What is the association between Polymethylmethacrylate (PMMA) and hypercalcemia?

Association Between PMMA and Hypercalcemia

Polymethylmethacrylate (PMMA) injections can cause severe hypercalcemia through granulomatous foreign body reactions that lead to extrarenal production of calcitriol. 1

Mechanism of PMMA-Induced Hypercalcemia

PMMA is commonly used as a filler for cosmetic procedures, but when injected in large volumes, it can trigger significant metabolic complications:

• Pathophysiology: PMMA injections can cause a granulomatous foreign body reaction that leads to:

  • Extrarenal production of calcitriol (1,25-dihydroxyvitamin D)
  • Increased intestinal calcium absorption
  • Resulting hypercalcemia 1, 2

• Clinical presentation: Patients may develop:

  • Severe hypercalcemia (corrected serum calcium >11.5 mg/dL)
  • Advanced chronic kidney disease
  • Symptoms including polyuria, gastrointestinal disturbances, dehydration, and decreased glomerular filtration rate 3, 1

Diagnosis of PMMA-Related Hypercalcemia

When evaluating hypercalcemia in a patient with history of PMMA injections:

1. Confirm hypercalcemia using albumin-corrected calcium calculation:

   • Corrected calcium (mg/dL) = Total calcium (mg/dL) + 0.8 × [4 - Serum albumin (g/dL)] 4

2. Essential laboratory tests:

   • Intact parathyroid hormone (iPTH) - typically suppressed
   • 1,25-dihydroxyvitamin D levels - typically elevated
   • 25-hydroxyvitamin D
   • Complete blood count
   • Renal function tests
   • Serum phosphorus and magnesium 4

3. Differential diagnosis should rule out:

   • Primary hyperparathyroidism
   • Malignancy-associated hypercalcemia
   • Other granulomatous disorders (sarcoidosis, tuberculosis) 4, 2

Management of PMMA-Induced Hypercalcemia

Treatment follows a stepwise approach:

1. Initial management:

   • Aggressive IV fluid resuscitation with normal saline (200-300 mL/hour initially)
   • Target urine output >3 L/day 4

2. Pharmacological intervention:

   • First-line: Bisphosphonates - zoledronic acid 4 mg IV over 15 minutes is preferred
   • For refractory cases or renal impairment: Denosumab
   • Adjunctive therapy: Glucocorticoids (particularly effective for granulomatous causes)
   • For immediate short-term management: Calcitonin 4

3. Monitoring:

   • Regular assessment of serum calcium, phosphate, magnesium
   • Renal function monitoring
   • Watch for hypocalcemia after treatment, especially with denosumab 4

Special Considerations

• Chronic kidney disease: PMMA-induced hypercalcemia can lead to or worsen CKD, requiring careful management to prevent vascular calcification and cardiovascular events 1

• Prevention: The cases highlight the importance of:

  • Adhering to regulations regarding PMMA use
  • Limiting PMMA to approved minimally invasive procedures in facial tissue
  • Avoiding large volume injections
  • Properly informing patients about potential complications 1

• Long-term management: Addressing the underlying cause is essential - in some cases, removal of the PMMA material may be necessary if feasible 4, 1

Pitfalls to Avoid

• Failing to consider PMMA injections in the differential diagnosis of unexplained hypercalcemia
• Using diuretics before correcting hypovolemia
• Inadequate hydration before bisphosphonate administration
• Treating laboratory values without addressing the underlying cause
• Delaying treatment of severe hypercalcemia 4

The association between PMMA injections and hypercalcemia, while documented in case reports, requires additional confirmation through larger follow-up studies 2. However, clinicians should be aware of this potential complication when evaluating patients with a history of cosmetic procedures involving PMMA.