Abaloparatide, a PTHrP analogon, is a peptide that selectively binds to the RG conformation of the parathyroid hormone type 1 receptor. As a result of its mechanism of action, it was hypothesized that abaloparatide would have a more pronounced anabolic action on bone compared with teriparatide. Abaloparatide has the potential to reduce both nonvertebral and vertebral fractures and to improve BMD in postmenopausal women with osteoporosis, regardless of age, prior fracture history, or BMD score, with a well-tolerated side effect profile. Based on the pivotal trials, abaloparatide has demonstrated noninferiority to teriparatide regarding the increase in BMD at the lumbar spine and the reduction of vertebral fracture risk, whereas it has demonstrated a greater increase in BMD at the femoral sites. Abaloparatide use is not recommended in patients who are at increased risk of osteosarcoma, Paget’s disease of the bone or unexplained elevations of alkaline phosphatase, open epiphyses, bone metastases or skeletal malignancies, hereditary disorders predisposing to osteosarcoma, or prior external beam or implant radiation therapy involving the skeleton.
On April 28, 2017, abaloparatide was approved by the FDA for subcutaneous injection for postmenopausal women with osteoporosis at high risk for fracture due to a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have not responded to or are intolerant to other available osteoporosis therapy. The recommended dose is 80 μg administered subcutaneously once daily. As of November 2023, The EMA’s Committee for Medicinal Products for Human Use also recommended approval of abaloparatide for treating osteoporosis in postmenopausal women at increased risk for fracture.
Further studies are needed to determine the long-term safety and efficacy of abaloparatide administration after a course of antiresorptive therapy (e.g., denosumab or bisphosphonates). An anabolic agent with less resorptive stimulation might address the unmet needs of a large group of osteoporotic patients who warrant more potent anti-osteoporotic treatment.