Endocrine Control of Calcium and Bones

Question 1

State 4 important functions of calcium in the body

Answer 1

1. nerve muscle excitability
2. fusion of and secretion from storage vessels
3. muscle contraction
4. intracellular second messenger
5. structural - skeleton/bone remodelling

Question 2

Where is the majority of the calcium stored in the body? And what is it called?

Answer 2

99% found in bones and teeth - hydroxyapatite

Question 3

What is the total concentration of Ca in ECF? How much is biologically active?

Answer 3

~2.5mM, and approximately half is ‘free’

Question 4

Is calcium well absorbed by the body? Why/why not?

Answer 4

No, as it it highly charged

Question 5

Name the three types of cells involved in the formation and resorption of bone

Answer 5

Osteoblasts
Osteocytes
Osteoclasts

Question 6

Which type of bone cell monitors the bone matrix and has an essential role in exchanging the Ca between ECF and bone?

Answer 6

Osteocytes

Question 7

What is the function of osteoblasts?

Answer 7

synthesise and secrete collagen and promote the deposition of CaPO4 crystals

Question 8

What is the function of osteoclasts?

Answer 8

promote bone resorption

Question 9

What is the purpose of the cortical and spongy bone?

Answer 9

Cortical = hard bone, mineralised for strength, 80%

Spongy =. trabecular bine, metabolically more active, big surface area, 20%

Question 10

Is the dissolution of bone a fast or slow process?

Answer 10

Slow

Question 11

How can calcium be quickly exchanged from bone into plasma?

Answer 11

Membrane bound Ca pump (hormonal control)

Question 12

Explain a primary signal for bone resorption.

Answer 12

Expression of RANKL on osteoblasts and its interaction with RANK on osteoclast progenitors

Question 13

What is RANK? Which cell is it present on?

Answer 13

receptor activator of nuclear factor kappa B (osteoclast progenitor cells)

Question 14

What is RANKL? And which cell is it present on?

Answer 14

RANK ligand (osteoblasts)

Question 15

Name the three hormones which regulate Ca metabolism and bone

Answer 15

Parathyroid hormone
Vitamin D3
Calcitonin

Question 16

Which hormone is secreted by the chief cells of the parathyroid gland? And what is its overall action?

Answer 16

Parathyroid hormone

increase Ca2+ and decrease PO4 in plasma

Question 17

What are the actions of the parathyroid hormone in the short term and long term?

Answer 17

Short term: stimulate Ca pump in osteocytes

Long term: stimulate osteoclasts and inhibit osteoblasts

Question 18

Explain the role of the kidney with regards to PTH

Answer 18

Decrease Ca loss by increasing tubular reabsorption of Ca2+ and decreasing tubular reabsorption of PO4

Question 19

What is the role of the GIT with regards to PTH?

Answer 19

Stimulates activation of Vitamin D3

Question 20

Which hormone involved in Ca metabolism is known as a pro-hormone?

Answer 20

Vitamin D

Question 21

Vitamin D can come from plants and animals, what are the respective terms for each?

Answer 21

Pro Vitamin D3 - 7-dehydro cholesterol

Pro Vitamin D2 - ergosterol

Question 22

What role does the sun have to play in the activation of Vitamin D?

Answer 22

The UV rays transform the vitamin d in skin (which is originally from diet) into its active form.

Question 23

Is the processing of Vitamin D in the liver regulated? What is the metabolite formed?

Answer 23

Not regulated

Calcifediol

Question 24

Is processing of Vitamin D is the kidneys regulated? What is the metabolic formed?

Answer 24

Highly regulated

Calcitriol

Question 25

What are the three main biological actions of Calcitriol in the blood?

Answer 25

Cell differentiation Activation of osteoblasts Calcium and phosphate homeostasis

Question 26

What is the overall MOA of Vitamin D3?

Answer 26

increase the amount of Ca in plasma

Question 27

Which hormone os produced in the thyroid gland in the c cells?

Answer 27

Calcitonin

Question 28

What is the overall MOA of calcitonin?

Answer 28

decrease Ca2+ in the plasma and increase PO4 in plasma (i.e., inhibits bone resorption

Question 29

Hyperparathyroidism is a disease of Ca metabolism. It involves which hormone and what is the direct consequence?

Answer 29

PTH hyper secretion which results in hypercalceamia

Question 30

What is the primary cause of hyperparathyroidism?

Answer 30

adenoma (cancer of parathyroid gland)

Question 31

What are the two secondary causes of hyperparathyroidism?

Answer 31

chronic renal failure | Nutritional

Question 32

What controls PTH release?

Answer 32

Plasma Ca2+ levels

Question 33

What are some of the effects of hyperparathyroidism?

Answer 33

Osteoporosis Increased Ca2+ excretion (issues with kidney) Decreased excitability of nerves and muscles - this seems unusual bc calcium is involved in excitation

Question 34

What is the main cause of hypoparathyroidism? And what can it lead to?

Answer 34

primary destruction of the parathyroid/thyroid gland (immune mediated or post-surgical), hypocalcaemia

Question 35

List three other causes of hypocalcaemia

Answer 35

pregnancy, lack of vitamin D, change in blood pH

Question 36

Hypocalcaemia is a serious condition - in what way can it cause death?

Answer 36

Increased neuromuscular excitability, death due to asphyxiation

Question 37

What is the MOA of the drug Calcitriol?

Answer 37

Increases Ca uptake from diet --> mobilises Ca from bones

Question 38

List three bisphosphonates that are used in the treatment of osteoporosis.

Answer 38

Risedronate, Alendronate, Zoledronate

Question 39

What is the MOA of the bisphosphonates?

Answer 39

Inhibit the activity of osteoclasts (effects can last months to years)

Question 40

Which SERM is used in osteoporosis? What is it MOA? Who are you more likely to treat with this drug?

Answer 40

Raloxefine, stimulate osteoblast activity, inhibit osteoclast activity. Women

Question 41

Why are women susceptible to osteoporosis?

Answer 41

Menopause = decrease in estrogen whereas the testosterone in men is converted to oestrogen in the bone

Question 42

What is the MOA of Denosumab?

Answer 42

inhibits RANKL, therefore decreases bone resorption