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MD1 Locomotor > Drugs Affecting Bone > Flashcards

Drugs Affecting Bone Flashcards

1
Q

What are the metabolic functions of bone?

A

Reservoir of calcium and phosphate

Acid-base balance

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2
Q

How much of the body’s calcium store is within bone?

A

98-99%

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3
Q

How much of the body’s phosphate store is within bone?

A

85%

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4
Q

What are the synthetic functions of bone?

A

Production of RBCs and WBCs

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5
Q

What proportion of bone is cortical and trabecular?

A

80% cortical

20% trabecular

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6
Q

Which bone type has the larger surface area: cortical or trabecular?

A

Trabecular

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7
Q

What is tetracycline?

A

Broad spectrum antibiotic

Calcium chelator

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8
Q

What happens if tetracycline is consumed during tooth development?

A

Yellow/brown discolouration of dentin

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9
Q

Is osteoid mineralised?

A

No

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10
Q

What proportion of bone matrix is osteoid and mature bone tissue?

A

25% osteoid

75% mature bone tissue

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11
Q

Why is bone remodelled?

A

Bone growth during skeletal development
Respond to mechanical stress
Mechanism to regulate calcium in extracellular fluid

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12
Q

What factors affect remodelling?

A 
Ageing
Physical factors
- Exercise
- Loading
Hormones
- Oestrogen
Drugs
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13
Q

Which bone type is preferentially affected in processes that affect bone remodelling?

A

Trabecular bone

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14
Q

Why is trabecular bone more affected in processes affecting bone remodelling?

A

Larger surface area
More metabolically active
Higher turnover

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15
Q

What are the five phases of bone remodelling?

A 
Activation
Resorption
Reversal
Formation
Quiescence
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16
Q

What happens during activation in bone remodelling?

A

Recruitment of osteoclast precursors

Differentiation to osteoclasts

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17
Q

What happens during resorption in bone remodelling?

A

Osteoclasts attach to bone surface and form ruffled border

Make pit in bone by secreting acids and enzymes

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18
Q

What happens during reversal in bone remodelling?

A

Sequestered growth factors from bone released

Recruit osteoblasts

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19
Q

What happens during formation in bone remodelling?

A

Osteoblasts lay down new osteoid

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20
Q

What happens during quiescence in bone remodelling?

A

Osteoblasts become osteocytes

Incorporated into bone matrix

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21
Q

What does parathyroid hormone do in bone remodelling?

A

Increased activity of

  • Osteoblasts
  • Osteoclasts
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22
Q

What does oestrogen do in bone remodelling?

A

Decreased osteoclast activity

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23
Q

What do glucocorticoids do in bone remodelling?

A

Increased osteoclast activity

Decreased osteoblast activity

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24
Q

What do sequestered cytokines do in bone remodelling, when they are released?

A

Increased osteoblast activity

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25
Q

What does calcitonin do in bone remodelling?

A

Decreased activity of osteoclasts

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26
Q

What does dexamethasone do?

A

Decreases OPG
Increases RANKL
Net effect of increasing osteoclasts

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27
Q

What regulates serum calcium levels?

A

Parathyroid hormone
Vitamin D
Calcitonin

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28
Q

How does parathyroid hormone increase plasma calcium?

A

Increasing calcitriol synthesis > indirectly increases calcium absorption in duodenum
Mobilising calcium from bone
Reducing renal calcium excretion

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29
Q

How does calcitonin decrease plasma calcium?

A

Decreases oteoclast activity and calcium resorption from bone
Inhibits calcium reabsorption in kidney

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30
Q

How does calcitriol increase plasma calcium?

A

Increases intestinal absorption
Decreases renal excretion
Increases osteoclast activity

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31
Q

How is vitamin D synthesised?

A

In skin
- 7-dehydrocholesterol > cholecalciferol (vitamin D3) by UV rays
Dietary intake
- Cholecalciferol from animal products
- Ergocalciferol (vitamin D2) from plant products
In liver: vitamin D2 and D3 converted to 25-hydroxyvitamin D
In kidney: converted to calcitriol

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32
Q

What is hypocalcaemia?

A

Low serum calcium

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33
Q

When can hypocalcaemia occur?

A

Vitamin D deficiency

34
Q

What is hypercalcaemia?

A

High serum calcium

35
Q

When can hypercalcaemia occur?

A

Some malignancies

36
Q

What is hypophosphataemia?

A

Low serum phosphate

37
Q

When can hypophosphataemia occur?

A

Nutritional deficiency states

38
Q

What is hyperphosphataemia?

A

High serum phosphate

39
Q

When can hyperphosphataemia occur?

A

Renal failure

40
Q

What are the risk factors for osteoporosis?

A

Ageing
Post-menopause
Corticosteroid use

41
Q

What is osteoporosis?

A

Reduction in bone mass more than 2.5 standard deviations below norm for healthy 30 year old women

42
Q

What is osteopaenia?

A

Reduction in bone mass 1-2.5 standard deviations below norm for healthy 30 year old women

43
Q

When does peak bone mass occur?

