Therapy of Hypoparathyroidism with PTH(1–84): A Prospective Four-Year Investigation of Efficacy and Safety

Context: PTH may be an effective treatment option for hypoparathyroidism, but long-term data are not available. Objective: We studied the effect of 4 yr of PTH(1–84) treatment in hypoparathyroidism. Design: Twenty-seven subjects were treated with PTH(1–84) for 4 yr, with prospective monitoring of calcium and vitamin D requirements, serum and urinary calcium, serum phosphorus, bone turnover markers, and bone mineral density (BMD). Results: Treatment with PTH(1–84) reduced supplemental calcium requirements by 37% (P = 0.006) and 1,25-dihydroxyvitamin D requirements by 45% (P = 0.008). Seven subjects (26%) were able to stop 1,25-dihydroxyvitamin D completely. Serum calcium concentration remained stable, and urinary calcium and phosphorus excretion fell. Lumbar spine BMD increased by 5.5 ± 9% at 4 yr (P < 0.0001). Femoral neck and total hip BMD remained stable. At 4 yr, distal radius BMD was not different from baseline. Bone turnover markers increased significantly, reaching a 3-fold peak from baseline values at 6–12 months (P < 0.05 for all), subsequently declining to steady-state levels at 30 months. Hypercalcemia was uncommon (11 episodes in eight subjects over 4 yr; 1.9% of all values), with most episodes occurring within the first 6 months and resolving with adjustment of supplemental calcium and vitamin D. Conclusions: PTH(1–84) treatment of hypoparathyroidism for up to 4 yr maintains the serum calcium concentration, while significantly reducing supplemental calcium and 1,25-dihydroxyvitamin D requirements. Lumbar spine BMD increases without significant changes at other sites. These data provide support for the safety and efficacy of PTH(1–84) therapy in hypoparathyroidism for up to 4 yr.