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BIOL0027 > Musculoskeletal Ageing: Osteoporosis, Osteoarthritis, and Sarcopenia > Flashcards

Musculoskeletal Ageing: Osteoporosis, Osteoarthritis, and Sarcopenia Flashcards

1
Q

What is functional reserve and how does it change with old age?

A

Ability to look after self

Decreases

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2
Q

What happens once the functional reserve threshold is reached?

A

Loss of independence

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3
Q

What is sarcopenia?

A

Loss of muscle mass, quality, strength

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4
Q

What is the impact of sarcopenia?

A

Decreases functional reserve - drives frailty, mortality

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5
Q

Does muscle strength or mass decline faster with age?

A

Strength

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6
Q

Is loss of muscle strength or mass the key risk factor for disability in old age?

A

Strength

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7
Q

Name a test of muscle strength

A

Grip strength

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8
Q

Which pathologies in ageing muscle underlie sarcopenia?

A

Decreased actin and myosin
Decreased mitos
Increased fat infiltration

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9
Q

Name the age-related risk factors for sarcopenia

A

Decreased anabolic hormones (e.g. IGF1, oestrogen, testosterone)
Anorexia of ageing
Increased catabolic stimuli (inflammatory cytokines)
Physical inactivity

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10
Q

Which is the biggest age-related risk factor for sarcopenia?

A

Physical inactivity

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11
Q

What is the effect of testosterone replacement therapy in old men?

A

Increased muscle mass and strength

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12
Q

What is the effect of oestrogen replacement therapy in old women?

A

Inconclusive

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13
Q

Why does anorexia of ageing occur?

A

Depression

Drug side effects

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14
Q

Which treatment can reverse sarcopenia?

A

Resistance training

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15
Q

Which pathway regulates muscle mass?

A

PI3k-Akt

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16
Q

Which pathway is upstream of the PI3k-Akt pathway?

A

Insulin/IIS signalling

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17
Q

What are the 2 pathways in PI3k-Akt signalling and their effects on muscle?

A

mTOR activation - increased protein synthesis - muscle growth
Myostatin causes PI3k inhibition - activates FOXO (transcription factor) - MuRF-1 expression - muscle breakdown

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18
Q

How do extreme periods of inactivity in the elderly affect muscles?

A

Decreased leg mass and strength
Decreased mTORC1 signalling
Increased MuRF-1 expression
Decreased protein synthesis

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19
Q

What is the evidence for a role of inflammation in sarcopenia?

A 
COPD patients have increased MuRF-1 expression
Sepsis patients (inactivity and pro-inflammatory state) have decreased strength
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20
Q

What is immunosenescence?

A

Decline in immune function with age - includes inflammageing

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21
Q

What is inflammageing?

A

Chronic inflammation with age

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22
Q

Which cell type produces IL-6?

A

Myocytes

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23
Q

Name a pro-inflammatory cytokine

A

IL-6

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24
Q

What is the effect of IL-6 on muscle?

A

Increases proteasomal activity - increases muscle breakdown

Induces insulin resistance - decreases Akt-mTOR activity

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25
Q

Which catabolic hormone is produced in the inflammatory response?

A

Cortisol

26
Q

Which enzyme synthesises cortisol?

A

11β-HSD1

27
Q

How do 11β-HSD1 levels change with age and what causes this?

A

Increase

Induced by TNFalpha and IL-6

28
Q

What is the effect of TNF-alpha administration in mice?

A

Increased proteasome activity, PI3-Akt suppression - muscle loss

29
Q

Name an anti-inflammatory cytokine

A

IL-10

30
Q

How do the levels of IL-10 change with age?

A

Decrease

31
Q

What is the effect of an IL-10 KO in mice?

A

Develop sarcopenia

32
Q

How does the number of leukocytes change in frail older people?

A

Increases

33
Q

How does neutrophil chemotactic ability change with age and what is the effect of this?

