Current and Emerging Treatments For the Management of Hypoparathyroidism

Sarah Khan; Aliya Khan

doi:10.58931/cdet.2025.3241

Authors

Sarah Khan, MD, FRCPC Trillium Health Partners, University of Toronto, Toronto, Ontario, Canada
Aliya Khan, MD, FRCPC, FACP, FACE, FASBMR Professor of Clinical Medicine, McMaster University, Hamilton, Ontario, Canada

DOI:

https://doi.org/10.58931/cdet.2025.3241

Abstract

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.

Author Biographies

Sarah Khan, MD, FRCPC, Trillium Health Partners, University of Toronto, Toronto, Ontario, Canada

Dr. Sarah Khan, MD, FRCPC is a staff clinician at the Bone Research and Education Clinic (BREC) and at Credit Valley Hospital (Trillium Health Partners). She graduated from the University of Toronto School of Medicine in 2015. She went on to complete her Internal Medicine Residency and Endocrinology Fellowship at the University of Toronto (UofT). She has a keen interest in treating patients with metabolic bone diseases at BREC. Outside of clinical work she is actively partaking as a
co-investigator in clinical trials to investigate new treatment options for patients with hypoparathyroidism. She is also pursing her Master of Education at the Ontario Institute of Studies in Education (OISE) at University of Toronto.

Aliya Khan, MD, FRCPC, FACP, FACE, FASBMR, Professor of Clinical Medicine, McMaster University, Hamilton, Ontario, Canada

Dr. Aliya Khan is a Clinical Professor of Medicine in the Division of Endocrinology and Geriatrics at McMaster University, Director of the Calcium Disorders Clinic, and Director of the Fellowship in Metabolic Bone Disease at McMaster University. She graduated from the University of Ottawa Medical School with honors. She trained in Internal Medicine, Geriatric Medicine and Endocrinology and completed a fellowship in Metabolic Bone Disease at the University of Toronto. She has published over 400 scientific papers and numerous chapters and books on osteoporosis and parathyroid disease. Dr. Khan led the development of global guidelines for parathyroid disease, osteonecrosis of the jaw, new diagnostic criteria for hypophosphatasia, treatment guidelines for X-linked hypophosphatemia in addition to Canadian guidelines for osteoporosis. She is the co-chair for developing international best practice recommendations on bone mineral density reporting supported by the 10 international scientific societies including ISCD, IOF and, Radiologic Society of North America. She is a clinician researcher and is the principal investigator evaluating novel therapies for parathyroid disease including PTH and PTH analogues as well PTH1 receptor agonists for the treatment of hypoparathyroidism including palopegteriparatide, natpara, eneboparatide as well as the calcilytic molecule encalaret for the treatment of autosomal dominant hypocalcemia, and cinacalcet for the medical management of primary hyperparathyroidism. She has received numerous national and international awards including the Queen’s Diamond Jubilee Medal for excellence, International Hypoparathyroidism Award, International Osteoporosis Foundation award for publishing excellence and recognized by Osteoporosis Canada for outstanding contributions to research and education. In 2024 she was the recipient of the Woman Physician of the Year Award by the American College of Physicians (ACP) honoring an outstanding woman physician with a distinguished career in areas of exceptional patient care, medical education and/or research. She also received the ACP Humanitarian of the Year Award given for outstanding contributions to humanism in medicine in 2024. In 2024 she received the Canadian Society of Endocrinology and Metabolism Dr. Jacques Genest Lecture Award. In December 2024 she was awarded the ORTOMED Medal from the Italian Society of Ortopedia e Medicina for outstanding contributions to metabolic bone disease. She is recognized as being in the top 0.1% of the world experts in hyperparathyroidism by Expertscape.

References

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Current and Emerging Treatments For the Management of Hypoparathyroidism

Authors

DOI:

Abstract

Author Biographies

Sarah Khan, MD, FRCPC, Trillium Health Partners, University of Toronto, Toronto, Ontario, Canada

Aliya Khan, MD, FRCPC, FACP, FACE, FASBMR, Professor of Clinical Medicine, McMaster University, Hamilton, Ontario, Canada

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