Short stature in pre-pubertal children with X-linked hypophosphatemia.

Objective: Short stature is a characteristic of X-linked hypophosphatemia (XLH). We aim to explore the factors that influence the height of pre-pubertal children with XLH.

Methods: Based on a randomized clinical trial of high/low doses of active vitamin D with neutral phosphate treatment for XLH children, we recruited 124 pre-pubertal children with XLH, and 46 participants completed the 24-month follow-up. Participants were separated into the short stature (height Z score<-2) and non-short stature groups (height Z score≥-2). Height, medication history, biochemical parameters, the Thacher rickets severity score (RSS), and bone age were evaluated.

Results: At baseline, 50.8% of participants were short stature. The height Z score of males (-2.35±1.18) was significantly inferior to that of females (-1.86±1.03), p=0.014. The height Z score had negative correlations with age when enrolled, initial age of medication, and RSS (β:-0.327~-0.251, p<0.01), but had a positive correlation with calcium-phosphorus product (β:0.213, p=0.015). Compared to the non-short stature group, the proportion of delayed bone age was higher in the short stature group (10.0% vs. 42.9%, p<0.001). At 24-month follow-up, the median height Z score increased from -1.91 to -1.74 (p=0.002), whose improvement had no significant differences between groups of male/female, high/low doses of calcitriol, and non-truncating/truncating variants.

Conclusion: In pre-pubertal children with XLH, a higher height Z score has associations with females, early initiation of treatment, better bone mineralization, and milder rachitic lesions. Conventional therapy improves their heights, but the efficacy does not depend on sex, active vitamin D dosage, or variant type.