Bone Metabolism & Remodelling Flashcards
when does bone development start (at how many weeks) during gestation? [1]
what are the two ways can develop bone? [2]
when does bone development start (at how many weeks) during gestation? [1]
6-7 weeks
what are the two ways can develop bone? [2]
- *intramembranous ossification:** direct bone formation, many skull bones
- *endochondral ossification:** most of skeleton, cartilage first & then bone
intramembranous ossifcation: describe direction of bone growth
bones develop at centres of ossification and grow outwards - connecting to neighbouring bone at cranial suture
how does endochondral ossification occur?
- Mesenchymal cells condense and differentiates into chondroblasts to produce hyaline cartilage model extracellular matrix (so they use collagen type 2 rather than collagen type 1).
- the perichondrium forms around cartilage model and holds all the mesenchymal cells next to the condensing bone
- To begin with, ECM is made more from collagen type 2, more proteoglycans: causes cartilage to grow in legnth and width (into the shape of the bone): causes to be further away from nutrient source
- chondrocytes now in the middle will begin to deteriorate as there is no blood supply into this cartilage
- this creates cavities, right in the centre, where the cartilage used to be. When they die, this triggers calcification as it triggers a Ph change: It releases vesicles in the chondrocytes with enzyme like alkaline phosphatase which changes the ph and encourages calcification of the matrix.
At this time, a blood vessel known as the nutrient artery can penetrate the perichondrium and begin to bring in osteoclasts from the haemopoietic cells to start remodelling: break down some of the spongy bone to create a marrow, or medullary, cavity in the centre.
Bone on the inside and bone on the outside grow towards each other to completely replace the cartilage.
where do you find epiphyseal growth plates in bone [2]?
what goes on at epiphyseal growth plates?
where do you find epiphyseal growth plates in bone [2]?
- minumun of 2: medial and distal end of bones (sometimes more)
- hyaline cartilage between epiphysis and diaphysis
what goes on at epiphyseal growth plates?
- hyaline cartliage replaced by bone to cause increase in bone lenght
which is your last bone to ossify? [1]
clavicle
what happens to bone in the middle, as it develops from child to adult? why?
what is name for what is left in the middle?
infant / child bone increases in width BUT at the same time, bone is lost in the centre via osteoclasts
otherwise would be too heavy / brittle
in centre = intra medullary cavity
what is cortical (compact) vs cancellous (trabecular / spongy bone)
- *cancellous (trabecular / spongy bone)**
- 20 % of mass BUT 80% of surface area
- 5-7% density of cortical bone
- trabecuale - plates and rods
- home for bone marrow
- *cortical bone (compact)**
- epiphysis - thin shell
- diaphysis - thicker layer to give support to outer edge of bone
what are the different types of bone marrow/ [2]
how does bone marrow change throughout lifetime? (infant –> adult)?
what are the different types of bone marrow? [2]
- **yellow - more adipocytes
- red - more haemopoetic cells**
how does bone marrow change throughout lifetime? (infant –> adult)?
- newborn - nearlly all red bone marrow
- adult - more yellow
when do you find woven bone in the body? [2]
what does it look like? [1]
when do you find woven bone in the body? [2]
- **immature childhood bone
- healing of fractures**
what does it look like? [1]
- lamella (layers of bones) not in orders
what is yellow and red?
red - lamellar bone
yellow - woven bone
what is the name of the inorganic substance that is precipitated over collagen fibres to calcify it? [1]
what is structure of ^ like on collagen fibres? [1]
what is the name of the inorganic substance that is precipitated over collagen fibres to calcify it? [1]
95% calcium hydroxyapatite
what is structure of ^ like on collagen fibres? [1]
- as crystals
which cells make bone ECM (type 1 collage / proteoglycans)? [1]
which cells are maintainers of bone? [1]
which cells make bone ECM (type 1 collage / proteoglycans)? [1]
osteoblasts
which cells are maintainers of bone? [1]
osteocytes
what substance is secreted that makes osteoclasts differentiate into osteoclasts? [1]
what substance is secreted that makes osteoclasts differentiate into osteoclasts? [1]
RANKL
where do you find osteoprogenitor (bone stem cell) [2]
what is fate of osteoblasts? [2]
where do you find osteoprogenitor (bone stem cell) [2]
- *- periosteum
- endosteum**
what is fate of osteoblasts? [2] become either:
- *- osteocyte
- lining cell:old osteoblast that arenot encased in own matrix** to help regulate calcium entry into and out of bone. can be reactivated by PTH
why does bone need to remodel? [2]
which part of bone has most bone remodelling? [1] why [2]
why does bone need to remodel? [2]
- -***before deterioration
- **along lines of mechanical stress
which part of bone has most bone remodelling? [1] why [2]
- trabecular bone: 3x10 more quicker than cortical
- *- larger sa
- responds to stress quicker**
what are the internal [1] and external signals [2] for bone remodelling?
what are the internal and external signals for bone remodelling?
- *internal factors**
- osteocytes processes extend in canaliculi & touch their neighbours
- osteocytes produce sclerostin to indicate bone health ! - stops osteoblasts coming
- when osteocytes stop producing sclerostin: indicates bad bone health
- *external factors**
- serum calcium level: low serum calcium causes the release of parathyroid hormone - causes osteoblasts to make RANK L
- pro-inflam cytokines: IL1, IL6, IL17 & TNF
what do osteoclasts look like? [1]
explain mechanism of bone remodelling occurs xox
osteoclasts - multinucleated macrophage relation
- look for areas of bone that need to be renewed
- make leak proof seal over the area
- secrete enzymes & HCl that will dissolve the calcium hydroxyapatite
- osteoclasts take up calcium & proteins pump into interstitial fluid
- osteoclasts find new area
- osteoblasts come in & fill lacuna with osteoid - firstly NOT MINERALISED
- *-** approx 7-10 days osteoid is mineralised
- osteoblast becomes encased & beomes osteocyte
where do we get most of calcium from for bone?
how do we maintain normal serum calcium levels? [3]
normal diet means we don’t need to use calcium stores in bone
how do we maintain normal serum calcium levels? [3]
- **intestinal absorb
- renal excretion
- skeletal mobilistain**
what is the effect of when low Ca2+ serum causes PTH to be secreted in? [3]
- low serum Ca2+ (below 2.2 mmol/L) stimulates parathyroid hormone (PTH) secretion
- PTH promotes
i) Ca2+ reabsorbtion from kindey and PO4 excretion
ii) @ kindey: synthesis of 1,25 dihydroxyvitamin D -> i_ncreases calcium absorbtion from gut_
iii) **Ca2+ reabsorbtion from bones - increases activity and no. osteoclasts - **PTH binds to osteoblasts; osteoblasts produce RANKL; osteoclasts have RANKL receptor; activates osteoclasts
how does PTH cause Ca2+ reabsorbtion from bones via the increase of activity and no. osteoclasts? [3]
Ca2+ reabsorbtion from bones - increases activity and no. osteoclasts
PTH binds to osteoblasts
osteoblasts produce RANKL
osteoclasts have RANKL receptor
activates osteoclasts
when Ca2+ levels are back to normal, how do we stop things that occured when it was low? [3]
- stop production of PTH
-
calcitonin: released from C cells in thyroid gland
i) inactivates osteoclasts
ii) increases Ca2+ bones can accept
iii) increases renal Ca2+ reabsorb
which two other hormones influence Ca2+ absorption?
- *oestrogen**
- increases Ca2+ in gut
- bone decreased reabsorb
glucocorticoid
