The aim of this study was to perform a head-to-head comparison of efficacy and safety profile between 60 mg denosumab (Den) subcutaneously (SC) per 6 months (Q6M) and 70 mg alendronate (Aln) orally per week (QW) for postmenopausal women with low bone mineral density. We searched electronic databases comparing efficacy and safety of Den SC Q6M and Aln QW in postmenopausal women. The primary outcomes of efficacy evaluation in included trials were incidence of clinical fracture in both groups and bone mineral density (BMD) at different skeletal sites. And adverse events (AEs), including incidence of neoplasms and infections, were considered as secondary outcomes. Following the instructions of 'Cochrane Handbook for systematic Reviews of Interventions 5.0.2', we identified eligible studies, evaluated the methodological quality and abstracted relevant data. Four heterogeneous randomised controlled trials (RCTs) involving 1942 women were identified. The results of review showed low evidence quality that supported the hypothesis the denosumab vs. alendronate could reduce risk of fracture [OR (95% CI) 1.42 (0.84 to 2.40), 11 more women per 1000 (from 4 fewer to 36 more), p = 0.19] but the moderate to high quality evidence suggesting treatment with 60 mg Den SC Q6M was more effective for postmenopausal women in increasing BMD [at distal radius (DR), total hip (TH), lumbar spine (LS), and femoral neck (FN)]. Hazards of neoplasms [OR (95% CI) 1.10 (0.65 to 1.86), 3 more per 1000 (from 10 fewer to 24 more), p = 0.62] or infections [OR (95% CI) 0.95 (0.79 to 1.15), 12 fewer per 1000 (from 53 fewer to 33 more,), p = 0.62] were appeared to be similar.Our review suggested within 1 year 60 mg Den SC Q6M treatment was more effective in increasing bone mass but could not reduce the fracture risk to a greater extent than 70 mg Aln QW therapy. Also the Den SC Q6M therapy did not increase the risks of neoplasms and infections compared with Aln QW.