Short answer: In the label's 3-year trial of 7,808 postmenopausal women, the most common Prolia side effects were back pain (34.7% vs 34.6% on placebo), pain in the arms or legs (11.7% vs 11.1%), muscle and bone pain, high cholesterol (7.2% vs 6.1%) and bladder infection. Prolia has a boxed warning: severe, sometimes fatal, low blood calcium in people with advanced kidney disease.
What Prolia is approved for: Prolia is a RANK ligand inhibitor approved for postmenopausal women with osteoporosis at high risk for fracture; to increase bone mass in men with osteoporosis at high risk for fracture; for steroid (glucocorticoid)-induced osteoporosis at high risk for fracture; and to increase bone mass in men on androgen deprivation therapy for nonmetastatic prostate cancer and women on adjuvant aromatase inhibitor therapy for breast cancer who are at high risk for fracture (section 1).
Source
PROLIA (denosumab) injection, for subcutaneous use, prescribing information and Medication Guide. Amgen. DailyMed, version published July 7, 2026. DailyMed setid 49e5afe9-a0c7-40c4-af9f-f287a80c5c88
WARNING: SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE
People with advanced chronic kidney disease (eGFR under 30 mL/min/1.73 m2), including those on dialysis, are at greater risk of severe low blood calcium after Prolia. Severe low calcium leading to hospital stays, life-threatening events and deaths has been reported. Chronic kidney disease-mineral bone disorder (CKD-MBD) markedly increases the risk. Before starting Prolia in advanced kidney disease, CKD-MBD is checked for, and treatment is supervised by a provider with expertise in CKD-MBD.
These are the label's own numbers from the Adverse Reactions section. Where the label compares with placebo (a dummy treatment), both columns are shown, so you can see how much more often a reaction happened on Prolia.
| Preferred Term | Prolia (N = 3886) n (%) | Placebo (N = 3876) n (%) |
|---|---|---|
| Back pain | 1347 (34.7) | 1340 (34.6) |
| Pain in extremity | 453 (11.7) | 430 (11.1) |
| Musculoskeletal pain | 297 (7.6) | 291 (7.5) |
| Hypercholesterolemia | 280 (7.2) | 236 (6.1) |
| Cystitis | 228 (5.9) | 225 (5.8) |
| Vertigo | 195 (5.0) | 187 (4.8) |
| Upper respiratory tract infection | 190 (4.9) | 167 (4.3) |
| Edema peripheral | 189 (4.9) | 155 (4.0) |
| Sciatica | 178 (4.6) | 149 (3.8) |
| Bone pain | 142 (3.7) | 117 (3.0) |
| Abdominal pain upper | 129 (3.3) | 111 (2.9) |
| Anemia | 129 (3.3) | 107 (2.8) |
| Insomnia | 126 (3.2) | 122 (3.1) |
| Myalgia | 114 (2.9) | 94 (2.4) |
| Angina pectoris | 101 (2.6) | 87 (2.2) |
| Rash | 96 (2.5) | 79 (2.0) |
| Pharyngitis | 91 (2.3) | 78 (2.0) |
| Asthenia | 90 (2.3) | 73 (1.9) |
| Pruritus | 87 (2.2) | 82 (2.1) |
| Flatulence | 84 (2.2) | 53 (1.4) |
| Spinal osteoarthritis | 82 (2.1) | 64 (1.7) |
| Gastroesophageal reflux disease | 80 (2.1) | 66 (1.7) |
| Herpes zoster | 79 (2.0) | 72 (1.9) |
3-year placebo-controlled trial of 7,808 postmenopausal women aged 60 to 91, all told to take at least 1000 mg calcium and 400 IU vitamin D a day. Deaths from any cause: 1.8% on Prolia vs 2.3% on placebo. Stopping because of side effects: 2.4% vs 2.1%.
| Preferred Term | Prolia (N = 394) n (%) | Oral Daily Bisphosphonate (Active-Control) (N = 384) n (%) |
|---|---|---|
| Back pain | 18 (4.6) | 17 (4.4) |
| Hypertension | 15 (3.8) | 13 (3.4) |
| Bronchitis | 15 (3.8) | 11 (2.9) |
| Headache | 14 (3.6) | 7 (1.8) |
| Dyspepsia | 12 (3.0) | 10 (2.6) |
| Urinary tract infection | 12 (3.0) | 8 (2.1) |
| Abdominal pain upper | 12 (3.0) | 7 (1.8) |
| Upper respiratory tract infection | 11 (2.8) | 10 (2.6) |
| Constipation | 11 (2.8) | 6 (1.6) |
| Vomiting | 10 (2.5) | 6 (1.6) |
| Dizziness | 9 (2.3) | 8 (2.1) |
| Fall | 8 (2.0) | 7 (1.8) |
| Polymyalgia rheumatica | 8 (2.0) | 1 (0.3) |
1-year analysis of a trial of 795 people on prednisone 7.5 mg a day or more, comparing Prolia with a daily oral bisphosphonate. Polymyalgia rheumatica means worsening of existing polymyalgia rheumatica.
