Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PHA223 > osteoporosis (Steve Darby) > Flashcards

osteoporosis (Steve Darby) Flashcards

1
Q

What is osteoporosis?

A

loss of bone mass due to reduced organic bone matrix and mineral content

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

causes of osteoporosis

A

increased bone resorption (osteoclasts)
decreased bone formation (osteoblasts)
both

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

causes of primary osteoporosis

A 
menopause (inc bone resorption)
age associated (dec bone formation)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

causes of secondary osteoporosis

A

drug/disease induced

  • severe malnutrition (anorexia, lack of Vit D)
  • endocrine (hypogonadism, hyperparathyroidism)
  • cancer
  • drug use
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What hormones control the homeostatic regulation of Ca?

A

calcitonin
PTH
Vit D

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

RANKL

A

receptor activated NF kappa B ligand

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How does an osteoclast precursor become an active osteoclast?

A

pre-osteoclast has RANK (receptor) on its surface
PTH stimulates release of RANKL
RANKL binds to RANK
causes the osteoclast precursor to become active
these then degrade bone

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

What is bone resorption?

A

degradation of bone

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

What substances cause bone resorption (degradation)?

A

RANKL

PTH

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

What is OPG?

A

oseteoprotegerin

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

What does OPG do?

A

inhibits bone resorption

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

How does inhibition of bone resorption occur?

A

bone releases OPG (oesteoprotegerin)
OPG binds to RANKL
this prevents RANKL from binding to RANK on the osteoclast precursor

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

How do oestrogens help in bone formation?

A

promote formation of pre-osteoblasts
prevent activation of T cells (T cells release RANKL)
prevent generaion of osteoclasts

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

What happens when oestrogen levels are decreased?

A

T cells become activated
RANKL increased (from T cells)
activates pre-osteoclasts, inc in bone resportion - bone loss

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

preventative measures for osteoporosis

A
  • oral Ca supplements (inc BMD in spine in postmenopause)
  • Vit D
  • HRT in peri/post menopause
  • smoking cessation
  • increased exercise (promotes bone remodelling)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

pharmacological treament options for osteoporosis

A 
bisphosphonates
denosumab
HRT
raloxifene
teriparatide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

2 types of therapies for established osteoporosis

A
  1. anti-resorptive therapies - dec markers of bone formation and bone resorption
    bisphosphonates, raloxifene, oestrogen, denosumab
  2. bone forming therapies (anabolic) - inc markers of bone formation over bone resorption
    calcitonin, teriparatide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

composition of calcified bone

A

25% organic matrix
5% water
70% hydroxyapatite

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is hydroxyapetite?

A

crystalline complex of Ca and P

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

What does pyrophosphate do?

A

binds and stabilises Ca and P in bone

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

Why can’t pyrophosphate be given orally?

A

it’s hydrolyses in GIT

ester bond broken into 2 phosphate groups

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

difference between pyrophosphate and bisphosphonates?

A

oxygen replaced with a carbon with 2 functional groups

P-C-P can’t be hydrolysed

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

R1 side chain of bisphosphonates

A

hydroxyl group

  • maximises effects to bind hydroxyapatite
  • increases Ca affinity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

R2 side chain on bisphosphonates

A

amino residue

- increaes potency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How do bisphosphonates work?

A
  • stabilise the hydroxyapatite matrix
  • inhibit bone resorption
  • inhibit osteoclast proliferation
  • inhibit osteoclast activity
  • inhibit malaveonate pathway -> to regulate osteoclast fxn
  • > reduce bone turnover and allow osteoblasts to function
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Why do bisphosphonates have poor absorption?

A

their polar nature

27
Q

How much bisphosphonate is absorped into bone?

A

50%

the rest excreted via kidneys

28
Q

half life of bisphosphonates

A

serum half life - 4-6hrs

tissue half life - 10yrs

29
Q

2nd generation of bisphosphonates

A

amino-bisphosphonates

  • > nitrogen containing drugs
  • > alendronic acid
30
Q

How often is alendronic acid taken?

A

once a week

31
Q

3rd generation bisphosphonates

A

amino-bisphosphonates

  • > nitrogen containing
  • > risedronate sodium (once a week)
32
Q

What is given if oral bisphosphonates not tolerated?

