Bone Pathology Lect 2, Path Exam 3

Front 1

3 functions of bone

Back 1

206 bones total in adult bodies
Functions
mechanical
mineral homeostasis
hematopoietic

Front 2

What are the components of bone?

Back 2

Organic Matrix (35%)
Cells (osteoprogenitor cells, osteoblasts, osteoclasts osteocytes, osteoblasts)
Proteins (Type I collagen and noncollagenous proteins)

Inorganic Elements(65%)
Calcium Hydroxyapatite
[Ca10(PO4)(OH)2]

Front 3

What are the bone forming cells? What does it start off as?

Back 3

Bone forming cells include osteoprogenitor cells, osteoblasts, and osteocytes. Osteoprogenitor cells are pluripotent stem cells, which with appropriate stimulation, produce osteoblasts.

Osteoblasts produced osteoid (unmineralized bone matrix composed primarily of Type I Collagen) and initiate the process of mineralization. They respond to parathyroid hormone, vitamin D and estrogen
as well as other cytokines and growth factors.

Once osteoblasts become surrounded by matrix, they are known as osteocytes.

Front 4

Describe osteoclasts

Back 4

Very large (up to 100 µm), multi-nucleated bone-resorbing cells.

Arise by the fusion of monocytes or macrophages.

Released enzymes that break down the collagen fibres of the matrix.

Stimulated by parathyroid hormone (produced by the parathyroid gland)

Inhibited by calcitonin (produced by specialized cells of the thyroid gland)

Front 5

Describe bone remodeling

Back 5

takes 4 months, ongoing process. Occurs throughout the lifetime of an individual.

Front 6

Describe 2 types of bone development and grwoth

Back 6

Intramembranous ossification - replacement of sheet like CT membranes w/ an bony tissue.
(Ex. skull bones)

Endochondral ossification - replaces of hyaline cartilage w/ bony tissue (ex. bones of skeleton)

Front 7

What are 2 microscopic differences in bone structure?

Back 7

1. woven bone - haphhazard, organization of collegen fibers and is mechanically weak. usually in embryo. Adult - abnormal, or after fractures.
2. lamellar bone - regular parallel alignment. collagen into sheets (lamellae) and is mechanicaly strong.

Front 8

Compact and spongy (cancellous bone)

Back 8

lacunae containing osteocytes - cancellous bones.

Front 9

Classification and structure of bones
1. long bones
2. short bones
3. flat bones
4. irregular bones

Back 9

Long bones = bones that are longer
than they are wide (bones of the thigh,
leg, arm, and forearm.

Short bones = roughly cube-shaped with
vertical and horizontal dimensions
approximately equal (bones of the wrist
and ankle)

Flat bones = thin, flattened, and usually
curved (bones of the cranium)

Irregular Bones = not in any of the above
three categories (The vertebrae and some
of the bones in the skull).

Front 10

Achondroplasia - one type of dwarifism

Back 10

Major cause of dwarfism.

Underlying etiology is a point mutation in the fibroblast growth factor receptor 3 (FGFR3) that results in its constitutive activation.

Unfortunately, activated FGFR3 inhibits chondrocyte proliferation; as a result, the normal epiphyseal growth plate expansion is suppressed and long bone growth is severely stunted.

Autosomal dominant.

The affected individuals are typically heterozygotes, since homozygosity leads to abnormalities in chest development and death from respiratory failure soon after birth.


Affects all bones that form from
a cartilaginous framework.

The most conspicuous changes include:
- Disproportionate shortening of
proximal extremities
- Bowing of the legs
- Lordotic (sway-backed) posture

Front 11

Thanatophoric dwafisim

Back 11

Lethal variant of dwarfism

1 in every 20,000 live births

FGFR3 mutations

Affected heterozygotes have:
- Extreme shortening of the
limbs
- Frontal bossing of the skull
- Extremely small thorax (cause
of fatal respiratory failure in
the perinatal period).

Front 12

Osteogenesis imperfecta

Back 12

Also known as "brittle bone disease", is caused by defective synthesis of type I collagen.

The molecular pathology underlying OI characteristically involves gene mutations in the coding sequences for α1 or α2 chains of type I collagen.


Findings include:
- Extreme skeletal fragility
- Blue sclerae
- Hearing loss
- Small misshapen teeth

Front 13

Osteoporosis

Back 13

Disease characterized by increased porosity of the skeleton resulting from reduced bone mass, which causes increased bone fragility and susceptibility to bone fractures.
Types
Disuse osteoporosis of a limb: localized
Metabolic bone disease: generalized (1ry and 2ry categories)

-trabecular bone is more effected, esp vertebra and head of the femur ( hip fractures are common)

Front 14

Primary osteoporosis

Back 14

senile and post menopausal

common 2ndary causes: durgs (corticosteroids), hypognoadism, alcohol abuse, vitamin D deficiency, hyperparathyroidism

hypothyroidism, malabsorption syndromes, hypercalciuria, multiple mysioma, calcium deficiency.

