Osteoporosis Flashcards
What is bone made of?
Hydroxyapatite crystals
Collagen
Function bone? (2)
Shape and support
Storage calcium and phosphate
State 3 main types cell in bone?
Osteoblasts- build bone- osteoid
Osteoclasts- digest bone- remodel
Osteocytes- osteoblasts trapped in bone- regulate mineral dep
What type of collagen is bone?
Type 1
What are 2 types of mature bone?
Compact (lamellar)- replaces woven bone
Spongy (trabecular
What is first bone laid down?
Property?
Immature (woven) bone
Matrix- osteoid not mineralised
Irregular arranged
What is split between organic and inorganic in bone matrix?
40% organic
60% inorganic
What is bone made of?
Organic
Collagen- type 1- tensile strength
Proteoglycans- compressive strength
Matrix proteins- promote bone formation and bone min.
Inorganic
Calcium hydroxyapatite- compressive strength
What is bone made of?
Organic
Collagen- type 1- tensile strength
Proteoglycans- compressive strength
Matrix proteins- promote bone formation and bone min.
Inorganic
Calcium hydroxyapatite- compressive strength
What is origin of osteocytes?
Mesenchymal
Osteoclast mono or multinucleated?
Multinucleated
Outline how bone remodelled?
Activation
Pre-osteoclasts attracted to remodelling sites- activated by RANK ligand produced by osteoblasts
Osteoclasts form
Resorption
Osteoclasts gif cavity (resorption pit) in spongy bone- release acids/cathespin K
Calcium released blood
Reversal
Mesenchymal stem cells differentiate into pre-osteoblasts
Formation
Preosteoblasts mature into osteoblasts at surface pit
Release osteoid at site- form soft, non-mineralised matrix
New matrix mineralised- calcium and phosphorus
Quiescence
Site remains dormant
Osteoprotegerin mop up RANK ligand prevent unnecessary remodelling
What activates osteoclasts?
What prod it?
RANK ligand- prod osteoblasts
What inhibits RANK ligand?
What prod it?
Osteoprotegerin
Osteoblasts
Function Rank ligand?
Produced osteoblasts
Stimulate osteoclast bone resorption
Function OPG?
Inhibit osteoclast differentiation
Does osteoclast inhibit or increase bone resorption?
Inhibit
Name 2 things decrease bone resorption?
OPG
Calcitonin
Name two things stimulate osteoclast activation?
RankL
PTH- stimulate adenyl cyclase- stimulate RankL prod
State 4 steps of fracture healing?
1) Haematoma formation
2) Bone generation- fibrocartilaginous callus formed
3) Bony callus formation
4) Bone remodelling
Explain fracture healing?
1) Haematoma formation
Blood vessels in broken bone tear and haemorrage
Clotted blood- haematoma at break site
Clotting process
Bone cells deprived nutrients die- osteocytes
2) Bone Generation - fibrocartilaginous callus formed
Capillaries grow- dead cells clear
Fibroblasts and osteoblasts start reform bone
Fibroblasts- collagen fibres
Osteoblasts- spongy bone (osteoid)
Fibrocartilaginous callus- hyaline and fibrocartilage
3) Bony callus formation
Fibrocartilaginous callus converted into bony callus
Spongy bone takes 2 months to join
Non-union if no healing in 26 weeks
4) Bone remodelling
Bony callus remodelled osteoclasts and osteoblasts
Simple woven to lamellar
Compact bone added
State 3 bone diseases?
Osteoporosis
Osteopenia
Osteomalacia
Define osteoporosis?
Bone brittle and fragile- loss tissue and reduced mineralisation
Increased resorption compared formation
Bone mineral density of -2.5 SD compared reference
Define osteopenia?
Protein and mineral content decreased
BMD of -1
Rickets
Define osteomalacia?
Softening bone- mineralisation doesn’t occur
Deficiency vit D/calcium
Function vitamin D?
Aid absorption calcium
State uses calcium?
Neurotransmission
Muscle contraction
Hormone secretion
Clotting cascade
What are 3 molecules regulate amount calcium?
Where synthesis/secrete
Calcitriol (vit D)- synthesis kidney
PTH- parathyroid glands
Calcitonin- thyroid glands
Function vitamin D?
Increase intestinal absorption calcium
Explain vit D synthesis?
1) 7-dehydrocholesterol converted into cholecalciferol (vitamin-D3) under influence UV radiation
2) In liver cholecalciferol converted 25-hydroxyvitaminD by 25-hydroxylase
3) In kidney 1a-hydroxlase converts 25-hydroxyvitaminD into 1,25-dihydroxyvitaminD (calcitriol)
Metabolically active
What occurs once calcitriol synthesised?
Released bloodstream
Stimulate intestinal epithelial cells increase synthesis calbindin D proteins
Calbindin-D proteins facilitate transport calcium from intestinal brush border to basolateral membrane- released into blood
Intestinal absorption calcium increased
Where does calcium exist in body?
99% bone
0.99 blood
0.01 cells
How much calcium?
1200g
What form does calcium exist in blood (3)?
Free ionised- diffusible, biologically active
Bound anions- diffusable, not biologically active
Bound proteins- albumin- not diffusable, not biologically active
What protein does calcium normally bind to?
Albumin
What occurs if low calcium in blood?
Reduce inhibition of chief cells in PTH gland
Additional PTH secreted
Raise calcium lvls
What cells secrete PTH?
Chief cells
How does PTH raise blood calcium lvls?
Increase bond resorption- PTH bind osteoblast- increase expression RANKL- stimulate preosteoclast to osteoclast- reabsorb bond and release calcium
Increase renal reabsorption calcium- PTH cause expression channels in DCT- increase resorption calcium- increase excretion phosphate
Increase synthesis calcitriol- in kidney PTH increases expression 1a Hydroxylase- catalyse conversion inactive 25-hydroxycholecalciferol into calcitriol
What inhibits secretion PTH from chief cells in parathyroid gland?
Why?
PTH and calcitriol inhibit secretion PTH from parathyroid gland
Negative feedback loop- ensure blood calcium lvls don’t rese past normal range
What occurs if calcium in blood rises above normal range?
Parafollicular cells in thyroid gland secrete calcitonin
Calcitonin inhibit osteoclasts- reduce bone resorption
What decrease calcium lvls? How?
Calcitonin- inhibit osteoclasts- decrease bone resorption
What are main constituents of hydroxyapatite?
Calcium
Phosphate
What occurs if calcium reabsorption increases?
Phosphorous excretion
Inverse relationship
