Hormones, The Skeleton and HRT

Question 1

What do Osteoblasts do?
→ What are they formed from?

Who do Osteoclasts do?
→ What are they formed from?

What do Osteocytes do?
→ What network do they have? What’s the function of it?

What type of activity favours bone resorption?
→ Give examples

What type of activity favours bone formation?

Answer 1

• Produce Osteoid and its mineralisation
  → MESENCHYMAL stem cells
• Resorbs bone with acid and enzyme secretions
  → HAEMATOPOIETIC stem cells
• Regulates bone remodelling in response to mechanical and endocrine stimuli
  → Lacunar-Canalicular network to communicate with cells on bone surface
• Unloading
  → Bedrest, Zero-gravity (space)
• Load-bearing exercise

Question 2

OSTEOCLAST DIFFERENTIATION:
What do Pre-Osteoclasts present on their surface?

What is produced? How does this lead to osteoclast differentiation?

What inhibits osteoclast differentiation? How?
→ What produces it?

Answer 2

• RANK receptor
• RANK-ligand produced by Pre-Osteoblasts, Osteoblasts, and Osteocytes, which binds to RANK receptor to stimulate osteoclast differentiation
• OPG (Osteoprotogerin) as it binds to RANK-L, preventing activation of RANK
  → OSTEOCYTES

Question 3

What’s the main effect of PTH on Ca?
→ What else does it do?

What’s the main effect of Vitamin D on Ca?
→ What else does it do?

What’s the main effect of Calcitonin on Ca?
→ What else does it do?

How does Oestrogen affect the Osteoblasts and Osteoclasts?

Answer 3

• ↑Ca in BLOOD
  → Stimulates conversion of Vit D in kidney (by 1-a hydroxylase), Increases Ca reabsorption in kidneys, Stimulates Bone remodelling
• ↑Ca
  → Increases Ca absorption from gut, Synergistic effects with PTH on bone
• ↓Ca
  → Inhibits Osteoclast function
• • PROTECTS OsteoBLASTS from Apoptosis
  • PROMOTES Apoptosis in OsteoCLASTS
  • Inhibits osteoclast differentiation

Question 4

OSTEOPOROSIS:
What’s the difference between it and Osteomalacia?

What is Osteopenia?

What are the 4 main causes of it?

When do Women have a higher risk of it?

Diagnosis:
What type of scan is used? What does this measure?

What is the T Score?

What is the Z Score?

Management:
What is the main class of drug given? What do they do?
→ Give examples

What else can be given?

What Lifestyle changes are recommeded?

When giving HRT, why is Oestrogen not given by itself?

Answer 4

• Osteoporosis is a loss of Bone MASS (Brittle bones), while Osteomalacia is a loss of Bone MINERALISATION (Softer bones)
• The bone loss that occurs before Osteoporosis
• • Hypogonadism (↓)
  • Excess glucocorticoids (e.g. Cortisol)
  • Hyperparathyroidism (↑PTH) - Leads to excess bone resorption compared to bone mineralisation
  • Hyperthyroidism (↑TH)
• During MENOPAUSE due to the drop in Oestrogen = quicker bone loss

• DEXA scan - measures BONE MINERAL DENSITY (BMD)
• Number of Standard deviations below average for young adult at peak bone density
• T score matched to age and/or group

• Bisphosphonates - Inhibits function of Osteoclasts
  → Risedronate, Alendronate
• • PTH analogues
  • Denosumab - human monoclonal antibody (MAB) against RANK ligand
  • Romosozumab - human MAB against sclerostin
• Take in enough Calcium and Vitamin D, and Exercise (favours bone formation)
• Oestrogen increases the risk of Endometrial cancer, so Progesterone is added to oppose these effects