A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
A 58-year-old woman presents to the office for routine follow-up. She recently underwent routine screening for bone density due to a history of hypothyroidism. She also has a history of gastroesophageal reflux disease (GERD) that is being treated with a proton-pump inhibitor (PPI) and more recently with a histamine2 receptor antagonist (H2RA), hypertension being treated with a thiazide diuretic, depression being treated with lithium, and hormone replacement therapy. Her results meet the criteria for osteopenia, with a T-score of -1.6. She is concerned about progressive bone loss and the risk of fractures. Which of the following medication classes should be discontinued?
-
A
Proton-pump inhibitorsCorrect. chronic PPI use is associated with increased fracture risk through decreased calcium absorption and other mechanisms; discontinue (or step down to H2RA) in patients with osteopenia or osteoporosis when GERD is otherwise manageable.
-
B
Thiazide diureticsIncorrect. Thiazide diuretics reduce urinary calcium excretion and are BENEFICIAL for bone density; they should be continued and are sometimes added as adjunctive therapy in osteoporosis.
-
C
LithiumIncorrect. Lithium has minimal direct effect on bone (concern is parathyroid effects, which can be monitored); it's a critical psychiatric medication and shouldn't be stopped to address mild osteopenia.
-
D
EstrogenIncorrect. Estrogen (HRT) is PROTECTIVE of bone density in postmenopausal women; stopping it would worsen bone loss (though HRT has other long-term risks).
-
E
Histamine2 receptor antagonistsIncorrect. H2RAs have a much smaller (if any) effect on bone density compared to PPIs and are often the safer alternative for acid suppression in patients with osteopenia; the patient's chronic PPI use is the primary medication to discontinue.
↑ Tap an answer to reveal the reasoning
Answer: A. This 58-year-old woman with multiple risk factors for osteoporosis (hypothyroidism, hormone replacement, lithium, PPI, thiazide, H2RA) has osteopenia (T-score -1.6) on screening. The question asks which medication CLASS should be discontinued to optimize her bone health.
Let's evaluate each medication's effect on bone:
- PROTON-PUMP INHIBITORS: chronic use is associated with INCREASED FRACTURE RISK, particularly hip, wrist, and spine. Mechanisms include decreased calcium absorption (calcium carbonate requires acid for dissolution; calcium citrate does not), decreased vitamin B12 absorption, and possibly direct effects on osteoclast function. The FDA has issued a warning about long-term PPI use and fracture risk.
- Thiazide diuretics: DECREASE urinary calcium excretion (by enhancing reabsorption in the distal tubule), which is BENEFICIAL for bone density. Often used as adjunctive therapy in patients with hypercalciuria-related osteoporosis. Should be CONTINUED.
- Lithium: mostly neutral or possibly mildly beneficial for bone density; primary concern is hyperparathyroidism, which can be evaluated. Lithium is also a critical medication for her depression and shouldn't be stopped without specific cause.
- Estrogen (HRT): is PROTECTIVE for bone density (postmenopausal HRT preserves BMD). Stopping would worsen bone loss; however, HRT has cardiovascular risks that may eventually require discontinuation.
- H2RA (newly started): less concerning for bone density than PPIs.
The correct answer is to discontinue the PPI. She can transition fully to the H2RA (less impact on calcium absorption) or no acid suppression if her GERD is controllable with lifestyle.
Clinical pearl: long-term PPI use is also associated with C. difficile infection, hypomagnesemia, B12 deficiency, and acute interstitial nephritis. Use the lowest effective dose for the shortest duration in patients at fracture risk.
**Why each option:**
**A.** Correct: chronic PPI use is associated with increased fracture risk through decreased calcium absorption and other mechanisms; discontinue (or step down to H2RA) in patients with osteopenia or osteoporosis when GERD is otherwise manageable.
**B.** Thiazide diuretics reduce urinary calcium excretion and are BENEFICIAL for bone density; they should be continued and are sometimes added as adjunctive therapy in osteoporosis.
**C.** Lithium has minimal direct effect on bone (concern is parathyroid effects, which can be monitored); it's a critical psychiatric medication and shouldn't be stopped to address mild osteopenia.
**D.** Estrogen (HRT) is PROTECTIVE of bone density in postmenopausal women; stopping it would worsen bone loss (though HRT has other long-term risks).