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J Cell Mol Med. 2019 Mar;23(3):2268-2271. doi: 10.1111/jcmm.14153. Epub 2019 Jan 13.

Circulating serum vitamin D levels and total body bone mineral density: A Mendelian randomization study.

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Department of orthopedics, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Gangwon, Republic of Korea.
Department of orthopedics, Taian City Central Hospital, Taian, Shandong, P.R. China.
Affiliated Hospital & Key Laboratory of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, P.R. China.
Second School of Clinical Medicine, Taishan Medical University, Taian, Shandong, P.R. China.


Until recently, randomized controlled trials have not demonstrated convincing evidence that vitamin D, or vitamin D in combination with calcium supplementation could improve bone mineral density (BMD), osteoporosis and fracture. It remains unclear whether vitamin D levels are causally associated with total body BMD. Here, we performed a Mendelian randomization study to investigate the association of vitamin D levels with total body BMD using a large-scale vitamin D genome-wide association study (GWAS) dataset (including 79 366 individuals) and a large-scale total body BMD GWAS dataset (including 66,628 individuals). We selected three Mendelian randomization methods including inverse-variance weighted meta-analysis (IVW), weighted median regression and MR-Egger regression. All these three methods did not show statistically significant association of genetically increased vitamin D levels with total body BMD. Importantly, our findings are consistent with recent randomized clinical trials and Mendelian randomization study. In summary, we provide genetic evidence that increased vitamin D levels could not improve BMD in the general population. Hence, vitamin D supplementation alone may not be associated with reduced fracture incidence among community-dwelling adults without known vitamin D deficiency, osteoporosis, or prior fracture.


Mendelian randomization; bone mineral density; vitamin D

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