Background:The effect of calcium supplementation on bone mineral accretion in people under 35 years old is inconclusive. To comprehensively summarize the evidence for the effect of calcium supplementation on bone mineral accretion in young populations (≤35 years).Methods:This is a systematic review and meta-analysis. The Pubmed, Embase, ProQuest, CENTRAL, WHO Global Index Medicus, Clinical Trials.gov, WHO ICTRP, China National Knowledge Infrastructure (CNKI), and Wanfang Data databases were systematically searched from database inception to April 25, 2021. Randomized clinical trials assessing the effects of calcium supplementation on bone mineral density (BMD) or bone mineral content (BMC) in people under 35 years old.Results:This systematic review and meta-analysis identified 43 studies involving 7,382 subjects. Moderate certainty of evidence showed that calcium supplementation was associated with the accretion of BMD and BMC, especially on femoral neck (standardized mean difference [SMD] 0.627, 95% confidence interval [CI] 0.338–0.915; SMD 0.364, 95% CI 0.134–0.595; respectively) and total body (SMD 0.330, 95% CI 0.163–0.496; SMD 0.149, 95% CI 0.006–0.291), also with a slight improvement effect on lumbar spine BMC (SMD 0.163, 95% CI 0.008–0.317), no effects on total hip BMD and BMC and lumbar spine BMD were observed. Very interestingly, subgroup analyses suggested that the improvement of bone at femoral neck was more pronounced in the peripeak bone mass (PBM) population (20–35 years) than the pre-PBM population (<20 years).Conclusions:Our findings provided novel insights and evidence in calcium supplementation, which showed that calcium supplementation significantly improves bone mass, implying that preventive calcium supplementation before or around achieving PBM may be a shift in the window of intervention for osteoporosis.Funding:This work was supported by Wenzhou Medical University grant [89219029].

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