A

Decreases

Inefficient neutrophil migration - causes tissue damage - causes inflammageing

34
Q

How can neutrophil chemotactic ability be restored in older people?

A

Pharmacological PI3K inhibition

35
Q

What are the 3 main factors causing sarcopenia in old age?

A

PI3K-Akt signalling dysregulation
Inflammation
Physical inactivity

36
Q

How does inflammageing affect cortisol production and what is the impact of this?

A

Increases - causes muscle breakdown

37
Q

What are the direct and indirect effects of PI3K-Akt signalling dysregulation on sarcopenia?

A

Direct - decreased muscle synthesis, increased degradation

Indirect - via inflammageing

38
Q

Is old age sarcopenia preventable?

A

Yes

39
Q

Which is the best form of physical activity to prevented the age-related decline in muscle strength?

A

Strength training

40
Q

Name 4 sarcopenia treatments

A

Exercise - best method
Hormone replacement - side effects
Vitamin D - mixed evidence
Myostatin antagonists - untested

41
Q

In which distinct areas is there continuous remodelling of bone?

A

Bone metabolic units

42
Q

Which cell type controls bone formation?

A

Osteoblasts

43
Q

Which cell type controls bone reabsorption?

A

Osteoclasts

44
Q

Why is a homeostatic balance required in bone?

A

Maintain bone mass and strength

45
Q

How do the levels of osteoblasts and osteoclasts change over the life-course?

A

Bone growth up to ~30yrs old - osteoblasts>osteoclasts
Midlife plateau - osteoblasts=osteoclasts
Decline after peak - osteoclasts>osteoblasts

46
Q

How does bone marrow fat change with ageing and what is the impact of this?

A

Increases

Favours differentation of mesenchymal stem cells (MSCs) to adipocytes - instead of osteoblasts - prevents bone growth

47
Q

What causes the age-related decline in MSC proliferative capacity?

A

Telomere shortening

Accumulation of DNA damage

48
Q

What is osteoporosis

A

Decline in bone mass and microarchitecture - less dense bone matrix

49
Q

What is an implication of osteoporosis?

A

Increases fracture risk

50
Q

What are the intrinsic (non-modifiable) osteoporosis risk factors?

A 
Gender (post-menopausal women)
Age
Small body size
Ethnicity (Caucasian/Asian)
Family history - part hereditary
51
Q

What was the effect on bone of older people with a later menopause or longer reproductive life in the NSHD?

A

Increased bone density

52
Q

What are the modifiable osteoporosis risk factors?

A

Sex hormones (low oestrogen/testosterone)
Low dietary calcium and vitamin D
Inactivity
Smoking

53
Q

Why does viamin D insufficiency worsen osteoporosis?

A

Vitamin D required for osteoblastogenesis

54
Q

Which scanning type can be used to asses bone mass density?

A

DEXA scanning

55
Q

What are the 3 main aims of osteoporosis treatments?

A

Inhibit osteoclasts
Increase osteoblast activity
Regulate bone marrow adipogenesis

56
Q

Name 3 osteoporosis treatments

A

Bisphosphonates
Vitamin D
Denosumab

57
Q

What is denosumab and how does it work?

A

Monoclonal antibody to RANKL
RANKL bound to RANK - on osteoclasts
Denosumab binding inhibits osteoclast activity

58
Q

What is zoledronate and how does it work?

A

Bisphosphonate
Affects mTOR signalling - decreases DNA damage - extends MSC lifespan - preserves ability to proliferate and differentiate

59
Q

What is osteoarthritis?

A

Breakdown of joint cartilage and underlying bone

60
Q

What are the risk factors for osteoarthritis and which is the biggest?

A

Age - biggest
Obesity
Genetics
Previous joint injury

61
Q

What are the 2 main mechanisms behind osteoarthritis?

A

Mechanical stress on joint

Inflammation

BIOL0027 (20 decks)

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