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

Abstract

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.

Keywords: Calcium; Fractures; Meta-analysis; Primary prevention; Vitamin D.