Hypoparathyroidism is a rare disorder in which parathyroid hormone (PTH) is markedly decreased or absent from the circulation. It is one of the few remaining hormone deficiency states for which replacement with the missing hormone has been heretofore unavailable. Without PTH, patients have abnormal calcium homeostasis characterized by hypocalcemia and high urinary calcium excretion. The current mainstay of therapy is calcium and vitamin D. This approach, however, has important clinical limitations. The large doses of calcium and vitamin D required are associated with risks of hypercalcemia, hypercalciuria and vitamin D toxicity. This approach also does not correct skeletal deficiencies due to lack of PTH. Because hypoparathyroidism is an orphan disease, investigators and funding agencies have all been reluctant to support the development of PTH as a therapy. Of the parathyroid hormone molecules that one might consider, the recent development of recombinant human PTH (1-84) is the most attractive because it is the native hormone, the very molecule that is missing in these individuals. Teriparatide [recombinant hPTH(1-34)] is another potential therapy but it is less attractive since it is an amino-terminal truncated form of PTH and would not provide the hypoparathyroid patient with native hormone. Although approved for osteoporosis, teriparatide has not been developed and is not approved for the treatment of hypoparathyroidism. Very little is known about the therapeutic effects of PTH (1-84) on calcium homeostasis in this population. Even less is known about the general quality of the skeleton in hypoparathyroidism and how it could be improved with PTH (1-84) therapy. This is an important concern, since in hypoparathyroidism, PTH deficiency is associated with markedly reduced bone turnover, a situation that can compromise bone strength. The major objective of this project is a therapeutic one, namely to determine whether PTH is an effective therapy for hypoparathyroidism. It builds upon data obtained from a smaller study funded, in part, by the FDA. By conducting a study that is now double-blinded and placebo controlled, the investigator expects to demonstrate clearly that PTH (1-84) treatment is a safe and effective way to overcome obstacles of management with calcium and vitamin D alone and to improve bone quality as well. With positive results from this trial with PTH (1-84), the investigator expects to be able to have the data reviewed by the FDA with the ultimate goal being approval of PTH (1-84) as a therapy for hypoparathyroidism. This sponsor-investigator expects PTH (1-84) to become the treatment of choice for this orphan disease.

Public Health Relevance

Bilezikian, John P. This project will continue and extend our ongoing investigation into the efficacy and safety of parathyroid hormone [PTH(1-84) for hypoparathyroidism, an orphan disease. We expect that data from this study will lead to approval of PTH(1-84) as a treatment for this disease. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page

National Institute of Health (NIH)
Food and Drug Administration (FDA)
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Special Emphasis Panel (ZFD1-OPD-N (S1))
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Columbia University (N.Y.)
Internal Medicine/Medicine
Schools of Medicine
New York
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Cusano, N E; Rubin, M R; Irani, D et al. (2013) Use of parathyroid hormone in hypoparathyroidism. J Endocrinol Invest 36:1121-7
Silva, B C; Costa, A G; Cusano, N E et al. (2011) Catabolic and anabolic actions of parathyroid hormone on the skeleton. J Endocrinol Invest 34:801-10
Costa, Aline G; Cremers, Serge; Rubin, Mishaela R et al. (2011) Circulating sclerostin in disorders of parathyroid gland function. J Clin Endocrinol Metab 96:3804-10
Bilezikian, J P; Rubin, M R; Finkelstein, J S (2005) Parathyroid hormone as an anabolic therapy for women and men. J Endocrinol Invest 28:41-9