“…Instrumental and methodological details have been published elsewhere (Cundy et al, 2015, Gamsjaeger et al, 2011a, Gamsjaeger et al, 2013, Gamsjaeger et al, 2010, Gamsjaeger et al, 2014a, Gamsjaeger et al, 2014b, Gamsjäger et al, 2009, Hofstetter et al, 2012). In the bone blocks, 600 individual measurements (each covering an area of ~ 1 × 1 μm) were obtained in randomly selected areas of interstitial bone, and the following Raman parameters calculated (Gamsjaeger et al, 2014b, Gamsjäger et al, 2009, Gamsjaeger et al, 2011b, Morris and Mandair, 2011): i) the mineral/matrix ratio (MM), ii) the relative proteoglycan content (PG), iii) the maturity/crystallinity (MMC) of the mineral crystallites, and iv) the relative content of two advanced glycation endproducts (AGEs), namely CML (ε- N -carboxymethyl- l -lysine) and PEN (Pentosidine) (Beattie et al, 2010, Beattie et al, 2011, Glenn et al, 2007, Pawlak et al, 2008). Pyrophosphate (PP) presence and spatial quantification in the bone tissue was determined using the Raman band around 360 cm − 1 (Chen et al, 2009, Cheng et al, 2009, Fuerst et al, 2010), normalized to mineral content (based on the v 2 PO 4 band), by RS imaging (210 × 130 μm areas) of open osteons.…”