alendronate
Brand: Fosamax
Prototype Drug
Drug Class: bisphosphonate
Drug Family: bone agent
Subclass: nitrogen-containing bisphosphonate
Organ Systems: endocrinemusculoskeletal
Mechanism of Action
Nitrogen-containing bisphosphonate that binds to hydroxyapatite in bone with high affinity. Osteoclasts ingest the drug during bone resorption; intracellularly, alendronate inhibits farnesyl pyrophosphate synthase in the mevalonate pathway, preventing isoprenylation of signaling proteins, impairing osteoclast function, and inducing osteoclast apoptosis.
farnesyl pyrophosphate synthase (FPPS) in osteoclasts
Indications
- osteoporosis (postmenopausal women)
- osteoporosis in men
- glucocorticoid-induced osteoporosis
- Paget's disease of bone
Contraindications
- esophageal abnormalities (achalasia, stricture, inability to stand/sit upright for 30 minutes)
- hypocalcemia
- CrCl <35 mL/min
Adverse Effects
Common
- esophageal irritation, esophagitis, ulceration (if not taken correctly)
- abdominal pain
- nausea
- musculoskeletal pain
Serious
- esophageal cancer (long-term; rare)
- osteonecrosis of the jaw (ONJ)
- atypical subtrochanteric femoral fractures (long-term use >5 years)
- severe musculoskeletal pain
- uveitis/ocular inflammation (rare)
Pharmacokinetics (ADME)
| Absorption | oral bioavailability ~0.6–0.7% (extremely low); reduced further by food, coffee, juice |
| Distribution | ~70% binds to bone; remainder distributed to soft tissue transiently |
| Metabolism | not metabolized |
| Excretion | renal excretion of absorbed drug; the rest remains in bone for years |
| Half-life | >10 years (in bone; terminal half-life reflects bone turnover) |
| Onset | months |
| Peak | months to years |
| Duration | years (bone retention) |
| Protein Binding | 78% to bone mineral |
| Vd | bone |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| calcium supplements, antacids, multivitamins | chelate bisphosphonate, reducing absorption to near zero | major |
| NSAIDs | additive GI irritation | moderate |
Nursing Considerations
- Strict administration protocol: take with 6–8 oz of plain water ONLY, first thing in the morning on an empty stomach; remain upright (sitting or standing) for at least 30 minutes; do not eat, drink, or take other medications for 30 minutes.
- Weekly dosing (70 mg) has replaced daily dosing (10 mg) to improve GI tolerability and adherence.
- Assess dental health before long-term treatment; avoid invasive dental procedures; educate about ONJ risk especially if patient is on corticosteroids.
- A drug holiday after 5 years of treatment is recommended for most patients (unless high fracture risk) to reduce atypical fracture risk; consult prescriber.
Clinical Pearls
- Bisphosphonates are retained in bone for years after discontinuation due to high bone affinity; a 5-year drug holiday remains a valid strategy for low-risk patients while maintaining 70–80% of fracture protection.
- Osteonecrosis of the jaw is rare but serious; risk is highest in cancer patients receiving IV bisphosphonates (not oral alendronate for osteoporosis), where the incidence is 1–2%.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
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