What are the side effects of Prolia (denosumab)?

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Last updated: March 27, 2025View editorial policy

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From the Guidelines

Prolia (denosumab) can cause several side effects, including hypocalcemia, arthralgias, and osteonecrosis of the jaw, which are significant concerns that require monitoring and preventive measures, as reported in the most recent study 1.

Common Side Effects

  • Back pain
  • Arm and leg pain
  • High cholesterol
  • Muscle pain
  • Bladder infections

Serious Side Effects

  • Low calcium levels (hypocalcemia)
  • Serious infections
  • Skin problems
  • Jaw bone problems (osteonecrosis)
  • Unusual thigh bone fractures
  • Increased risk of broken bones after stopping the medication

Mechanism and Prevention

Prolia works by blocking a protein called RANKL, which helps reduce bone breakdown, but this mechanism can also affect immune function and calcium metabolism, explaining many of these side effects. Patients taking Prolia should:

  • Ensure adequate calcium and vitamin D intake
  • Report any new pain or unusual symptoms to their doctor
  • Maintain good dental hygiene
  • Not stop the medication without medical supervision Regular follow-up appointments are important to monitor for these potential side effects, as recommended in the guidelines 1.

Key Considerations

  • Hypocalcemia is a significant concern, and supplemental calcium and vitamin D are recommended to prevent it, as noted in the study 1.
  • Osteonecrosis of the jaw is a rare but serious side effect, and patients should receive a comprehensive dental examination and maintain good oral hygiene, as advised in the guidelines 1.
  • The optimal duration of denosumab therapy is unclear, but it is recommended to continue treatment for up to 2 years, with less-frequent dosing considered in patients with responsive or stable disease, as suggested in the study 1.

From the FDA Drug Label

What are the possible side effects of Prolia? Prolia may cause serious side effects. See "What is the most important information I should know about Prolia? " It is not known if the use of Prolia over a long period of time may cause slow healing of broken bones The most common side effects of Prolia in women who are being treated for osteoporosis after menopause are: back pain pain in your arms and legs high cholesterol muscle pain bladder infection The most common side effects of Prolia in men with osteoporosis are: back pain joint pain common cold (runny nose or sore throat) The most common side effects of Prolia in patients with glucocorticoid-induced osteoporosis are: back pain high blood pressure lung infection (bronchitis) headache The most common side effects of Prolia in patients receiving certain treatments for prostate or breast cancer are: joint pain back pain pain in your arms and legs muscle pain

Prolia can cause serious side effects including: Increased risk of severe low calcium levels in your blood (hypocalcemia). Prolia may lower the calcium levels in your blood. If you have low blood calcium before you start receiving Prolia, it may get worse during treatment. Serious allergic reactions. Serious allergic reactions have happened in people who take Prolia Severe jaw bone problems (osteonecrosis). Severe jaw bone problems may happen when you take Prolia Unusual thigh bone fractures. Some people have developed unusual fractures in their thigh bone Increased risk of broken bones, including broken bones in the spine, after stopping, skipping or delaying Prolia. Serious infections. Serious infections in your skin, lower stomach area (abdomen), bladder, or ear may happen if you take Prolia.

The possible side effects of Prolia include:

  • Common side effects:
    • Back pain
    • Pain in arms and legs
    • High cholesterol
    • Muscle pain
    • Bladder infection
    • Joint pain
    • Common cold
    • High blood pressure
    • Lung infection
    • Headache
  • Serious side effects:
    • Increased risk of severe low calcium levels in the blood (hypocalcemia)
    • Serious allergic reactions
    • Severe jaw bone problems (osteonecrosis)
    • Unusual thigh bone fractures
    • Increased risk of broken bones after stopping, skipping, or delaying Prolia
    • Serious infections 2 2

From the Research

Side Effects of Prolia (Denosumab)

  • Hypocalcemia: a potentially life-threatening side effect, especially in patients with renal impairment or vitamin D insufficiency 3, 4, 5
  • Hypophosphatemia: a condition characterized by low phosphate levels in the blood, which can cause neurological symptoms and severe fatigue 4, 6
  • Rebound effect: a severe increase in markers of bone remodeling, rapid decrease of bone density values, and risk of multiple spontaneous vertebral fractures after discontinuation of denosumab 7
  • Electrolyte abnormalities: denosumab can cause changes in calcium and phosphate levels, which can be resistant to repletion 4
  • Muscle cramps and myoclonic jerks: symptoms that can occur due to hypocalcemia or hypophosphatemia 3, 6
  • Fatigue and paralysis: severe symptoms that can occur due to hypocalcemia or hypophosphatemia 5, 6
  • Osteomalacia: a condition characterized by softening of the bones, which can be exacerbated by denosumab treatment 5

Patient Monitoring

  • Close clinical follow-up is necessary to monitor for potential side effects 7
  • Calcium levels should be monitored pre- and post-treatment, especially in patients with renal impairment or vitamin D insufficiency 3, 5
  • Phosphate levels should be monitored regularly, especially in patients with normal kidney function 6
  • Early and regular monitoring of Ca, Pi, and PTH, as well as early supplementation of phosphate and/or vitamin D as needed, can help reduce the risk of complications 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Denosumab-associated symptomatic hypophosphatemia in normal kidney function: two case reports.

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2024

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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