Growth hormone & endocrine research
Abaloparatide (Tymlos): Research Overview
Parathyroid hormone analogue approved for osteoporosis and studied in bone research.
Also known as Tymlos · BA058 · PTHrP analogue
What is Abaloparatide?
Abaloparatide is an FDA-approved anabolic bone-building agent and synthetic analog of parathyroid hormone-related protein (PTHrP). It selectively activates the PTH1 receptor to stimulate new bone formation while minimizing bone resorption. In the phase III ACTIVE trial, abaloparatide showed superior BMD increases at the hip compared to teriparatide, with substantial fracture risk reduction.
What is Abaloparatide researched for?
- FDA-approved for postmenopausal women with osteoporosis at high risk for fracture or who have failed other therapies.
- FDA-approved for men with osteoporosis at high risk for fracture or intolerant to other treatments.
- Phase III trials demonstrated substantial reduction in vertebral and nonvertebral fractures.
- ACTIVExtend trial showed benefits of abaloparatide followed by alendronate for maintained bone protection.
How does Abaloparatide work?
Abaloparatide works through selective activation of the parathyroid hormone 1 receptor (PTH1R), a G protein-coupled receptor expressed on osteoblasts and osteocytes. It preferentially binds to the RG (relaxed, G-protein-coupled) conformational state of PTH1R, which elicits a transient downstream cyclic AMP signaling response favoring anabolic bone formation over resorption.
Reported targets: PTH1R
References
Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis (ACTIVE Trial) Miller PD, Hattersley G, Riis BJ, et al. JAMA
2016
Abaloparatide showed substantial reduction in vertebral fractures and greater BMD increases at spine, hip, and femur compared to placebo and teriparatide.
ACTIVExtend Trial: Abaloparatide Followed by Alendronate Cosman F, Miller PD, Williams GC, et al. Mayo Clinic Proceedings
2017
18 months abaloparatide followed by alendronate significantly reduced vertebral and nonvertebral fractures.
Phase 2 Dose-finding Study of BA058 in Postmenopausal Women
Leder BZ, O'Dea LS, Zanchetta JR, et al. · Journal of Clinical Endocrinology and Metabolism · 2015
Significant BMD increases at 40 and 80 mcg doses; abaloparatide showed superior anabolic effects on hips vs teriparatide.
Controlled clinical trial
Profile of Abaloparatide and Its Potential in Postmenopausal Osteoporosis Tella SH, Kommalapati A, Correa R Cureus
2017
Abaloparatide preferentially binds RG conformational state of PTH1R, producing more anabolic bone effects.
Common questions
Why is abaloparatide limited to 2 years of use?
Cumulative lifetime use is limited to 2 years due to theoretical osteosarcoma risk observed in rodent studies at very high doses. This is a precautionary measure based on animal data, and the ACTIVExtend trial demonstrated that benefits can be maintained by transitioning to alendronate after 18 months of abaloparatide.
Is abaloparatide better than teriparatide (Forteo)?
Yes. In the phase III ACTIVE trial, abaloparatide showed superior BMD increases at the hip compared to teriparatide, with substantial fracture risk reduction. It also carries lower hypercalcemia risk than teriparatide despite more potent bone-building activity.
What causes the dizziness and palpitations reported with abaloparatide?
Dizziness, palpitations, and vertigo occur in a subset of users, likely due to transient hypotension or hemodynamic changes from rapid PTH receptor activation. These effects typically subside with continued use as the body adapts. Orthostatic hypotension is a rare but serious warning sign requiring discontinuation.