Bone Pathology

Question 1

osteocytes are located in [….] (dents in bone), and are sustained via their [……] (a functional syncitium).

Answer 1

lacunae canaliculae

Question 2

osteoblasts and chondrocytes are derived from […..] cells. The cells are typically located in the […..] layers of bone.

Answer 2

osteoprogenitor cells (mesenchymal stem cells) endosteum and periosteum

Question 3

osteoclasts are derived from a [….] lineage, are multinucleated, and function to [….] bone. These are stimulated by an increase in […..].

Answer 3

monocyte resorb PTH

Question 4

describe the interplay between RANKL and OPG and M-CSF

Answer 4

bone breakdown/turnover is controlled by relative amount of Osteoprotegrin (blocks RANKL) and RANKL produced by osteoblasts and expressed on their surface. RANKL binds to RANK receptor on the osteoclast precursor.—>stimulated NFkB to cause differentiation into mature osteoclast. M-CSF, macrophage colony stimulating factor, secreted by osteoblasts, binds its receptor on precursor osteoclasts. M-CSF induces the expression of RANK on precursor osteoclasts, priming them for differentiation/activation.

Question 5

T/F Osteoclasts are stimulated by increases in PTH

Answer 5

TRUE.

Question 6

which layer of bone is the blood supply and nerves located?

Answer 6

found in the periosteum (dense outer layer). as opposed to endosteum, inner layer.

Question 7

what is the origin story of long bones from infant stage?

Answer 7

in infants, a model of the bone is built of hyaline cartilage. chondrocytes then proliferate—>hypertrophy—>degenerate and are then replaced with osteoblasts.

Question 8

what do osteoblasts lay down to create bone? what is it composed of

Answer 8

osteoid, contains: 1. 90% collagen type I 2. protein, GAG’s 3. growth factors and cytokines NB: when osteoid is broken down, growth factors are released, triggering its own regeneration

Question 9

under what conditions would you find woven bone vs lamellar bone?

Answer 9

woven bone is present during the healing or growing phase, whereas lamellar bone is established (tidy, well ordered, strong pattern).

Question 10

annual bone turnover rate in adults? 1) 40-50% 2)1-2% 3)5-10% 4)25%

Answer 10

3) 5-10% NB: 200x faster in children

Question 11

describe the organization of the basic multicellular unit of bone (BMU) in normal bone remodelling?

Answer 11

osteoclasts up front, osteoblasts behind, and capillary up the middle.

Question 12

the osteoid produced by osteoblasts contains all of the following except: 1. collagen type 1 2. proteoglycans 3. cytokines and growth factor 4. calcium and phophate

Answer 12

4! no calcium and phosphate, but osteoid does secrete the enzymes that will eventually upregulate these minerals….

Question 13

name each of these fractures? (based on orientation of fracture line)

Answer 13

Question 14

name this fracture?

Answer 14

Colle’s fracture (displaced fracture)

characeristic dinner fork appearance of this fracture

Question 15

name that fracture type

Answer 15

open (compound) fracture

as opposed to a closed (simple) fracture

Question 16

name that fracture

Answer 16

comminuted fracture (A fracture in which a bone is broken, splintered, or crushed into a number of pieces.)

Question 17

what type of fracture is assoc with repeated low force injury to normal bone?

Answer 17

STRESS FRACTURE

NB: better visualized with nuclear imaging

Question 18

describe the stages of fracture healing

Answer 18

1. inflammatory phase
   - bleeding and haematoma formation
   - vascular granulation tissue
2. Reparative phase
   - Soft callus (cartilage, fibrous tissue) turns into —> hard callus (woven bone)
3. remodelling phase

Question 19

what occurs in the first hours to days following a fracture?

Answer 19

inflammatory phase, including

1. haematoma formation (fibrin mesh creates framework,damaged matrix releases growth factors and cytokines, stem cells activated to start repair )

AND

2. granulation tissue formation

NB: stem cells differentiate very early to start repair…if its a very stable fracture they will go stragiht to osteoblasts, otherwise they follow the sequence osteoblast>chondrocyte>fibroblast

Question 20

What happens in the period days/weeks after fracture?

Answer 20

reparative phase: soft callus.

• periosteum repairs itself over the outside.
• cartilage holds the fractured ends together but provides no structural integrity

Question 21

what happens in period weeks/months after fracture?

Answer 21

reparative phase: hard callus

soft callus–>hard callus

-osteoid formation and ossification take place

–>woven bone forms

–>endochondral ossification takes place

NB: hard callus is thicker where the fracture was

Question 22

what happens in the period months/years after fracture?

Answer 22

remodelling

(bone is completely reconstituted)

• osteoclasts are followed by osteoblasts; woven bone is turned into lamellar bone
• transition occurs along lines of stress

Question 23

what are 3 main clinical management principles for optimizing fracture healing?

Answer 23

1. reduction (minimize the gap between bones)
2. fixation (minimize strain or movement)
3. minimize other factors that slow healing (smoking, infection, poor blood supply)

Question 24

how long does a fracture typically take to heal?

Answer 24

6-8 weeks, but:

• longer for lower limb
• faster in kids
• longer in elderly
• femur is esp bad
• spiral fractures better

NB: non union may occur, may require bone grafting. could cause ‘pseudo-arthrosis’ where cells around broken bone ends behave like a joint.

Question 25

what type of infections tend to get infected? pathogen?

Answer 25

compound/open fractures tend to get infected.

osteomyelitis= infection of bone/marrow.

–>commonly staph aureus.

–>can cause sepsis

Question 26

avascular necrosis (AVN) /osteonecrosis impact?

Answer 26

fractures that interrupt blood supply and leave parts of bone ischaemic.

ex. neck of femur, scaphoid bone (radial artery)

Question 27

by what process does the soft callus turn into hard callus?

Answer 27

endochondral ossification

Question 28

which of the cells from normal bone will eventually produce a soft callus

Answer 28

osteoprogenitor cells

Question 29

at which point is it thought that osteoprogenitor cells decide which type of cells to differentiate into?

Answer 29

inflammatory phase - haematoma formation

Question 30

which cells are these?

Answer 30

osteoblasts

Question 31

which primary tumour gives rise to metastases to bone?

Answer 31

Question 32

gross pathological characteristics of bony mets?

Answer 32

Question 33

how do patients with bony mets present?

Answer 33

Question 34

causes and manifestations of osteoporosis?

Answer 34

genetic, nutritional, and physical activity.

results in reduced mass of otherwise normal bone.

—>increased risk of fracture.

Question 35

osteomalacia in adults and rickets in children may occur due to…..

Answer 35

vitamin D deficiency

—>impaired bone mineralization

—->more osteoid produciton

–>loss of structural rigidity

Question 36

how does hyperparathyroidism affect bone?

Answer 36

primary: parathyroid tumor or hyperplasia
secondary: prolonged hypercalcaemia or hyperphostaemia

Causes:

-increased RANK-L activity (osteoclastic activity)

–>compensatory increase in osteoblastic activity

NB: intermittent doses of PTH actually just stimulate osteoblasts without stimulating osteoclasts