The search for calcium receptor antagonists (calcilytics)

Area of Science:

• Endocrinology
• Pharmacology
• Bone Biology

Background:

• The calcium-sensing receptor (CaR) on parathyroid cells regulates parathyroid hormone (PTH) secretion.
• CaR antagonists (calcilytics) can increase PTH levels, offering therapeutic potential.
• NPS 2143 is an orally active calcilytic that increases circulating PTH.

Purpose of the Study:

• To investigate the effects of calcilytic compounds, specifically NPS 2143, on PTH secretion and bone metabolism.
• To evaluate the potential of NPS 2143 as a therapeutic agent for bone loss conditions like osteoporosis.

Main Methods:

• Administration of NPS 2143 to ovariectomized, osteopenic rats.
• Assessment of plasma PTH levels and bone turnover markers.
• Evaluation of bone mineral density and trabecular bone volume.

Main Results:

• NPS 2143 rapidly increased circulating PTH levels by 3- to 4-fold.
• NPS 2143 treatment increased bone turnover in osteopenic rats.
• Combined administration with estradiol significantly enhanced bone mass and density, exceeding estradiol's effects alone.

Conclusions:

• Calcilytic compounds can stimulate endogenous PTH secretion to promote new bone formation.
• NPS 2143 demonstrates anabolic effects on bone without causing parathyroid gland hyperplasia.
• Calcilytics represent a potential alternative to exogenous PTH for osteoporosis treatment.