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osteoporosis Flashcards

1
Q

What are proportions of men and women that will develop a fracture due to osteoporosis?

A

1 in 2 women

1 in 5 men

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2
Q

What do DXA scans measure?

A

bone mineral density

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3
Q

What properties of bone are determinants of bone strength?

A

bone mineral density
size
microarchitecture

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4
Q

What is the mechanism behind postmenopausal osteoporosis?

A

increased bone turnover with negative bone balance
ie resorption is greater than bone formation
there is net bone loss
disruption of bone architecture

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5
Q

what are the two most important determinants of fracture risk?

A

age

bone density

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6
Q

what is the definition of osteoporosis?

A

a systemic skeletal disease characterised by LOW BONE MASS and MICROARCHITECTURAL DETERIORATION of bone tissue, with a consequent increase in BONE FRAGILITY and susceptibility to FRACTURE

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7
Q

What are the common fractures seen in osteoporosis?

A

femoral neck
vertebrae
Colle’s fracture - distal radius

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8
Q

Is osteoporosis a normal part of ageing?

A

no

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9
Q

At what age do we reach our peak bone mass?

A

25

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10
Q

What are the factors that contribute to bone strength?

A

bone mineral density
bone quality
bone size

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11
Q

What factors influence bone mineral density?

A

peak bone mass

rate of bone loss

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12
Q

what factors contribute to bone quality?

A

bone turnover
architecture
mineralisation

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13
Q

osteoporosis is the commonest metabolic bone disease? T or F

A

true

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14
Q

Explain the bone remodelling cycle

A
  1. remodelling initiated by a chemical or mechanical signal
  2. the osteoclasts start to resorb bone
  3. osteoblasts replace the bone that was resorbed
  4. every time the cycle goes round you get the same of bone are you started with
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15
Q

Explain the pathophysiology of postmenopausal osteoporosis

A
  1. as oestrogen levels fall, remodelling happens more frequently and faster = higher bone turnover than usual and resorption is greater than formation
  2. each time the remodelling cycle happens, there is a more bone loss
  3. this affects trabecular bone more than cortical bone as trabecular bone has a greater surface area
  4. so there microarchitectural disruption - the cortex of the bone is thinner and trabeculae have lost their connectivity
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16
Q

How does bone change with ageing?

A

the osteocytes - the bone’s mechanosensors - sense that there is less horizontal strain on the bone than vertical strain, so horizontal trabeculae are not conserved and there is a decrease in trabecular thickness and decrease in connections between the horizontal trabeculae
decreased trabeculae strength
increased susceptibility to fracture

remodelling unit activation frequency increases with ageing and so a much larger proportion of bone is lost

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17
Q

What does the Eular buckling theory say?

A

a structure without horizontal supports is significantly weaker than one that has both horizontal and vertical supports

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18
Q

How is osteoporosis diagnosed?

A 
bone densitometry ie DXA scan 
T score (which is found from doing DXA)
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19
Q

What is low bone mineral density associated with?

A

fractures

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20
Q

Which sites does DXA look at?

A

lumbar spine
proximal femur = hip
distal radius

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21
Q

What does DXA stand for?

A

dual energy x-ray absorptiometry

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22
Q

What is bone mineral density?

A

how many grams of calcium appetite there is per cm squared

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23
Q

What is the T score?

A

a standard deviation score

compared with gender-matched young adult average (ie compared to the peak bone mass)

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24
Q

What does a T score of greater than -1.0 mean?

A

normal

25
Q

what does a T score of -1.0 to -2.5

A

osteopenia

26
Q

what T score indicates osteoporosis?

A

less than -2.5 (ie getting more negative than -2.5)

27
Q

What is severe osteoporosis in terms of the T score?

A

a T score of less than -2.5 plus fracture

28
Q

What are the causes and risk factors of osteoporosis?

A 
inflammatory disease 
endocrine disease 
reduced skeletal loading 
medication 
previous fracture 
family history of osteoporosis or fracture
alcohol
smoking
29
Q

Why does inflammatory disease predispose to osteoporosis?

A

inflammatory cytokines increase bone resorption
stromal cells of the bone marrow produce RANK-L, IL-1, IL-6, TNF alpha
osteoclasts carry receptors for these inflammatory markers, so drives bone resorption
T cells in the peripheral blood can also produce TNF which binds to receptors on osteoclasts and causes them to resorb bone

30
Q

Give examples of inflammatory conditions that can cause osteoporosis

A

RA
seronegative arthritis
connective tissue disorders
IBD

31
Q

Which endocrine diseases/hormonal factors can causes osteoporosis?

