Handling Parathormone Receptor Type 1 in Skeletal Diseases: Realities and Expectations of Abaloparatide.

Musculoskeletal disorders represent an elevated socioeconomic burden for developed aging societies. Osteoporosis (OP) has been treated with antiresorptive therapies or with teriparatide that was until recently the only anabolic therapy. However, approval of osteoporosis treatment in postmenopausal women with abaloparatide, which is an analog of parathyroid hormone-related peptide (PTHrP), has created a new alternative for OP management. The success of this new treatment is related to differential mechanisms of activation of PTH receptor type 1 (PTH1R) by abaloparatide and PTH. Here, we address the distinguishing mechanisms of PTH1R activation; the effects of PTH1R stimulation in osteoblast, osteocytes, and chondrocytes; the differences between PTH and abaloparatide actions on PTH1R; potential safety concerns; and future perspectives about abaloparatide use in other musculoskeletal disorders. Management of musculoskeletal disorders such as osteoporosis and osteoarthritis are a major challenge for developed countries associated with a high socioeconomic burden given the high prevalence of these diseases and the aging population. Treatment of osteoporosis has been addressed by anabolic or antiresorptive therapies. Abaloparatide, a peptide that signals through the parathormone 1 receptor (PTH1R) has been recently added to the armamentarium of bone anabolic therapies. Selective activation of PTH1R is the key of abaloparatide success in decreasing risk of fracture and increasing bone mineral density in postmenopausal women. Use of abaloparatide might be extended to other musculoskeletal disorders. [ABSTRACT FROM AUTHOR]