Robbins - Bone (Ch. 26) Flashcards by Andrew Herrmann

Bone matrix is made of an organic component called ___ and a mineral component. It is made of predominantly type ___ collagen.

Osteoid

Type 1

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Which type of bone is common in neonates, but abnormal in adults?

Which type of bone is normal in adults?

Woven bone

Lamellar bone

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Within bone, multinucleated macrophages derived from circulating monocytes…

Cell type?

Osteoclasts

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Osteoclasts use what to resorb bone?

Acid and matrix metalloproteases (MMPs)

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In neonates, long bones are formed though a process called ____

In neonates, flat bones are formed through a process called ____

Endochondral ossification

Intramembranous ossification

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Where are RANK, RANKL, and OPG expressed?

What is OPG?

RANK activation causes what?

RANK = osteoclasts
RANKL = osteoblasts
OPG = osteoblasts

Decoy receptor that can bind RANKL and prevent its interaction w/ RANK

NFkB activation, maintaining osteoclast survival

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Peak bone mass is achieved when?

Resorption begins when?

Early adulthood, after cessation of skeletal growth

30s

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Dystoses vs. Dysplasia

Dystoses = abnormal mesenchymal cell migration or differentiation during fetal growth (LOCALIZED)

Dysplasia = mutations in signal molecule or matrix constituents, causing GLOBAL disorganization of bone

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Examples of dystoses (4)

Aplasia (bone or digit)
Supernumary digit
Syndactyly (abnormal fusion)
Craniosynostosis (abnormal fusion)

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Examples of dysplasias (5 diseases)

Brachydactyly types D, E
Cleidocranial dysplasia
Achondroplasia
Osteogenesis imperfecta
Osteopetrosis

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Short, broad terminal phalanges of 1st digits

Gene mutation? What is is?

Brachydactyly types D, E

HOXD13 – transcription factor

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Abnormal clavicles, multiple small bones around the skull symphyses (Wormian bones), supernumerary teeth, patent fontanelles

Gene mutation? What is it?

Cleidocranial dysplasia

RUNX2 – transcription factor

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Short stature, short proximal limbs, normal thorax, large head with frontal bossing, depression of root of nose

Most common cause of ____

Gene mutation? What is it?

Achondroplasia

Dwarfism

FGFR3 – receptor

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Osteogenesis imperfecta – due to what?

Other name?

Deficiency in synthesis of COLLAGEN TYPE 1

Brittle bone disease

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Describe collagen type 1 structure

Packs of fibers made of fibrils. Each fibril is packs of triple helices that are crosslinked

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Osteogenesis imperfecta – genetic mutations

Results in what structural abnormality?

COL1A1 (alpha-1) and COL1A2 (alpha-2) – chains of type 1 collagen

Defective assembly of higher order collagen polypeptides

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Which subtype of osteogenesis imperfecta is fatal in utero?

Tend to develop multiple ____

Subtype 2

Intrauterine fractures

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Multiple fractures (maybe postnatal or prepubertal), blue sclerae, hearing loss, dental imperfections

Osteogenesis imperfecta

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Reduced bone resorption, diffuse symmetric skeletal sclerosis…disease?

Due to what?

Other names? (2)

Osteopetrosis

Abnormal osteoclasts

Marble bone disease, Albers-Schönberg disease

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Although dense, bones in osteopetrosis are abnormally ___, and they ___ easily

Brittle, fracture

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Osteopetrosis – mutation?

Result?

Carbonic anhydrase 2 (CA2)

Impaired acidification of osteoclastic resorption pit, thus impaired solubilization of hydroxyapatite

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Osteopetrosis – other association?

What to expect on routine labs?

Renal tubular acidosis

Hyperchloremic (normal anion gap) metabolic acidosis

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3 bone-related findings in osteopetrosis

Diffuse sclerosis (brittle), especially of ends of long bones
No medullary canal
Narrowed neural foramina

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What are the significant findings that correlate w/ the bone defects in osteopetrosis?

Erlenmeyer flask deformities, repeated fractures
Anemia, leukopenia (repeated infections, hepatosplenomegaly)
Compression of spinal nerves 2, 7, and/or 8 (optic atrophy, deafness, facial paralysis)
Hydrocephaly

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Elderly (70+) caucasian w/ a disorder of increased, but disordered and structurally unsound, bone mass Other name?

Paget disease Osteitis Deformans

Paget disease - most common genetic cause Molecular result? Juvenile Paget disease -- genetic causes (2)

SQSTM1 gene activating mutation Enhanced RANK signaling, increasing activity of NF-kB RANK activating mutation OPG inactivating mutation

Paget disease - 3 phases

- Osteolytic phase - Mixed clast-blast phase - Sclerotic (burned-out) phase

Mosaic pattern of dense lamellar bone with prominent cement lines that conjoin poorly-oriented units of lamellar bone What phase is this? In osteolytic phase, what do osteoclasts look like? What do they form on the bone? In the mixed phase, what do you see?

Paget disease Sclerotic (burned-out) phase Abnormally large, multi-nucleated (10-100 nuclei) Many resorption pits Osteoclasts AND osteoblasts lining the surface of the bones, marrow replaced by connective tissue

Paget disease - most commonly involves what bones?

