Sketchy Pharm: Bisphosphonates, Raloxifene, Denosumab, Calcitonin

Question 1

The bisphosphonates preferentially bind to ________________.

Answer 1

hydroxyapatite (like the T-rex’s big appetite –represented by his agape mouth –over the DONATE box)

Question 2

How do bisphosphonates ultimately work?

Answer 2

When osteoclasts bind to the bisphosphonates bound to hydroxyapatite, they get stuck and undergo apoptosis.

(This is represented by the Osteo-Class student with his arm stuck in the DONATE box and his popping balloon.)

They also prevent the further recruitment of osteoclasts (like the chaperone preventing more students from entering).

Question 3

Bisphosphonates are excellent at treating _________________.

Answer 3

hypercalcemia of malignancy (represented by the PP stealing kid being escorted out over the bone with crabs)

Question 4

Other than malignancy, bisphosphonates are also great for ________________.

Answer 4

Paget’s (same with calcitonin)

Think of the disorganized skeleton in the background.

Question 5

Three side effects of bisphosphonates are _________________.

Answer 5

esophagitis (crumbling neck of the diplodocus), osteonecrosis of the jaw (falling jaw of the diplodocus), and hypocalcemia (spilled ice cream on the museum floor) –all more common with IV administration

Question 6

How does estrogen accomplish its main bone protective effect?

Answer 6

It prevents the differentiation of osteoclasts (just like the postmenopausal woman preventing the next Osteo-Class from entering the museum).

Question 7

Explain how raloxifene works.

Answer 7

It is a selective estrogen receptor modifier. It is an agonist on the bone and an antagonist on the uterus and breast. Thus, it prevents bone resorption and prevents breast/uterine cancer.

Question 8

How does PTH affect bone?

Answer 8

It stimulates osteoblasts to make RANK-L to activate osteoclasts.

(Think of the PTH PhD – in paleontology –convincing the Osteo-Builder to give his cRANK tool to the Osteo-Class student.)

Question 9

Denosumab binds to ______________.

Answer 9

RANK-L to prevent activation of osteoclasts

Think of the DiNO man grabbing the cRANK.

Question 10

Calcitonin directly inhibits ______________.

Answer 10

osteoclasts (like the calcitonin curator escorting kids out)

Question 11

Calcitonin’s main use is to _______________.

Answer 11

prevent hypercalcemia of malignancy (by inhibiting release of calcium from bone); it is also used in Paget’s

(Think of the calcitonin curator standing over the crab symbol and pointing down.)