This is fine, and is equivalent to making a change (e.g., an
annotation) to the PDF manually in a PDF reader and saving it back
to the file. You just need to make sure that the modification time
of the file has been changed, which is what Zotero uses to determine
whether to sync it.
This won't start a file sync right away, since it's essentially just
modifying the file outside of Zotero, but the file will be uploaded
in an upcoming file sync as with any other external file change. If
you want to make sure it happens sooner, you can run
`Zotero.Notifier.trigger('open', 'file',
item.id);`, which is what
gets called when an attachment is opened to indicate that the file
should be checked for potential changes at the next sync.