Drugs Affecting Bone

Question 1

Why is there a greater incidence of osteoporotic fractures in the vertebrae and femoral neck?

Answer 1

because more trabecular bone is remodelled than cortical bone and these sites have a higher density of trabecular bone

Question 2

What alters bone remodelling?

Answer 2

age, load bearing exercise, hormones, drugs

Question 3

What stimulates osteoblasts to RANKL?

Answer 3

PTH, calcitriol and IL-6

Question 4

What stimulates osteoblasts to produce osteoid?

Answer 4

the cytokines released from the matrix when bone is broken down (IGF and TGF beta)

Question 5

What is the action of oestrogen on bone remodelling?

Answer 5

oestrogen decreases osteoclast activity

Question 6

What is the action of glucocorticoids on bone remodelling?

Answer 6

increases osteoclast activity and decreases osteoblast activity

Question 7

What is the action of calcitonin on bone remodelling?

Answer 7

decreases activity of osteoclasts

Question 8

In what ways does vitamin D increase plasma calcium?

Answer 8

increased intestinal absorption, decreased renal excretion, increased osteoclast activity

Question 9

In what ways does PTH increase plasma calcium?

Answer 9

increasing vitamin D synthesis, mobilising calcium from bone, reducing renal excretion

Question 10

What is osteoporosis?

Answer 10

reduction in bone mass more than 2.5 standard deviations below the norm for a healthy 30 year old woman

Question 11

What is osteopaenia?

Answer 11

a less severe form of osteoporosis (1-2.5 standard deviations below the norm)

Question 12

What bone changes are seen in osteoporosis?

Answer 12

trabecular thinning and loss of trabecular connectivity

Question 13

Which antiresorptive agents are used to treat bone disorders?

Answer 13

bisphosphonates, oestrogen receptor modulators, RANKL inhibitors

Question 14

Which bone anabolic agents are used to treat bone disorders?

Answer 14

PTH, calcium, vitamin D, calcitonin

Question 15

What is the mechanism of action of bisphosphonates?

Answer 15

absorbed into bone matrix because they are an analogue of pyrophosphate and are then ingested by osteoclasts during bone resorption and cause apoptosis of osteoclasts

Question 16

Why do bisphosponates only require administration once a week?

Answer 16

because they remain in the bone for a long period of time

Question 17

What are the adverse effects of bisphosphonates?

Answer 17

oesophagitis and possible oesophageal cancer, atypical fractures and osteonecrosis of the jaw

Question 18

What is the mechanism of action of raloxifene?

Answer 18

selective oestrogen receptor modulator - agonist at oestrogen receptor in bone and tissue and antagonist at oestrogen receptor in mammary tissue and uterus - decreases osteoclast proliferation, differentiation and activation and promotes osteoclasts apoptosis - increases life span of osteoblasts and osteocytes

Question 19

What is the mechanism of action of denosumab?

Answer 19

it is a human monoclonal antibody which binds RANKL and inhibits its activity and therefore reduce osteoclast activity

Question 20

What does PTH acutely promote?

Answer 20

osteoblast development and activity

Question 21

What does PTH in continuous high exposure promote?

Answer 21

osteoclast activity

Question 22

What are oral calcium used to treat?

Answer 22

as an adjunct therapy in osteoporosis

Question 23

What are the side effects of oral calcium?

Answer 23

GI disturbances

Question 24

What is vitamin D used to treat?

Answer 24

rickets, osteomalacia, hypoparathyroidism, chronic renal disease

Question 25

What is calcitonin used to treat?

Answer 25

hypercalcaemia associated with neoplasia