Wk 15: Bone disorders + osteoporosis Flashcards
What are osteoblasts?
- bone forming: produce collagenase bone matrix
- Secrete alkaline phosphatase: promotes deposition of calcium phosphate salts to calcify bone
What are osteocytes?
Inactive mature bones after bone matrix formed
What are osteoclasts?
- Multinucleated cells concerned w/ bone resorption
- Remove bone matrix by phagocytosis, dissolve bone salts + release calcium + phosphate ions in circulation
Outline the mechanism of action of bone remodelling
- PTH, shear stress, TGF-B cause osteoblast precursor to express RANKL
- RANKL bind to RANK on osteoclast precursor
- Binding interaction w/ macrophage colony stimulating factor cause osteoclast precursor to diff. into mature osteoclast
- Mature osteoclast resorb bone, matrix bound factors (TGF-B, IGF-1), growth factors + cytokines released
- Stimulates osteoblast precursor to develop into mature osteoblast - refills resorption cavities excavated by osteoclast
What is the typical presentation of osteoporosis?
- Back pain
- Loss of height
- Fracture
What is the typical presentation of paget’s disease?
- Deformity of long bones
- Pain in hips
What is the typical presentation of osteomalacia?
- Generalised bone pain
- Muscle weakness
- Uncommon
What are the causes of osteoporosis?
- Result of endocrine disorder/malignancy
- Aging
- Postmeno women
- Men >50
- LT oral corticosteroids
How does menopause cause osteoporosis?
- Dec serum oestrogen
- Inc IL-1 + 6 + TNF
- Inc expression of RANK + RANKL
- Inc osteoclast activity
How does aging cause osteoporosis?
- Dec replicative activity of osteoprogenitor cells
- Dec synthetic activity of osteoblast
- Dec activity of matrix-bound growth factors
- Red physical activity
Outline the pathophysiologic of osteoporosis
- Inc cytokines = activation of osteoclast
- Deeper, larger resorption cavities in bone bc osteoclast longer lifespan
- Fragile bones bc mechanosensing is decreased tf microdamage in bone
- Bone fracture
What are the drugs that inc risk of osteoporosis?
- Oral glucocorticoids
- Pioglitazone
- PPI
- Thyroxine
- Phenytoin, CMZ
- Immunosuppressive agent
What are indicators of low bone mineral density?
- Low BMI
- Crohn
- Prolonged immobility
- Untreated premature meno
What is the T score for osteopenia?
-1 + 12.5
What is the T score for osteoporosis?
< -2.5
What is the lifestyle advice for preventing osteoporosis?
- Exercise: walking, jogging, rowing + weight lifting
- Calcium intake
- Oral bisphosphonates for prevention of postmeno osteo
What do bisphosphonates do?
Inhibit bone resorption + inc BMD by altering osteoclast activation + function
Give examples of oral bisphosphonates
- Alendronic acid
- Ibandronic acid
- Risedronate sodium
When are oral bisphosphonates recommended?
- Eligible for risk assessment
- 10 year probability of osteoporotic fragility fracture = 1%
Give examples of IV bisphosphonates
- Ibandronic acid
- Zoledronic acid
When are IV bisphosphonates recommended?
- Eligible for risk assessment
- 10 year probability of osteoporotic fragility fracture = 10%
- 10 year probability = 1% + difficulty taking oral bisphosphonates
What are the patient counselling on bisphosphonates?
- Oral on empty stomach + water only, no food for 30 minutes
- Don’t lie for at least 30 mins after alendronic acid
- Oral = GI disturbances
- Alendronic acid avoided if eGFR <35
- Zoledronic acid caution in severe hepatic impairment
What are the side effects of bisphosphonates?
- Oesophageal irritation
- Flu like
- GI disturbance
- Headache
- MSK pain
What is first line treatment of bisphosphonates?
- Oral
- IV zoledronic (5mg per year)/ teriparatide if intolerant
Selective oestrogen receptor modulator (SERM)
- Raloxifene
- Selective agonist or antagonist activities on tissues responsive to oestrogen
- Stim osteoblast + inhibit clast
- Agonist on bone + partially on cholesterol metabolism
- Antagonist hypothalamus, uterine + breast tissue
- 1st pass metabolism
Teriparatide
- Recombinant fragment of parathyroid hormone
- Stimulates new bone formation + inc structural integrity + bone strength
- Inc blast by activating blast in bone
- Red blast apoptosis
How is teriparatide given?
20 mcg OD SC injection for 24 months
What are the side effects of teriparatide?
- Nausea
- Oesophageal reflux
- Hypotension
Give examples of disorders involved in softening the bones
- Osteomalacia - calcium/phosphate deficient
- Rickets - Vit D deficient
What are drugs used for paget disease?
- Bisphosphonates
- Calcitonin
