There's no way to tell for sure exactly how many coins are lost. 21 million should be understood as the upper limit of available coins.
This is the right way to approach the question. I've seen some estimates from people I really respect (like Jameson Lopp) who put the number at something like 4 million +. So that's a potentially huge chunk of the total supply. No matter what though, it's all based on guesswork. One day, millions of old coins might scare the crap out of people when they get moved and that'll throw a wrench into any analysis about lost coins.
But we should consider - such lost exists... Always possible - and it is ongoing for long long time... Or?