Osteoporosis Pharm

Question 1

What are 3 broad classes of drugs used for osteoporosis?

Answer 1

1) Vitamin D
2) Anti-resorptive agents
3) Anabolic agents

Question 2

What is the most cost effective way to diagnose osteoporosis?

Answer 2

1) Have you ever had a fragility fracture
2) Look for kyphosis and height loss

Question 3

What are 4 antiresorptive agents used for osteoporosis?

Answer 3

1) Bisphosphonates (eg. risedronic acid, alendronic acid, zoledronic acid)

2) RANK ligand inhibitors (eg. denosumab)

3) Oestrogen agonist/antagonist (eg. raloxifene)

4) Calcitonins

Question 4

What are 2 anabolic agents used in osteoporosis?

Answer 4

1) PTH therapies (eg. Teriparatide)

2) Sclerostin inhibitors (eg. romosozumab)

Question 5

What is Colecalciferol usually formulated with?

Answer 5

1) Calcium carbonate
2) Alendronic acid

Question 6

Vitamin D is a ________-soluble vitamin.

Answer 6

Fat-soluble

Question 7

What is the moa of colecalciferol?

Answer 7

1) Converted in liver to calcifedol
2) Calcifedol converted in kidney to active form calcitriol
3) Calcitriol:
i) ↑Ca absorption in gut
ii) maintains [Ca] and [PO4] optimal for bone mineralisation
iii) regulates PTH levels

Question 8

What are 3 AEs of colecalciferol?

Answer 8

1) Hypercalcemia
2) Hypercalciuria
3) GI discomfort (N&V, constipation)

Rare:
4) Allergic rxn (eg. rash, pruritus)

Question 9

What are 3 contraindications for colecalciferol?

Answer 9

1) Hypercalcemia
2) Hypervitaminosis D
3) Severe renal impairment

Question 10

What are 4 DDIs of colecalciferol?

Answer 10

1) Thiazide diuretics
- ↑risk of hyperCa

2) Corticosteroids
- ↓Ca abs → ↓Vit D efficacy

3) Orlistat, Bile acid sequestrants
- ↓fat abs → ↓Vit D abs

4) Anticonvulsants
- ↑Vit D metabolism → ↓efficacy

Question 11

What is the moa of bisphosphonates?

Answer 11

↑osteoclast cell death → ↓bone loss

Question 12

What are 3 examples of bisphophonates and how are they administered?

Answer 12

1) Risedronic acid (Oral)
2) Alendronic acid (Oral)
3) Zoledronic acid (IV)

Question 13

Oral bisphosphonates must be taken __________________.

Answer 13

Oral bisphosphonates:
- on empty stomach
- >240ml of water
- wait >30mins before taking food

Question 14

What are 4 AEs of oral bisphosphonates?

Answer 14

1) Atypical femoral fractures (prolonged use)
2) Severe bone/joint/muscle pain
3) Upper GI mucosal irritation
4) Ocular effects (eg. iritis, uveitis)
5) HypoCa
6) Osteonecrosis of jaw and external auditory canal

Oral:
7) Nausea
8) Abdo pain
9) Heartburn-like symptoms

IV:
10) Flu-like symptoms

Question 15

What are 4 contraindications of bisphosphonates?

Answer 15

1) HypoCa
2) Abnormalities of oesophagus that delay emptying
3) Severe renal impairment
4) Pregnancy
5) Lactation

Question 16

What is the moa of Denosumab?

Answer 16

Human mAb α-RANKL → prevent development of osteoblasts → ↓bone resorption

Question 17

How and how often is denosumab administered?

Answer 17

SQ every 6mths
- Co-administer 1000mg Ca + >400 IU Vit. D daily

Question 18

What are 4 AEs of denosumab?

Answer 18

1) Muscle/back/bone/joint pain
2) N&V
3) Constipation or diarrhoea
4) Slight tiredness
5) ↑cholesterol

Rare:
6) Atypical femur fractures
7) Osteonecrosis of the jaw

Question 19

Which 2 osteoporosis drugs CANNOT be discontinued without transition to another osteoporosis drug?

