Short answer: Reclast (zoledronic acid) is a bisphosphonate given as a 5 mg infusion into a vein, once a year for osteoporosis treatment.1 Prolia (denosumab) is a 60 mg shot under the skin every 6 months.2 Reclast's most common reactions are flu-like symptoms within 3 days of the infusion; Prolia has a boxed warning on severe low calcium in advanced kidney disease. Neither label reports a trial against the other.
| Reclast (zoledronic acid) | Prolia (denosumab) | |
|---|---|---|
| Drug type | Bisphosphonate1 | RANK ligand inhibitor2 |
| Schedule | 5 mg infusion over at least 15 minutes: once a year to treat osteoporosis, every 2 years to prevent it, once for Paget's1 | 60 mg under the skin every 6 months2 |
| Approved for | Treat and prevent postmenopausal osteoporosis; men; treat and prevent steroid-induced osteoporosis; Paget's disease1 | High fracture risk: postmenopausal women, men, steroid-induced osteoporosis, men on androgen deprivation, women on aromatase inhibitors2 |
| Trial size | 7,736 women1 | 7,808 women2 |
| Side effects above placebo | Fever 17.9% vs 4.6%; headache 12.4% vs 8.1%; muscle pain 11.7% vs 3.7%; flu-like illness 8.8% vs 2.7%1 | Back pain 34.7% vs 34.6%; arm or leg pain 11.7% vs 11.1%; high cholesterol 7.2% vs 6.1%2 |
| Boxed warning | None1 | Severe low calcium with advanced kidney disease2 |
| Before a dose | Drink at least 2 glasses of fluid1 | Daily calcium 1000 mg and at least 400 IU vitamin D2 |
With Reclast, most side effects started within 3 days of the infusion: fever, muscle pain, flu-like illness and chills (5.4% vs 1.0%) ran well above placebo.1 Prolia's trial showed side effects close to placebo, with back pain at 34.7% vs 34.6%.2 These numbers come from separate trials with different people, lengths and methods, so they are not a head-to-head comparison.
Both labels warn about low calcium, jaw bone death and unusual thigh fractures. Reclast also warns about kidney problems; Prolia's boxed warning covers severe low calcium when eGFR is under 30.12
Which one fits is for your prescriber, especially with kidney disease. More detail: Reclast side effects, Prolia side effects, the Reclast and Prolia dosing schedules, and the Prolia missed-dose page.