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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
What does calcitonin do in bone remodelling?
Decreased activity of osteoclasts
26
What does dexamethasone do?
Decreases OPG Increases RANKL Net effect of increasing osteoclasts
27
What regulates serum calcium levels?
Parathyroid hormone Vitamin D Calcitonin
28
How does parathyroid hormone increase plasma calcium?
Increasing calcitriol synthesis > indirectly increases calcium absorption in duodenum Mobilising calcium from bone Reducing renal calcium excretion
29
How does calcitonin decrease plasma calcium?
Decreases oteoclast activity and calcium resorption from bone Inhibits calcium reabsorption in kidney
30
How does calcitriol increase plasma calcium?
Increases intestinal absorption Decreases renal excretion Increases osteoclast activity
31
How is vitamin D synthesised?
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
32
What is hypocalcaemia?
Low serum calcium
33
When can hypocalcaemia occur?
Vitamin D deficiency
34
What is hypercalcaemia?
High serum calcium
35
When can hypercalcaemia occur?
Some malignancies
36
What is hypophosphataemia?
Low serum phosphate
37
When can hypophosphataemia occur?
Nutritional deficiency states
38
What is hyperphosphataemia?
High serum phosphate
39
When can hyperphosphataemia occur?
Renal failure
40
What are the risk factors for osteoporosis?
Ageing Post-menopause Corticosteroid use
41
What is osteoporosis?
Reduction in bone mass more than 2.5 standard deviations below norm for healthy 30 year old women
42
What is osteopaenia?
Reduction in bone mass 1-2.5 standard deviations below norm for healthy 30 year old women
43
When does peak bone mass occur?
30
44
What effect does menopause have on changes in bone density?
Accelerates decline
45
What effect does old age have on changes in bone density?
Steady state decline
46
What is lost in osteoporosis?
Cells Matrix Loss of trabeculae and thinning
47
What effect does the loss and thinning of trabeculae have in osteoporosis?
Reduces cross-sectional area > loads on bone relatively greater
48
What types of drugs are antiresorptive agents in bone disorders?
Bisphosphonates Selective oestrogen receptor modulators (SERMs) RANK-L inhibitors Calcitonin
49
What types of drugs are anabolic agents in bone disorders?
Parathyroid hormone Oral calcium Oral vitamin D analogues
50
What are the different structures of bisphosphonates?
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
How do bisphosphonates work?
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
What are the routes of administration of bisphosphonates?
Oral - daily/weekly | IV
53
What is the absorption of bisphosphonates?
Poorly absorbed | Low bioavailability
54
What are the adverse effects of bisphosphonates?
Adverse GI effects | - Oesophagitis
55
What are the benefits of bisphosphonates?
Reduced fracture risk
56
What are the possible risks of bisphosphonates?
Oesophageal cancer Atypical fractures Osteonecrosis of jaw
57
What is the rationale of administering oestrogen?
Hormone replacement therapy to prevent bone density loss
58
What does oestrogen do in the bone?
Decreases bone resorption by decreasing osteoclast - Proliferation - Differentiation - Activation Promotes osteoclast apoptosis Increases life span of osteoblasts and osteocytes
59
Does oestrogen increase bone mass?
No, maintains mass and slows loss
60
What are the risks of administering oestrogen?
Increased risk of - Cardiovascular disease - Breast cancer
61
What has replaced hormone replacement therapy in the treatment of osteoporosis?
SERMs
62
What is raloxifene?
SERM - Agonist at oestrogen receptors in bone and cardiovascular tissue - Antagonist at oestrogen receptors in mammary tissue and uterus
63
How is raloxifene administered?
Once daily orally
64
What are the risks of raloxifene?
Increased risk of - Deep vein thrombosis - Pulmonary embolism
65
What is denosumab?
Human mAb binding soluble and membrane-bound RANK-L
66
What does denosumab do?
``` Inhibits RANK-L activity Reduces osteoclast - Differentiation - Survival - Activity ```
67
What has treatment with denosumab been shown to do in post-menopausal women?
Decrease bone turnover markers | Increase bone density
68
What is strontium ranelate?
Anti-resorptive and anabolic | Dual action bone agent
69
Why does strontium ranelate have a black box warning?
Cardiovascular effects > increased incidence of myocardial infarction
70
When is strontium ranelate used?
Last line of treatment in severe osteoporosis
71
What type of calcitonin is used as treatment?
Salcatonin | - From salmon
72
How is salcatonin administered?
Subcutaneous/intramuscular injection | Nasal spray
73
When is salcatonin used?
Paget's disease Hypercalcaemia associated with neoplasia With other agents in osteoporosis
74
What is the paradoxical behaviour of parathyroid hormone?
Acutely promotes osteoblast development and activity | Continuous/high exposure promotes osteoclast activity
75
When is parathyroid hormone used as a treatment?
Severe osteoporosis when alternatives are unsuitable
76
How is parathyroid hormone administered?
Once daily subcutaneous
77
What does parathyroid hormone administration increase the risk of?
Multiple myeloma
78
When are oral calcium salts used?
Adjunctive therapy in osteoporosis
79
What are the side effects of oral calcium salts?
GI disturbances
80
When is vitamin D used?
In treatment of deficiency states
81
In which diseases does vitamin D deficiency occur?
Rickets in children Osteomalacia in adults Endocrine dysfunction > hypoparathyroidism Chronic renal disease > calcitriol not generated
82
How is vitamin D administered?
Orally in form of - Calcitriol - Vitamin D2 - Vitamin D3

MD1 Locomotor (17 decks)

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