Teriparatide

Origin and structure

Parathyroid hormone (PTH) is a protein of 84 amino acids made by the parathyroid glands in the neck, and the body's main regulator of calcium and phosphate. Its biological activity sits in the first 34 amino acids. In a multicentre trial published in 1980 (BMJ), 21 people with osteoporosis received this fragment, hPTH(1-34), as a daily injection for 6 to 24 months; biopsies of the pelvic bone showed on average 70% more trabecular (spongy) bone, and the new bone looked normal under the microscope. Eli Lilly later developed a recombinant version under the code LY333334; its international name is teriparatide.

Teriparatide has exactly the sequence of the first 34 amino acids of human PTH (formula C181H291N55O51S2, about 4,118 daltons). Forsteo is made in E. coli bacteria with recombinant DNA technology; Teriparatide Sun, authorised in the EU in 2022 as a hybrid medicine, is made by chemical synthesis instead. After an injection under the skin the peptide peaks in the blood after about 30 minutes, has a half-life of about one hour and can no longer be measured after three hours.

Related medicines use the same hormone in other ways. Full-length PTH(1-84) was authorised in the EU as Preotact for osteoporosis from 2006 to 2014, and as Natpar for hypoparathyroidism (too little parathyroid hormone) from 2017 until its EU authorisation was withdrawn on 1 July 2026. Palopegteriparatide (Yorvipath), authorised in the EU in November 2023 and in the US in August 2024 for chronic hypoparathyroidism, is teriparatide attached to a carrier that releases it steadily over 24 hours. Abaloparatide (Eladynos, Tymlos) is a related bone-building peptide modelled on PTH-related peptide (PTHrP).

How it works

Teriparatide binds the same receptor as natural PTH, with the same affinity, on bone-forming cells (osteoblasts) and in the kidney. What it does to bone depends on the pattern of exposure. A constant excess of PTH, as in an overactive parathyroid gland (hyperparathyroidism), can break bone down, because it stimulates resorption more than formation. A single daily injection instead causes a brief peak, and with that pattern teriparatide stimulates the osteoblasts more than the bone-resorbing osteoclasts, so that new bone is laid down on the spongy bone inside and on the surfaces of the dense outer bone. In the US registration trial, spine bone density rose in 96% of the women treated.

Like natural PTH, it also moves calcium. Blood calcium starts to rise about two hours after each dose, peaks after four to six hours (a median rise of 0.4 mg/dL) and is back to baseline after 16 to 24 hours, which is why blood for a calcium test is taken at least 16 hours after the last injection. Steady exposure serves a different purpose: palopegteriparatide releases teriparatide continuously over 24 hours to replace the missing hormone in hypoparathyroidism, not to build bone.

Is teriparatide approved?

Yes. Teriparatide is a prescription medicine for osteoporosis in the EU, the Netherlands and the US, for adults at increased or high risk of fracture. It is not approved for children or for young adults whose growth plates are still open.

In the Netherlands the Farmacotherapeutisch Kompas lists Forsteo (from Eli Lilly Nederland in Utrecht, which also holds the EU marketing authorisation), the biosimilars Movymia and Sondelbay, and teriparatide from other makers. They are reimbursed from basic health insurance: Annex 1A of the Dutch health-insurance regulation lists them, including Teriparatide Teva and Teriparatide Sun, with a reimbursement limit, in one cluster with abaloparatide and romosozumab, and Annex 2 sets no extra conditions. The Kompas advises starting fracture prevention with a bisphosphonate and considering teriparatide when bisphosphonates or denosumab cannot be used, when a third fracture occurs during treatment, or as the first treatment for postmenopausal women with severe osteoporosis and a high fracture risk; afterwards, a drug that slows bone breakdown, preferably a bisphosphonate, should follow.

• EU: Forsteo was authorised on 10 June 2003 for osteoporosis in postmenopausal women; men at increased fracture risk were added in 2007, and osteoporosis caused by long-term glucocorticoid (corticosteroid) treatment in 2008. Biosimilars followed: Terrosa and Movymia (January 2017), Livogiva (2020), Sondelbay (2022), Kauliv (2023) and Zandoriah (April 2026), plus the chemically synthesised Teriparatide Sun (2022). The maximum course was extended from 18 to 24 months in 2009. The product information caps treatment at 24 months, once in a lifetime, and states that fewer vertebral and non-vertebral fractures were shown, but not fewer hip fractures.
• US: Forteo was approved on 26 November 2002 for postmenopausal women and men at high fracture risk, with a boxed warning about osteosarcoma and use beyond two years not recommended; glucocorticoid-induced osteoporosis followed in July 2009. On 16 November 2020 the FDA removed the boxed warning and allowed treatment beyond two years for patients who remain at, or return to, a high fracture risk. Bonsity was approved in October 2019 and the first generics in November 2023. In August 2026 the Forteo label added a warning and a contraindication for severe allergic reactions, including anaphylaxis.
• Japan: besides daily teriparatide, a once-weekly injection of teriparatide acetate (Teribone) was approved in September 2011.

