Abaloparatide

Origin and structure

Abaloparatide is a synthetic peptide of 34 amino acids, modelled on parathyroid hormone-related peptide (PTHrP). PTHrP is a different hormone from parathyroid hormone (PTH), but both act on the same receptor, the PTH type 1 receptor (PTH1R). The first 21 amino acids of abaloparatide are identical to those of PTHrP(1-34), the first 34 amino acids of the natural hormone. Eight of the last 13 positions are changed, one of them to the non-natural amino acid 2-aminoisobutyric acid (Aib), and the end of the chain is amidated. The result shares 76% of its sequence with PTHrP(1-34) and 41% with PTH(1-34), the fragment sold as teriparatide (formula C174H300N56O49, about 3,961 daltons).

Ipsen held the original patents and in September 2005 licensed the compound to Radius Health, which developed it under the code BA058. In Japan, Teijin Pharma took it to market. After an injection under the skin, abaloparatide peaks in the blood after about half an hour and has a half-life of about one hour; about 36% of the dose reaches the circulation. Each daily dose therefore gives a short pulse of receptor activity.

It is sold as Tymlos in the US (Radius Health), as Eladynos in the EU (Theramex) and as Ostabalo in Japan (Teijin Pharma). Tymlos and Eladynos are prefilled pens holding 30 daily doses of 80 micrograms; they are kept in the fridge until first use and at room temperature for at most 30 days after that.

How it works

Bone is constantly broken down and rebuilt. After the menopause, when oestrogen levels fall, too little new bone is made to replace what is lost, and the bones thin. PTH and PTHrP both signal through PTH1R on bone cells, and the timing decides the outcome: continuous exposure favours net bone breakdown and a rise in blood calcium, while a short daily pulse favours the formation of new bone. Abaloparatide, like teriparatide, relies on that daily pulse. It stimulates the bone-forming osteoblasts, and new bone is laid down on the surfaces of both the spongy inner bone and the dense outer bone.

What sets abaloparatide apart is the way it binds. The receptor has two high-affinity shapes, called R0 and RG. In cell studies (Endocrinology 2016), abaloparatide bound more selectively to RG than PTH(1-34) did, and the cAMP signal it triggered inside the cell faded faster. The authors proposed that this shorter signal explains why, in animals, abaloparatide built bone with less accompanying breakdown and a smaller rise in blood calcium than PTH(1-34). In people that is not settled: in its 2022 assessment the EMA did not agree that the bone-marker data from ACTIVE strongly supported abaloparatide being more selective for bone formation than teriparatide.

In women treated for 18 months, the bone-formation marker P1NP was 93% above baseline after one month and still 45% above baseline at 18 months, while the breakdown marker CTX peaked at 26% above baseline after three months and was back at baseline by 18 months. Blood calcium rises briefly after each dose, peaks about four hours later and returns to baseline within 24 hours.

Is abaloparatide approved?

Yes. Abaloparatide is a prescription medicine for osteoporosis in the EU, the US and Japan. The EU approval came more than five years after the US one, and only after an earlier refusal.

Radius filed its first EU application in November 2015. On 22 March 2018 the EMA's human medicines committee (CHMP) recommended refusing it, and after a re-examination it confirmed that recommendation on 26 July 2018. Data from two European trial sites had to be excluded because the trial had not been run there according to Good Clinical Practice, and without them ACTIVE no longer showed a statistically significant effect on non-vertebral fractures. The committee was also concerned about effects on the heart, such as a faster heart rate and palpitations, in a group of women already at raised cardiovascular risk.

The second application added a placebo-controlled trial in Japan, a bone-biopsy study, a new analysis of hip scans and a US insurance-claims study that compared abaloparatide with teriparatide and found no rise in serious cardiovascular events. The CHMP gave a positive opinion on 13 October 2022, and the European Commission authorised Eladynos on 12 December 2022 for osteoporosis in postmenopausal women at increased risk of fracture. The assessment noted that the effect on non-vertebral fractures was still not statistically significant, but saw no scientific reason to assume the drug protects only the spine. Eladynos is under additional monitoring, and its product information asks for blood pressure, heart status and an ECG to be assessed before treatment starts.