Axial skeleton, proximal femur

Localized severe bone pain w/ overlying skin warmth, can't hold head up, enlarged facial features, invagination of skull base, anterior bowing of femurs and tibias

Paget disease

Paget disease - associated disease Why?

High-output heart failure AV shunt within increased blood flow to hyper-vascular bone

Paget disease - possible benign tumors Bad tumor?

Giant cell tumors, giant cell granulomas, extra-osseous masses of hematopoietic tissue Sarcoma

Painful bone, thick coarsened cortices and cancellous bone, wedge-shaped lytic leading edge

Paget disease

3 clinical signs of osteoporosis (only need 1)

- BMD > 2.5 SDs below mean PBM in young adults - Atraumatic fracture(s) - Vertebral compression fracture(s)

Most common 2 forms of osteoporosis (w/ cause for each)

- Senile (reduced osteoblast replication and activity in older age) - Post-menopausal (reduced estrogen --> increased osteoclast activity and inflammatory cytokines and RANK/RANKL)

Hallmark of osteoporosis histologically Typically affects which bone type the most?

Normal bone, reduced in quantity Cancellous

Painful thoracic and lumbar regions, increased lumbar lordosis and thoracic kyphosis, multiple/easy fractures Most common fractures Most serious complications (major causes of death)

Osteoporosis Femoral neck, pelvis, spine PE and pneumonia -- from hospitalization and immobility

Best way to diagnose osteoporosis Can it be diagnosed w/ labs? What about plain X-ray?

Dual energy X-ray absorptiometry (DEXA) NO ONLY if lost 30-40%

# Define fracture types: - Simple - Compound - Comminuted - Displaced

Simple = intact overlying skin Compound = bone communicates w/ skin surface Comminuted = bone is fragmented Displaced = ends are not aligned

# Define fracture types: - Stress - Greenstick - Pathologic

Stress = slow-developing after increased physical activity w/ repetitive load forces Greenstick = extending only partially through the bone (infants w/ soft bones) Pathologic = bone weakened by underlying disease process

By the end of the 1st week after a fracture, what has formed? Phases it took to get there

Soft tissue callus (procallus) Hematoma organization, matrix production in adjacent tissues, remodeling of fractured ends into UNCALCIFIED fusiform tissue

By the end of 2 weeks after a fracture, what has formed? How did it get there?

Bony callus Woven bone formed by osteoprogenitor cells, w/ some mesenchymal cells becoming chondrocytes that make fibrocartilage and hyaline cartilage which undergoes endochondral ossification

How does the bone eventually become strong lamellar bone again?

W/ weight bearing, unstressed bone is reabsorbed while stressed bone become lamellar

Osteonecrosis - what is it? 2 most common causes? Others?

Infarction (avascular necrosis) of the medullary cavity or entire bone segment FRACTURE, CORTICOSTEROIDS, bisphosphonate therapy, alcohol abuse, pregnancy, infection, radiation sickle cell, CT diseases, etc.

What actually causes the infarction in osteonecrosis? (4)

Vascular insufficiency from injury, thromboembolism, external pressure, or venous occlusion

Localized bone pain w/ activity that over time becomes constant 2 infarct types

Osteonecrosis Subchondral (wedge-shape) Medullary

Osteomyelitis - what is it?

Inflammation of bone and marrow, secondary to infection

Pyogenic osteomyelitis in otherwise healthy individual -- most common organism?

Staph. aureus

Healthy child that develops pyogenic osteomyelitis -- most likely mode of spread Most common site of infection w/in the bone? How does the bacteria usually get in (in this case)?

Hematogenous Metaphyseal plate Trivial mucosal injuries (defecation, vigorous chewing, minor skin infections)

Adult develops pyogenic osteomyelitis -- most likely methods of infection (3)

Open fractures Surgical procedures Diabetic feet sores

Adult has GU tract infection or IV drug abuser, develops osteomyelitis -- most likely organisms? (3)

E. coli Pseudomonas Klebsiella

Neonate develops osteomyelitis -- most likely organisms? (2)

Group B strep | H. influenzae

Adult w/ sickle cell disease develops osteomyelitis -- most likely organism?

Salmonella

Fever, malaise, chills, leukocytosis, intense throbbing pain over specific area. Lytic focus of bone destruction surrounded by zone of sclerosis

Osteomyelitis

Potential subtle presentations of osteomyelitis in: - Baby - Adult

Baby = unexplained fever Adult = localized pain

Diagnosing osteomyelitis

Biopsy, bone culture

Localized pain, low-grade fever, chills, weight loss. Caseous necrosis and granulomas on CT of bone. Will also have what? Serious complication? What is it? Serious complication will present how?

Mycobacterial (TB) osteomyelitis Extra-osseous TB infection somewhere Pott Disease -- TB hematogenous spread into vertebrae and vertebral discs Scoliosis or kyphosis w/ neurologic defects from cord/nerve compression

Mycobacterial osteomyelitis, Pott disease develops. Common associated soft tissue infection

Psoas muscle abscess

Child, saber shin, edematous granulation tissue w/ many plasma cells, necrotic bone How to diagnose organism?

