Basic Science Flashcards

1
Q

Higher Young’s Modulus of elasticity means what?

A

MORE STIFFNESS
Young’s modulus is a measure of the ability of a material to withstand changes in length when under lengthwise tension or compression. Equal to the longitudinal stress divided by the strain.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What molecule or signal causes undifferentiated mesenchymal stem cells to differentiate into osteoprogenitor cells?

A

Runx2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the most specific marker of MATURE osteoblast?

A

Osteocalcin (stimulated by 1,25(OH) Vitamin D

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What molecule activates osteoclasts?

A

RANKL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What molecule binds RANKL to limit its activity (inhibit osteoclasts)?

A

Osteoprotegrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What molecule inhibits osteoblasts?

A

Sclerostin

  • Sclerostin sequesters Wnts which are signaling molecules that promote osteoblast bone formation
  • Sclerostin secretion is based on mechanical loading, decreased sclerostin in high areas of strain.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What antiseptics inhibit osteoblast bone formation?

A

Hydrogen peroxide, Betadine, Bacitracin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

In relation to osteoblast activity - pulsatile PTH does what?

A

Stimulates osteoblast by producing Alk phos and Type I collagen
*High levels of PTH signal release of RANKL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

In relation to osteoblast activity - 1,25(OH) vitamin D3 does what?

A

Stimulates osteoblast and leads to matrix and alk phos stimulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

In relation to bone activity - Estrogen does what?

A

Inhibits bone resorption through Adenylyl cyclase inhibition

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

In relation to bone activity - glucocorticoids do what?

A

Inhibit bone production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

In relation to bone activity - Prostaglandins do what?

A

Stimulate bone resorption through Adenylyl cyclase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Osteocytes are former _______

A

Osteoblasts, which are surrounded by newly formed matrix

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Osteocytes are connected and communicate via __________

A

Gap junctions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Osteocytes control extracellular __________ and ________

A

calcium, phosphorous

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Osteocytes are stimulated by ______ and inhibited by_______

A

calcitonin (helps absorb extracellular calcium), PTH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Osteoclasts resorb bone by…
Binding _______
Increasing __________
Synthesizing__________

A

Binding bone surface through integrins (specifically αvβ3 or vitronectin receptor), having a “Ruffled border” to increase the surface area of resorption, synthesizing TRAP (tartrate-resistant acid phosphate - lowers pH utilizing carbonic anhydrase and thus increases solubility of hydroxyapatite crystals), cathepsin K, MMPs, lysosomal cysteine proteinases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

RANKL is released by _________ and has a receptor on __________ and functions to _______. Lastly, RANKL is inhibited by _________.

A

osteoblasts, osteoclast precursor cells, activate them into mature osteocytes leading to bone resorption, osteoprotegerin (OPG)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q
Does activation of the following signaling molecules promote bone formation or resorption?
RANKL
Calcitonin
IL-1
IL-10
Bisphoshonates
1,25 dihydroxy vitamin D
Prostaglandin E2
IL-6
MIP-1A
OPG (osteoprotegerin)
Estrogen
TGF beta
A

RANKL - resorption (binds to RANK receptor on osteoclasts)
Calcitonin - formation (inhibits osteoclasts by interacting with osteoclast surface receptors)
IL-1 - resorption (stimulates osteoclast differentiation)
IL-10 - formation
Bisphoshonates - formation
1,25 dihydroxy vitamin D - resportion (stimulates RANKL)
Prostaglandin E2 - resorption (activates adenylyl cyclase)
IL-6 resorption (myeoloma)
MIP-1A - resorption (myeoloma)
OPG - formation (sequesters RANKL)
Estrogen - formation (decrease RANKL)
TGF beta - formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Wolff’s Law

A

Remodeling occurs in response to mechanical stress
(The compression side of bone is electronegative, stimulating osteoblasts
(formation))

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Hueter-Volkmann law

A

Mechanical loading can influence the rate of growth.
-Compressive forces inhibit growth (gymnasts tend to be shorter); tension stimulates it
This type of remodeling occurs in small packets of cells
known as basic multicellular units (BMUs).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Endochondral bone formation occurs by _________ replacing _________. Two examples are…

A

bone replacing cartilage. Physeal growth (longitudinal growth) and fracture callous.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

In endochondral bone growth this gene/protein promotes chondrocyte differentiation.

A

Sox-9

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

The zones of physeal growth

A

Reserve: cells store lipids and proteoglycans.
Proliferative: cellular proliferation and stacking of chondrocytes.
Hypertrophic
-Maturation: Chondrocytes increase 5x in size, accumulate calcium in their mitochondria.
-Degeneration: Chondrocytes die.
-Provisional Calcification: Chondrocytes release calcium.

*Osteoblasts then migrate from sinusoidal vessels and replace cartilage as scaffolding for bone formation.

25
Q

___________ inhibits chondrocyte maturation.

A

PTHrP

Subsequently IHH is produced by chondrocytes and regulates the expression of PTHrP (PTH related peptide).

26
Q

In the hypertrophic zone of the physis, Type _____ collagen is produced by chondrocytes and is important for mineralization.

A

X

27
Q

Attach the disease with its respective pathologic area within the physis.
Gaucher’s
Diastrophic Dysplasia

A

Reserve zone

*where cells store lipids and proteoglycans.

