Abaloparatide
Also known as: Tymlos, Eladynos, BA058, ITM-058, PTHrP(1-34) analog
FDA-approved prescription drug (Tymlos) for osteoporosis at high fracture risk in postmenopausal women and in men; approved in the EU as Eladynos
5 notable studies · 5 references
TLDR
Abaloparatide is an FDA-approved synthetic PTHrP(1-34) analog that activates the PTH1 receptor to build bone; a large phase 3 trial showed fewer new vertebral and nonvertebral fractures than placebo in postmenopausal women with osteoporosis, and a separate trial showed BMD gains in men, but its evidence is specific to osteoporosis and does not support research-market claims beyond that.
At a Glance
Classification: Synthetic 34-amino-acid analog of parathyroid hormone-related protein (PTHrP 1-34); parathyroid hormone type 1 receptor (PTH1R) agonist; anabolic (bone-forming) osteoporosis agent
Abaloparatide is a synthetic 34-amino-acid peptide modeled on the N-terminal region of human PTHrP. It activates the PTH type 1 receptor, the same receptor targeted by teriparatide. Unlike most compounds in the research-peptide market, abaloparatide is an approved prescription drug. In the US it is marketed as Tymlos for the treatment of osteoporosis in postmenopausal women at high risk of fracture, and its label was later expanded to men with osteoporosis at high risk of fracture. In the EU it is marketed as Eladynos. Its evidence base includes: • A large phase 3 fracture trial in postmenopausal women (ACTIVE) • An extension study of sequential abaloparatide followed by alendronate (ACTIVExtend) • A randomized trial in men (ATOM) • Receptor-pharmacology and animal bone studies. In ACTIVE, new vertebral fractures were less frequent with abaloparatide than placebo over 18 months, and hypercalcemia was less frequent than with open-label teriparatide.
What Is Abaloparatide?
Parathyroid hormone (PTH) and PTH-related protein (PTHrP) are two natural hormones that share one receptor, PTH1R. When that receptor is stimulated intermittently (short daily exposure), the net effect on bone favors formation. When it is stimulated continuously, the net effect favors bone resorption and raised blood calcium. Abaloparatide was designed from the PTHrP(1-34) sequence with substitutions intended to tune how it binds the receptor. Teriparatide → PTH(1-34), the first 34 residues of parathyroid hormone Abaloparatide → modified PTHrP(1-34) analog Both → PTH1R agonists used as anabolic osteoporosis therapies They are related, but not the same molecule.
What Are Researchers Studying?
Postmenopausal osteoporosis and fracture prevention
This is abaloparatide's best-established use. The ACTIVE phase 3 trial randomized 2,463 postmenopausal women with osteoporosis to blinded abaloparatide, blinded placebo, or open-label teriparatide for 18 months. New vertebral fractures were less frequent with active treatment than placebo, and bone mineral density increased more with abaloparatide than placebo.
Sequential therapy
Anabolic agents are usually followed by an antiresorptive drug to preserve the bone gained. In ACTIVExtend, women who completed ACTIVE received up to 24 months of alendronate. Over the full 43 months, new vertebral fractures occurred in 0.9% of the abaloparatide-then-alendronate group versus 5.6% of the placebo-then-alendronate group.
Male osteoporosis
The ATOM trial randomized 228 men aged 40-85 with osteoporosis to abaloparatide or placebo for 12 months. Lumbar spine BMD rose about 8.5% with abaloparatide versus about 1.2% with placebo. Fracture reduction was not the primary endpoint.
Receptor-conformation pharmacology
Laboratory work proposes that abaloparatide binds preferentially to a transient (RG) conformation of PTH1R rather than the more sustained (R0) conformation, giving shorter signaling responses than PTH(1-34). This is offered as one explanation for its lower calcemic effect, though how much it explains clinical differences is still debated.
How Does It Work?
Abaloparatide ↓ PTH type 1 receptor (PTH1R) on osteoblast-lineage cells and kidney ↓ cAMP / protein kinase A signaling, with relatively transient receptor engagement ↓ intermittent exposure favors bone formation over resorption ↓ increased bone mineral density and reduced fracture risk in the trial populations studied. The mechanism is a well-characterized hormone-receptor pathway, not a speculative one.
What Does the Research Show?
