Depends what you mean by content (a book? a component? a paragraph within a component?). In general, if you are changing the bookData object, you should create a new reader. Monocle has populated all sorts of properties based on the original book data, and repopulating those would amount to creating a new reader object anyway.
If you are changing the content of a component, you can use the monocle:componentmodify event when the component loads. If you're doing it at other times, you need to iterate across the pages and drill down into the component iframes manually, then call reader.recalculateDimensions() to re-paginate the content.
Cheers,
— J