In a post‑menopausal woman with severe osteoporosis refractory to anti‑resorptive therapy, what are the indications, dosing (20 µg subcutaneous daily), maximum treatment duration, contraindications, and required monitoring for teriparatide?

Teriparatide for Severe Osteoporosis in Postmenopausal Women

For a postmenopausal woman with severe osteoporosis refractory to anti-resorptive therapy, teriparatide 20 µg subcutaneous daily is indicated as a second-line anabolic agent, with treatment limited to a maximum of 2 years during the patient's lifetime, requiring baseline and 1-month serum calcium monitoring. 1, 2

Indications

Teriparatide is specifically indicated for postmenopausal women at very high fracture risk who have failed or are intolerant to bisphosphonates. 1, 3 The American College of Physicians defines very high risk as:

• T-score ≤ -3.5 at hip or spine 3
• Multiple prevalent vertebral fractures 3
• Fractures occurring despite adequate bisphosphonate therapy 3
• History of osteoporotic fractures with severe bone loss 1, 3

The FDA approval encompasses postmenopausal women with osteoporosis at high risk for fracture or those who have failed or are intolerant to other available osteoporosis therapy. 2

Dosing

The standard dose is 20 µg administered subcutaneously once daily into the thigh or abdominal region. 2

• Each pen contains 620 µg/2.48 mL (250 µg/mL), providing 28 daily doses of 20 µg 2
• Initial administration should occur under circumstances where the patient can sit or lie down due to risk of orthostatic hypotension 2
• Calcium supplementation should be limited to 1,000-1,200 mg daily from combined dietary and supplement sources 3, 4
• Vitamin D supplementation of 600-800 IU daily is recommended 3

Maximum Treatment Duration

Teriparatide use is limited to 2 years during a patient's lifetime. 2, 4 This restriction is based on osteosarcoma development in rat carcinogenicity studies, though the boxed warning was removed in 2023 after post-marketing surveillance of 200,000 patients showed no increased osteosarcoma risk. 2, 3

Use beyond 2 years should only be considered if the patient remains at or has returned to very high fracture risk. 2

After discontinuation, sequential anti-resorptive therapy is mandatory to preserve bone gains and prevent rebound vertebral fractures. 1, 3, 5

Contraindications

Absolute contraindications include: 2

• Hypersensitivity to teriparatide or excipients 2
• Open epiphyses (pediatric patients) 2, 3
• Paget's disease of bone or other metabolic bone diseases 2, 3
• Bone metastases or history of skeletal malignancies 3, 2
• Prior external beam or implant radiation therapy involving the skeleton 3, 2
• Hereditary disorders predisposing to osteosarcoma 2

Relative contraindications and cautions: 2

• Underlying hypercalcemic disorders (avoid use) 2
• Active or recent urolithiasis (consider risk/benefit carefully) 2
• Worsening cutaneous calcification (discontinue if develops) 2

Required Monitoring

Baseline assessment must include: 3

• Bone mineral density testing with DEXA scan 3
• Fracture risk assessment using FRAX tool 3
• Vertebral imaging with VFA or spinal X-ray 3
• Complete metabolic panel including serum calcium 2, 4
• Vitamin D levels 3
• Evaluation for secondary causes of osteoporosis 3

Ongoing monitoring: 2, 4

• Serum calcium measurement after 1 month of treatment 2, 4
• If mild hypercalcemia develops, withdraw dietary calcium supplements or reduce dosing frequency 4
• Yearly clinical fracture risk assessment 1
• BMD testing every 2-3 years depending on risk factors 1

Critical Clinical Considerations

Avoid concurrent bisphosphonate therapy during teriparatide treatment, as combination therapy is not more effective than teriparatide monotherapy and may blunt the anabolic response. 4, 6, 7

Transient orthostatic hypotension may occur with initial doses, requiring patients to sit or lie down during first administrations. 2

Patients on digoxin require special attention, as transient hypercalcemia may predispose to digitalis toxicity. 2

Generic bisphosphonates should be prescribed first-line when possible rather than teriparatide, as teriparatide is significantly more expensive and bisphosphonates have the most favorable balance of benefits, harms, and cost. 1, 3 Teriparatide is reserved for patients who have documented failure of bisphosphonates or cannot tolerate them. 1, 3