What is the recommended treatment approach for postmenopausal women or older adults with a history of osteoporotic fractures using Terzapatide?

Teriparatide Treatment for Postmenopausal Women and Older Adults with Osteoporotic Fractures

Teriparatide should be reserved exclusively for postmenopausal women and older adults at very high risk for fracture—specifically those over 74 years old, with recent fractures (within 12 months), multiple prior osteoporotic fractures, or who have failed bisphosphonate therapy—and must be followed by mandatory transition to bisphosphonate or denosumab therapy to prevent rapid bone loss. 1, 2

Patient Selection Criteria

Teriparatide is not first-line therapy. The American College of Physicians recommends bisphosphonates as initial treatment for osteoporosis due to superior cost-effectiveness, availability of generic formulations, and high-certainty evidence for fracture reduction. 3, 4

Very high-risk patients appropriate for teriparatide include: 1, 2

• Age >74 years
• Recent fracture within the past 12 months
• Multiple clinical osteoporotic fractures (≥2)
• T-score ≤-3.0
• FRAX score ≥20% for major osteoporotic fracture or ≥3% for hip fracture
• Failed or intolerant to bisphosphonate therapy after adequate trial
• Contraindications to both bisphosphonates and denosumab

Treatment Protocol

Dosing and Administration: 5

• 20 mcg subcutaneously once daily into the thigh or abdominal region
• Maximum duration: 18-24 months (should not exceed 2 years in a patient's lifetime unless they return to very high fracture risk) 1, 5
• Initial administration should occur under supervision where the patient can sit or lie down due to orthostatic hypotension risk 5

Essential Concurrent Therapy: 3, 2

• Calcium supplementation: 1,000-1,200 mg daily
• Vitamin D supplementation: 800-1,000 IU daily (targeting serum 25(OH)D ≥30-50 ng/mL)
• Weight-bearing and resistance exercises
• Fall prevention counseling

Monitoring Requirements

Safety monitoring during treatment: 2, 5

• Serum calcium at 1 month after initiation, then as clinically indicated
• Urinary calcium monitoring for hypercalcemia risk
• Mild hypercalcemia managed by reducing calcium supplements or adjusting dosing frequency

Mandatory Post-Treatment Transition

Critical: Patients MUST transition to antiresorptive therapy immediately after completing teriparatide to maintain bone gains and prevent rebound fractures. 3, 1, 2 Discontinuation without follow-up antiresorptive therapy results in rapid bone loss and serious risk for multiple vertebral fractures. 3

Preferred sequential agents: 2

• Bisphosphonates (alendronate or zoledronic acid)
• Denosumab (particularly for patients with GI contraindications to oral bisphosphonates)

Expected Outcomes

Fracture risk reduction with teriparatide: 1

• Radiographic vertebral fractures: 69 fewer events per 1,000 patients (high certainty)
• Any clinical fractures: 27 fewer events per 1,000 patients (high certainty)
• Clinical vertebral fractures: 45 fewer events per 1,000 patients (low certainty)

Bone density improvements: 2

• Lumbar spine BMD: 10% increase
• Hip BMD: 3% increase

Contraindications to Verify Before Prescribing

Absolute contraindications: 2, 5

• Hypersensitivity to teriparatide or excipients
• Paget's disease of bone
• Prior skeletal radiation therapy
• Bone metastases or history of skeletal malignancies
• Active malignancies prone to bone metastases
• Osteosarcoma risk (based on rat studies showing increased incidence) 5

Common Pitfalls to Avoid

• Never use teriparatide as first-line therapy when bisphosphonates are appropriate—this violates cost-effectiveness principles and guideline recommendations 3, 4
• Never discontinue teriparatide without immediate transition to antiresorptive therapy—this causes rapid bone loss and rebound fracture risk 3, 2
• Never combine teriparatide with bisphosphonates concurrently—this reduces teriparatide's anabolic effect 6, 7
• Never exceed 2 years of lifetime teriparatide use unless the patient returns to very high fracture risk 1, 5
• Never prescribe without ensuring adequate calcium and vitamin D supplementation, but limit total daily calcium to 1,500 mg to avoid hypercalcemia 6

Adverse Effects

Teriparatide may increase risk for serious adverse events and probably increases withdrawal due to adverse events (low to moderate certainty evidence). 3 However, osteonecrosis of the jaw and atypical femoral fractures—the serious long-term complications associated with bisphosphonates—are not associated with teriparatide. 3