What are the side effects of Prolia (denosumab)?

Side Effects of Prolia (Denosumab)

Prolia (denosumab) has several common side effects including arthralgia, nasopharyngitis, headache, extremity pain, upper respiratory infection, constipation, urinary tract infection, rash, and asymptomatic hypocalcemia, with more serious concerns including osteonecrosis of the jaw, atypical femur fractures, and severe hypocalcemia. 1

Common Side Effects

Denosumab is associated with several common side effects that patients should be aware of:

• Musculoskeletal symptoms:

  • Arthralgia (joint pain) - 14.3% of patients 1
  • Back pain - 11.5% of patients 1
  • Pain in extremities - 9.9% of patients 1
  • Muscle pain - 6.0% of patients 1

• Infections and respiratory issues:

  • Nasopharyngitis
  • Upper respiratory infections
  • Increased risk of infections (risk ratio 1.26) 1
  • Urinary tract infections

• Skin reactions:

  • Rash/eczema (odds ratio 1.96) 1
  • Dermatitis and other dermatologic reactions 2

• Gastrointestinal issues:

  • Mild upper gastrointestinal symptoms (odds ratio 1.74) 1
  • Constipation

• Other common side effects:

  • Headache
  • Hypocalcemia (especially within first month of treatment) 1, 2

Serious Side Effects

1. Hypocalcemia

• Can be severe, especially in patients with kidney disease 2
• Symptoms include muscle spasms, twitches, cramps, numbness, and tingling in fingers, toes, or around the mouth 2
• More pronounced with denosumab than with other osteoporosis treatments 3
• Particularly concerning in patients with renal impairment 1

2. Osteonecrosis of the Jaw (ONJ)

• Rare but serious complication 1
• Risk factors include:
  • Poor oral hygiene
  • Invasive dental procedures
  • Longer duration of treatment 2
• Requires dental examination before starting therapy 4, 2

3. Atypical Femur Fractures

• Rare but serious complication with long-term use 2
• Symptoms include new or unusual pain in hip, groin, or thigh 2
• May occur with other atypical fractures 1

4. Rebound Bone Loss After Discontinuation

• Rapid bone loss can occur when stopping denosumab 5
• Risk of multiple vertebral fractures after discontinuation 2, 5
• Particularly concerning in patients with:
  • Previous vertebral fractures
  • Greater on-treatment BMD gains 5
• Requires transition to another antiresorptive agent when discontinuing 4

5. Serious Allergic Reactions

• Can include hypotension, trouble breathing, throat tightness, facial swelling 2
• May require immediate medical attention

6. Other Serious Concerns

• Rare cases of severe hepatotoxicity have been reported 6
• Potential for immobility as a newly discovered adverse reaction 3
• Menopausal symptoms reported in some patients 3

Risk Comparison

The overall safety profile of denosumab is generally favorable compared to placebo:

Adverse Effects	Denosumab	Placebo
Discontinuation due to adverse events	2.4%	2.1%
Serious adverse events	23.8%	23.9%

1

Special Populations and Considerations

Renal Impairment

• Denosumab is preferred over bisphosphonates in patients with renal impairment 1
• Does not require renal function monitoring, unlike bisphosphonates 1
• However, patients with severe renal impairment are at higher risk for hypocalcemia 2

Cancer Patients

• Effective for preventing bone loss in cancer patients receiving endocrine therapy 7
• Used in both men with prostate cancer on androgen deprivation therapy and women with breast cancer on aromatase inhibitors 7

Elderly Patients

• May be underutilized in elderly patients despite their higher fracture risk 1
• No dose adjustments based on age are necessary 1

Monitoring Recommendations

1. Before starting treatment:

   • Comprehensive dental examination 1, 4
   • Baseline calcium and vitamin D levels 4
   • Correction of vitamin D deficiency (goal >32 ng/mL) 4

2. During treatment:

   • Regular monitoring of calcium levels 1, 4
   • Vitamin D levels intermittently 1
   • Watch for signs of ONJ or atypical fractures 2

3. When discontinuing:

   • Plan for transition to another antiresorptive agent 4, 5
   • Monitor for rebound bone loss 5

Practical Advice for Patients

• Take calcium and vitamin D supplements as directed 2
• Report any new thigh, hip, or groin pain immediately 2
• Maintain good oral hygiene and inform dentists about denosumab treatment 2
• Do not stop treatment without discussing with healthcare provider 2
• Store medication properly (refrigerated at 36°F to 46°F) 2

By understanding these side effects and following proper monitoring protocols, patients and healthcare providers can maximize the benefits of denosumab while minimizing risks.