What is the recommended use of Teriparatide (parathyroid hormone-related protein) for osteoporosis treatment?

Teriparatide for Osteoporosis Treatment

Primary Recommendation

Teriparatide should be reserved exclusively for patients with severe osteoporosis 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—administered as 20 mcg subcutaneously daily for up to 24 months, followed by mandatory bisphosphonate therapy. 1, 2, 3

Patient Selection Criteria

Very High Risk Definition

Teriparatide is indicated only for patients meeting all of the following severity criteria 1, 2, 4:

• Age typically >74 years 1, 2
• Recent fracture within past 12 months 1, 2, 4
• History of multiple clinical osteoporotic fractures 1, 2, 4
• Multiple concurrent fracture risk factors 1, 4
• Documented failure or intolerance to bisphosphonates or other osteoporosis therapies 1, 2, 4, 3

Treatment Hierarchy

The American College of Physicians establishes a clear algorithmic approach 1, 2:

1. First-line: Oral bisphosphonates for all patients with osteoporosis 2, 5
2. Second-line: Denosumab for patients with contraindications to bisphosphonates 2
3. Third-line: Teriparatide only for very high-risk patients who meet the above criteria 2, 4

This conditional recommendation reflects low-certainty evidence for teriparatide in females and insufficient evidence to recommend for males 1.

Administration Protocol

Dosing and Duration

• Dose: 20 mcg subcutaneously once daily into thigh or abdominal region 3
• Maximum duration: 24 months during patient's lifetime 3, 6
• Initial administration should occur under supervision where patient can sit or lie down due to orthostatic hypotension risk 3
• Use beyond 24 months should only be considered if patient remains at or returns to very high fracture risk 3

Supplementation Requirements

• Calcium: 1,000-1,500 mg daily (total from diet and supplements) 3, 7
• Vitamin D: 400-1,200 IU daily (up to 1,000 IU/day per some protocols) 3, 7
• Monitor serum calcium after 1 month of treatment 7

Fracture Reduction Efficacy

Compared to Placebo

Teriparatide demonstrates significant fracture reduction at 24 months 1:

• Any clinical fractures: 27 fewer events per 1,000 patients (high certainty) 1, 2
• Radiographic vertebral fractures: 69 fewer events per 1,000 patients (high certainty) 1, 2
• Clinical vertebral fractures: 45 fewer events per 1,000 patients (low certainty) 1, 2
• Hip fractures: No significant difference (low certainty) 1

Compared to Bisphosphonates

At 24-month assessment 1, 2:

• Radiographic vertebral fractures: 66 fewer events per 1,000 patients (moderate certainty) 1, 2
• Any clinical fracture: 46 fewer events per 1,000 patients (low certainty) 1, 2
• Serious adverse events: No significant difference (low certainty) 1

The fracture benefit appears to increase with longer treatment duration, supporting the full 24-month course 6.

Absolute Contraindications

Teriparatide must be avoided in 4, 3:

• Open epiphyses (children and young adults with growing bones) 4, 3
• Paget's disease of bone 4, 3
• Prior external beam or implant radiation therapy involving skeleton 4, 3
• Bone metastases or history of skeletal malignancies 5, 4, 3
• Metabolic bone diseases predisposing to osteosarcoma 3
• Known hypercalcemic disorders 4, 3
• Hypersensitivity to teriparatide or excipients 3

Critical Safety Considerations

Osteosarcoma Risk

While teriparatide caused osteosarcoma in rat studies, no increased risk has been observed in adult humans treated with teriparatide 3. The FDA removed the boxed warning for osteosarcoma in November 2023 3. However, avoid use in patients with increased baseline osteosarcoma risk 4, 3.

Common Adverse Effects

Patients frequently experience 1, 4:

• Nausea, dizziness, vomiting 1, 4
• Headache, palpitations 1, 4
• Leg cramps 1, 4
• Increased withdrawal due to adverse events: 17-127 more events per 1,000 patients (moderate certainty) 1

Hypercalcemia Management

• Mild transient hypercalcemia may occur 3, 7
• Monitor serum calcium at 1 month 7
• Manage by reducing calcium supplements or decreasing PTH dosing frequency 7
• Discontinue if worsening cutaneous calcification develops 3

Orthostatic Hypotension

• Transient orthostatic hypotension may occur with initial doses 3
• Patients should sit or lie down during/after injection if lightheaded 3
• Symptoms typically resolve; if persistent, consult healthcare provider 3

Mandatory Sequential Therapy

Discontinuation of teriparatide without follow-up antiresorptive therapy results in rapid bone loss and increased fracture risk 1, 2, 4. This is a critical pitfall to avoid.

Post-Teriparatide Protocol

• Immediately transition to bisphosphonate therapy after completing teriparatide 1, 2, 4
• This sequential approach maintains bone density gains achieved during teriparatide treatment 1, 2
• Without antiresorptive follow-up, bone mineral density gradually decreases, though may remain above baseline for 30 months 8

Special Populations

Glucocorticoid-Induced Osteoporosis

Teriparatide is indicated for men and women with glucocorticoid-induced osteoporosis at high fracture risk 5, 3. The American College of Rheumatology recommends teriparatide after oral bisphosphonates when bisphosphonates are not appropriate 5.

Men with Osteoporosis

Teriparatide increases bone mass in men with primary or hypogonadal osteoporosis at high fracture risk 3, 8. Men treated with teriparatide showed 83% reduction in moderate or severe vertebral fractures (p=0.01) 8. However, the American College of Physicians did not make a recommendation for males due to insufficient evidence 1.

Perioperative Spine Surgery

For osteoporotic patients undergoing spinal instrumentation, teriparatide demonstrates superiority over bisphosphonates 5:

• Reduced screw loosening: 7% vs 13% with bisphosphonates 5
• Improved fusion rates: 82% vs 68% 5
• Earlier fusion: 8 months vs 10 months 5

Drug Interactions

Digoxin

Transient hypercalcemia from teriparatide may predispose patients to digitalis toxicity 3. Monitor digoxin levels and cardiac symptoms in patients on concurrent therapy.

Concurrent Bisphosphonate Use

Avoid concurrent therapy with bisphosphonates during teriparatide treatment, as bisphosphonates diminish the bone anabolic potential of teriparatide 7, 9. Previous bisphosphonate treatment may also reduce teriparatide efficacy 9.

Pregnancy and Lactation

• Consider discontinuing when pregnancy is recognized 3
• Breastfeeding is not recommended during teriparatide therapy 3

Cost-Effectiveness Context

Teriparatide is significantly more expensive than bisphosphonates 7, 10. Cost-utility estimates support reserving teriparatide for severe osteoporosis patients at highest fracture risk, particularly those with established fractures or T-scores ≤-3.5 7, 10.