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)
16
Q
What is sclerostin?
A
- Wnt signaling inhibitor
- essential negative feedback on bone formation
- Its absence = excessive bone formation (Van Buchem disease, sclerosteosis)
- A brake on bone formation, mechanical stress can take this brake off
17
Q
What is osteoporosis?
A
- Bone disease in which there is a loss of bone mass
- Affects both cortical and trabecular bone
- Bone is more fragile and fractures more easily
18
Q
What is osteomalacia?
A
Loss of bone mineralisation
19
Q
What are some endocrine causes of osteoporosis?
A
- Hypogonadism (oestrogen deficiency)
- Excess glucocorticoids (endogenous or exogenous)
- HyperPTH
- HyperT
20
Q
What methods of diagnosis are there?
A
- Bone mineral density measurement (BMD)
- Dual-energy X-ray absorptiometry (DEXA scan)
21
Q
What are T-score and Z-score?
A
- T - number of SDs below average for young adult at peak bone density
- Z score - matched to age and or/group
22
Q
What do different T-scores mean?
A
- -1 or above = normal
- Between -1 and -2.5 = osteopenia
- Lower than -2.5 = osteoporosis (+ presence of fracture = severe osteoporosis)
23
Q
How does bone density change with age?
A
- We hit peak bone density at around 25
- We will all get osteopenia and maybe even osteoporosis if we live long enough.
- All depends on lifestyle factors
- If you already have low peak bone mass, you will hit osteoporosis threshold faster
- Menopause causes a massive decrease in bone density
24
Q
Give 5 treatments for osteoporosis
A
- Oestrogen
- Bisphosphonates - inhibit function of osteoclasts (risedronate, alendronate)
- PTH analogues
- Denosumab - antibody against RANKL
- Ensure adequate intake of Vit D and Calcium
- Appropriate weight-bearing exercise
25
Q
What are some clinical features of the menopause?
A
- Vasomotor symptoms (hot flushes) are early sign
- No more ovarian oestrogen after
- Rely on small conversions from androgens in adipose
- Will accelerate bone loss and can lead to osteoporosis
26
Q
What are the NICE guidelines for HRT?
A
- HRT is most effective treatment for relief of vasomotor symptoms, although others are available
- For most symptomatic menopausal women, the benefits outweigh the risks
- Any increase in risk of breast cancer…disappears after HRT is stopped
