Parathyroid hormone (1-84)
The whole parathyroid hormone, made recombinantly, used as daily replacement when the glands fail
Parathyroid hormone (1-84) is the complete hormone the parathyroid glands release to hold blood calcium steady. Made recombinantly and sold as Natpara, it was approved as hormone replacement for hypoparathyroidism, where the glands are missing or damaged. Its maker stopped producing it, and US supply ended on December 31, 2025. It differs from teriparatide, which is only the first 34 amino acids.
Last FDA label of a product discontinued in the US (not a current US recommendation): 50 mcg, Once daily, in the thigh, Subcutaneous Details ↓
Recommended Dosing
Last FDA label of a product discontinued in the US (not a current US recommendation)
From the last US prescribing information of a product discontinued in the US (see the regulatory status on this page). It records what that label said while the product was sold there; it is not a current US recommendation. Other doses studied, if any, are in the full dosing data below.
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
Work out syringe units → · New to syringes? · All dosing data ↓
What is it?
Parathyroid hormone (PTH) is the body's main calcium thermostat. When blood calcium dips, the parathyroid glands release this 84-amino-acid hormone, which pulls calcium from bone, makes the kidneys hold on to calcium and let go of phosphate, and switches on active vitamin D. In hypoparathyroidism the glands no longer make enough. The traditional treatment, large doses of calcium tablets and active vitamin D, does not control calcium and phosphate well and can load the kidneys.
Recombinant human PTH(1-84) is the whole hormone, identical to the natural one. That sets it apart from teriparatide, a 34-residue fragment approved for osteoporosis, and from the newer long-acting prodrug palopegteriparatide. In the phase 3 REPLACE trial, 53% of adults on rhPTH(1-84) halved their calcium and active vitamin D doses while keeping blood calcium in range, against 2% on placebo. FDA approved it as Natpara on January 23, 2015, as an add-on to calcium and vitamin D for patients not well controlled on those alone.
Longer studies have followed small groups for up to a decade. In 24 patients treated for eight years, supplemental calcium fell by 57% and active vitamin D by 76%, urinary calcium dropped by 38% and kidney function held steady; quality-of-life scores rose and stayed up. A retrospective comparison found kidney filtration stable over five years on rhPTH(1-84) while it declined in untreated patients. A randomised trial reported in 2025 found less symptom burden and fatigue than conventional therapy alone.
The main practical problem is that a once-daily injection of a hormone with a half-life of about three hours cannot mimic the gland's steady output. One study found blood calcium peaking around seven hours after each dose, with asymptomatic high calcium in 71% of patients on a fixed 100 mcg dose, which is why the label insists on individual titration and frequent calcium checks. Stopping it suddenly can drop calcium sharply.
Natpara's US history was short. The label carried a boxed warning about osteosarcoma, seen in rats given the hormone, and the drug was sold only through a REMS programme. It was recalled in the US in 2019 over a problem with its delivery device. In October 2022 Takeda announced that it would stop making it worldwide at the end of 2024; its final letter to US prescribers set December 31, 2025 as the last day of shipments under its special use programme, and advised moving patients to another approved treatment.
Before any of that, PTH(1-84) was tested in osteoporosis. Daily 100 mcg injections raised spine density and lowered new vertebral fractures in an 18-month trial of 2,532 women, and the PaTH trial showed that adding alendronate blunted its bone-building effect, while alendronate afterwards preserved the gain. It was never approved for osteoporosis in the US, where teriparatide and abaloparatide fill that role.
Mechanism of Action
PTH(1-84) acts on the type 1 parathyroid hormone receptor in bone and kidney, replacing the missing hormone rather than adding a drug effect on top of normal levels.
Bone
Releases calcium from bone and raises bone turnover markers; given intermittently in osteoporosis it built trabecular bone (PMIDs 14500804, 26684150).
Kidney
Increases calcium reabsorption and phosphate loss, so urinary calcium and serum phosphate fall (PMIDs 31310310, 24802860).
