Teriparatide

Chemical Identity

Property	Value
Chemical Formula	C181H291N55O51S2
Molecular Weight	4117.7 Da
CAS Number	52232-67-4
Peptide Class	Recombinant PTH Fragment (1-34)
Route	SC injection

Structure

Teriparatide (Forteo) is recombinant human parathyroid hormone(1-34), the biologically active N-terminal fragment of the 84-amino acid PTH molecule. The 34-amino acid peptide retains full receptor-binding and activation capacity while being more stable and practical to produce than full-length PTH.

Mechanism of Action

Teriparatide binds PTH1 receptors on osteoblasts and osteocytes, activating cAMP/PKA signaling. Intermittent dosing (once daily) preferentially stimulates osteoblast differentiation and bone formation over bone resorption, unlike continuous PTH exposure which favors resorption. This increases bone mass and improves microarchitecture.

Clinical Applications

• Postmenopausal osteoporosis: High fracture risk (Forteo)
• Male osteoporosis: High fracture risk
• Glucocorticoid-induced osteoporosis: High-risk patients
• Fracture prevention: 65% reduction in vertebral fractures (Fracture Prevention Trial)

Pharmacokinetics

• Half-life: 1 hour
• Tmax: 30 minutes
• Bioavailability: 95%
• Metabolism: Hepatic (non-specific proteolysis)
• Dosing: 20 mcg SC daily for up to 24 months
• Route: SC injection (thigh or abdomen)

Safety and Side Effects

Hypercalcemia (mild), dizziness, leg cramps, nausea, and orthostatic hypotension. Contraindicated in Paget’s disease, prior radiation therapy, hypercalcemia, and elevated alkaline phosphatase of unknown origin. Boxed warning for osteosarcoma risk in rodents (clinical significance debated).

References

• Neer, R.M., et al. (2001). Effect of PTH(1-34) on fractures and bone mineral density. New England Journal of Medicine, 344, 1434-1441.
• Saag, K.G., et al. (2007). Teriparatide versus alendronate for glucocorticoid-induced osteoporosis. New England Journal of Medicine, 357, 2028-2039.