What the research shows

The approvals rest on placebo-controlled trials in postmenopausal women and in men, and teriparatide was later compared head to head with bisphosphonates and with abaloparatide. The main results:

• Fracture Prevention Trial (NEJM 2001): 1,637 postmenopausal women, 90% with at least one vertebral fracture, received teriparatide at two doses or placebo; the trial was stopped early because of the rat findings, after a median of 19 months of treatment. On the dose that was later licensed, new vertebral fractures occurred in 5.0% against 14.3% on placebo (a 65% relative reduction), non-vertebral fragility fractures in 2.6% against 5.5%, and spine bone density rose by 9.7% against 1.1%. The higher dose added bone density but no extra fracture protection, and caused more side effects.
• Hip fractures: the trials were too small to show an effect, and the EU product information says none was shown. A 2019 meta-analysis of 23 randomised trials (8,644 people, 34 hip fractures in total), co-written by Lilly staff, estimated 56% fewer hip fractures (odds ratio 0.44, 95% CI 0.22 to 0.87).
• Men: in 437 men with primary or hypogonadal osteoporosis, in a trial stopped early after a median of 11 months, spine bone density rose by 5.9% against 0.5% on placebo. An effect on fractures was not shown.
• Glucocorticoid-induced osteoporosis (NEJM 2007): 428 women and men on long-term glucocorticoids were randomised to teriparatide or alendronate for 18 months. Spine bone density rose by 7.2% against 3.4%, and new vertebral fractures occurred in 0.6% against 6.1%; non-vertebral fractures did not differ (5.6% against 3.7%).
• VERO (Lancet 2018, funded by Lilly): 1,360 postmenopausal women with severe osteoporosis, double-blind against risedronate for 24 months. New vertebral fractures occurred in 5.4% against 12.0% (risk ratio 0.44) and clinical fractures in 4.8% against 9.8%; the difference in non-vertebral fractures (4.0% against 6.1%) was not statistically significant.
• ACTIVE (JAMA 2016): 2,463 postmenopausal women received blinded abaloparatide or placebo, or open-label teriparatide, for 18 months. New vertebral fractures occurred in 0.6% on abaloparatide, 0.8% on teriparatide and 4.2% on placebo; high blood calcium was less frequent with abaloparatide (3.4% against 6.4%).
• After stopping: in 1,262 women followed for a median of 18 months after the Fracture Prevention Trial, women who had received the licensed dose had a 41% lower risk of a new vertebral fracture than former placebo users, although other osteoporosis drugs were allowed. Bone density falls once teriparatide stops; in DATA-Switch (Lancet 2015), women who moved from teriparatide to denosumab kept gaining bone, while the reverse order led to temporary or ongoing bone loss.
• Weekly injections, TOWER (JCEM 2012): 578 Japanese people aged 65 to 95 with an earlier vertebral fracture; after 72 weeks, new vertebral fractures in 3.1% against 14.5% on placebo (relative risk 0.20).
• Fracture healing (off-label, JBMR 2010): 102 postmenopausal women with a wrist fracture received eight weeks of injections or placebo. The main hypothesis, faster healing on the higher dose, was not confirmed; healing was faster on the standard dose (7.4 against 9.1 weeks) only in a post-hoc analysis that the authors said should be interpreted with caution.

Osteosarcoma and the two-year limit

In two-year studies in Fischer 344 rats, daily teriparatide injections started at a young age caused osteosarcoma, a malignant bone tumour, at every dose tested, at 3 to 60 times the human exposure; in the highest-dose groups 40 to 50% of the rats were affected, against none of the untreated controls. A second study showed that the risk depended on dose and duration: no tumours appeared in adult rats given the lowest dose for 6 or 20 months. Monkeys treated for 18 months and followed for three more years developed no bone tumours, and the EU product information judges the relevance for humans probably minor because rat and human bone differ.

The rat finding came while the human trials were running, and they were stopped early, with a median of 19 months of treatment in women and 11 months in men. Regulators then approved the drug with limits: in the US a boxed warning and no use beyond two years, in the EU a maximum of 18 months, extended in 2009 to the current 24 months. Lilly ran long-term surveillance. In two US studies that linked insurance claims to cancer registries, 3 osteosarcomas were found among 379,283 users and none among 153,316, a risk similar to comparison groups, although the US label notes that the data could not fully control for confounding. A 15-year US surveillance study of osteosarcoma patients (J Bone Miner Res 2021) found no more earlier teriparatide use than expected from background rates.

On that basis the FDA removed the boxed warning in November 2020, and its label now lets doctors consider treatment beyond two years for patients who remain at or return to high fracture risk, while stating that data beyond two years are limited. The EU has not followed: the Forsteo product information, last updated in January 2026, still caps treatment at 24 months, not to be repeated, until further clinical data become available. Rare cases of osteosarcoma have been reported in treated patients, and both labels advise against teriparatide for people who already have a higher risk, such as those with Paget's disease, earlier radiation of the skeleton, bone tumours or metastases, or open growth plates.

