The damage on the Zweihander is almost always going to be better, mainly since dual-wielding has no real value versus using a two-handed weapon outside of some super uncommon damage type resistance/immunity situations. The knuckle dusters aren't even the best unarmed weapons you can get your hands on; the clear demonstones have better damage than it.
The only circumstances where the Zweihander gets out-muscled is if you're specifically playing a taur/feral, which adds an additional 40 base damage for a total of 60, and/or you're using Cloak of Flame at max level to add another 50 fire damage to your unarmed attacks, which goes over the top of it. For all practical purposes, though, it's significantly cheaper to simply get a Zweihander and then kill 95% of enemies in the first turn with a giant crit, especially since you don't need to reach physique cap to make the most of it.
This is what happens when I put perk points to get the maximum unarmed damage AND melee damage with Physique at 100
It seems at 78 Physique, the Knuckle Duster is on par with the Zweihander, assuming you have all Melee and Unarmed perks, including the one you get from training with Hannah. This is on a human by the way, no other race bonuses.
The benefit of knuckle dusters over the Zweihander is that you can equip a Flashlight in the offhand slot, negating any darkness penalties at night.
The Clear Demonstones do have better damage but their cost is exorbitant (if you don't know how to make money or don't want to game it too much)
Knuckle Duster damage with 100 Physique
Zweihander damage
Knuckle Duster damage with 78 Physique
Opaque Demonstone damage at 78 Physique
Clear Demonstone damage at 78 Physique
