Parathyroid hormone-related protein
The hormone behind most cancer-related high calcium, and a short fragment tested as an osteoporosis drug
Parathyroid hormone-related protein (PTHrP) is a protein many tissues make for local signalling. Its front end resembles parathyroid hormone and works through the same receptor, so when a tumour pours it into the blood, calcium rises. Doctors measure it to diagnose that kind of high calcium. Its first 36 amino acids, PTHrP(1-36), have been injected in small human osteoporosis trials but never approved; the approved drug abaloparatide is a separate, modified molecule.
Used in human trials: 400 or 600 mcg, Once daily, Subcutaneous (PrOP trial, postmenopausal women) Details ↓
Recommended Dosing
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?
PTHrP was found by people trying to explain a puzzle. Some cancers raise blood calcium without spreading to bone, a condition called humoral hypercalcaemia of malignancy, and for years the cause was assumed to be parathyroid hormone made by the tumour. It turned out to be a different protein whose first few amino acids resemble PTH closely enough to switch on the same receptor in bone and kidney. In 1990, assays aimed at two regions of PTHrP found it raised in the blood of 30 patients with this syndrome and low or undetectable in healthy people.
Outside cancer, PTHrP is a local signal rather than a circulating hormone. It is made in many tissues, the gene is cut and spliced into several isoforms, and the protein is trimmed after it is made into a family of peptides with different jobs. It is abundant in breast milk and in umbilical cord blood, where it appears to come from the fetus. Mutations that switch off one copy of PTHLH cause brachydactyly type E, a hereditary shortening of the bones of the hands and feet, often with short stature.
In cancer, PTHrP is the usual reason for high calcium. In a 2026 Korean series of 289 patients with PTHrP-driven hypercalcaemia, lung, head and neck cancers and myeloma were most common, and median survival after the calcium rose was only 46 days. Measuring PTHrP alongside PTH and active vitamin D helps separate this from other causes. In breast cancer, tumours that make PTHrP and its receptor have been linked to bone spread and worse survival in some series.
Researchers then turned the hormone around. Given in short daily pulses, PTH builds bone, so researchers tested synthetic PTHrP(1-36) in women. Single injections up to almost 2 mg were tolerated, three months at about 400 micrograms a day was followed by a 4.7% rise in spine density, and in a head-to-head trial PTHrP(1-36) at 400 or 600 micrograms a day raised spine density as much as teriparatide while stirring bone breakdown less. The catch was blood calcium, which rose at the higher doses.
PTHrP(1-36) itself was never developed into a product. Abaloparatide, an FDA-approved osteoporosis drug, is a modified analogue of PTHrP's first 34 residues; its trials are carded on its own entry, not here. Nothing about PTHrP supports injecting it outside a trial: the human studies were short, used daily doses in the hundreds of micrograms, and saw high calcium as the dose-limiting effect.
Mechanism of Action
PTHrP's first 36 or so amino acids bind the type 1 PTH receptor in bone and kidney, the same receptor parathyroid hormone uses; the rest of the protein is processed into other peptides with separate actions.
Bone
Continuous exposure raises bone breakdown and suppresses formation; short daily pulses raised formation markers and density more than breakdown (PMIDs 21544866, 23661240).
Kidney
Reduces calcium loss in urine and increases phosphate loss, which contributes to high calcium in cancer (PMIDs 12679445, 9362423).
Growth plates
Loss of one working PTHLH copy shortens the hand and foot bones (brachydactyly type E) (PMID 20170896).
Published Research
The studies behind PTHrP, read from their PubMed abstracts. They fall into three groups: injection and infusion studies of PTHrP(1-36) in people, measurements of PTHrP in cancer and normal physiology, and the genetics of PTHLH.
PrOP: head to head with teriparatide
In 105 postmenopausal women with low bone density randomised for three months, daily PTHrP(1-36) at 400 or 600 mcg raised spine density as much as teriparatide 20 mcg and also raised hip density, while increasing bone turnover markers less; the 400 mcg dose caused brief mild high calcium and three women on 600 mcg needed a lower dose.
First osteoporosis trial
In 16 postmenopausal women with osteoporosis on oestrogen, three months of daily PTHrP at about 400 mcg (6.56 mcg/kg) was followed by a 4.7% rise in lumbar spine density in the PTHrP group and a rise in osteocalcin, without raising markers of bone breakdown or causing significant adverse events.
