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Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe.

- BMJ (2010)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

ABSTRACT

Objectives: 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.

Design: Individual patient data analysis using pooled data from randomised trials.

Data sources: 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).

Study selection: 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.

Data synthesis: 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.

Conclusion: 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.

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Fig 5 Sensitivity analysis: influence of removing individual studies from analysis. CaD=calcium and vitamin D trials; D=vitamin D trials; w/o=without
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fig5: Fig 5 Sensitivity analysis: influence of removing individual studies from analysis. CaD=calcium and vitamin D trials; D=vitamin D trials; w/o=without

Mentions: In the influence analysis for vitamin D trials, the hazard ratio remained close to 1.0 irrespective of exclusion of any one study in both the any fracture scenario and the hip fracture scenario (fig 5). For calcium and vitamin D trials, the hip fracture analysis was sensitive to exclusion of contributing studies, leading to a mean effect close to 1.0 if the Larsen study was excluded. The corresponding any fracture analysis was robust, with mean hazard ratios indicating relatively little difference in effect on point estimates across calcium and vitamin D studies. The Larsen trial was unique in using a cluster randomised factorial design, in which environmental modification and drug review were added in two study arms. We repeated the hip fracture analysis across the calcium and vitamin D studies excluding the two arms of the Larsen study that included environmental intervention. In this post hoc analysis, the effect of calcium and vitamin D on hip fractures had a hazard ratio of 0.82 (0.67 to 0.99, P=0.045). For vitamin D studies, mean effects were between 1.00 (exclusion of Smith study) and 1.18 (exclusion of Lyons study). Considering 20 μg of ergocalciferol to be equivalent to 10 μg rather than 20 μg of cholecalciferol affected only the vitamin D studies. This did not alter the findings (any fracture: hazard ratio 1.01, 0.90 to 1.14, P=0.83 for lower dose and 1.01, 0.82 to 1.24, P=0.95 for higher dose).


Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe.

- BMJ (2010)

Fig 5 Sensitivity analysis: influence of removing individual studies from analysis. CaD=calcium and vitamin D trials; D=vitamin D trials; w/o=without
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2806633&req=5

fig5: Fig 5 Sensitivity analysis: influence of removing individual studies from analysis. CaD=calcium and vitamin D trials; D=vitamin D trials; w/o=without
Mentions: In the influence analysis for vitamin D trials, the hazard ratio remained close to 1.0 irrespective of exclusion of any one study in both the any fracture scenario and the hip fracture scenario (fig 5). For calcium and vitamin D trials, the hip fracture analysis was sensitive to exclusion of contributing studies, leading to a mean effect close to 1.0 if the Larsen study was excluded. The corresponding any fracture analysis was robust, with mean hazard ratios indicating relatively little difference in effect on point estimates across calcium and vitamin D studies. The Larsen trial was unique in using a cluster randomised factorial design, in which environmental modification and drug review were added in two study arms. We repeated the hip fracture analysis across the calcium and vitamin D studies excluding the two arms of the Larsen study that included environmental intervention. In this post hoc analysis, the effect of calcium and vitamin D on hip fractures had a hazard ratio of 0.82 (0.67 to 0.99, P=0.045). For vitamin D studies, mean effects were between 1.00 (exclusion of Smith study) and 1.18 (exclusion of Lyons study). Considering 20 μg of ergocalciferol to be equivalent to 10 μg rather than 20 μg of cholecalciferol affected only the vitamin D studies. This did not alter the findings (any fracture: hazard ratio 1.01, 0.90 to 1.14, P=0.83 for lower dose and 1.01, 0.82 to 1.24, P=0.95 for higher dose).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

ABSTRACT

Objectives: 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.

Design: Individual patient data analysis using pooled data from randomised trials.

Data sources: 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).

Study selection: 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.

Data synthesis: 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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus