 80% to 90% of the cases of culture-positive pyogenic osteomyelitis
In almost 50% of suspected cases, no organisms can be isolated.
dead bone is called
sequestrum
surrounded by involucrum- sclerotic bone
Clinical Course
of osteomyelitis
Hematogenous osteomyelitis sometimes manifests as an acute systemic illness with malaise, fever, chills, leukocytosis, and marked-to-intense throbbing pain over the affected region.
In other instances, the presentation is subtle, with only unexplained fever (most often in infants) or localized pain (most often in adults).
The diagnosis is strongly suggested by the characteristic radiographic findings of a lytic focus of bone destruction surrounded by a zone of sclerosis. In some untreated cases blood cultures are positive, but biopsy and bone cultures are required to identify the pathogen in most instances. The combination of antibiotics and surgical drainage is usually curative.
tuberculous osteomyelitis
Potts disease
see terrible kyphosis, etc.
Bone Tumors and Tumor-Like Lesions
benign lesions - often asymptomatic incidental findings.
Many tumors–> pain or a slow-growing mass.
sometimes- first hint of a tumor’s presence is a pathologic fracture.
- usually need biopsy
Benign tumors»_space;> malignant
benign- usually first three decades of life,
older adults- likely to be malignant.
Osteosarcoma - most common primary cancer of bone, followed by chondrosarcoma and Ewing sarcoma
8- year old with bone tumor
21-year old
40-year old
Ewings
Osteosarc
Chondrosarc
Giant cell tumor arises from
epiphysis
Bone-Forming Tumors
Osteoid osteoma and osteoblastoma are benign bone-producing tumors that have identical histologic features but differ in size, sites of origin, and symptoms
Osteosarcoma
malignant tumor in which the cancerous cells produce osteoid matrix or mineralized bone
It is the * most common primary malignant tumor of bone
- occurs in all age groups but has a bimodal age distribution; * 75% occur in persons younger than 20 years of age. The smaller second peak occurs in older adults, who frequently suffer from conditions known to predispose to osteosarcoma—Paget disease, bone infarcts, and prior radiation.
Overall, men > women
- Any bone can be involved.
- usually arise in the * metaphyseal region of the long bones of the extremities, and almost 50% occur about the knee (i.e., distal femur or proximal tibia)
Clinical features
of osteosarcoma
Osteosarcomas typically present as painful, progressively enlarging masses. Sometimes a sudden fracture of the bone is the first symptom.
Radiographs usually show a * large destructive, mixed lytic and blastic mass with infiltrative margins. The tumor frequently breaks through the cortex and lifts the periosteum, resulting in reactive periosteal bone formation. The triangular shadow between the cortex and raised ends of periosteum, known radiographically as * Codman triangle, is indicative of an aggressive tumor.
It is characteristic but not diagnostic of osteosarcoma
treatment and prognosis
of osteosarcoma
-multimodality approach that includes neoadjuvant chemotherapy–> surgery.
The prognosis of osteosarcoma has improved substantially since the advent of chemotherapy
These aggressive neoplasms spread hematogenously to the lungs.
- outcome for patients with metastases, recurrent disease or secondary osteosarcoma is still poor (<20% 5-year survival rate).
cartilage forming tumors by age and location
Young and high on the bone (epiphysis)- chondroblastoma (10-30)
old- clear cell chondrosarcoma 25-60)
young- chondromyxoid fibroma
young- enchondroma (10-40), conventional chondrosarcoma (50-80)
Osteochondroma
= exostosis, is a benign cartilage-capped tumor that is attached to the underlying skeleton by a bony stalk. It is the most common benign bone tumor; about 85% are solitary
Clinical Course
of osteochnodromas
usually stop growing at the time of growth plate closure.
Symptomatic tumors are cured by simple excision.
Rarely in sporadic cases, but more commonly in those with multiple hereditary exostosis (5% to 20%), osteochondromas progress to chondrosarcoma.
Chondromas
= benign tumors of hyaline cartilage that usually occur in bones of enchondral origin. They can arise within the medullary cavity, where they are known as * enchondromas, or on the surface of bone, where they are called * juxtacortical chondromas.
Enchondromas are the most common of the intraosseous cartilage tumors and are usually diagnosed in individuals 20 to 50 years of age. Typically, they appear as * solitary metaphyseal lesions of tubular bones of the hands and feet.
The radiographic features consist of circumscribed lucencies with central irregular calcifications, a sclerotic rim and an intact cortex. * Ollier disease and Maffucci syndrome are nonhereditary disorders characterized by multiple enchondromas. Maffucci syndrome is, in addition, distinguished by presence of spindle cell hemangiomas.
