Bone Mineralization Drugs

Question 1

Discuss the regulatory actions of calcium.

Answer 1

High calcium levels result in the conversion of vitamin D to its inactive form D3 instead of the active 1,25 and inhibits PTH secretion.

Question 2

Describe the clinical uses of calcium.

Answer 2

Calcium salts are used to tx hypocalcemia. IV calcium salts (usually Ca++ chloride and Ca++ gluconate) for severe cases.

Question 3

What can you give with calcium for rapid rise of serum Ca++ levels in severe hypocalcemia?

Answer 3

Calcitriol. Raises levels within 24-48h.

Question 4

What are the daily recommendations for calcium intake?

Answer 4

19-50 y.o.: 1000mg

>50 y.o.: 1200mg

Question 5

Describe the mechanism of action and clinical use of Teriparatide.

Answer 5

It is thought to preferentially activate osteoblasts for the treatment of osteoporosis. It increases serum Ca++ (like PTH). Available as injection.

Question 6

What adverse effect is associated with Teriparatide?

Answer 6

Increased risk of osteosarcoma

Question 7

Describe the effects of PTH at low/intermittent levels.

Answer 7

Builds up bone- stimulates conversion of osteoblast precursors to active osteoblasts for bone formation

Question 8

Describe the action of PTH at high levels.

Answer 8

Breaks down bone- kidneys decrease Ca++ excretion and bones resorb Ca++, and enhances vitamin D production in the kidney. Ultimate goal of increasing serum Ca++ levels.

Question 9

What is the net result of excess PTH?

Answer 9

To raise serum Ca++ and reduce phosphate.

Question 10

Describe the metabolism of Vitamin D.

Answer 10

It circulates bound to plasma protein and is converted via skin, liver, and finally kidneys to reach active form calcitriol.

Question 11

Describe the actions of calcitriol (active vitamin D).

Answer 11

It acts as a hormone, binding receptors in many tissues and inducing Ca++-binding proteins in the intestine and modulates Ca++ flux across brush border and basolateral membranes. Also stimulates osteoblast synthesis and this induces increases osteoclast activity. Regulates PTH secretion.

Question 12

What is the result of Vitamin D toxicity?

Answer 12

hypercalcemia

Question 13

What is the net effect of active Vitamin D?

Answer 13

Raises both serum Ca++ and phosphate.

Question 14

What are the clinical uses of Vitamin D?

Answer 14

Prophylaxis for deficiency and hypoparathyroidism

Question 15

What special consideration effects Vitamin D administration?

Answer 15

Renal failure. These patients can’t convert inactive vitamin D to calcitriol very well, so you need to give them calcitriol.

Question 16

Discuss the general purpose of bisphosphonate use.

Answer 16

These drugs are non-hormonal agents affecting bone mineral homeostasis, concentrating at sites of active remodeling in bone. They are used to treat osteoporosis and Paget’s disease

Question 17

Name the three bisphosphonates discussed in lecture and their mechanism of action.

Answer 17

“AIR”: alendronate, ibandronate, risedronate

They interfere with cholesterol synthesis thus inhibiting activation of osteoclasts

Question 18

Which of the three bisphosphonates discussed in lecture is 3rd generation and thus more potent?

Answer 18

Risedronate

Question 19

Discuss longterm use of bisphosphonates.

Answer 19

Longterm use may lessen their benefits because they suppress bone turnover, preventing remodeling/healing of cracks.

Question 20

Describe the pharmacokinetics of bisphosphonates.

Answer 20

They are poorly absorbed and should be taken on an empty stomach with water, sitting upright to prevent esophagitis.

Question 21

How often are bisphosphonates taken?

Answer 21

Alendronate is taken once weekly, Ibandronate and Risedronate are taken once monthly.

Question 22

Describe the actions of calcitonin.

Answer 22

It regulates circulating Ca++ levels by reducing Ca++ retention and opposing osteoclast action. It also lowers phosphate levels via bone and kidney action.

Question 23

Describe the clinical use for calcitonin.

Answer 23

It is used to treat Paget’s disease

Question 24

In what forms is calcitonin available for administration?

Answer 24

Nasal spray and parenteral injection

Question 25

Describe the actions of estrogen on bone mineralization.

Answer 25

It inhibits osteoclasts by upregulating the decoy receptor OPG (binds RANKL to prevent osteoclast differentiation), decreases production of several osteoclast-stimulating cytokines (IL-1, IL-6, TNF-a), and it increases production of collagen/other proteins/markers of differentiated osteoblasts

Question 26

What is the result of estrogen deficiency in men?

Answer 26

Osteopenia (low bone density) and failure to close epiphyses

Question 27

What risks increase with estrogen use?

Answer 27

Coronary events, stroke, PE, and breast CA

Question 28

What is the clinical indication for estrogen replacement regarding bone mineralization?

Answer 28

Osteoporosis in women

Question 29

Discuss the benefits of using Raloxifene over estrogen.

Answer 29

It is a selective estrogen receptor modulator (SERM) with reduced risk of breast or endometrial cancer

Question 30

What is the major drawback of Raloxifene use?

Answer 30

Worsening of vasomotor sx

Question 31

Describe the mechanism of action of Denosumab.

Answer 31

It mimics the effect of OPG (the RANKL decoy) by blocking osteoclast formation and activation. It increases bone mineral deposition and decreases bone turnover

Question 32

How often is Denosumab administered?

Answer 32

Every 6 months

Question 33

Describe the mechanism of action of Cinacalcet.

Answer 33

It binds to the Ca++-sensing receptor that when bound can be activated at lower concentrations of Ca++, resulting in reduced PTH synthesis and secretion.

Question 34

What are the clinical uses for Cinacalcet?

Answer 34

It is used to treat hypercalcemia d/t hyperparathyroidism

Question 35

Describe the general actions of calcium.

Answer 35

Bone formation, neuronal excitability, neurotransmitter release, muscle contraction, membrane integrity, and blood coagulation.