Fosamax (Alendronate) Dosing Limits and Contraindications
For osteoporosis treatment, alendronate is dosed at 70 mg once weekly (or 10 mg daily), and therapy should be reassessed after 5 years to determine whether to continue or initiate a drug holiday, with absolute contraindication in patients with creatinine clearance <35 mL/min. 1, 2
Standard Dosing Regimens
Treatment of Osteoporosis
- 70 mg once weekly is the preferred regimen for postmenopausal osteoporosis treatment, therapeutically equivalent to 10 mg daily dosing 1, 3, 4
- 10 mg daily is an alternative dosing option with identical efficacy 1, 3
- Alendronate/cholecalciferol combination: 70 mg plus 2,800 IU or 5,600 IU vitamin D once weekly 1, 2
Prevention of Osteoporosis
- 35 mg once weekly for prevention in at-risk postmenopausal women 1, 2
- 5 mg daily as an alternative prevention regimen 1, 2
Glucocorticoid-Induced Osteoporosis
- 5 mg daily for adults ≥40 years receiving ≥7.5 mg/day prednisone-equivalent 2
- 10 mg daily for postmenopausal women not on estrogen replacement, providing greater BMD gains (≈4% vs ≈1.5%) 2
Duration of Therapy: The Critical 5-Year Decision Point
Treat for 5 years, then reassess fracture risk to decide continuation versus drug holiday. 2
- After 5 years of continuous therapy, patients at low fracture risk should be considered for drug discontinuation, as fracture protection may persist for up to 5 years after stopping 2
- Patients at high fracture risk may benefit from continued therapy beyond 5 years 2
- The trend in clinical practice is toward interrupting bisphosphonate therapy after 5-10 years due to concerns about rare adverse effects with long-term use 1, 2
- Do not routinely monitor BMD during the initial 5-year treatment period, as patients benefit from therapy even if BMD does not increase 2
Absolute Contraindications
Renal Impairment: The Hard Cutoff
Alendronate is absolutely contraindicated when creatinine clearance is <35 mL/min/1.73 m². 1, 2, 5
- No dose adjustment needed for eGFR ≥35 mL/min/1.73 m² 2
- Risk of drug accumulation and lack of safety data below this threshold 2
- Oral bisphosphonates have better renal safety than IV formulations in patients with reduced kidney function 1, 5
Esophageal and Upper GI Contraindications
- Abnormalities of the esophagus that delay esophageal emptying 1, 2
- Inability to stand or sit upright for at least 30 minutes after dosing 1, 2
- Patients at increased risk of aspiration should not receive alendronate solution 1
Metabolic Contraindications
- Hypocalcemia must be corrected before initiating therapy 1, 2
- Hypersensitivity to any component of the product 1, 2
Mandatory Concurrent Supplementation
All patients must receive adequate calcium and vitamin D supplementation to optimize outcomes and prevent hypocalcemia. 1, 2, 5
- Calcium: 1,000-1,200 mg elemental calcium daily, taken at least 30 minutes apart from alendronate 2, 5
- Vitamin D: 800-1,000 IU daily, targeting serum 25(OH)D ≥30 ng/mL 1, 2, 5
- For patients with 25(OH)D <30 ng/mL, give ergocalciferol 50,000 IU weekly for 8 weeks, then recheck levels 1, 2
- Correct vitamin D deficiency before starting therapy to prevent severe hypocalcemia 1, 5
Administration Requirements to Minimize Esophageal Risk
- Take with a full glass (6-8 oz) of plain water only 6
- Take after an overnight fast, at least 30 minutes before first food, beverage, or other medication 6
- Remain upright (sitting or standing) for at least 30 minutes after dosing 1, 2
- Once-weekly dosing may reduce esophageal irritation risk compared to daily dosing 3, 7
Rare but Serious Adverse Effects: The Long-Term Risks
Osteonecrosis of the Jaw (ONJ)
- Incidence with osteoporosis dosing: <1 to 28 cases per 100,000 person-years 1, 2
- Risk increases with duration beyond 2 years 2
- Perform dental examination and prophylactic care before starting therapy 1, 5
- Avoid unnecessary invasive oral surgery while on treatment 1
Atypical Femoral Fractures
- Incidence: 3.0 to 9.8 cases per 100,000 patient-years 2
- Risk increases with prolonged therapy duration 2
When to Switch or Stop Therapy
If a patient fractures ≥12 months after starting alendronate OR shows clinically significant BMD loss after 1-2 years, switch to another osteoporosis medication class. 2
- Switch options: IV bisphosphonate, denosumab, romosozumab, or parathyroid hormone analog 2
- Critical warning: Never switch directly from denosumab to teriparatide or abaloparatide, as this causes transient bone density loss at hip and spine 2
- If poor adherence or absorption suspected with oral therapy, transition to IV bisphosphonate or alternative agent 2
Special Populations
Cancer Treatment-Induced Bone Loss
- Initiate alendronate 70 mg weekly when T-score <-2.0 OR T-score ≥-2.0 with ≥2 risk factors (age >65, smoking, BMI <24, family history hip fracture, prior fragility fracture, glucocorticoid use >6 months) 2, 5
- Continue for duration of endocrine therapy or up to 5 years 2, 5
- In men on androgen deprivation therapy, alendronate increased BMD of hip and spine by 2.3% and 5.1% respectively after 12 months 2
Renal Transplant Recipients
- Consult metabolic bone disease specialist before initiating bisphosphonates to exclude renal osteodystrophy 2
- Pamidronate 90 mg over 4-6 hours is recommended for patients with severe renal impairment (serum creatinine >3.0 mg/dL or CrCl <30 mL/min) 1
Pediatric Use (Ages 4-17)
- For children on chronic glucocorticoids (≥0.1 mg/kg/day for >3 months) who have sustained osteoporotic fracture, oral or IV bisphosphonate therapy is conditionally recommended 2
- In children with low or moderate fracture risk, optimize calcium/vitamin D and weight-bearing exercise rather than initiating pharmacotherapy 2