"Ryan has gone off to hospital," said Ospreys head coach Steve Tandy.
"I think he has got a dislocation of his thumb. It may have popped through the skin as well.
"We have been patching Richard (Hibbard) up since he hurt the same shoulder playing for Wales against Samoa in November, if I am honest.
"The way he goes about his business and turns up every week is just a ridiculous effort from the boy.
"We just had to take the kid off because he would have done himself harm otherwise."
Fellow Osprey Ashley Beck was last week ruled out until the end of February with an ankle injury, while Blues lock Bradley Davies will have an operation on a similar setback later this week.
Wales will definitely be without Luke Charteris, Rhys Priestland and Aaron Jarvis for the entirety of their Grand Slam defence, while last year's player of the tournament, Dan Lydiate, is not due to return to club action until the beginning of next month and 2009 Test Lion Alun Wyn Jones is unlikely to feature until the latter part of the campaign.
Wales kick off the Six Nations at home to Ireland on February 2, before travelling to France, Italy and Scotland and then hosting England on March 16.