"Mirror mode" is a very clever idea from mangis, and knowing how it works I think it's very difficult if not impossible for Jagex to detect, even with native code.
The first method Maxi posted about has been hypothesised about for a long time, but back when this was originally discovered (~2009-2010) Jagex never used it in an attempt to identify bots (although this may not be the case with OSRS). Some of the methods of bot detection in older clients (3xx-4xx) are simple, such as ensuring the client window is focused when a user clicks (which it would be if a real user was clicking) and sending data about the position and timing of the mouse clicks (both of which OSRS still does). 3xx has no additional systems, but 4xx might (which is what the OSRS client is based upon, if anyone is unfamiliar with RS builds).
RS3 has a nice system jacmob created but OSRS does not have this implemented (at least, not yet).