Skeletal (congenital) syphilis Silver stain or immunohistochemistry

Skeletal metastases of cancer are generally ___ and located in the ____

Multifocal | Axial skeleton

Man w/ multiple osteoblastic lesions in axial skeleton...most likely underlying condition

Prostate carcinoma

Multiple osteolytic lesions in the axial skeleton...most common underlying cancers (4)

Kidney, lung, GI, melanoma

Common childhood cancers that metastasize to bone (5)

``` Neuroblastoma Wilms tumor Osteosarcoma Ewing sarcoma Rhabdomyosarcoma ```

Symptoms of bone mets (5)

``` Significant pain BM suppression Hypercalcemia Pathologic fracture Spinal cord/root compression ```

A primary bone tumor is likely to be (benign/malignant) in younger ages and (benign/malignant) in older ages

Benign (0-30) Malignant

Cartilage-forming bone tumors usually produce what? (2)

Hyaline or myxoid cartilage

Adolescent male, solitary bone tumor that extends out from the metaphysis of the distal femur w/ a bony stalk, a hyaline cartilage cap, and a continuous medullary cavity Undergoes ____ Other name for this tumor?

Osteochondroma Endochondral ossification Exostosis

Child, multiple osteochondromas Genetics?

Multiple hereditary exostosis syndrome EXT1 or EXT2

Small, solitary gray-blue bone lesion at the metaphyseal area of a metacarpal, metatarsal, or phalanx. Circumscribed lucency of hyaline cartilage w/ small irregular calcifications inside. 2 types of this

Chondroma - Enchondroma (w/in medullary cavity) - Juxtacortical chondroma (on surface of bone)

Multiple enchondromas Genetics?

Ollier disease IDH1 or IDH2

Multiple enchondromas + spindle cell hemangiomas Increased risk of what other cancers? (2)

Maffucci syndrome Ovarian carcinoma Brain glioma

40+ y/o patient w/ painful enlarging mass in the pelvis, shoulder, or ribs. Large bulky tumors of glistening gray-white cartilaginous nodules. Foci of flocculent densities w/in the calcified matrix. Variants? (4) Sub-variants? (2) Most common?

Chondrosarcoma ``` Conventional (hyaline-producing) - Central (medullary) - Peripheral (juxtacortical) Clear cell Dedifferentiated Mesenchymal ``` Conventional central

Osteoid osteoma and osteoblastoma...What are they? Symptom? Compare and contrast... - Size - Location - Content - NSAIDs - Treatment

Bone-producing tumors Severe nocturnal pain Osteoid osteoma - under 2 cm - appendicular (femur, tibia) - cortex w/ thick rind of reactive bone - Relieved by aspirin/NSAIDs - Tx = radiofrequency ablation Osteoblastoma - over 2 cm - posterior spine - NO bony reaction - NOT relieved by aspirin - Tx = curettage or excision

Round/oval mass of hemorrhagic gritty tan tissue. Well-circumscribed, randomly interconnecting trabeculae of woven bone w/ prominent rim of osteoblasts. Many dilated and congested capillaries. 2 options?

Osteoid osteoma | Osteoblastoma

Most common primary malignancy of bone overall

Osteosarcoma

Teenager, painful progressively-enlarging bone mass or sudden fracture of the metaphyseal region of femur or tibia (or UE). Mixed osteolytic and osteoblastic mass w/ infiltrative margins. Multiple lesions in the lungs. Other subjected populations? Most common locations?

Osteosarcoma - metastatic Older w/ Paget, bone infarct, or prior radiation Metaphyseal region of long bones of extremities

Osteosarcoma -- aggressive radiographic sign

Codman triangle -- lifting of periosteum off of the bone surface

Osteosarcoma -- most common genetic

RB mutation (70%)

Varied cell sizes and shapes, large hyperchromatic nuclei, bizarre giant cells w/ many abnormal (tripolar) mitoses. Vascular invasion. Osteoid deposition.

Osteosarcoma

Caucasian child, painful enlarging mass w/ tender, warm, swollen overlying skin. Fever, elevated sed rate, anemia, and leukocytosis. Undifferentiated primitive round cells that are cohesive. Cell type?

Ewing sarcoma Neuroectodermal

Destructive medullary lytic tumor w/ permeative margins that extend into the surrounding tissues. Reactive ONION-SKIN bone deposition

Ewing sarcoma

Ewing sarcoma -- genetics

(11;22) EWS-FLI1

Early adolescent. Pain, fracture, limb length discrepancies. Well-circumscribed, intra-medullary lesion of curvilinear woven bone (Chinese characters). No osteoblastic rimming. Fibroblastic proliferation. Genetics? Causes what?

Fibrous dysplasia GNAS1 -- Gs/cAMP mediated interruption of normal osteoblast differentiation from precursors

Fibrous dysplasia + intramuscular myxomas

Mazabraud syndrome

Polyostotic fibrous dysplasia, brown skin spots, precocious puberty

McCune-Albright syndrome

Robbins - Bone (Ch. 26) Flashcards

(85 cards)