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Flashcards in Robbins - Bone (Ch. 26) Deck (85)
1

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

Osteoid

Type 1

2

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

Which type of bone is normal in adults?

Woven bone


Lamellar bone

3

Within bone, multinucleated macrophages derived from circulating monocytes...

Cell type?

Osteoclasts

4

Osteoclasts use what to resorb bone?

Acid and matrix metalloproteases (MMPs)

5

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

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

Endochondral ossification

Intramembranous ossification

6

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

7

Peak bone mass is achieved when?

Resorption begins when?

Early adulthood, after cessation of skeletal growth

30s

8

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

9

Examples of dystoses (4)

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

10

Examples of dysplasias (5 diseases)

Brachydactyly types D, E
Cleidocranial dysplasia
Achondroplasia
Osteogenesis imperfecta
Osteopetrosis

11

Short, broad terminal phalanges of 1st digits

Gene mutation? What is is?

Brachydactyly types D, E

HOXD13 -- transcription factor

12

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

13

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

14

Osteogenesis imperfecta -- due to what?

Other name?

Deficiency in synthesis of COLLAGEN TYPE 1

Brittle bone disease

15

Describe collagen type 1 structure

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

16

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

17

Which subtype of osteogenesis imperfecta is fatal in utero?

Tend to develop multiple ____

Subtype 2

Intrauterine fractures

18

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

Osteogenesis imperfecta

19

Reduced bone resorption, diffuse symmetric skeletal sclerosis...disease?

Due to what?

Other names? (2)

Osteopetrosis

Abnormal osteoclasts

Marble bone disease, Albers-Schönberg disease

20

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

Brittle, fracture

21

Osteopetrosis -- mutation?

Result?

Carbonic anhydrase 2 (CA2)

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

22

Osteopetrosis -- other association?

What to expect on routine labs?

Renal tubular acidosis

Hyperchloremic (normal anion gap) metabolic acidosis

23

3 bone-related findings in osteopetrosis



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

24

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

25

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

Other name?

Paget disease

Osteitis Deformans

26

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

27

Paget disease - 3 phases

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

28

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

29

Paget disease - most commonly involves what bones?

Axial skeleton, proximal femur

30

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

31

Paget disease - associated disease

Why?

High-output heart failure

AV shunt within increased blood flow to hyper-vascular bone

32

Paget disease - possible benign tumors

Bad tumor?

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

Sarcoma

33

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

Paget disease

34

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)

35

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)

36

Hallmark of osteoporosis histologically

Typically affects which bone type the most?

Normal bone, reduced in quantity

Cancellous

37

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

38

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%

39

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

40

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

41

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

42

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

43

How does the bone eventually become strong lamellar bone again?

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

44

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.

45

What actually causes the infarction in osteonecrosis? (4)

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

46

Localized bone pain w/ activity that over time becomes constant

2 infarct types

Osteonecrosis

Subchondral (wedge-shape)
Medullary

47

Osteomyelitis - what is it?

Inflammation of bone and marrow, secondary to infection

48

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

Staph. aureus

49

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)

50

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

Open fractures
Surgical procedures
Diabetic feet sores

51

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

E. coli
Pseudomonas
Klebsiella

52

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

Group B strep
H. influenzae

53

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

Salmonella

54

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

Osteomyelitis

55

Potential subtle presentations of osteomyelitis in:
- Baby
- Adult

Baby = unexplained fever

Adult = localized pain

56

Diagnosing osteomyelitis

Biopsy, bone culture

57

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

58

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

Psoas muscle abscess

59

Child, saber shin, edematous granulation tissue w/ many plasma cells, necrotic bone

How to diagnose organism?

Skeletal (congenital) syphilis

Silver stain or immunohistochemistry

60

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

Multifocal
Axial skeleton

61

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

Prostate carcinoma

62

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

Kidney, lung, GI, melanoma

63

Common childhood cancers that metastasize to bone (5)

Neuroblastoma
Wilms tumor
Osteosarcoma
Ewing sarcoma
Rhabdomyosarcoma

64

Symptoms of bone mets (5)

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

65

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

Benign (0-30)

Malignant

66

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

Hyaline or myxoid cartilage

67

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

68

Child, multiple osteochondromas

Genetics?

Multiple hereditary exostosis syndrome

EXT1 or EXT2

69

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)

70

Multiple enchondromas

Genetics?

Ollier disease

IDH1 or IDH2

71

Multiple enchondromas + spindle cell hemangiomas

Increased risk of what other cancers? (2)

Maffucci syndrome

Ovarian carcinoma
Brain glioma

72

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

73

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

74

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

75

Most common primary malignancy of bone overall

Osteosarcoma

76

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

77

Osteosarcoma -- aggressive radiographic sign

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

78

Osteosarcoma -- most common genetic

RB mutation (70%)

79

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

Osteosarcoma

80

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

81

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

Ewing sarcoma

82

Ewing sarcoma -- genetics

(11;22) EWS-FLI1

83

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

84

Fibrous dysplasia + intramuscular myxomas

Mazabraud syndrome

85

Polyostotic fibrous dysplasia, brown skin spots, precocious puberty

McCune-Albright syndrome