Vitamin D deficiency and insufficiency.

30–35 ng/ml [6]. Priemel et al. [7], in their autopsy study, found that about 40% of bone samples from individuals with serum 25-OHD of 20–32 ng/ml still had elevated osteoid volumes typical for vitamin D deficiency. However, no osteomalacia was found in samples taken from individuals with serum levels higher than 32 ng/ml. In a meta-analysis, Bischoff-Ferrari and colleagues [8] showed that a significant fracture risk reduction occurs only in individuals with serum 25-OHD levels > 30 ng/ml. In addition to the roles of vitamin D in calcium homeostasis and bone health, newer data have demonstrated the association between vitamin D status and the prevalence of extra-skeletal diseases, such as cancer, cardiovascular diseases and autoimmune diseases [9,10]. Those who support the newer higher definition of vitamin D insufficiency (25-OHD between 20 and 30 ng/ml) indicate that the lowest risk for such diseases is found in subjects with serum 25-OHD levels above 30 ng/ ml [11]. Contrary to the newer definitions of vitamin D deficiency and insufficiency, the Institute of Medicine, a division of the American National Academy of Science, indicated in a recent report [12] that serum 25-OHD level ≥ 20 ng/ml (50 nmol/L) is enough to sustain normal calcium absorption and bone density and to minimize the risk of osteomalacia and rickets, and that there is no evidence base to establish the optimal level of 25-OHD at > 30 ng/ml for the extra-skeletal diseases. Bouillon [13] also supports the position that intestinal calcium absorption and bone density are already optimal when 25-OHD level exceeds 20 ng/ml and that only marginal further improvement is achieved by higher serum 25-OHD lev25 D is the most abundant circulating metabolite of vitamin D. Almost all vitamin D produced in the skin or obtained from food or supplements is converted in the liver to 25-OHD1. Moreover, the serum half-life of 25-OHD is almost 2–3 weeks. Thus, serum 25-OHD level is a sensitive index of vitamin D status [1]. The development of radioassays for 25-OHD 40 years ago has made it possible to measure serum 25-OHD concentration and to define an individual’s vitamin D status [1-3]. Early studies indicated that serum 25-OHD under 5–8 ng/ml is invariably associated with rickets in children and with osteomalacia in adults, and levels under 12–15 ng/ ml are usually associated with secondary hyperparathyroidism or subtle osteomalacia. These cutoff levels of 25-OHD have been used for the definitions of vitamin D deficiency and insufficiency respectively. In the last 15 years a newer definition of vitamin D deficiency and insufficiency has emerged, which is supported by several research groups [4,5]. It has been suggested that vitamin D deficiency should be defined as a serum 25-OHD level < 20 ng/ml (50 nmol/L) and vitamin D insufficiency < 30 ng/ml (75 nmol/L). This position is based on several lines of evidence. There is an improvement in intestinal calcium absorption efficiency as serum 25-OHD levels rise to the range of