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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?

25
what does a T score of -1.0 to -2.5
osteopenia
26
what T score indicates osteoporosis?
less than -2.5 (ie getting more negative than -2.5)
27
What is severe osteoporosis in terms of the T score?
a T score of less than -2.5 plus fracture
28
What are the causes and risk factors of osteoporosis?
``` inflammatory disease endocrine disease reduced skeletal loading medication previous fracture family history of osteoporosis or fracture alcohol smoking ```
29
Why does inflammatory disease predispose to osteoporosis?
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
Give examples of inflammatory conditions that can cause osteoporosis
RA seronegative arthritis connective tissue disorders IBD
31
Which endocrine diseases/hormonal factors can causes osteoporosis?
``` hyperthyroidism primary hyperparathyroidism Cushing's syndrome - cortisol male hypogonadism anorexia athletes iatrogenic and naturally early menopause ```
32
Which hormones increase bone turn over?
thyroid hormone PTH cortisol LOW oestrogen, LOW testosterone
33
which hormone is increased in Cushing's disease?
cortisol
34
what does increased cortisol do to bone?
increases bone resorption | induces osteoblast apoptosis
35
which drugs can cause hormonal changes that lead to osteoporosis?
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
How does depo-provera reduce BMD?
Suppression of ovulation with use of DMPA can lead to a decrease in oestrogen levels
37
What are the two ways that skeletal loading may be reduced?
people with a low body weight | immobility
38
How do GnRH analogues cause osteoporosis?
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
What is a really useful questions to ask about FH?
did you mother have a hip fracture
40
How does smoking causes osteoporosis?
increases bone resorption and drives faster metabolism of Vit D
41
Name factors that are taken account of in the FRAX score
``` 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
What does the FRAX score tell you?
10 year probability of fracture
43
What is the first line treatment for osteoporosis?
Bisphosphonates
44
what are the two mechanisms of action of osteoporosis treatments?
anti-resorptive | anabolic
45
what do anti-resorbtive drugs drugs do?
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
name the anti-resorptive drugs that are used
bisphosphonates HRT denosumab
47
how do anabolic osteoporosis treatments work?
increase osteoblast activity and bone formation
48
name an anabolic osteoporosis treatment
Teriparatide
49
what are the adv of HRT?
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
what are the disadv of HRT?
``` breast cancer stroke CVD VTE - venous thromboembolic disease vaginal bleeding ```
51
name some adv of bisphosphonates
cheep effective have been used for many years some forms can be given once a year so pts have higher compliance
52
name some bisphosphonates
alendronate risedronate ibandronate basically end in -dronate
53
how do bisphosphonates work?
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
How does Denosumab work?
monoclonalAb to RANK-L so prevents the communication of osteoclasts with osteoblasts via RANK-L so switches off bone resorption
55
What are the advantages of Denosumab?
rapid acting very potent anti-resorptive good fracture risk reduction
56
what is the disadv of Denosumab?
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
How does Teripartide work?
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
What are the effects of teriparatide?
reduces the risk of fractures by MORE THAN 50% | increases BMD, improves trabecular structure

MSK (12 decks)

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