Therapy of hypoparathyroidism with PTH(1-84): a prospective four-year investigation of efficacy and safety

Abstract

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.

Figures

Fig. 1.

Changes in calcium and 1,25-dihydroxyvitamin D supplementation. Calcium requirements decreased by 6 months from baseline whereas 1,25-dihydroxyvitamin D requirements decreased by 36 months. Data are expressed as mean ± se. *, P < 0.05 compared with baseline; †, P < 0.01 compared with baseline.

Fig. 2.

Changes in serum calcium, urinary calcium, and serum phosphorus. Serum calcium was no different from baseline after 6 months through study conclusion. During the first 6 months of the study, there were small but significant increases from baseline within the normal range. Urinary calcium decreased significantly at months 12 and 36 and tended to be lower at 48 months. Serum phosphorus decreased and remained in the normal range throughout the study period. Data are expressed as mean ± se. *, P < 0.05 compared with baseline.

Fig. 3.

Changes in BMD. Lumbar spine BMD increased, whereas the total hip and femoral neck did not change and the distal one third radius BMD decreased. Data are expressed as mean ± se. *, P < 0.05 compared with baseline; ‡, P < 0.0001 compared with baseline.

Fig. 4.

Changes in markers of bone formation (P1NP, BALP, OCN; A) and resorption (CTX, TRAP; B) over 4 yr of PTH(1–84). With PTH(1–84) treatment, all bone turnover markers increased significantly, peaking up to 3-fold from baseline values at 6–12 months and subsequently declining to steady-state levels at 30 months. BALP, Bone-specific alkaline phosphatase; OCN, N-mid osteocalcin; CTX, collagen type 1 cross-linked C-telopeptide. Data are expressed as mean ± se. *, P < 0.05 compared with baseline; †, P < 0.01 compared with baseline; ‡, P < 0.0001 compared with baseline.