28
Q

Attach the disease with its respective pathologic area within the physis.
Achondroplasia
Gigantism
Multiple Hereditary Exostosis

A

Proliferative zone

29
Q

Attach the disease with its respective pathologic area within the physis.
Hypertrophic zone, specifically the maturation zone.

A

SCFE

30
Q

Attach the disease with its respective pathologic area within the physis.
Hypertrophic zone, specifically the Degenerative zone.

A

Rickets

31
Q

Attach the disease with its respective pathologic area within the physis.
Hypertrophic zone, specifically the Provisional Calcification zone.

A

Salter Harris Fx

32
Q

Attach the disease with its respective pathologic area within the bone.
Corner Fx
Scurvy

A

Primary spongiosa

33
Q

Name type of fracture healing based on the characteristic: <2% strain

A

Primary bone healing

34
Q

Name type of fracture healing based on the characteristic: intramembranous via haversian remodeling (cutting cones)

A

Primary bone healing

35
Q

Name type of fracture healing based on the characteristic: absolute stability (ie. compression plating)

A

Primary bone healing

36
Q

Name type of fracture healing based on the characteristic: <10% strain

A

Secondary bone healing

37
Q

Name type of fracture healing based on the characteristic: Enchondral via callous (cartilage model)

A

Secondary bone healing

38
Q

Name type of fracture healing based on the characteristic: relative stability (IMN, ex-fix, cast)

A

Secondary bone healing

39
Q

Name the 3 stages of fracture healing.

A
  1. Inflammation
  2. Repair
  3. Remodeling
40
Q

Name the stage of fracture healing:

  • Hematoma -> Macrophages, neutrophils & cytokines (PDGF, TNF-alpha, TGF-beta, IL-1, IL-6)
  • Fibroblasts form granulation tissue, mesenchymal stem cells -> osteoblasts via runx-2/osterix
A

Inflammation stage

41
Q

Name the stage of fracture healing:

  • Soft callous -> Primary callous (woven bone) via enchondralossification, within 2 weeks
  • Type II cartilage (soft callous), Type I cartilage (bone)
  • Low strain -> osteoblastic signaling; High strain -> chondrocyte signaling
  • Amount of callous inversely related to immobilization
A

Repair stage

42
Q

Name the stage of fracture healing:
-Hypertrophic chondrocytes calcify extracellular matrix via proteases and Type X collagen
-Multiple factors are expressed as bone is formed including BMPs, TGF-Betas, IGFs, osteocalcin,
collagen I, V and XI
-New bone remodeled by osteoblasts/ osteoclasts; woven bone replaced by lamellar and shaped through Wolff’s Law

A

Remodeling phase

43
Q

What is the most important factor for fracture healing?

A

Blood supply, which peaks at 2 weeks.

44
Q

This synthetic bone graft has high compressive strength, degrades slowly, is osteoconductive and uncludes hydroxyapatite…

A

Calcium phosphate

Level I evidence shows that calcium-phosphate bone substitutes allow for bone defect filling, early rehabilitation, and prevention of articular subsidence in distal radius and tibial plateau fractures

45
Q

T score of osteopenia

A

-1 to -2.5

46
Q

Indications for pharmacologic treatment of osteopenia or osteoporosis.

A

Postmenopausal women and men >50 yo with:

  • hip/vertebral body fx
  • T-score between -1.0 and -2.5 at femoral neck or spine and 10 year risk of hip fracture >3% or FRAX score >20%
  • T-score
47
Q

MOA of denosumab

A

Antibody that binds RANKL and prevents osteoclast activation

48
Q

MOA of Teraperatide (Forteo)

A

Essentially a recombinant PTH that binds receptors on osteoblasts and promotes ANABOLIC bone formation.
Risks: transient hypercalcemia, Paget’s disease -> osteosarcoma

49
Q

BMP____ is directly responsible for osteoinduction and osteogenesis.

A

BMP2

50
Q

Why is Rifampin commonly used synergistically with other antibiotics?

A

It has great potential to penetrate cells.

  • Rifampin is lipophilic and can easily cross cellular walls and membranes to exert its bactericidal action to block RNA polymerase and subsequent RNA transcription.
  • Effective against intracellular phagocytized Staph aureus.
51
Q

MOA of Rivaroxaban

A

Selective factor 10a inhibitor

52
Q

MOA of Aspirin

A

Cyclooxygenase inhibitor which reduces thromboxane A2.

53
Q

MOA of Warfarin

A

Vitamin K antagonist and reduces the production of clotting factors II, VII, IX, X

54
Q

MOA of Heparin/LMWH

A

Activation of antithrombin III which then inhibits the clotting factors IIa, III, Xa

55
Q

Tendons are 95% Type ______ collagen

A

Type I collagen. The remaining 5% is proteoglycans and small mix of other collagen types (mostly collagen type III). Proteoglycans help keep water content in tendons (Decorin is most common proteoglycan found in tendons).

56
Q

Osteoblasts synthesize Type _______ collagen

A

Type 1 collagen

57
Q

PTH binds _______ which secrete secondary messanger molecule to activate _______

A

osteoblasts; osteoclasts

58
Q

Bone is compose of Type ___ colllagen

A

Type 1

bONE

59
Q

_______ is the major determinant of fracture healing and peaks at _______ weeks

A

Blood flow; 2 weeks