Active vitamin D
Stimulates production of 1,25-dihydroxyvitamin D, shifting its daily rhythm after each injection (PMID 23649554).
Published Research
The studies behind full-length parathyroid hormone, read from their PubMed abstracts. Trials of teriparatide, PTH(1-34), are on the teriparatide entry.
REPLACE: the phase 3 trial
In 134 adults with long-standing hypoparathyroidism, 53% given rhPTH(1-84) (50 mcg a day, titrated to 75 and 100 mcg) cut their oral calcium and active vitamin D by at least half while keeping calcium normal at 24 weeks, against 2% on placebo; adverse event rates were similar.
REPEAT: the open-label follow-on
In 24 Hungarian patients treated for another 24 weeks with a simpler titration, 75% met the response target and 58% stopped oral calcium and active vitamin D altogether; urinary calcium and phosphate fell, and there were no serious adverse events.
Eight years of treatment
In 24 patients followed for eight years, supplemental calcium fell 57% and active vitamin D 76%, serum calcium stayed stable, urinary calcium dropped 38% and kidney function held; spine and hip density rose while forearm density fell.
More than ten years of exposure
In 39 patients with a mean of about 10.8 years on rhPTH(1-84), calcium, phosphate and urinary calcium stayed in range through a further three-year extension, bone markers and density were stable and no new safety signals appeared.
Calcium peaks after each injection
In 38 patients after six months on a fixed 100 mcg daily dose or placebo, PTH peaked 15 minutes after injection and fell to baseline by 16 hours (half-life 2.2 h); ionised calcium peaked about 7 hours after dosing, and 71% had asymptomatic high calcium, so the authors judged 100 mcg too high for some.
Single-dose kinetics
After single 50 and 100 mcg injections in patients with hypoparathyroidism, the half-life was about 2.5 to 3 hours and PTH returned to baseline by about 12 hours; the hormone raised calcium and lowered phosphate more effectively than calcitriol alone.
Kidney function over five years
Comparing 69 trial patients on rhPTH(1-84) with 53 untreated patients from a health-system database, mean eGFR rose 2.8 mL/min/1.73 m² over five years on treatment and fell 8.0 without it; groups differed in some baseline conditions.
Quality of life over eight years
In 20 patients, rhPTH(1-84) improved five of eight SF-36 domains, with mental scores improved through eight years and physical scores through six; those with the worst baseline scores and the biggest cuts in calcium supplements improved most.
Symptoms, in a randomised trial
In 93 patients with symptomatic chronic hypoparathyroidism, 26 weeks of rhPTH(1-84) at 25–100 mcg a day improved a hypoparathyroidism symptom score, fatigue and physical health scores more than placebo, with no new safety signals.
Pregnancy and breastfeeding: one case
A woman with post-surgical hypoparathyroidism stopped rhPTH(1-84) early in two pregnancies and used it while breastfeeding; both children were healthy at follow-up, and her second pregnancy coincided with the 2019 US recall over the delivery device.
Osteoporosis: vertebral fractures
In 2,532 postmenopausal women given 100 mcg daily or placebo for 18 months, PTH(1-84) raised spine density by 6.9% and reduced new or worse vertebral fractures, though the size of the reduction depended on assumptions about the many dropouts; high urine and blood calcium and nausea were more frequent.
PaTH: combined with alendronate
In 238 women given PTH(1-84) 100 mcg daily, alendronate, or both for a year, spine density rose in all groups, but trabecular density gained about twice as much on PTH alone, and the combination blunted bone formation, suggesting alendronate dampens its anabolic effect.
PaTH: what comes after
Women who followed a year of PTH(1-84) with a year of alendronate kept and increased their density gains (31% trabecular spine increase on CT), while those switched to placebo lost much of what they had gained.
Dosing Data
These are the last US Natpara label's doses (revised April 2022). Natpara is no longer supplied in the US: Takeda ended shipments on December 31, 2025, so the figures explain the trials and past prescribing rather than a dose anyone can now fill.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Parathyroid hormone (1-84) is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: we hold no copy of the preparation section of the label behind Parathyroid hormone (1-84)'s dose. Its label, named in Recommended Dosing above, is the source; the reconstitution calculator does the arithmetic for any vial.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Parathyroid hormone (1-84), before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Parathyroid hormone (1-84) stays intact once mixed.
