Drugs Affecting Bone

Question 1

Osteoid is made up by

Answer 1

Collagen, cytokines and growth factors

Question 2

how much bone is remodelled per year in adults?

Answer 2

25% trabecular

3% cortical

Question 3

osteoporosis occurs at sites of high [trabecular bone]

Answer 3

Neck of femur

Vertebrae

Question 4

the reabsorption of bone causes the release of cytokines from the mineralised osteoid such as —1— and their function is to activate —-2—- and induce —3—

Answer 4

1 IGF and TGF-ß
2 Osteoblast
3 Bone deposition

Question 5

hormones that decrease osteoclast activity include?

Answer 5

oestrogen, calcitonin

Question 6

hormones that increase osteoblast activity?

Answer 6

PTH, embedded cytokines, calcitonin

Question 7

some of the functions of calcitriol include?

Answer 7

Increases intestinal CA+2 absorption
Decreases renal excretion
Increases osteoclast activity

Question 8

some of the functions of PTH include?

Answer 8

increases osteoblast production of RANKL
Decreases osteoblast production of Osteoprotegerin
Increases kidney hydroxylation of vitamin D to its active form
reduces renal Ca+2 excretion

Question 9

some of the functions of calcitonin include?

Answer 9

decreases osteoclast activity (by inducing OPG production)
increases bone deposition
decreases Ca reabsorption from the kidney

Question 10

What is the definition of osteoporosis?

Answer 10

reduction in bone mass of more than 2.5 SD bellow the norm for healthy 30yo women
[loss of both cells and matrix]

Question 11

what is the definition os osteopaenia?

Answer 11

reduction in bone mass 1-2.5 SD bellow the norm for healthy 30yo women

Question 12

what are some of the changes observed in osteoporosis?

Answer 12

trabecular thinning

loss of trabecular connectivity

Question 13

what are the main two types of drugs used in bone disorders?

Answer 13

Block osteoclast Activity (Antiresorptive Agents)

Boost osteoblast activity (Bone Anabolic Agents)

Question 14

Block osteoclast Activity (Antiresorptive Agents) include

Answer 14

*Biphosphonates
Selective oestrogen receptor modulators
RANKL inhibitors

Question 15

Boost osteoblast activity (Bone Anabolic Agents) include

Answer 15

Vitamin D analogues
PTH
Ca+2
Vitamin D

Question 16

how do biphosphonates work? [alendronate]

Answer 16

Deposited into bone by osteoblasts
Released and phagocytosed by osteoclast
induces apoptosis of the osteoclast and inhibits their recruitment

Question 17

Biphosphonates are

Answer 17

Enzyme Resistant Analogues of pyrophosphate (P-O-P)

Question 18

how often do biphosphonates need to be administered?

Answer 18

once a week but they persist in bone for a long time
patient must walk or be sited after ingestion (risk of oesophagitis –> lead to increased risk of oesophageal cancer if taken for more than 3 years)
once taken it is fo’life yo

Question 19

how does oestrogen work?

Answer 19

Decreases reabsorption
Decreases differentiation and proliferation of osteoclasts
Promotes osteoclast apoptosis

Question 20

oestrogen analogues increase bone mass T/F

Answer 20

F, just maintenance of left behind and slows bone loss

Question 21

What medication is given instead of oestrogen (as it has a risk for cardiovascular complications and breast cancer?)

Answer 21

Selective Oestrogen Receptor Modulators (SERMs) [Raloxifene]

Question 22

mechanism of action of SERMs

Answer 22

Agonist at cardiovascular tissue and bone

Antagonist at mammary tissue and uterus

Question 23

Mechanism of action of RANKL inhibitors [denosumab]

Answer 23

binds to Receptor Activator of Nuclear Kappa Beta ligand (RANKL) to block its binding to RANK on osteoclasts (necessary for differentiation, survival and activity)

Question 24

RANKL inhibitors are able to

Answer 24

decrease bone turnover and increase bone density

Question 25

PTH activity on bone depends on —1– in what way

Answer 25

[] and periodicity of exposure
Low dosages causes anabolism of bone
High prolonged doses causes catabolism of bone

Question 26

Oral calcium salts has as a side-effect

Answer 26

GIT disturbances

Question 27

Vitamin D is used in the treatment of

Answer 27

deficiency of Vitamin D
Hypoparathyroidism
Chronic Renal Disease

Question 28

what main forms of vitamin D are available? and how is it used?

Answer 28

Vit D2 [ergocalciferol] (for liver conversion)
Calcitriol
–> prophylactically

Question 29

is treatment recommended in women with osteopenia?

Answer 29

no, except if there are fractures

Question 30

What si the recommended treatment for osteoporosis?

Answer 30

HRT (between 50-60)

>60 Raloxifene and Biphosphonates Ca+ and VitD