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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 1 Flow chart of analysis. RCT=randomised controlled trial
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fig1: Fig 1 Flow chart of analysis. RCT=randomised controlled trial

Mentions: We searched, with no language restrictions, for publications between January 1966 and July 2008 in Medline, Embase, and the Cochrane Central Register of Controlled Trials by using MeSH terms: [Fractures, bone] combined with [Vitamin D], [Ergocalciferol] or [Cholecalciferol]. We also searched for text words in title and abstract: “Fractu*” or “Bone fractu*”, in combination with “Vitamin D”, ”Cholecalciferol”, or “Colecalciferol”. We included studies if they were randomised (individual or cluster), had at least one intervention arm in which vitamin D was given and one arm without vitamin D, used fracture as an outcome, and included at least 1000 patients. The decision to include only studies above this size was driven by concerns that each study, while contributing additional cases, would also further reduce the mass of shared study variables for aggregated analysis. We identified 248 abstracts (fig 1); 47 covered clinical trials of vitamin D with a fracture outcome—36 with n<1000 and 11 with n≥1000. We contacted the corresponding authors of these 11 trials. Four groups were unwilling or unable to provide patient level data.9 15 16 17 Seven groups agreed to participate.


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

- BMJ (2010)

Fig 1 Flow chart of analysis. RCT=randomised controlled trial
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Fig 1 Flow chart of analysis. RCT=randomised controlled trial
Mentions: We searched, with no language restrictions, for publications between January 1966 and July 2008 in Medline, Embase, and the Cochrane Central Register of Controlled Trials by using MeSH terms: [Fractures, bone] combined with [Vitamin D], [Ergocalciferol] or [Cholecalciferol]. We also searched for text words in title and abstract: “Fractu*” or “Bone fractu*”, in combination with “Vitamin D”, ”Cholecalciferol”, or “Colecalciferol”. We included studies if they were randomised (individual or cluster), had at least one intervention arm in which vitamin D was given and one arm without vitamin D, used fracture as an outcome, and included at least 1000 patients. The decision to include only studies above this size was driven by concerns that each study, while contributing additional cases, would also further reduce the mass of shared study variables for aggregated analysis. We identified 248 abstracts (fig 1); 47 covered clinical trials of vitamin D with a fracture outcome—36 with n<1000 and 11 with n≥1000. We contacted the corresponding authors of these 11 trials. Four groups were unwilling or unable to provide patient level data.9 15 16 17 Seven groups agreed to participate.

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