Finding the top dose
In 41 healthy postmenopausal women given rising daily doses for three weeks, 500 and 625 mcg were tolerated without serious adverse events, while 750 mcg caused mild high calcium; the authors linked this to more active vitamin D and gut absorption rather than bone breakdown.
Single doses up to 2 mg
In 22 healthy young adults given single injections escalating from about 570 mcg to 1,946 mcg, PTHrP(1-36) was well tolerated: the highest blood calcium was 10.6 mg/dL in one person at the top dose, and only one subject had symptoms.
Active when injected under the skin
In 21 women given subcutaneous PTHrP(1-36) at 0.82, 1.64 or 3.28 mcg/kg, blood PTHrP rose, phosphate fell, kidney markers of PTH-receptor activity rose and active vitamin D increased, at doses that did not change serum calcium.
46-hour infusions against PTH(1-34)
Infused at the same rate for 46 hours in healthy young volunteers, PTHrP(1-36) and PTH(1-34) raised calcium and phosphate loss similarly and both cut urinary calcium below the level expected for the calcium rise, but PTH tended to raise active vitamin D more.
A week-long infusion as a model of cancer hypercalcaemia
Seven-day infusions of PTHrP(1-36) or PTH(1-34) at the highest tolerated rates caused mild sustained high calcium and increased bone breakdown, but suppressed bone formation by 30-40% until the infusion stopped, a pattern the authors compared with hypercalcaemia of malignancy.
Measuring it in cancer hypercalcaemia
Two new assays found PTHrP low or undetectable in 60 healthy people and raised in 30 patients with humoral hypercalcaemia of cancer, falling after some tumours were removed; levels were normal in hyperparathyroidism, and breast milk contained a lot of it.
Which cancer patients have high calcium
Comparing 60 hypercalcaemic and 45 normocalcaemic cancer patients, higher plasma PTHrP and lower PTH and active vitamin D were each associated with high calcium, and the authors recommended measuring all three.
PTHrP and bisphosphonate response
Among 315 patients with cancer-related high calcium treated with ibandronate in a randomised dose trial, 53% of those tested had raised PTHrP, rising to 76% in lung and upper airway cancers, and kidney calcium retention was increased in most.
Outcomes in 289 patients
In records from eight Korean hospitals, PTHrP-driven hypercalcaemia arose mostly in solid tumours, led by lung cancer; median survival after it appeared was 46 days, and death risk was four times that of cancer patients whose high calcium had other causes.
PTHrP and its receptor in breast cancer
PTHrP was found in 68% of 170 early breast cancers and all 43 bone metastases; tumours making both PTHrP and its receptor had the worst five-year outcome, with 32% mortality against 6% when neither was present.
Blood levels in breast cancer with normal calcium
In 48 breast cancer patients with normal calcium, most had PTHrP levels like healthy people on three assays, but four were raised on one assay, and nearly every tumour stained for PTHrP.
Pregnancy and the newborn
PTHrP levels were similar in pregnant and non-pregnant women, but higher in cord blood than in the mother and higher in the umbilical artery than vein, suggesting the fetus makes it, possibly to draw calcium across the placenta.
In breast milk
In milk from 14 breastfeeding women, PTHrP was lower in the first days than from day 7 to 60, and calcium supplements did not change it.
PTHLH mutations shorten hands and feet
A deletion covering PTHLH in one large family, and four point mutations in other patients, caused autosomal dominant brachydactyly type E with short stature; one missense change was shown to destroy the protein's function.
A splice-site PTHLH variant
In a Belgian family with short metacarpals and metatarsals but normal calcium and phosphate, a variant next to PTHLH exon 3 caused a frameshift in the transcript, explaining a pattern previously mistaken for pseudo-pseudohypoparathyroidism.
Stature in PTHLH brachydactyly
A new nonsense variant caused brachydactyly type E and short stature in a mother and son; the authors' review of published cases found short stature common but not universal, and more frequent with early truncating variants.
PTHrP and cancer
This chapter reviews how PTHrP was discovered and measured, its role in tumour growth and bone and other metastases, and current and possible treatments for cancer-related high calcium.
A prohormone with many products
This review describes PTHrP as a protein cut after it is made into several peptides, each with its own receptors and effects, notes how widely it is expressed and how early in development, and confirms its role in hypercalcaemia of malignancy.
How PTHrP causes high calcium
This review explains that PTHrP's N-terminal region acts like PTH on a shared receptor to release bone calcium and reduce calcium loss in urine, that it is detectable in most patients with humoral hypercalcaemia, and that it may help breast cancer grow in bone.
