Limits...
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.

Show MeSH

Related in: MedlinePlus

Fig 2 Interaction tests on logistic regression base model, 36 months intention to treat scenario. Each panel shows summary of 10 separate interaction analyses, testing statistical significance of each treatment by covariate interaction term added to base model. Coefficients differing significantly from 1.0 indicate presence of interaction (non-proportional hazards) between covariate and treatment; coefficients below 1.0 indicate greater treatment response (lower risk of fracture), and coefficients above 1.0 indicate smaller treatment response (higher risk of fracture). HRT=hormone replacement therapy
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Fig 2 Interaction tests on logistic regression base model, 36 months intention to treat scenario. Each panel shows summary of 10 separate interaction analyses, testing statistical significance of each treatment by covariate interaction term added to base model. Coefficients differing significantly from 1.0 indicate presence of interaction (non-proportional hazards) between covariate and treatment; coefficients below 1.0 indicate greater treatment response (lower risk of fracture), and coefficients above 1.0 indicate smaller treatment response (higher risk of fracture). HRT=hormone replacement therapy

Mentions: Increasing age (hazard ratio per decade 1.34, 95% confidence interval 1.29 to 1.39), male sex (0.52, 0.47 to 0.58), previous hip fracture (1.86, 1.62 to 2.14), previous vertebral fracture (1.71, 1.31 to 2.22), other fracture (1.45, 1.35 to1.57), baseline bisphosphonate use (1.54, 1.22 to 1.92), and baseline hormone replacement therapy (0.69, 0.63 to 0.76) contributed significantly to the risk of any fracture. Strongly statistically significant interaction terms were route of vitamin D administration (P=0.02), dosing interval (P=0.02), and co-administration of calcium (P=0.006), indicating significant modification of response to treatment (fig 2). Bisphosphonate use was of borderline significance (P=0.07). Previous fractures did not significantly interact with treatment response (P=0.64 to 0.79 depending on site), nor did we find an interaction with age, sex, or hormone replacement therapy. As previous fractures did not modify the response, we included the Lyons study, which had no information on previous fractures, in the analysis.


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

- BMJ (2010)

Fig 2 Interaction tests on logistic regression base model, 36 months intention to treat scenario. Each panel shows summary of 10 separate interaction analyses, testing statistical significance of each treatment by covariate interaction term added to base model. Coefficients differing significantly from 1.0 indicate presence of interaction (non-proportional hazards) between covariate and treatment; coefficients below 1.0 indicate greater treatment response (lower risk of fracture), and coefficients above 1.0 indicate smaller treatment response (higher risk of fracture). HRT=hormone replacement therapy
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Fig 2 Interaction tests on logistic regression base model, 36 months intention to treat scenario. Each panel shows summary of 10 separate interaction analyses, testing statistical significance of each treatment by covariate interaction term added to base model. Coefficients differing significantly from 1.0 indicate presence of interaction (non-proportional hazards) between covariate and treatment; coefficients below 1.0 indicate greater treatment response (lower risk of fracture), and coefficients above 1.0 indicate smaller treatment response (higher risk of fracture). HRT=hormone replacement therapy
Mentions: Increasing age (hazard ratio per decade 1.34, 95% confidence interval 1.29 to 1.39), male sex (0.52, 0.47 to 0.58), previous hip fracture (1.86, 1.62 to 2.14), previous vertebral fracture (1.71, 1.31 to 2.22), other fracture (1.45, 1.35 to1.57), baseline bisphosphonate use (1.54, 1.22 to 1.92), and baseline hormone replacement therapy (0.69, 0.63 to 0.76) contributed significantly to the risk of any fracture. Strongly statistically significant interaction terms were route of vitamin D administration (P=0.02), dosing interval (P=0.02), and co-administration of calcium (P=0.006), indicating significant modification of response to treatment (fig 2). Bisphosphonate use was of borderline significance (P=0.07). Previous fractures did not significantly interact with treatment response (P=0.64 to 0.79 depending on site), nor did we find an interaction with age, sex, or hormone replacement therapy. As previous fractures did not modify the response, we included the Lyons study, which had no information on previous fractures, in the analysis.

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