The Worcester tight-head will undergo ankle surgery to correct a long-standing problem on Thursday and is unlikely to play again this season.
Horsman, who qualified to play for Wales on residency grounds last October, emerged as an integral part of Ruddock's Six Nations plans after breaking into the side during the autumn internationals.
Horsman had been playing through the pain since October and the decision was taken that surgery could not be delayed any longer.
"The news comes as a blow to our ambitions to retain the Six Nations title," said Ruddock.
"Chris Horsman came through the autumn Tests with flying colours. His positive attitude to the scrummage rubbed off on other players and his work outside the scrum was also impressive.
"It's a big blow to Wales but I really feel for Chris who had only just broken into the team. It must be very disappointing for him on a personal basis.
"We wish him a complete recovery, bearing in mind that we also have him in our mid to long term plans with the World Cup in mind.
"The news should give other players the chance to go all out to prove themselves ahead of the Six Nations campaign. As with all injuries, it is a chance for players to grab the opportunity with both hands and try to hang onto the red jersey if they get it."
Adam Jones, a member of last year's Grand Slam side, is the obvious replacement and Ruddock will at least have British & Irish Lions prop Gethin Jenkins back in action.
But Wales will miss Horsman's raw power, particularly in their Six Nations opener against England and Andrew Sheridan at Twickenham.
Horsman made an immediate impact for Wales. He was sin-binned at a crucial time in the defeat to South Africa last November and was warned by Ruddock over his conduct.
He responded by turning in a powerful display the following week as the Welsh pack overpowered Australia at the Millennium Stadium during a famous 24-22 triumph.