wk 10

Question 1

What is the MoA of bisphosphonates (Alendronate, Ibandronate, Risedronate, Zoledronic acid)?

Answer 1

Inhibit osteoclast-mediated bone resorption.

DONATE: "-dronate" suffix of bisphosphonates (e.g alendronate, pamidronate, zoledronate), the first line treatment for osteoporosis cropped symbol image 4 5. Two P coins: bisphosphonates have a chemical structure similar to pyrophosphate cropped symbol image 5 6. Large T-rex appetite: bisphosphonates attach to hydroxyapatite in bone 7. Classmate stuck in donation box: osteoclasts bind to the bisphosphonate, inhibiting their adherence to the bony surface 8. Class waiting to enter: osteoclast precursors 9. Preventing class from entering: bisphosphonates decrease the development and recruitment of osteoclast precursors 10. Classmate's popping balloon: bisphosphonates induce osteoclast apoptosis 11. Elevated calci-yum icecream: bisphosphonates are useful in the acute treatment of hypercalcemia 12. Massive calcified rock with metastatic crab fossils: hypercalcemia of malignancy is a common cause of severe hypercalcemia requiring acute treatment (with bisphosphonates and calcitonin) 13. Disorganized bone display: bisphosphonates and calcitonin are useful in the management of Paget disease (uncontrolled osteoclast resorption with secondary disorganized bone formation)

Question 2

What are common and rare adverse effects of bisphosphonates?

Answer 2

Common: Esophagitis, myalgias; Rare: Osteonecrosis of the jaw (ONJ), atypical fractures, hypocalcemia.

Corroded neck: bisphosphonates can cause upper GI side effects (e.g. acid reflux, esophagitis, esophageal ulcers) 15. Crumbling jaw bone: bisphosphonates can cause osteonecrosis of the jaw (rare)

Question 3

What is the MoA of Denosumab (Prolia)?

Answer 3

Reduces osteoclast formation by inhibiting RANK-L.

Crank-drill: receptor activator of nuclear factor kappaB ligand (RANKL) 25. Active classmate with crank-drill: RANKL binds to RANK on the osteoclast, increasing its activity 26. Dino suit man grabbing crank-drill: denosumab (monoclonal antibody against RANKL) is useful in the treatment of osteoporosis 27. Antibody spikes: denosumab is a monoclonal antibody

Question 4

What are adverse effects of Denosumab?

Answer 4

Injection site reactions, ONJ, atypical fractures, hypocalcemia.

Question 5

What is the MoA of Tamoxifen?

Answer 5

Estrogen agonist in bone and uterus, antagonist in breast tissue.

Question 6

What are adverse effects of Tamoxifen?

Answer 6

Hot flashes, edema, arthralgia, flu-like symptoms; Serious: Thrombosis, stroke, endometrial cancer.

Question 7

What is Tamoxifen used for?

Answer 7

Breast cancer.

Question 8

Does Tamoxifen help with osteoporosis?

Answer 8

No, it hasn’t been studied for osteoporosis.

Question 9

What is the MoA of Raloxifene?

Answer 9

Estrogen agonist in bone, antagonist in breast and uterus.

Female guarding class entrance: estrogen inhibits differentiation of osteoclast precursors 20. Relax: raloxifene (a selective estrogen receptor modulator - SERM) is useful in the treatment and prevention of postmenopausal osteoporosis 21. Relaxing the waiting classmates: raloxifene has estrogen agonist activity in bone (inhibits osteoclast differentiation) and estrogen antagonist activity in breast and uterus (reduced risk of breast cancer