PTH (parathyroid hormone) is the full-length 84-amino-acid recombinant human parathyroid hormone (MW ~9425 g/mol) marketed as Natpara. It was FDA-approved in January 2015 as an adjunct to calcium and vitamin D for the control of hypocalcemia in patients with hypoparathyroidism, making it the first FDA-approved PTH replacement therapy. Natpara is available only through a restricted Risk Evaluation and Mitigation Strategy (REMS) program due to a potential risk of osteosarcoma observed in animal studies.
Category: Bone / PTH Analog. Evidence rating: A (strong human clinical data).
Clinical status: FDA-approved (Natpara for hypoparathyroidism, 2015; voluntary recall 2019 due to device issue; returned to market)
Recombinant PTH(1-84) binds to the PTH1 receptor (PTH1R), a G protein-coupled receptor expressed on osteoblasts, renal tubular cells, and other tissues. Activation of PTH1R stimulates adenylyl cyclase and phospholipase C signaling, increasing serum calcium through three principal mechanisms:…
Safety considerations: Common (>=5%): hypocalcemia, hypercalcemia, headache, paresthesia, nausea, diarrhea, vomiting, arthralgia, hypoesthesia; Black box warning: osteosarcoma observed in rats treated with near-lifetime exposure; clinical relevance to humans uncertain but restricts use to patients who cannot be adequately controlled on calcium and vitamin D alone; Available only through REMS program (Natpara REMS) requiring prescriber certification, patient enrollment, and pharmacy certification.
Reviewed by the PeptideAtlas Editorial Team.
| Molecular weight | ~9425 g/mol |
|---|---|
| CAS number | 12583-68-5 |
| Half-life | ~2.5 hours (subcutaneous) |
| Bioavailability | ~53% subcutaneous |
| Production method | recombinant |
| Anti-doping status | not-listed |
| US regulatory status | FDA-approved (Natpara, January 2015) for hypoparathyroidism. Available only through REMS. Voluntary recall of certain lots in 2019 due to rubber septum particulate issue; returned to market. |
Related peptides: Abaloparatide, Teriparatide.
Teriparatide (Forteo) is the 1-34 amino acid fragment of PTH and is approved for osteoporosis. Natpara (PTH 1-84) is the full-length 84-amino-acid hormone and is approved specifically for hypoparathyroidism. They bind the same receptor but have different indications, dosing, and pharmacokinetic profiles.
In preclinical studies, rats treated with PTH for nearly their entire lifespan developed osteosarcoma (bone cancer). Although this risk has not been confirmed in humans, the FDA requires the REMS program to ensure the benefits outweigh potential risks, limiting use to patients inadequately controlled on calcium and vitamin D alone.
In September 2019, Takeda issued a voluntary recall of specific lots due to the potential for rubber particulates from the cartridge septum. The product was temporarily unavailable but has since returned to market with an updated device.