Evaluation of the age-specific relationship between PTH and vitamin D metabolites

A commonly used method for determining vitamin D sufficiency is the suppression of excess PTH secretion. Conventionally, the main circulating vitamin D metabolite 25(OH)D is used for this assessment, however, the cut-off data for this parameter vary widely in the literature. The role of other metabolites as markers of vitamin D status is actively debated. The aim of our study was to assess the relationship between PTH, age and parameters characterizing vitamin D status, both "classical" - 25(OH)D₃, and "non-classical" - 24,25(OH)₂D₃ and 25(OH)D₃/24,25(OH)₂D₃ (vitamin D metabolite ratio, VMR). This prospective non-controlled cohort study included 162 apparently healthy Caucasian adult volunteers. When PTH was binarized according to the median value, at VMR < 14.9, 25(OH)D₃ > 9.7 ng/mL and 24,25(OH)₂D₃ > 0.64 ng/mL there was a pronounced relationship between PTH and age (p = 0.001, p = 0.023 and p = 0.0134 respectively), with the prevalence of higher PTH levels in older individuals and vice versa. Moreover, at an age of <40.3 years, there was a pronounced relationship between PTH and VMR (p < 0.001), and similarly at an age of <54.5 years, there was a pronounced relationship between PTH and 25(OH)D₃ (p = 0.002) as well as between PTH and 24,25(OH)₂D₃ (p = 0.0038): in younger people, higher PTH values prevailed only in the range of vitamin D insufficiency, while in the older age group this relationship was not demonstrated and PTH values were in general above the median. VMR controlled the correlation between PTH and age more strongly than metabolites 25(OH)D₃ and 24,25(OH)₂D₃ (p = 0.0012 vs. p > 0.05 and p = 0.0385 respectively). The optimal threshold was found equal to 11.7 for VMR such that the relationship between PTH and age in the subset of participants with VMR < 11.7 was characterized by a correlation coefficient of ρ = 0.68 (p < 0.001), while the cohort with VMR > 11.7 was characterized by a very weak correlation coefficient of ρ = 0.12 (p = 0.218), which is non-significant. In summary, our findings suggest that the relationship between PTH and vitamin D is age-dependent, with a greater susceptibility to elevated PTH among older individuals even with preserved renal function, likely due to the resistance to vitamin D function. We propose VMR can be considered as a potential marker of vitamin D status. These findings require confirmation in larger population-based studies.