Hypoparathyroidism and treatment with recombinant human PTH

ABSTRACT

Introduction: Hypoparathyroidism is a rare endocrine disease, most frequently due to surgical damage to the parathyroids. Hypocalcemia, caused by this disease, can affect the function of most organs, but in particular neurological, cognitive, muscular, and cardiac functions. The long term consequences of hypoparathyroidism can include ectopic calcifications, renal complications and impaired quality of life. At last, in hypoparathyroidism higher bone mineral density and lower bone turnover markers are described, and these factors could have an impact on the risk of fracture, but still it is unclear.

Areas covered: This disease is usually treated with calcium, calcitriol, or an active vitamin D analog. Although the standard therapy can adequately control patients, sometimes very high doses are required to maintain serum calcium levels in the normal range, with poor compliance and risk of long term complications. This article analyzes the recent therapeutic approach with the use of recombinant human PTH (rhPTH), through a systematic review of English articles regarding the use of rhPTH (1–84) and (1–34).

Expert opinion: The possibility of having a therapeutic alternative, such as the rhPTH could represent a great opportunity. However, further studies are necessary to clarify several aspects especially regarding long term effects of rhPTH.

KEYWORDS:

• Hypoparathyroidism
• therapy
• parathyroid hormone
• rhPTH (1-84)
• PTH (1-84)
• rhPTH (1-34)
• PTH (1-84)

Article highlights

• Hypoparathyroidism is an endocrine disease characterized by hypocalcemia and hyperphosphatemia in presence of undetectable or inappropriately low levels of parathyroid hormone (PTH).

• Conventional treatment of chronic hypoparathyroidism consists mainly of calcium supplements and calcitriol, whose chronic use at high dose can lead to long-term complications, particularly renal impairment and ectopic calcifications.

• Several studies have recently investigated hormone replacement therapy with rhPTH (1-34) and rhPTH (1-84), as treatment for patients with chronic hypoparathyroidism not adequately controlled with standard treatment.

• Some studies demonstrated that injections twice-a-day of rhPTH (1-34) showed a good control of mean serum calcium levels, a reduction in the need for calcium and active vitamin D supplements, but did not obtain a significant reduction in 24-hour urinary calcium excretion compared to standard therapy. Moreover, the studies with rhPTH (1-34) therapy delivered by an infusion pump showed, instead, a near normalization of the diurnal rhythm of serum calcium, and a significant reduction of 24-hour urinary calcium excretion, compared with twice-a-day injections subcutaneous of rhPTH (1-34).

• rhPTH (1-84) provides the natural hormone, lacking in this disorder, and has an effective half-life longer than rhPTH (1-34). The studies showed that this drug permits a reduction in the need for calcium and active vitamin D supplements, maintaining normal mean serum calcium levels compared to conventional therapy, a reduction in 24-hour urinary calcium excretion at 24 weeks compared to baseline (‘REPLACE’ trial), and showed significant transient reductions of 24-hour urinary calcium excretion in long term study (6 years) compared to baseline.

• Several future investigations are necessary regarding evaluation of long-term efficacy and safety of rhPTH treatment.

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Declaration of interest

ML Brandi is a consultant for Alexion, Abiogen, Amgen, Bruno Farmaceutici, Eli Lilly, Merck, Shire Pharmaceuticals, SPA and Servier. She receives research support from Shire Pharmaceuticals, Amgen, Eli Lilly, and Merck. 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.

Additional information

Funding

This paper was not funded.