What are the side effects, typical treatment duration, and potential transition medications for Forteo (teriparatide) in postmenopausal women and men with high-risk osteoporosis?

Forteo (Teriparatide) for Osteoporosis

Overview and Indications

Forteo is reserved exclusively for patients with severe osteoporosis at very high fracture risk—specifically those with recent fractures, multiple prior osteoporotic fractures, failure of bisphosphonate therapy, or intolerance to other treatments—and should never be used as first-line therapy. 1, 2, 3

Forteo is FDA-approved for: 4

• Postmenopausal women with osteoporosis at high fracture risk
• Men with primary or hypogonadal osteoporosis at high fracture risk
• Men and women with glucocorticoid-induced osteoporosis at high fracture risk

Side Effects and Safety Profile

Common Side Effects (>10%)

• Arthralgia (joint pain), generalized pain, and nausea are the most frequent adverse effects 4
• Injection-site pain, headaches, leg cramps, and dizziness occur commonly 5, 6

Serious Adverse Events

• Teriparatide may increase serious adverse events and probably increases withdrawal due to adverse effects (moderate certainty evidence) 1
• Hypercalcemia occurs more frequently with teriparatide than other osteoporosis agents 1, 4
• Orthostatic hypotension may occur transiently with initial doses—patients should be able to sit or lie down during first administrations 4

Critical Safety Warnings

Avoid teriparatide in patients with: 4

• Open epiphyses (pediatric patients)
• Metabolic bone diseases including Paget's disease
• Bone metastases or history of skeletal malignancies
• Prior external beam or implant radiation therapy involving skeleton
• Hereditary disorders predisposing to osteosarcoma
• Active or recent urolithiasis (kidney stones may worsen) 4
• Underlying hypercalcemic disorders 4

The osteosarcoma warning based on rat studies has been removed from the boxed warning as of November 2023, though caution remains in high-risk populations 4

Treatment Duration

The maximum treatment duration is 24 months during a patient's lifetime. 2, 3, 4, 7

• Treatment duration is typically 18-24 months 7
• Use beyond 2 years should only be considered if the patient remains at or has returned to very high fracture risk 4
• The 24-month limit was historically based on osteosarcoma concerns in animal models, though this risk has not been demonstrated in humans 8

Transition Medication After Forteo

Patients MUST transition to antiresorptive therapy (bisphosphonates or denosumab) immediately after completing teriparatide to preserve bone density gains and prevent rebound vertebral fractures. 1, 2, 3, 5

Transition Algorithm:

First-line transition: Bisphosphonates 1, 3

• Alendronate is the most commonly used transition agent
• Begin immediately after completing teriparatide course
• Failure to transition results in rapid bone loss and increased fracture risk 3, 5

Second-line transition: Denosumab 1, 3

• Reserved for patients with contraindications to bisphosphonates
• Also prevents loss of teriparatide-induced bone gains

Critical Pitfall to Avoid:

Never combine teriparatide with bisphosphonates during active treatment—concurrent therapy is not more effective than teriparatide monotherapy and may actually blunt the anabolic effect 5, 8, 9

Clinical Efficacy

Teriparatide demonstrates: 2, 3

• High-certainty evidence for reducing any clinical fractures (27 fewer events per 1,000 patients)
• High-certainty evidence for reducing radiographic vertebral fractures (69 fewer events per 1,000 patients)
• Low-certainty evidence for reducing clinical vertebral fractures (45 fewer events per 1,000 patients)
• Low-certainty evidence showing no significant reduction in hip fractures 2

Compared to bisphosphonates, teriparatide: 3

• Reduces radiographic vertebral fractures by 66 fewer events per 1,000 patients (moderate certainty)
• May reduce any clinical fracture by 46 fewer events per 1,000 patients (low certainty)

Administration Details

• Dose: 20 mcg subcutaneously once daily 4, 7
• Inject into thigh or abdominal region 4
• Supplied as 620 mcg/2.48 mL pen containing 28 daily doses 4
• Ensure adequate calcium (≤1,500 mg/day total) and vitamin D (≤1,000 IU/day) supplementation 8
• Monitor serum calcium after 1 month of treatment; further monitoring generally unnecessary unless hypercalcemia develops 8

Cost Considerations

Teriparatide is the most expensive osteoporosis treatment at $22,156 average annual cost per Medicare beneficiary, approximately 4-fold more expensive than romosozumab ($5,574 annually) 2

This high cost reinforces why bisphosphonates remain first-line therapy and teriparatide should be reserved only for severe cases meeting very high-risk criteria 1, 3

Special Populations

Pregnancy and Lactation: 4

• Consider discontinuing when pregnancy is recognized
• Breastfeeding is not recommended

Pediatric Use: 4

• Safety and effectiveness not established
• Avoid use due to increased baseline risk of osteosarcoma in patients with open epiphyses

Renal Insufficiency: 1

• Evidence is insufficient regarding efficacy in patients with renal dysfunction

Glucocorticoid-Induced Osteoporosis: 1

• Moderate-quality evidence supports teriparatide use in patients taking glucocorticoids