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This is an approved / prescription medicine. Do not use without a prescription and medical supervision.

EMA-approvedaka PTH, Natpara, Yorvipath

Parathyroid hormone — Complete Research Guide (2026)

Last updated 2026-06-30

TL;DR

Parathyroid hormone (also known as PTH) is a peptide catalogued under Hormones & Metabolic (Full-length rhPTH (1-84)). It is described as: PTH1R. Documented context: Hypoparathyroidism. Neutral reference entry; EU status: EU-approved prescription medicine.

What is Parathyroid hormone?

Recombinant human parathyroid hormone (1-84), marketed as Natpara in the US and Natpar in Europe, is the full-length 84-amino-acid hormone produced by recombinant DNA technology. The FDA approved it in 2015 as an adjunct to calcium and active vitamin D for adults with hypoparathyroidism not well controlled on those alone; the EMA approved Natpar in 2017.

IMPORTANT: it carries an FDA boxed warning for a potential risk of osteosarcoma (a bone cancer), based on rat studies. It was later subject to US supply problems, including a 2019 recall and subsequent discontinuation of the US product. Its pivotal human evidence is the randomized phase 3 REPLACE trial.

How does Parathyroid hormone work?

The recombinant hormone replaces deficient endogenous parathyroid hormone, acting on kidney and bone to increase renal calcium reabsorption, promote phosphate excretion, and stimulate conversion of vitamin D to its active 1,25-dihydroxy form, thereby raising serum calcium toward normal.

What does the research say about Parathyroid hormone?

  • In the phase 3 REPLACE trial, rhPTH(1-84) let most patients substantially reduce or eliminate calcium and active vitamin D supplements while maintaining serum calcium. [1]
  • It lowered serum phosphate and increased renal production of active 1,25-dihydroxyvitamin D in hypoparathyroid patients. [2]
  • Calcium control with a reduced supplement burden was maintained across up to 5 years of continued treatment. [3]

Clinical research & studies

The references below are the primary sources cited throughout this guide. Each links directly to PubMed or the regulator. Where evidence is preclinical (animal or in-vitro), that is stated rather than implied.

  • [1] Efficacy and safety of recombinant human parathyroid hormone (1-84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study — Mannstadt M et al., Lancet Diabetes and Endocrinology 2013. (Randomized double-blind placebo-controlled phase 3 trial)
  • [2] Effects of parathyroid hormone rhPTH(1-84) on phosphate homeostasis and vitamin D metabolism in hypoparathyroidism: REPLACE phase 3 study — Clarke BL et al., Endocrine 2017. (Phase 3 trial secondary analysis)
  • [3] Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism — Mannstadt M et al., Journal of Clinical Endocrinology and Metabolism 2019. (Long-term open-label extension)
  • [4] A Phase I Randomized Trial of Once-Daily Versus Twice-Daily Recombinant Human Parathyroid Hormone (1-84) for Hypoparathyroidism — Ing SW et al., JBMR Plus 2023. (Randomized phase I trial)
  • [5] The PARADIGHM (physicians advancing disease knowledge in hypoparathyroidism) registry for patients with chronic hypoparathyroidism: study protocol and interim baseline patient characteristics — Gittoes N et al., BMC Endocrine Disorders 2021. (Observational registry protocol)

Dosing context

This is not medical advice or a usage recommendation. Dosing figures are reported research context only, cited from the published literature.

In its approved use it was given as a once-daily subcutaneous injection, individually titrated against serum calcium while calcium and vitamin D were adjusted downward.

All dosing and titration were physician-directed with mandatory monitoring; no self-administration figures are given here.

Side effects & safety profile

The drug carries an FDA boxed warning for a potential risk of osteosarcoma observed in rodent (rat) carcinogenicity studies; because of this it is reserved for patients who cannot be well controlled on calcium and active vitamin D alone, and long-term registries have tracked outcomes.

Common adverse effects include hypercalcemia and hypocalcemia (notably around dose changes), nausea, headache, and paresthesia.

Beyond the safety signal, the US product had a manufacturing recall (2019) and was subsequently discontinued in the United States, affecting availability; treatment decisions belong with a specialist and this page is educational only.

Stacking & combinations

It is used as an adjunct that lets calcium and active vitamin D be tapered under supervision, not combined with other peptides or hormones for enhancement.

Finding Parathyroid hormone vendors

Finding Parathyroid hormone vendors

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Frequently asked questions

It was FDA-approved in 2015 (Natpara) as an add-on to calcium and active vitamin D for adults with hypoparathyroidism not controlled on those alone; the EMA approved Natpar in 2017.

References

  1. [1] Efficacy and safety of recombinant human parathyroid hormone (1-84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study — Mannstadt M et al., Lancet Diabetes and Endocrinology 2013. PMID: 24622413. View sourceStudy: Randomized double-blind placebo-controlled phase 3 trialrhPTH(1-84) allowed most patients to cut or stop calcium and active vitamin D while maintaining serum calcium.
  2. [2] Effects of parathyroid hormone rhPTH(1-84) on phosphate homeostasis and vitamin D metabolism in hypoparathyroidism: REPLACE phase 3 study — Clarke BL et al., Endocrine 2017. PMID: 27734257. View sourceStudy: Phase 3 trial secondary analysisTreatment reduced serum phosphate and raised active 1,25-dihydroxyvitamin D.
  3. [3] Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism — Mannstadt M et al., Journal of Clinical Endocrinology and Metabolism 2019. PMID: 31369089. View sourceStudy: Long-term open-label extensionCalcium control and reduced supplement need were maintained over up to 5 years.
  4. [4] A Phase I Randomized Trial of Once-Daily Versus Twice-Daily Recombinant Human Parathyroid Hormone (1-84) for Hypoparathyroidism — Ing SW et al., JBMR Plus 2023. PMID: 37457880. View sourceStudy: Randomized phase I trialCompared pharmacodynamics of once-daily versus twice-daily rhPTH(1-84) dosing.
  5. [5] The PARADIGHM (physicians advancing disease knowledge in hypoparathyroidism) registry for patients with chronic hypoparathyroidism: study protocol and interim baseline patient characteristics — Gittoes N et al., BMC Endocrine Disorders 2021. PMID: 34801015. View sourceStudy: Observational registry protocolDescribes a long-term registry tracking outcomes, including safety, in chronic hypoparathyroidism patients.
This article is for educational and research purposes only. Peptides discussed here are not approved for human consumption by the FDA, EMA, or equivalent regulators outside of specific clinical contexts. Always consult a licensed medical professional before any therapeutic use.