Bone Health and Linear Growth in Children with Familial Hypoparathyroidism Treated with Human Parathyroid Hormone 1-34.

Context: Our study explores the impact of human PTH 1-34 injections (PTH therapy) on growth, areal bone mineral density (BMD), and bone quality (measured by trabecular bone score, TBS) in hypoparathyroidism due to autoimmune polyendocrine syndrome type 1 (APS-1) or an activating variant of the calcium sensing receptor (CaR).

Objective: To assess associations of 1) age and PTH therapy duration with age-standardized Z-scores for height (HAZ), BMD (BMD-Z), and TBS (TBS-Z) in CaR or APS-1, and 2) APS-1 disease severity with BMD-Z and TBS-Z.

Methods: This secondary analysis pooled linear growth and lumbar spine (LS) DXA data from studies of hypoparathyroidism with mean baseline age of 13.7±5.5y. Comparing the two diagnostic etiologies (18 APS-1 and 9 CaR), we examined the impact of age and PTH duration on HAZ, LS-BMD-Z, and LS-TBS-Z using longitudinal mixed-effects modeling.

Results: During PTH therapy, mean HAZ remained below zero in the APS-1 group at all ages, whereas HAZ increased in the CaR group (age by group interaction p<0.0001). Mean LS-BMD-Z were normal (BMD-Z:0±1) for both groups. Mean LS-TBS-Z were near or above zero and differed by group; CaR showed an upward trajectory according to time on PTH whereas the APS-1 group maintained a LS-TBS-Z of approximately 0 (time by group interaction p=0.02). The APS-1 group with greater disease severity (≥7 manifestations) had lower LS-BMD-Z and LS-TBS-Z compared to the less severe APS-1 or CaR groups.

Conclusion: Our study highlights distinct growth and BMD patterns in APS-1 and CaR and underscores the need for careful monitoring and tailored treatment strategies to optimize growth and bone health.