From the Guidelines
Denosumab commonly causes side effects including hypocalcemia, arthralgias, and osteonecrosis of the jaw, with an incidence of 1%–2% for the latter, as reported in a recent study 1.
Side Effects of Denosumab
The side effects of denosumab can be categorized into common and serious but less common effects. Common side effects include:
- Hypocalcemia, which is more common with denosumab compared to zoledronic acid, with an incidence of 13% vs 6% 1
- Arthralgias
- Osteonecrosis of the jaw, which affects 1%–2% of patients, often with preexisting dental problems 1
Serious Side Effects
More serious but less common side effects of denosumab include:
- Spinal cord compression, with an incidence of 3% vs 4% compared to zoledronic acid 1
- Need for radiation, with an incidence of 19% vs 21% compared to zoledronic acid 1
- Pathologic fracture, with an incidence of 14% vs 15% compared to zoledronic acid 1
Prevention and Management
To minimize the risk of side effects, patients should:
- Ensure adequate calcium and vitamin D intake while on denosumab to prevent hypocalcemia 1
- Maintain good oral hygiene and undergo baseline dental evaluation for high-risk individuals to reduce the risk of osteonecrosis of the jaw 1
- Report any jaw pain, unusual thigh pain, or signs of infection to their healthcare provider promptly 1
From the FDA Drug Label
Prolia may cause serious side effects including: Increased risk of severe low calcium levels in your blood (hypocalcemia). Serious allergic reactions. Severe jaw bone problems (osteonecrosis). Unusual thigh bone fractures. Increased risk of broken bones, including broken bones in the spine, after stopping, skipping or delaying Prolia. Serious infections. Dermatologic Adverse Reactions Musculoskeletal Pain
The side effects of denosumab (Prolia/Xgeva) include:
- Hypocalcemia: increased risk of severe low calcium levels in the blood
- Allergic reactions: serious allergic reactions, including anaphylaxis, rash, urticaria, facial swelling, and erythema
- Osteonecrosis: severe jaw bone problems
- Atypical fractures: unusual thigh bone fractures
- Infections: serious infections, including cellulitis and endocarditis
- Dermatologic reactions: dermatitis, eczema, and rashes
- Musculoskeletal pain: severe bone, joint, and/or muscle pain
- Increased risk of broken bones: after stopping, skipping, or delaying Prolia Other common side effects include:
- Back pain
- Pain in arms and legs
- High cholesterol
- Muscle pain
- Bladder infection
- Joint pain
- Common cold
- Lung infection
- Headache
- Arthralgia
- Pain in extremity
- Musculoskeletal pain
- Cataracts 2, 2, 2
From the Research
Side Effects of Denosumab
The side effects of denosumab (Prolia/Xgeva) include:
- Hypocalcaemia, which can be severe and life-threatening, especially in patients with renal impairment 3, 4, 5
- Osteonecrosis of the jaw (ONJ) 6
- Atypical femoral fractures (AFF) 6
- Rebound effect characterized by increased markers of bone remodeling, rapid decrease of bone density values, and risk of multiple spontaneous vertebral fractures after discontinuation of denosumab 7
Risk Factors for Side Effects
Certain patients are at higher risk of developing side effects from denosumab, including:
- Those with renal impairment, especially if eGFR < 30 ml/min/1.73m(2) 4
- Those with vitamin D insufficiency 4
- Those with chronic kidney disease 3, 5
Monitoring and Prevention
To minimize the risk of side effects, it is essential to:
- Monitor calcium levels closely in patients with established risk factors for hypocalcaemia 3, 7
- Correct hypocalcaemia or vitamin D deficiency before starting denosumab treatment 7
- Administer denosumab injections scrupulously every 6 months (± 3 weeks) 7
- Consider administering a potent bisphosphonate after discontinuation of denosumab to minimize or avoid the rebound effect 7