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ObjectivesThe aim of this study was to evaluate the effect of antiosteoporotic drugs on preventing periprosthetic bone loss in calcar 6 and 12 months after total hip arthroplasty.MethodsThe network meta-analysis was conducted guided by the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline. A systematic literature search was conducted and 21 studies that enrolled a total of 955 patients with 9 antiosteoporotic drugs met the inclusion criteria. Network meta-analysis and conventional meta-analysis were carried out for calculating standard mean difference (SMD) and the surface under cumulative ranking curve (SUCRA) of the bone mineral density (BMD) in calcar (Gruen zone 7) as well as bone turnover markers (BTMs) including bone-specific alkaline phosphatase (BSAP) and collagen type I cross-linked N telopeptide (NTX) at 6 and 12 months between different antiosteoporotic drugs.ResultsAt 6 months after total hip arthroplasty, zoledronate (SUCRA=86.4%), risedronate (SUCRA=51.3%) and etidronate (SUCRA=44.5%) were effective in retaining BMD in calcar; zoledronate was significantly more effective than etidronate (SMD=0.65, 95% CI 0.03 to 1.27). Teriparatide (SUCRA=84.5%), denosumab (SUCRA=82.5%), zoledronate (SUCRA=69.2%), alendronate+alfacalcidol (SUCRA=66.2%) and etidronate (SUCRA=51.5%) were the top five drugs in retaining BMD in calcar at 12 months after total hip arthroplasty and the efficacy were comparable. After simultaneously excluding studies in which the prosthesis were cement and the drug dosages as well as treatment durations were inconsistent with those in treating osteoporosis, the above results were robust with the exception that alendronate showed significant efficacy compared with placebo (SMD=1.22, 95% CI 0.46 to 1.99) and was comparable with those effective drugs at 12 months. Long-term residual effect was corroborated only in etidronate, alendronate and zoledronate from previous studies. BTMs were significantly decreased as early as 6 months (SMD of BSAP −0.49, 95% CI −0.84 to −0.13; SMD of NTX −0.93, 95% CI −1.21 to −0.64) and sustained until 12 months (SMD of BSAP −0.27, 95% CI −0.50 to −0.03; SMD of NTX −0.84, 95% CI −1.11 to −0.56) during the prophylaxis.ConclusionsAntiosteoporotic drugs showed prophylactic efficacy on periprosthetic bone loss after total hip arthroplasty in calcar, the effectiveness varied. Zoledronate was the best recommendation due to its optimal efficacy both within 6 and 12 months as well as its residual effect in the long term. BTMs could be used as indicators for monitoring through the treatment. More head-to-head clinical trials are needed to confirm those findings.