Side effects and warnings

In the two placebo-controlled trials in women and men, serious adverse events occurred in 16% on teriparatide against 19% on placebo, and 7% against 6% stopped early because of side effects. Events that were more frequent than on placebo included pain (21.3% against 20.5%), joint pain (10.1% against 8.4%), nausea (8.5% against 6.7%), dizziness (8.0% against 5.4%), depression (4.1% against 2.7%) and leg cramps (2.6% against 1.3%). The EU product information lists pain in the arms or legs as very common and muscle cramps as common, and nausea, headache and dizziness as the most frequently reported reactions.

Blood calcium can rise for a few hours after each dose: at least one raised value four to six hours after the injection was found in 11% of women and 6% of men on teriparatide, against 2% and 0% on placebo, but repeat measurements confirmed it in only 3% and 1%. Uric acid rose above normal in 3% against 1%, without more gout. In the first doses some people feel dizzy or faint on standing up; in short studies in healthy volunteers this happened to 5%, usually within four hours, and it passed when they lay down.

Both labels warn about possible worsening of active or recent kidney stones and about digoxin toxicity through the calcium rise, and the EU lists anaphylaxis as a rare reaction. The US label also warns about severe allergic reactions, including anaphylaxis, which since August 2026 rule out further use, and about calciphylaxis and worsening calcium deposits in the skin, reported after approval, with kidney failure, autoimmune disease and use of warfarin or corticosteroids as risk factors. Serious back cramps or pain within minutes of an injection have been reported. In the EU teriparatide must not be used with high blood calcium, severe kidney impairment, bone diseases other than primary or glucocorticoid-induced osteoporosis (including Paget's disease and hyperparathyroidism), unexplained raised alkaline phosphatase, earlier radiation of the skeleton, bone cancer or metastases, or during pregnancy and breastfeeding.

Frequently asked questions

Is teriparatide (Forsteo) reimbursed in the Netherlands?

Yes, as a prescription medicine. Forsteo, the biosimilars Movymia and Sondelbay, Teriparatide Teva and Teriparatide Sun are listed in Annex 1A of the Dutch health-insurance regulation, with a reimbursement limit, in the same cluster as abaloparatide and romosozumab, and Annex 2 attaches no extra conditions. The Farmacotherapeutisch Kompas advises a bisphosphonate first for most people and keeps teriparatide for specific situations: severe osteoporosis in postmenopausal women with a high fracture risk, a third fracture during treatment, or when bisphosphonates or denosumab cannot be used.

Why is teriparatide limited to two years?

Because rats given daily teriparatide for most of their lives developed osteosarcoma, a bone cancer, and the drug had not been studied in people for longer than two years. The EU first allowed 18 months, extended this to 24 months in 2009, and still allows only one such course per lifetime. In 2020 the FDA, after years of surveillance data, allowed longer treatment for patients who remain at or return to high fracture risk, while noting that data beyond two years are limited.

Does teriparatide cause bone cancer in humans?

An increased risk has not been seen in human studies. In two large US studies linking insurance claims to cancer registries, 3 osteosarcomas were found among 379,283 users and none among 153,316, similar to comparison groups, and a 15-year surveillance study of osteosarcoma patients found no more earlier teriparatide use than expected. Rare cases have been reported after approval, the US label notes that these observational data could not fully control for confounding, and the labels advise against it for people who already have a higher risk, such as those with Paget's disease or earlier radiation of the skeleton.

What happens after teriparatide is stopped?

The gained bone density starts to fall unless another treatment follows. The Farmacotherapeutisch Kompas advises switching to a drug that slows bone breakdown, preferably a bisphosphonate. In the DATA-Switch trial, women who went from teriparatide to denosumab kept gaining bone density, whereas switching the other way round caused temporary or ongoing bone loss.

What is the difference between teriparatide and abaloparatide?

Both are daily bone-building injections that act on the PTH1 receptor. Teriparatide is a fragment of parathyroid hormone itself; abaloparatide is modelled on PTH-related peptide. Abaloparatide is authorised in the EU as Eladynos (2022) for postmenopausal women only, for at most 18 months, and in the US as Tymlos (2017). In the ACTIVE trial both cut new vertebral fractures to under 1%, against 4.2% on placebo, and high blood calcium was less frequent with abaloparatide.

Is teriparatide banned in sport?

Teriparatide is not named on WADA's 2026 Prohibited List or on the 2027 List that takes effect on 1 January 2027, and neither names a parathyroid hormone analogue among its peptide hormones and growth factors. Because it is an approved medicine, class S0 for unapproved substances does not cover it either. Class S2.3 does end with a catch-all for other growth factors that affect muscle, tendon or ligament, but it gives no PTH example. The Dopingautoriteit's Dutch translation of the 2026 list has the same wording.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.

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