Answer 19

1) Denosumab
2) PTH therapies (eg. teriparatide)

Question 20

What are 2 contraindications of denosumab?

Answer 20

1) HypoCa
2) Pregnancy

Question 21

What are 5 factors that support the decision to treat a px for osteoporosis?

Answer 21

1) High fracture risk (FRAX)
2) Past fracture
3) Low BMD (T score <2.5)
4) >65 y/o
5) High risk of falls/bone loss

Question 22

Which osteoporosis drug should be avoided in a px with reflux esophagitis?

Answer 22

Oral bisphosphonates

Question 23

Which osteoporosis drug is safe for px with renal impairment?

Answer 23

Denosumab

Question 24

What Ix have to be performed before giving SQ denosumab or IV bisphosphonate therapy?

Answer 24

1) Check creatinine and 25-OH Vit. D levels
2) Replete Vit. D
3) Give Ca supplement if renal impairment

Question 25

What is the moa of raloxifene?

Answer 25

Selective oestrogen receptor modulator
- mixed oestrogen receptor agonism and antagonism
- mimics effects of oestrogen on bone density in postmenopausal women

Question 26

What are 2 main AEs of raloxifene?

Answer 26

1) Breast cancer (some ↑risk some ↓risk)
2) Blood clots
3) Hot flashes

Question 27

What are 2 indications for raloxifene?

Answer 27

1) Bone health in younger women
2) Women whose other menopausal symptoms also require treatment

Question 28

What is the moa of calcitonin?

Answer 28

1) ↓blood Ca → ↓PTH effects
2) Inhibit osteoclastic bone resorption

Question 29

How can calcitonin be administered?

Answer 29

1) Nasal spray
2) IV
3) SQ
4) IM

Question 30

What are 3 AEs of calcitonin?

Answer 30

1) Red streaks on skin
2) Injection site rxn
3) Warmth & redness of face, neck, arms, upper chest

Question 31

What are 2 contraindications of calcitonin?

Answer 31

1) Hypersensitivity
2) HypoCa

Question 32

What is the moa of romosozumab?

Answer 32

Humanised mouse mAb α-sclerostin
- removes sclerostin inhibition of canonical Wnt signalling pathway that regulates bone growth → ↑ bone formation + ↓bone resorption

Question 33

What is the main indicati0on for romosozumab?

Answer 33

Women at high risk of fracture/intolerant to other osteoporosis therapies

Question 34

How is romosozumab administered?

Answer 34

SQ once monthly for 12 mths

Question 35

What are 3 AEs of romosozumab?

Answer 35

1) MI
2) CV death
3) Stroke
4) Transient HypoCa
5) HS rxn

Rare:
6) Osteonecrosis of the jaw
7) Atypical femur fractures

Question 36

What are 3 contraindications of romosozumab?

Answer 36

1) Hypersensitivity
2) Uncorrected hypoCa
3) Hx of MI/stroke within 1 year

Question 37

How is Teriparatide administered?

Answer 37

once daily for max 24mths in lifetime

Question 38

What are 4 AEs of Teriparatide?

Answer 38

1) Serious calciphylaxis
2) Worsening of precious stable cutaneous calcification
3) Transient orthostatic hypotension
4) Transient and minimal hyperCa

Question 39

What is the moa of teriparatide?

Answer 39

PTH analogue → ↑bone formation and bone strength

Question 40

What are 4 AEs of Teriparatide?

Answer 40

1) Hypersensitivity
2) Pre-existing hyperCa
3) Skeletal malignancies/bone metastases
4) Metabolic bone diseases (eg. Paget’s disease, hyperparathyroidism)
5) Unexplained ↑ALP
6) Previous implant/external beam radiation therapy to skeleton
7) Hereditary disorders predisposing to osteosarcoma
8) Severe renal impairment
9) Pregnancy