Bones, Joints And Soft Tissue Pt. 1

Question 1

What is bone matrix?

Answer 1

The extracellular component of bone; consists of osteoid (organic component), mineral component and inorganic (hardness due to hydroxyapatide)

Question 2

What is osteoid?

Answer 2

Made of type I collagen with small amount of glycosaminoglycans and other proteins

Question 3

Which protein is present in osteoid?

Answer 3

Osteopontin (aka osteocalcin) produced by osteblasts; functions in bone formation, mineralization and Ca homeosatsis; marker for osteblastic activity

Question 4

What are the 2 histological forms of bone?

Answer 4

Woven and lamellar

Question 5

What is woven bone?

Answer 5

Produced rapidly during retal development and fracture repair; haphazard arrangement of collagen (less structural integrity); abnormal in adults but not specific for any bone disease

Question 6

What is lamellar bone?

Answer 6

Slow production, parallel collagen, stronger than woven

Question 7

What is the function of osteoblasts?

Answer 7

Surface of matrix; synthesize, transport and assemble matrix; regulates mineralization

Question 8

What are osteocytes?

Answer 8

Inactive osteoblasts with decreased cytoplasm; contol Ca and phosphate levels; direct mechanical forces (mechanotransduction) translates them into biological activity

Question 9

What are osteoclasts?

Answer 9

Multinucleated macrophages derived from circulating monocytes; function in bone resorption

Question 10

What are the two types of bone development?

Answer 10

Endochondral and intramembranous ossifcation

Question 11

What is endochondral ossification?

Answer 11

Occurs in long bones; cartilage mold = analgen, central medullary canal created by chondroblasts; osteoblasts deposit cortex beneath periosteum of diaphysis —> radial growth (primary center of ossificaiton); deposits of new bone at the bottom of growth plates (epiphyses) —> longitudinal growth (secondary centers of ossifcation)

Question 12

What is intramembranous ossifcation?

Answer 12

Occurs in flat bones; mesenchyme directly ossified by osteoblasts, no cartilage analgen; appositional growth (direct deposit of new bone on pre-existing surface)

Question 13

When is peak bone mass achieved?

Answer 13

In early adulthood after cessation of skeletal growth; 4th decade: resorption >formation —> decreased skeletal mass

Question 14

What is the function of RANK during bone homeostasis and remodeling?

Answer 14

Receptor activator for NFkB on osteoclast precursors; when stimulated by RANKL, activates TF NFkB (essential for generation and survival of osteoclasts); allows for breakdown of bone

Question 15

RANKL is expressed on which cell type?

Answer 15

Osteoblasts and marrow stromal cells

Question 16

What is the function of osteoprotegerin (OPG) in bone homeostasis and remodeling?

Answer 16

OPG decoy receptor made by osteoblasts; can bind RANKL and prevent its interaction with RANK; builds bone

Question 17

Which systemic factors promote osteoclast differentiation and bone turnover?

Answer 17

PTH, IL-1, and glucocorticoids

Question 18

Which systemic factors block osteoclast differentiaton or activity by promoting OPG expression (factors that favor bone deposition)?

Answer 18

Bone morphogenic proteins (vitamin D) and sex hormones (estrogen, testosterone)

Question 19

What is the function of WNT proteins in bone homeostasis?

Answer 19

WNT proteins produced by OPG cells bind to LRP5 and 6 receptors on osteoblasts thus triggering activation of beta-catenin and production of OPG

Question 20

What inhibits the WNT/B-catenin pathway?

Answer 20

Sclerostin (produced by osteocytes) which suppresses bone formation

Question 21

The balance between net bone formation and resorption is modulated by what?

Answer 21

RANK and WNT

Question 22

What is the function of M-CSF in bone homeostasis?

Answer 22

M-CSF receptor on osteoclast precurose stimulates tyrosine kinase cascade that is crucial for generation of osteoclasts

Question 23

Which genes are affected in brachydactyly types D and E?

