Hormones, the skeleton and HRT Flashcards
1
Q
What are the different types of bone?
A
- Cortical (compact) bone
- Cortical composes the main part of the shaft, around the outside
- Trabecular (spongy, cancellous) bone
- Trabecular is in the head of the bone
2
Q
What is the bone’s cellular structure?
A
- Bone is made mainly of organic material like collagen, then the rest is made up of calcium salts and hydroxyapatite
3
Q
Osteoclast vs osteoblast vs osteocytes (lineage)
A
- Haematopoeitic stem cells give rise to the blood cells in our body, but also osteoclasts
- Mesenchymal stem cells give rise tto osteoblasts via various precursors
- Terminally differentiated osteoblasts = osteocytes
- Life cycle of all is determined by control of differentiation and apoptosis
4
Q
Osteoblasts vs osteoclasts effects
A
- Osteoblasts - lay down organic matrix (osteoid) then progress to cause mineralisation to mature bone
- Osteoclasts secrete acid and proteolytic enzymes to digest and eat away the bone - as they do this they release calcium into the circulation
- The balance = bone remodelling
5
Q
What are osteocytes?
A
- terminally differentiated post-mitotic osteoblasts
- Entombed within lacunae in the bone matrix
- Communicate with each other and bone surface via cellular processes (dendrites), which run along canaliculi
- Forms lacunar-canalicular network
- May live for decades
6
Q
What is the lacunar-canalicular network?
A
Allows communication between osteocytes and from them to surface cells and the systemic circulation
7
Q
What are the major functions of osteocytes?
A
- Can regulate the balance between bone resorption and bone production
- Respond to mechanical stimuli (bone loading) and endocrine stimuli
- Also act as an endocrine organ - produce FGF23, which acts on the kidney to inhibit the rate of vit D conversion, and increase phosphate secretion
8
Q
What may cause resorption of bone?
A
- Lack of exercise and mechanical stress
- Bedbound patients, elderly and astronauts
9
Q
What hormones act on bone ‘metabolism’?
A
- PTH
- VIT D
- Calcitonin
10
Q
What does PTH do?
A
- negative feedback/ control of serum Ca
- Released in response to decreases in Ca
- Stimulates conversion of Vit D in kidney via 1-a-hydroxylase
- Increases Ca reabsorption in kidney
- Stimulates bone remodelling - high PTH levels causes breakdown.
- However can also be used to treat bone loss by stimulating anabolic effects
11
Q
What are the actions of vit d?
A
- Synergistic with PTH
- Increases Ca absorption from gut
- Promotes differentiation of osteoclast and osteoblast lineages
- Inhibits PTH release
- Inhibits 1-a-hydroxylase
12
Q
What is Calcitonin?
A
- Hormone from C-cells of the thyroid gland
- negative feedback regulation of serum Ca - released in response to high Ca
- inhibits osteoclast function
- no evidence for importance in humans - has been used for bone loss treatment
13
Q
What are the actions of oestrogen on bone?
A
- Regulates remodelling
- Shortens lifecycle (promotes apoptosis) of osteoclasts
- Lengthens lifecycle (protects from apoptosis) of osteoblasts
- Increases bone formation
14
Q
What is the process of osteoclast induction?
A
- RANK = receptor activator for NF-kB
- RANK is a surface receptor on pre-osteoclasts, stimulating osteoclast differentiation - activated by RANKL
- RANKL is produced by pre-osteoclasts, osteoblasts and osteocytes - binds to RANK and stimulates osteoclast differentiation
- OPG (osteoprotogerin) - decoy receptor produced by osteocytes. Binds to RANKL, preventing activation of RANK
15
Q
What modulators are released from osteocytes to regulate bone remodelling?
A
- Osteoclasts - promotion (M-CSF and RANKL), inhibition (OPG, NO)
- Osteoblasts - promotion (PGE2, NO, ATP - activate Wnt signalling), inhibition (sclerostin, DKK1 and SFRP1 - all inhibit Wnt signalling)