Front 15

Describe the pathogenesis of osteoporosis

Back 15

In adults there is a dynamic equilibrium between bone formation by osteoblasts, maintenance by osteocytes, and resorption by osteoclasts.

Osteoporosis occurs when the balance tilts in favor of resorption.

Front 16

Osteoporosis diagnosis and treatment

Back 16

Specialized radiographic techniques to estimate bone loss include dual-energy absorptiometry and quantitative computed tomography.

Prevention and treatment begins with adequate dietary calcium intake, vitamin D supplementation, and a regular exercise regimen, starting before the age of 30 to increase the peak bone density.

Bisphosphonate (decreases bone resorption).

Front 17

Osteopetrosis

Back 17

Rare genetic disorders characterized by reduced osteoclast-mediated bone resorption and therefore defective bone remodeling.

Literally "stone bone“

The precise nature of the osteoclast dysfunction is unknown in most cases.

Fractures, cranial nerve problems and recurrent infections seen.

Patients often develop impressive hepatosplenomegaly due to expansive extramedullary hematopoiesis.

very heavy bones! Hematopoiesis doesn't occur in bone.
Not enough osteoclastic activity

Front 18

Paget disease

Back 18

-more common in older people

Characterized by repetitive episodes of frenzied, regional osteoclastic activity and bone resorption (osteolytic stage), followed by exuberant bone formation (mixed osteoclastic-osteoblastic stage), and finally by apparent exhaustion of cellular activity (osteosclerotic stage).

The net effect is a gain in bone mass; however, the newly formed bone is disordered and lacks strength.

-too much osteoclastic activity

Histological pattern: Histologic hallmark is the
mosaic pattern of lamellar bone.

This pattern, which is likened to a jigsaw puzzle, is produced by prominent cement lines that anneal haphazardly oriented units of lamellar bone.

Current evidence suggests that paramyxovirus infection may cause Paget disease.

It is monostotic (tibia, ilium, femur, skull, vertebra, and humerus) in about 15% of cases and polyostotic (pelvis, spine, and skull) in the remainder.

The axial skeleton or proximal femur is involved in up to 80% of cases.

Even though no bone is immune,

Front 19

Describe the tumors that can develop in those with Paget disease

Back 19

-variety of tumor and tumor like conditions can develop

Benign lesions include: giant cell tumor, giant cell reparative granuloma, and extraosseous masses of hematopoiesis.

Most dreaded complication is the development of sarcoma, which occurs in 0.7% to 0.9% of all patients with Paget disease but increases to 5% to 10% in those patients with severe polyostotic disease.

The sarcomas are usually osteosarcoma, malignant fibrous histiocytoma, or chondrosarcoma, and they arise in the long bones, pelvis, skull, and spine.

In the absence of malignant transformation, Paget disease is usually not a serious or life-threatening disease. Most patients have mild symptoms that are readily suppressed by calcitonin and bisphosphonates.

Front 20

Rickets/Osteomalacia

Back 20

Characterized by a defect in matrix mineralization, most often related to a lack of vitamin D or some disturbance in its metabolism.

The term rickets refers to the disorder in children in which deranged bone growth produces distinctive skeletal deformities.

In the adult, the disorder is called osteomalacia because the bone that forms during the remodeling process is undemineralized.

This results in osteopenia and predisposition to insufficiency fractures.

Front 21

Hyperparathyroidism

Back 21

Parathyroid hormone (PTH) plays a central role in calcium homeostasis via its effects on:
Osteoclast activation
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


Excessive or inappropriate levels of PTH can result from autonomous parathyroid secretion (primary hyperparathyroidism) or can occur in the setting of underlying renal disease (secondary hyperparathyroidism).

In either setting, hyperparathyroidism leads to significant skeletal changes related to unabated osteoclast activity.

The hallmark of PTH excess is increased osteoclastic activity, with bone resorption.

Front 22

What is a clinical manifestation of hyperparathyroidism

Back 22

In some instances, collections of osteoclasts, reactive giant cells and hemorrhagic debris form the brown tumor of hyperparathyroidism.

Cystic change is common in such lesions (hence the name osteitis fibrosa cystica).

