Bone Disease in Primary Hyperparathyroidism-Changes Occurring in Bone Metabolism and New Potential Treatment Strategies

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Nov 9

PMID 39519190

Authors

Mirella Iwanowska

Magdalena Kochman

Alicja Szatko

Wojciech Zgliczynski

Piotr Glinicki

Affiliations

Soon will be listed here.

Abstract

Primary hyperparathyroidism (PHPT) is a common endocrinopathy, predominantly caused by a single parathyroid adenoma that is responsible for the excessive secretion of parathyroid hormone (PTH)-the hallmark of disease. Excess of this hormone causes remarkable changes in bone metabolism, including an increased level of bone remodeling with a predominance of bone resorption. Those changes lead to deterioration of bone structure and density, especially in cortical bone. The main treatment for PHPT is surgical removal of the adenoma, which normalizes PTH levels and terminates the progression of bone disease and leads to its regeneration. However, because not all the patients are suitable candidates for surgery, alternative therapies are needed. Current non-surgical treatments targeting bone disease secondary to PHPT include bisphosphonates and denosumab. Those antiresorptives prevent further bone loss, but they lack the ability to regenerate already degraded bone. There is ongoing research to find targeted drugs capable of halting resorption alongside stimulating bone formation. This review presents the advancements in understanding the molecular mechanisms responsible for bone disease in PHPT and assesses the efficacy of new potential therapeutic approaches (e.g., allosteric inhibitors of the PTH receptor, V-ATPase, or cathepsin inhibitors) aimed at mitigating bone loss and enhancing bone regeneration in affected patients.

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