Abaloparatide

Chemical Identity

Property	Value
Chemical Formula	C178H294N56O52
Molecular Weight	3961 Da
CAS Number	247062-33-5
Peptide Class	Synthetic PTHrP Analog (34 amino acids)
Route	SC injection

Structure

Abaloparatide (Tymlos) is a synthetic 34-amino acid analog of parathyroid hormone-related protein (PTHrP). It shares 41% sequence homology with PTHrP(1-34) and 76% with hPTH(1-34). Key substitutions enhance selectivity for the RG (anabolic) conformation of the PTH1 receptor.

Mechanism of Action

Abaloparatide binds PTH1R with preferential activation of the cyclic AMP (RG) signaling pathway over the beta-arrestin (R0) pathway. This selective activation provides sustained anabolic bone formation with less stimulation of bone resorption and less hypercalcemia compared to teriparatide.

Clinical Applications

• Postmenopausal osteoporosis: High fracture risk (Tymlos)
• Fracture prevention: 86% reduction in vertebral fractures (ACTIVE trial)
• Male osteoporosis: Approved for men
• Combination therapy: With denosumab (DATA trial showed additive effects)

Pharmacokinetics

• Half-life: 1.7 hours
• Tmax: 0.5 hours
• Bioavailability: ~70%
• Metabolism: Proteolytic degradation
• Dosing: 80 mcg SC daily for up to 24 months
• Route: SC injection (abdomen)

Safety and Side Effects

Hypercalcemia (3%, lower than teriparatide), dizziness, nausea, headache, palpitations, and injection site reactions. Less hypercalcemia and hypercalciuria than teriparatide. Boxed warning for osteosarcoma risk in rodents.

References

• Miller, P.D., et al. (2016). ACTIVE trial: abaloparatide for osteoporosis. New England Journal of Medicine, 374, 2229-2238.
• Leder, B.Z., et al. (2015). Abaloparatide versus teriparatide: ACTIVExtend. Journal of Bone and Mineral Research, 30, 976-984.