The pair, who were in the country to study Spanish, set off for a hike in the highlands in Boquete, an area 260 miles west of Panama City, and never returned. The area is popular with foreign tourists.
The rucksack contained mobile phones, glasses and bras, and was found in a river near the Costa Rica border.
A Dutch rescue team and Panama authorities have been combing the area’s footpaths and hills, and the police are investigating the possibility of foul play.
A Facebook page has been set up to help spread the word about the missing girls.
Image credit: RTV Utrecht/YouTube