An inflection point of serum 25-hydroxyvitamin D for maximal suppression of parathyroid hormone is not evident from multi-site pooled data in children and adolescents

Abstract

In adults, maximal suppression of serum parathyroid hormone (PTH) has commonly been used to determine the sufficiency of serum 25-hydroxyvitamin D [25(OH)D]. In children and adolescents, the relationship between serum 25(OH)D and PTH is less clear and most studies reporting a relationship are derived from relatively small samples and homogeneous cohorts. Our objective was to determine the relationship between serum 25(OH)D and PTH in children and adolescents from a large and diverse U.S. cohort and to identify a point of inflection of serum 25(OH)D for maximal suppression of serum PTH. Data from 735 participants, ages 7-18 y, were pooled from 3 study sites located in Indiana, Texas, and Massachusetts. A two-phase linear spline was used to model the relationship between serum 25(OH)D and PTH. The value of serum 25(OH)D for maximal suppression of serum PTH was identified as the inflection point of the spline. Before adjustment for site, the inflection point of serum 25(OH)D for maximal suppression of serum PTH was 92.4 nmol/L (95% CI: 62.2, 130.7). After adjusting for site, the point of inflection was poorly defined and the relationship between serum 25(OH)D and PTH appeared to be linear. The lack of an inflection point of serum 25(OH)D for maximal suppression of PTH brings into question the value of using maximal suppression of serum PTH as a basis for determining optimal serum 25(OH)D for healthy children and adolescents.

FIGURE 1

The relationship between serum 25(OH)D and PTH in healthy children and adolescents before (A) and after (B) adjustment of PTH for site. (A) Two-phase linear spline of serum 25(OH)D and serum PTH without adjustment for site. The equation for the line when serum 25(OH)D < 92.4 nmol/L is serum PTH (ng/L) = 59.14–0.35D, where D is serum 25(OH)D (nmol/L). The equation of the line when serum 25(OH)D ≥ 92.4 nmol/L is serum PTH (ng/L) = 42.43–0.16D. The solid line is the fitted two-phase linear spline and the surrounding dashed lines represent the 95% CI around the spline. The vertical lines represent the 95% CI around the inflection point for serum 25(OH)D. (B) Linear function of serum 25(OH)D and serum PTH after adjustment for site. Serum PTH was adjusted for site by subtracting the difference between the site mean and the grand mean. Therefore, serum PTH was adjusted for the Massachusetts site by subtracting 9.5 ng/L, for the Indiana site by adding 5.8 ng/L, and for the Texas site by adding 8.4 ng/L. For 1 observation, the site-adjusted serum PTH was <0 ng/L, so 0 was used for plotting purposes. The linear function is: serum PTH (ng/L) = 51.60–0.22D, where D is serum 25(OH)D, nmol/L. The solid line is the fitted linear function and the surrounding dashed lines represent the 95% CI around the linear function.

FIGURE 2

Serum PTH concentrations in boys (A) and girls (B) at different Tanner stages. Values are means ± SE, n = 9–81. Means without a common letter differ, P < 0.05.