England forward Billy Vunipola will miss the Quilter International fixtures against South Africa, New Zealand, Japan and Australia after fracturing his left arm in the weekend's European victory over Glasgow Warriors.
No 8 Vunipola will have surgery on Tuesday and is expected to be out of action for around 12 weeks.
His brother Mako Vunipola as well as Nick Isiewke are also set for a spell on the sidelines.
Forward Isiekwe suffered an ankle sprain and is waiting to be assessed by a consultant with regards to the full extent of the injury.
Prop Mako picked up a calf strain and his progress will be monitored, said the club in a statement.
