What is the treatment for hypercalcemia?

Treatment of Hypercalcemia

The treatment of hypercalcemia should begin with aggressive IV fluid resuscitation with normal saline, followed by bisphosphonates, with zoledronic acid 4 mg IV over 15 minutes being the preferred first-line treatment for moderate to severe hypercalcemia. 1

Initial Management Based on Severity

Mild Hypercalcemia (Total calcium <12 mg/dL)

• Often asymptomatic and may not require acute intervention 2
• Oral hydration and addressing the underlying cause
• Discontinuation of contributing medications (thiazide diuretics, calcium supplements, vitamin D or A supplements) 1
• Encourage ambulation to promote normal bone remodeling

Moderate to Severe Hypercalcemia (Total calcium ≥12 mg/dL or symptomatic)

1. Aggressive IV fluid resuscitation

   • Normal saline (0.9% NaCl) to restore extracellular volume and enhance renal calcium excretion 1
   • Target: Correction of volume depletion and maintenance of high urine output

2. Bisphosphonates (after adequate hydration)

   • First-line: Zoledronic acid 4 mg IV over 15 minutes 1
   • Alternative: Pamidronate IV
   • Dose adjustment required for renal impairment 1
   • Onset of action: 24-48 hours, with maximum effect in 3-6 days

3. Loop diuretics (only after adequate volume restoration)

   • Enhances calcium excretion 1
   • Caution: Never use before volume restoration as this can worsen dehydration

Special Therapeutic Considerations

For Immediate Short-term Management

• Calcitonin can be used for rapid but short-term calcium reduction 1, 3
  • FDA-approved for early treatment of hypercalcemic emergencies 3
  • Initial dose: 4 International Units/kg body weight every 12 hours SC or IM
  • May increase to 8 International Units/kg every 12 hours if response inadequate
  • Maximum dose: 8 International Units/kg every 6 hours 3
  • Advantage: Rapid onset of action
  • Limitation: Tachyphylaxis develops within 2-3 days

For Renal Impairment

• Denosumab is recommended for:
  • Hypercalcemia refractory to bisphosphonates
  • Patients with severe renal impairment 1
  • Preferred in patients with renal disease

For Specific Etiologies

• Glucocorticoids for:

  • Vitamin D toxicity
  • Granulomatous disorders (e.g., sarcoidosis)
  • Some lymphomas 1, 2

• Dialysis with calcium-free or low-calcium solution:

  • For patients with renal failure not caused by dehydration
  • For severe, life-threatening hypercalcemia unresponsive to other measures 4

Treatment Based on Underlying Cause

Primary Hyperparathyroidism

• Parathyroidectomy for symptomatic patients or those meeting surgical criteria
• For patients >50 years with serum calcium <1 mg/dL above upper limit and no evidence of skeletal/kidney disease, observation may be appropriate 2

Malignancy-Related Hypercalcemia

• Treat the underlying cancer
• Continue bone-targeting treatment (bisphosphonates or denosumab) for up to 2 years 1
• Frequency of dosing (monthly vs. every 3 months) based on individual response 1

Monitoring and Follow-up

• Regular monitoring of:

  • Serum calcium, phosphate, magnesium
  • Renal function and electrolytes 1
  • Calculate corrected calcium: Total calcium (mg/dL) + 0.8 × [4 - Serum albumin (g/dL)]

• For patients on calcium-lowering therapy for osteoporosis:

  • Ensure adequate calcium intake (at least 1000 mg elemental calcium per day)
  • Vitamin D supplementation (at least 400 International Units per day) 3

Common Pitfalls to Avoid

• Administering loop diuretics before adequate hydration, which can worsen dehydration and hypercalcemia 1
• Failing to correct calcium for albumin, leading to inaccurate diagnosis 1
• Inadequate hydration before bisphosphonate administration, which can worsen renal function 1
• Not monitoring for hypocalcemia after treatment, especially with denosumab 1
• Treating the laboratory value without addressing the underlying cause 1
• Delaying treatment of severe hypercalcemia, which can lead to serious complications 1