skeletal system

Question 1

4 main functions of skeletal system

Answer 1

mechanical - support attachment muscles, ligaments, tendons

protective - internal organs

haematopoiesis - blood cell formation

metabolic - reserves of calcium and phosphate

Question 2

2 types of bone

Answer 2

trabecular bone (inner)

cortical/ compact bone

Question 3

what are bones made up of (3)

Answer 3

water

protein (collagen type 1 fibres, growth factors, matrix proteins)

minerals (mineralised with hydroxyapatite)

Question 4

chemical formula of hydroxyapatite

Answer 4

Ca10(PO4)6(OH)2

Question 5

what % of bones does water make up

Answer 5

20%

Question 6

what % of bones do proteins make up

Answer 6

35%

Question 7

what % of bones do minerals make up

Answer 7

45%

Question 8

what is the role of hydroxyapatite

Answer 8

makes bones rigid, allows collagen to be stronger in bones than skin

Question 9

3 cells bones are connected with

Answer 9

osteoclasts
ostoblasts
osteocytes

Question 10

how are osteoclasts formed

Answer 10

mononucleated precursor cells

fuse together

multi-nucleated osteoclast progenitor cell

mature

active osteoclasts

Question 11

function of osteoclasts

Answer 11

break down/ remove bone

Question 12

function of osteoblasts

Answer 12

synthesise new bone by laying down collagen fibres

fibres then mineralised by hydroxyapatite - stronger

Question 13

where are osteoblasts located

Answer 13

bone surface

Question 14

where are osteoclasts located

Answer 14

bone surface

Question 15

where are osteocyte cell bodies located

Answer 15

in bone cavity called lacuna

Question 16

where are osteocyte projections located

Answer 16

tunnels in bone called canaliculi

Question 17

function of osteocyte projections

Answer 17

communication throughout bone

Question 18

where do osteocytes originate from

Answer 18

osteoblasts trapped in the bone

Question 19

evidence suggests ___ release collagen fibres so may have a role in building bone

Answer 19

osteocytes

Question 20

bones have ____/____ due to load/ mechanical stress so require constant repair

Answer 20

micro-breaks/ micro-fractures

microfractures damage osteocyte projections, osteocytes release signals to osteoclasts and osteoblasts to begin bone remodelling

Question 21

what is the bone remodelling cycle (4 steps)

Answer 21

quiescence - aka bone lining cells (inactive)

when active, reabsorption (cells recruit osteoclast to remove damaged portion of bone)

reversal (osteoblasts recruited, lay down new collagen fibres to replace bone)

formation (osteoblasts) - mineralisation
returns to quiescence again

Question 22

___ must be equal to ___ for healthy bones

Answer 22

bone loss/ reabsorption

bone gain/ synthesis

Question 23

what is bone reabsorption

Answer 23

removal of bone tissue

Question 24

how does bone reabsorption occur (osteoclast function)

Answer 24

osteoclast breaks down hydroxyapatate/ tissue in bones, release minerals

calcium transferred from bone to blood

can be used elsewhere in the body

Question 25

post menopause there is a dec. in oestrogen production which impacts osteoclasts. how and why

Answer 25

oestrogen inhibits maturation of osteoclast progenitor cells into mature ostoclasts that reabsorb bone

Question 26

RECHECKhow is bone remodelling induced

Answer 26

microfractures damage osteocyte projections, osteocytes release signals to osteoclasts and osteoblasts to begin bone remodelling

Question 27

extensive bone remodelling can cause

Answer 27

hypercalciumia

Question 28

in bone reabsorption, calcium transferred from bone to blood, can be used elsewhere in the body. example of use

Answer 28

pregnancy, female bone density dec as activated osteoclasts to break down skeletal structure and release calcium for developing embryo

Question 29

post menopause dec. oestrogen production oestrogen blocks ostoclasts dec blocking, inc bone breakdown potentially leading to osteoporosis. treatment?

Answer 29

HRT - admin exog oestrogen

Question 30

what is an osteoclast progenitor cell

Answer 30

multiple mononucleated cells formed into a multinucleated progenitor cell (not yet mature- no ruffle border) eventually matures over time for bone reabsorption

Question 31

hetereotopic assification (HO)

Answer 31

bone formation in wrong place

Question 32

what causes hetereotopic assification disease

Answer 32

single point missence mutation of activin A receptor type 1 (ACVR1) (AA R for H at 206 in GS domain)

Question 33

activin A receptor type 1 (ACVR1)

Answer 33

mediator of bone morphogenic proteins

Question 34

osteosclerosis

Answer 34

abnormal hardening of bone, inc bone density - overactivation of osteoblasts

Question 35

how common is pagets disease

Answer 35

1-3% in older than 45-55 10% in older than 80

Question 36

osteoporosis

Answer 36

reduction in bone density due to inc bone reabsorption - more fragile inc osteoclast activity more common in women

Question 37

final correct - oestrogen __ osteoclast maturation. women are thus more at risk of osteoporosis

Answer 37

promotes

Question 38

mutation of ___ results in fibrodysplasia ossificans progressive

Answer 38

ACVR1

Question 39

Studies have demonstrated that the thalidomide metabolite _______ can impair angiogenesis

Answer 39

CPS49

Question 40

3D co culture models

Answer 40

learning about these cells has become easier through 3d co culture models, using primary human osteocytes/blasts/clasts, which express typical markers like RANKL, ALPL after being cultured

Question 41

current research focus to learn abt these cells

Answer 41

in vitro bone models are difficult to create, so focused on recreating certain bone aspects like tumour models or bone marrow

Question 42

fibrodysplasia ossificans progressiva

Answer 42

rare progressive heterotropic ossification of soft tissues forming skeletal tissue instead following trauma (e.g. dental work) cause - ACVR1 gene substitution mutation dysregulating BMP bone morphogenic protein signalling

Question 43

fibrodysplasia ossificans progressiva treatment efforts/ detetcion

Answer 43

diffiicult to detect, uncurable patients can have slightly different secondary symptoms - e.g. some mental impairment, some alopecia - inc difficulty in management and early diagnosis

Question 44

oct 2023 case study

Answer 44

5 year old girl - knees grown inwards, stunted growth, teeth issues diagnosed with hyphophosphatemic rickets and growth hormone deficiency treatment failed, genetic testing taken place discovered mutation linked to amelogenesis imperfecta (AI) which tends to just affect tooth enamel , but mutation caused systemic phosphate loss COMPLEX PATHOPHYSIOLOGY OF BONE DISORDERS

Question 45

why is paget's disease difficult to diagnose early

Answer 45

can be asymptomatic, can have varying symptoms like deafness and bone pain

Question 46

paget's disease possible causes - 3 but unconfirmed what it acc is ygm

Answer 46

mutation in gene that produces sequestome 1 which is involved in osteoclast function, leads to inc susceptibility of paget's disease genetic/ environmental factors initiated by slow virus as nuclear inclusion of viral component in osteoclasts found in pd patients

Question 47

paget's disease progression

Answer 47

excessive osteoclast bone resorption, followed by compensatory osteoblast activity forming unstable bone and abnormal bone remodelling

Question 48

clinical gaf

Answer 48

hypercalciumia osteosclerosis osteoporosis fibrodysplasia ossificans progressive paget's disease

Question 49

future advancements

Answer 49

research - 3D co culture models