A very interesting article on Teleread today.
I use a side opening cover for both my ereaders and a STM Skinny Cover for my iPad. When I settle down for serious reading, I hold my ereader's cover like I would a book and never suffer from wrist issues.
When using my iPad, it rests on my lap as it does get too heavy to hold like a book.
It does boil down to individual experiences but the article is appropriate to all of us really. Well worth a read.