Erik ten Hag admits Casemiro is at risk of injury but insists it applies to all of Manchester United's regular players.
Casemiro, 30, started in all three cup games against Nottingham Forest and Reading in the last 10 days and even came on for 30 minutes in the League Cup quarter-final win over Charlton last month.
The Brazilian has lined up in 12 of United's last 13 Premier League games, completing 90 minutes in 11, and only sat out the defeat at Arsenal through suspension.
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Since his full United debut against Real Sociedad on September 8, Casemiro has started on the bench in three of United's 25 matches.
Bruno Fernandes has only ever missed one United game through injury or illness during his three years with the club and he has been benched twice this term.
"He's important but in top football there's a risk and we know that," Ten Hag said of Casemiro. "We know players get injured and you can't avoid it. Of course, if you want to be successful in the season you need your key players on board and that's definitely the truth.
"I think it's not possible to have two Casemiros or two Christian Eriksens. I think in that part we can be a bit deeper but also I think we said before the season that we want to restore Man United but it will take time. It will take seasons to get back the days when you can compete for everything and for the highest trophies in the world.
"It is (a risk) for every player and Bruno is also playing every game. Those players are capable of it and that's why they are so good. You can always rely on them as a club and that's why they have won so many trophies.
"Casemiro at Real Madrid, I think also there he played so many games."
Earlier this week, Ten Hag expressed his annoyance at Reading striker Andy Carroll's reckless fouling in their 3-1 FA Cup defeat at United, as well as Crystal Palace striker Jean-Philippe Mateta's unpunished elbow on Lisandro Martinez.
United were inexplicably not awarded a penalty in the midweek win against Forest when Remo Freuler hacked Wout Weghorst on the shin. The VAR Michael Salisbury did not advise the on-pitch referee David Coote to review the foul.
United sought an explanation from the Professional Game Match Officials Board over why their wall was placed farther back for Lucas Digne's successful free-kick in the defeat to Aston Villa in November, but Ten Hag downplayed recent decisions against them.
"No, you have to accept it in football, it is how it is," he stressed. "We have to accept we have to be without Christian Eriksen for a couple of months. It is a big setback but it is what it is and we have to deal with it and it’s the same with the decisions of the referee and you don’t have to lose focus or energy on it. We focus on our game.
"Sometimes that’s the case (that the decisions are a concern) but we trust in the refereeing in the UK."
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