(A) Comparison of simulated total hip bone mineral density (BMD, black curves) and clinical data (dots), including aging behavior (green dots) and treatment behavior (black dots) of various sequential drug treatments, including denosumab, romosozumab, alendronate, and teriparatide. Hybrid aging/treatment datasets were created combining data from Looker et al., 1998 (aging dataset, green dots in panel A; in total subjects 20 years and older), as well as Recknor et al., 2015 (blosozumab 180 mg Q2W: ), McClung et al., 2018 (placebo/deno.: , alendro./romo./deno.: ), and Leder et al., 2015 (deno./teri.: , teri. + deno./deno.: ) (treatment datasets, black dots in panels A and B) as indicated, see ‘Methods.’ (B) Zoom into the treatment regions shown in panel (A) including BMD (black) and baseline changes of the bone resorption marker C-terminal telopeptide (CTX, red) and the bone formation marker procollagen type 1 amino-terminal propeptide (P1NP, blue). Colored bars above the plots indicate the medication scheme (see legend). Data points show population averages; average types and error bar types as reported in the respective original publication. In both panels, BMD is displayed as a fraction of its value at years.