Buffalo Bills defensive end Mark Anderson is out indefinitely with a knee injury sustained in Sunday's 45-3 loss to the San Francisco 49ers, and it doesn't sound promising that he'll be back any time soon.

Anderson, according to Bills GM Buddy Nix, is scheduled to meet (or has already met) with popular athletic orthopedist Dr. James Andrews regarding the injury, indicating that the issue could be significant. Nix told BuffaloBills.com that the injury will not end Anderson's season, but for the foreseeable future, at least, it looks like the Bills will be rolling with three defensive ends.

Those ends, of course, are Mario Williams, Chris Kelsay and Kyle Moore. Now would be a great time for Williams, the highest-paid defender in NFL history, to break out of his early-season funk. Expect to see him rotate between left and right end - which he did quite a bit in San Francisco - while Kelsay and Moore platoon on the other side. Kelsay will start in lieu of Anderson and will get the majority of first-team reps.

Coupled with the fact that defensive tackle Spencer Johnson - dealing with a high ankle sprain - did not travel out west with the team, it's looking very possible that the team will enter their Week 6 matchup against the Arizona Cardinals with just six healthy defensive linemen. That does not bode well for a run defense that has given up 558 rushing yards in their last two games, regardless of how poor Arizona's running game is (73 yards in the same time frame).