MedScape reports that daily supplements of calcium plus vitamin D, but not of vitamin D alone, are associated with significantly reduced fracture risk, according to the results of a patient level-pooled analysis reported in the January 12 issue of the BMJ.
“A large randomised controlled trial in women in French nursing homes or apartments for older people showed that calcium and vitamin D supplementation increased serum 25-hydroxyvitamin D, decreased parathyroid hormone, improved bone density, and decreased hip fractures and other non-vertebral fractures,” write B. Abrahamsen, from Copenhagen University Hospital Gentofte, in Copenhagen, Denmark, and colleagues from the DIPART (vitamin D Individual Patient Analysis of Randomized Trials) Group.
“Subsequent randomised trials examining the effect of vitamin D supplementation — with or without calcium — on the incidence of fractures have produced conflicting results. … We used individual patient data methods to do a meta-analysis of randomised controlled trials of vitamin D — with or without calcium — in preventing fractures and investigated if treatment effects are influenced by patients’ characteristics.”
The goals of the study were to identify characteristics affecting the antifracture efficacy of vitamin D or vitamin D plus calcium regarding any fracture, hip fracture, and clinical vertebral fracture and to evaluate the effects of dosing regimens and coadministration of calcium.
Selection criteria were randomized trials with at least 1 intervention group in which vitamin D was given, in which there were at least 1000 participants, and in which fracture was an outcome. The investigators identified 7 major randomized trials of supplementation with vitamin D plus calcium or with vitamin D alone, enrolling a total of 68,517 participants.
Mean age was 69.9 years (range, 47 – 107 years), and 14.7% of participants were men. Significant interaction terms were identified with logistic regression analysis, followed by Cox’s proportional hazards models incorporating age, sex, fracture history, and use of hormone therapy and bisphosphonates.
Overall risk for fracture was decreased in trials using vitamin D with calcium (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.86 – 0.99; P = .025), and risk for hip fracture was also decreased (HR for all studies, 0.84; 95% CI, 0.70 – 1.01; P = .07; HR for studies using 10 μg of vitamin D given with calcium, 0.74; 95% CI, 0.60 – 0.91; P = .005).
There were no significant effects for vitamin D alone in daily doses of 10 μg or 20 μg, nor was there any apparent interaction between fracture history and treatment response. No interaction was noted for age, sex, or use of hormone replacement therapy.
“This individual patient data analysis indicates that vitamin D given alone in doses of 10-20 μg is not effective in preventing fractures,” the study authors write. “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.”
Limitations of this study include lack of data for 4 of the 11 identified studies meeting inclusion criteria, and insufficient information about compliance to do a per protocol analysis. In addition, only a single study provided data for vitamin D given alone at the lower dose.
“We must emphasise that this analysis does not allow for a direct comparison of vitamin D against vitamin D given with calcium, but only comparisons between each intervention and no treatment,” the study authors conclude.
“Whether intermittent doses of vitamin D given without calcium supplements can reduce the risk of fractures remains unresolved from the studies in this analysis. Additional studies of vitamin D are also needed, especially trials of vitamin D given daily at higher doses without calcium.”
In an accompanying editorial, Dr. Opinder Sahota, from Queen’s Medical Centre in Nottingham, United Kingdom, notes that these findings are important because they show that vitamin D alone, irrespective of dose, does not reduce the risk for fracture.
“Although the evidence is still confusing, there is growing consensus that combined calcium and vitamin D is more effective than vitamin D alone in reducing non-vertebral fractures,” Dr. Sahota writes.
“Higher doses are probably necessary in people who are more deficient in vitamin D, and treatment is probably more effective in those who maintain long term compliance. Further studies are needed to define the optimal dose, duration, route of administration, and dose of the calcium combination.”
Here are some of my other blogs on vitamin D: