Osteoporosis Drugs

Question 1

Why is estrogen replacement not used to treat osteoporosis anymore?

Answer 1

Delays loss of bone density and decreases risk of fractures.

**BUT it increases risk of breast cancer and thromboembolic events.

Question 2

Bisphosphonates: MOA

Answer 2

Long-term inhibitors of bone resorption.

Bind to hydroxyapatite, Inhibit osteoclast action.
Long skeletal retention and duration of action.
Poor GI absorption, so must be given as IV injection.
Potency depends on side chains.

Can stay bound to hydroxyapatite for months to years.

Question 3

What are the bisphosphonates?

Answer 3

Alendronate, risedronate, zoledronic acid.

Question 4

Calcitonin: MOA

Answer 4

Rapidly acting inhibitor of bone resorption. It inhibits osteoclasts directly.

Rapid onset and offset of effect.

Binds to specific receptors on osteoclasts. Reduces osteoclast activity and number.

Activity of different forms depends on species of origin (salmon>human).

Not as powerful as bisphosphonates.

Question 5

Calcitonin: Method of administration

Answer 5

Polypeptide for subcutaneous or intranasal administration.

Question 6

What is inhibitor of RANK ligand with anti-osteoporotic activity?

Answer 6

Denosumab

Question 7

Denosumab: MOA

Answer 7

Monoclonal Ab against RANKL.

Binds to RANKL and prevents action of RANK.

Long duration of action: Months.

Question 8

How does RANKL work naturally?

Answer 8

If you have excess PTH, this activates osteoblasts.

But under continuous, prolonged stimulation by PTH, osteoblasts release RANKL which acts on osteoclast receptors (RANK) and activates them. This leads to increased bone resorption. This overwhelms effect of osteoblasts.

Denosumab blocks RANK ligand.

Reduces fracture risk greatly.

Question 9

What is a synthetic PTH analog?

Answer 9

Teriparatide

Question 10

Teriparatide: MOA

Answer 10

Anabolic agent which promotes new bone formation. Needs to be given in daily small amounts!!!

First 34 aa of human PTH.

Binds to specific receptors on osteoblasts. Increases osteoblast numbers and new bone formation.

Prolonged or continuous administration leads to increased osteoclast activation and bone loss.

Question 11

Teriparatide: Method of administration.

Answer 11

Polypeptide for subcutaneous daily administration.

Question 12

What is a selective estrogen receptor modulator?

Answer 12

Raloxifene

Question 13

Raloxifene: MOA

Answer 13

Anti-osteoporosis.

Anti-estrogen effects: Breast cancer

Pro-estrogen effects: Bone, serum lipids.

Question 14

Why isn’t this saving?

Answer 14

Not sure.