Handcuffing a running back means to draft his backup in case he gets hurt. This is important to do IF your running back is on a high-powered offense. You have to think “if my guy goes down, will the next guy up have good production.” If the starter is a special talent, it doesn’t always make sense to have the handcuff because the numbers won’t be anywhere close. Another thing that can happen is that the team decides to split carries among backups if there is an injury. No one wants to own a backup running back who only gets 10-12 carries.
So much of fantasy football is about volume. In many cases, when a star RB goes down, the depth chart is blurry behind him, and teams go with “running back-by-committee” backfields. This term is a killer for fantasy football players. The guys you really want to look at owning are the second stringers who already get some touches to spell the starter anyway.