Abaloparatide exhibits greater osteoanabolic response and higher cAMP stimulation and b-arrestin recruitment than teriparatide

Physiological Reports, 2019 · DOI: 10.14814/phy2.14225 · Published: October 1, 2019

Pharmacology Endocrinology Musculoskeletal Medicine

Simple Explanation

This study compares two drugs, abaloparatide and teriparatide, used to treat osteoporosis. Both drugs are similar but have different effects on bone. The researchers found that abaloparatide was better at increasing bone formation and improving bone structure compared to teriparatide in mice. In cell studies, abaloparatide also showed a stronger activation of certain cellular pathways that promote bone growth.

Study Duration

30 days

Participants

WT female C57BL/6J mice

Evidence Level

Not specified

Key Findings

1
Abaloparatide caused a greater dose-dependent increase in cortical thickness than teriparatide.
2
Abaloparatide promoted greater elevation of procollagen type 1 intact N-terminal propeptide, a bone formation marker.
3
Abaloparatide had a markedly lower EC50 for cAMP formation and b-arrestin recruitment than teriparatide.

Research Summary

This study compared the effects of abaloparatide and teriparatide on bone structure, turnover, and signaling pathways in mice and cells. The results showed that abaloparatide had a greater osteoanabolic response than teriparatide, with increased trabecular and cortical bone thickness and higher bone formation markers. In vitro, abaloparatide demonstrated more efficient coupling of PTHR1 to Gs-cAMP and b-arrestin signaling, suggesting a mechanism for its superior efficacy.

Practical Implications

Therapeutic Potential

Abaloparatide may offer a more effective treatment option for osteoporosis due to its enhanced bone formation and improved bone microarchitecture.

Signaling Pathways

The study highlights the importance of Gs-cAMP and b-arrestin signaling pathways in mediating the anabolic effects of PTHR1 agonists.

Drug Development

Understanding the differential effects of abaloparatide and teriparatide can aid in the development of next-generation PTHR1-based bone therapeutics.

Study Limitations

1
The study was conducted on mice, and the results may not directly translate to humans.
2
The study focused on specific bone markers and signaling pathways, and other factors may contribute to the overall efficacy of the drugs.
3
A more comprehensive analysis including longer and shorter time course is needed for careful evaluation of the catabolic and anabolic activity of both abaloparatide and teriparatide.

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