Parathyroid hormone

Parathyroid hormone is the main signal that keeps blood calcium steady. It raises calcium in three ways: it helps the kidney tubules reabsorb calcium, it converts vitamin D into its active form so the gut absorbs more calcium, and it speeds bone turnover, which releases calcium from bone into the blood¹. People with hypoparathyroidism lack enough of this hormone and are usually treated with large amounts of oral calcium and active vitamin D, which do not reliably control blood minerals and can lead to long-term complications². Natpara replaced the missing hormone itself as an injection under the skin; in studies, blood calcium peaked about 10 to 12 hours after a single injection¹.

In the REPLACE phase 3 trial, 134 adults with long-standing hypoparathyroidism were randomized to the hormone or placebo for 24 weeks while their calcium and active vitamin D were reduced. 53% on the hormone met the main goal, at least halving those supplements while keeping blood calcium stable, compared with 2% on placebo; overall adverse-event rates were similar between groups². An open-label extension at 12 US centers followed 49 adults, 40 of whom completed five years: blood calcium stayed in a steady range, urine calcium and serum phosphate fell, kidney function was unchanged, and 70% met the composite efficacy goal at five years³. Bone turnover markers rose, peaked around one year, then settled at levels still above baseline³. A 2026 case report describes switching a patient to palopegteriparatide ahead of the withdrawal⁴.

FDA-approved in January 2015 as Natpara, as an add-on to calcium and vitamin D for hypoparathyroidism in people not well controlled on those alone¹. Global production ended in 2024, FDA's drug-shortage list marks it discontinued (Drugs@FDA still shows it as a prescription product), and the EU authorisation for Natpar was withdrawn in July 2026 at the company's request over unresolved supply issues^4,5,6.

The label carried a boxed warning: parathyroid hormone caused osteosarcoma, a bone cancer, in rats, and a human risk could not be excluded, so it was reserved for people not controlled on standard therapy, avoided in those at higher bone-cancer risk, and supplied only through a restricted program. Other warnings were severe high calcium, severe low calcium when treatment stopped, digoxin toxicity and allergic reactions. Common effects included tingling, low or high calcium, headache, nausea, diarrhea, vomiting and joint pain¹.

1. FDA label: Natpara (2022)FDA
2. Mannstadt et al., Lancet Diabetes Endocrinol 2013PubMed
3. Mannstadt et al., J Clin Endocrinol Metab 2019PubMed
4. Chiardi & Trimboli, JCEM Case Rep 2026PubMed
5. FDA Drug Shortages: Parathyroid Hormone InjectionFDA
6. EMA: Natpar (withdrawn)European Medicines Agency