Bones Flashcards
What is the mechanical role of bone?
Structural support and muscle attachment
What is the protective role of bone?
Protects vital organs
Bone marrow
What is the metabolic role of bone?
Ion homeostasis
Calcium and phosphate
What is bone?
Specialised connective tissues
Extracellular matrix calcifies
30% organic: collagen and non-collagenous protein
70% inorganic: calcification, formation of hydroxyapatite
What are the cells within bone?
Osteoclasts
Osteoblasts
Bone lining cells
Osteocyte
What is an osteoclast?
Bone resorption
What is an osteoblast?
Bone forming
What are bone lining cells?
Specialist inactive osteoblastlast
Initiate bone forming
What are osteocytes?
Mechanosensing cells
What is the basic structure of bone?
Cortical, compact bone
Spongy, trabecular bone
Surrounded by periosteum
What do osteoblasts do?
Formation of bone matrix
Regulation of mineralisation
Regulation of osteoclast differentiation
Precursors of bone living cells and osteocytes
What do osteoblasts differentiate from?
Stromal precursor cells
What do osteoblasts express?
RUNX2 and Osx
How do osteoblasts differentiate?
Unknown HOX genes Bone morphogenic proteins Wnt PTH
What can protect against osteoblast apoptosis?
Intermittent PTH
What do osteoclasts do?
Bone resorption
Calcium homeostasis
What do osteoclasts develop from?
Arise from mononuclear cells
Either from the marrow or circulating monocytes
What signals are necessary for osteocyte differentiation?
Macrophage colony stimulating factor
RANKL
What is the order of osteoclast differentiation?
Bone marrow precursor Pre-osteoclast Proliferate Fused prokaryon Active osteoclast
What does an active osteoclast express?
F4/80 -ve
Trap +ve
CTR +ve
Beta3 +ve
How do osteoclasts function?
Move by chemotaxis Cell is highly polarised Creates a sealed environment Secretes acids and enzymes Bone is resorbed by combination of enzymes Forms a Howships lacuna
What is the RANKL/OPG system?
Signalling between osteoblasts and osteoclasts
Receptor activator of Nf-kappabeta (RANK) is a receptor on osteoclasts
RANKL produced by osteoblasts and stromal cells and some lymphocytes
RANK+RANKL causes osteoclast differentiation and activation
What is osteoprogerin?
Osteoprogerin is a dummy receptor for RANKL
What happens if over express osteoprogerin?
Too much inhibition of bone resorption
Osteopetrosis
What can cause osteoporosis?
Loss of osteoprogerin
RANKL overexpression
What can cause osteopetrosis?
Overexpression of osteoprogerin
Absence of RANKL
Absence of RANK
Factors increasing RANKL expression?
Parathyroid hormone
Oestrogen deficiency
Inflammatory cytokines
Glucocorticoids
How do osteocytes form?
Osteoblasts are incorporated into the bone matrix
During bone ossification and mineralisation
Integrated into osteocyte network
What is the function of osteocytes?
Regulation of local mineralisation
Mechanosensing
Initiation of bone remodelling cycle
Sclerostin and BMPs
What regulates osteocytes?
Shear stress
Damage
Canalicular fluid flow
How does bone remodel in trabecular bone?
Bone resorption
Formation of osteoid
Osteoid mineralisation
New bone
How is cortical bone remodelled?
Via the Haversian system
What are bone remodelling units?
Cutting zone
Reversal zone
Closing cone
Where does bone grow?
Periosteal surfaces
What is the definition of osteoporosis?
A progressive systemic skeletal disease
Characterised by low bone mass
Micro-architectural deterioration
Increase in fragility and susceptibility
What fractures are common of osteoporosis?
Head of ulna wrist fracture (Colles’)
Spinal collapse
Vertebral fractures
Fratured neck of femur
What are the causes of osteoporosis?
Oestrogen deficiency
Glucocorticoids
Vitamin D/ calcium deficiency
Ageing
What does oestrogen do to the skeleton?
Maintain skeletal health
Oestrogen deficiency results in increased bone resorption
Oestrogen receptors are expressed in osteoblasts not osteoclasts
Oestrogen deficiency leads to increased expression of RANKL
Can oestrogen be used as a therapy?
Oestrogen treatment as HRT Given by mouth, patch or implant Reduces bone resorption Increase bone density Reduces fracture risk Complications of DVT, breast cancer, uterine cancer, heart disease and dementia
How do SERMs work?
Selective oestrogen receptor modulators
Tamoxifen
Increases bone mineral density
What is Raloxifene?
Increases bone mineral density at all sites
Decreases risk of breast cancer
Cardiovascular risk is uncertain
Partial agonist on bone, decreases BMD in pre-menopausal
What are bisphosphonates?
Alendronate
Potent inhibitor of bone resorption
Inhibits intracellular signalling pathway
Increases osteoclast apoptosis
What are advantages of bisphonates?
Bone selective Relatively few side effects Improve cortical and trabecular bone Once daily/weekly tablet Equal effect in men and women
What are the disadvantages of bisphonates?
Incorporated into the skeleton
Unknown long-term effect
Risk of blocking repair of microfractures
Uncommon fractures: diaphyseal of femur
Why is vitamin D important?
Vitamin D is essential for calcium absorption and osteoblast differentiation
What happens if vitamin D is absent?
Osteomalacia
Mild deficiency impairs osteoblast function
What happens to the parathyroid if calcium is deficient?
Secondary hyperparathyroidism
Stimulates osteoclastic activity
Increases resorption
PTH receptors on osteoblasts increase RANKL
How can we treat calcium and vitamin D deficiency?
Supplementation
Whats the effect of hyperparathyroidism?
Bone loss due to bone resorption
What is the effect of PTH injection?
Increased bone formation
Essential in differentiation of osteoblasts
What effect do glucocorticoids have on bone?
Fracture risk increases with the use of steroids
Decrease activity of osteoblasts
Mitigate osteoclasts
Treated with bisphosphonates or intermittent PTH injection
