Although we have not systematically studied the effects of 2′′-O-RhamnosylIcariside II in treating osteoporosis by targeting HIF-1α in osteoclasts, we preliminarily found that 2′′-O-RhamnosylIcariside II significantly inhibited the number of osteoclasts both in vitro and in vivo in a dose-dependent manner by TRAP staining analysis (Supplementary Figure S2 and Figure 12). This evidence concerns the gene ACP5 and osteoporosis.