Hypoparathyroidism: a review of clinical trials and recent approvals

Hypoparathyroidism is a rare endocrine disorder caused by deficient secretion or action of parathyroid hormone (PTH), leading to hypocalcaemia, hyperphosphataemia, and disrupted calcium-phosphate homeostasis. Postsurgical hypoparathyroidism is the most common form, whereas autoimmune, genetic, metabolic, and infiltrative causes are less frequent. Chronic PTH deficiency is associated with renal, skeletal, neuromuscular, ocular, and soft tissue complications that impair quality of life.

Conventional treatment with oral calcium and active vitamin D corrects hypocalcaemia but fails to replace the physiological actions of PTH on the kidney and skeleton. Consequently, patients may develop hypercalciuria, nephrocalcinosis, and persistent symptoms. Recent advances in PTH replacement therapy have shifted management toward hormone replacement. Recombinant PTH formulations and long-acting agents, particularly palopegteriparatide (TransCon PTH), have demonstrated improved biochemical control, reduced reliance on calcium and vitamin D supplementation, lower urinary calcium excretion, restoration of bone turnover, and better patient-reported outcomes. Other investigational therapies, including eneboparatide, MBX 2109, and calcilytics, are expanding the therapeutic landscape.

This review summarizes the epidemiology, pathophysiology, clinical manifestations, complications, and current management of hypoparathyroidism, highlighting emerging therapies designed to restore physiological PTH activity and improve long-term clinical outcomes.