Research-grade abaloparatide is none of these products. It has no marketing authorisation, is not made under a medicines licence and may not be used in people. We do not sell abaloparatide.

• Netherlands: Eladynos (Theramex) is available on prescription. Since 1 February 2026 basic health insurance has reimbursed it, in Annex 1A in one cluster with teriparatide and romosozumab, with no extra conditions in Annex 2, after the Zorginstituut concluded that the three are interchangeable, with no clinically relevant differences in benefits or harms. The manufacturer asked for reimbursement for severe osteoporosis in postmenopausal women at very high risk of fracture. The Farmacotherapeutisch Kompas names the bisphosphonates alendronic acid and risedronic acid as first choice for fracture prevention, and advises considering a bone-forming drug (abaloparatide, romosozumab or teriparatide) straight away in postmenopausal women with severe osteoporosis.
• US: Tymlos was approved on 28 April 2017 for postmenopausal women with osteoporosis at high risk of fracture. Its boxed warning about osteosarcoma was removed in December 2021. On 19 December 2022 the label was extended to men with osteoporosis at high risk of fracture, to increase bone density. In August 2026, following an FDA safety-labelling request for parathyroid hormone products, the label added a warning and a contraindication for severe allergic reactions, including anaphylaxis. The label advises against more than 2 years of use in a lifetime.
• Japan: Ostabalo (Teijin Pharma) was approved in 2021 for women and men with osteoporosis at high risk of fracture, for at most 18 months of treatment.

What the research shows

The evidence rests on a single fracture trial, ACTIVE, and its extension, plus trials that measured bone density rather than fractures. The main results:

• Dose finding (JCEM 2015): 222 postmenopausal women received abaloparatide at one of three doses, teriparatide or placebo for 24 weeks. Spine bone density rose 6.7% on 80 micrograms, against 1.6% on placebo and 5.5% on teriparatide, and total-hip density rose more on 40 and 80 micrograms (2.0% and 2.6%) than on teriparatide (0.5%).
• ACTIVE (JAMA 2016): 2,463 postmenopausal women with osteoporosis at 28 sites in 10 countries received blinded abaloparatide or placebo, or open-label teriparatide, for 18 months. New vertebral fractures on X-ray occurred in 0.6% on abaloparatide, 0.8% on teriparatide and 4.2% on placebo, relative reductions of 86% and 80%. Non-vertebral fractures by month 19: 2.7%, 3.3% and 4.7%; the reduction was just significant for abaloparatide (hazard ratio 0.57, p = 0.049) and not for teriparatide (hazard ratio 0.72). Spine bone density rose 9.2% against 0.5% on placebo.
• ACTIVE as assessed in the EU: once the two sites with Good Clinical Practice problems were excluded, 2,070 of the 2,463 women remained. Vertebral fractures still fell (0.5% against 4.2% on placebo), but non-vertebral fractures no longer differed significantly from placebo (2.7% against 3.6%; teriparatide 2.0%).
• ACTIVExtend (JCEM 2018): 1,139 women from the abaloparatide and placebo groups moved on to alendronate for 24 months. Over the full 43 months, 0.9% of those who had started on abaloparatide had a new vertebral fracture, against 5.6% of those who had started on placebo (an 84% relative reduction), and bone density kept rising on alendronate. Five women who had started on placebo had a hip fracture, against none who had started on abaloparatide.
• ATOM (JBMR 2022): 228 men with osteoporosis (mean age 68) were randomised 2:1 to abaloparatide or placebo for 12 months. Bone density rose 8.5% against 1.2% at the spine, 2.1% against 0.0% at the total hip and 3.0% against 0.2% at the femoral neck. The trial measured bone density, not fractures.
• Japan (PMDA review, 2021): in a 78-week placebo-controlled trial in 212 Japanese women and men aged 55 to 85, spine bone density rose 16.3% on abaloparatide against 3.8% on placebo.
• US claims data (Osteoporos Int 2022): 11,616 women starting abaloparatide were matched with 11,616 starting teriparatide. Over 19 months non-vertebral fractures were similar (hazard ratio 0.89, 95% CI 0.77 to 1.03), hip fractures were less frequent on abaloparatide at the edge of significance (0.78, 0.62 to 1.00), and major cardiovascular events were similar. In 2022 the EMA weighed an updated analysis of the same claims database and pointed to biases in its design and analysis that are hard to quantify.

