Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe.
OBJECTIVE
To identify participants' characteristics that influence the anti-fracture efficacy of vitamin D or vitamin D plus calcium with respect to any fracture, hip fracture, and clinical vertebral fracture and to assess the influence of dosing regimens and co-administration of calcium.


METHODS
Individual patient data analysis using pooled data from randomised trials.


METHODS
Seven major randomised trials of vitamin D with calcium or vitamin D alone, yielding a total of 68 517 participants (mean age 69.9 years, range 47-107 years, 14.7% men).


METHODS
Studies included were randomised studies with at least one intervention arm in which vitamin D was given, fracture as an outcome, and at least 1000 participants.


RESULTS
Logistic regression analysis was used to identify significant interaction terms, followed by Cox's proportional hazards models incorporating age, sex, fracture history, and hormone therapy and bisphosphonate use.


RESULTS
Trials using vitamin D with calcium showed a reduced overall risk of fracture (hazard ratio 0.92, 95% confidence interval 0.86 to 0.99, P=0.025) and hip fracture (all studies: 0.84, 0.70 to 1.01, P=0.07; studies using 10 microg of vitamin D given with calcium: 0.74, 0.60 to 0.91, P=0.005). For vitamin D alone in daily doses of 10 microg or 20 microg, no significant effects were found. No interaction was found between fracture history and treatment response, nor any interaction with age, sex, or hormone replacement therapy.


CONCLUSIONS
This individual patient data analysis indicates that vitamin D given alone in doses of 10-20 microg is not effective in preventing fractures. By contrast, calcium and vitamin D given together reduce hip fractures and total fractures, and probably vertebral fractures, irrespective of age, sex, or previous fractures.
D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002118:Calcium / Q000627:therapeutic use*; D019587:Dietary Supplements; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control*; D006620:Hip Fractures / Q000517:prevention & control; D006801:Humans; D008297:Male; D016032:Randomized Controlled Trials as Topic; D055502:Secondary Prevention; D016103:Spinal Fractures / Q000517:prevention & control; D014481:United States; D014807:Vitamin D / Q000627:therapeutic use*
D050071:Bone Density Conservation Agents; D014807:Vitamin D; D002118:Calcium