Answer 23

HOXD13

Question 24

What is the clincal phenotype seen with brachydactyly types D and E?

Answer 24

Short, broad terminal phalanges of first digits

Question 25

Which genes are affected in cleidocranial dysplasia?

Answer 25

RUNX2

Question 26

What is the clincal phenotype seen with celidocranial dysplasia?

Answer 26

Abnormal clavicles, Wormian bones, supernumeray teeth

Question 27

Which gene is affected in achondroplasia?

Answer 27

FGFR3

Question 28

What is the clinical phenotype seen with achondroplasia?

Answer 28

Short stature, rhizomelic shortening of limbs, frontal bossing, midface deficiency

Question 29

What gene is affected in thanatophoric dysplasia?

Answer 29

FGFR3

Question 30

What is the clinical phenotype seen with thanatophoric dysplasia?

Answer 30

Severe limb shortening and bowing, frontal bossing, depressed nasal bridge

Question 31

What gene is affected in achondrogenesis type 2 and what is the clincal phenotype?

Answer 31

COL2A1; short trunk

Question 32

Which gene is affected in osteoporosis with RTA?

Answer 32

CA2

Question 33

What is the clinical phenotype seen with osteopetrosis with RTA?

Answer 33

Increased bone density, fragility and RTA

Question 34

What are Wormian bones?

Answer 34

Extra bones within cranial sutures

Question 35

What is osteopetrosis?

Answer 35

Aka marble bone disease; decreased bone resorption due to deficient osteoclastic development/function —> diffuse, symmetrical skeletal sclerosis

Question 36

Most AR forms of osteopetrosis are caused by mutations in which gene?

Answer 36

TCIRG1 which encodes a subunit of the osteoclast vacuolar H-ATPase that is also necessary for acidification of the resorption pit

Question 37

What is osteopenia?

Answer 37

Decreased bone mass 1-2.5 SD below the mean of peak bone mass

Question 38

Once maximal skeletal mass is attained, what occurs with every resorption and formation cyccle?

Answer 38

Small deficits in bone formation accrues

Question 39

How does an estrogen deficiency affect bone?

Answer 39

Decreased estrogen —> increases both resorption and formation but formation < resorption leading to a high turnover rate; also leads to increased cytoknes (IL-6, TNF and IL-1) which increases RANKL —> decreased OPG —> osteoclast recruitment and activity

Question 40

What is von Recklinghausen disease of bone?

Answer 40

Increased bone cell activity, peritrabecular fibrosis and cystic brown tumors is hallmark of severe hyperparathyroidism = generalized osteitis fibrosis cystica

Question 41

What is a simple fracture?

Answer 41

Overlying skin intact

Question 42

What is a compound fracture?

Answer 42

Bone communicates with the skin surface (protrudes thru skin)

Question 43

What is a comminuted fracture?

Answer 43

Bone is fragmented (several pieces)

Question 44

What is a displaced fracture?

Answer 44

Ends of the bone at the fracture site are not aligned

Question 45

What is a stress fracture?

Answer 45

Slowly developing fracture that follows a period of increased physical activity in which the bone is subjected to repetitive loads

Question 46

What is a greenstick fracture?

Answer 46

Extending only partially through the bone, common in infants when bones are soft (looks like broken stick)

Question 47

What is a pathologic fracture?

Answer 47

Involving bone weakened by an underlying diseaes process, such as a tumor

Question 48

What can predispose someone to osteonecrosis?

Answer 48

Alcohol abuse, bisphosphonate therapy, CT disease, chronic pancreatitis, Gaucher disease, pregnancy, radiation therapy, sickle cell crisis, tumors and dysbarism (decompression sickness)

Question 49

What is sclerosing osteomyelitis of Garre?

Answer 49

Type of chronic osteomyelitis; Occurs in the jaw and associated with extensive new bone formation that obscures much of the underlying osseous structure