Osteoporosis

Question 1

What is bone made of?

Answer 1

Hydroxyapatite crystals
Collagen

Question 2

Function bone? (2)

Answer 2

Shape and support
Storage calcium and phosphate

Question 3

State 3 main types cell in bone?

Answer 3

Osteoblasts- build bone- osteoid
Osteoclasts- digest bone- remodel
Osteocytes- osteoblasts trapped in bone- regulate mineral dep

Question 4

What type of collagen is bone?

Answer 4

Type 1

Question 5

What are 2 types of mature bone?

Answer 5

Compact (lamellar)- replaces woven bone
Spongy (trabecular

Question 6

What is first bone laid down?
Property?

Answer 6

Immature (woven) bone
Matrix- osteoid not mineralised
Irregular arranged

Question 7

What is split between organic and inorganic in bone matrix?

Answer 7

40% organic
60% inorganic

Question 8

What is bone made of?

Answer 8

Organic
Collagen- type 1- tensile strength
Proteoglycans- compressive strength
Matrix proteins- promote bone formation and bone min.

Inorganic
Calcium hydroxyapatite- compressive strength

Question 8

What is bone made of?

Answer 8

Organic
Collagen- type 1- tensile strength
Proteoglycans- compressive strength
Matrix proteins- promote bone formation and bone min.

Inorganic
Calcium hydroxyapatite- compressive strength

Question 9

What is origin of osteocytes?

Answer 9

Mesenchymal

Question 10

Osteoclast mono or multinucleated?

Answer 10

Multinucleated

Question 11

Outline how bone remodelled?

Answer 11

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

Question 12

What activates osteoclasts?
What prod it?

Answer 12

RANK ligand- prod osteoblasts

Question 13

What inhibits RANK ligand?
What prod it?

Answer 13

Osteoprotegerin
Osteoblasts

Question 14

Function Rank ligand?

Answer 14

Produced osteoblasts
Stimulate osteoclast bone resorption

Question 15

Function OPG?

Answer 15

Inhibit osteoclast differentiation

Question 16

Does osteoclast inhibit or increase bone resorption?

Answer 16

Inhibit

Question 17

Name 2 things decrease bone resorption?

Answer 17

OPG
Calcitonin

Question 18

Name two things stimulate osteoclast activation?

Answer 18

RankL
PTH- stimulate adenyl cyclase- stimulate RankL prod

Question 19

State 4 steps of fracture healing?

Answer 19

1) Haematoma formation
2) Bone generation- fibrocartilaginous callus formed
3) Bony callus formation
4) Bone remodelling

Question 20

Explain fracture healing?

Answer 20

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

Question 21

State 3 bone diseases?

Answer 21

Osteoporosis
Osteopenia
Osteomalacia

Question 22

Define osteoporosis?

Answer 22

Bone brittle and fragile- loss tissue and reduced mineralisation
Increased resorption compared formation
Bone mineral density of -2.5 SD compared reference

Question 23

Define osteopenia?

Answer 23

Protein and mineral content decreased
BMD of -1
Rickets

Question 24

Define osteomalacia?

Answer 24

Softening bone- mineralisation doesn't occur Deficiency vit D/calcium

Question 25

Function vitamin D?

Answer 25

Aid absorption calcium

Question 26

State uses calcium?

Answer 26

Neurotransmission Muscle contraction Hormone secretion Clotting cascade

Question 27

What are 3 molecules regulate amount calcium? Where synthesis/secrete

Answer 27

Calcitriol (vit D)- synthesis kidney PTH- parathyroid glands Calcitonin- thyroid glands

Question 28

Function vitamin D?

Answer 28

Increase intestinal absorption calcium

Question 29

Explain vit D synthesis?

Answer 29

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

Question 30

What occurs once calcitriol synthesised?

Answer 30

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

Question 31

Where does calcium exist in body?

Answer 31

99% bone 0.99 blood 0.01 cells

Question 32

How much calcium?

Answer 32

1200g

Question 33

What form does calcium exist in blood (3)?

Answer 33

Free ionised- diffusible, biologically active Bound anions- diffusable, not biologically active Bound proteins- albumin- not diffusable, not biologically active

Question 34

What protein does calcium normally bind to?

Answer 34

Albumin

Question 35

What occurs if low calcium in blood?

Answer 35

Reduce inhibition of chief cells in PTH gland Additional PTH secreted Raise calcium lvls

Question 36

What cells secrete PTH?

Answer 36

Chief cells

Question 37

How does PTH raise blood calcium lvls?

Answer 37

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

Question 38

What inhibits secretion PTH from chief cells in parathyroid gland? Why?

Answer 38

PTH and calcitriol inhibit secretion PTH from parathyroid gland Negative feedback loop- ensure blood calcium lvls don't rese past normal range

Question 39

What occurs if calcium in blood rises above normal range?

Answer 39

Parafollicular cells in thyroid gland secrete calcitonin Calcitonin inhibit osteoclasts- reduce bone resorption

Question 40

What decrease calcium lvls? How?

Answer 40

Calcitonin- inhibit osteoclasts- decrease bone resorption

Question 41

What are main constituents of hydroxyapatite?

Answer 41

Calcium Phosphate

Question 42

What occurs if calcium reabsorption increases?

Answer 42

Phosphorous excretion Inverse relationship