What is the difference between Forteo (teriparatide) and Prolia (denosumab) for treating osteoporosis?

Forteo vs Prolia for Osteoporosis Treatment: Key Differences and Recommendations

Forteo (teriparatide) and Prolia (denosumab) have fundamentally different mechanisms of action and are appropriate for different clinical scenarios in osteoporosis treatment, with Prolia generally being preferred as first-line therapy for most patients due to its ease of administration and safety profile.

Mechanism of Action

• Forteo (teriparatide):

  • Anabolic agent (bone-forming)
  • Recombinant parathyroid hormone (PTH 1-34)
  • Stimulates new bone formation by increasing osteoblast activity 1, 2
  • Administered daily via subcutaneous injection for up to 2 years

• Prolia (denosumab):

  • Antiresorptive agent (prevents bone breakdown)
  • Human monoclonal antibody against RANKL
  • Inhibits osteoclast formation, function, and survival 3, 4
  • Administered every 6 months via subcutaneous injection

Efficacy in Fracture Reduction

• Forteo (teriparatide):

  • Reduces vertebral fractures by approximately 70%
  • Reduces non-vertebral fractures by approximately 45%
  • Limited evidence for hip fracture prevention 2
  • Particularly effective for patients with severe osteoporosis and vertebral fractures

• Prolia (denosumab):

  • Reduces vertebral, non-vertebral, and hip fractures 3, 5
  • Consistently increases BMD across all skeletal sites
  • Maintains efficacy for up to 10 years of treatment 5

Patient Selection

Prolia (denosumab) is appropriate for:

• Postmenopausal women with osteoporosis at high risk for fracture 3
• Men with osteoporosis at high risk for fracture 3
• Patients with glucocorticoid-induced osteoporosis receiving ≥7.5 mg prednisone daily for at least 6 months 6
• Patients receiving androgen deprivation therapy for prostate cancer 3
• Patients receiving aromatase inhibitor therapy for breast cancer 3
• Patients with renal impairment (eGFR < 35 ml/min) 6

Forteo (teriparatide) is appropriate for:

• Patients at very high risk of fracture (especially vertebral fractures) 1
• Patients who have failed or are intolerant to antiresorptive therapies 1
• Patients with severe osteoporosis with multiple fractures 7

Administration and Duration

• Forteo (teriparatide):

  • Daily subcutaneous injection
  • Limited to 2 years of treatment due to regulatory restrictions 7
  • Requires transition to an antiresorptive agent after completion 6, 8

• Prolia (denosumab):

  • Subcutaneous injection every 6 months
  • No specific time limitation for treatment
  • Requires careful management if discontinued to prevent rebound bone loss 6, 4

Safety Considerations

Forteo (teriparatide):

• Black box warning for potential risk of osteosarcoma (based on rat studies) 7
• Contraindicated in patients with:
  • Paget's disease of bone
  • Open epiphyses
  • Prior radiation therapy involving the skeleton
  • History of bone metastases or malignancy prone to metastasize to bone 1, 7
• Potential side effects include:
  • Hypercalcemia
  • Orthostatic hypotension
  • Nausea, dizziness, headache 7

Prolia (denosumab):

• Risk of severe hypocalcemia, especially in patients with advanced kidney disease 3
• Potential side effects include:
  • Osteonecrosis of the jaw (rare)
  • Atypical femur fractures (rare)
  • Skin reactions
  • Risk of multiple vertebral fractures upon discontinuation if not followed by another antiresorptive 3, 5, 4

Sequential Therapy Considerations

• After completing Forteo (teriparatide) treatment, transition to an antiresorptive agent is essential to maintain BMD gains 6, 8
• Denosumab has shown superior BMD maintenance after teriparatide compared to zoledronic acid or no treatment 8
• The American College of Physicians conditionally recommends using romosozumab or teriparatide followed by a bisphosphonate in women with very high fracture risk 1

Practical Recommendations

1. For most patients with osteoporosis: Consider Prolia (denosumab) due to its convenient dosing schedule (every 6 months), consistent efficacy, and good safety profile.

2. For patients with very high fracture risk (multiple fractures, very low BMD, or failure of other therapies): Consider Forteo (teriparatide) for 2 years, followed by Prolia or a bisphosphonate.

3. For patients with renal impairment: Prolia may be preferred over bisphosphonates, but requires careful monitoring of calcium levels, especially in advanced kidney disease.

4. For patients with history of cancer: Exercise caution with Forteo due to theoretical concerns about bone malignancy; Prolia may be a safer option.

5. For patients requiring long-term therapy: Prolia offers the advantage of no specific time limitation, whereas Forteo is restricted to 2 years.

Common Pitfalls to Avoid

• Failing to transition to an antiresorptive agent after completing Forteo treatment
• Abrupt discontinuation of Prolia without follow-up therapy
• Inadequate calcium and vitamin D supplementation with either medication
• Using Forteo in patients with history of skeletal malignancy
• Not monitoring for hypocalcemia in patients on Prolia, especially those with renal impairment