Current and Emerging Treatments For the Management of Hypoparathyroidism

Chronic hypoparathyroidism is a rare endocrine disorder marked by parathyroid hormone (PTH) deficiency, leading to hypocalcemia and its associated complications. Conventional therapy with oral calcium and active vitamin D fails to address the hormonal deficit and poses risks such as hypercalciuria and nephrocalcinosis. Recent advances in PTH replacement therapy have shifted the treatment paradigm. Palopegteriparatide, a long-acting prodrug of PTH (1–34), is now U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA)-approved, demonstrating effective calcium homeostasis, reduced reliance on conventional therapy, and potential renal benefits. Discontinuation of rhPTH (1–84) has accelerated interest in emerging alternatives such as eneboparatide, calcilytics (e.g., encaleret), MBX2109, and oral PTH1 receptor agonists. These novel therapies target PTH signalling through diverse mechanisms—offering injectable and oral options with improved safety, efficacy, and quality-of-life outcomes. This review synthesizes current evidence on approved and investigational treatments, underscoring their mechanisms, clinical impacts, and roles in personalized care for chronic hypoparathyroidism.