For hip fracture , at a 15 % relative risk , the effect estimate lay between the futility boundary and the inferior boundary , meaning there is reliable evidence that vitamin D supplementation does not reduce hip fractures by this amount , but uncertainty remains as to whether it might increase hip fractures .
The effect estimate lay within the futility boundary at thresholds of 0·5 % for total hip , forearm , and total body bone mineral density , and 1·0 % for lumbar spine and femoral neck , providing reliable evidence that vitamin D does not alter these outcomes by these amounts .
INTERPRETATION Our findings suggest that vitamin D supplementation does not prevent fractures or falls , or have clinical ly meaningful effects on bone mineral density .
There were no differences between the effects of higher and lower doses of vitamin D. There is little justification to use vitamin D supplements to maintain or improve musculoskeletal health .
BACKGROUND The effects of vitamin D on fractures , falls , and bone mineral density are uncertain , particularly for high vitamin D doses .
We aim ed to determine the effect of vitamin D supplementation on fractures , falls , and bone density .
Effect of vitamin D3 on bone turnover markers in critical illness: post hoc analysis from the VITdAL-ICU study
Summary In this post hoc analysis of the VITdAL-ICU study , an RCT in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml  , vitamin D3 did not have a significant effect on β-Crosslaps and osteocalcin . Introduction Observational studies have shown accelerated bone loss in ICU survivors . A reversible contributor is vitamin D deficiency . In a post hoc analysis of the VITdAL-ICU study , we evaluated the effect of high-dose vitamin D3 on the bone turnover markers ( BTM ) β-Crosslaps ( CTX ) and osteocalcin ( OC ) . Methods The VITdAL-ICU study was a r and omized , double-blind , placebo-controlled trial in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml who received placebo or high-dose vitamin D3 ( a loading dose of 540,000 IU and starting 1 month after the loading dose five monthly maintenance doses of 90,000 IU ) . In this analysis on 289 survivors ( 209 telephone , 80 personal follow-up visits )  , BTM were analyzed on days 0 , 3 , 7 , 28 , and 180 ; self-reported falls and fractures were assessed . Bone mineral density ( BMD ) was measured after 6 months . Results At baseline , CTX was elevated ; OC was low in both groups — after 6 months , both had returned to normal . There were no differences between groups concerning BTM , BMD , falls , or fractures . In linear mixed effects models , CTX and OC showed a significant change over time ( p < 0.001 , respectively ) , but there was no difference between the vitamin D and placebo group ( p = 0.688 and p = 0.972 , respectively ) . Conclusions Vitamin D supplementation did not have a significant effect on BTM . Further studies should assess the effectiveness of vitamin D  on musculoskeletal outcomes in ICU survivors
For hip fracture , at a 15 % relative risk , the effect estimate lay between the futility boundary and the inferior boundary , meaning there is reliable evidence that vitamin D supplementation does not reduce hip fractures by this amount , but uncertainty remains as to whether it might increase hip fractures .
The effect estimate lay within the futility boundary at thresholds of 0·5 % for total hip , forearm , and total body bone mineral density , and 1·0 % for lumbar spine and femoral neck , providing reliable evidence that vitamin D does not alter these outcomes by these amounts .
INTERPRETATION Our findings suggest that vitamin D supplementation does not prevent fractures or falls , or have clinical ly meaningful effects on bone mineral density .
There were no differences between the effects of higher and lower doses of vitamin D. There is little justification to use vitamin D supplements to maintain or improve musculoskeletal health .
BACKGROUND The effects of vitamin D on fractures , falls , and bone mineral density are uncertain , particularly for high vitamin D doses .
We aim ed to determine the effect of vitamin D supplementation on fractures , falls , and bone density .