Abstract :After fifteen years of studies, in 2017 the Food and Drug Administration approved a new
osteoanabolic drug, Abaloparatide (ABL), with the indication of the treatment of post-menopausal
osteoporosis in women at high risk of fracture, i.e. with history of fragility fracture, multiple risk factors
or unable to assume other anti-osteoporosis drugs for intolerance or inefficacy [1]. Abaloparatide
is recombinant human parathyroid hormone-related peptide 1–34 [rhPTH (1-34)], developed by
Radius Health, with 71% homology with Parathyroid Hormone-related Peptide (PTHrP) (1-34) and
41% homology to PTH (1-34) [1-3]. Compared to PTH and PTHrP ligands, ABL presents a higher
affinity and greater selectivity for the G protein-dependent receptor conformation of PTHR1 [3]. This
provides Abaloparatide particular pharmacodynamic features with a stronger anabolic effect and a
modest stimulation of bone resorption compared to its analogous teriparatide (TPTD) [1]. The FDA
approval of Abaloparatide derives from the results of ACTIVE (Abaloparatide Comparator Trial
in Vertebral Endpoints, trial registration NCT 01343004) and ACTIV Extend trials. The ACTIVE
phase 3 trial [1], assessing the efficacy and safety of Abaloparatide (80 µg daily subcutaneous) vs.
placebo during 18 months in postmenopausal osteoporosis, showed that Abaloparatide increases
bone mineral density and reduces major osteoporotic fractures better and with a more rapid onset
of action than TPTD (20 µg daily subcutaneous), which was used as an open label active comparator
(i.e. a drug that this currently marketed for managing PMO) [2].