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

Trends Endocrinol Metab. 2019 Oct;30(10):756-766. doi: 10.1016/j.tem.2019.07.014. Epub 2019 Aug 11.

Abstract

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.

Keywords: abaloparatide; bone; musculoskeletal disorders; osteoporosis; parathyroid hormone; parathyroid hormone related peptide.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Female
  • Humans
  • Middle Aged
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteocytes / drug effects
  • Osteocytes / metabolism
  • Osteoporosis / drug therapy
  • Osteoporosis / metabolism
  • Osteoporosis, Postmenopausal / drug therapy
  • Osteoporosis, Postmenopausal / metabolism
  • Parathyroid Hormone-Related Protein / therapeutic use*
  • Receptor, Parathyroid Hormone, Type 1 / metabolism*
  • Teriparatide / therapeutic use

Substances

  • Parathyroid Hormone-Related Protein
  • Receptor, Parathyroid Hormone, Type 1
  • Teriparatide
  • abaloparatide