MSK pharm – Osteoporosis agents

a) Bisphosphonates (Alendronate, Zoledronic acid)

b)

• Inhibit osteoclast activity, thereby inhibiting bone resorption.
• Should be noted that the endogenous hormone calcitonin also inhibits osteoclast activity (HY).

HY side-effects of bisphosphonates for USMLE?

• By far and away, pill-induced esophagitis is the highest yield side-effect of bisphosphonates. That is, the patient can get a GERD-like presentation with burning in the throat/chest while taking, e.g., alendronate and you need to know this is merely a side-effect of the drug. Should be noted that potassium supplements can also cause pill-induced esophagitis.
• Osteonecrosis of the jaw is a zebra side-effect that most students tend to fixate on, and by all means you should be aware of it, but it’s to my observation it’s quite low-yield for USMLE compared to pill-induced esophagitis.

In patients who’ve already had fracture(s).

USMLE sequence for osteoporosis Tx = weight-bearing exercise → calcium + vitamin D → bisphosphonate (e.g., alendronate) → teriparatide or denosumab.

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It’s HY for USMLE to know that weight-bearing exercise is the number-one treatment + preventative measure for osteoporosis. In other words, even if the patient already has low bone density on DEXA scan, if they ask what should be done for the patient, still choose weight-bearing exercise first if listed.

• 72F + osteoporosis; which of the following will best decrease fracture risk in this patient? –> answer = “going for daily long walks”; wrong answer = “swimming daily” (on NBME exam).

Calcium + vitamin D are the first-line pharmacologic therapy for osteoporosis. Then a bisphosphonate is added if the patient has history of fractures.

• 74F + osteoporosis + taking calcium and vitamin D; the addition of which pharmacologic agent could best decrease this patient’s fracture risk? –> answer = alendronate (whichever bisphosphonate is listed).

Bisphosphonates are given to patients who are commencing oral steroids indefinitely, or who are receiving numerous courses of steroids.

Remember that corticosteroids cause osteoporosis (compression fracture / point tenderness of the spine) and avascular necrosis (hip pain) in younger patients.

• 32M + SLE + receiving third two-week course of oral prednisone in the past six months for flare control; what’s the next best step in management? –> answer = “immediate bisphosphonate therapy,” or “alendronate now” (HY in particular on FM shelf).

0.9% NaCl normal saline

Pamidronate

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What are other really HY times on the USMLE that bisphosphonates are used?

• Given to patients who are commencing oral steroids indefinitely, or who are receiving numerous courses of steroids. Remember that corticosteroids cause osteoporosis (compression fracture / point tenderness of the spine) and avascular necrosis (hip pain) in younger patients.
  • 32M + SLE + receiving third two-week course of oral prednisone in the past six months for flare control; what’s the next best step in pharmacologic management? –> answer = “immediate bisphosphonate therapy,” or “alendronate now” (HY in particular on FM shelf).
• First-line agent given after IV normal saline for hypercalcemia.
  • 21M + primary hyperparathyroidism + serum calcium of 14.3 mEq/L (NR 8.4-10.2); what’s the next best step in treatment? –> answer = 0.9% normal saline.
  • 21M + primary hyperparathyroidism + serum calcium of 14.3 mEq/L (NR 8.4-10.2) + receives infusion of saline + what’s the next best step in management? ; what’s the next best step in management? –> answer = “pamidronate” (frequently the bisphosphonate used for hypercalcemia).

Increases bone density by stimulating osteoblasts.

N-terminus analogue of PTH.

Endogenous PTH normally binds to osteoblasts, which in turn express RANK-L, which binds to RANK receptor on osteoclasts → ↑ bone resorption → decrease in bone density. Student says, “Wait, then how does that make sense then that we’d give a drug that’s structurally similar to PTH?” → teriparatide stimulates osteoblasts without the concomitant activation of osteoclasts → increase in bone density. Weird, but it’s what the drug does.

Don’t give to patients with history of bone tumors.

Don’t give to patients with Paget disease of bone (↑ risk of osteosarcoma).

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MOA of teriparatide?

• Increases bone density by stimulating osteoblasts.
• N-terminus analogue of PTH.
• Endogenous PTH normally binds to osteoblasts, which in turn express RANK-L, which binds to RANK receptor on osteoclasts → ↑ bone resorption → decrease in bone density. Student says, “Wait, then how does that make sense then that we’d give a drug that’s structurally similar to PTH?” → teriparatide stimulates osteoblasts without the concomitant activation of osteoclasts → increase in bone density. Weird, but it’s what the drug does.

Monoclonal antibody against RANK-L → leads to decreased RANK-L/RANK interaction → better preservation of bone density.

Used for severe osteoporosis with history of fractures while on multiple medications.

Bisphosphonates (e.g., alendronate, zoledronic acid)

Teriparatide

MOA of teriparatide?

• Increases bone density by stimulating osteoblasts.
• N-terminus analogue of PTH.
• Endogenous PTH normally binds to osteoblasts, which in turn express RANK-L, which binds to RANK receptor on osteoclasts → ↑ bone resorption → decrease in bone density. Student says, “Wait, then how does that make sense then that we’d give a drug that’s structurally similar to PTH?” → teriparatide stimulates osteoblasts without the concomitant activation of osteoclasts → increase in bone density. Weird, but it’s what the drug does.

Bit of an asshole distinction. But the USMLE will do this.

Always choose weight-bearing exercise first if listed (e.g., long walks). Don’t choose swimming; it’s wrong.

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