Side effects and warnings

In ACTIVE, the side effects reported more often than on placebo were more calcium in the urine (11% against 9%), dizziness (10% against 6%), nausea (8% against 3%), headache (8% against 6%), palpitations (5% against 0.4%), and fatigue and upper abdominal pain (3% against 2% each). In the first month, 58% had redness at the injection site (28% on placebo), 11% swelling and 10% pain. Serious adverse events were about as common as on placebo (10% against 11%), but more women stopped abaloparatide because of side effects (10% against 6%), most often for nausea, dizziness, headache or palpitations. In men (ATOM), the most common were redness at the injection site (13%), dizziness (9%) and joint pain (7%).

Abaloparatide may widen blood vessels, and it speeds up the heart: in healthy volunteers the heart rate was about 15 beats per minute higher 15 minutes after a dose, and the effect faded within about six hours. Blood pressure can drop on standing, typically within four hours of an injection, with dizziness, palpitations or nausea. The labels therefore have the first doses given where the patient can sit or lie down; the EU information asks for the first injection or injections to be given under the guidance of a healthcare professional, and for blood pressure, heart status and an ECG to be assessed before starting. Blood calcium above the normal limit four hours after a dose was found in 3% (0.1% on placebo) and uric acid above normal in 25% (6% on placebo), without more gout. 41% developed antibodies against abaloparatide, with no visible effect on safety or efficacy.

In a two-year study in rats, daily injections at 4 to 28 times the human exposure caused a dose-dependent rise in osteosarcoma, a bone cancer, which reached 87% of males and 62% of females at the highest dose. Whether this applies to people is unknown: osteosarcoma has been reported in patients treated with a PTH analogue, but observational studies have not found a higher risk, and data beyond two years of use are limited. The labels therefore cap the treatment time and exclude people with a raised baseline risk, such as children and young adults with open growth plates, and people with Paget's disease, bone cancer or bone metastases, or earlier radiation of the skeleton. The EU information also rules out pregnancy, breastfeeding, women who can still become pregnant, high blood calcium, severe kidney impairment and unexplained raised alkaline phosphatase. Since August 2026 the US label also warns of allergic reactions, including anaphylaxis.

Abaloparatide versus teriparatide

Teriparatide (Forsteo in the EU since 2003) consists of the first 34 amino acids of human PTH. Both drugs are daily injections that act on PTH1R and build new bone, and in ACTIVE they were tested side by side, with teriparatide given open-label. The main differences:

