Therapy of hypoparathyroidism with intact parathyroid hormone

Abstract

Hypoparathyroidism, a disorder characterized by low parathyroid hormone (PTH), is generally treated with oral calcium and vitamin D supplementation. We investigated the effects of PTH(1-84) treatment in 30 hypoparathyroid subjects for 24 months. PTH(1-84) treatment in hypoparathyroidism significantly reduced supplemental calcium and 1,25-dihydroxyvitamin D requirements without generally altering serum and urinary calcium levels.

Introduction: Hypoparathyroidism, a disorder characterized by low PTH, is associated with hypocalcemia, hypercalciuria, and increased bone mineral density (BMD). Conventional therapy with calcium and 1,25-dihydroxyvitamin D can maintain the serum calcium concentration, but doses are high, and control is variable. We investigated the effects of human PTH(1-84) treatment in hypoparathyroidism.

Methods: Thirty subjects with hypoparathyroidism were treated in an open-label study of PTH(1-84) 100 µg every other day by subcutaneous injection for 24 months, with monitoring of calcium and vitamin D supplementation requirements, serum and 24 h urinary calcium excretion, and BMD by dual energy X-ray absorptiometry.

Results: Requirements for supplemental calcium decreased significantly (3,030±2,325 to 1,661±1,267 mg/day (mean±SD); p<0.05), as did requirements for supplemental 1,25-dihydroxyvitamin D (0.68±0.5 to 0.40±0.5 µg/day; p<0.05). Serum calcium levels and 24 h urinary calcium excretion were mostly unchanged at 24 months. BMD increased at the lumbar spine by 2.9±4% from baseline (p<0.05), while femoral neck BMD remained unchanged and distal one third radial BMD decreased by 2.4±4% (p<0.05).

Conclusion: PTH(1-84) treatment in hypoparathyroidism significantly reduces supplemental calcium and 1,25-dihydroxyvitamin D requirements without generally altering serum and urinary calcium levels.

Figures

Fig. 1

Changes in turnover markers in dosing study in five patients. The five patients were assigned to either PTH(1–84) 100 μg every day (n=2), every other day (n=2), or every third day (n=1) for 6 months. a Change in bone formation markers. b Change in bone resorption markers

Fig. 2

Changes in calcium and 1,25-dihydroxyvitamin D supplementation. Calcium requirements decreased at 3, 9, 12, 18, and 24 months from baseline while 1,25-dihydroxyvitamin D requirements decreased by 1 month. Data are mean±SD; *p

Fig. 3

Changes in serum calcium, serum phosphate, and urinary calcium. Serum calcium increased at months 2 to 6 but was no different from baseline at 1, 9, 12, 18, and 24 months. Serum phosphate decreased into the normal range at month 3 and remained in the normal range through 24 months. The shaded area shows the normal ranges of serum calcium and phosphate. Urinary calcium increased at 3 months but, otherwise, did not change. The heavier and lighter dashed lines shows the upper limit of normal urinary calcium levels in men and women, respectively. Data are mean±SD; *p<0.05 as compared to baseline

Fig. 4

Changes in bone mineral density. Lumbar spine bone mineral density (BMD) increased, while the femoral neck did not change and the distal one third radius BMD decreased. Data are mean±SD; *p< 0.05 as compared to baseline