Drugs affecting calcium regulation MCQs With Answer

Introduction

Drugs affecting calcium regulation are central to managing disorders of bone and mineral metabolism encountered in M.Pharm practice—ranging from osteoporosis and Paget’s disease to hypercalcemia of malignancy and chronic kidney disease–related mineral bone disorder. This quiz set explores the pharmacology, mechanisms, clinical uses, adverse effects and interactions of agents that alter calcium homeostasis: vitamin D analogs, bisphosphonates, denosumab, calcimimetics, PTH analogs, calcitonin, anti-sclerostin antibodies and diuretics affecting renal calcium handling. The questions emphasize mechanistic depth, therapeutic rationale and safety considerations relevant to advanced pharmacology training and clinical decision-making.

Q1. Which mechanism best describes how nitrogen-containing bisphosphonates (e.g., alendronate) inhibit osteoclast-mediated bone resorption?

• Chemoattraction blockade of osteoclast precursors via CXCR4 inhibition
• Inhibition of farnesyl pyrophosphate synthase in the mevalonate pathway, causing osteoclast apoptosis
• Direct antagonism of RANKL binding to RANK on osteoclasts
• Activation of the calcium-sensing receptor on osteoclasts leading to reduced activity

Correct Answer: Inhibition of farnesyl pyrophosphate synthase in the mevalonate pathway, causing osteoclast apoptosis

Q2. Denosumab’s antiresorptive effect is primarily mediated by which of the following actions?

• Binding and neutralizing sclerostin to stimulate Wnt signaling
• Monoclonal antibody binding to RANKL, preventing osteoclast maturation
• Direct stimulation of osteoprotegerin production by osteoblasts
• Increasing renal calcium reabsorption through the calcium-sensing receptor

Correct Answer: Monoclonal antibody binding to RANKL, preventing osteoclast maturation

Q3. Which adverse effect is most classically associated with long-term bisphosphonate therapy?

• Osteosarcoma in adults
• Osteonecrosis of the jaw and atypical femoral fractures
• Severe hypercalcemia due to bone resorption
• Progressive renal stone formation

Correct Answer: Osteonecrosis of the jaw and atypical femoral fractures

Q4. Cinacalcet is indicated in secondary hyperparathyroidism because it:

• Is a vitamin D analog that increases intestinal calcium absorption
• Acts as a positive allosteric modulator of the calcium-sensing receptor on parathyroid cells, lowering PTH secretion
• Inhibits osteoclast activity by blocking RANKL
• Stimulates renal 1-alpha hydroxylase to increase calcitriol production

Correct Answer: Acts as a positive allosteric modulator of the calcium-sensing receptor on parathyroid cells, lowering PTH secretion

Q5. Teriparatide’s unique anabolic effect on bone is best explained by its:

• Continuous PTH receptor stimulation leading to osteoclast activation
• Intermittent PTH receptor activation promoting osteoblast differentiation and activity
• Antagonism of sclerostin to increase Wnt signaling
• Inhibition of farnesyl pyrophosphate synthase in osteoblasts

Correct Answer: Intermittent PTH receptor activation promoting osteoblast differentiation and activity

Q6. A patient on oral alendronate should be counseled to avoid coadministration with which of the following to maximize absorption?

• Proton pump inhibitors (e.g., omeprazole)
• Food and beverages containing calcium, magnesium or iron
• Concurrent vitamin D supplementation
• Non-steroidal anti-inflammatory drugs

Correct Answer: Food and beverages containing calcium, magnesium or iron

Q7. Which of the following is the most appropriate initial pharmacologic therapy for severe hypercalcemia of malignancy with evidence of osteolysis?

• High-dose vitamin D (calcitriol)
• Intravenous bisphosphonate (e.g., zoledronic acid)
• Oral calcium supplements
• Cinacalcet for immediate calcium lowering

Correct Answer: Intravenous bisphosphonate (e.g., zoledronic acid)

Q8. Which statement about denosumab discontinuation is correct?

• Bone turnover remains suppressed for months after stopping, with no increased fracture risk
• Stopping denosumab can cause rapid loss of bone density with rebound vertebral fractures due to osteoclast activation
• It causes permanent changes in osteoclast precursors, so no follow-up treatment is required
• Discontinuation results in sustained hypocalcemia for weeks

Correct Answer: Stopping denosumab can cause rapid loss of bone density with rebound vertebral fractures due to osteoclast activation

Q9. Which vitamin D metabolite is most active and directly binds the nuclear vitamin D receptor to regulate gene transcription?

• 25-hydroxycholecalciferol (calcifediol)
• 1,25-dihydroxycholecalciferol (calcitriol)
• Cholecalciferol (vitamin D3)
• 24,25-dihydroxycholecalciferol

Correct Answer: 1,25-dihydroxycholecalciferol (calcitriol)

Q10. Which diuretic class increases urinary calcium excretion and can worsen hypocalcemia or renal calcium loss?

