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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 3 Cumulative fracture incidence for vitamin D (darker lines) and controls (lighter lines). Vitamin D and calcium studies and vitamin D studies are shown separately. Inset shows treatment effect and 95% confidence intervals. CaD=calcium and vitamin D; D=vitamin D
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fig3: Fig 3 Cumulative fracture incidence for vitamin D (darker lines) and controls (lighter lines). Vitamin D and calcium studies and vitamin D studies are shown separately. Inset shows treatment effect and 95% confidence intervals. CaD=calcium and vitamin D; D=vitamin D

Mentions: The analysis covered 7202 fractures over 177 203 person years. Placebo fracture rates were higher in the vitamin D trials than in the trials combining vitamin D with calcium, as these studies recruited older participants (table 1). We found no significant effect of vitamin D without calcium (hazard ratio 1.01, 0.92 to 1.12, P=0.80) (fig 3). Studies in which vitamin D was combined with calcium showed reduced fracture risk (hazard ratio 0.92, 0.86 to 0.99, P=0.025). We adjusted the analysis for study, age, and sex, as well as for baseline hormone replacement and bisphosphonate use. Stratification by route of administration showed a significant effect of oral vitamin D (hazard ratio 0.93, 0.87 to 0.99, P=0.02) but not injected vitamin D (1.11, 0.95 to 1.31, P=0.20). Results were unaffected by exclusion of users of hormone replacement therapy and bisphosphonates. We found no significant treatment by study interaction in either group of studies (calcium and vitamin D studies P=0.67 to 0.78, vitamin D studies P=0.14 to 0.44).


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

- BMJ (2010)

Fig 3 Cumulative fracture incidence for vitamin D (darker lines) and controls (lighter lines). Vitamin D and calcium studies and vitamin D studies are shown separately. Inset shows treatment effect and 95% confidence intervals. CaD=calcium and vitamin D; D=vitamin D
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Fig 3 Cumulative fracture incidence for vitamin D (darker lines) and controls (lighter lines). Vitamin D and calcium studies and vitamin D studies are shown separately. Inset shows treatment effect and 95% confidence intervals. CaD=calcium and vitamin D; D=vitamin D
Mentions: The analysis covered 7202 fractures over 177 203 person years. Placebo fracture rates were higher in the vitamin D trials than in the trials combining vitamin D with calcium, as these studies recruited older participants (table 1). We found no significant effect of vitamin D without calcium (hazard ratio 1.01, 0.92 to 1.12, P=0.80) (fig 3). Studies in which vitamin D was combined with calcium showed reduced fracture risk (hazard ratio 0.92, 0.86 to 0.99, P=0.025). We adjusted the analysis for study, age, and sex, as well as for baseline hormone replacement and bisphosphonate use. Stratification by route of administration showed a significant effect of oral vitamin D (hazard ratio 0.93, 0.87 to 0.99, P=0.02) but not injected vitamin D (1.11, 0.95 to 1.31, P=0.20). Results were unaffected by exclusion of users of hormone replacement therapy and bisphosphonates. We found no significant treatment by study interaction in either group of studies (calcium and vitamin D studies P=0.67 to 0.78, vitamin D studies P=0.14 to 0.44).

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