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1. Introduction
The major functions of vitamin D are related to calcium and bone metabolism. Many studies in recent years have further postulated an important role of vitamin D in several other physiological systems [1]. For example, vitamin D has been suggested to stimulate insulin secretion and decrease insulin resistance [2] and to also exert anti-cancer activity, including anti-proliferative and anti-inflammatory effects [3].
The established general biomarker for the vitamin D status is 25(OH)D, which reacts to dietary vitamin D intake as well as endogenous vitamin D production [4,5]. Lips [6] proposed to classify vitamin D deficiency according to serum 25(OH)D levels into three stages: severe deficiency (<12.5 nmol/L; <5 ng/mL), moderate deficiency (12.5-25 nmol/L; 5-10 ng/mL), and mild deficiency or insufficiency (25-50 nmol/L; 10-20 ng/mL). The thresholds for severe deficiency and partly also moderate deficiency are more or less accepted by the scientific community. However, the thresholds for insufficiency and repletion or optimal status have been controversial, especially since 2011. At that time the Institute of Medicine (IOM) suggested a minimum serum level of 50 nmol/L (20 ng/mL) as the value at which 97.5% of the vitamin D needs of the population would be covered [7,8]. In contrast to the IOM, the Endocrine Society defined vitamin D deficiency as a 25(OH)D below 20 ng/mL (50 nmol/L) and vitamin D insufficiency as a 25(OH)D of 21-29 ng/mL (52.5-72.5 nmol/L) [9].
The discrepancy between the Endocrine Society and IOM clinical guidelines is the result of different ratings of the effects of vitamin D on bone health [10,11]. For example, a previous review of randomized controlled trials (RCT) and cohort studies by Bischoff-Ferrari et al. [12] suggested that for the endpoints bone mineral density (BMD), lower extremity function, dental health, risk of falls, fractures, and colorectal cancer the most advantageous serum concentrations of 25(OH)D exceeds 75 nmol/L (30 ng/mL), and the best results were achieved at levels between 90 and 100 nmol/L (36-40 ng/mL).
In addition to its widely studied effects on bone and mineral metabolism, low 25(OH)D levels have also been associated with development of T2DM [13], hypertension [14], hyperlipidemia [15], and cardiovascular diseases [16]. Therefore, in addition to relating the 25(OH)D status to bone health, relevant 25(OH)D concentrations should also be discussed by including results...