Resected rib, harboring an expansile
brown tumor adjacent to the costal cartilage

Front 23

Describe the following types of fractures
1. simple
2. comminuted
3. compound (open)
4. pathologic fracture
5. stress fracture

Back 23

Fractures can be complete or incomplete
Simple – overlying tissue is intact
Comminuted – the bone is splintered
Compound (open) - communicates with
skin surface

Pathologic fracture = break in the bone
already altered by a disease process

Stress fracture – fracture that follows
a period of increased physical activity in
which the bone is submitted to
repetitive stress

Front 24

Describe fracture healing

Back 24

-hematoma formation initiates fibroblasts, and early granulation tissue
-attracts osteoclasts and osteoblasts to begin forming bone. This is during reparative phase.

Front 25

Osteonecrosis

Back 25

Avascular necrosis.


Ischemic necrosis with resultant bone infarction occurs relatively frequently.

Mechanisms contributing to bone ischemia include:
- Vascular compression or disruption
(e.g., following a fracture)
- Steroid administration
- Thromboembolic disease (e.g., nitrogen
bubbles in caisson disease)
- Primary vessel disease (e.g., vasculitis)

Front 26

What does osteomyelitis designate?

Back 26

-any inflmmation of bone and marrow cavity.


Although any microorganism can cause osteomyelitis, the most common etiologic agents are pyogenic bacteria and Mycobacterium tuberculosis.

-usually found in immunosuppressed individuals. can happen in those who are otherwise healthy

Front 27

What are most cases of acute osteomyelitis caused by?

Back 27

Most cases of acute osteomyelitis are caused by bacteria.

The offending organisms reach the bone by one of three routes:
(1) hematogenous dissemination (most common); (2) extension from an infection in adjacent joint or soft tissue; or (3) traumatic implantation after compound fractures or orthopedic procedures.

Overall, Staphylococcus aureus is the most frequent causal organism.

Escherichia coli and group B streptococci are important causes of acute osteomyelitis in neonates, whereas Salmonella is an especially common pathogen in individuals with sickle cell disease.

Mixed bacterial infections, including anaerobes, are typically responsible for osteomyelitis developing after bone trauma. In as many as 50% of cases, no organisms can be isolated.

Front 28

What does osteomyeltitis manifest as?
What is the diagnosis, treatment?

Back 28

Osteomyelitis classically manifests as an acute systemic illness with malaise, fever, leukocytosis, and throbbing pain over the affected region.

Diagnosis is suggested by characteristic radiologic findings: a destructive lytic focus surrounded by a sclerotic rim. In many untreated cases, blood cultures are positive, but biopsy and bone cultures are usually required to identify the pathogen.

A combination of antibiotics and surgical drainage is usually curative, but up to a quarter of cases do not resolve and persist as chronic infections.

Front 29

What is chronic osteomyeltitis characterized by?

Back 29

Chronic osteomyelitis is also complicated by pathologic fracture, secondary amyloidosis, endocarditis, sepsis, development of squamous cell carcinoma in the sinus tract, and rarely osteosarcoma.

Front 30

Tuberculous osteomyelitis

Back 30

Bone infection complicates an estimated 1% to 3% of cases of pulmonary tuberculosis.

The organisms usually reach the bone through the bloodstream, although direct spread from a contiguous focus of infection (e.g., from mediastinal nodes to the vertebrae) can also occur.

With hematogenous spread, long bones and vertebrae are favored sites.

The lesions are often solitary but can be multicentric, particularly in patients with an underlying immunodeficiency.

Tuberculosis of the vertebral bodies, or Pott disease, is an important form of osteomyelitis.

Front 31

Osteoma

Back 31

Benign lesions of bone

Most commonly encountered in the head and neck, including the paranasal sinuses.

Usually solitary

They are not invasive and do not undergo malignant transformation.

Front 32

Describe osteoid osteoma and osteoblastoma

Back 32

Both have similar histologic features and only difference is that osteoblastoma is bigger

Osteoid osteomas and osteoblastomas are benign neoplasms with very similar histologic features.

Both lesions typically arise during the teenage years and 20s, with a male predilection (2:1 in osteoid osteomas).

They are distinguished primarily by their size, site of origin, and their radiographic appearance as well-circumscribed lesions, usually involving the cortex and rarely the medullary cavity


Osteoid osteomas arise most often in the proximal femur and tibia, and are by definition less than 2 cm, whereas osteoblastomas are larger.

Localized pain is an almost universal complaint with osteoid osteomas, and is usually relieved by aspirin. Osteoblastomas arise most often in the vertebral column; they also cause pain, although it is often more difficult to localize and is not responsive to aspirin.