How it is taken
As the approved label gives it: Subcutaneous (Once daily, in the thigh; Label: starting dose).
Source: Last FDA label of a product discontinued in the US (not a current US recommendation): the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: a half-life of about 3 hours (3.02 h at 50 mcg, 2.83 h at 100 mcg). After about five half-lives almost none is left.
How long the doses were given: Label: starting dose: Cut active vitamin D by 50% if calcium is above 7.5 mg/dL; recheck calcium in 3–7 days; Label: titration: Increase no more often than every 4 weeks.
When effects appear: unknown; no source on this page gives a time to effect for Parathyroid hormone (1-84). Results reported in the studies are under Published Research.
Source: half-life: Natpara (parathyroid hormone) for injection US prescribing information, revised April 2022, the last version on Drugs@FDA (BLA 125511, supplement 28); not on DailyMed: Takeda stopped manufacturing at the end of 2024 and ended US supply on December 31, 2025, section 12.3; Last FDA label of a product discontinued in the US (not a current US recommendation), the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: High blood calcium, often without symptoms, peaking hours after the injection; Low calcium when doses are missed or treatment stops; High urinary calcium and nausea in the osteoporosis trial; Falling forearm bone density in long-term use. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Parathyroid hormone (1-84). Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the studies above”).
Interactions
Unknown: a PubMed search for human interaction studies of Parathyroid hormone (1-84) (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Parathyroid hormone (1-84) products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Parathyroid hormone (1-84)'s expected mass, 9,424.8 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Discontinued (FDA-approved January 23, 2015 as Natpara (BLA 125511, NPS Pharmaceuticals, later Takeda) as an adjunct to calcium and vitamin D to control hypocalcaemia in hypoparathyroidism, with a boxed osteosarcoma warning and a REMS). Sport: Unsettled (S0 may apply).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the studies above.
Contraindications & Cautions
From the boxed warning and warnings of the last US Natpara label (revised April 2022, Drugs@FDA).
Legal Status
Natpara was an FDA-approved biologic that its maker has stopped making; US supply ended in 2025.
Frequently Asked Questions
?Is this the same as teriparatide?
No. Teriparatide is PTH(1-34), the first 34 amino acids, approved for osteoporosis. This entry is the full 84-amino-acid hormone, which was approved for hypoparathyroidism.
?Can I still get Natpara?
Not in the US. Takeda ended shipments on December 31, 2025 and asked prescribers to move patients to another approved treatment.
?Why does calcium swing on it?
One daily injection with a half-life of about three hours gives a peak, not a steady level. Calcium peaked about seven hours after dosing in one study, so the dose is titrated and calcium checked often.
?What about the osteosarcoma warning?
Rats given parathyroid hormone developed bone tumours depending on dose and duration. The label said a human risk could not be excluded and limited use to patients not controlled on standard treatment.
?Was it used for osteoporosis?
It was tested: it raised spine density and reduced vertebral fractures in a large trial, but it was never approved for osteoporosis in the US.
References
- [clinical-trial] Mannstadt M, et al. "Efficacy and safety of recombinant human parathyroid hormone (1-84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study." Lancet Diabetes Endocrinol, 2013;1(4):275-83. PMID: 24622413.
- [clinical-trial] Lakatos P, et al. "AN OPEN-LABEL EXTENSION STUDY OF PARATHYROID HORMONE RHPTH(1-84) IN ADULTS WITH HYPOPARATHYROIDISM." Endocr Pract, 2016;22(5):523-32. PMID: 26684150.
- [clinical-trial] Tay YD, et al. "Therapy of Hypoparathyroidism With rhPTH(1-84): A Prospective, 8-Year Investigation of Efficacy and Safety." J Clin Endocrinol Metab, 2019;104(11):5601-5610. PMID: 31310310.
