A 34-amino-acid PTHrP analog sold as Tymlos: an FDA-approved daily injection that builds bone in women and men with osteoporosis.
Also called Tymlos, Eladynos, Abaloparatide-SC, ABL-SC, PTHrP(1-34) analog, Abaloparatide transdermal system, Abalo-TDS
When Abaloparatide's status or evidence changes, it's in the next morning's email.
Abaloparatide is a synthetic 34-amino-acid peptide modeled on parathyroid hormone-related protein (PTHrP), a cousin of parathyroid hormone. Like teriparatide, it is a bone builder: a daily injection under the skin of the belly switches on bone-forming cells, so the skeleton gains bone instead of just losing it more slowly. Radius Health sells it as Tymlos. FDA approved it in April 2017 for postmenopausal women with osteoporosis at high risk of fracture, and in December 2022 added men with osteoporosis at high risk. The EU approved it as Eladynos in December 2022.
The main trial, ACTIVE, gave 2,463 postmenopausal women abaloparatide 80 mcg, placebo or open-label teriparatide for 18 months. New spine fractures were 0.6% on abaloparatide and 4.2% on placebo, an 86% relative reduction, and other fractures fell from 4.7% to 2.7%. High blood calcium was less common than on teriparatide, 3.4% vs 6.4%. In the ATOM trial of 228 men, spine bone density rose 8.5% vs 1.2% on placebo in 12 months. FDA approved the men's indication on bone density, not fracture data.
The common problems are dizziness (10% vs 6% on placebo), nausea, palpitations and a racing heart in the hour after a dose, which is why the first doses are given sitting or lying down. Rats given high doses developed osteosarcoma; FDA removed the boxed warning in December 2021 and moved osteosarcoma to the label's warnings section, but the label still says use beyond 2 years in a lifetime is not recommended. A skin-patch version missed its main goal in 2021: spine bone density rose 7.1% on the patch and 10.9% on the injection.
What it binds to, and what happens inside the body after that, step by step.
Abaloparatide activates the PTH type 1 receptor, the same receptor teriparatide uses, which turns on cAMP signaling in bone cells. Lab work shows it prefers one shape of that receptor (the RG conformation), giving shorter signals than teriparatide. Brief daily signals favor bone formation over bone breakdown, so bone builds up on both inner spongy bone and outer cortical bone.
Human results and animal results are kept apart below. A result in rats tells you a mechanism is plausible. It does not tell you what happens in a person.
One large phase 3 RCT (ACTIVE, 2,463 women) shows abaloparatide cuts new spine fractures by 86% and other fractures by 43% versus placebo over 18 months, with gains held when followed by alendronate. A 228-man RCT shows bone density gains but was not designed to measure fractures. It has never been compared head to head with teriparatide in a blinded fracture trial; one claims-database study of 23,232 women found similar nonvertebral fracture rates.
2,463 postmenopausal women with osteoporosis, 18 months (824 abaloparatide, 821 placebo, 818 open-label teriparatide)
New spine fractures 0.6% vs 4.2% on placebo (86% relative reduction); high calcium 3.4% vs 6.4% on teriparatide.
Read the study1,139 women from ACTIVE switched to open-label alendronate
At 25 months, new spine fractures were 0.55% vs 4.4% (87% reduction) and nonvertebral fractures 2.7% vs 5.6%.
Read the study228 men aged 40 to 85 with osteoporosis, 12 months
Spine bone density rose 8.48% vs 1.17% on placebo; total hip 2.14% vs 0.01%.
Read the study11,616 matched women per group, US claims database (observational)
Nonvertebral fractures were similar (hazard ratio 0.89, not significant); hip fractures hazard ratio 0.78; heart events similar.
Read the study511 postmenopausal women with osteoporosis, open-label noninferiority trial, 12 months
Spine bone density rose 7.1% on the 300 mcg patch vs 10.9% on the 80 mcg injection; the patch failed noninferiority.
Read the studyCell and membrane assays
Abaloparatide binds the RG receptor conformation more selectively than PTH(1-34) and gives a shorter cAMP response.
Read the studyWhen a new Abaloparatide study in people is published, the daily email covers it.
These are questions the published research has not answered.
FDA approved Tymlos on April 28, 2017 with a boxed warning for osteosarcoma. The December 2021 label removed the boxed warning; the osteosarcoma risk now sits in Warnings and Precautions, with the advice to avoid it in people with open growth plates, Paget's disease, bone metastases, past skeletal radiation or inherited osteosarcoma risk. The men's indication was approved December 19, 2022 based on bone density in the ATOM trial. The label still says use for more than 2 years in a lifetime is not recommended, unlike the teriparatide label, which loosened that limit in 2020. Not named on the WADA Prohibited List.
When the FDA or WADA changes Abaloparatide's status, it's in the next morning's email.
How much of Abaloparatide is left after a single dose
Simple first-order model from the published half-life. Real clearance varies with dose, route, kidney and liver function and formulation. This is not a dosing schedule.
This table records the doses that trials and approved labels used, with the source for each row. It is a record of research, not a recommendation, and it is open to free members.
Which symptoms are expected and which mean stop and get help: side effects and red flags.
Tap a claim to see what the studies found.
It is based on a different hormone, PTHrP, and shares only 41% of its sequence with PTH(1-34). Both act on the same receptor, but abaloparatide favors a different receptor shape.
In ACTIVE it caused less high calcium (3.4% vs 6.4%), but teriparatide was open-label and the trial was not built to compare fractures. A claims study found similar nonvertebral fracture rates.
FDA added men with osteoporosis at high fracture risk in December 2022, based on a 228-man trial where spine bone density rose 8.5% vs 1.2%.
The transdermal patch failed its noninferiority goal in 2021 and is not approved.
These pairings come up often. Almost none have been tested together in a trial, and the evidence note on each says so plainly.
Builds bone with abaloparatide for 18 months, then holds the gain with an oral bisphosphonate.
EvidenceTested in ACTIVExtend: 1,139 women. At 25 months, new spine fractures were 0.55% vs 4.4% in women who had placebo before alendronate. This is a sequence, not two drugs at once.
Not supplied as a powder. Tymlos is a ready-to-use solution in a 30-dose pen: before first use, refrigerate at 2 to 8 C (36 to 46 F) (label).
No mixing needed. After first use, keep at 20 to 25 C (68 to 77 F) for up to 30 days. Do not freeze or expose to heat (label).
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