Clinical Course
of chondromas
growth potential of chondromas is limited. Treatment depends on the clinical situation and is usually observation or curettage.
Solitary chondromas rarely undergo sarcomatous transformation, but those associated with enchondromatosis do so more frequently.
Individuals with Maffucci syndrome are also at risk of developing other types of malignancies, including ovarian carcinomas and brain gliomas.
Chondrosarcoma
Chondrosarcomas are malignant tumors that * produce cartilage. They are subclassified histologically as * conventional (hyaline cartilage producing), clear cell, dedifferentiated, and mesenchymal variants*.
- 2nd most common malignant matrix-producing tumor of bone. Individuals usually in their * 40s or older.
- commonly * arise in the axial skeleton, especially the pelvis, shoulder, and ribs. Unlike benign enchondroma, the distal extremities are rarely involved. On * imaging, the calcified matrix appears as foci of flocculent densities.
chondrosarcoma on imaging
produces prominent endosteal scalloping radiographically. The calcified matrix appears as * foci of flocculent densities
Clinical Course
of chondrosarcomas
Chondrosarcomas usually present as painful, progressively enlarging masses. There is a direct correlation between the grade and the biologic behavior of the tumor.
Fortunately, most conventional chondrosarcomas are grade 1 tumors with 5-year survival rates of 80% to 90% (versus 43% for grade 3 tumors). Grade 1 chondrosarcomas rarely metastasize, whereas 70% of grade 3 tumors spread hematogenously, especially to the lungs.
The treatment of conventional chondrosarcoma is wide surgical excision. The mesenchymal and dedifferentiated tumors are also excised and additionally treated with chemotherapy because of their more aggressive clinical course
Ewing Sarcoma Family Tumors
** 11,22
malignant bone tumor characterized by primitive round cells without obvious differentiation. Recently, * Ewing sarcoma and primitive neuroectodermal tumor (PNET) have been unified into a single category: the Ewing sarcoma family tumors (ESFT) based on shared clinical, morphologic, biochemical and molecular features
Of all bone sarcomas, ESFT have the * youngest average age at presentation, since approximately 80% are younger than 20 years.
ESFT usually arise in the * diaphysis of long tubular bones, especially the femur and the flat bones of the pelvis. They present as painful enlarging masses, and the affected site is frequently tender, warm, and swollen. Some affected individuals have * systemic findings that mimic infection, including fever, elevated sedimentation rate, anemia, and leukocytosis. Plain radiographs show a destructive lytic tumor with permeative margins that extends into the surrounding soft tissues. The characteristic periosteal reaction produces layers of reactive bone deposited in an onion-skin fashion
Clinical Course
of Ewings
ESFT are aggressive malignancies treated with neoadjuvant chemotherapy followed by surgical excision with or without irradiation.
The advent of effective chemotherapy has achieved 5-year survival of 75% and long-term cure in 50%.
The amount of chemotherapy-induced necrosis is an important prognostic finding
Giant Cell Tumor
Giant cell tumor is so named because the histology is dominated by multinucleated osteoclast-type giant cells, giving rise to the synonym osteoclastoma.
It is a relatively uncommon benign (don’t metastasize), but locally aggressive, neoplasm.
It usually arises in individuals in their 20s to 40s
See Soap Bubble on X-ray
Clinical Course
of Giant Cell tumors
typically treated with curettage, but 40% to 60% recur locally.
Up to 4% of tumors metastasize to the lungs, but these sometimes spontaneously regress and they are seldom fatal.
Recently, the RANKL inhibitor, denosumab has shown promise as an adjuvant therapy in giant cell tumor
Aneurysmal Bone Cyst
Aneurysmal bone cyst * (ABC) is a tumor characterized by multiloculated blood-filled cystic spaces. Interestingly, radiographic and histologic findings typical of ABC can also be seen as a secondary reaction to other primary bone tumors.
Primary ABC affects all age groups but generally occurs during the first 2 decades of life and has no sex predilection. It most frequently develops in the * metaphysis of long bones and the posterior elements of vertebral bodies. The most common signs and symptoms are pain and swelling
Radiographically, ABC is usually an eccentric, expansile lesion with well-defined margins. Most lesions are completely lytic and often contain a thin shell of reactive bone at the periphery. Computed tomography and magnetic resonance imaging may demonstrate internal septa and characteristic * fluid-fluid levels
Clinical Course of aneurysmal bone cyst
is surgical, usually curettage or, in certain situations, en bloc resection.
