Therapy of Hypoparathyroidism With rhPTH(1-84): A Prospective, 8-Year Investigation of Efficacy and Safety

Abstract

Context: Conventional treatment of hypoparathyroidism is associated with decreased renal function and increased bone mineral density (BMD).

Objective: To evaluate the effects of 8 years of recombinant human parathyroid hormone (1-84) [rhPTH(1-84)] therapy on key biochemical and densitometric indices.

Design: Prospective open-label trial.

Setting: Tertiary medical center.

Participants: Twenty-four subjects with hypoparathyroidism.

Intervention: Treatment with rhPTH(1-84) for 8 years.

Main outcome measures: Supplemental calcium and vitamin D requirements, serum calcium and phosphorus levels, calcium-phosphate product, urinary calcium excretion, estimated glomerular filtration rate (eGFR) and BMD.

Results: PTH therapy was associated with progressive reduction in supplemental calcium (57%; P < 0.01) and active vitamin D (76%; P < 0.001) requirements over 8 years. Serum calcium concentration was stable; urinary calcium excretion declined 38% (P < 0.01). eGFR remained stable and was related to baseline eGFR and serum calcium levels. Calcium-phosphate product was below the recommended limit; serum phosphorus remained within normal range. Lumbar spine and total hip BMD increased, peaking at 4 (mean ± SE, 4.6% ± 1.5%; P = 0.01) and 8 years (2.6% ± 1.1%; P = 0.02), whereas femoral neck BMD did not change and one-third radius BMD decreased (mean ± SE, -3.5% ± 1.1%; P = 0.001). BMD at all sites was higher throughout the 8 years than in the age- and sex-matched reference population. Hypercalcemia and hypocalcemia were uncommon.

Conclusion: rhPTH(1-84) is a safe and effective treatment for hypoparathyroidism for 8 years. Long-term reductions in supplemental requirements and biochemical improvements with stable renal function are maintained.

Trial registration: ClinicalTrials.gov NCT02910466.

Copyright © 2019 Endocrine Society.

Figures

Figure 1.

Annual changes in key clinical and biochemical indices. Changes are shown in serum calcium and phosphate levels, calcium-phosphate product, calcium supplemental dose, calcitriol supplemental dose, and hydrochlorothiazide dose over the 8-y study duration. *P < 0.05 vs baseline; **P < 0.01 vs baseline. HCTZ, hydrochlorothiazide.

Figure 2.

Annual changes in renal indices. Changes are shown in serum creatinine level, estimated glomerular filtration rate (eGFR; according to the Modification of Diet in Renal Disease equation), and urinary calcium excretion over the 8-year study duration. *P < 0.05 vs baseline; **P < 0.01 vs baseline.

Figure 3.

Annual changes in skeletal densitometric indices. Changes are shown in lumbar spine, total hip, femoral neck, and one-third radius over the 8-y study duration. *P < 0.05 vs baseline; **P < 0.01 vs baseline.