• Thiazide diuretics
• Loop diuretics (e.g., furosemide)
• Potassium-sparing diuretics
• Carbonic anhydrase inhibitors

Correct Answer: Loop diuretics (e.g., furosemide)

Q11. Calcitonin lowers serum calcium acutely by which mechanism?

• Stimulating renal 1-alpha hydroxylase to produce calcitriol
• Direct inhibition of osteoclast-mediated bone resorption and increasing renal calcium excretion
• Blocking intestinal calcium absorption via TRPV6 channels
• Antagonizing PTH receptor signaling in osteoblasts

Correct Answer: Direct inhibition of osteoclast-mediated bone resorption and increasing renal calcium excretion

Q12. The risk of hypocalcemia during denosumab treatment is increased in patients with which condition?

• Primary hyperparathyroidism with high bone turnover
• Chronic kidney disease with low 1,25(OH)2D production and vitamin D deficiency
• Hypervitaminosis D
• High dietary calcium intake

Correct Answer: Chronic kidney disease with low 1,25(OH)2D production and vitamin D deficiency

Q13. Which of the following best describes the mechanism of romosozumab in increasing bone formation?

• It is an intermittent PTH analog that increases osteoblast number
• Monoclonal antibody against sclerostin, thereby enhancing Wnt/β-catenin signaling and bone formation
• RANKL inhibitor that indirectly stimulates osteoblasts
• Vitamin D receptor agonist that increases intestinal calcium absorption

Correct Answer: Monoclonal antibody against sclerostin, thereby enhancing Wnt/β-catenin signaling and bone formation

Q14. Which pharmacokinetic property of bisphosphonates accounts for their prolonged skeletal retention?

• High lipophilicity leading to deposition in adipose tissue
• Strong affinity for hydroxyapatite in bone matrix and incorporation into bone mineral
• Extensive hepatic metabolism producing long-acting metabolites
• Binding to plasma proteins with long half-life

Correct Answer: Strong affinity for hydroxyapatite in bone matrix and incorporation into bone mineral

Q15. Which of the following is the most important counseling point when initiating oral bisphosphonate therapy?

• Take it with a high-calcium meal to enhance absorption
• Remain upright for at least 30 minutes and take with plain water on an empty stomach to reduce esophageal irritation and improve absorption
• Expect immediate pain relief within 24 hours
• Discontinue vitamin D while on bisphosphonates

Correct Answer: Remain upright for at least 30 minutes and take with plain water on an empty stomach to reduce esophageal irritation and improve absorption

Q16. Glucocorticoids can cause bone loss by which primary mechanism relevant to calcium regulation?

• Increasing intestinal calcium absorption via upregulation of TRPV6
• Decreasing renal calcium excretion to cause secondary hyperparathyroidism
• Inhibiting osteoblast function and reducing intestinal calcium absorption leading to negative calcium balance
• Direct activation of osteoclasts through RANKL agonism

Correct Answer: Inhibiting osteoblast function and reducing intestinal calcium absorption leading to negative calcium balance

Q17. Which therapeutic strategy is recommended to reduce the acute phase reaction (fever, myalgia) that can occur after IV bisphosphonate infusion?

• Pre-treatment with oral bisphosphonate
• Pre-treatment with acetaminophen or NSAID and ensuring adequate hydration
• Administering denosumab instead of bisphosphonate immediately
• High-dose vitamin D bolus prior to infusion

Correct Answer: Pre-treatment with acetaminophen or NSAID and ensuring adequate hydration

Q18. A patient with sarcoidosis develops hypercalcemia. Which pharmacologic agent is most likely to be effective because granulomatous disease increases extrarenal 1-alpha hydroxylase activity?

• Zoledronic acid IV
• Glucocorticoids to suppress macrophage 1-alpha hydroxylase activity
• Cinacalcet to decrease PTH secretion
• High-dose calcitriol supplementation

Correct Answer: Glucocorticoids to suppress macrophage 1-alpha hydroxylase activity

Q19. Which lab change would you expect after starting an effective calcimimetic (cinacalcet) in a patient with secondary hyperparathyroidism?

• Increase in serum PTH and increase in serum calcium
• Decrease in serum PTH and decrease in serum calcium
• Increase in serum PTH and decrease in serum phosphorus
• No change in serum PTH but increased urinary calcium excretion

Correct Answer: Decrease in serum PTH and decrease in serum calcium

Q20. Which of the following statements is true regarding vitamin D toxicity and pharmacologic implications?

• Vitamin D toxicity presents with hypocalcemia and is treated with high-dose vitamin D
• Excess vitamin D causes hypercalcemia; management includes stopping vitamin D, hydration, bisphosphonates and possibly glucocorticoids depending on etiology
• Vitamin D has no interaction with thiazide diuretics on calcium levels
• Calcitriol has a longer half-life than cholecalciferol and less risk of hypercalcemia

Correct Answer: Excess vitamin D causes hypercalcemia; management includes stopping vitamin D, hydration, bisphosphonates and possibly glucocorticoids depending on etiology

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