Guoyu Guan,1 Yanping Du,2,* Wenjing Tang,2 Minmin Chen,2 Weijia Yu,2 Huilin Li,2 Qun Cheng2,* 

1Department of Geriatrics, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Osteoporosis and Bone Disease, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Qun Cheng, Department of Osteoporosis and Bone Disease, Huadong Hospital, Fudan University, No. 221, Yan’an West Road, Shanghai, 200040, People’s Republic of China, Email chengqun@fudan.edu.cn Yanping Du, Department of Osteoporosis and Bone Disease, Huadong Hospital, Fudan University, No. 221, Yan’an West Road, Shanghai, 200040, People’s Republic of China, Email yanpingdu@fudan.edu.cn

Purpose: This study aimed to investigate the impacts of prior anti-osteoporosis treatments on bone mineral density (BMD) changes in Chinese postmenopausal women with osteoporosis following 1-year Denosumab (Dmab) therapy.
Patients and Methods: This retrospective cohort study enrolled 381 postmenopausal women, all receiving a 1-year Dmab treatment. Participants were stratified into five groups based on prior anti-osteoporosis treatments: no treatment (NT), alendronate (ALN), zoledronic acid (ZOL), teriparatide (TPT), and raloxifene (RAL). Potential factors influencing BMD changes were screened using least absolute shrinkage and selection operator (LASSO). The selected variables were then incorporated into a multivariate regression model to identify independent risk factors. Finally, after adjusting for confounders, the impacts of prior anti-osteoporosis treatment on sequential Dmab responses were evaluated.
Results: 1) Further BMD increases were observed after sequential 1-year Dmab with prior use of other anti-osteoporosis drugs; 2) Compared to the NT group, ZOL significantly reduced BMD changes at the lumbar spine (LS), femoral neck (FN), and total hip (TH) (LS: β = − 0.01, P = 0.016; FN: β = − 0.01, P = 0.010; TH: β = − 0.01, P = 0.011); Significant negative associations with FN BMD changes were observed for the ALN group (β = − 0.01, P< 0.001), and the RAL group (β = − 0.01, P = 0.010) compared to the NT group; TPT showed no significant differences with the NT group at all sites; 3) Multiple analysis revealed baseline BMD were independently associated with changes in BMD (LS: β = − 0.04, P = 0.009; FN: β = − 0.19, P < 0.001; TH: β = − 0.14, P < 0.001).
Conclusion: These findings indicated that prior anti-osteoporosis treatments differentially influenced BMD responses to 1-year Dmab therapy. While patients who had previously been treated with ZOL had limited subsequent BMD improvement, patients who had previously used TPT and had lower baseline BMD benefited more.

Keywords: denosumab, alendronate, zoledronic acid, teriparatide, raloxifene, sequential treatment, bone mineral density, postmenopausal osteoporosis