Wk.10 L3 - Pharmacological treatment for osteoporosis

Question 1

LO

Answer 1

• Recall the cellular reasons that drive bone loss in osteoporosis
• Outline what the serum markers are of bone turnover are and how they respond to treatments
• Describe the difference between anti-resorptive and bone anabolic treatments
• Outline the mechanism of action of the two main anti-resorptives in clinical use
• Outline the mechanism of action of the two main anabolic agents in clinical use

Question 2

Osteoporosis

Answer 2

• characterized by compromised bone structure and strength, predisposing to an increased risk of fracture
• 1 in 3 women and 1 in 5 men over 50years

Question 3

Bone Turnover

Answer 3

Osteoblats
Osteocytes
Osteoclasts

Question 4

Bone turnover markers reflecting activity

Answer 4

Osteoblasts:
- Pro-collagen 1
- P1NP

Osteoclasts:
- Collagen 1
- CTX

Question 5

Osteoporosis – imbalanced bone remodelling

Answer 5

Too much bone absorption by osteoclasts and not enough formation by osteoblasts

Question 6

Pharmacological treatment of osteoporosis targets
remodelling

Answer 6

Anti-resorptive drugs
- Target osteoclasts, blocking their formation and function

Bone anabolic agents
- Boost osteoblasts activity and increased bone formation

Question 7

Therapeutics Which Regulate Bone Turnover

Answer 7

Bisphosphonates:
- Binds to bone mineral and are taken up by osteoclasts, causing loss of function
- Increases BMD and decreases risk of fracture
- Reduces bone turnover markers CTX and P1NP

Denosumab (Anti-RANKL):
- Blocks formation of osteoclasts rather than function
- By binding to the RANKL ligand, it inhibits the ligand from binding to osteoclasts precursers, preventing them from maturing into osteoclasts
- Reduces bone turnover markers CTX and
P1NP

Stopping Anti-RANKL medications leads to rapid bone loss

Question 8

Bone Anabolic Therapies

Answer 8

Parathyroid Hormone Therapy:
* Increases bone resorption indirectly by increasing osteoblasts signaling to osteoclasts to increase serum Ca 2+
* Continuous PTH (as if secreted by parathyroid) leads to a net increase in bone resorption
* Intermittent PTH (daily s.c.) achieves an overall anabolic effect

Teriparatide:
* Daily injection
* Increases bone density and P1NP and CTX remodelling markers

Question 9

Osteocytes

Answer 9

Release RANKL ligand which matures osteoclasts

Regulates osteoblast formation through release of scerostin which inhibits osteoblast activity

Anti-Sclerostin agents

Question 10

Anti-Sclerostin Agents

Answer 10

• Binds to and inhibits sclerostin
• Allowing osteoblasts to be active
• Increases BMD by increasing P1NP and decreasing CTX activity

Monthly injection

Question 11

Key Learning Outcomes

Answer 11

1) Recall the cellular reasons that drive bone loss in osteoporosis
- osteoclasts and osteoblasts imbalanced

2) Outline what the serum markers are of bone turnover are and how they respond to treatments
- CTX bone resorption – decrease with antiresorptive agents, P1NP bone formation – increases with anabolic agents

3) Describe the difference between anti-resorptive and bone anabolic treatments
- AR target osteoclast formation/function A- target osteoblasts

4) Outline the mechanism of action of the two main anti-resorptives in clinical use
- BP’s block osteoclast function, Dmab blocks osteoclast formation

5) Outline the mechanism of action of the two main anabolic agents in clinical use
- PTH increases osteoblast formation, Romo suppresses the anti-osteoblast protein sclerostin