In general I would answer your question, “Yes”. Most MDT and HDT suspensions are too stiff for a standard fifth wheel.
Unlike the major three pickup manufacturers you have many more options when you have a MDT or HDT built from scratch. For example the first thing the Freightliner salesman asked me was “do you want Huck bolts or grade 8 bolts in your frame. How many batteries do you want? Where do you want the batteries located? Etc.
My build sheet on my truck is 41 pages long. I had many choices of rear axles and suspensions. So it might be possible to use a very light rear axle and suspension, and thus get by without an air hitch.
For my truck I chose to go heavy. I have a 21,000 lb rear axle and a 26,000 lb rear Airliner suspension. The only time I see my truck’s rear suspension move a lot is when I am hauling my dozer, or if I have three round hay bales on the truck in addition to a flat bed gooseneck loaded with round bales.
The manufacturer of my fifth wheel, Teton, states in their frame warranty that you must use some type of air hitch if you pull the trailer with a MDT or HDT. The air hitch can either be on the trailer or the truck.
I use a TrailAir hitch on my fifth wheel. I chose this because the air hitch is on the trailer. I then can use a simple fifth wheel hitch on my truck. This way I can easily remove my fifth wheel hitch and convert my truck bed to a flat bed. In five minutes I can remove my fifth wheel hitch and replace the bed trough with steel plates that convert my bed to a flat bed.
I was born and raised on a ranch. I have owned pickups all my life. A well designed flat bed is far more useful for hauling than any standard pickup bed.