RE: Vitamin D status and bone health: a possible inverse association
A large body of data from randomized clinical trials and large meta-analyses have shown no clear evidence for a beneficial effect of vitamin D on bone mineral density or fracture risk . Notably, recent studies have demonstrated that high vitamin D levels (above the physiological requirements) can exert a deleterious effects on bone health ,. Furthermore, it has been shown that high-levels of vitamin D can lead to impaired muscle function  and increase the risk of falling  - both important fracture risk factors. These findings are in line with previous RCTs showing more falling and increased fracture risk in individuals randomized to high-dose vitamin D ,.
We welcome the additional evidence provided by Sugiyama et al. surrounding the potential mechanism(s) by which vitamin D can have a negative effect on bone heath. Overall, we agree with Sugiyama that the borderline inverse findings in our study  might be pertinent, as they convey a message similar to those from the aforementioned studies. Still, in our Mendelian randomization study the 95% confidence intervals of genetically-determined vitamin D levels include the null, reason why these results should be interpreted with caution.
Moreover, in our study we tested the evidence for casual effects of fracture risk across 15 different traits. Therefore, after correcting the significance threshold for multiple testing (alpha = 0.05/15 = 0.003) the borderline significant vitamin D results (P=0.07) are far from significant. In the face of high rates of vitamin D supplementation use , our results, combined with those from recent trials, do not support its widespread use in the general population for the prevention of fracture risk. In addition, we agree with the contention that, potential harm from vitamin D over-supplementation should not be disregarded.
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Competing interests: No competing interests