Extra Martin Skeletel Path

Question 1

Two histologic forms of bone and 3 features of each?

Answer 1

Woven: produced quick, less structural integrity, used in fetal development and fracture repair
Lamellar: strong, parallel collagen and slow production

Question 2

Explain what an osteoclast is and what do they secrete to break down bone?
What is an osteocyte and what is their main function?

Answer 2

Multi nucleated macrophages
Secrete MMPs to break down bone

Inactivated osteoblast that controls calcium and phosphate levels

Question 3

Talk about what she wanted us to know about bone peak bone mass?

Answer 3

Peak bone mass occurs about 30 and then in the 4h decade, resorption is now greater than formation for the rest of our life and we begin to lose skeletal mass.

Question 4

Talk about the dynamic between RANK and RANKL in breaking down bone?

Answer 4

RANK is a receptor that activates the NF Kappa beta pathway on osteoclasts.
RANKL is the ligand found on the osteoblast that then activates RANK, turning on NFKB pathway and breaking down bone.

Question 5

What is the role of OPG?

Answer 5

This is a decoy receptor on osteoblasts that can bind RANKL and prevent it from interacting with RANK and activated osteoclasts. So it is pro build.

Question 6

What is the role of the WNT/B cat pathway with regulation of bone breakdown and building?
What inhibits the WNT pathway?

Answer 6

Activating the WNT/B cat pathway leads to production of OPG in the osteoblast, which eventually leads to pro build.

Sclerostin

Question 7

Balance between net bone formation and break down is modulated by what two main things?

Answer 7

RANK and WNT

Question 8

3 things she mentioned encourage build?

3 things she mentioned encourage breakdown?

Answer 8

Estrogen, testosterone and Vit D

PTH, IL1 and gluco

Question 9

MCSF stimulate generation of what?

What is the signaling mechanism osteoclasts and osteoblasts use between one another?

Answer 9

Osteoclasts

paracrine

Question 10

What type of mutations are we dealing with in developments disorders of bone?

Answer 10

Inherited mutations

Question 11

What is the mutated gene for the following bone disorders?
Brachydactyly D and E?
Clefdocranial dysplasia?
Achondroplasia?
Thanatopphoric dysplasia?
Achondrogensis Type 2?
Osteopetrosis?

Answer 11

HoxD13
RUNX2
FGFR3
FGFR3
COL2A1
CA2

Question 12

Clinical features of the following bone disorders to know?
Brachydactyly D and E?
Clefdocranial Dysplasia?
Thanatophoric Dysplasia?
Achondrogenesis Type 2?

Answer 12

Short, fat terminal phalanges of first digit
Abnormal clavicles and Wormian bodies (extra bones within cranial sutures)
Severe limb shortening and bowing
Short trunk

Question 13

Thanatophoric Dysplasia is the most common cause of what?
What is the biochemical cause?
2 clinical features?
What happens to these patients at birth?

Answer 13

This is like achondroplasia but some differences.
Most common lethal form of dwarfism.
Different gain of function mutation in FGFR3
Small chest cavity
Die at birth

Question 14

Mutations in LPR5 receptor can lead to two bone disorders?

Mutations in RANKL would lead to what problem?

Answer 14

Osteoporosis or osteopetrosis

Problems with osteoclast

Question 15

What is the difference between osteogenesis type 1 and type 2?

Answer 15

Type 1: normal life span with childhood fractures that decrease with time. Collagen is normal, just less of it. Autosomal dominant
Type 2: usually fatal in utero with multiple intrauterine fractures and respiratory failure. Collagen is not normal. Autosomal recessive

Question 16

Put the 4 types of OI in order of severity?

Which ones have blue sclera and which one has white sclera?

Answer 16

1,4,3, and 2.

123 have blue and 4 has white.

Question 17

What are the two forms of osteopetrosis, what are their inheritance patterns, and what patient population do they affect most commonly?

Answer 17

Severe infantile type, AR, children of Mediterranean and Arab especially.
Mild type more in teens and adults, AD.

Question 18

What is a sign on x ray of bones in a person with osteopetrosis?

Answer 18

The ends of the bones look like an Erlenmeye flask

Question 19

What is going on with MPS and how does this affect bone?

Answer 19

Lysosomal storage diseases caused by a deficiency in enzymes, mostly acid hydrolase enzymes, to break down mucopolysacharides. These guys build in cells and tissues and cause various health problems. In bone and cartilage, they can cause apoptosis and destroy it.

Question 20

How do we define osteopenia and osteoporosis as far as bone density levels?
What event signifies osteoporosis?

Answer 20

1-2.5 SD below the mean
At least 2.5 SD below the mean

Atraumatic or vertebral compression fracture signifies it.

Question 21

5 major factors in the development of osteoperosis?

Answer 21

Age, exercise, genetic factors, calcium state, hormonal influences

Question 22

2 ways low estrogen accelerates bone loss?

Answer 22

Stimulates osteoclast activity via RANKL

Stimulates inflammatory cytokines IL6, TNFA, and IL1

Question 23

Characteristic morph change of osteoporotic vertebral bodies?

Answer 23

Decreases horizontal trabeculae and increased vertical trabeculae

Question 24

Explain the progression of the trabeculae and cortex in osteoporosis?

Answer 24

Tracbulae thins first and quicker. The cortex will thin too but it takes longer.

Question 25

1 genetic factor, 2 nutritional factors, 1 environmental factor that leads to osteoporosis?
Why would we do blood tests when diagnosing an individual with osteoporosis?

Answer 25

White
Not enough calcium, too much phosphorus (soda)
Smoking
To see if there is a secondary cause like hyperparathyroidism or renal failure

Question 26

3 things typically seen with the clinical course of osteoporosis?
3 treatments?

Answer 26

Vertebral fractures in T and L spine, lumbar lordosis, and kyphoscoliosis

Bisphosphonates, hormone therapy, and denosumba (anti RANKL)

Question 27

Most parents disease patients get it in what way?

What is the gene mutated in Paget’s disease that leads to the osteoclasts going wild?

Answer 27

Most is familial.

SQSTM1

Question 28

On radiograph of the head for Paget’s disease, what is the term they use to identify pagets on x ray?

Answer 28

Cotton wool sign

Question 29

What is the hallmark morph feature of pagets?

What are the 3 phases of pagets?

Answer 29

Mosaic pattern of lamellar bone seen in the sclerotic phase.

1. Lytic phase with huge osteoclasts with 100 nuclei
2. Mixed phase with clasts and blasts.
3. Burnt out phase, osteosclerotic phase.

Question 30

What type of fractures do we see in pagets?

Answer 30

Chalk stick type fractures in long bones