Post-target management of anti-resorptive agents based on mechanistic differences:bisphosphonate drug holidays versus denosumab sequential therapy
WANG Qin
CHEN De-cai
Abstract：The management of osteoporosis with anti-resorptive agents requires distinct post-treatment strategies based on the differences in pharmacological mechanisms after achieving therapeutic targets.Bisphosphonates(e.g.,zoledronic acid,alendronate)exhibit a"residual effect"due to their skeletal retention,allowing for a drug holiday once treatment goals are met[e.g.,no new fractures,bone mineral density(BMD)improvement to target T-score]and the initial treatment course is completed.During this period,annual monitoring of BMD and bone turnover markers is mandatory,with therapy re-initiated upon deterioration of markers.In contrast,denosumab requires continuous exposure for sustained efficacy.Discontinuation of the drug triggers rebound osteoclast activation,leading to rapid bone loss and a sharp increase in fracture risk.Thus,treatment must not be interrupted immediately without transition.Upon target achievement or when drug discontinuation is necessary,prompt sequential therapy with bisphosphonates(preferably zoledronic acid)is needed to suppress rebound effects,followed by CTX-guided assessment for additional dosing.Clinical challenges include suboptimal adherence and inappropriate discontinuation,particularly unstructured denosumab withdrawal.Future efforts should focus on optimizing sequential protocols and developing novel monitoring models to achieve personalized long-term management.
Keywords：osteoporosisantiresorptive agentsdrug holidaysequential therapydenosumab discontinuationtreatment to target
Publication Date：2025-08-01
Online Publishing Date：2025-10-09(First online date of this platform, not the publication date of the document)
Pages：6( 642-647 )