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

B. Abrahamsen, T. Masud, A. Avenell, F. Anderson, H. E. Meyer, C. Cooper, H. Smith, A. Z. LaCroix, D. Torgerson, A. Johansen, R. Jackson, L. Rejnmark, J. Wactawski-Wende, K. Brixen, L. Mosekilde, John A Robbins, R. M. Francis

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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 μg 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 μg or 20 μg, 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 μg 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.

Original languageEnglish (US)
Article numberb5463
Pages (from-to)139
Number of pages1
JournalBMJ (Online)
Volume340
Issue number7738
DOIs
StatePublished - Jan 16 2010

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Vitamin D
Calcium
Hip Fractures
Information Storage and Retrieval
Hormone Replacement Therapy
Diphosphonates
Gonadal Steroid Hormones
Proportional Hazards Models
Logistic Models
Regression Analysis
Hormones
Confidence Intervals
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

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Abrahamsen, B., Masud, T., Avenell, A., Anderson, F., Meyer, H. E., Cooper, C., ... Francis, R. M. (2010). Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. BMJ (Online), 340(7738), 139. [b5463]. https://doi.org/10.1136/bmj.b5463

Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. / Abrahamsen, B.; Masud, T.; Avenell, A.; Anderson, F.; Meyer, H. E.; Cooper, C.; Smith, H.; LaCroix, A. Z.; Torgerson, D.; Johansen, A.; Jackson, R.; Rejnmark, L.; Wactawski-Wende, J.; Brixen, K.; Mosekilde, L.; Robbins, John A; Francis, R. M.

In: BMJ (Online), Vol. 340, No. 7738, b5463, 16.01.2010, p. 139.

Research output: Contribution to journalArticle

Abrahamsen, B, Masud, T, Avenell, A, Anderson, F, Meyer, HE, Cooper, C, Smith, H, LaCroix, AZ, Torgerson, D, Johansen, A, Jackson, R, Rejnmark, L, Wactawski-Wende, J, Brixen, K, Mosekilde, L, Robbins, JA & Francis, RM 2010, 'Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe', BMJ (Online), vol. 340, no. 7738, b5463, pp. 139. https://doi.org/10.1136/bmj.b5463
Abrahamsen B, Masud T, Avenell A, Anderson F, Meyer HE, Cooper C et al. Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. BMJ (Online). 2010 Jan 16;340(7738):139. b5463. https://doi.org/10.1136/bmj.b5463
Abrahamsen, B. ; Masud, T. ; Avenell, A. ; Anderson, F. ; Meyer, H. E. ; Cooper, C. ; Smith, H. ; LaCroix, A. Z. ; Torgerson, D. ; Johansen, A. ; Jackson, R. ; Rejnmark, L. ; Wactawski-Wende, J. ; Brixen, K. ; Mosekilde, L. ; Robbins, John A ; Francis, R. M. / Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. In: BMJ (Online). 2010 ; Vol. 340, No. 7738. pp. 139.
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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 μg 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 μg or 20 μg, 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 μg 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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AU - Cooper, C.

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N2 - 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 μg 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 μg or 20 μg, 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 μg 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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