Abaloparatide

What it is

Abaloparatide is a synthetic peptide of 34 amino acids. According to the European product information, it is 41 percent identical to the parathyroid hormone fragment PTH(1-34) and 76 percent identical to the parathyroid hormone-related peptide PTHrP(1-34). It thus belongs to the same family as teriparatide, which has been injected against osteoporosis for years.

It was developed by Radius Health. The US Food and Drug Administration (FDA) approved it in 2017 under the name Tymlos. The European Medicines Agency (EMA) refused a first application in 2018; after a new procedure, it has been approved throughout the EU as Eladynos since December 12, 2022. The holder of the EU marketing authorization is Theramex.

Unlike many peptides discussed in the scene, abaloparatide is therefore not a research chemical. It is a tested medicine with product information, a side effect table and pharmacovigilance.

How it works

Bone is constantly broken down and newly formed. Most osteoporosis medicines, such as bisphosphonates or denosumab, slow the breakdown. Abaloparatide works on the other side: it docks onto the PTH1 receptor of the bone-forming cells and stimulates them to form new bone substance, on the surface of the trabeculae inside as well as on the solid outer layer.

The rhythm is decisive. Permanently high parathyroid hormone breaks bone down, short daily peaks build it up. The half-life of abaloparatide is about 1 hour. In cell experiments, it preferentially bound to a receptor conformation that triggers only short signals (Hattersley et al. 2016). This is meant to explain why it builds bone while raising calcium levels less than teriparatide, but it is a laboratory finding.

In humans, the chain of action is measurable. The bone formation marker PINP rose 93 percent above baseline after 1 month in the pivotal trial and was still 45 percent above it after 18 months. Bone mineral density at the lumbar spine increased by 9.2 percent in 18 months, by 0.5 percent on placebo.

What the studies show

ACTIVE, JAMA 2016

Phase 3 trial at 28 centers in 10 countries with 2,463 postmenopausal women, mean age 69. They injected abaloparatide, placebo or open-label teriparatide daily for 18 months. The primary endpoint, new vertebral fractures on abaloparatide versus placebo, was met: according to the US prescribing information, 0.6 versus 4.2 percent. Fractures outside the spine occurred in 2.7 versus 4.7 percent in the US analysis, a relative reduction of 43 percent with p = 0.049. Hypercalcemia was less frequent than on teriparatide, 3.4 versus 6.4 percent.

ACTIVExtend, J Clin Endocrinol Metab 2018

Follow-on study with 558 women from the abaloparatide group and 581 from the placebo group, all of whom received alendronate for up to 24 months. Over the full 43 months, the rate of new vertebral fractures was 0.9 versus 5.6 percent, a relative reduction of 84 percent. In an additional analysis for the authorities, there was no hip fracture in the abaloparatide follow-on group and 5 in the placebo follow-on group.

ATOM in men, J Bone Miner Res 2022

228 men with osteoporosis aged 40 to 85, assigned in a 2 to 1 ratio to abaloparatide or placebo, 12 months. The primary endpoint was bone mineral density of the lumbar spine: plus 8.48 versus plus 1.17 percent. Fractures were not an endpoint; the study was too small and too short for that.

ACTIVE-J, J Clin Endocrinol Metab 2022

Randomized, double-blind study in Japan with women and men over 78 weeks. Bone mineral density of the lumbar spine rose by 12.5 percent compared with placebo. New vertebral fractures occurred only in the placebo group, 4 vertebrae in 3 participants.

Where the data stop

The strongest objection concerns fractures outside the spine. In 2018 the EMA excluded the data from 2 study centers because work there had not been carried out according to the rules of good clinical practice. In the European analysis with 2,070 women, the rate of such fractures after 19 months was 2.7 percent on abaloparatide and 3.6 percent on placebo, not statistically different. In the extension up to month 43, too, the difference, 4.2 versus 6.7 percent, was not significant according to the EU product information. The US analysis, by contrast, found a barely significant reduction. The 2026 meta-analysis speaks of moderate certainty for this effect.

Hip fractures were not a separate endpoint in any of the studies evaluated here; the figures from ACTIVExtend come from an additional analysis. In men, only bone mineral density is established, not fracture protection. The only comparison with another medicine, teriparatide in ACTIVE, was open-label and not blinded. And for use without osteoporosis, for example for prevention or for healing injuries, there are no human data.

Status, approval and legal

Approved in the US as Tymlos since 2017, for postmenopausal women with a high fracture risk and now also to increase bone mineral density in men with osteoporosis. Approved in the EU as Eladynos since December 12, 2022, only for postmenopausal women with an increased fracture risk. The medicine is prescription-only and is subject to additional monitoring in the EU. According to the product information, the approved dose is 80 micrograms once daily under the skin; the total duration is limited to a maximum of 18 months in the EU, and in the US use for more than 2 years in a lifetime is not recommended. After completion, according to the EU product information, a switch to other osteoporosis medicines such as bisphosphonates is possible. These details come from the product information and are not a usage recommendation. In the German translation of the 2026 WADA Prohibited List, abaloparatide is not listed by name; anyone involved in competitive sport clarifies this with NADA before a prescription.

Safety

The most common complaints in ACTIVE, according to the US prescribing information, were increased calcium in the urine, dizziness (10 versus 6 percent), nausea (8 versus 3 percent), headache and palpitations (5 versus 0.4 percent). Redness at the injection site occurred in 58 percent in the first month, compared with 28 percent on placebo. 10 percent stopped treatment because of side effects, compared with 6 percent on placebo. After the first injection, the pulse rose by a mean of 7.9 beats per minute, by 1.2 on placebo; serious cardiac events were equally rare in all groups. Because the EMA viewed the cardiac effect critically in particular, the EU product information requires blood pressure, cardiac status and an ECG before starting. It is not used, among other things, in pre-existing hypercalcemia, severe kidney impairment, bone tumors or previous radiation of the skeleton, or during pregnancy and breastfeeding. In a 2-year rat study, osteosarcomas occurred in a dose-dependent manner, at 4 to 28 times human exposure; whether this applies to humans is unknown.

Sources

• Miller et al., JAMA 2016 – ACTIVE trial
• Bone et al., J Clin Endocrinol Metab 2018 – ACTIVExtend
• Czerwinski et al., J Bone Miner Res 2022 – ATOM in men
• Matsumoto et al., J Clin Endocrinol Metab 2022 – ACTIVE-J
• Cosman et al., J Clin Endocrinol Metab 2020 – cardiovascular safety in ACTIVE
• Hattersley et al., Endocrinology 2016 – binding to PTH1 receptor conformations
• Bonifacio et al., J Clin Med 2026 – meta-analysis
• EMA – Eladynos, product information (German)
• EMA 2018 – refusal of the first marketing authorization application
• DailyMed – Tymlos, US prescribing information