Abaloparatide

A synthetic 34-amino-acid analog of parathyroid hormone-related protein, FDA approved since 2017 as a daily anabolic osteoporosis injection, that activates the PTH type 1 receptor with a bias toward short-lived signaling to stimulate bone formation.

Also referenced as: Abaloparatide acetate, BA058, BA-058, Tymlos, Eladynos, Ostabalo, Abaloparatide-SC

Also appears in: Longevity

What is Abaloparatide?

Abaloparatide is a synthetic 34-amino-acid peptide analog of parathyroid hormone-related protein, specifically of the PTHrP(1-34) fragment. The approved labeling puts its sequence at 76% homology to human PTHrP(1-34) and only 41% to human PTH(1-34), which is the precise reason it should not be described as a PTH(1-34) analog: that description belongs to teriparatide, a different molecule with a different parent hormone. Developed under the code BA058 and marketed in the U.S. as Tymlos, it was approved on April 28, 2017 for postmenopausal women with osteoporosis at high risk of fracture and on December 19, 2022 to increase bone density in men with osteoporosis at high risk of fracture.

It appears in the research-peptide market as one of the few bone-anabolic agents with a full approval record behind it. Vendors list it by generic name, usually as lyophilized powder, and it attracts attention from people reading about fracture prevention, bone density, and the broader “longevity” framing of musculoskeletal aging rather than from any laboratory-reagent role.

How it works

Abaloparatide is an agonist of the parathyroid hormone type 1 receptor (PTH1R), the same receptor PTH and PTHrP both activate. Its distinguishing feature is not the receptor but how it engages it:

• Conformation-selective receptor binding — PTH1R exists in two high-affinity states, R0 (G-protein-independent, associated with prolonged signaling) and RG (G-protein-coupled, associated with transient signaling). Abaloparatide binds the RG conformation with markedly greater selectivity than PTH(1-34) does, and as a consequence produces shorter-lived cAMP responses in PTH1R-expressing cells. The authors proposed this transient signaling as the mechanistic basis for a net anabolic effect with less stimulation of bone resorption (Hattersley et al., Endocrinology, 2016, 157(1):141–149)
• Dose-dependent gains in bone mineral density — in a 24-week Phase 2 dose-ranging study of 222 postmenopausal women, daily 20, 40, and 80 mcg doses raised lumbar spine BMD by 2.9%, 5.2%, and 6.7% respectively versus 1.6% on placebo and 5.5% on teriparatide 20 mcg; total hip gains at the two higher doses exceeded both placebo and teriparatide (Leder et al., Journal of Clinical Endocrinology & Metabolism, 2015, 100(2):697–706)
• Less hypercalcemia than the PTH(1-34) comparator — hypercalcemia was a prespecified safety endpoint in the pivotal ACTIVE trial, and its incidence was 3.4% on abaloparatide versus 6.4% on open-label teriparatide (risk difference −2.96; P = .006), consistent with the shorter signaling profile described above (Miller et al., JAMA, 2016, 316(7):722–733)
• Anabolic window, then antiresorptive consolidation — like other PTH1R agonists, abaloparatide is used for a limited course and followed by an antiresorptive; the ACTIVExtend program tested exactly that sequence, with alendronate maintaining and extending the BMD gained during abaloparatide treatment (Bone et al., Journal of Clinical Endocrinology & Metabolism, 2018, 103(8):2949–2957)

Research status

Abaloparatide has a complete Phase 3 program and multiple regulatory approvals, together with one clearly failed formulation.

