Issues of trial selection and subgroup considerations in the recent meta-analysis of Zhao and colleagues on fracture reduction by calcium and vitamin D supplementation in community-dwelling older adults

Summary Zhao and colleagues are addressing an important question about the efficacy of calcium and vitamin D on fracture risk reduction among community-dwelling adults age 50+. However, we are concerned about four aspects of their approach, which may affect the validity of their conclusions and implications for public health. Introduction We discuss the recent meta-analysis by Zhao and colleagues on the primary prevention of fractures of calcium and vitamin D as well as their combination among community-dwelling adults age 50+. Methods Zhao and colleagues included 33 trials that recruited a total of 51,145 community-dwelling participants age 50 years and older, including any randomized clinical trial with a placebo or no treatment in the control group. Results The authors found no significant association of calcium and/or vitamin D with risk of hip fracture compared with placebo or no treatment and concluded that the routine use of calcium, vitamin D, and the combination in community-dwelling older people is not supported by their findings. We discuss four concerns regarding this meta-analysis, including the target population, the selection of trials with regard to blinding and duration of follow-up, and the lack of adjustment for adherence to the interventions and subgroup analysis by bolus versus daily dosing for vitamin D. Conclusion Based on the four concerns raised in this letter and the fact that there will be a manyfold increase in the data on vitamin D supplementation in community-dwelling senior adults from large ongoing trials, we believe that it is too early to recommend the cessation of vitamin D with or without calcium for the prevention of fractures among community-dwelling adults.