UNLABELLED: We assessed the impact of weight loss strategies including calorie restriction and exercise training on BMD in adults using a systematic review of randomized controlled trials. Weight reduction results in reduced BMD at the hip, but has less effect on the spine. Both calorie restriction and a combination of calorie restriction and exercise result in a decrease in hip bone density, whereas weight loss response to exercise training without dietary restriction leads to increased hip BMD. INTRODUCTION: Findings are not consistent on the effect of weight loss on bone mineral density (BMD). We conducted a systematic review on the randomized controlled trials to assess the effect of weight loss strategies, including calorie restriction and exercise programs on BMD in adults. METHODS: A structured and comprehensive search of MEDLINE and EMBASE databases was undertaken up to March 2016. Study-specific mean differences (MD) were pooled using a random-effects model. Subgroup analysis and meta-regression were used to find possible sources of between-study heterogeneity. RESULTS: Thirty-two randomized controlled trials met predetermined inclusion criteria. The meta-analysis revealed no significant difference on total BMD (MD 0.007, 95 % CI -0.020-0.034, p = 0.608). In contrast, the pooled data of studies showed a significant effect of weight loss on hip BMD (MD -0.008, 95 % CI -0.09 to -0.006 g/cm(2), p < 0.001) and also lumbar spine BMD (MD -0.018 g/cm(2), 95 % CI -0.019 to -0.017, p < 0.001). BMD in the hip site decreased after more than 4 months, especially in those who were obese. Moreover, calorie restriction interventions longer than 13 months showed a significant decreased in lumbar spine BMD. CONCLUSION: Weight loss led to significant decreases at the hip and lumbar spine BMD but not at the total. Weight loss response following calorie restriction resulted in a decrease in hip and lumbar spine bone density especially more than 1 year; whereas an exercise-induced weight loss did not.