title: Abaloparatide.
abstract: Abaloparatide is an investigational analog of human PTHrP (1-34) being developed for the treatment of osteoporosis. The amino-acid sequence of abaloparatide is identical to that of PTHrP in the first 20 amino-acids, while over half of the remaining amino-acids are different. Some studies in animals and in humans reported that abaloparatide presented a potent anabolic activity with reduced effects on bone resorption as compared to that observed with teriparatide. This may be due to a more transient signaling response of abaloparatide related to differing affinities of the two drugs to the specific conformations of the PTH1 receptor. In the ACTIVE study, a phase 3 fracture prevention trial, 2460 postmenopausal osteoporotic women at high risk for fracture were randomized to receive 18-months of either daily abaloparatide 80 μg s.c., placebo or teriparatide 20 μg s.c. The reduction in vertebral fracture rate with respect to placebo was 86% in the abaloparatide group and 80% in the teriparatide group. Abaloparatide also produced a significant 43% reduction in the rate of nonvertebral fractures (2.7vs4.0% with placebo, p=0.04) whereas teriparatide determined a 28% reduction (2.9vs4.0% with placebo, p=NS). Abaloparatide or teriparatide showed similar increases in BMD at lumbar spine, while the patients of the abaloparatide group showed significantly greater increases in BMD at both total hip (4.18vs3.26%) and femoral neck (3.60vs2.66%). Therefore, if the preliminary data of the ACTIVE study is confirmed, abaloparatide may become an important option for the anabolic treatment of postmenopausal osteoporosis.
authors.affiliation: Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gonnelli
authors.affiliation: Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Caffarelli
keywords: PTHrP analogs; abaloparatide; anabolics; osteoporosis