ic14 osteoporosis pharmacology

Question 1

moa of biphosphonates

Answer 1

slow bone loss by increasing osteoclast cell death

Question 2

sources of calcium

Answer 2

PTH is released when low plasma calcium levels are detected
1) dietary = PTH increases vit D synthesis in kidney = increase calcium absorption from intestines
2) kidney = affected by parathyroid hormone = increase calcium reabsorption in the urine
3) bone = increase calcium release from bones (activate osteoclasts) via PTH + vit D

Question 3

vit D source

Answer 3

skin and UVB
convert 7 dehydrocholesterol = vit d3 (cholecalciferol) = stored in liver
= activated by kidney to 25(oh)vitD

PTH stimulates activation of vit D3 to 1,25 dihydroxyvitD by increasing 1-alpha hydroxylase

Question 4

what is denosumab

Answer 4

human monoclonal antibody against RANKL, required for binding with RANK receptors on osteoclasts for its formation, differentiation, activation, survival

Question 5

some adr of denosumab

Answer 5

MSK: muscle, back, bone or joint pain
GI: n/v, constipation or diarrhoea

slight tiredness

increased cholesterol levels

Question 6

why do not discontinue denuosumab?

Answer 6

increased risk of spinal column fractures when discontinued

Question 7

pregnancy status for denosumab

Answer 7

X for pregnancy

Question 8

place in thrapy for oestrogen in osteoporosis?

Answer 8

can help to maintain bone density
BUT
increased risk of breast cancer ,blood clots, stroke.

used for
(i) bone health in younger women
(ii) women with other menopausal sx requiring tx

Question 9

what is raloxifene

Answer 9

selective oestrogen receptor modulator
- mixed oestrogen receptor agonism and antagonism
- mimc effets of oestrogen on bone density in postmenopausal women

lowers risk of some breast cancers but still increases risk to blood clots
- also causes hot flashes

Question 10

role of calcitonin (moa and indication)

Answer 10

reduces BLOOD calcium and opposes effects of PTH
= inhibit osteoclast activity in bones

HOWEVER, not frequently used

naturally released by thyroid glands to regulate ca2+ lv in blood by decreasing it.

UPTODATE: Osteoporosis, postmenopausal (intranasal or injection): Treatment of osteoporosis in patients >5 years postmenopause.

Question 11

adr of calcitonin

Answer 11

red streaks on skin; redness of face, neck, arms, and occasionally upper chest

feeling of warmth

injection site reaction

Question 12

contraindications of calcitonin

Answer 12

hypersx and hypocalcaemia

Question 13

MOA of romosozumab (and what it is)

Answer 13

humanised mouse monoclonal antibody against sclerostin

removes sclerostin inhibition of canonical Wnt signalling pathway that regulates bone growth in osteoblasts (allows for differentiation of pre osteoblast to osteoblast) = increase bone formation and decrease bone resorption.

Question 14

indication of romosozumab

Answer 14

women at high risk of fracture
OR
who have failed or are intolerant to other osteoporosis therapies

Question 15

directions for use of romosozumab

Answer 15

once monthly for 12 months (SC injection)

Question 16

adr of romosozumab

Answer 16

MI, increased risk of CV death, stroke

hypersensitivity reactions (angioedema, erythema multiforme, urticaria, dermatitis, rash)

transient hypocalcemia

may also cause ONJ and atypical femur fractures

Question 17

contraindications of romosozumab

Answer 17

hypersx
uncorrected hypocalcaemia
history of mI or stroke (within the last year)

Question 18

what are the parathyroid hormone therapies and what is the direction of use?

Answer 18

parathyroid hormone similars EG teriparatide
intermittent high dose exposure to PTH has the opposite effect, suppressing bone resorption and favouring bone growth = increase bone strength

SC injection OD (once daily)
max 24 months

Question 19

adr of PTH therapy

Answer 19

serious calciphylaxis
worsening of previous stable cutaneous calcification
transient and minimal elevations of serum Ca or hypercalcemia

transient orthostatic hypotension

Question 20

c/i of PTH therapy

Answer 20

1) hypersensitivity

2) pre-existing hypercalcaemia

3) previous implant or external beam radiation therapy to the skeleton

4) other metabolic bone diseases (Paget’s disease, hyperparathyroidism)

5) skeletal malignancies, bone metastases
6) hereditary disorders predisposing to osteosarcoma

7) unexplained elevations of alkaline phosphatase
8) severe renal impairment

9) pregnancy

Question 21

when to use teriparatide?

Answer 21

when biphosphonates contraindicated or not effective?

women at high risk of fractures?

Question 22

what are the anabolic agents and what are the antiresorptive agents

Answer 22

anabolic:
- PTH therapies
- sclerostin inhibitors

antiresorptive
- bisphosphonates
- RANKL inhibitors
- ostrogen agonist/antagonist
- calcitonin