Abaloparatide

Summary

Abaloparatide is a synthetic analogue of human PTHrP(1-34) approved for the treatment of postmenopausal osteoporosis in women at high risk of fracture, and more recently for men with osteoporosis. It preferentially activates the RG conformation of PTH1R, resulting in anabolic bone effects with a potentially more favorable benefit-risk profile than teriparatide.

Mechanism of Action

Selective activator of the RG conformation of the PTH1 receptor (PTH1R), mimicking the anabolic effects of PTHrP. Stimulates osteoblast activity, promoting bone formation while having less effect on bone resorption compared to teriparatide.

Routes of Administration

Goals & Uses

• Treatment of male osteoporosisBone HealthModerate
• Reduction of vertebral fracture riskBone HealthHigh
• Increase in bone mineral density (BMD)Bone HealthHigh
• Anabolic bone therapy before antiresorptive treatmentBone HealthModerate
• Reduction of nonvertebral fracture riskBone HealthHigh

Contraindications

• Prior external beam or implant radiation therapy to the skeletonRadiation HistoryHigh
• Pediatric patients or open epiphysesAge/developmentalHigh
• HypercalcemiaMetabolic DisorderHigh
• Bone metastases or skeletal malignancyOncologyHigh
• Paget's disease of boneBone DisorderHigh

Adverse Effects

• HypercalcemiaMetabolicUncommon
• Injection site reactionsLocalCommon
• HypercalciuriaMetabolicCommon
• NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
• OsteosarcomaOncologyRare
• Orthostatic hypotension/dizzinessCardiovascularCommon

Drug Interactions

• Antiresorptive agents (bisphosphonates, denosumab)Low
• Calcium supplementsModerate
• Thiazide diureticsModerate

Population Constraints

• PregnancyReproductive SafetyAbsolute
• Pediatric patientsAgeAbsolute
• Prior osteosarcoma or high-risk bone conditionsOncologyAbsolute
• Renal impairment (severe, CrCl <30 mL/min)RenalRelative

Regulatory Status

• European UnionUnknownNot approved by EMA as of last available data; regulatory status in EU not confirmed.
• United StatesApprovedApproved: Postmenopausal women with osteoporosis at high risk for fracture, Men with osteoporosis at high risk for fractureApproved by FDA April 2017 (postmenopausal women); expanded June 2022 (men). Boxed warning for osteosarcoma. 2-year lifetime cumulative use limit.
• United KingdomUnknownNot confirmed as approved by MHRA post-Brexit as of last available data.

FDA approved in April 2017 (Tymlos) for postmenopausal women with osteoporosis at high fracture risk. Extended approval for men with osteoporosis in June 2022. Carries a boxed warning regarding osteosarcoma risk (based on rat studies), limiting cumulative use to 2 years over a lifetime.

Evidence & Sources

No sources recorded yet.