URINARY HYDROXYPYRIDINIUM CROSS-LINKS OF COLLAGEN IN POPULATION-BASEDSCREENING FOR OVERT VERTEBRAL OSTEOPOROSIS - RESULTS OF A PILOT-STUDY

The urinary pyridinium crosslinks pyridinoline (PYD) and deoxypyridino line (DPD) have been shown to provide valid indices of bone resorption . At present, both crosslink components are determined by reversed-pha se HPLC, a time-consuming method precluding the use of these markers f or routine purposes. Therefore, efforts have been made to develop simp le immunoassays for the rapid measurement of urinary crosslinks, and t heir application to large-scale osteoporosis screening has been propos ed. To evaluate the applicability and diagnostic validity of pyridiniu m crosslink measurements for screening purposes, urinary concentration s of total and free PYD and DPD were determined by HPLC and immunoassa y technique (ELISA) in a sample of 269 individuals (male to female rat io = 130:139; age 50-81 years) recruited at random within a population survey of vertebral osteoporosis. On a molar basis, ELISA measures of crosslink-related epitopes were highly correlated with both total and free PYD and DPD as determined by HPLC (r > 0.82, p < 0.001). Age-spe cific means for creatinine-corrected total and free pyridinium crossli nks were significantly higher in females than in males (p < 0.001). In both sexes, neither age nor anthropometric variables (weight, height, and body mass index) showed a linear effect on the urinary crosslink/ creatinine ratio. On average, 50% of the total amount of urinary cross links were present in free form. For both PYD and DPD, this proportion was significantly higher in women than in men (p < 0.05), but no chan ge was observed with age or anthropometric, measures. The excretion of pyridinium crosslinks was higher in osteoporotic (n = 18) than in non osteoporotic individuals(n = 208) from the same population. However, t his difference was statistically significant (p < 0.05) only for total PYD, total DPD, and free DPD as determined by HPLC, whereas no signif icant difference was seen with the ELISA. However, ROC analysis showed none of the crosslink measurements to provide sufficient diagnostic v alidity for screening purposes with regard to vertebral osteoporosis. Our results demonstrate that (1) the immunoassay technique provides me asurements of pyridinium crosslinks that are highly correlated with HP LC findings; (2) beyond age 50, urinary concentrations of total and fr ee pyridinium crosslinks are not linearly influenced by age or anthrop ometric factors but change with sex independently of osteoporotic stat us; and (3) although pyridinium crosslink excretion provides a valid a nd clinically useful measure of bone resorption, a single determinatio n lacks the sensitivity necessary to screen successfully for vertebral osteoporotic fractures.