It still drives me mad, but just a little bit less mad.

My recollection is that it makes no difference whether I save my spreadsheets as. I had it under Windows 7 Professional (32-bit), and I now have it under Win-10 Home (64-bit). I do not remember having the problem before then, but I might have. If you have problems with your keyboards media keys regarding shortcuts in Excel, use the Fn key to fix them. I am using Excel-2010, and have been since, well, 2011. Close Excel and delete the file that contains the Real Statistics Resource. Sometimes I also set the macro up to run if I enter a keyboard shortcut (eg Ctrl-Shift-F, where the F stands for the state the buttons have got themselves into). Uncheck the Xrealstats option on the dialog box that appears and click the OK button. I get this to run automatically either when the spreadsheet opens or when it saves. So on spreadsheets where it rears its ugly head I now write a VBA macro that re-sets the buttons'.

Extensive google searches confirmed that I wasn't alone, but offered neither explanation nor fix. I am not in a position to test whether checking 'print object' helps, because all my spreadsheets need that to be unchecked. The only 'pattern' I can notice is that it TENDS to occur only in my larger spreadsheets. Other of my spreadsheets (seem to) never exhibit the problem. I have a couple of spreadsheets that have this tendency - move around a bit and/or re-size themselves occasionally and at apparently random times.

Excel command buttons stopped working