ACTIVE (NCT01343004). The Abaloparatide Comparator Trial In Vertebral Endpoints randomized 2,463 postmenopausal women at 28 sites in 10 countries to 18 months of daily blinded abaloparatide 80 mcg (n = 824), placebo (n = 821), or open-label teriparatide 20 mcg (n = 818). New morphometric vertebral fractures occurred in 0.58% of the abaloparatide group versus 4.22% of placebo (relative risk 0.14; P < .001), and the Kaplan-Meier nonvertebral fracture rate was 2.7% versus 4.7% (hazard ratio 0.57; P = .049). The approved label reports the same primary result as 0.6% versus 4.2%, an 86% relative risk reduction, and the nonvertebral result as a 43% relative risk reduction (Miller et al., JAMA, 2016, 316(7):722–733). JAMA published a correction in January 2017 that extended data markers cut off one month early on a Kaplan-Meier plot and amended a supplementary figure legend; the fracture numbers were not changed.

ACTIVExtend (NCT01657162). Of 1,243 eligible ACTIVE completers, 1,139 (92%) enrolled in an open-label extension in which all participants received alendronate 70 mg weekly for up to 24 months. A prespecified 6-month interim analysis was published first (Cosman et al., Mayo Clinic Proceedings, 2017, 92(2):200–210). Over the full 43-month period from ACTIVE baseline, new radiographic vertebral fractures occurred in 0.9% of the abaloparatide-then-alendronate group versus 5.6% of placebo-then-alendronate, an 84% relative risk reduction, with lower Kaplan-Meier rates for the other fracture types and no hip fractures in the abaloparatide sequence versus five in the placebo sequence (Bone et al., Journal of Clinical Endocrinology & Metabolism, 2018, 103(8):2949–2957).

ATOM (NCT03512262). The Abaloparatide for the Treatment of Men with Osteoporosis study randomized 228 men aged 40 to 85 (2:1, abaloparatide 80 mcg versus placebo) for 12 months. Lumbar spine BMD rose 8.48% versus 1.17%, total hip 2.14% versus 0.01%, and femoral neck 2.98% versus 0.15% (all P < 0.0001). The trial was powered for bone density, not fractures, which is why the men’s indication is worded as increasing bone density rather than reducing fracture risk (Czerwinski et al., Journal of Bone and Mineral Research, 2022, 37(12):2435–2442).

wearABLe (NCT04064411) — a failure. A Phase 3 open-label noninferiority study randomized 511 postmenopausal women to daily abaloparatide delivered by a solid microstructured transdermal system (300 mcg) or by subcutaneous injection (80 mcg). At 12 months lumbar spine BMD rose 7.14% with the patch versus 10.86% with injection, a treatment difference of −3.72% (95% CI −5.01% to −2.43%) that missed the 2.0% noninferiority margin; total hip gains were 1.97% versus 3.70% (Lewiecki et al., Journal of Bone and Mineral Research, 2023, 38(10):1404–1414). After FDA feedback that an additional pivotal trial would be needed before any filing, the sponsor announced on June 1, 2022 that it was ceasing all work on the transdermal program. A Phase 1b study of the same device in 22 postmenopausal women had earlier reported a consistent pharmacokinetic profile and bone-formation-marker (s-PINP) increases similar to those seen with injection (Miller et al., Clinical Drug Investigation, 2021, 41(3):277–285), which is a reminder that surrogate pharmacology does not guarantee a BMD result.

Regulatory record. U.S. approval on April 28, 2017 (postmenopausal women) and December 19, 2022 (men); Japan in March 2021 as Ostabalo, with an indication worded simply as osteoporosis at high risk of fracture and no sex restriction (the Japanese Phase 3 program enrolled men as well as women); European Union marketing authorization on December 12, 2022 as Eladynos, for postmenopausal women at increased risk of fracture, with a maximum treatment duration of 18 months. On December 22, 2021, the FDA approved removal of the osteosarcoma boxed warning from the U.S. label after a review of long-term post-marketing data on abaloparatide and the PTH-analog class, while retaining and revising the osteosarcoma text in Warnings and Precautions. The most recent U.S. label change, approved August 3, 2026 and dated 08/2026, followed an April 20, 2026 FDA safety-labeling notification under section 505(o)(4) to parathyroid hormone products and added a hypersensitivity-reactions warning covering anaphylaxis, angioedema, and urticaria. A March 2025 supplement was a labeling-only change. No new indication was approved in 2025 or 2026, and no complete response letter is on record for the molecule.

