What is the most common side effect of Prolia (denosumab)?

Most Common Side Effects of Prolia (Denosumab)

The most common side effects of Prolia (denosumab) are musculoskeletal pain, including back pain, pain in extremities, arthralgia (joint pain), and muscle pain. 1

Primary Side Effect Profile

Denosumab's side effect profile can be categorized as follows:

Musculoskeletal Symptoms (Most Common)

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

Other Common Side Effects

• Upper respiratory infections and nasopharyngitis 2, 1
• Urinary tract infections 1
• Constipation 3
• Rash/eczema (OR 1.96) 2
• Mild upper gastrointestinal symptoms (OR 1.74) 2
• Headache 1

Metabolic Effects

• Hypocalcemia, especially within the first month of treatment 1, 4
  • Particularly concerning in patients with renal impairment 5, 6

Serious but Less Common Side Effects

Increased Risk of Infection

• Moderate-quality evidence shows increased risk for infection (risk ratio 1.26) 2
• Bacterial cellulitis has been reported at slightly higher rates than placebo (1.3% vs. 0.6%) 2

Severe Adverse Events

• Osteonecrosis of the jaw (ONJ)

  • Incidence ranges from 0.1% to 2.1% depending on dosing frequency and duration 2
  • Risk factors include poor oral hygiene and invasive dental procedures 1

• Atypical femur fractures

  • Rare but serious complication 1
  • Two events of atypical femoral fracture were confirmed through 8 years of denosumab therapy in the FREEDOM extension study 2

Risk Factors for Adverse Events

Certain patient populations may be at higher risk for specific side effects:

• Patients with renal impairment are at increased risk for hypocalcemia 5, 6
• Patients with high bone turnover states (e.g., hyperthyroidism) may experience more severe hypocalcemia 5
• Patients on dialysis require special monitoring due to risk of profound hypocalcemia 6

Monitoring Recommendations

To minimize adverse effects:

• Ensure adequate calcium and vitamin D supplementation before and during treatment 2, 1
• Monitor calcium levels, particularly in patients with renal impairment 1
• Consider dental examination before starting therapy where feasible 2
• Be vigilant for signs of ONJ or atypical fractures during treatment 1

Discontinuation Rates

The overall discontinuation rate due to adverse events with denosumab is low (2.4% vs. 2.1% for placebo), suggesting that most side effects are manageable 1.

In conclusion, while denosumab has several potential side effects, the most common ones are musculoskeletal in nature, with back pain, joint pain, and extremity pain being the most frequently reported adverse events in clinical practice.