The Buffalo Bills watched two defensive players leave the game to injuries early in the fourth quarter against the Detroit Lions.

Detroit Lions quarterback Jared Goff (16) is chased by Buffalo Bills linebacker Matt Milano (58) / Junfu Han / USA TODAY NETWORK

Rookie safety Cole Bishop and veteran linebacker Matt Milano experienced lower body injuries. Both were labeled as questionable to return.

Bishop, who was starting with Taylor Rapp and Damar Hamlin both unavailable, went down on a first-down play with cramping in his lower leg. He was carted into the locker room for treatment.

On the same Lions’ possession, Baylon Spector replaced Milano at linebacker. In his third game back from a preseason biceps injury, Milano went out with a groin problem.

It was Spector’s first game action since Week 9. He injured his calf in practice leading up to the November 10 game against Indianapolis and subsequently landed on IR. The former seventh-round draft pick was activated on Saturday.

Meanwhile, Kareem Jackson came off the bench in place of Bishop. The 36-year-old veteran made his Bills’ debut as a practice squad call-up. Jackson, a 2010 first-round pick, has made 203 regular season appearances prior to joining Buffalo back in training camp.

The Lions marched 70 yards into the end zone with the two substitutes on the field. The touchdown cut the Bills’ lead to 38-28 with 12:00 remaining.

Neither Bishop nor Milano returned to the game as Buffalo closed out a 48-42 road win, ending Detroit’s 11-game win streak.

NFL Buffalo Bills safety Cole Bishop / Trevor Ruszkowski-Imagn Images