Active work. ClinicalTrials.gov currently lists a Phase 4 study of abaloparatide added to ongoing denosumab versus denosumab alone (NCT04467983, Hospital for Special Surgery, active and not recruiting, estimated primary completion September 2026) and a Phase 3 open-label study of a follow-on abaloparatide injection against teriparatide in postmenopausal women registered by a Chinese manufacturer in 2025 (NCT06898060, not yet recruiting). There is no registered human program in anti-aging, performance, or general wellness indications.

Common dosage forms

• Prefilled multidose pen (approved product) — a single-patient-use pen containing 3,120 mcg in 1.56 mL (2,000 mcg/mL) that delivers 30 daily doses of 80 mcg in 40 µL each. The pen is stored refrigerated before first use and at room temperature for up to 30 days after first use.
• Cartridge formats abroad — the Japanese product is supplied as a cartridge for a dedicated electronic injector. The original 3 mg cartridge approved in March 2021 was not launched because of Japan’s 14-day prescription limit for new drugs; a 1.5 mg, 14-day cartridge was approved on August 31, 2022 and launched in January 2023.
• Transdermal patch — a microneedle-array system reached Phase 3 but was never approved and the program has been discontinued; it is not a marketed format.
• Research supply — lyophilized abaloparatide acetate powder in vials, conventionally labeled in milligrams, intended for reconstitution. Approved products are dosed in micrograms; a vial labeled in milligrams holds a quantity of a different order than a single approved dose.

Key considerations

• The approval is real but narrow, and it comes with a time limit. Abaloparatide is approved for osteoporosis at high fracture risk in postmenopausal women (fracture-reduction claim) and in men (bone-density claim only); its FDA Approved status reflects that an FDA-approved drug product containing the molecule exists. The U.S. label states that safety and efficacy have not been evaluated beyond 2 years and that use for more than 2 years during a patient’s lifetime is not recommended; the EU authorization caps treatment at 18 months. Nothing in the record supports open-ended or repeated courses, and nothing extends to wellness or anti-aging framing.
• The osteosarcoma signal was downgraded, not retired. Rats given abaloparatide developed dose-dependent osteosarcoma at 4 to 28 times the human exposure at the clinical dose. The boxed warning was removed in December 2021, but the current label still advises avoiding use in people with open epiphyses, Paget’s disease or other metabolic bone disease, bone metastases or prior skeletal malignancy, prior external-beam or implant radiation involving the skeleton, or hereditary disorders predisposing to osteosarcoma, and notes limited data on osteosarcoma risk beyond 2 years of use.
• The acute safety profile is well characterized. Labeled warnings cover orthostatic hypotension typically within 4 hours of injection (the first several doses should be given where the patient can sit or lie down), hypercalcemia (not recommended with pre-existing hypercalcemia or primary hyperparathyroidism), and hypercalciuria with a possible contribution to urolithiasis. Hypersensitivity reactions including anaphylaxis and angioedema were added to the label in 2026 as a class finding for parathyroid hormone products.
• It is a PTHrP analog, not a PTH analog — and not interchangeable with teriparatide. Abaloparatide and teriparatide both activate PTH1R and are often grouped together, but they derive from different parent hormones, differ in receptor-conformation selectivity, and produced different hypercalcemia rates in head-to-head data. Descriptions calling abaloparatide “a form of PTH” or “synthetic PTH(1-34)” are inaccurate. The brand names Tymlos (U.S.), Eladynos (EU), and Ostabalo (Japan) all refer to the same molecule.
• The transdermal failure matters for how the data are read. The same molecule at a higher nominal dose through a patch produced materially smaller BMD gains than the injection, which means the published fracture and BMD results belong to the subcutaneous 80 mcg regimen specifically. Results should not be assumed to transfer to other routes, doses, or uncharacterized material, and the label’s clinical data were generated entirely with the approved product.