What is the first‑line osteoporosis therapy for a post‑menopausal woman or older man who cannot receive denosumab (Prolia) due to an allergic reaction, and what alternatives are recommended if bisphosphonates are contraindicated?

Osteoporosis Treatment When Allergic to Prolia

Oral bisphosphonates (alendronate or risedronate) are the first-line treatment for postmenopausal osteoporosis and should be initiated immediately when denosumab cannot be used due to allergy. 1

Primary Treatment Algorithm

First-Line: Oral Bisphosphonates

• Alendronate or risedronate are preferred based on proven vertebral, non-vertebral, and hip fracture reduction, low cost, and extensive safety data 1
• Dosing options for alendronate: 70 mg weekly or 10 mg daily 1
• Dosing options for risedronate: 35 mg weekly, 5 mg daily, or 150 mg monthly 1
• These agents must be taken with specific instructions: on an empty stomach with 8 oz water, remaining upright for at least 30 minutes to prevent esophageal irritation 1

Contraindications to Oral Bisphosphonates

Oral bisphosphonates should be avoided in patients with:

• Esophageal emptying disorders or inability to sit/stand upright for 30 minutes (high risk of pill esophagitis) 1
• Creatinine clearance <35 mL/min 1
• Hypocalcemia (must be corrected first) 1

Second-Line Options When Oral Bisphosphonates Are Not Appropriate

Intravenous Zoledronic Acid

• Zoledronic acid 5 mg IV annually is the preferred alternative when oral bisphosphonates cannot be used 1
• Particularly indicated for patients with:
  • Gastrointestinal intolerance to oral agents 1
  • Malabsorption syndromes 1
  • Poor adherence or dementia 1
• Contraindication: creatinine clearance <35 mL/min 1
• Requires adequate hydration during infusion to minimize renal risk 1

Teriparatide (Anabolic Agent)

• Consider teriparatide for patients with very severe osteoporosis (T-score ≤-3.5 or prevalent vertebral fractures) who cannot tolerate bisphosphonates 1
• Administered as daily subcutaneous injection 1
• Reduces vertebral and non-vertebral fractures 1
• Higher cost and injection burden limit its use as first-line therapy 1

Raloxifene (Selective Estrogen Receptor Modulator)

• Raloxifene 60 mg daily can be considered in younger postmenopausal women at lower fracture risk 1
• Reduces vertebral fractures but not proven to reduce hip or non-vertebral fractures 1
• Should not be used in women at highest risk for hip fracture 1

Essential Concurrent Therapy

All patients must receive calcium and vitamin D supplementation regardless of which osteoporosis medication is chosen:

• Calcium: 1,000-1,200 mg daily (total from diet and supplements) 1
• Vitamin D: 800-1,000 IU daily 1
• Check serum 25-hydroxyvitamin D levels and target ≥30 ng/mL 1
• For deficiency (25-OH vitamin D <30 ng/mL): ergocalciferol 50,000 IU weekly for 8 weeks, then recheck 1
• Vitamin D deficiency must be corrected before starting IV bisphosphonates to prevent severe hypocalcemia 1

Critical Monitoring and Follow-Up

• Bone mineral density (BMD) testing at 24 months to assess treatment response 2
• Monitor serum calcium, especially in first weeks after starting IV bisphosphonates 1
• Assess for adherence with oral agents (major cause of treatment failure) 1
• Dental evaluation before starting any bisphosphonate in high-risk patients to minimize osteonecrosis of the jaw risk 1

Important Clinical Pitfalls

Avoid these common errors:

• Do not delay treatment while waiting for BMD testing in patients with prior fragility fractures 1
• Never discontinue osteoporosis therapy without transitioning to another agent, as this increases fracture risk 3
• Do not use denosumab in organ transplant patients on multiple immunosuppressants due to infection risk 1
• Ensure proper administration technique for oral bisphosphonates to prevent esophageal complications 1

Treatment Duration

• Bisphosphonates are typically prescribed for 3-5 years initially, with continuation based on ongoing fracture risk assessment 1
• Patients who remain at high risk after initial treatment course should continue therapy 1
• Zoledronic acid demonstrates sustained fracture reduction for up to 10 years 1