Short answer: Fosamax (alendronate) is a bisphosphonate tablet taken once a week at home.1 Prolia (denosumab) is a RANK ligand inhibitor given as a 60 mg shot by a healthcare provider every 6 months, with daily calcium and vitamin D.2 Prolia has a boxed warning on severe low calcium in advanced kidney disease; Fosamax has none. Neither label reports a trial against the other.
| Fosamax (alendronate) | Prolia (denosumab) | |
|---|---|---|
| Drug type | Bisphosphonate tablet1 | RANK ligand inhibitor (antibody) injection2 |
| Schedule | 70 mg by mouth once a week (or 10 mg daily)1 | 60 mg under the skin every 6 months, given by a healthcare provider2 |
| Approved for | Postmenopausal osteoporosis (treat and prevent); men; steroid-induced osteoporosis; Paget's disease1 | High fracture risk: postmenopausal women, men, steroid-induced osteoporosis, men on androgen deprivation and women on aromatase inhibitors2 |
| Kidney limits | Not recommended with creatinine clearance under 35 mL/min1 | Boxed warning on severe low calcium with eGFR under 30, including dialysis2 |
| Side effects in label trials | Abdominal pain 6.6% vs 4.8%; musculoskeletal pain 4.1% vs 2.5%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 |
| Missed dose | Take the next morning; then back to the usual day1 | Given as soon as possible; next shots every 6 months from that date2 |
No. Both slow the cells that break down bone, but by different routes. Fosamax is a bisphosphonate that binds to bone.1 Prolia is an antibody that blocks RANK ligand, a signal those cells need.2 The practical difference is the schedule: a weekly tablet with a strict empty-stomach routine, or a shot twice a year in a clinic.12
Both labels warn about low calcium, jaw bone death and unusual thigh fractures.12 Fosamax also warns about esophagus irritation, which is why it is taken upright with a full glass of water.1 Prolia's boxed warning covers severe, sometimes fatal, low calcium in people with advanced kidney disease.2 These numbers come from separate trials with different people, lengths and methods, so they are not a head-to-head comparison.
Choosing between them is a talk with your prescriber. More detail: Fosamax side effects, Prolia side effects, the Fosamax and Prolia dosing schedules, and the Fosamax and Prolia missed-dose pages.