Teriparatide
Teriparatide is a recombinant PTH(1-34) fragment used to stimulate osteoblast activity and new bone formation in severe osteoporosis, the first anabolic skeletal agent.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C181H291N55O51S |
| Molecular Weight | 4117.72 g/mol |
| CAS Number | 52232-67-4 |
| IUPAC Name | Human PTH(1-34) fragment |
| Peptide Class | Parathyroid Hormone Analog |
| Sequence Homology | Identical to human PTH(1-34) |
Structure
Teriparatide is the recombinant human parathyroid hormone (PTH) fragment comprising amino acids 1-34 of the full-length 84-amino acid hormone. This N-terminal fragment retains full biological activity at the PTH/PTHrP receptor. The peptide is produced by recombinant DNA technology in Escherichia coli.
Mechanism of Action
Teriparatide acts as an anabolic agent for bone when administered intermittently (daily injection). It binds to PTH1 receptors on osteoblasts and osteocytes, stimulating:
- Osteoblast proliferation and differentiation
- RANKL expression (paradoxically increasing bone resorption transiently)
- Net bone formation exceeding resorption with daily dosing
- Wnt/β-catenin signaling pathway activation
This intermittent PTH exposure produces a net anabolic effect, contrasting with the catabolic effect of continuous PTH elevation in hyperparathyroidism.
Clinical Applications
Teriparatide (Forteo) is approved for:
- Severe osteoporosis: Postmenopausal women and men at high fracture risk
- Glucocorticoid-induced osteoporosis: In patients at high risk for fracture
- Treatment failure: Patients who have failed or are intolerant to other osteoporosis therapies
In the pivotal trial, teriparatide reduced vertebral fractures by 65% and non-vertebral fractures by 53% over 18 months.
Pharmacokinetics
- Half-life: 1 hour (subcutaneous)
- Tmax: 30 minutes after subcutaneous injection
- Bioavailability: 95%
- Metabolism: Hepatic and renal proteolysis
- Duration of therapy: Limited to 24 months due to osteosarcoma risk in preclinical studies
Safety and Side Effects
Common adverse effects include orthostatic hypotension (especially after first dose), dizziness, nausea, leg cramps, and hypercalcemia. Contraindicated in patients at increased risk for osteosarcoma (Paget disease, prior radiation therapy, open epiphyses). The 24-month treatment limit was established based on osteosarcoma findings in rats, though this has not been confirmed in humans.
References
- Neer, R.M., et al. (2001). Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. New England Journal of Medicine, 344, 1434-1441.
- Saag, K.G., et al. (2007). Teriparatide or alendronate in glucocorticoid-induced osteoporosis. New England Journal of Medicine, 357, 2028-2039.
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