PTH(1-84) replacement therapy for the treatment of hypoparathyroidism

Abstract

Hypoparathyroidism is a rare disease characterized by hypocalcemia and insufficient circulating levels of parathyroid hormone (PTH). Conventional therapy includes calcium and active vitamin D supplementation, often in large doses. Therapy with calcium and vitamin D, however, does not address certain problematic aspects of the disease, including abnormal bone metabolism and reduced quality of life. Hypoparathyroidism is the only classic endocrine deficiency disease for which the missing hormone, PTH, is not yet an approved treatment. PTH(1-84) may soon become a therapeutic option for patients with hypoparathyroidism. PTH(1-84) has been demonstrated to maintain serum calcium while reducing or eliminating requirements for calcium and active vitamin D supplementation. Data from bone densitometry, bone turnover markers and histomorphometry of bone biopsy specimens show positive structural and dynamic effects on the skeleton. PTH replacement therapy may also be associated with improved quality of life. PTH(1-84) replacement therapy for hypoparathyroidism is promising, although further acquisition of long-term data is needed.

Keywords:

• hypoparathyroidism
• natpara
• parathyroid
• parathyroid hormone
• PTH(1-84)

Financial & competing interests disclosure

The authors would like to acknowledge the following funding sources: National Institutes of Health grants DK069350 and DK095944 and Food and Drug Administration grant 002525. MR Rubin receives research support from NPS Pharmaceuticals. JP Bilezikian is a consultant for Eli Lilly, NPS Pharmaceuticals, Merck and Amgen and receives research support from NPS Pharmaceuticals and Amgen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Hypoparathyroidism is the only classic endocrine deficiency disease for which the missing hormone, parathyroid hormone (PTH), is not yet an approved treatment.

• PTH(1-84) is a promising therapeutic option for patients with hypoparathyroidism.

• PTH(1-84) therapy has been demonstrated to decrease calcium and active vitamin D requirements while maintaining serum calcium and to improve the abnormal bone remodeling state in subjects with hypoparathyroidism.

• Given the chronic nature of the disease and the need for ongoing PTH therapy, further long-term data are necessary.