Lecture 30: Bone Minerals

Question 1

What is the principal reservoir for calcium and phosphate?

Answer 1

Bone

Question 2

Why is regulation of Calcium and Phosphate important?

Answer 2

• Health/strength of bones
• Ca balance has effects on electrical excitability of cells
• Ca is an essential intracellular signal

Question 3

What are the major targets of Ca2+ and PO43- control?

Answer 3

The Gut, Kidney and Bone

Question 4

What is resorption?

Answer 4

The breakdown of bone which allows calcium to go into the bloodstream

Question 5

what do Osteoblasts cause?

Answer 5

Deposition of bone

Question 6

What do osteoclasts cause?

Answer 6

Resorption of bone

Question 7

What are the major regulators of bone remodelling?

Answer 7

Vitamin D metabolites and PTH

Question 8

How can Osteoclasts be activated?

Answer 8

Osteoclasts must be activated by osteoblasts that release the Rank Ligand which binds to osteoclasts and binds to the Rank receptor on osteoclasts

Question 9

What are Parathyroid Hormones effects on the bone?

Answer 9

It promotes bone resorption indirectly through RANKL so it increases Ca and PO4 levels

Question 10

What are Parathyroid Hormones effects on the Kidney?

Answer 10

It promotes Ca absorption and promotes PO4 excretion

Question 11

What is the net effect of Parathyroid hormone?

Answer 11

It increases calcium and PO4 in the blood

Question 12

Where is parathyroid hormone released from?

Answer 12

The parathyroid gland

Question 13

What is PTH made is response to?

Answer 13

Reduced levels of circulating calcium

Question 14

Why does PTH promote phosphate excretion in the kidneys?

Answer 14

So it doesn’t form precipitates, crystals and stones

Question 15

How does PTH affect vitamin D in the kidneys?

Answer 15

It promotes the processing of vitamin D to its active form

Question 16

What causes PTH to be released?

Answer 16

Decreased levels of circulating calcium

Question 17

How does the parathyroid gland sense the level of circulating calcium?

Answer 17

It has calcium-sensitive receptors

Question 18

What kind of Hormone is Vitamin D?

Answer 18

A steroid hormone

Question 19

What is vitamin D metabolized in the liver to form?

Answer 19

• Calcitriol (1,25-hydroxy vitamin D3)

* Calciferol (24,25-hydroxy D3)

Question 20

What is the active form of the Vitamin D metabolites?

Answer 20

Calcitriol (1,25-hydroxy vitamin D3)

Question 21

How is vitamin D metabolized?

Answer 21

First the liver converts vitamin D3 to 25-OH-D3 and then the kidney converts this to Calcitriol and Secalciferol

Question 22

What causes Secalciferol (24,25-hydroxy D3) to be produced?

Answer 22

High circulating levels of calcium or high levels of the calcitriol form

Question 23

What does Vitamin D do?

Answer 23

Promotes the resorption of calcium to increase levels in the blood

Question 24

What promotes the kidneys to produce Calcitriol (1,25-hydroxy vitamin D3)

Answer 24

High levels of PTH and low levels of circulating calcium

Question 25

How does Vitamin D3 affect the kidney?

Answer 25

It increases calcium reabsorption from bones and promotes phosphate excretion

Question 26

How does vitamin D3 affect the bone?

Answer 26

It promotes bone resorption and increases calcium and phosphate levels in the blood

Question 27

How does vitamin D3 affect the gut?

Answer 27

It promotes the uptake of calcium and phosphate from the gut to increase circulating levels

Question 28

What is the net effect of the active form of vitamin D3?

Answer 28

It increases circulating calcium and phosphate

Question 29

Where does PTH exert it effects?

Answer 29

In kidneys and osteoblasts

Question 30

What does PTH stimulation of vitamin D do?

Answer 30

It leads to vitamin D effects in gut, kidney and bone

Question 31

What are the normal circulating levels of calcium?

Answer 31

2.2 mM total calcium, 1mM free caclcium

Question 32

How can hypocalcemia be resolved short term?

