Bone and Oesteoporosis Flashcards
What is the bone trabecular structure composed of?
Bone is predominantly composed of Type I Collagen fibres that mineralise
• Cancellous bone (spongy bone) has a complex trabecular structure (provides strength without weight).
• Bone tissue is cellular, highly vascularised
What are osteoclasts?
Monocytes that are fused together
Bone resorption
Lifespan of 12 days
What are osteoblasts
Responsible for bone formation
Lifespan of 2-100days
What are osteocytes?
Responsible for local mineral deposition and bone matrix
Stimulate preosteoclasts to form osteoclasts
Lifespan 25 years
How do osteoblasts and osteoclasts control the degree of bone reabsorption?
- RANK Ligand (RANKL) is secreted by osteoblasts. RANKL binds to RANK receptor on osteoclasts and activates them.
- Osteoblasts also secrete osteoprotegerin (OPG) * OPG acts as a decoy receptor for RANKL
* Balance of RANKL/OPG determines the degree of bone resorption
What is osteopenia?
Increase bone loss but not serious of a problem
What is osteoporosis?
Loss of bone, additional bone loss
Most common bone disease
What are the risk factors of osteoporosis ?
Age
Female
Menopause (hormone driven) - estrogen controlled
Family history
Rheumatoid arthritis and IBD/Crohn’s
Nutrition - low calcium and vitamin D
Smoking, alcohol, caffeine
Lack of physical activity
How is osteoporosis diagnosed?
Mainly dual energy X-ray absorptiometry (DEXA) scan - measures bone mineral density (BMD) g/cm2
why is there fracture risk of osteoporosis?
Increases with age as bone mass declines
Reduced calcium absorption makes bones weaker and susceptible to fracture upon a fall
High incidence, particularly in females
Common sites are the wrist, vertebrae, hi
How you assess fracture risk?
FRAX tool based on BMD and clinical risk factors
Clinical risk factors:
Age
Gender
BMI
previous fracture
Smoker
GC drug use
RA
Excessive alcohol
Secondary osteoporosis
What are the main aims of osteoporosis drug therapies?
- Increase bone mineral density
- Reduce fracture risk
What are some therapies for osteoporosis?
- Hormone replacement therapies (HRT)
- Known that estrogen is important for maintenance of bone mass
- Estrogen deficiency increases risk of osteoporosis and osteoporosis-linked
fracture - Decline in estrogen levels in post-menopausal women corresponds to steeper decline in bone mass
- Bisphosphonates ( first line treatment )
-high affinity for bone tissue
- long half life (10years)
- bisphosphonates engulfed by osteoclasts which inhibits bone resorption
What is targeted in osteoporosis therapy?
Osteoclasts- targeting (mainly used)
Osteoblasts targeting
What are some examples of bisphophonates?
alendronate
ibandronate
risedronate
zoledronic acid (by IV infusion)
what drugs are targeting osteoblasts?
- synthetic PTH - boosts activity for osteoblast maturation
- Wnt - non-canonical WNT signal = increases LRP stimulation = canonical WNT signal = bone formation
