Bone Developmental Disorders- Handorff

Question 1

What is osteoid

Answer 1

All of the inorganic matrix that is laid down beore bone is mineralized

Question 2

What are the active cell types in bone?

Answer 2

Osteoprogenitor cells

Osteoblasts, Osteocytes, Osteoclasts

Question 3

What are osteoprogenitor cells?

Answer 3

Pluripotent mesenchymal stem cells

Question 4

What can drive osteoprogenitor cells into becoming osteoblasts?

Answer 4

CBFA-1 stimulation

Question 5

Osteoblasts do what

Answer 5

form bone

Question 6

Osteoclasts

Answer 6

degrade bone

Question 7

Osteocytes

Answer 7

Sense mechanical stress and regulate serum calcium and phosphate

Question 8

What bone cell synthesizes osteoid?

Answer 8

Osteoblasts

Question 9

What is osteoid

Answer 9

Type I Collagen which makes up about 90% of the 35% organic bone

Question 10

Osteoblasts mediate osteoclast activity, they hyave PTH receptors

Answer 10

true. this can be significant during diseases such as hyperparathyroidism where too much PTH is developed

Question 11

Remember that in certain diseases, the communication between osteoblasts and osteoclasts is screwed up

Answer 11

ok

Question 12

Osteocytes are encased in?

Answer 12

Lacunae?

Question 13

How do osteocytes communicate?

Answer 13

Through canaliculi

Question 14

What do osteoclasts do?

Answer 14

remodel and resorb bone

Question 15

Osteoclasts require what cytokines for differentiation?

Answer 15

IL-1, IL-3, IL-6, IL-11, GM-CSF, M-CSF

Question 16

Osteoclasts reside where?

Answer 16

Howship Lacunae

Question 17

What do osteoclasts look like?

Answer 17

Multinucleated

Question 18

How does Osteoclast differentiation occur?

Answer 18

Osteoclasts are derived from the same cells that make macrophages. RANK ligand binds to RANK receptor. This occurs in the background of M-CSF and causes precursor cells to produce functional osteoclasts.

Question 19

What is OPG

Answer 19

Osteoprotegrin, It protects bone from resorption by acting as a decoy receptor for RANKL, preventing it from binding the RANK receptor on osteoclast precursors.

Question 20

Osteogenesis Imperfecta is a ——- of diseases which share common mutatins in what?

Answer 20

family, type 1 collagen

Question 21

Type 1 OI…

Answer 21

Make too little pro-alpha1. Normal stature, lax joints, deafness

Question 22

Type 2 OI

Answer 22

Pro-alpha 1 is too short, collagen is made but degraded intracellularly. The bones break in utero which kills the child

Question 23

Type III

Answer 23

Triple Helix doesn’t form well.

Child is short, many fractures, kyphosis, hard of hearing, bad cases are lethal

Question 24

Type iV

Answer 24

Pro alpha 2 is too short, short stature, somewhat fragile bones.

Question 25

OI is usually autosomal …… except for……..

Answer 25

dominant, type II (either auto recessive or new autosomal dominant

Question 26

What are the four major clinical criteria for OI

Answer 26

osteoporosis, blue sclerae, dentigenesis imperfecta, premature otosclerosis
Must have two of these for clinical diagnosis

Question 27

Blue sclerae are associated with

Answer 27

heritable disorders of connective tissue. They appear predominantly in OI and to a lesser extent in pseudoxanthoma elasticum, Ehlers Danlos, Marfan disease

Question 28

Why are the sclera blue?

Answer 28

The sclera are so thin that the underlying choroid is visible

Question 29

What are the two types of OI?

Answer 29

Congenita- bad, Tarda- not as bad

Question 30

Achondroplasia is autosomal…..

Answer 30

dominant

Question 31

What is the problem in achondroplastic patients>

Answer 31

Impaired formation of long bones by the endochondral process.

Question 32

The achondroplasia locus is the receptor for>

Answer 32

fibroblast growth factor 3 receptor

Question 33

What is the one danger to life associated with achondroplasia>

Answer 33

Deformity at the foramen magnum, where minor trauma can dislocate the skull from neck bones and compress the brainstem.

Question 34

What does bone histology look like in osteopetrosis

Answer 34

bony trabeculae are irregular and increased in number, contain residual strips of unremodeled cartilage.

Question 35

Features of osteopetrosis

Answer 35

osteoclast dysfunction, bones lack a medullary canal (they have no trabecullar marrow), Ends of bones are mishapen

Question 36

Describe the osteoclast dysfunction in osteopetrosis

Answer 36

osteoclasts fail to resorb bone tissue, this results in bone marrow becoming accluded by weak, woven bone.

Question 37

The most severe form of osteopetrosis is?

Answer 37

ARO (auto recessive osteopetrosis), it arises in infants

Question 38

Osteopetrosis patients are generally neutropenic and anemic

Answer 38

truth

Question 39

Osteoporosis pathogenesis

Answer 39

Resorbed cavities are too large and newly formed packets are too small….these both result in formation resorption mismatch. Increased numbers of remodelling units also lead to increased bone loss

Question 40

Know the pathogenesis of osteoporosis slide

Answer 40

ok

Question 41

Osteoporosis affects 200 million women worldwide

Answer 41

2/3 of them 80 and older, 1/3 60-70

Question 42

Hip fracture is associated with….

Answer 42

high early mortality

Question 43

Paget Disease

Answer 43

Unbalanced and excessive osteoclast and osteoblast function. Increased bone turnover

Question 44

Paget pts are predisposed to

Answer 44

osteogenic sarcoma, chondrosarcoma, malignant fibrous histiocytoma

Question 45

Key clinical points for Pagets disease?

Answer 45

Thick skull, deafness, kyphosis, pain, bowed legs

Question 46

Osteomalacia is

Answer 46

failure of the bone to mineralize properly in an adult

Question 47

Causes of osteomalacia:

Answer 47

in kids, inadequate intake of vit D or calcium (Ricketts)

Question 48

Val Kossa stain

Answer 48

stains calcium black