Osteoperosis

Question 1

Core concept of calcium homeostasis and bone

Answer 1

• Body prioritises blood Ca2+ over bone strength
• Bone acts as dynamic calcium reservoir
• Low blood Ca2+ → calcium released from bone
• Chronic loss → osteoporosis and fragility fractures (esp. postmenopausal women)

Question 2

Normal calcium range and major functions

Answer 2

• Normal plasma calcium: 2.1–2.6 mmol/L
• Roles: nerve excitability, muscle contraction, clotting, bone structure
• Stabilises sodium channels in nerves

Question 3

Effects of high vs low extracellular calcium on nerves

Answer 3

• High Ca2+: nerves less excitable
• Low Ca2+: overexcitable → tetany and seizures

Question 4

Intracellular roles of calcium

Answer 4

• Stored in ER and mitochondria
• Second messenger signalling
• Hormone secretion
• Neurotransmitter release
• Muscle contraction

Question 5

Hypocalcaemia symptoms, causes and treatment

Answer 5

• Symptoms: seizures, Chvostek sign, Trousseau sign
• Causes: parathyroid damage, renal failure, vitamin D deficiency
• Treatment: IV calcium

Question 6

Hypercalcaemia symptoms and causes

Answer 6

• Acute: thirst, polyuria, nausea, abdominal pain
• Chronic: constipation, bone pain, kidney stones
• Causes: cancer, hyperparathyroidism, bone resorption

Question 7

Forms of calcium in blood

Answer 7

• Ionised (active) 50%
• Protein bound 40% (albumin)
• Anion bound 10%
• Correct calcium if albumin abnormal

Question 8

Hormonal regulators of calcium

Answer 8

• PTH from parathyroid glands
• Calcitonin from thyroid C-cells
• Vitamin D (calcitriol) activated in kidney
• Organs: bone, kidney, intestine

Question 9

Trigger for PTH secretion

Answer 9

• Detected by CaSR in parathyroid chief cells
• Small drop in Ca2+ → large PTH rise

Question 10

Overall effect of PTH

Answer 10

• Increases calcium
• Decreases phosphate
• Keeps Ca but dumps phosphate to avoid binding

Question 11

PTH actions in kidney

Answer 11

• ↑ calcium reabsorption
• ↓ phosphate reabsorption (excreted)
• Activates vitamin D via 1α-hydroxylase

Question 12

Activated vitamin D (calcitriol) actions

Answer 12

• ↑ intestinal calcium absorption
• ↑ renal calcium reabsorption
• Supports bone mineralisation via osteoblasts
• Amplifies PTH effects

Question 13

PTH effects on bone

Answer 13

• Rapid phase: osteocytes release calcium (minutes)
• Slow phase: osteoclast activation and bone resorption
• Chronic elevation → osteoporosis

Question 14

Calcitonin actions

Answer 14

• Released with high Ca2+
• Inhibits osteoclasts
• Increases urinary Ca excretion
• Promotes bone deposition
• Minor physiological role in adults

Question 15

Integrated calcium regulation

Answer 15

• Low Ca2+: ↑ PTH, ↑ bone resorption, ↑ renal Ca reabsorption, ↑ vitamin D
• High Ca2+: ↑ calcitonin, ↓ bone resorption, ↑ urinary excretion

Question 16

Bone types and fracture sites

Answer 16

• Cortical bone 75% (strong outer)
• Trabecular bone 25% (metabolically active)
• Trabecular bone affected first
• Common fractures: vertebrae, wrist, hip neck

Question 17

Bone cells and functions

Answer 17

• Osteoclast: resorb bone
• Osteoblast: form bone
• Osteocyte: sensing and regulation

Question 18

Secondary hyperparathyroidism

Answer 18

• Caused by chronic low Ca absorption
• Vitamin D deficiency, renal disease, ageing
• Chronically elevated PTH slowly destroys bone
• Calcium may appear normal

Question 19

Renal osteodystrophy mechanism

Answer 19

• Kidney failure → ↓ vitamin D activation
• ↑ phosphate, ↓ calcium
• ↑ PTH → bone resorption

Question 20

Definition and consequences of osteoporosis

Answer 20

• Reduced bone density due to formation < resorption
• Fragility fractures
• Vertebral collapse
• Hip fractures

Question 21

Why postmenopausal women are high risk

Answer 21

• Oestrogen inhibits osteoclasts
• Promotes osteoblast survival
• Opposes PTH
• Loss of oestrogen → accelerated bone loss

Question 22

Oestrogen effects on bone and calcium

Answer 22

• ↓ RANKL and osteoclast formation
• ↑ osteoclast apoptosis
• ↑ osteoblast survival
• ↑ gut Ca absorption
• ↑ renal Ca reabsorption

Question 23

Lifestyle risk factors for osteoporosis

Answer 23

• Low calcium intake
• Vitamin D deficiency
• Smoking
• Alcohol
• Inactivity
• Low BMI

Question 24

Medical and drug risk factors

Answer 24

• Early menopause, hyperparathyroidism, renal disease
• Rheumatoid arthritis, GI disease, myeloma
• Glucocorticoids, heparin, PPIs, SSRIs, chemotherapy

Question 25

How glucocorticoids cause osteoporosis

Answer 25

- Inhibit osteoblasts - Increase osteoclast activity - Reduce Ca absorption - Increase renal Ca loss

Question 26

Calcium and vitamin D treatment

Answer 26

- Increase bone mineral density - Reduce fractures - Renal disease: give alfacalcidol

Question 27

Bisphosphonate mechanism

Answer 27

- Bind bone and released during resorption - Taken up by osteoclasts - Cause osteoclast apoptosis - Nitrogen-containing inhibit signalling - Non-nitrogen form toxic ATP analogues

Question 28

Other osteoporosis treatments

Answer 28

- HRT reduces resorption - SERMs (raloxifene) oestrogen-like in bone - Denosumab anti-RANKL - Calcitonin rarely used

Question 29

Vitamin D deficiency diseases and causes

Answer 29

- Osteomalacia in adults - Rickets in children - Poor diet, malabsorption, renal and liver disease

Question 30

Vitamin D deficiency treatment and monitoring

Answer 30

- Calcium + vitamin D supplementation - Monitor hypercalcaemia and kidney stones

Question 31

Hypercalcaemia treatment

Answer 31

- IV fluids - Diuretics - Bisphosphonates - Calcitonin - Cinacalcet

Question 32

Cinacalcet mechanism

Answer 32

- Activates CaSR - Reduces PTH secretion

Question 33

FRAX tool purpose

Answer 33

- Estimates 10-year fracture risk - Guides treatment decisions

Question 34

Key revision logic for calcium homeostasis

Answer 34

- Bone stores calcium - PTH preserves blood Ca at expense of bone - Vitamin D absorbs Ca - Oestrogen protects bone - Menopause removes protection - Osteoporosis when resorption > formation