A 
hyperthyroidism
primary hyperparathyroidism 
Cushing's syndrome - cortisol
male hypogonadism
anorexia 
athletes 
iatrogenic and naturally early menopause
32
Q

Which hormones increase bone turn over?

A

thyroid hormone
PTH
cortisol
LOW oestrogen, LOW testosterone

33
Q

which hormone is increased in Cushing’s disease?

A

cortisol

34
Q

what does increased cortisol do to bone?

A

increases bone resorption

induces osteoblast apoptosis

35
Q

which drugs can cause hormonal changes that lead to osteoporosis?

A

glucocorticoids - eg work like cortisol
androgen deprivation eg men treated with prostate cancer
aromatase inhibitors to reduce oestrogen levels in breast cancer
depo-provera - progesterone only
GnRH anologues

36
Q

How does depo-provera reduce BMD?

A

Suppression of ovulation with use of DMPA can lead to a decrease in oestrogen
levels

37
Q

What are the two ways that skeletal loading may be reduced?

A

people with a low body weight

immobility

38
Q

How do GnRH analogues cause osteoporosis?

A

GnRH agonists - When used continuously for periods of longer than 2 weeks, they stop the production of oestrogen by a series of mechanisms.
used for endometriosis

39
Q

What is a really useful questions to ask about FH?

A

did you mother have a hip fracture

40
Q

How does smoking causes osteoporosis?

A

increases bone resorption and drives faster metabolism of Vit D

41
Q

Name factors that are taken account of in the FRAX score

A 
age 
sex
weight 
height 
previous fracture 
parent fractured hip
current smoking 
glucocorticoids 
RA
secondary osteoporosis 
alcohol intake >3 units per day 
femoral neck BMD
42
Q

What does the FRAX score tell you?

A

10 year probability of fracture

43
Q

What is the first line treatment for osteoporosis?

A

Bisphosphonates

44
Q

what are the two mechanisms of action of osteoporosis treatments?

A

anti-resorptive

anabolic

45
Q

what do anti-resorbtive drugs drugs do?

A

decrease osteoclast activity and bone turnover - ie reduce the amount of bone that is in turnover at any one time and allow the osteoblasts to catch up

46
Q

name the anti-resorptive drugs that are used

A

bisphosphonates
HRT
denosumab

47
Q

how do anabolic osteoporosis treatments work?

A

increase osteoblast activity and bone formation

48
Q

name an anabolic osteoporosis treatment

A

Teriparatide

49
Q

what are the adv of HRT?

A

reduce the risk of fractures by 50%
stop bone loss - so BMD increases
prevents hot flushes and other menopausal symptoms
reduces risk of colon cancer

50
Q

what are the disadv of HRT?

A 
breast cancer 
stroke 
CVD
VTE - venous thromboembolic disease
vaginal bleeding
51
Q

name some adv of bisphosphonates

A

cheep
effective
have been used for many years
some forms can be given once a year so pts have higher compliance

52
Q

name some bisphosphonates

A

alendronate
risedronate
ibandronate

basically end in -dronate

53
Q

how do bisphosphonates work?

A

inhibit an enzyme in the cholesterol synthesis pathway called farnesyl pyrophosphate synthase
the bisphosphonate has a high affinity for hydroxyapetite so it sticks to the bone surface and osteoclasts ingest the bone and so ingest the bisphosphonate and the inhibition of the enzyme happens
osteoclasts lose their functionality and can’t make its ruffled border to stick to the bone and can’t secrete H+ to digest the bone

54
Q

How does Denosumab work?

A

monoclonalAb to RANK-L so prevents the communication of osteoclasts with osteoblasts via RANK-L
so switches off bone resorption

55
Q

What are the advantages of Denosumab?

A

rapid acting
very potent anti-resorptive
good fracture risk reduction

56
Q

what is the disadv of Denosumab?

A

rebound increase of bone turnover when stopped
so need to have an injection every 6 weeks and if this is not at the exact time, then the turnover overshoots and becomes higher than it was in the first place and so at higher risk of fracture

57
Q

How does Teripartide work?

A

PTH analogue
it is the first 34 a.a. of PTH and is given as a daily injection
intermittent exposure to PTH activates osteoblasts more than osteoclasts so stimulates bone formation and increases BMD

58
Q

What are the effects of teriparatide?

A

reduces the risk of fractures by MORE THAN 50%

increases BMD, improves trabecular structure

MSK (12 decks)

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