MyDefrag is able to touch the compressed registry data located on the disk in \Windows\System32\Config, they are highly compressed and are unload into memory at boot-up. These specific files are touched in the MyDefrag optimization process.
The only method of registry "defragmenting" that is beneficial is by compacting the free-space inside and between the hives, hence making the registry smaller, using a program like
NTREGOPT (supports x64 and Vista/7).
Anything else (including NTREGOPT in some cases) isn't really a beneficial process, at all.