Abstract
Parathyroid hormone (PTH) is an 84-amino acid peptide produced by the parathyroid glands that regulate calcium homeostasis through actions on the kidney, intestine and bone. PTHs actions are mediated through a family of receptors that activate the adenylyl cyclase and/or phospholipase Cβ signaling pathways. These receptors are widely expressed and hence present opportunities for the development of therapeutics for a wide variety of indications. The clinical development of PTH is most advanced for the treatment of postmenopausal osteoporosis. Osteoporosis is a disease characterised by low bone mass, structural deterioration of bone and increased risk of fracture. All currently approved therapies for osteoporosis (e.g., estrogen, bisphosphonates, calcitonin and selective estrogen receptor modulators) are antiresorptive agents that suppress osteoclasts to allow osteoblasts to fill in existing remodelling space and prevent further bone loss. Intermittent, low-dose PTH therapy leads a new class of bone anabolic agents capable of going beyond just filling in existing remodelling space and building strong new bone in patients with established osteoporosis who are at high risk of fracturing. Recombinant hPTH-(1-34) (also called Teriparatide or Forteo™) has completed Phase III clinical trials and is under regulatory review by the United States Food and Drug Administration. The native hPTH-(1-84) and novel small PTH analogs are close behind in development. New data are emerging which suggest that injected PTHs may also be used to restore bone loss resulting from immobilisation, exposure to microgravity or excessive glucocorticoid use, and to promote fracture healing. Topical PTH is also being assessed as a treatment for psoriasis.
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