Teriparatide
Teriparatide is the N-terminal 34-amino-acid fragment of human parathyroid hormone, PTH(1-34). It is an FDA-approved bone-forming (anabolic) agent, marketed as Forteo, used for osteoporosis in people at high risk of fracture.
Overview
Teriparatide consists of the first 34 amino acids of human parathyroid hormone, an 84-residue hormone that regulates calcium and phosphate balance. The N-terminal region carries the activity needed to activate the PTH type 1 receptor, so this fragment reproduces the main actions of the full hormone at the receptor. Although sustained high PTH levels, as in hyperparathyroidism, cause bone loss, intermittent exposure to PTH(1-34) was found in animals and people to stimulate bone formation more than resorption.
Teriparatide became the first anabolic osteoporosis drug approved in the United States, marketed by Eli Lilly as Forteo. Its approval rested on the Fracture Prevention Trial in postmenopausal women with osteoporosis, which reported reductions in new vertebral and nonvertebral fractures compared with placebo. It is now available in several jurisdictions as branded, biosimilar or follow-on products. It occupies a distinct place from antiresorptive drugs such as bisphosphonates, which mainly slow bone breakdown.
Compare: Teriparatide vs abaloparatide.
Structure
Teriparatide is a linear 34-residue peptide identical to residues 1-34 of human parathyroid hormone: Ser-Val-Ser-Glu-Ile-Gln-Leu-Met-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser-Met-Glu-Arg-Val-Glu-Trp-Leu-Arg-Lys-Lys-Leu-Gln-Asp-Val-His-Asn-Phe (SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF), with a free C-terminal acid. The branded product is produced recombinantly in Escherichia coli, whereas some other products are made by chemical synthesis. It contains two methionines (positions 8 and 18) and one tryptophan, all oxidation-prone, and several asparagine residues that can deamidate.
Mechanism
Teriparatide activates the PTH type 1 receptor (PTH1R), a class B G protein-coupled receptor expressed on osteoblasts and renal tubular cells, signaling mainly through cyclic AMP and protein kinase A, with additional phospholipase C signaling. Intermittent receptor activation increases osteoblast number and activity, partly by reducing osteoblast apoptosis, activating bone-lining cells and modulating inhibitors such as sclerostin, so that formation exceeds resorption. Continuous exposure shifts the balance toward resorption. The precise basis of this anabolic window is still studied.
Research
Postmenopausal osteoporosis
The Fracture Prevention Trial randomized postmenopausal women with prior vertebral fractures to teriparatide or placebo and reported reduced risk of new vertebral and nonvertebral fractures together with increases in bone mineral density. These results, published in 2001, supported FDA approval. Subsequent studies compared teriparatide with antiresorptive agents and examined sequencing, since bone density gains are generally maintained only if an antiresorptive drug follows. Treatment courses studied in these trials were time-limited, and data beyond them come mainly from extension and observational studies.
Men and glucocorticoid-induced osteoporosis
Clinical trials extended teriparatide research to men with osteoporosis and to people with osteoporosis associated with long-term glucocorticoid therapy, including a comparison with a bisphosphonate in the glucocorticoid setting. These studies contributed to approved indications in such populations. Researchers should consult current labeling for the exact indications in a given jurisdiction. Trial designs and endpoints in these populations differed from the pivotal postmenopausal study, and bone mineral density was often the main outcome.
Osteosarcoma signal and labeling
In long-term rat toxicology studies, teriparatide was associated with osteosarcoma at a range of exposures, which led to a boxed warning and limits on lifetime treatment duration in the original US labeling. Human surveillance studies have not shown a clear increase in osteosarcoma, and US labeling was later revised. The rat findings are still cited when discussing PTH-pathway anabolic agents, and current labeling should be checked for present wording.
Fracture healing and other research
Investigators have explored teriparatide in fracture healing, osteonecrosis of the jaw, hypoparathyroidism and dental and orthopedic settings. Much of this work consists of animal studies, small trials and case series, with mixed results. These uses are not approved indications. Full-length PTH(1-84) and other PTH analogues have been studied separately, particularly for hypoparathyroidism. Their findings should be interpreted cautiously. Larger controlled trials would be needed to clarify them.
