The two-stroke 250 only has the trans. to lubricate with the sump fluid. The crank and piston bearings, as well as the rings and cylinder are lubricated by the pre-mix oil.
The thumper 250 has nearly the identical transmission to lubricate, but also the crank and piston bearings, the cylinder walls, solid valve lifters, and the cam lobes and plain bearings the dual overhead cams ride in.
So yes, the thumper is harder on the sump fluid than the 2 cycle engine.
I have owned both types of engines for years and I always follow the same OCI for all of them. No more than 4-6 hours total run time. And I also feel the oil is probably still up to task at that point...but my concern after those hours is contamination from the clutch assembly, which is something that happens and can't be stopped.
So, the answer to an engine that sees frequent contamination is to change the fluid out on an early and often basis.
Well built oils with bargain basement prices, like Super-flo, fits the bill quite well for both 2 and 4 cycle bike engines.