Dosing Data
PTHrP is not an approved medicine and has no label. These are the daily amounts of synthetic PTHrP(1-36) given to postmenopausal women in published osteoporosis trials, as their abstracts state.
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-related protein is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
An arithmetic example, not a recommendation: a 5 mg vial mixed with 2 mL of bacteriostatic water holds 2,500 mcg per mL, so every 10 units on a U-100 insulin syringe hold 250 mcg. 400 mcg, the first amount in the “PrOP trial, postmenopausal women” row (400 or 600 mcg) is 16.0 units (0.160 mL). If your vial or water differ, the numbers change: use the reconstitution calculator.
Source: dose: Used in human trials, PMID 23661240 (Dosing Data below); vial and water: the calculator's default example, not a vial size we have a source for.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Parathyroid hormone-related protein, 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-related protein stays intact once mixed.
How it is taken
As it was given in human studies: Subcutaneous (Once daily; PrOP trial, postmenopausal women).
For injection technique, sites and needle disposal, see the mixing guide.
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: not established by a measurement cited on this entry.
How long the doses were given: PrOP trial, postmenopausal women: 3 months; First osteoporosis trial: 3 months; Dose-finding study (500 and 625 mcg tolerated; 750 mcg caused mild high calcium): 3 weeks.
When effects appear: unknown; no source on this page gives a time to effect for Parathyroid hormone-related protein. Results reported in the studies are under Published Research.
Source: Used in human trials, 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, mild and often brief, more frequent at 600 mcg a day and above; Raised active vitamin D, which may add to calcium absorption; Symptoms in one subject at a single dose near 2 mg; Suppressed bone formation during continuous infusion. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Parathyroid hormone-related protein. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the human studies of PTHrP(1-36) above”).
Interactions
Unknown: a PubMed search for human interaction studies of Parathyroid hormone-related protein (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-related protein 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. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a medicine itself). Sport: Prohibited (S0 catch-all).
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 human studies of PTHrP(1-36) above.
Contraindications & Cautions
PTHrP has no label, so there are no official contraindications.
Legal Status
PTHrP is not a medicine; it is measured as a laboratory marker and has been given only in research.
Frequently Asked Questions
?Is PTHrP the same as abaloparatide?
No. Abaloparatide is a modified analogue based on PTHrP's first 34 residues and is FDA-approved for osteoporosis; its trials are on its own entry. PTHrP(1-36) itself was tested in small trials and never approved.
?Why do doctors test PTHrP?
To find the cause of high calcium in someone with cancer. A raised PTHrP with low PTH points to the tumour making it.
?Did PTHrP(1-36) work for osteoporosis?
In three-month trials it raised spine density, about as much as teriparatide in one head-to-head study, but it caused high calcium at the higher doses and was not developed further as itself.
?What does the PTHLH gene do?
It encodes PTHrP. Losing one working copy causes brachydactyly type E, short hand and foot bones, often with short stature.
?Where is PTHrP found normally?
In many tissues as a local signal, and at high levels in breast milk and in umbilical cord blood.
References
- [clinical-trial] Horwitz MJ, et al. "A comparison of parathyroid hormone-related protein (1-36) and parathyroid hormone (1-34) on markers of bone turnover and bone density in postmenopausal women: the PrOP study." J Bone Miner Res, 2013;28(11):2266-76. PMID: 23661240.
- [clinical-trial] Horwitz MJ, et al. "Short-term, high-dose parathyroid hormone-related protein as a skeletal anabolic agent for the treatment of postmenopausal osteoporosis." J Clin Endocrinol Metab, 2003;88(2):569-75. PMID: 12574182.
- [clinical-trial] Horwitz MJ, et al. "Parathyroid hormone-related protein for the treatment of postmenopausal osteoporosis: defining the maximal tolerable dose." J Clin Endocrinol Metab, 2010;95(3):1279-87. PMID: 20061412.
- [clinical-trial] Horwitz MJ, et al. "Safety and tolerability of subcutaneous PTHrP(1-36) in healthy human volunteers: a dose escalation study." Osteoporos Int, 2006;17(2):225-30. PMID: 16151606.
- [clinical-trial] Henry JG, et al. "Parathyroid hormone-related protein-(1-36) is biologically active when administered subcutaneously to humans." J Clin Endocrinol Metab, 1997;82(3):900-6. PMID: 9062504.