The recurrence rate is low, and spontaneous regression may occur following incomplete removal
Fibrous Cortical Defect and Nonossifying Fibroma
Fibrous cortical defects (also known as metaphyseal fibrous defects) are extremely common, * present in 30% to 50% of children older than 2 years.
The vast majority arise eccentrically in the * metaphysis of the distal femur and proximal tibia, and almost half are bilateral or multiple.
Often they are small, about 0.5 cm in diameter. Those that grow to * 5 or 6 cm in size are classified as nonossifying fibromas;* these are usually not detected until adolescence or adulthood
Clinical Course
of fibrous cortical defects
- asymptomatic and are detected incidentally on radiographic studies.
The findings are sufficiently specific on plain radiography that * biopsy is rarely necessary. Most fibrous cortical defects have limited growth potential and undergo spontaneous resolution within several years, being replaced by normal cortical bone.
The few that progressively * enlarge into nonossifying fibromas may present with pathologic fracture or require biopsy and curettage to exclude other types of tumors
Fibrous Dysplasia
a benign tumor that has been likened to a localized developmental arrest; all of the components of normal bone are present, but they do not differentiate into mature structures. The lesions arise during skeletal development, and appear in several distinctive but sometimes overlapping clinical patterns
Monostotic: involvement of a single bone
Polyostotic: involvement of multiple bones
- Mazabraud syndrome: fibrous dysplasia (usually polyostotic) and soft tissue myxomas
- McCune-Albright syndrome: polyostotic disease, associated with café-au-lait skin pigmentations and endocrine abnormalities, especially precocious puberty
Clinical Course
of monostotic fibrous dysplasia
- Monostotic fibrous dysplasia occurs equally in boys and girls, * usually in early adolescence, and often stops enlarging at the time of growth plate closure. The femur, tibia, ribs, jawbones, calvarium, and humerus are most commonly affected.
The lesion is frequently asymptomatic and usually * discovered incidentally but it may cause pain, fracture, and discrepancies in limb length. The lesion is readily recognized radiologically by its typical ground-glass appearance and well-defined margination. Symptomatic lesions are cured by curettage.
clinical course of polyostotic fibrous dysplasia
earlier age
continue to cause problems into adulthood.
femur, skull, tibia, humerus, ribs, fibula, radius, ulna, mandible, and vertebrae.
- Patients may require multiple corrective orthopedic surgical procedures. Bisphosphonates can be used to reduce the severity of the bone pain. A rare complication, usually in the setting of polyostotic involvement, is malignant transformation of a lesion into a sarcoma.
Metastatic Tumors
most common form of skeletal malignancy, greatly outnumbering primary bone cancers. The pathways of spread include (1) direct extension, (2) lymphatic or hematogenous dissemination, and (3) intraspinal seeding (via the Batson plexus of veins). Any cancer can spread to bone, but in adults more than 75% of skeletal metastases originate from cancers of the prostate, breast, kidney, and lung. * Skeletal metastases are typically multifocal.
The radiographic appearance of metastases may be purely * lytic (bone destroying), purely * blastic (bone forming), or mixed lytic and blastic. Furthermore, some cancers are associated with predominantly one pattern or the other.
For example, * prostatic adenocarcinoma is predominantly blastic whereas carcinomas of the * kidney, lung, and gastrointestinal tract and malignant melanoma produce lytic lesions
“PBKTL”
Lead Kettle
Prostate, breast, kidney, thyroid, and lung
Robbins Key Concepts- bone tumors and tumor-like lesions
Primary bone tumors- classified according to the normal cell or matrix they produce. Most primaries are benign; metastases- esp adenocarcinomas- more common.
Major primaries:
- bone-forming: osteoblastoma and osteoid osteoma consist of benign osteoblasts that synthesize osteoid. Osteosarcoma is a tumor of malignant osteoblasts, predominatnly involving adolescents with an aggressive clinical course.
Cartilage forming- osteochondroma is a pollypoid exostosis with a cartilage cap. Sporadic and syndromic forms arise from mutations in the EXT genes. Chnodromas are benign inframedullary tumors producing hyaline cartilage, usually arising in the digits. Chondrosarcomas are malignant tumors of cartilage, involving the axial skeleton in adults.
Ewing sarcoma family of tumors- consists of aggressive malignant small round cell tumors most often associated with t(11,22)
Fibrous cortical defect and fibrous dysplasia- unusual examples of disorders cuased by gain-of-function mutations that occur during development.
