Introduction
Forteo (teriparatide) is a recombinant human parathyroid hormone analog (rhPTH [1-34]) approved by the FDA in 2002 for the treatment of osteoporosis. It represents the first anabolic agent for osteoporosis treatment that stimulates new bone formation rather than inhibiting bone resorption. Forteo is indicated for patients at high risk of fracture and has demonstrated significant efficacy in reducing vertebral and nonvertebral fractures.
Mechanism of Action
Teriparatide acts as an agonist at the parathyroid hormone (PTH) receptor, mimicking the effects of endogenous PTH. Unlike continuous PTH exposure which promotes bone resorption, intermittent daily administration of teriparatide preferentially stimulates osteoblastic activity over osteoclastic activity. This leads to increased osteoblast number and function, enhanced bone formation, and improved bone microarchitecture. The drug increases intestinal calcium absorption and renal calcium reabsorption while simultaneously stimulating bone formation through activation of lining cells and increased differentiation of preosteoblasts into mature osteoblasts.
Indications
- Treatment of osteoporosis in postmenopausal women at high risk for fracture
- Increase of bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture
- Treatment of glucocorticoid-induced osteoporosis in men and women at high risk for fracture
- Treatment of osteoporosis associated with sustained systemic glucocorticoid therapy (≥5 mg/day prednisone equivalent for ≥3 months)
Dosage and Administration
Standard dosing: 20 mcg administered subcutaneously once daily into the thigh or abdominal wall Duration of therapy: Limited to 2 years lifetime maximum due to osteosarcoma risk observed in rat studies Administration technique: Use provided delivery device (prefilled pen); rotate injection sites Special populations:- Renal impairment: Not recommended in severe impairment (CrCl <30 mL/min)
- Hepatic impairment: No dosage adjustment necessary
- Geriatric patients: No dosage adjustment required
- Pediatric patients: Safety and effectiveness not established
Pharmacokinetics
Absorption: Rapidly absorbed following subcutaneous administration; peak concentrations achieved in approximately 30 minutes Distribution: Volume of distribution is approximately 0.12 L/kg; not extensively bound to plasma proteins Metabolism: Hepatic metabolism via nonspecific proteolytic enzymes; not metabolized by cytochrome P450 system Elimination: Half-life of approximately 1 hour when administered subcutaneously; cleared primarily by hepatic and renal extraction Excretion: Primarily renal (approximately 55% of dose) with smaller amounts excreted in fecesContraindications
- Hypersensitivity to teriparatide or any component of the formulation
- Pediatric and young adult patients with open epiphyses
- History of skeletal malignancies or bone metastases
- Metabolic bone diseases other than osteoporosis (including hyperparathyroidism and Paget's disease)
- Unexplained elevations of alkaline phosphatase
- Prior radiation therapy involving the skeleton
- Pregnancy
Warnings and Precautions
Black Box Warning:- Osteosarcoma risk: In rat studies, teriparatide caused dose-dependent increase in osteosarcoma
- Use limited to 2 years lifetime maximum
- Not recommended for patients at increased baseline risk of osteosarcoma
- Hypercalcemia: May occur; monitor serum calcium 16-24 hours after injection
- Orthostatic hypotension: May occur within 4 hours of injection; initial doses should be administered with patient seated or lying down
- Urolithiasis: Use with caution in patients with active or history of urolithiasis
- Cardiac disease: Use caution in patients with cardiac disease due to potential for increased heart rate
- Hepatic impairment: Limited data available in severe hepatic impairment
Drug Interactions
Digoxin: Teriparatide may transiently increase serum calcium, potentially increasing risk of digitalis toxicity Furosemide: Coadministration may increase risk of hypercalcemia Thiazide diuretics: May reduce urinary calcium excretion, potentially increasing risk of hypercalcemia Systemic corticosteroids: May antagonize effects of teriparatide Other bone-active agents: Concurrent use with bisphosphonates not recommended; sequential therapy preferredAdverse Effects
Common (≥5%):- Dizziness (9-13%)
- Leg cramps (5-8%)
- Nausea (8-9%)
- Arthralgia (10-13%)
- Injection site reactions (erythema, pain, swelling) (7-11%)
- Headache (7-10%)
- Hypercalcemia (∼3%)
- Orthostatic hypotension (∼5%)
- Increased uric acid (∼3%)
- Antibody formation (∼3%; neutralizing antibodies rare)
Monitoring Parameters
Baseline assessment:- Bone mineral density measurement
- Serum calcium, phosphorus, alkaline phosphatase
- Renal function (BUN, creatinine)
- 25-hydroxyvitamin D levels
- Urinary calcium excretion (if history of nephrolithiasis)
- Serum calcium 16-24 hours after injection (at 1 month, then every 3-6 months)
- Bone mineral density annually
- Monitor for symptoms of orthostatic hypotension
- Assessment of new bone pain
- Renal function periodically
- Consider transition to antiresorptive therapy to maintain bone density gains
- Continued fracture risk assessment
Patient Education
Administration instructions:- Inject once daily at approximately the same time each day
- Proper injection technique and site rotation
- Storage requirements: refrigerate; do not freeze
- Discard pen after 28 days even if medication remains
- Ensure adequate calcium (1000-1200 mg/day) and vitamin D (800-1000 IU/day) intake
- Regular weight-bearing exercise as tolerated
- Fall prevention strategies
- Report any persistent nausea, vomiting, constipation, lethargy, or muscle weakness
- Sit or lie down if feeling dizzy after injection
- Notify all healthcare providers of teriparatide use
- Understand lifetime treatment limitation (2 years maximum)
- Report any new bone pain or tenderness
- Importance of regular monitoring appointments
- Adherence to treatment duration limitations
- Post-treatment management plan
References
1. FDA Prescribing Information: Forteo (teriparatide) injection. 2022. 2. Neer RM, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001;344(19):1434-1441. 3. Saag KG, et al. Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med. 2007;357(20):2028-2039. 4. Miller PD, et al. Long-term safety and efficacy of teriparatide in postmenopausal women with osteoporosis. J Bone Miner Res. 2019;34(2):304-311. 5. Cosman F, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016;375(16):1532-1543. 6. Eastell R, et al. Pharmacological management of osteoporosis in postmenopausal women: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2019;104(5):1595-1622. 7. Camacho PM, et al. American Association of Clinical Endocrinologists/American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis—2020 update. Endocr Pract. 2020;26(Suppl 1):1-46.