The simulation would be flawed. Von Braun wheels would have very significant Coriolis effects, so it'd be hard to distinguish whether any issues are due to reduced gravity or the Coriolis effects.
Bone density and muscle loss effects shouldn't be significantly effected by coriolis effects. Such effects may likely cause nausea in many people, but it is very likely that test subjects who can adapt to it and live comfortably during the period of study could be found.
My very rusty physics tells me that walking one way along the inside of the wheel would make you weigh less, and the other way would make you weigh more - is this what you're referring to? Would trying to work 'normally' in this kind of situation induce nausea, or make your food fall off your tray etc? It would be a shame if you went to all the effort to make a Von Braun wheel in space to simulate gravity, only to find that you had to stand still to do anything practical.
(I assume the astronauts in 2001 A Space Odyssey jogged in the direction that made themselves weigh more, to make their workout more intense.)
Coriolis forces acting on the human vestibular system can directly induce motion sickness just from turning your head. If it turns out humans cannot acclimate through long term exposure, the only remedy is to increase the wheel radius.
The Coriolis effects can be made to be mostly negligible, with a big enough wheel.
A big wheel may be too costly, but it can be replaced by either 2 identical bodies with a long link between them, or with a single body linked to a counterweight, in which case the cost would be only marginally greater than for the current spaceships.
