What are the alternative treatments to Prolia (denosumab) and Alendronate for osteoporosis?

Alternative Treatments to Prolia and Alendronate for Osteoporosis

For patients who cannot use Prolia (denosumab) or alendronate, zoledronic acid is the recommended alternative treatment for osteoporosis, followed by other options including risedronate, teriparatide, and abaloparatide depending on fracture risk and patient characteristics. 1, 2

First-Line Alternatives

Zoledronic Acid

• Strongest alternative to Prolia and alendronate based on high-quality evidence
• Administered intravenously at 4 mg every 6 months for 3-5 years 1
• Benefits:
  • Reduces risk of hip, vertebral, and non-vertebral fractures 1
  • Higher adherence rates compared to oral medications 3
  • Preferred for patients with compliance issues 2
  • Can be used in patients with upper GI disorders that preclude oral bisphosphonates

Risedronate

• Oral bisphosphonate alternative to alendronate
• Reduces risk of vertebral and non-vertebral fractures 1
• Available in daily, weekly, or monthly dosing formats 1
• Improves BMD at lumbar spine (4.39%), total hip (2.46%), and femoral neck (1.95%) 1

Second-Line Alternatives

Teriparatide

• Bone-forming agent (anabolic) rather than anti-resorptive
• Recommended for patients at very high risk of fracture 1, 2
• Significantly improves BMD at lumbar spine (8.19%) and femoral neck (1.33%) 1
• Should be followed by an anti-resorptive agent to maintain gains 1
• Limited to 2 years of treatment due to regulatory restrictions

Abaloparatide

• Newer anabolic agent for patients at very high fracture risk 1
• Weak recommendation for use in men with osteoporosis 1
• Should be followed by anti-resorptive therapy

Ibandronate

• Alternative bisphosphonate option
• Improves lumbar spine BMD (2.58%) and total hip BMD (2.13%) 1
• Less evidence for reduction in hip fractures compared to other bisphosphonates 1

Selection Algorithm Based on Patient Characteristics

1. For patients with renal impairment (eGFR <35 mL/min):

   • Denosumab is preferred if not contraindicated 2, 4
   • Avoid bisphosphonates or adjust dosing 2

2. For patients at very high fracture risk:

   • Consider sequential therapy starting with bone-forming agent (teriparatide or abaloparatide) followed by anti-resorptive agent 1, 2

3. For patients with compliance issues:

   • Zoledronic acid (IV administration every 6-12 months) 1, 3
   • Denosumab if not contraindicated (subcutaneous injection every 6 months) 2

4. For patients with upper GI issues:

   • IV zoledronic acid 3
   • Denosumab if not contraindicated 2

Important Considerations

Safety Profiles

• Bisphosphonates (zoledronic acid, risedronate, ibandronate):

  • Risk of osteonecrosis of jaw (uncommon: 0.01-0.3%)
  • Atypical femoral fractures (rare)
  • Zoledronic acid: potential for atrial fibrillation, arthralgia, flu-like symptoms 1

• Anabolic agents (teriparatide, abaloparatide):

  • Upper GI symptoms
  • Hypercalcemia
  • Headaches 1

Treatment Duration

• Bisphosphonates: Consider treatment holiday after 5 years 1, 2
• Anabolic agents: Limited to 2 years of treatment per regulatory guidelines 1

Monitoring

• Assess adherence to anti-resorptive therapy using biochemical markers of bone turnover 1
• Ensure vitamin D and calcium repletion in all patients 1, 2

Caveat

When discontinuing denosumab, it is essential to transition to a bisphosphonate to prevent rebound bone loss and increased vertebral fracture risk. Typically, zoledronic acid (4-5 mg IV) should be administered 5-6 months after the last denosumab injection 2, 4.