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 .
Design, history and results of the Thiazolidinedione Intervention with vitamin D Evaluation (TIDE) randomised controlled trial
Conflicting data regarding cardiovascular effects of thiazolidinediones ( TZDs ) and extra-skeletal effects of vitamin D supported the need for a definitive trial . The Thiazolidinedione Intervention with vitamin D Evaluation ( TIDE ) trial aim ed to assess the effects of TZDs ( rosiglitazone and pioglitazone ) on cardiovascular outcomes and the effects of vitamin D ( cholecalciferol ) on  cancers and mortality . A large multicentre 3 × 2 factorial double-blind placebo-controlled r and omised trial recruited from outpatient primary care and specialty clinics in 33 countries . From June 2009 to July 2010 , 1,332 people with type 2 diabetes and other cardiovascular risk factors aged ≥50 years whose HbA1c was 6.5–9.5 % ( 48–80 mmol/mol ) when using two or fewer glucose-lowering drugs were r and omised by a central computer system to placebo ( n = 541 ) , rosiglitazone 4–8 mg/day ( n = 399 ) or pioglitazone 30–45 mg/day ( n = 392 ) ; 1,221 participants were r and omised to placebo ( n = 614 ) or vitamin D 1,000 IU/day ( n = 607 ) . Participants and all study personnel were blind to treatment allocation . The primary outcome for the TZD arm was the composite of myocardial infa rct ion , stroke or cardiovascular death , and for the vitamin D arm it was cancer or all-cause death . All r and omised participants were included in the primary analysis . From the study design , 16,000 people were to be followed for approximately 5.5 years . However , the trial was stopped prematurely because of regulatory concerns after a mean of 162 days without consideration of the accrued data . In the TZD arm , the cardiovascular outcome occurred in five participants ( 0.9 % ) in the placebo groups and three participants ( 0.4 % ) in the TZD groups ( two allocated to pioglitazone , one to rosiglitazone ) . In the vitamin D arm , the primary outcome occurred in three participants ( 0.5 % ) in the placebo group and in two participants ( 0.3 % ) receiving vitamin D. Adverse events were comparable in all groups . Uncertainty persists regarding the clinical ly relevant risks and benefits of TZDs and vitamin D because of the early cancellation of this comprehensive trial . Clinical Trials.gov NCT00879970 The study was funded by GlaxoSmithKline
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 .