What is Forteo (Teriparatide)?
Forteo is the brand name for teriparatide, a recombinant human parathyroid hormone analog (PTH 1-34) that is the first and only FDA-approved anabolic (bone-building) agent for treating severe osteoporosis in patients at very high risk for fracture. 1
Mechanism of Action
Teriparatide is fundamentally different from other osteoporosis medications because it stimulates new bone formation rather than simply preventing bone loss. 2, 3 The drug consists of the first 34 amino acids of the 84-amino acid human parathyroid hormone, which represents the biologically active region. 1 It directly stimulates osteoblasts to build new bone tissue through two mechanisms: remodeling-based bone formation (within active remodeling sites) and modeling-based bone formation (on previously inactive bone surfaces). 4
FDA-Approved Indications
Teriparatide is specifically indicated for three patient populations at high risk for fracture: 1
- Postmenopausal women with osteoporosis who have failed or are intolerant to other available osteoporosis therapy
- Men with primary or hypogonadal osteoporosis who have failed or are intolerant to other available osteoporosis therapy
- Men and women with glucocorticoid-induced osteoporosis who have failed or are intolerant to other available osteoporosis therapy
Clinical Efficacy
Teriparatide demonstrates high-certainty evidence for fracture reduction, decreasing any clinical fractures by 27 fewer events per 1000 patients and radiographic vertebral fractures by 69 fewer events per 1000 patients compared to placebo. 5 The drug primarily increases trabecular bone in the lumbar spine and femoral neck, with less significant effects at cortical bone sites. 2 However, it may not significantly reduce hip fracture risk (low certainty evidence). 5
Administration and Dosing
- Route: Subcutaneous injection once daily 1
- Dose: 20 micrograms per day, delivered via a pre-filled pen device 1
- Sites: Thigh or abdomen (lower stomach area), rotating injection sites 1
- Duration: Each pen contains 28 days of medication and must be discarded after 28 days even if solution remains 1
Critical Treatment Limitations
Teriparatide is strictly limited to a maximum of 24 months of treatment over a patient's lifetime due to osteosarcoma risk observed in animal studies. 5, 6, 1 This is a black box warning, though postmarketing surveillance over 9 years found no cases of osteosarcoma attributable to teriparatide use in humans. 6, 1
After discontinuation, teriparatide MUST be immediately followed by antiresorptive therapy (bisphosphonates or denosumab) to preserve bone density gains and prevent rapid bone loss or rebound vertebral fractures. 5, 6
Common Adverse Effects
The most frequently reported side effects include: 7, 6
- Upper gastrointestinal symptoms (nausea, vomiting, gastritis): OR 3.26 compared to placebo
- Hypercalcemia: OR 12.9 compared to placebo—the most pronounced metabolic effect
- Headache: OR 1.46 compared to placebo
- Leg cramps and musculoskeletal pain 6
- Renal side effects (OR 2.36) and hypercalciuria (OR 2.44) 6
- Orthostatic hypotension and palpitations upon injection 6, 1
Patients should be instructed to sit or lie down immediately after injection if they experience lightheadedness or palpitations. 1
Absolute Contraindications
Teriparatide should never be used in patients with: 6, 1
- Paget's disease of bone
- Prior skeletal radiation therapy
- Bone metastases or history of bone cancer
- Open epiphyses (children and young adults whose bones are still growing)
- Unexplained elevations of alkaline phosphatase
- Hypercalcemia
The National Comprehensive Cancer Network specifically contraindicates teriparatide in patients with history of malignancy prone to metastasize to bone, though it could be cautiously considered in severe osteoporosis with remote cancer history if benefits outweigh theoretical risks. 5
Place in Therapy
Teriparatide is NOT a first-line treatment—bisphosphonates remain first-line therapy due to more favorable balance among benefits, harms, patient values, and cost. 5 The American College of Physicians recommends reserving teriparatide exclusively for postmenopausal women with primary osteoporosis at very high fracture risk, defined as: 5
- Recent fracture
- History of multiple clinical osteoporotic fractures
- Multiple risk factors for fracture
- Failure of other available osteoporosis therapy
Cost Considerations
Teriparatide is the most expensive osteoporosis treatment, with an average annual cost of $22,156 per Medicare beneficiary—approximately 4-fold more expensive than romosozumab ($5,574 annually). 5 Despite high acquisition costs, it may be cost-effective in carefully selected high-risk patients who have failed other therapies. 2, 3
Comparison with Romosozumab
When choosing between teriparatide and romosozumab for very high-risk patients: 5
- Choose romosozumab when the patient has no history of myocardial infarction or stroke within the past year and cost is a significant concern
- Choose teriparatide when the patient has recent cardiovascular events or significant cardiovascular disease, as romosozumab increases cardiovascular events compared to alendronate (HR 1.9,95% CI 1.1-3.1)
Key Clinical Pearls
- Teriparatide should not be combined with bisphosphonates during active treatment, as combination therapy is not more effective than teriparatide monotherapy. 2, 8
- The beneficial effects on vertebral fracture prevention and BMD persist following treatment cessation when followed by antiresorptive therapy. 3
- The full continuous 24-month course results in improved skeletal health and outcomes compared to shorter treatment periods, as fracture risk reduction appears to increase with longer duration of therapy. 4
- Patients should be counseled about supplemental calcium and vitamin D requirements during treatment. 1