Cristina Vassalle ^*

• Gabriele Monasterio Tuscany Foundation (CNR), Pisa, Italy

the measurement of vitamin D still represents a challenge; immunoanalytical techniques still retain variability in inter-laboratory comparisons, whereas mass spectrometry presents many different difficulties (e.g costs, time and complexity, matrix effects, derivatization step) (1). Interestingly, other vitamin D-related metabolites may have biological roles, and are expected to be evaluated in the future (2).In any case, at present the high prevalence of vitamin D deficiency is a worldwide major public sanitary issue in every stage of life, including children and adolescents, where an inadequate status can have implications on future health (3,4). In this regard, as many as five contributions focusing on different children issues are included in this special issue (see Table ). Some other contributions explore the beneficial effects of vitamin D supplementation, although dosing recommendations for vitamin D supplementation may considerably vary to achieve maximum benefits, also depending on the clinical setting and specific cohort evaluated. Importantly, there is still no international general consensus on how to define diagnostic thresholds for vitamin D insufficiency and deficiency. For it concerns bone health, the Endocrine Society in 2011 guidelines defined as adequate serum 25(OH)D levels higher than 75 nmol/L (30 ng/mL) and values higher than 50 nmol/L (20 ng/mL) as deficient (5); instead, the Institute of Medicine (IOM, now National Academy of Medicine, 2011) considered vitamin D sufficiency for values higher than 50 nmol/L (20 ng/mL), insufficiency between 30 and 50 nmol/L (12-20 ng/mL); deficiency for levels lower than 30 nmol/L (12 ng/mL) (6). Generally, the most used cut-off, especially when applied to the general population, remains set at 50 nmol/L (20 ng/mL) (7). However, in 2024 a new Endocrine Society Clinical Practice Guideline for vitamin D for the prevention of disease was published, which provide recommendations against routine 25(OH)D screening and in favor of empiric vitamin D supplementation for most groups and conditions (8). The implications of these new vitamin D guidelines, which introduce such a new approach, must be further discussed and evaluated in the real-life situations.It must taken into account that many determinants may affect vitamin D levels; differences may be due to methodological issues (e.g seasonal sampling, variability in the vitamin D assays), characteristics of the studied populations (e.g age, sex, calcium intake), and life-style habits (physical activity, outdoor activities and sun exposure) (1). There may be tissue-specificity related to different tissue requirement, in turns possibly associated to the onset and development of different pathophysiological conditions. Moreover, the majority of evidence derived from studies conducted in adults, and even the threshold used to define vitamin D deficiency or insufficiency may not be appropriate when applied to children and/or adolescents.Thus, for non-classical actions, more research is needed concerning the optimal 25(OH)D levels to maintain and clarify the suitability of 25(OH)D reference levels (in turn useful to decide the recommended vitamin D intake to maintain most people above this threshold, providing adequacy)