Human research
SUBSTANTIAL for postmenopausal osteoporosis (fracture endpoints in a phase 3 RCT). MODERATE for men (BMD endpoints in an RCT). Abaloparatide's human evidence is far stronger than that of almost any research-market peptide, but it is specific to osteoporosis in the populations studied. It does not establish effects for injury healing, joint repair, or general "bone optimization" in healthy people.
Animal research
Ovariectomized rat studies show dose-dependent increases in bone mass and strength, including a one-year study.
In-vitro research
Receptor-binding and signaling studies characterize its selectivity for PTH1R conformations.
Notable Studies
Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial
humanJournal: JAMA. Phase 3 double-blind RCT (ACTIVE) of 2,463 postmenopausal women randomized to abaloparatide, placebo, or open-label teriparatide for 18 months. New vertebral and nonvertebral fractures were reduced versus placebo, BMD increased, and hypercalcemia was less common with abaloparatide (3.4%) than teriparatide (6.4%).
Limitations: Teriparatide arm was open-label; 18-month duration; sponsor-funded; trial was not powered for a head-to-head fracture comparison with teriparatide.
View publication →ACTIVExtend: 24 Months of Alendronate After 18 Months of Abaloparatide or Placebo for Postmenopausal Osteoporosis
humanJournal: Journal of Clinical Endocrinology & Metabolism. Women completing ACTIVE received up to 24 months of alendronate. Across 43 months, new vertebral fractures occurred in 0.9% of the abaloparatide/alendronate group versus 5.6% of the placebo/alendronate group (84% relative risk reduction), with further BMD gains.
Limitations: Extension of a prior trial; both groups received alendronate during the extension; sponsor-funded.
View publication →The Efficacy and Safety of Abaloparatide-SC in Men With Osteoporosis: A Randomized Clinical Trial
humanJournal: Journal of Bone and Mineral Research. 228 men with osteoporosis were randomized 2:1 to abaloparatide or placebo for 12 months. BMD gains were greater with abaloparatide at the lumbar spine (8.48% vs 1.17%), total hip, and femoral neck. Common adverse events included injection-site reactions, dizziness, and nasopharyngitis.
Limitations: BMD endpoint rather than fractures; 12 months only; modest size; sponsor-funded.
View publication →Binding Selectivity of Abaloparatide for PTH-Type-1-Receptor Conformations and Effects on Downstream Signaling
in-vitroJournal: Endocrinology. Compared how abaloparatide, PTH(1-34), and PTHrP(1-34) bind two high-affinity PTH1R conformations (R0 and RG). Abaloparatide showed greater selectivity for RG, associated with more transient signaling, offering a mechanistic hypothesis for its lower calcemic effect.
Limitations: Cell and membrane assays; animal and human relevance of the conformation model is inferred, not proven.
View publication →One year of abaloparatide, a selective peptide activator of the PTH1 receptor, increased bone mass and strength in ovariectomized rats
animalJournal: Bone. Osteopenic ovariectomized rats received daily abaloparatide at three dose levels for 12 months. Bone mass increased dose-dependently at the spine, tibia, and femur, and biomechanical testing showed increased bone strength.
Limitations: Rodent model; rodent bone biology and long-term safety findings do not translate directly to humans.
View publication →What We Still Don't Know
Head-to-head fracture superiority versus teriparatide or romosozumab (not established by a dedicated fracture trial) Fracture-reduction data in men (ATOM measured BMD, not fractures) Long-term outcomes beyond the studied treatment and extension periods How much the receptor-conformation model explains clinical differences from teriparatide Any benefit outside osteoporosis (e.g., fracture healing, tendon or joint repair); these uses are not established.
Related Compounds
Recent publications
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Sources & References
- Miller PD, et al. Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial. JAMA. 2016.
- Bone HG, et al. ACTIVExtend: 24 Months of Alendronate After 18 Months of Abaloparatide or Placebo for Postmenopausal Osteoporosis. J Clin Endocrinol Metab. 2018.
- Czerwinski E, et al. The Efficacy and Safety of Abaloparatide-SC in Men With Osteoporosis: A Randomized Clinical Trial. J Bone Miner Res. 2022.
- Hattersley G, et al. Binding Selectivity of Abaloparatide for PTH-Type-1-Receptor Conformations and Effects on Downstream Signaling. Endocrinology. 2016.
- Varela A, et al. One year of abaloparatide, a selective peptide activator of the PTH1 receptor, increased bone mass and strength in ovariectomized rats. Bone. 2017.
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