Abaloparatide

Abaloparatide is a synthetic 34-amino-acid analogue of parathyroid hormone-related protein, PTHrP(1-34). It is an FDA-approved anabolic agent for osteoporosis, marketed as Tymlos, that acts on the PTH type 1 receptor.

Last reviewed 2026-10-25 by the PeptideWiki editorial team. Editorial policy.

Overview

Abaloparatide is a modified version of the N-terminal 34 residues of parathyroid hormone-related protein (PTHrP), a protein that shares the PTH type 1 receptor with parathyroid hormone and has important roles in development and in hypercalcemia of malignancy. Its sequence keeps the PTHrP N-terminal region, which is closely related to PTH at the receptor-activating positions, while the C-terminal portion was altered to improve stability and receptor-binding characteristics.

Abaloparatide was developed as an anabolic osteoporosis agent with the aim of building bone while limiting effects on resorption and calcium. Its approval was based on the ACTIVE trial in postmenopausal women with osteoporosis, which compared it with placebo and with open-label teriparatide. It is marketed as Tymlos, and FDA approval was later extended to men with osteoporosis; current labeling should be checked for details. Like teriparatide, it is given for a limited period and is typically followed by antiresorptive therapy.

Compare: Teriparatide vs abaloparatide.

Structure

Abaloparatide is a 34-residue synthetic peptide with a C-terminal amide. Its N-terminal half largely follows the human PTHrP(1-34) sequence, while multiple substitutions in the C-terminal portion, including the non-proteinogenic amino acid α-aminoisobutyric acid (Aib), were introduced to stabilize the helical structure involved in receptor binding. Unlike teriparatide, it contains no methionine, which reduces one important oxidation pathway. The presence of Aib means that mass calculations require the correct residue mass for this non-standard amino acid. Pharmaceutical material is a synthetic acetate salt.

Mechanism

Abaloparatide is an agonist of the PTH type 1 receptor (PTH1R), which signals mainly through Gs, cyclic AMP and protein kinase A. Receptor studies reported that, compared with PTH(1-34), abaloparatide binds preferentially to a G protein-dependent receptor conformation (often called RG) rather than a conformation associated with prolonged signaling (R0). This has been proposed to produce more transient cyclic AMP signaling, possibly favoring formation over resorption and producing less hypercalcemia. How fully this model explains clinical differences remains debated.

Research

The ACTIVE trial

The ACTIVE phase 3 trial randomized postmenopausal women with osteoporosis to abaloparatide, placebo or open-label teriparatide and reported a reduction in new vertebral fractures with abaloparatide compared with placebo, along with gains in bone mineral density. Results were published in 2016. Comparisons with teriparatide were exploratory because that arm was open-label. An extension study evaluated sequential treatment with alendronate after abaloparatide.

Men with osteoporosis

A subsequent trial evaluated abaloparatide in men with osteoporosis, assessing changes in bone mineral density at the spine and hip compared with placebo. These results contributed to the expansion of the US label to include men. Fracture outcomes were not the primary endpoint in this population, which is common in osteoporosis trials in men. Analyses also examined safety measures, including serum calcium and cardiovascular parameters, in this population.

Receptor conformation research

Abaloparatide has been an important tool in studying how ligands for the same receptor can produce different signaling. Work comparing PTH, PTHrP and their analogues at PTH1R conformations has informed a broader understanding of ligand-biased or kinetically distinct signaling in class B G protein-coupled receptors. These studies are largely in vitro and in animal models. Whether conformational selectivity fully accounts for differences observed between drugs in people is still discussed.

Safety and formulation

Rat toxicology studies with abaloparatide, as with teriparatide, showed osteosarcoma, which shaped early US labeling. Clinical trials reported lower rates of hypercalcemia than with teriparatide in some analyses. Abaloparatide was approved as a subcutaneous pen, and a transdermal patch formulation has also been studied. Current labeling should be consulted for safety language and approved formulations. Direct comparisons with teriparatide on hard fracture endpoints remain limited.

Regulatory status

Abaloparatide is FDA-approved, marketed as Tymlos, for osteoporosis in postmenopausal women at high risk for fracture, with approval later extended to men with osteoporosis at high risk of fracture; check current labeling for exact indications and duration language. Its approval status outside the United States varies by jurisdiction. For sport, check the current WADA Prohibited List.

Status changes often. See the regulatory tracker for dated updates.

Quality and identity testing

A certificate of analysis should confirm identity by mass spectrometry, with the observed mass matching the expected mass for the full sequence including the α-aminoisobutyric acid residue and C-terminal amide, and report HPLC purity with the chromatogram. Because the sequence is related to PTHrP and to teriparatide, MS/MS or peptide mapping helps distinguish it from unmodified PTHrP(1-34). Characteristic impurities for a 34-residue synthetic peptide include deletion and truncated sequences, deamidation, and a C-terminal free acid in place of the amide. The acetate content and net peptide content should be stated.

For a walkthrough of each section of a certificate, see how to read a COA.

Storage and stability

Store lyophilized abaloparatide sealed at -20 °C or colder, protected from light and moisture, and let vials reach room temperature before opening. Pharmaceutical pens have specific refrigeration and in-use storage instructions on their labeling. Although it lacks methionine, the peptide can still deamidate and aggregate in solution, especially with agitation or at elevated temperature. Prepare research solutions in sterile buffer, keep them cold, aliquot for longer storage at -20 °C or below, and avoid repeated freeze-thaw cycles.

Download the Abaloparatide data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.

Latest research

Frequently asked questions

Related compounds

• Teriparatide

  Teriparatide is the N-terminal 34-amino-acid fragment of human parathyroid hormone, PTH(1-34). It is an FDA-approved bone-forming (anabolic) agent, marketed as Forteo, used for osteoporosis in people at high risk of fracture.

• Calcitonin (salmon)

  Salmon calcitonin is a 32-amino-acid peptide hormone with a disulfide-bridged ring and C-terminal prolinamide that inhibits osteoclast bone resorption. It is FDA-approved as Miacalcin for conditions including Paget's disease of bone and hypercalcemia.

References

1. Miller PD, Hattersley G, Riis BJ, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA. 2016. Find on PubMed
2. PubMed: all indexed literature on Abaloparatide
3. ClinicalTrials.gov: registered studies mentioning Abaloparatide