The relative influence of serum ionized calcium and 25-hydroxyvitamin D in regulating PTH secretion in healthy subjects

Abstract

Background: While the inverse relationship between serum ionized calcium (Ca²⁺) and PTH is well-established, the relationship between 25(OH)D and PTH showed conflicting results. The study aimed to evaluate the relative contributions of age, sex, serum Ca²⁺, ionized magnesium (Mg²⁺), 25(OH)D and 1,25(OH)₂D in regulating PTH secretion in healthy subjects.

Methods: This is a secondary analysis of an observational study performed from March 2014 to July 2015 carried out in 2259 blood donors (1652 men and 607 women, age range 18-68 years). Subjects with parathyroid disorders and taking drugs that affect mineral metabolism were excluded.

Results: Significant correlations [between Ca²⁺ and PTH (r = -0.223, p < 0.001), 25(OH)D and PTH (r = -0.178, p < 0.001) and between PTH and age (r = 0.322, p < 0.001)] were found. As a preliminary step to multivariate analysis, a regression tree analysis was performed using PTH as response variable and age, Ca²⁺, Mg²⁺, 25(OH)D, 1,25(OH)₂D and sex as explanatory variables to determine the effect of each covariate on the response variable. For subjects <38 years, 25(OH)D was the most important parameter in regulating PTH. For subjects ≥38 both 25(OH)D and Ca²⁺ levels regulated PTH secretion. Subjects with 25(OH)D < 13 ng/mL had average higher PTH; in this group only, subjects with Ca²⁺ ≥ 1.30 mmol/L had average lower PTH compared to subjects with Ca²⁺ < 1.30. The multivariate analysis showed that all variables had a significant effect (p < 0.001) on PTH. Anova Type III errors c indicated that 25(OH)D accounted for 32.1% of the total variance in PTH, Ca²⁺ accounted for 18% of the total variance, BMI for 14.3%, and 1,25(OH)₂D for 11.1%. The remaining percentage was attributable to age and sex. This was confirmed by the regression tree approach, where 25(OH)D and Ca²⁺ accounted for the largest variation in the average levels of PTH.

Discussion: Under stable conditions 25(OH)D plays a significant role in regulating PTH secretion. Under conditions of relative vitamin D sufficiency, Ca²⁺ also plays an important role.

Keywords: Aging; Menopause; Osteoporosis; Parathyroid hormone; Vitamin D.