Fabregat-Bolufer Aleix B, Escolà-Rodríguez Alba, Bedini-Chesa José Luís, Casals Gregori, Morales-Ruiz Manuel, Filella Xavier
Biochemistry and Molecular Genetics Department, CDB, Hospital Clínic of Barcelona, Barcelona, Spain.
Pharmacy Department, Division of Medicines, Hospital Clínic of Barcelona, Barcelona, Spain.
Clin Chim Acta. 2025 Mar 1;569:120155. doi: 10.1016/j.cca.2025.120155. Epub 2025 Jan 30.
To establish accurate population-based reference intervals (RIs) for serum 25-hydroxyvitamin D [25(OH)D] using the refineR indirect method and real-world data (RWD), accounting for demographic, methodological, and seasonal factors.
A retrospective analysis of 130,030 serum 25(OH)D samples collected from 2018 to 2022 at a tertiary hospital in Barcelona was performed. Samples were measured using VDSP-certified Liaison and Atellica immunoassays. The refineR algorithm was employed to establish RIs, utilizing Box-Cox transformations to adjust for data distribution. Demographic variables (sex and age), assay differences, medical department and seasonal variations were analysed. RIs were verified using a subset of healthy individuals.
The median serum 25(OH)D level was 25 ng/mL (62.5 nmol/L). Vitamin D deficiency (≤20 ng/mL, ≤50 nmol/L) was observed in 34.2% of samples, and severe deficiency (≤12 ng/mL, ≤30 nmol/L) in 12.6%. The default Box-Cox transformation estimated RIs of 11.5-64.5 ng/mL (28.7-161.2 nmol/L), while the modified Box-Cox transformation yielded RIs of 14.2-65.9 ng/mL (35.5-164.7 nmol/L). Women exhibited wider RIs (14.5-68.6 ng/mL, 36.2-171.5 nmol/L) compared to men (11.6-57.3 ng/mL, 29-143.2 nmol/L). Method-specific RIs were 10.2-58.6 ng/mL (25.5-146.5 nmol/L) for the Liaison assay and 9.9-59.3 ng/mL (24.7-133.2 nmol/L) for the Atellica assay. The lowest RIs were observed in outpatients (4.3-46.4 ng/mL, 10.7-116 nmol/L) and endocrinology patients (5.5-43.9 ng/mL, 13.7-109.7 nmol/L). Seasonal variation significantly impacted RIs, with higher levels during summer months.
The refineR algorithm effectively established population-based RIs for serum 25(OH)D in Barcelona, revealing significant demographic and seasonal variations. Redefining 25-hydroxyvitamin D thresholds based on population-specific data may reduce unnecessary screening and supplementation, minimizing associated risks. This study highlights the need for population-, seasonal-, and method-specific RIs to improve vitamin D assessment and management.
采用refineR间接法和真实世界数据（RWD），建立基于人群的血清25-羟维生素D[25(OH)D]准确参考区间（RI），同时考虑人口统计学、方法学和季节因素。
对2018年至2022年在巴塞罗那一家三级医院采集的130,030份血清25(OH)D样本进行回顾性分析。样本采用经VDSP认证的Liaison和Atellica免疫测定法进行检测。使用refineR算法建立RI，利用Box-Cox变换调整数据分布。分析人口统计学变量（性别和年龄）、测定差异、医学科室和季节变化。使用一部分健康个体对RI进行验证。
血清25(OH)D水平中位数为25 ng/mL（62.5 nmol/L）。34.2%的样本存在维生素D缺乏（≤20 ng/mL，≤50 nmol/L），12.6%存在严重缺乏（≤12 ng/mL，≤30 nmol/L）。默认的Box-Cox变换估计RI为11.5 - 64.5 ng/mL（28.7 - 161.2 nmol/L），而改良的Box-Cox变换得出的RI为14.2 - 65.9 ng/mL（35.5 - 164.7 nmol/L）。女性的RI范围（14.5 - 68.6 ng/mL，36.2 - 171.5 nmol/L）比男性（11.6 - 57.3 ng/mL，29 - 143.2 nmol/L）更宽。Liaison测定法的特定方法RI为10.2 - 58.6 ng/mL（25.5 - 146.5 nmol/L），Atellica测定法为9.9 - 59.3 ng/mL（24.7 - 133.2 nmol/L）。门诊患者（4.3 - 46.4 ng/mL，10.7 - 116 nmol/L）和内分泌科患者（5.5 - 43.9 ng/mL，13.7 - 109.7 nmol/L）的RI最低。季节变化对RI有显著影响，夏季月份水平较高。
refineR算法有效地为巴塞罗那的血清25(OH)D建立了基于人群的RI，揭示了显著的人口统计学和季节差异。根据特定人群数据重新定义25-羟维生素D阈值可能会减少不必要的筛查和补充，将相关风险降至最低。本研究强调需要针对人群、季节和方法的特定RI，以改善维生素D评估和管理。
