What is the indication for Teriparatide (parathyroid hormone-related protein) therapy?

Teriparatide Indications

Teriparatide is indicated for postmenopausal women with primary osteoporosis at very high risk for fracture, men with primary or hypogonadal osteoporosis at high risk for fracture, and men and women with glucocorticoid-induced osteoporosis—all who have failed or are intolerant to other osteoporosis therapies. 1

FDA-Approved Indications

The FDA label specifies three primary indications for teriparatide 1:

• Postmenopausal women with osteoporosis at high risk for fracture, defined as having a history of osteoporotic fracture, multiple risk factors for fracture, or who have failed or are intolerant to other available osteoporosis therapy 1

• Men with primary or hypogonadal osteoporosis at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy 1

• Men and women with glucocorticoid-induced osteoporosis (daily dosage equivalent to 5 mg or greater of prednisone) at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy 1

Guideline-Based Patient Selection Criteria

The American College of Physicians recommends teriparatide specifically for postmenopausal women with "very high risk" for fracture, not as first-line therapy. 2 This represents a more restrictive recommendation than the FDA label.

Defining "Very High Risk" Patients

Very high risk is characterized by 2, 3, 4:

• Age >74 years (mean age in clinical trials) 2
• Recent fracture within the past 12 months 2, 3
• History of multiple clinical osteoporotic fractures 2, 3, 4
• Multiple risk factors for fracture 2, 3
• Failure of other available osteoporosis therapies 2, 3, 4

Approximately 10% of women older than 50 years in the general U.S. population meet these very high-risk criteria 2.

Treatment Algorithm and Positioning

Teriparatide should NOT be used as first-line therapy—bisphosphonates remain the initial treatment of choice for osteoporosis. 2, 3, 4

Recommended Treatment Sequence

1. First-line therapy: Bisphosphonates (alendronate, risedronate, zoledronic acid) for both postmenopausal women (strong recommendation) and men (conditional recommendation) 2

2. Second-line therapy: Denosumab for patients with contraindications to or adverse effects from bisphosphonates 2

3. Third-line therapy: Teriparatide (or romosozumab) reserved exclusively for very high-risk patients 2, 3

Critical Treatment Limitations

Teriparatide treatment is limited to a maximum of 24 months, and MUST be followed by bisphosphonate therapy to prevent rapid bone loss. 2, 3, 1 Discontinuation without sequential antiresorptive therapy results in rapid bone loss and increased fracture risk 2.

Use of teriparatide for more than 2 years during a patient's lifetime should only be considered if a patient remains at or has returned to having a high risk for fracture. 1

Clinical Efficacy Evidence

Teriparatide demonstrates significant fracture reduction in very high-risk populations 2, 3:

• Any clinical fractures: 27 fewer events per 1000 patients (high certainty) 2, 3
• Radiographic vertebral fractures: 69 fewer events per 1000 patients (high certainty) 2, 3
• Clinical vertebral fractures: 45 fewer events per 1000 patients (low certainty) 2
• Hip fractures: May result in no significant difference (low certainty) 2, 4

Compared to bisphosphonates, teriparatide reduces radiographic vertebral fractures by 66 fewer events per 1000 patients (moderate certainty) 2, 3.

Important Caveats and Contraindications

Avoid teriparatide in patients with increased baseline risk of osteosarcoma, including 1:

• Patients with open epiphyses (pediatric use contraindicated) 1
• Metabolic bone diseases including Paget's disease 1
• Bone metastases or history of skeletal malignancies 1
• Prior external beam or implant radiation therapy involving the skeleton 1
• Hereditary disorders predisposing to osteosarcoma 1

Additional contraindications and precautions 1:

• Hypersensitivity to teriparatide or excipients 1
• Underlying hypercalcemic disorders 1
• Active or recent urolithiasis (consider risk/benefit) 1
• Risk of orthostatic hypotension with initial doses 1

Cost Considerations

Teriparatide is the most expensive osteoporosis treatment, with an average annual cost per Medicare beneficiary of $22,156, compared to bisphosphonates ($39-$2,700) 2. The absolute cost is even higher when accounting for mandatory sequential bisphosphonate therapy after discontinuation 2.