Local excision is the treatment of choice; incompletely resected lesions can recur. Malignant transformation is r

Front 33

Osteosarcoma

Back 33

Bone-producing malignant mesenchymal tumor.

Most common primary malignant tumor of bone, with 75% occurring in patients younger than 20 years of age, the second smaller incidence peak occurs in elderly patients.

Most tumors arise in the metaphyseal region of the long bones of the extremities, with almost 60% occurring about the knee, 15% around the hip, 10% at the shoulder, and 8% in the jaw.

The most common type of osteosarcoma is primary, solitary, intramedullary, and poorly differentiated, producing a predominantly bony matrix.

Front 34

Osteosarcoma pathogenesis

Back 34

Several genetic mutations are closely associated with the development of osteosarcoma.

Retinoblastoma (RB) gene mutations occur in 60% to 70% of sporadic tumors.

Spontaneous osteosarcomas also frequently exhibit mutations in genes that regulate the cell cycle including p53, cyclins, cyclin-dependent kinases, and kinase inhibitors.

Front 35

What are the clinical manifetations of osteosarcoma? Treatment?

Back 35

At the time of diagnosis, approximately 10% to 20% of patients have demonstrable pulmonary metastases.

Despite aggressive behavior, standard treatment with chemotherapy and limb-salvage therapy currently yields long-term survivals of 60% to 70%.

Front 36

What is secondary osteosarcomas?

Back 36

Secondary osteosarcomas occur in an older age group than do primary osteosarcomas. They most commonly develop in the setting of Paget disease or previous radiation exposure.

Secondary osteosarcomas are highly aggressive tumors that do not respond well to therapy

Front 37

Osteochondroma

Back 37

Osteochondromas are also called exostoses; they are relatively common benign cartilage-capped outgrowths attached by a bony stalk to the underlying skeleton.

Osteochondromas vary from
1-20 cm in size. The cap is benign hyaline cartilage, resembling disorganized growth plate undergoing endochondral ossification.

usually occur near the end of the long bone, and characterized by outpocketing.

Front 38

Chondroma

Back 38

Benign tumors of hyaline cartilage.

When they arise within the medulla, they are termed enchondromas.

When they arise on the bone surface they are called juxtacortical chondromas.

Front 39

Chondrosarcoma. Diference between low grade and high grade chondrosarcoma?

Back 39

within the medullary cavity of the bone to form an expansile glistening mass that often erodes the cortex.

They exhibit malignant hyaline and myxoid cartilage.

Tumor grade is determined by cellularity, cytologic atypia, and mitotic activity

Low-grade tumors resemble normal cartilage.

Higher grade lesions contain pleomorphic chondrocytes with frequent mitotic figures. Multinucleated cells are present with lacunae containing two or more chondrocytes.

Front 40

What part of the body do chondrosarcomas typically arise?

Back 40

Chondrosarcomas commonly arise in the pelvis, shoulder, and ribs presenting as painful, progressively enlarging masses.

There is also a direct correlation between grade and biologic behavior of the tumor.

Front 41

What are some prognostic factors of chondrosarcoma?

Back 41

Fortunately, most conventional chondrosarcomas are indolent and low-grade, with a 5-year survival rate of 80% to 90% (vs 43% for grade 3 tumors); grade 1 tumors rarely metastasize, whereas 70% of the grade 3 tumors disseminate.

Size is another prognostic feature, with tumors larger than 10 cm being significantly more aggressive than smaller tumors.

Chondrosarcomas metastasize hematogenously, preferentially to the lungs and skeleton.

Conventional chondrosarcomas are treated with wide surgical excision (chemotherapy for the mesenchymal and dedifferentiated variants because of their aggressive clinical course).

Front 42

Ewing sarcoma and primitive neuroectodermal tumor

Back 42

Primary malignant small round-cell tumors of bone and soft tissue.

Most patients are 10 to 15 years old.

Approximately 95% of patients with Ewing tumor have t(11;22) (q24;q12) or t(21;22) (q22;q12).

Front 43

Where do ewing sarcoma and PNETs tyically arise? What does treatment involve?

Back 43

Ewing sarcoma and PNET’s typically present as painful enlarging masses in the diaphyses of long tubular bones (especially the femur) and the pelvic flat bones.

Treatment includes chemotherapy and surgical excision with or without radiation.

Front 44

Metastic disease

Back 44

Metastatic tumors are the most common malignant tumor of bone.

In adults more than 75% of skeletal metastases originate from cancers of the prostate, breast, kidney, and lung.

In children, neuroblastoma, Wilms' tumor, osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma are the common sources of bony metastases.