Replacement Therapy with PTH(1–84)

  • Mishaela R. Rubin
  • Natalie E. Cusano
  • John P. BilezikianEmail author


Hypoparathyroidism, a rare disorder of mineral metabolism, is characterized biochemically by low serum calcium and low or undetectable parathyroid hormone (PTH) levels. Conventional therapy of hypoparathyroidism attempts to address these abnormalities by treatment with large, pharmacologic dosages of oral calcium, parent vitamin D, and/or active vitamin D. Yet there has been a clear need to improve the management of hypoparathyroidism with an approach that goes beyond the use of pharmacologic amounts of calcium and vitamin D. Hypoparathyroidism is the only classic hormone deficiency state for which approved replacement therapy is not available. Studies conducted over the past decade have investigated the use of PTH(1–84), the full length, native PTH molecule, as a therapy of hypoparathyroidism. The data from these studies indicate that PTH(1–84) is able to address many of the biochemical, renal, skeletal, and neuropsychological features of hypoparathyroidism to a greater extent than conventional treatment.


Hypoparathyroidism PTH(1–84) Serum calcium Quality of life Hypercalciuria Bone mineral density Bone turnover Histomorphometry 


  1. 1.
    Bilezikian JP, Khan A, Potts JT Jr et al (2011) Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research. J Bone Miner Res 26(10):2317–2337CrossRefPubMedCentralPubMedGoogle Scholar
  2. 2.
    Powers J, Joy K, Ruscio A, Lagast H (2013) Prevalence and incidence of hypoparathyroidism in the United States using a large claims database. J Bone Miner Res 28(12):2570–2576CrossRefPubMedGoogle Scholar
  3. 3.
    Winer KK, Yanovski JA, Cutler GB Jr (1996) Synthetic human parathyroid hormone 1–34 vs calcitriol and calcium in the treatment of hypoparathyroidism. JAMA 276(8):631–636CrossRefPubMedGoogle Scholar
  4. 4.
    Winer KK, Yanovski JA, Sarani B, Cutler GB Jr (1998) A randomized, cross-over trial of once-daily versus twice-daily parathyroid hormone 1–34 in treatment of hypoparathyroidism. J Clin Endocrinol Metab 83(10):3480–3486PubMedGoogle Scholar
  5. 5.
    Winer KK, Ko CW, Reynolds JC et al (2003) Long-term treatment of hypoparathyroidism: a randomized controlled study comparing parathyroid hormone-(1–34) versus calcitriol and calcium. J Clin Endocrinol Metab 88(9):4214–4220CrossRefPubMedGoogle Scholar
  6. 6.
    Winer KK, Sinaii N, Peterson D, Sainz B Jr, Cutler GB Jr (2008) Effects of once versus twice-daily parathyroid hormone 1–34 therapy in children with hypoparathyroidism. J Clin Endocrinol Metab 93(9):3389–3395CrossRefPubMedCentralPubMedGoogle Scholar
  7. 7.
    Winer KK, Sinaii N, Reynolds J, Peterson D, Dowdy K, Cutler GB Jr (2010) Long-term treatment of 12 children with chronic hypoparathyroidism: a randomized trial comparing synthetic human parathyroid hormone 1–34 versus calcitriol and calcium. J Clin Endocrinol Metab 95(6):2680–2688CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Sikjaer T, Rejnmark L, Rolighed L, Heickendorff L, Mosekilde L (2011) The effect of adding PTH(1–84) to conventional treatment of hypoparathyroidism: a randomized, placebo-controlled study. J Bone Miner Res 26(10):2358–2370CrossRefPubMedGoogle Scholar
  9. 9.
    Mannstadt M, Clarke BL, Vokes T et al (2013) Efficacy and safety of recombinant human parathyroid hormone (1–84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study. Lancet Diabetes Endocrinol 1(4):275–283CrossRefPubMedGoogle Scholar
  10. 10.
    Cusano NE, Rubin MR, McMahon DJ et al (2013) Therapy of hypoparathyroidism with PTH(1–84): a prospective four-year investigation of efficacy and safety. J Clin Endocrinol Metab 98(1):137–144CrossRefPubMedCentralPubMedGoogle Scholar
