bone physiology

Question 1

bone fucntions include:

Answer 1

– support and protection
– movement
– a Ca2+ (and PO4
3-) store
– a bone marrow store

Question 2

bone is a —- matrix which is mainly —– with some —–

Answer 2

-mineralised organic
- type 1 collagen fibers ( 90-95%)
which provides tensile strength with some proteoglycans ~5% which provides compressive strength

Question 3

2 types of bones:
1 —- :
– also known as ‘cortical bone’
– dense, stiff structure
– low porosity (5-25%)
– most human bone is compact (~80%)
2- —- :
– also known as ‘cancellous or spongy bone’
– spongy, light structure
– high porosity (up to 70%)
the combination of these 2 types provide —– despite being —-

Answer 3

• compact
• trabecular
• mechanical strength
• lightweight

Question 4

• in long bones —- from the shaft aka diaphysis
• trabecular bone is found at the — aka —–
• between epiphysis and the metaphysis is the —–
• Growth of the long bones occur at —- the until —– when it fuses w —-

Answer 4

• cortical bone
• ends aka epiphysis/metaphysis
• epiphyseal growth plate
• growth plate until 18
• fuses w metaphysis

Question 5

1-durig fatal life , bones are modelled in —- and then —- aka —-
2- During childhood/adolescence, cartilage proliferates at the ——- controlled by ——–
3- once laid down the collagen is mineralised with —- during —– and its now —-

Answer 5

• cartlige ( type 1 colagen )
• mineralised
• ossification
• growth plate elongating the long bones
• controlled by: growth hormone and insulin-like growth hormone (IGF-1)
• hydroxipiate
• ossification
  -hydroxyapatite formula: Ca10(PO4)6(OH)2

Question 6

-the —- form around
Haversian canals containing
blood vessels and nerves
- each osteon is formed of —-
- between lamellae are — where —- are located

Answer 6

osteon
concentric rings or lamellae
– separated from the adjacent
osteon by a cement line
- lacunae
- osteocytes

Question 7

3 mian types of cells bones:
1- —– :
– promote bone formation
– lay down osteoid and initiate mineralisation
2- —– :
– promote bone reabsorption
– remove mineralisation and liberate Ca2+ and PO4
3- —–:
– transfer mineral from inner regions of bone to the growth surfaces

Answer 7

1- osteoblast
2- osteoclast
3- osteocyte

Question 8

-Osteoblasts are modified ——derived from —— stem cells
- osteoblast can lay down —- and facilitate the ——
- excess osteoblast are —- some get embedded in the lining of the new bone and become become —– -in the lacunae between the lamellae

Answer 8

• fibresblast
  -mesenuchimal stem cells
• osteoid of type 1 collagen
• ossification of the osteiod
• removed
• osteocytes

Question 9

-osteocyte are derived from —- which transfers — from —- of the bone to —- surfaces
- osteocytes have —- into the bone and can sense — on the bone
- these projections passes — to —

Answer 9

• osteoblast
• minerals
• inner region
• growth surfaces
• cytoplasmic projections
• mechanical load
• info
• osteoblast

Question 10

-Osteoclasts are derived from the ——
- attracted to and resorb —- and create —– pits
-Solubilise the mineral at —- , —- the organic matrix ( requires factors from ——- )
-Indirectly stimulated by —- that promotes —- it:

Answer 10

-macrophage lineage of cells
-mineralized bone and create resorption pits
- low pH , phagocytose
- osteoblasts
- PTH
- promotes bone reabsorption
- it:
– remove mineralisation and liberate Ca2+ and PO4
3-
– PTH acts on osteoblasts and their activation ultimately activates osteoclasts

Question 11

bone remodelling:
From maturity, while bone growth has stopped —- doesnt
– adult skeleton remodelled every 10 years
– 1 million BMUs operating at any one time (3-4 million BMUs initiated each year)

Answer 11

bone turnover

Question 12

bones are constantly balancing the mineralisation through activation of:

Answer 12

osteoblast and osteoclast which :
– enables adaptation to mechanical loading
– enables fracture healing
– prevents “bone fatigue” by continually renewing bone matrix
in response to: osteocyte signalling, PTH/vitamin D signalling and other
growth factors

Question 13

Osteocyte detected mechanical strain is relayed to ——

Answer 13

osteoblast and also PTH signalling

Question 14

-Osteoblasts stimulate —- to activate circulating monocytes
- monocytes become —- and move to region to be —-
- growth factors stimulates —– leading to lat down of new — for mineralisation

Answer 14

NFkB ( – increase NFκB activator RANK-L and decrease NFκB inhibitor osteoprotegrin )
- osteoclast
- reabsorbed
- osteoblast formation
- osteoid
( over the ~120 day cycle there is no net loss of bone)

Question 15

bone remodelling :

Answer 15

• Resorption phase (2 weeks)
  – bone lining cells pull away from bone surfaces to
  be resorbed
  – osteoclasts are attracted to bone surfaces
  – pockets of bone resorbed by osteoclasts, creation
  of resorption pits, osteoclast apoptosis
• Reversal phase (2 weeks)
  – resorbed bone surface prepared for subsequent
  bone deposition, formation of cement line]
• Formation phase (13 weeks)
  – resorption of bone releases stored growth factors
  – osteoblasts attracted to resorption sites and
  deposit osteoid, which then mineralises
  – osteoblasts are trapped in bone matrix and
  become osteocytes or become bone lining cells
  – cover bone surfaces that are not actively being
  remodelled