Blood calcium below 8.5 mg/dL at any visit: 1.7% on Prolia vs 0.4% on placebo, with the low point about 10 days after a dose. In a study without calcium and vitamin D, calcium under 7.5 mg/dL or symptoms occurred in 29% of people with creatinine clearance under 30 and 29% on hemodialysis.
Nonfatal serious infections: 4.0% vs 3.3% on placebo. Skin infections such as cellulitis leading to hospital care: 0.4% vs under 0.1%. Endocarditis in 3 people on Prolia and none on placebo. Skin reactions such as dermatitis, eczema and rash: 10.8% vs 8.2%.
Among women who stopped Prolia and stayed in the study, 6% had new spine fractures and 3% had multiple new spine fractures, a mean of 17 months (range 7 to 43) after the last injection.
Men with osteoporosis (1 year): back pain 8.3% vs 6.7% on placebo, joint pain 6.7% vs 5.8%, nasopharyngitis 6.7% vs 5.8%.
Men on hormone therapy for prostate cancer and women on aromatase inhibitors: joint pain 14.3% vs 13.0%, back pain 11.5% vs 10.5%. Cataracts in the prostate cancer trial: 4.7% vs 1.2%.
Pancreatitis: 0.2% vs 0.1% on placebo, all 8 Prolia cases serious, including one death. New cancers: 4.8% vs 4.3%, with no established causal link.
The Warnings and Precautions part of the label lists these. Each line gives the label's heading and what it means in plain words.
Severe low blood calcium. Prolia can cause severe low calcium, including deaths. Existing low calcium is corrected first, and everyone takes calcium and vitamin D. People prone to low calcium have calcium, phosphorus and magnesium checked 10 to 14 days after each injection. In advanced kidney disease, calcium is checked weekly for the first month and monthly after that.
Other denosumab products. People on Prolia should not receive other denosumab products at the same time.
Allergic reactions. Anaphylaxis has been reported, with low blood pressure, shortness of breath, throat tightness, face and airway swelling, itching and hives. Prolia is stopped after a significant reaction.
Osteonecrosis of the jaw. Jaw bone death has been reported, usually linked to tooth extraction or infection with slow healing. An oral exam comes before starting, and a dental exam is recommended for people with risk factors. Risk may grow with longer use.
Unusual thigh bone fractures. Atypical low-trauma fractures of the thigh bone have been reported, often after weeks to months of dull thigh pain. New thigh, hip or groin pain is checked for a fracture.
Multiple spine fractures after stopping. After Prolia stops, bone turnover rises above pretreatment levels by 9 months and bone density returns to baseline within 18 months. New spine fractures occurred as early as 7 months after the last dose. If Prolia is stopped, the label says to move to another antiresorptive medicine.
Serious infections. Serious skin, abdominal, urinary and ear infections and endocarditis were more frequent on Prolia. Risk may be higher with a weakened immune system or immune-suppressing medicines.
Skin reactions. Dermatitis, eczema and rash were more common on Prolia, mostly not at the injection site. Stopping is considered for severe symptoms.
Bone, joint and muscle pain. Severe, sometimes disabling pain has been reported, starting from one day to several months after starting. Stopping is considered for severe symptoms.
Suppressed bone turnover. Prolia strongly suppresses bone remodeling. The long-term effect is unknown and may contribute to jaw problems, atypical fractures and slow fracture healing.
Who should not use it. People with low blood calcium, pregnant women, and people with a past whole-body allergic reaction to any part of Prolia.
From the Medication Guide that comes with Prolia:
Dose Track has a side-effect log. Each entry records the symptom, a severity (none, mild, moderate, severe or life-threatening), the date and an optional note, and can be tied to a specific dose or logged on its own. The history screen shows what you logged over time, which makes it easier to tell your prescriber when a reaction started and whether it is easing. The app records what you enter; it does not judge whether a symptom is serious. For anything on the label's call-your-doctor list, call your doctor.
This page is what the FDA label says, in plain words. It is not medical advice. Follow your prescriber, and ask them or your pharmacist about anything here.