Osteoporosis

Question 1

Desribe the MoA of bisphosphonates

Answer 1

Bisphosphonate molecules attach to osteoclasts where they disrupt bone resorption

Question 2

Describe the indications and side effects of bisphosphonates

Answer 2

Post-menopausal osteoporosis
Male osteoporosis
Corticosteroid induced osteoporosis
Osteoporosis – primary prevention

Side effects:
GI upset and osteonecrosis of jaw; atypical fractures

Question 3

List some notable information on bisphosphonates, including its compliance and therapeutic effect, and include examples

Answer 3

EXTRA:
- poor compliance: Weekly medications, Risendronate now monthly, IV Zolendronic Acid – annual infusion
- 50% compliance for orals
- improves bone density
reduced compact and trabecular bone fractures

e.g.s alendronate risendronate

Question 4

Describe hte MoA and indications of SERM

Answer 4

Antiresorptive
Acts on estrogen receptors andindicated in post-menopausal osteoporosis

• Acts on estrogen receptors in bone and not in the breast tissue

Question 5

Decribe the effects of SERM

Answer 5

Improves boen density and reduces vertebral bone fractures

Question 6

Describe the indications and extra information on calcitriol

Answer 6

• antiresorptive
  indication: osteoporosis
• improves bone density but does not reduce bone fractures

Question 7

Describe MoA and indications of RANKLi

Answer 7

MoA:

Monoclonal antibody, fully human, to the receptor activator of RANKL. Inhibition of osteoclast formation

• Denosumab is an IgG2 immunoglobulin isotype, which has a long half-life and allows for subcutaneous (SC) injection of this agent every 6 months.
  
  • if not taken within window, increased risk of fractures. Commitment is important. Move patient to a different treatment e.g. bisphosphonates if deno no longer suitable

Indications:
Post menopausal osteoporosis
Male osteoporosis
Osteoporosis – primary prevention

Question 8

Provide an example of a RANKLi and comment on its therapeutic effects

Answer 8

Denosumab

Improves bone density
Reduces compact, and trabecular bone fractures (v, non-v, hip) in post meno

Question 9

Describe the MoA and indications of parathyroid hormone

Answer 9

Anabolic
MoA:PTH homolog. Intermittent exposure activates osteoblasts.

• Chronically elevated PTH will deplete bone stores.
• Intermittent exposure to PTH - activate osteoblasts more than osteoclasts. -
• Once-daily injections of teriparatide have a net effect of stimulating new bone formation leading to increased bone mineral density.

Indications:Post-menopausal osteoporosis

Question 10

Describe side effects and one example of PTH homolog

Answer 10

Sarcoma if used for longer then 18 months

Teriparatide

Question 11

Describe dual agents

Answer 11

Strontium Ralenate

Dissociates bone remodelling – increases bone formation. Induces preosteoblasts. Inhibits osteoclast formation.

SEs: Hypertension, PH and CVA, Thrombosis

Extra: Reduces compact and trabecular bone fractures.

Question 12

Describe romosozumab

Answer 12

Romosozumab
- Sclerostin is produced by osteocytes.
- increase bone resorption and decrease bone formation
- Lack of sclerostin – increase bone density
- Romosozumab monoclonal antibody that binds to sclerostin and inhibits its action
- 2 injections -monthly subcutaneous injections