Parathyroid hormone-related protein was identified as the factor secreted by certain tumours that causes hypercalcaemia. It shares its N-terminal region with PTH and activates the same PTH1 receptor, but it normally acts locally in tissues such as growth plate cartilage, breast and skin.

How does abaloparatide differ from teriparatide?

Teriparatide is based on PTH(1-34), while abaloparatide is based on PTHrP(1-34). Both activate PTH1R, but abaloparatide preferentially binds the RG conformation, producing briefer cAMP signalling. This difference is the focus of extensive comparative research.

What does conformational selectivity mean?

Receptors can adopt different three-dimensional states. A ligand that preferentially binds one state can produce a distinct signalling pattern from another ligand acting on the same receptor. Abaloparatide's preference for the RG state of PTH1R is a well-studied example among class B receptors.

Abaloparatide — Research Monograph

Overview

Abaloparatide (BA058) is a 34-amino-acid synthetic peptide analogue of parathyroid hormone-related protein (PTHrP). PTHrP was originally identified as the cause of humoral hypercalcaemia of malignancy and was later recognised as an important local regulator of cartilage and bone development. Abaloparatide shares substantial sequence identity with PTHrP(1-34), with substitutions designed to enhance stability and modify receptor interactions.

Developed by Radius Health, abaloparatide was approved by the FDA in 2017 and by the European Medicines Agency in 2022 for osteoporosis in people at high fracture risk, and it is an approved prescription medicine in those regions. Its evaluation centred on the ACTIVE trial, which included a teriparatide comparison arm. Abaloparatide is of particular scientific interest because it engages the same receptor as teriparatide yet favours a different receptor conformation, providing a natural experiment in how signalling duration shapes biological outcomes. Researchers use abaloparatide to study PTH1R conformational selectivity, bone anabolism, osteoblast biology and calcium handling, often in direct comparison with teriparatide.

Mechanism studied

Abaloparatide
PTH1R (RG conformation)
Osteoblast activation
Bone formation

Abaloparatide binds the PTH1 receptor, the same class B G protein-coupled receptor activated by PTH and PTHrP. Studies by Thomas Gardella and colleagues showed that PTH1R adopts at least two high-affinity conformations: R0, which can remain bound to ligand independently of G protein and supports prolonged cAMP signalling, and RG, which requires G protein coupling and gives more transient signalling. Abaloparatide binds RG preferentially, producing shorter cAMP responses than teriparatide. This is hypothesised to favour osteoblastic bone formation while limiting stimulation of resorption and calcium mobilisation. Downstream effects include osteoblast activation, sclerostin suppression and changes in RANKL expression.

Research highlights

01Developed by Radius Health from a PTHrP(1-34) template; approved by the FDA in 2017 and the EMA in 2022.
02Receptor-conformation research distinguished R0 and RG states of PTH1R, offering an explanation for differences from teriparatide.
03The ACTIVE trial compared abaloparatide with placebo and open-label teriparatide.
04Comparative rodent and primate studies examine cortical and trabecular bone responses to transient versus prolonged signalling.
05Open questions include how conformational selectivity translates to tissue-specific responses in bone and kidney.

Latest published research

407 papers on PubMed →

Live feed from PubMed (NCBI) for “Abaloparatide”, updated 2026-10-30. Listing a paper is not an endorsement of its findings.

Registered studies

25 on ClinicalTrials.gov →

From the public ClinicalTrials.gov registry for “Abaloparatide”, updated 2026-10-30. Shown for research context only; Purity Peptides products are not for human use.

Key references

[1]Manufacturer's prescribing information — FDA / EMA / ANVISA
[2]Miller et al., 2016 — JAMA 316:722–733

FAQ

Parathyroid hormone-related protein was identified as the factor secreted by certain tumours that causes hypercalcaemia. It shares its N-terminal region with PTH and activates the same PTH1 receptor, but it normally acts locally in tissues such as growth plate cartilage, breast and skin.
Teriparatide is based on PTH(1-34), while abaloparatide is based on PTHrP(1-34). Both activate PTH1R, but abaloparatide preferentially binds the RG conformation, producing briefer cAMP signalling. This difference is the focus of extensive comparative research.
Receptors can adopt different three-dimensional states. A ligand that preferentially binds one state can produce a distinct signalling pattern from another ligand acting on the same receptor. Abaloparatide's preference for the RG state of PTH1R is a well-studied example among class B receptors.

FOR RESEARCH USE ONLY.Not for human or veterinary use. Not intended to diagnose, treat, cure, or prevent any disease.

Abaloparatide

Overview

Mechanism studied

Research highlights

Latest published research

Registered studies

Key references

FAQ

01What is PTHrP?

02How does abaloparatide differ from teriparatide?

03What does conformational selectivity mean?

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