A

IV bisphosphonates

-> Zoledronic acid (annually)

33
Q

cautions with zoledronic acid

A

osteonecrosis of the jaw

34
Q

renal function and bisphosphonates

A

alendronic acid eGFR <35

ridedronate eGFR < 30

35
Q

How to take bisphosphonates?

A

taken once weekly

empty stomach to avoid binding to Ca in food

36
Q

oral forms of bisphosphonates

A

alendronic acid

risedronate

37
Q

IV formulations of bisphosphonates

A

pamidronate disodium

zoledronic acid

38
Q

s/e of bisphosphonates

A

GI disturbance - nausea, abdominal pain, diarrhoea/constipation
severe oesophagitis (oral)
headache
dizziness
MSK pain
transient pyrexia, flu-like symptons (IV)
osteonecrosis of the jaw (esp IV)

39
Q

How does Denosumab mimick natural inhibition of bone resorption?

A

it mimicks OPG

40
Q

How does denosumab work?

A

binds to RANKL to prevent osteoclast activation

41
Q

How often is denosumab given?

A

6 monthly injection

42
Q

How is the oestrogen receptor activated?

A
  • HRT casuses helix H12 to fold over the E2 binding site
  • conformational change enables ER to bind to trascriptional cofactors and DNA
  • initiates ER target gene transcription
  • promotes cellular growth and bone formation
43
Q

Why is HRT not used as much for osteoporosis teratment today?

A

risk of breask cancer and thrombosis

44
Q

What HRTs are used?

A

SERMs - selective estrogen receptor modulators

45
Q

example of SERM

A

raloxifene

46
Q

Is raloxifene an ER agonist/antagonist in osteoclasts?

A

ER agonist (turns on the receptor, activates bones to reform/remodel)

-> ER antagonist in breast tissue, turns off the receptor

47
Q

What does raloxefine do?

A

reduces osteoclast activity

48
Q

advantages/diasdvantages with SERMs (raloxifene)

A
  • doesn’t inc risk of breast cancer

- doesn’t prevent hot flushes/menopause symptoms

49
Q

2nd generation SERM

A

Lasofoxifene

50
Q

What does raloxifene bind to in the nucleus of bone cells?

A

RRE - Raloxifene response element (bone)

51
Q

difference betwen estradiol and raloxifene

A 
ESTRADIOL (antagonist)
- binds to ER
- moves into nucleus
- binds to ERE in breast tissue and switches on genes
RALOXIFENE (agonist)
- binds to ER
- moves into nucleus of bones
- binds to RRE (not present in breast tissue), helper proteins help with this
52
Q

What does PTH do with bones?

A

stimulates intestinal absorption of Ca and promotes bone resorption

53
Q

How does PTH stimulate resorption?

A
  1. osteoprogenitor cells become osteoclasts in presence of PTH (activates osteoclasts)
  2. promotes deep osteocytes to mobilise Ca
  3. surface of osteocytes are stimulated by PTH to increase the flow of Ca out of bone
54
Q

biphasic effect of PTH

A

promotes bone resorption by binding to PTH1R

if given daily, promotes bone formation

55
Q

How does PTH stimulate bone resorption?

A

increases osteoclastic activity through upregulation of RANKL
downregulation of OPG secretion by osteoblasts

56
Q

How does PTH increase bone formation?

A

indirectly via autocrine and paracrine pathways through release of IGF-1, FGF-2 and amphiregulin from osteoblasts

57
Q

PTH given intermittently (naturally)

A

binds to PTH1R on osteoclasts

-> breakdown of bone

58
Q

PTH given continuously/daily

A

binds to PTH1R on osteoblasts

-> bone formation (osteogenesis)

59
Q

How does Teriparatide work?

A
  • activates PTHR
  • activates osteoblasts - OPG stimulation, natural RANKL inhibitor
  • decreases osteoclasts
60
Q

When is Teriparatide used?

A

severe cases

61
Q

brand name of teriparatide

A

Forteo

62
Q

What does teriparatide do?

A

stimulates new bone formation

increased BMD

63
Q

How is teriparatide given?

A

daily injections

not ORAL because it’s a hormone so it’s degraded by GIT

PHA223 (43 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions