Long-Term Parathyroid Hormone 1-34 Replacement Therapy in Children with Hypoparathyroidism.

OBJECTIVE: To determine whether multiple daily injections of parathyroid hormone (PTH) 1-34 are safe and effective as long-term therapy for children with hypoparathyroidism. STUDY DESIGN: Linear growth, bone accrual, renal function, and mineral homeostasis were studied in a long-term observational study of PTH 1-34 injection therapy in 14 children. METHODS: Subjects were 14 children with hypoparathyroidism attributable to autoimmune polyglandular syndrome type 1 (N = 5, ages 7-12 years) or calcium receptor mutation (N = 9, ages 7-16 years). Mean daily PTH 1-34 dose was 0.75 ± 0.15 µg/kg/day. Treatment duration was 6.9 ± 3.1 years (range 1.5-10 years). Patients were evaluated semiannually at the National Institutes of Health Clinical Center. RESULTS: Mean height velocity and lumbar spine, whole body, and femoral neck bone accretion velocities were normal throughout the study. In the first 2 years, distal one-third radius bone accrual velocity was reduced compared with normal children (P < .003). Serum alkaline phosphatase correlated with PTH 1-34 dose (P < .006) and remained normal (235.3 ± 104.8 [SD] U/L, N: 51-332 U/L). Mean serum and 24-hour urine calcium levels were 2.05 ± 0.11 mmol/L (N: 2.05-2.5 mmol/L) and 6.93 ± 1.3 mmol/24 hour (N: 1.25-7.5 mmol/24 hour), respectively-with fewer high urine calcium levels vs baseline during calcitriol and calcium treatment (P < .001). Nephrocalcinosis progressed in 5 of 12 subjects who had repeated renal imaging although renal function remained normal. CONCLUSIONS: Twice-daily or thrice-daily subcutaneous PTH 1-34 injections provided safe and effective replacement therapy for up to 10 years in children with hypoparathyroidism because of autoimmune polyglandular syndrome type 1 or calcium receptor mutation.

Long-term treatment of 12 children with chronic hypoparathyroidism: a randomized trial comparing synthetic human parathyroid hormone 1-34 versus calcitriol and calcium.

CONTEXT: Hypoparathyroidism is among the few hormonal insufficiency states not treated with replacement of the missing hormone. This is the first randomized controlled study in children comparing treatment with synthetic human PTH 1-34 and calcitriol. OBJECTIVE: The primary objective was to assess the efficacy and safety of long-term PTH 1-34 vs. calcitriol treatment in the maintenance of normal serum calcium values and renal calcium excretion in children with hypoparathyroidism. SETTING: The study was conducted at a clinical research center. SUBJECTS: Subjects included 12 children aged 5-14 yr with chronic hypoparathyroidism and without severe renal or hepatic insufficiency. STUDY DESIGN: The study was a 3-yr randomized parallel trial comparing twice-daily calcitriol (plus calcium and cholecalciferol in four daily doses) vs. s.c. PTH 1-34 treatment, with weekly or biweekly monitoring of serum and urine calcium. RESULTS: Mean predose serum calcium levels were maintained at, or just below, the normal range, and urine calcium levels remained in the normal range throughout the 3-yr study, with no significant differences between treatment groups. Creatinine clearance, corrected for body surface area, did not differ between groups and remained normal throughout the study. Markers of bone turnover were mildly elevated during PTH 1-34 therapy and remained within the normal range during calcitriol therapy. Mean bone mineral density Z-scores at the anterior-posterior lumbar spine, femoral neck, distal radius, and whole body remained within the normal range and did not differ between groups throughout the study. Similarly, height and weight percentiles did not differ between treatment groups and remained normal throughout the 3-yr follow-up. CONCLUSION: We conclude that PTH 1-34 therapy is safe and effective in maintaining stable calcium homeostasis in children with hypoparathyroidism. Additionally, PTH 1-34 treatment allowed normal skeletal development because there were no differences in bone mineral accrual, linear growth, or weight gain between the two treatment arms over the 3-yr study period.

Long-term treatment of hypoparathyroidism: a randomized controlled study comparing parathyroid hormone-(1-34) versus calcitriol and calcium.

Hypoparathyroidism is one of the few remaining hormonal insufficiency states for which replacement therapy is unavailable. Previous short-term controlled trials have shown PTH to be a safe and effective treatment of hypoparathyroidism. In this randomized, parallel group, open-label trial, we compared synthetic human PTH-(1-34) (PTH) with conventional therapy, calcitriol and calcium, over a 3-yr period. Twenty-seven patients with confirmed hypoparathyroidism, aged 18-70 yr, were randomized to either twice daily sc PTH or oral calcitriol and calcium. The primary end points were calcium levels in serum and urine. Secondary end points were creatinine clearance, markers of bone turnover, and bone mineral density. Throughout the 3-yr study period, serum calcium levels were similar in both treatment groups within or just below the normal range. Mean urinary calcium excretion was within the normal range from 1-3 yr in PTH-treated patients, but remained above normal in the calcitriol group. Bone mineral content and bone mineral density showed no significant between-group differences over the 3-yr study period. We conclude that treatment with twice daily sc PTH provides a safe and effective alternative to calcitriol therapy and is able to maintain normal serum calcium levels without hypercalciuria for at least 3 yr in patients with hypoparathyroidism.