Parathyroid Hormone, Calcium and Bone

Question 1

What are the target serum calcium levels?

Answer 1

2.1-2.6mM/L

Question 2

What can calcium be bound to in circulation?

Answer 2

Albumin

Question 3

What percentages of calcium are free and bound to albumin?

Answer 3

50% each

Question 4

What is the half life of PTH?

Answer 4

8mins

Question 5

What type of receptor does PTH bind to?

Answer 5

GPCR

Question 6

What effect does hypocalcaemia have on PTH secretion?

Answer 6

Increases it

Question 7

What effect does increased PTH secretion have on bone (and what is caused)?

Answer 7

• Increased bone resorption
• Increased serum calcium

Question 8

What effect does increased PTH secretion have on kidney (and what is caused)?

Answer 8

• Increased urinary phosphate (inc. bone resorption –> inc. serum calcium)
• Decreased urinary calcium (inc. serum calcium)
• Increased 1,25D3 production (inc. calcium + phosphate absorption in intestine –> inc. serum calcium + phosphate)

Question 9

What is the active form of vitamin D?

Answer 9

1,25-dihydroxyvitamin D3 (1,25D3)

Question 10

How is 1,25D3 produced?

Answer 10

• Either vitamin D3 made from 7-dehydrocholesterol when UV light hits skin or obtained from source (eg. fish, eggs)
• Liver converts vitamin D3 into 25-hydroxyvitamin D3 (25D3)
• Kidney (with PTH) converts 25D3 to 1,25D3 using 1α-hydroxylase

Question 11

Where is calcitonin produced?

Answer 11

Thyroid c-cells (parafollicular cells)

Question 12

What stimulates calcitonin release?

Answer 12

Hypercalcaemia

Question 13

What is the effect of calcitonin?

Answer 13

Inhibit bone resorption

Question 14

What effect does hypercalcaemia have on PTH secretion?

Answer 14

Decreases it

Question 15

What effect does decreased PTH secretion have on bone (and what is caused)?

Answer 15

Decreased bone resorption (dec. serum calcium)

Question 16

What effect does decreased PTH secretion have on kidney (and what is caused)?

Answer 16

• Decreased urinary phosphate (dec. bone resorption –> dec. serum calcium)
• Increased urinary calcium (dec. serum calcium)
• Decreased 1,25D3 production (dec. calcium + phosphate absorption in intestine –> dec. serum calcium + phosphate)

Question 17

Where is fibroblast growth factor 23 (FGF23) produced?

Answer 17

Osteocytes

Question 18

What effects does increased FGF23 have?

Answer 18

• Increased urinary phosphate
• Decreased urinary calcium
• Suppresses renal synthesis of 1,25D3

Question 19

What effect does hyperphosphataemia have on PTH secretion?

Answer 19

Increases it

Question 20

By action of what substances is serum phosphate reduced in hyperphosphataemia?

Answer 20

• Mainly FGF23
• Some PTH

Question 21

What is primary hyperparathyroidism?

Answer 21

Raised serum PTH due to a parathyroid tumour

Question 22

What does primary hyperparathyroidism cause?

Answer 22

• Hypercalcaemia
• Low serum phosphate
• Loss of negative feedback from hypercalcaemia

Question 23

Symptoms of primary hyperparathyroidism

Answer 23

• Lethargy/confusion
• Thirst/polyuria
• Renal stones
• Constipation
• Pancreatitis
• Joint pain
• Fracture
• Depression
• Hypertension

Question 24

How is primary hyperparathyroidism treated?

Answer 24

Surgery

Question 25

Difference between rickets and osteomalacia

Answer 25

- Rickets affects growing skeleton (children) - Osteomalacia affects adult skeleton

Question 26

What is rickets/osteomalacia?

Answer 26

Deficiency of vitamin D (and/or calcium)

Question 27

What causes rickets/osteomalacia?

Answer 27

- Lack of mineralisation of osteoid - Failure to absorb sufficient calcium from GIT

Question 28

What is osteoid?

Answer 28

Collagen component of bone

Question 29

Symptoms of rickets

Answer 29

- Bow legs - Swollen joints

Question 30

Symptoms of osteomalacia

Answer 30

- Bone pain - Pseudofractures

Question 31

How is rickets/osteomalacia treated?

Answer 31

Vitamin D replacement (dietary or through sunlight)

Question 32

What is secondary hyperparathyroidism?

Answer 32

Raised serum PTH secondary to renal disease

Question 33

Mechanism of how secondary hyperparathyroidism occurs

Answer 33

- Abnormal kidney function (disease) > Dec. urinary phosphate > Inc. urinary calcium > Dec. 1,25D3 production - Bones sense raised serum phosphate levels and produce lots of FGF23 > Further dec. 1,25D3 production - Intestine absorbs less calcium + phosphate - Hypocalcaemia feedback to parathyroid > Inc. PTH secretion

Question 34

How is secondary hyperparathyroidism treated?

Answer 34

- Phosphate binders - Vitamin D analogues

Question 35

Symptoms of chronic kidney disease-mineral and bone disorder (CKD-MBD) and what causes them?

Answer 35

- Osteomalacia-type symptoms > Dec. calcium and 1,25D3 after kidney disease (same as lead-up to secondary hyperparathyroidism) - Bone disease and increased fracture risk > Secondary hyperparathyroidism causes drastically increased PTH > Causes lots of bone resorption

Question 36

What is oncogenous osteomalacia (cause + result)

Answer 36

- Caused by benign tumour secreting FGF23 - Means high serum FGF23 and low serum 1,25D3

Question 37

What is X-linked hypophosphaemic rickets?

Answer 37

Mutations in PHEX gene lead to elevated FGF23 and suppressed 1,25D3

Question 38

What is osteoporosis?

Answer 38

Loss of bone mass/density (mineral and non-mineral bone decreased)

Question 39

Types of osteoporosis (description of each)

Answer 39

- Osteoporosis of aging = gradual decline in bone density from early adult peak - Postmenopausal osteoporosis = rapid decline in female bone density following decline in estrogen at menopause - Steroid-induced osteoporosis = decline in bone density associated with use of steroids as therapy for inflammatory diseases

Question 40

Treatment options for osteoporosis

Answer 40

- Hormone replacement therapy > Estrogen - Inhibition of osteoclast development > Denosumab is a RANK ligand antibody > Blocks RANK ligand on osteoblasts from interacting with RANK on osteoclasts > Decreased differentiation of pre-osteoclasts - Inhibition of osteoclast activity > Bisphosphonates disrupt intracellular enzymes required for osteoclast activity - Stimulation of osteoblast activity > Teriparatide is the first 34 AAs of PTH > Is anabolic stimulator of bone formation

Question 41

How can osteoporosis be prevented?

Answer 41

- Exercise - Vitamin D and calcium - Avoid smoking - Avoid high alcohol intake

Question 42

Cell types in bone

Answer 42

- Osteocytes - Osteoblasts - Osteoclasts

Question 43

Where are osteocytes found specifically?

Answer 43

Embedded in calcified bone matrix

Question 44

What do osteoblasts do?

Answer 44

Bone forming cells: - Produce matrix constituents - Aid calcification

Question 45

What do osteoclasts do?

Answer 45

Bone resorbing cells: - Produce acid (resorbs mineral) and enzymes (resorb matrix)

Question 46

How are osteoclasts matured?

Answer 46

- Originally osteoclast precursor - RANK ligand on osteoblast binds RANK on precursor - Makes mature osteoclast