• Molecule and dose: teriparatide is PTH(1-34) at 20 micrograms a day; abaloparatide is a modified PTHrP(1-34) at 80 micrograms a day.
• Fractures: in ACTIVE both cut vertebral fractures by a similar amount (86% and 80% against placebo). The direct comparison of non-vertebral fractures was not significant (hazard ratio 0.79, 95% CI 0.43 to 1.45). Major osteoporotic fractures were less frequent on abaloparatide (1.5% against 3.1%, hazard ratio 0.45, 95% CI 0.21 to 0.95), but the trial's main comparison was with placebo.
• Bone density: spine gains were similar, about 9% in both groups; hip gains were slightly larger on abaloparatide (total hip 3.3% against 3.0%, femoral neck 2.7% against 2.3% in the EU analysis).
• Side effects: high blood calcium four hours after a dose was less common on abaloparatide (3.4% against 6.4%), but orthostatic hypotension, palpitations, nausea, dizziness and headache were more common, and more women stopped abaloparatide because of side effects (9.9% against 6.8%).
• Course length and storage: the EU caps Eladynos at 18 months and Forsteo at 24 months; in the US, Tymlos is not recommended for more than 2 years in a lifetime. Abaloparatide pens may be kept at room temperature (below 25 °C in the EU) for 30 days after first use, while Forsteo pens must stay in the fridge.
• Licensed uses and price cluster: in the EU teriparatide is also licensed for men and for osteoporosis caused by long-term glucocorticoid treatment, Eladynos only for postmenopausal women. The Zorginstituut found no clinically relevant differences in benefits or harms between abaloparatide, teriparatide and romosozumab, and placed them in one reimbursement cluster.

Frequently asked questions

Is abaloparatide available in the Netherlands, and is it reimbursed?

Yes, on prescription, as Eladynos. Since 1 February 2026 basic health insurance has reimbursed it, in the same GVS cluster as teriparatide and romosozumab, with no extra conditions attached. The reimbursement request covered severe osteoporosis in postmenopausal women at very high risk of fracture. The Farmacotherapeutisch Kompas names bisphosphonates as first choice for fracture prevention, and advises considering a bone-forming drug such as abaloparatide straight away in postmenopausal women with severe osteoporosis. We do not sell abaloparatide.

Is abaloparatide better than teriparatide?

Not clearly. In ACTIVE both cut vertebral fractures by a similar amount, and the direct comparison of non-vertebral fractures was not significant. Abaloparatide gave slightly larger hip density gains, less high blood calcium and fewer major osteoporotic fractures, but more women stopped it because of side effects, and the teriparatide group was not blinded. The Zorginstituut found no clinically relevant difference in benefits or harms between the two, or with romosozumab.

Why is abaloparatide limited to 18 months?

Because of a finding in rats: in a two-year study, daily injections caused osteosarcoma, a bone cancer, in a dose-dependent way, starting at 4 times the human exposure. In people, observational studies of PTH analogues have not shown a higher risk, but data beyond two years of use are limited. The EU caps treatment at 18 months in total, the length of the ACTIVE trial. The US label advises against more than 2 years in a lifetime, and dropped its boxed warning in 2021.

Is abaloparatide approved for men?

In the US and Japan, yes. The FDA extended Tymlos to men with osteoporosis at high risk of fracture in December 2022, to increase bone density, based on ATOM: in 228 men, spine bone density rose 8.5% after a year, against 1.2% on placebo. That trial did not measure fractures. In the EU, Eladynos is licensed only for postmenopausal women.

What happens when a course of abaloparatide ends?

Labels and guidelines expect another drug to follow. The EU product information mentions bisphosphonates, and the Dutch osteoporosis guideline, as summarised by the Zorginstituut, expects a drug that slows bone breakdown, preferably a bisphosphonate, to start straight afterwards and to continue for at least two years. In ACTIVExtend, women who switched from abaloparatide to alendronate kept their lower rate of vertebral fractures, and their bone density rose further over two years.

Is abaloparatide banned in sport?

Abaloparatide is not named on WADA's 2026 Prohibited List or on the 2027 List that takes effect on 1 January 2027, and because it is an approved medicine, class S0 for unapproved substances does not cover it. Class S2.3 does end with a catch-all for any other growth factor or growth-factor modulator that affects muscle, tendon or ligament, blood-vessel growth, energy use, recovery capacity or fibre type, but neither list names a PTH analogue. Athletes who are prescribed it can check their situation with the Dopingautoriteit.

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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