Answer 32

The patient can be given calcium or an active D3 metabolite that will increase blood calcium levels

Question 33

What can Hypocalcemia cause?

Answer 33

Hyperactivity of cells

Question 34

What is an early symptom of Hypocalcemia?

Answer 34

Trousseau's sign

Question 35

what is a longer-term danger of Hypocalcemia?

Answer 35

Secondary hyperparathyroidism

Question 36

What is secondary hyperparathyroidism?

Answer 36

A hyperactive parathyroid due to low plasma calcium due to kidney failure that stops reabsorption of Ca2+. So the parathyroid wants to increase circulating hormone by releasing PTH but there is no calcium being absorbed so its consistently being released

Question 37

What does secondary hyperparathyroidism lead to?

Answer 37

The breakdown and weakening of bones

Question 38

What usually causes long term Hypocalcemia?

Answer 38

* Hypoparathyroidism | * Vitamin D deficiency

Question 39

How does Hypoparathyroidism cause Hypocalcemia?

Answer 39

A defect in the parathyroid gland that doesn't allow it to produce parathyroid hormone

Question 40

How is secondary hypoparathyroidism caused by hypocalcemia treated?

Answer 40

With vitamin D and calcium supplementation

Question 41

How can Vitamin D deficiency cause Hypocalcemia?

Answer 41

The inability to generate vitamin D metabolites

Question 42

How can hypocalcemia caused by vitamin D deficiency be resolved?

Answer 42

By dietary correction or ingestion of active Vit D3 metabolites (calcitriol), sunshine

Question 43

What is Hypercalcemia?

Answer 43

Too much circulating calcium

Question 44

What does acute hypercalcemia cause?

Answer 44

Loss of cellular excitability, lethargy, coma, pain in bones due to excessive PTH

Question 45

What causes Hypercalcemia long-term?

Answer 45

Primary hyperparathyroidism

Question 46

What can primary hyperparathyroidism be due to?

Answer 46

A tumor

Question 47

What is treatment form primary hyperparathyroidism?

Answer 47

* Resection of the gland * Bisphosphonates, calcitonin, inhibitors of bone resorption * Calcimimetics

Question 48

What are Calcimimetics?

Answer 48

Drugs that mimic the effects of calcium on the calcium receptors causing negative feedback and decrease the amount of parathyroid hormone released

Question 49

What is Osteoporosis?

Answer 49

A loss in bone density

Question 50

Why is osteoporosis seen in post-menopausal women?

Answer 50

because estrogen promotes bone deposition

Question 51

What is one of the ways the osteoporosis can be treated and what are their downsides?

Answer 51

Hormone replacement - but they have serious adverse effects like cancers

Question 52

What are other common causes of osteoporosis aside from hormones?

Answer 52

* Glucocorticoid administration | * Hyperparathyroidism

Question 53

What is Teripide used to treat?

Answer 53

Osteoporosis

Question 54

How does Teriparatide work?

Answer 54

It acts on osteoblasts to activate them but because it doesn't give enough for them to activate osteoclasts causing deposition

Question 55

What are Bisphosphonates used to treat?

Answer 55

Osteoporosis

Question 56

How do Bisphosphonates work?

Answer 56

They inhibit osteoclast resorption of bone through inhibiting glucocorticoids. They also have a toxic effect on osteoclasts

Question 57

How do glucocorticoids affect the deposition of bone?

Answer 57

They tend to promote the activity of osteoclasts which cause resorption of bones and suppress the activity of osteoblasts

Question 58

Why do bisphosphonates have a toxic effect on osteoclasts?

Answer 58

The phosphonate groups of the bisphosphonates have a high affinity for Ca2+ so they accumulate in bone allowing osteoclasts to target them

Question 59

What is Osteoprotegerin used to treat?

Answer 59

Osteoporosis

Question 60

How does Osteoprotegerin work?

Answer 60

It competes with RANK by binding to RANKL and inhibiting activation which inhibits bone resorption by osteoclasts

Question 61

What is Denosumab used to treat?

Answer 61

Osteoporosis

Question 62

How does Denosumab work?

Answer 62

It is an antibody against RANKL, and mimics osteoprotegerin