3 years ago

Optimal dosing and delivery of PTH and its analogues for osteoporosis and hypoparathyroidism – translating the pharmacology.

D. Tay, J.P. Bilezikian, S. Cremers
In primary hyperparathyroidism (PHPT), bone loss results from the resorptive effects of excess parathyroid hormone (PTH). Under physiological conditions, PTH has actions that are more targeted to homeostasis and to bone accrual. The predominant action of PTH, either catabolic, anabolic, or homeostatic, can be understood in molecular and pharmacokinetic terms. When administered intermittently, PTH increases bone mass, but when present continuously and in excess (e.g., PHPT), bone loss ensues. This dual effect of PTH depends not only on the dosing regimen, continuous or intermittent, but also on how the PTH molecule interacts with various states of its receptor (PTH/PTHrP receptor) influencing downstream signaling pathways differentially. Altering the amino-terminal end of PTH or PTHrP could emphasize the state of the receptor that is linked to an osteoanabolic outcome. This concept led to the development of a PTHrP analogue that interacts preferentially with the transiently linked state of the receptor emphasizing an osteoanabolic effect. On the other hand, designing PTH or PTHrP analogues with prolonged state of binding to the receptor would be expected to be linked to a homeostatic action associated with the tonic secretory state of the parathyroid glands that's advantageous in treating hypoparathyroidism. Ideally, further development of a drug delivery system that mimics the physiological tonic, circadian, and pulsatile profile of PTH would be optimal. This review discusses basic, translational and clinical studies that may well lead to newer approaches to the treatment of osteoporosis as well as to different PTH molecules that could become more advantageous in treating hypoparathyroidism.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/bcp.13455

You might also like
Never Miss Important Research

Researcher is an app designed by academics, for academics. Create a personalised feed in two minutes.
Choose from over 15,000 academics journals covering ten research areas then let Researcher deliver you papers tailored to your interests each day.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.