Isak won't be involved for [Newcastle](https://www.thenorthernecho.co.uk/sport/football/newcastleunited/) against Liverpool on Monday night, with Howe saying the striker's situation and stance is unchanged.
Howe hasn't spoken to Isak at all this week, and was disappointed to see the latest episode of the saga play out in public on Tuesday night when the Swedish international broke his silence with a social media post, with the Magpies quickly responding with a statement of their own.
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Isak said in his statement the "relationship can't continue", but Newcastle won't sell unless they sign two strikers and Liverpool bid £150m.
It leaves Newcastle in a situation where they either lose their best player or are left with a striker who currently wants out.
Howe said: The club has to act in the best interests of Newcastle and we will do that in every situation.
"I think it is a lose-lose situation to a degree for us because I don’t think we can come out of this winning in any situation.
"That is why I have said all summer it is a difficult situation for the club to manage.
"We love Alex in the sense of what he has done for this football club since he has been here, what he has contributed, what he has given, how professional he’s been.
"This has just been an unfortunate few months that looks like it is coming to an end. And it will come to an end pretty quickly and then we can focus on the football again."
Howe reiterated his desire to get Isak back on the pitch in black and white but says the striker must be "totally committed".
Howe said: "He's contracted to us. He's our player. My wish is he would be playing on Monday night but he won't be, which is regrettable. But 100% I want to see him back in a Newcastle shirt."
Howe was saddened by this week's public developments.
"My emotion was one of disappointment in the respect of these things are being made public," he said.
"For me, all of these things, ideally, should be face to face, club on player.
"Yes, in public, it’s great for you guys, it’s great news, but it doesn’t reflect well on us or Alex. That would be my preference, it always is.
"But the modern day world, that’s sort of what happens. From the club’s persecutive, they thought they had to act and reply. For me, it’s a sad moment trying to deal with it all."
Despite what's gone on, Howe says Isak's teammates would welcome him back into the dressing room.
"There's no doubt how the players will feel, they will feel the same way I do," he said.
"Alex is an outstanding player and a very, very good person, a good character, a good lad. He wants to succeed in his career.
"This has been a really difficult situation for him and for the players to see us without him.
"The players have handled it really well. If Alex decided to come back and play for us the players would welcome him back."
Howe is equally insistent that Isak's relationship with supporters can be repaired, despite the public show of anger from the away end at Villa Park on Saturday.
"I believe it can \[be repaired\]," he said.
"I believe the supporters will always react off how a player plays and gives the team.
"This has been an unfortunate situation but there are always two sides to every story.
"There's always more than even I will know, because there are conversations and things that have taken place far away from me and my knowledge off it."