44
Q

What effect does menopause have on changes in bone density?

A

Accelerates decline

45
Q

What effect does old age have on changes in bone density?

A

Steady state decline

46
Q

What is lost in osteoporosis?

A

Cells
Matrix
Loss of trabeculae and thinning

47
Q

What effect does the loss and thinning of trabeculae have in osteoporosis?

A

Reduces cross-sectional area > loads on bone relatively greater

48
Q

What types of drugs are antiresorptive agents in bone disorders?

A

Bisphosphonates
Selective oestrogen receptor modulators (SERMs)
RANK-L inhibitors
Calcitonin

49
Q

What types of drugs are anabolic agents in bone disorders?

A

Parathyroid hormone
Oral calcium
Oral vitamin D analogues

50
Q

What are the different structures of bisphosphonates?

A

Enzyme resistant analogues of pyrophosphate
- Accumulate in bone
Non-nitrogen containing bisphosphonates
- Accumulate in osteoclasts
Nitrogen containing bisphosphonates
- Higher potency
- Interfere with anchoring of osteoclasts

51
Q

How do bisphosphonates work?

A

Inhibit recruitment of osteoclasts
Promote apoptosis of osteoclasts
Incorporated in bone matrix > ingested by osteoclasts during bone resorption
Accumulate at site of bone mineralisation > remain for long periods

52
Q

What are the routes of administration of bisphosphonates?

A

Oral - daily/weekly

IV

53
Q

What is the absorption of bisphosphonates?

A

Poorly absorbed

Low bioavailability

54
Q

What are the adverse effects of bisphosphonates?

A

Adverse GI effects

- Oesophagitis

55
Q

What are the benefits of bisphosphonates?

A

Reduced fracture risk

56
Q

What are the possible risks of bisphosphonates?

A

Oesophageal cancer
Atypical fractures
Osteonecrosis of jaw

57
Q

What is the rationale of administering oestrogen?

A

Hormone replacement therapy to prevent bone density loss

58
Q

What does oestrogen do in the bone?

A

Decreases bone resorption by decreasing osteoclast
- Proliferation
- Differentiation
- Activation
Promotes osteoclast apoptosis
Increases life span of osteoblasts and osteocytes

59
Q

Does oestrogen increase bone mass?

A

No, maintains mass and slows loss

60
Q

What are the risks of administering oestrogen?

A

Increased risk of

  • Cardiovascular disease
  • Breast cancer
61
Q

What has replaced hormone replacement therapy in the treatment of osteoporosis?

62
Q

What is raloxifene?

A

SERM

  • Agonist at oestrogen receptors in bone and cardiovascular tissue
  • Antagonist at oestrogen receptors in mammary tissue and uterus
63
Q

How is raloxifene administered?

A

Once daily orally

64
Q

What are the risks of raloxifene?

A

Increased risk of

  • Deep vein thrombosis
  • Pulmonary embolism
65
Q

What is denosumab?

A

Human mAb binding soluble and membrane-bound RANK-L

66
Q

What does denosumab do?

A 
Inhibits RANK-L activity
Reduces osteoclast
- Differentiation
- Survival
- Activity
67
Q

What has treatment with denosumab been shown to do in post-menopausal women?

A

Decrease bone turnover markers

Increase bone density

68
Q

What is strontium ranelate?

A

Anti-resorptive and anabolic

Dual action bone agent

69
Q

Why does strontium ranelate have a black box warning?

A

Cardiovascular effects > increased incidence of myocardial infarction

70
Q

When is strontium ranelate used?

A

Last line of treatment in severe osteoporosis

71
Q

What type of calcitonin is used as treatment?

A

Salcatonin

- From salmon

72
Q

How is salcatonin administered?

A

Subcutaneous/intramuscular injection

Nasal spray

73
Q

When is salcatonin used?

A

Paget’s disease
Hypercalcaemia associated with neoplasia
With other agents in osteoporosis

74
Q

What is the paradoxical behaviour of parathyroid hormone?

A

Acutely promotes osteoblast development and activity

Continuous/high exposure promotes osteoclast activity

75
Q

When is parathyroid hormone used as a treatment?

A

Severe osteoporosis when alternatives are unsuitable

76
Q

How is parathyroid hormone administered?

A

Once daily subcutaneous

77
Q

What does parathyroid hormone administration increase the risk of?

A

Multiple myeloma

78
Q

When are oral calcium salts used?

A

Adjunctive therapy in osteoporosis

79
Q

What are the side effects of oral calcium salts?

A

GI disturbances

80
Q

When is vitamin D used?

A

In treatment of deficiency states

81
Q

In which diseases does vitamin D deficiency occur?

A

Rickets in children
Osteomalacia in adults
Endocrine dysfunction > hypoparathyroidism
Chronic renal disease > calcitriol not generated

82
Q

How is vitamin D administered?

A

Orally in form of

  • Calcitriol
  • Vitamin D2
  • Vitamin D3

MD1 Locomotor (17 decks)

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