CHANGES WITH AGE IN THE URINARY-EXCRETION OF HYDROXYLYSYLPYRIDINOLINE(HP) AND LYSYLPYRIDINOLINE (LP)

There is increasing evidence that the measurement of urinary hydroxyly sylpyridinoline (HP or PYD) and lysylpyridinoline (LP or DPD) by HPLC (high performance liquid chromatography) is potentially useful in clin ical and pharmacological studies. HP and LP are promising markers of b one resorption because their levels in urine reflect the breakdown of mature collagen fibrils mainly of skeletal tissues. HP and LP are two non-reducible cross-links of mature collagen which are formed by a seq uence of post-translational modifications. HP is a derivative of three residues of hydroxylysine and is present in almost all mature tissues (e.g. tendon, vessel walls, cartilage, dentine and bone). LP is a der ivative of two residues of hydroxylysine and one residue of lysine and is present mainly in dentine and bone. Neither cross-link is found in normal human skin. We have isolated and purified HP and LP from comme rcially available bone gelatine by a preparative reverse-phase column HPLC. These two components were used as external standards for sample analysis. In the present study we analysed the urinary excretion of HP and LP in a group of 264 male and 279 female healthy subjects aged fr om 6 months to 65 years. A continuous decline of both cross-link compo nents during childhood paralleled by a decrease of the HP:LP-ratio was observed. The levels of HP and LP were 2.5-5 times higher in infants (0.5-1 year) than in children (5-10 years) and 15-20 times higher than in adults (26-65 years). After the age of 17 years, both parameters r emained at low levels. These data allow a precise quantitative monitor ing of bone resorption in patients with metabolic bone diseases or dur ing pharmacological interventions.