Question 16

ca+2 and physiological regulation:

Answer 16

• Ca2+ movement across membranes is important in triggering many physiological mechanisms
• Some examples are :
  – neurotransmitter release at a synapse
  – smooth muscle contraction
  – heart muscle contraction
  – secretory mechanisms for hormones
  – secretory mechanisms for gut enzymes

Question 17

-ca+2 is found in 3 forms:
- In general most ohysiolofical fucntions are mediated by —-
- acid base status affects level of —- ca+2 as:

Answer 17

• • ionised (free) - about 45%
• bound to protein - about 45%
• bound to small anions - about 10%
  (e.g. phosphate, citrate and oxalate)
• most mediated by ionised form ca+2
• bound ca+2 as:
  – increase [H+] displaces Ca2+ from protein increasing free [Ca2+]
  – decrease [H+] promotes Ca2+ binding to protein decreasing free [Ca2+]
  (CHECK SLIDE 21 22)

Question 18

-the —- is a major controller of free ca+2 in the body .
-this hormone is released by — in —- at —-
- ca+2 is detected by —–
- ca +2 decreases —-
- ca+2 inhibits —-

Answer 18

-peptide hormone PTH
- PTH is released from chief cells in the four parathyroid glands at low plasma [Ca2+]
- Ca2+ is detected by a membrane bound G- protein receptor coupled to cAMP
– Ca2+ decreases cAMP and inhibits PTH release
( check slide 26)

Question 19

-PTH regulates —— by stimulating —–
- PTH indirectly stimulates —– to promote bone reasbpriton
- this is mediated by the — of production of mixture of —-
- The reabsorption of bone minerals increases the —–

Answer 19

• plasma Ca+2 by stimulating bone reabsportion
  -PTH indirectly stimulates osteoclasts to promote bone reabsorption
  – reabsorption of mineral out of bone: i.e. breakdown
• increase
• cytokines
• plasma [Ca2+] but also
  plasma phosphate
  – bone mineral is hydroxyapatite: Ca10(PO4)6(OH)2

Question 20

PTH actions on the kidney modulate the raised —– and —–
PTH promotes the reasbprtion of —-
and inhibits —–
PTH also stimulates —–

Answer 20

-plasma ca+2 and phosphate from bone reasbsoption
- Ca+2 ( thick ascending limb of loop of henle )
- inhibits phosphate reabsorption ( proximal and distal tubule which promotes phosphate excretion )
- stimulates 1alpha-hydrolase enzyme which is a key step in the sythesis of active form of vitamin d

Question 21

-the active form of vitamin d is:
- it undergoes —– in the liver catalysed by — and its – a rate limiting step in production of the active form
- activation is —- in the — which is catalysed by — and the —- is an important regulatory site
- —- is a steroid like structure so acts on intracellular receptors

Answer 21

• 1,25 dihydroxycholecalciferol (DHCC) aka calcitriol
• 25-hydroxylation
• catysled by 25-hydoxylase
• not a rate limiting step
• 1α-hydroxylation in the kidney
• catalysed by 1alpha-hydroxylase
  -kidney
• vitamin d
  ( check slide 29 pls)

Question 22

ca+2 absorption occurs in the — as they are absorbed through —- and binds to —- example: they —- pump out at the —-

Answer 22

• duodenum
• ca+2 channels
• bidning protein as calbindin
• actively pump out at the basolateral side

Question 23

true or false:
vitamin d promotes the increase in the synthesis of ca+2 channels as well as phosphate absorption in the gut

Answer 23

true

Question 24

-in —- vitamin d promotes ca+2 and po4 -3 reabsorption
- the overall effect of vitamin d is the increase of the ——- and — in bone

Answer 24

• kidney tubules
• flux of ca+2 and phosphate

Question 25

-Systemic skeletal disease characterised by low bone mass and
microarchitectural deterioration of bone tissue
– reduced osteoid and mineralisation
– bone fragility and susceptibility to fracture
is known as —-

Answer 25

osteoporosis

Question 26

in osoteprosis:
- increase – population will increase the risk due to the reduced avativity/loading and the reduced —- function
- — of females will suffer a feature after the age of — . which s compared to — of males will suffer fracture after that age — .
- can be due to :
- females are more likely to suffer a hip fracture than develop —-

Answer 26

• ageing
• anabolic function
• • 33%
• 50
  -20%
• post-menopausal ( importance of estrogen inhibition of osteoclast )
• breast cancer

Question 27

vitamin d deficiency:
—- in children which is the abnormal amount of unmineralised ostieods, characterised be bowing of log leg bones
—- in adults bone weakens due to unmierlaised osteoid , but longitudinal bone growth has been completed as there is no bowing of legs

Answer 27

• rickets
• osteomalacia
  ( info: * Circulating [25(OH)D] of <50 nmol/L are said to be deficient
  – UV strength at this latitude is too low to generate sufficient Vit D Oct-Mar
  – sunblock, covering up in the sun, dark skin colour all decrease UV exposure
  – renal disease cannot make enough vitamin D)

Question 28

-Bone growth stops with the fusing of the ——- in the long bones
- —— continues throughout life and is mediated by osteoblasts, osteoclasts and osteocytes
- —- and — control plasma Ca2+ levels and with it bone mineralisation
- Vitamin D deficiency among other factors can alter —- availability
and —– bone mineralisation

Answer 28

-epiphyseal plate
- bone turnover
- vitamin d and PTH
- ca+2
- decrease