Regulatory status
Teriparatide is FDA-approved, marketed as Forteo, for osteoporosis in people at high risk for fracture; check current labeling for specific populations and duration language. Biosimilar or follow-on teriparatide products are available in some jurisdictions, and it is approved in many countries. For sport, check the current WADA Prohibited List.
Status changes often. See the regulatory tracker for dated updates.
Quality and identity testing
A certificate of analysis should confirm identity by mass spectrometry, with the observed mass matching the expected mass shown on this page, and report HPLC purity with the chromatogram; peptide mapping adds confidence for a 34-residue sequence. Compound-specific degradation includes oxidation of Met8 and Met18, each adding about 16 Da and known to reduce receptor activity, tryptophan oxidation, and deamidation of asparagine residues. Truncated or extended forms, such as fragments lacking terminal residues, should be resolved. For recombinant material, host-cell protein and endotoxin testing are relevant. The counter-ion and net peptide content should be stated.
Open Teriparatide in the sequence analyzer to see the expected [M+H]+ and multiply charged ions for an MS identity check.
For a walkthrough of each section of a certificate, see how to read a COA.
Storage and stability
Store lyophilized teriparatide sealed at -20 °C or colder, protected from light and moisture; pharmaceutical solutions are kept refrigerated and should not be frozen, per labeling. The two methionines make the peptide notably sensitive to oxidation, so minimize headspace air, avoid peroxide-containing excipients and consider inert-gas overlay. Prepare research solutions in sterile, slightly acidic buffer, keep them cold, aliquot for longer storage at -20 °C or below, and avoid repeated freeze-thaw cycles and vigorous agitation.
Download the Teriparatide data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.
Latest research
The newest PubMed-indexed papers that mention Teriparatide in their title or abstract, retrieved through Europe PMC and refreshed automatically. Inclusion is not an endorsement of a paper's findings.
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Frequently asked questions
Is teriparatide the same as parathyroid hormone?
Teriparatide is the first 34 amino acids of human parathyroid hormone, which in full is 84 residues long. This N-terminal fragment contains the region needed to activate the PTH type 1 receptor, so it reproduces the hormone's main receptor actions. Full-length PTH(1-84) is a separate product studied mainly in hypoparathyroidism.
Is teriparatide FDA approved?
Yes. Teriparatide is FDA-approved and marketed as Forteo for osteoporosis in people at high risk of fracture. Other teriparatide products are available in some markets. Current labeling should be consulted for the specific populations covered and any language on treatment duration.
Why does intermittent PTH build bone when high PTH causes bone loss?
Sustained elevation of PTH, as in hyperparathyroidism, increases bone resorption. Brief, intermittent receptor activation instead favors osteoblast activity, so bone formation exceeds resorption. The molecular basis of this difference, sometimes called the anabolic window, involves osteoblast survival, lining-cell activation and sclerostin, and remains an active research area.
What is the difference between teriparatide and abaloparatide?
Teriparatide is PTH(1-34), while abaloparatide is a modified analogue of PTH-related protein (1-34). Both activate the PTH type 1 receptor, but abaloparatide was reported to favor a different receptor conformation, which may alter signaling duration. Both are FDA-approved anabolic agents for osteoporosis.
Related compounds
- Abaloparatide
Abaloparatide is a synthetic 34-amino-acid analogue of parathyroid hormone-related protein, PTHrP(1-34). It is an FDA-approved anabolic agent for osteoporosis, marketed as Tymlos, that acts on the PTH type 1 receptor.
- Calcitonin (salmon)
Salmon calcitonin is a 32-amino-acid peptide hormone with a disulfide-bridged ring and C-terminal prolinamide that inhibits osteoclast bone resorption. It is FDA-approved as Miacalcin for conditions including Paget's disease of bone and hypercalcemia.
References
- Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001. Find on PubMed
- PubMed: all indexed literature on Teriparatide
- ClinicalTrials.gov: registered studies mentioning Teriparatide
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