DENVER – In a league with such a fine line for margin of error, the Colts were left pondering "what-ifs" for a second straight week in starting the 2016 season.

Beating yourself is no recipe for dethroning the defending Super Bowl champs and that is what happened to the Colts on Sunday afternoon.

Missed tackles and turnovers leading directly to points told the Colts' story in Week Two.

The Colts had more fourth-quarter chances for their first victory of 2016, but Denver closed the door shut with game-clinching plays.

"This is a tough one to swallow," Chuck Pagano said after the 34-20 loss, "because we had a ton of opportunities."

Sunday saw the injury theme of 2016 continue for the Colts.

Two more injuries in the secondary, to cornerback Darius Butler (hamstring) and safety Clayton Geathers (undisclosed), put the defense in another difficult situation, but the unit hung in there to give the offense an opportunity late.

Down 13-6 at halftime, the Colts put together a 13-play, 79-yard drive out of intermission with Robert Turbin's five-yard touchdown run tying things up.

The Broncos added a field goal later in the third, but the Colts began the fourth with a chance to take the lead.

With the Colts trailing 16-13, an off day for Andrew Luck had one costly mistake.

Facing a third-and-15 at the Indy 35-yard line, Luck tried to squeeze one into Jacoby Brissett. Reading it the entire way, Denver Pro Bowl cornerback Aqib Talib jumped the pass attempt and returned the pick 46 yards the other way.

"I know Andrew would love to have it back," Pagano said of the Talib pick six, pushing Denver's lead to 23-13. "We all would love to have it back.

"You have to take care of the football in that situation. If we don't have the first down, we don't have the first down."

It was up to the Colts' battered defense to try and keep things interesting. And Ted Monachino's unit did that.

After the Colts and Broncos traded punts, Luck bounced back to lead a 12-play, 80-yard touchdown drive with Frank Gore tiptoeing his way into the end zone from seven yards out.

Gore's touchdown trimmed the deficit to 23-20 with a little more than four minutes remaining.

The defense held Denver to a field goal, setting the stage for Luck and the offense, down six, with 1:51 to go.

But on the offense's first play of a potential game-winning drive, Denver's Von Miller showed why he's paid like a franchise quarterback. Miller beat Joe Reitz off the edge and his strip sack of Luck was returned 15 yards by linebacker Shane Ray to cap the Broncos victory.

"Von Miller being Von Miller," is how Pagano described one last opening evaporating for the visitors.

The Colts will now return to Indianapolis, still in search of a win in 2016.

It was a second straight week of the game in-balance late, but the inability to make enough winning plays again being the difference.

"It's very frustrating, but you've got to finish," Pagano said after the Week Two loss. "And that's what we will go back to work on.

"I know we have a good football team. But we've got to figure out a way to close it out."