- [clinical-trial] Horwitz MJ, et al. "Direct comparison of sustained infusion of human parathyroid hormone-related protein-(1-36) [hPTHrP-(1-36)] versus hPTH-(1-34) on serum calcium, plasma 1,25-dihydroxyvitamin D concentrations, and fractional calcium excretion in healthy human volunteers." J Clin Endocrinol Metab, 2003;88(4):1603-9. PMID: 12679445.
- [clinical-trial] Horwitz MJ, et al. "A 7-day continuous infusion of PTH or PTHrP suppresses bone formation and uncouples bone turnover." J Bone Miner Res, 2011;26(9):2287-97. PMID: 21544866.
- [pubmed] Burtis WJ, et al. "Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hypercalcemia of cancer." N Engl J Med, 1990;322(16):1106-12. PMID: 2320080.
- [pubmed] Motellón JL, et al. "Parathyroid hormone-related protein, parathyroid hormone, and vitamin D in hypercalcemia of malignancy." Clin Chim Acta, 2000;290(2):189-97. PMID: 10660809.
- [clinical-trial] Rizzoli R, et al. "Serum parathyroid hormone-related protein levels and response to bisphosphonate treatment in hypercalcemia of malignancy." J Clin Endocrinol Metab, 1999;84(10):3545-50. PMID: 10522993.
- [pubmed] Kim J, et al. "Parathyroid hormone-related protein-mediated hypercalcemia of malignancy: insights from a multicenter clinical data warehouse." Korean J Intern Med, 2026;41(5):907-915. PMID: 42754527.
- [pubmed] Linforth R, et al. "Coexpression of parathyroid hormone related protein and its receptor in early breast cancer predicts poor patient survival." Clin Cancer Res, 2002;8(10):3172-7. PMID: 12374685.
- [pubmed] Bucht E, et al. "Parathyroid hormone-related protein in patients with primary breast cancer and eucalcemia." Cancer Res, 1998;58(18):4113-6. PMID: 9751621.
- [pubmed] Seki K, et al. "Parathyroid hormone-related protein during pregnancy and the perinatal period." Gynecol Obstet Invest, 1994;37(2):83-6. PMID: 8150375.
- [clinical-trial] Cross NA, et al. "The effects of calcium supplementation, duration of lactation, and time of day on concentrations of parathyroid hormone-related protein in human milk: a pilot study." J Hum Lact, 1998;14(2):111-7. PMID: 9775843.
- [pubmed] Klopocki E, et al. "Deletion and point mutations of PTHLH cause brachydactyly type E." Am J Hum Genet, 2010;86(3):434-9. PMID: 20170896.
- [pubmed] Reyes M, et al. "A Heterozygous Splice-Site Mutation in PTHLH Causes Autosomal Dominant Shortening of Metacarpals and Metatarsals." J Bone Miner Res, 2019;34(3):482-489. PMID: 30458061.
- [pubmed] Huang H, et al. "Case Report: A novel PTHLH nonsense variant in a mother-son pair with brachydactyly type E and short stature, with a genotype-stature review." Front Endocrinol (Lausanne), 2026;17:1875896. PMID: 42539507.
- [review] Grunbaum A, et al. "Parathyroid hormone-related protein (PTHrP) and malignancy." Vitam Horm, 2022;120:133-177. PMID: 35953108.
- [review] Orloff JJ, et al. "Parathyroid hormone-related protein as a prohormone: posttranslational processing and receptor interactions." Endocr Rev, 1994;15(1):40-60. PMID: 8156938.
- [review] Rankin W, et al. "Parathyroid hormone-related protein and hypercalcemia." Cancer, 1997;80(8 Suppl):1564-71. PMID: 9362423.
- [pubmed] Everhart-Caye M, et al. "Parathyroid hormone (PTH)-related protein(1-36) is equipotent to PTH(1-34) in humans." J Clin Endocrinol Metab, 1996;81(1):199-208. PMID: 8550752.
- [pubmed] Plotkin H, et al. "Dissociation of bone formation from resorption during 2-week treatment with human parathyroid hormone-related peptide-(1-36) in humans: potential as an anabolic therapy for osteoporosis." J Clin Endocrinol Metab, 1998;83(8):2786-91. PMID: 9709948.
- [other] UniProt P12272 (PTHR_HUMAN), chain residues 37-177 and its peptides, parathyroid hormone-related protein; read October 28, 2026. https://www.uniprot.org/uniprotkb/P12272/entry
Sources & Citations
Studies were read from their PubMed abstracts, October 28, 2026; protein structure from UniProt P12272; no label exists.
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.