I think that once filled with a screw and additionally sealed as needed, no air loss would result and there would be no audible sound degradation.

That being said, when I drilled holes in the back of my HKs to mount them on the wall as surrounds until i could afford to order QS8s, I was terrified that the drill would knock a fair size chunk of MDF off in the inside and it would be inside there making a vibrating, buzzing sound forever.

With great power comes Awesome irresponsibility.