Wk 15: Osteoporosis therapies Flashcards
What is the main cause of osteoporosis?
- Inc bone resorption (osteoclasts)
- Dec bone formation (osteoblast)
What is primary osteoporosis caused by?
- Menopause
- Age associated
What is secondary osteoporosis caused by?
- Malnutrition: Anorexia nervosa (Lack Vit D)
- Hypogonadism
- Hyperparathyroidism
- Pathological fractures
- Drug use
How are osteoclasts activated/inhibited?
- RANKL binds to RANK on osteoclast precursor -> prod active osteoclast
- OPG released by bones bind to RANKL to stop production
Give examples of simple preventative measures
- Oral calcium supplements inc bone mineral density in spine in postmeno
- Vit D
- HRT in peeri/post
- Smoking cessation
- Inc exercise
What are pharmacological treatment options?
Bisphosphonates:
- Oral: alendronic acid, risedronate
- Parenteral: zoledronic acid
- Denosumab (IV)
- HRT
- Raloxifene
- Teriparatide
What is the mechanism of bisphosphonates?
- Inhibit osteoclast proliferation
- Inhibit osteoclast activity
- Inhibit mevalonate pathway in osteoclast
- Result: red bone degradation + allows osteoblast function
How is bisphosphonates taken?
Once weekly on empty stomach to avoid binding to Ca2+ in food
What are the adverse effects of bisphosphonates?
- GI (oral)
- Alendronic + risedronate: severe oesophagitis + oesophageal strictures
- Headache, vertigo + MSK pain
- Transient pyrexia + flu like symptoms (IV)
- Osteonecrosis (IV)
What is the mechanism of action of denosumab?
- Mimics OPG
- Bind to RANKL to prevent osteoclast activation
- Use monoclonal antibody specific to RANKL
- 6 month injection
Outline the mechanism of action of HRT
- Helix 12 fold over E2 binding site
- ER binds to transcriptional cofactors + DNA
- Initiates ER target gene transcription
- Promote cellular growth + bone formation
Raloxifene
- ER antagonist in breast tissue
- ER agonist in osteoclast tf red osteoclast activity
What is the parathyroid hormone?
Indirectly stimulates intestinal absorption of calcium + promotes bone resorption:
- Osteoprogenitor cells become osteoclasts presence of PTH
- PTH promotes deep osteocytes to mobilize calcium
- Surface osteocytes stimulated by PTH to inc flow of calcium out of bone
- Dec renal excretion of calcium
What does the parathyroid hormone usually do?
- Binds PTH1R receptor
- Promotes bone resorption
Teriparatide (forteo)
- Anabolic: bone forming not anti-resorptive
- Recombinant portion of PTH
- Activates PTH receptor
- Activates osteoblast
- For severe cases
- Daily injection
- Stimulates new bone formation leading to inc bone mineral density