  11. 11.
    Product Monograph: Forteo (2004) Eli Lilly, CanadaGoogle Scholar
  12. 12.
    Sikjaer T, Rejnmark L, Mosekilde L (2011) PTH treatment in hypoparathyroidism. Curr Drug Saf 6(2):89–99CrossRefPubMedGoogle Scholar
  13. 13.
    Fox J, Wells D, Garceau R (2011) Relationships between pharmacokinetic profile of human PTH(1–84) and serum calcium response in postmenopausal women following 4 different methods of administration. J Bone Miner Res 26(Suppl 1)Google Scholar
  14. 14.
    Sikjaer T, Amstrup AK, Rolighed L, Kjaer SG, Mosekilde L, Rejnmark L (2013) PTH(1–84) replacement therapy in hypoparathyroidism: a randomized controlled trial on pharmacokinetic and dynamic effects after 6 months of treatment. J Bone Miner Res 28(10):2232–2243CrossRefPubMedGoogle Scholar
  15. 15.
    Cusano NE, Rubin MR, McMahon DJ et al (2013) The effect of PTH(1–84) on quality of life in hypoparathyroidism. J Clin Endocrinol Metab 98(6):2356–2361CrossRefPubMedCentralPubMedGoogle Scholar
  16. 16.
    Sikjaer T, Rolighed L, Hess A, Fuglsang-Frederiksen A, Mosekilde L, Rejnmark L (2014) Effects of PTH(1–84) therapy on muscle function and quality of life in hypoparathyroidism: results from a randomized controlled trial. Osteoporos Int 25(6):1717–1726CrossRefPubMedGoogle Scholar
  17. 17.
    Mitchell DM, Regan S, Cooley MR et al (2012) Long-term follow-up of patients with hypoparathyroidism. J Clin Endocrinol Metab 97(12):4507–4514CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Underbjerg L, Sikjaer T, Mosekilde L, Rejnmark L (2013) Cardiovascular and renal complications to postsurgical hypoparathyroidism: a Danish nationwide controlled historic follow-up study. J Bone Miner Res 28(11):2277–2285CrossRefPubMedGoogle Scholar
  19. 19.
    Sikjaer T, Rejnmark L, Thomsen JS et al (2012) Changes in 3-dimensional bone structure indices in hypoparathyroid patients treated with PTH(1–84): a randomized controlled study. J Bone Miner Res 27(4):781–788CrossRefPubMedGoogle Scholar
  20. 20.
    Lindsay R, Cosman F, Zhou H et al (2006) A novel tetracycline labeling schedule for longitudinal evaluation of the short-term effects of anabolic therapy with a single iliac crest bone biopsy: early actions of teriparatide. J Bone Miner Res 21(3):366–373CrossRefPubMedGoogle Scholar
  21. 21.
    Rubin MR, Dempster DW, Sliney J Jr et al (2011) PTH(1–84) administration reverses abnormal bone-remodeling dynamics and structure in hypoparathyroidism. J Bone Miner Res 26(11):2727–2736CrossRefPubMedCentralPubMedGoogle Scholar
  22. 22.
    Rubin M, Zwahlen A, Dempster D et al (2013) PTH(1–84) administration alters three dimensional cancellous bone structure in hypoparathyroidism. J Bone Miner Res (Supp 1). Accessed Oct 2013
  23. 23.
    Watanabe A, Yoneyama S, Nakajima M et al (2012) Osteosarcoma in Sprague-Dawley rats after long-term treatment with teriparatide (human parathyroid hormone (1–34)). J Toxicol Sci 37(3):617–629CrossRefPubMedGoogle Scholar
  24. 24.
    Jolette J, Wilker CE, Smith SY et al (2006) Defining a noncarcinogenic dose of recombinant human parathyroid hormone 1–84 in a 2-year study in Fischer 344 rats. Toxicol Pathol 34(7):929–940CrossRefPubMedGoogle Scholar
  25. 25.
    Andrews EB, Gilsenan AW, Midkiff K et al (2012) The US postmarketing surveillance study of adult osteosarcoma and teriparatide: study design and findings from the first 7 years. J Bone Miner Res 27(12):2429–2437CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2015

Authors and Affiliations

  • Mishaela R. Rubin
    • 1
  • Natalie E. Cusano
    • 1
  • John P. Bilezikian
    • 1
    Email author
  1. 1.Metabolic Bone Disease Unit, Columbia University Medical Center, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA

Personalised recommendations