Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism

J Clin Endocrinol Metab. 2019 Nov 1;104(11):5136-5147. doi: 10.1210/jc.2019-01010.


Context: Conventional hypoparathyroidism treatment with oral calcium and active vitamin D is aimed at correcting hypocalcemia but does not address other physiologic defects caused by PTH deficiency.

Objective: To evaluate long-term safety and tolerability of recombinant human PTH (1-84) [rhPTH(1-84)].

Design: Open-label extension study; 5-year interim analysis.

Setting: 12 US centers.

Patients: Adults (N = 49) with chronic hypoparathyroidism.

Intervention(s): rhPTH(1-84) 25 or 50 µg/d initially, with 25-µg adjustments permitted to a 100 µg/d maximum.

Main outcome measure(s): Safety parameters; composite efficacy outcome was the proportion of patients with ≥50% reduction in oral calcium (or ≤500 mg/d) and calcitriol (or ≤0.25 µg/d) doses, and albumin-corrected serum calcium normalized or maintained compared with baseline, not exceeding upper limit of normal.

Results: Forty patients completed 60 months of treatment. Mean albumin-corrected serum calcium levels remained between 8.2 and 8.7 mg/dL. Between baseline and month 60, levels ± SD of urinary calcium, serum phosphorus, and calcium-phosphorus product decreased by 101.2 ± 236.24 mg/24 hours, 1.0 ± 0.78 mg/dL, and 8.5 ± 8.29 mg2/dL2, respectively. Serum creatinine level and estimated glomerular filtration rate were unchanged. Treatment-emergent adverse events (AEs) were reported in 48 patients (98.0%; hypocalcemia, 36.7%; muscle spasms, 32.7%; paresthesia, 30.6%; sinusitis, 30.6%; nausea, 30.6%) and serious AEs in 13 (26.5%). At month 60, 28 patients (70.0%) achieved the composite efficacy outcome. Bone turnover markers increased, peaked at ∼12 months, and then declined to values that remained above baseline.

Conclusion: Treatment with rhPTH(1-84) for 5 years demonstrated a safety profile consistent with previous studies and improved key biochemical parameters.

Trial registration: NCT01297309.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Calcitriol / therapeutic use
  • Calcium / blood
  • Calcium / therapeutic use
  • Calcium, Dietary / therapeutic use
  • Female
  • Hormone Replacement Therapy / adverse effects*
  • Hormone Replacement Therapy / methods*
  • Humans
  • Hypoparathyroidism / drug therapy*
  • Male
  • Middle Aged
  • Parathyroid Hormone / adverse effects*
  • Parathyroid Hormone / therapeutic use*
  • Recombinant Proteins
  • Treatment Outcome


  • Calcium, Dietary
  • Parathyroid Hormone
  • Recombinant Proteins
  • Calcitriol
  • Calcium

Associated data