Ikegami and colleagues [1] have recently reported that a direct association may exist between insufficiency of 25-hydroxyvitamin D [25(OH)D], bone turnover markers and prior vertebral fractures, independent of parathyroid hormone (PTH) activity. In 330 postmenopausal Japanese women with osteoporosis and normal PTH levels who had never been treated for osteoporosis, serum 25(OH)D levels, bone formation and resorption markers and presence of prior vertebral fractures were analyzed. In subjects with low 25(OH)D levels but normal calcium metabolism and PTH levels, an association was found with low serum osteocalcin/bone alkaline phosphatase (OC/BAP) ratio, low serum inorganic phosphorus levels and presence of prior vertebral fractures. This study revealed that vitamin D may have a direct effect on bone turnover and that 25(OH)D insufficiency is related to higher than normal prevalence of vertebral fractures.

Comment
The serum 25(OH)D level is the best indicator of overall vitamin D status, reflecting vitamin D dietary intake, formation from sunlight exposure and conversion of vitamin D from adipose stores in the liver [2]. With the recent changes in laboratory reference ranges, a normal serum level is 30–76 ng/ml; levels below 10 ng/ml are considered deficient and levels below 20 ng/ml are classified as insufficient [3]. The relationship of PTH and 25(OH)D is not curvilinear and there is no absolute threshold level of serum 25(OH)D at which PTH levels rise [4]. Effects of insufficient vitamin D levels on bone turnover were thought to be mediated indirectly through PTH. The study by Ikegami and colleagues clearly shows that this may not be the case and that 25(OH)D may directly influence bone turnover and vertebral fractures. The number of bone markers with different clinical properties is increasing. Direct vitamin D effects on bone markers are yet to be understood.

Levels of 25(OH)D are inversely correlated with body mass index (BMI) and incidence of metabolic syndrome. High BMI has been shown to be a risk factor for vertebral fractures in postmenopausal women with osteoporosis [5]. One in three women and one in two men with BMI ≥ 40 kg/m2 are vitamin D-deficient [6]. This has also been shown in this study of postmenopausal Japanese women with osteoporosis who have a higher BMI than subjects with sufficient vitamin D levels. The clinical implication of this finding is that one should look for 25(OH)D insufficiency and vertebral fractures in obese subjects with osteoporosis.

Teodora Beljic Zivkovic
Faculty of Medicine, University of Belgrade, ’Zvezdara’ University Medical Center, Belgrade, Serbia

References
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http://www.ncbi.nlm.nih.gov/pubmed/21713425
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http://www.ncbi.nlm.nih.gov/pubmed/16026981
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http://www.ncbi.nlm.nih.gov/pubmed/19578807
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http://www.ncbi.nlm.nih.gov/pubmed/19667169