What are the alternatives to Fosamax (alendronate) for treating osteoporosis?

Alternatives to Fosamax (Alendronate) for Osteoporosis Treatment

For postmenopausal women and men with primary osteoporosis, other bisphosphonates (risedronate or zoledronic acid) are the preferred first-line alternatives to alendronate, with denosumab as the recommended second-line option when bisphosphonates cannot be used. 1

First-Line Bisphosphonate Alternatives

Risedronate and zoledronic acid are equally effective alternatives to alendronate for initial treatment. 1 These bisphosphonates demonstrate comparable efficacy in reducing fracture risk:

• Risedronate is available as 5 mg daily, 35 mg weekly, 75 mg on two consecutive days monthly, or 150 mg monthly 1
• Zoledronic acid is administered as 5 mg intravenously every year for treatment or every 2 years for prevention 1
• All three bisphosphonates (alendronate, risedronate, zoledronic acid) reduce vertebral, nonvertebral, and hip fractures with high-certainty evidence 1

Important caveat: Ibandronate should not be considered equivalent—there is no evidence it reduces hip fractures, making it inferior to other bisphosphonates 1

Second-Line Alternative: Denosumab

Denosumab (60 mg subcutaneously every 6 months) is recommended as second-line therapy when bisphosphonates are contraindicated or cause adverse effects. 1 This applies to both postmenopausal women (moderate-certainty evidence) and men (low-certainty evidence) 1

Key considerations for denosumab:

• Demonstrated favorable long-term net benefit in postmenopausal women with osteoporosis, prior fractures, and previous bisphosphonate treatment 1
• Critical warning: If denosumab is discontinued for more than 6 months, bisphosphonate treatment (e.g., zoledronic acid) must be initiated to suppress rebound osteolysis 1
• Cannot extend dosing intervals beyond 4 weeks 1

Alternative for Younger Postmenopausal Women

Raloxifene (60 mg daily) can be considered as initial treatment specifically in younger postmenopausal women. 1 However, this recommendation comes with significant limitations:

• Raloxifene reduces only radiographic vertebral fractures, not hip or nonvertebral fractures 1
• Associated with serious harm risk including thromboembolism 1
• The American College of Physicians recommends against using raloxifene for osteoporosis treatment due to the harm-benefit profile 1

Severe Osteoporosis Alternative: Teriparatide

Teriparatide (20 mcg subcutaneously daily) is reserved for patients with severe osteoporosis or those who have already sustained fractures. 1 This is not a routine alternative but rather reserved for high-risk situations:

• Reduces vertebral and nonvertebral fractures 1
• Typically used only after bisphosphonate failure or in very high-risk patients 1

Agents NOT Recommended as Alternatives

Calcitonin should not be used except in patients with less serious osteoporosis who cannot tolerate any other treatment, as it has weaker efficacy data compared to all other options 1

Menopausal estrogen therapy (with or without progestogen) should not be used for osteoporosis treatment due to lack of fracture reduction benefit in established osteoporosis and association with serious harms 1

Mandatory Concurrent Therapy with All Alternatives

Regardless of which alternative is chosen, all patients must receive calcium 1,000-1,200 mg daily and vitamin D 600-800 IU daily, with target serum 25(OH)D level ≥30 ng/mL. 2 This is not optional—it is an essential component of any osteoporosis treatment regimen 2

Safety Monitoring Required for All Alternatives

Before initiating any alternative:

• Dental examination must be completed, with invasive dental procedures finished before starting treatment 2, 1
• Serum creatinine and creatinine clearance must be checked—intravenous bisphosphonates are generally not recommended if creatinine clearance <30 mL/min 2
• Fracture risk stratification is mandatory using BMD T-score and FRAX calculation to ensure treatment is appropriate 2

Common Pitfall to Avoid

Do not treat low-risk patients with any osteoporosis medication—the American College of Rheumatology strongly recommends against this due to known harms without evidence of benefit 2. Treatment should only be initiated in patients with prior osteoporotic fracture, BMD T-score ≤-2.5, or elevated FRAX scores 2