- [clinical-trial] Rubin MR, et al. "Extended Treatment With Recombinant Human Parathyroid Hormone (1-84) in Adult Patients With Chronic Hypoparathyroidism." Endocr Pract, 2024;30(3):200-208. PMID: 38086524.
- [clinical-trial] Sikjaer T, et al. "PTH(1-84) replacement therapy in hypoparathyroidism: a randomized controlled trial on pharmacokinetic and dynamic effects after 6 months of treatment." J Bone Miner Res, 2013;28(10):2232-43. PMID: 23649554.
- [clinical-trial] Clarke BL, et al. "Pharmacokinetics and pharmacodynamics of subcutaneous recombinant parathyroid hormone (1-84) in patients with hypoparathyroidism: an open-label, single-dose, phase I study." Clin Ther, 2014;36(5):722-36. PMID: 24802860.
- [pubmed] Chen KS, et al. "Five-year Estimated Glomerular Filtration Rate in Patients With Hypoparathyroidism Treated With and Without rhPTH(1-84)." J Clin Endocrinol Metab, 2020;105(10):e3557-65. PMID: 32738041.
- [clinical-trial] Tabacco G, et al. "Quality of Life in Hypoparathyroidism Improves With rhPTH(1-84) Throughout 8 Years of Therapy." J Clin Endocrinol Metab, 2019;104(7):2748-2756. PMID: 30776291.
- [clinical-trial] Brandi ML, et al. "rhPTH(1-84) for hypoparathyroidism: a randomized study of patient-reported outcomes." Eur J Endocrinol, 2025;193(2):310-319. PMID: 40711996.
- [pubmed] Liao EP, et al. "Use of rhPTH(1-84) for hypoparathyroidism during early pregnancy and lactation." Endocrinol Diabetes Metab Case Rep, 2023;2023(2). PMID: 37335755.
- [clinical-trial] Greenspan SL, et al. "Effect of recombinant human parathyroid hormone (1-84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: a randomized trial." Ann Intern Med, 2007;146(5):326-39. PMID: 17339618.
- [clinical-trial] Black DM, et al. "The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis." N Engl J Med, 2003;349(13):1207-15. PMID: 14500804.
- [clinical-trial] Black DM, et al. "One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis." N Engl J Med, 2005;353(6):555-65. PMID: 16093464.
- [fda] Drugs@FDA (openFDA): BLA125511, NATPARA (parathyroid hormone), NPS Pharmaceuticals; original approval January 23, 2015; marketing status Prescription. Read October 28, 2026.
- [other] UniProt P01270 (PTH_HUMAN), chain residues 32-115, parathyroid hormone; read October 28, 2026. https://www.uniprot.org/uniprotkb/P01270/entry
- [other] European Medicines Agency, Natpar (parathyroid hormone) EPAR page: conditional marketing authorisation April 24, 2017; withdrawn July 1, 2026 at the request of the holder, Takeda. https://www.ema.europa.eu/en/medicines/human/EPAR/natpar. Read October 28, 2026.
- [fda-pi] Natpara (parathyroid hormone) for injection US prescribing information, Shire-NPS, revised April 2022. Drugs@FDA, BLA 125511, supplement 28: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125511s028lbl.pdf (not on DailyMed: no longer supplied). Read October 28, 2026.
- [fda] Takeda Pharmaceuticals U.S.A., letter to US patients: Natpara global manufacturing to stop at the end of December 2024, following October 2022 communications. Posted by FDA: https://www.fda.gov/media/182120/download. Read October 28, 2026.
- [fda] Takeda Pharmaceuticals U.S.A., final notice to prescribers dated December 1, 2025: the Natpara Special Use Program closes and no shipments are made after December 31, 2025. Posted by FDA: https://www.fda.gov/media/189952/download. Read October 28, 2026.
Sources & Citations
Studies were read from their PubMed abstracts; doses, half-life and warnings from the last US Natpara label on Drugs@FDA (revised April 2022); the end of supply from Takeda's letters to US patients and prescribers posted by FDA, read October 28, 2026.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.