Effects of age, menopause and osteoporosis on free, peptide-bound and total pyridinium crosslink excretion

We evaluated urinary excretion of free pyridinoline (PYD)-deoxypyridinoline (DPD) by an enzymelinked immunosorbent assay (ELISA) method, free and total PYD by high-performance liquid chromatography (HPLC), free DPD by ELISA, chemiluminiscent immunoassay (CLEIA) and HPLC, total DPD by HPLC, and N-telopeptides (NTX) and C-telopeptides (CTX) by ELISA in 234 women distributed into three groups: 43 healthy young women (aged 26.2 +/- 2.5 years), 56 control postmenopausal women (aged 55.9 +/- 4.5 years) and 133 untreated osteoporotic women (aged 55.1 +/- 4.0 years). The control postmenopausal women had increased values of all markers considered, except NTX, compared with healthy young women. The osteoporotic postmenopausal women had significantly increased values compared with control postmenopausal women for free DPD by HPLC and free DPD by ELISA or CLEIA. HPLC, ELISA and CLEIA showed adequate correlation to measure free PYD and DPD. Control postmenopausal women had significantly decreased values of the fraction of free PYD and DPD (48.4% and 32.0%, respectively), as did the osteoporotic postmenopausal women (48.0% and 46.1%), compared with healthy young women (55.3% and 57.0%). We found a significant negative correlation comparing age with fraction of free PYD and DPD, but a positive correlation with total PYD and DPD, considering or not the osteoporotic postmenopausal women. T-score and Z-score values derived from healthy young women and control postmenopausal women for PYD, DPD, NTX and CTX measured by immunoassays were calculated to detect changes in bone turnover, DPD by ELISA or CLEIA showing the highest Z-score. The sensitivity and specificity of the different assays were evaluated using a receiver operating characteristic (ROC) curve. With a specificity of 90% the sensitivity of the markers considered was low (from 33% for DPD by CLEIA to 11% for PYD-DPD by ELISA), but increased considerably with a specificity of 75%. In conclusion, urinary pyridinium crosslink derivatives increase with age and after the menopause, and rise slightly in women with osteoporosis, there being a negative correlation among age and the fraction of free PYD and DPD of the total urinary excretion. Among the resorption markers most often available in clinical laboratories, free DPD by ELISA or CLEIA was the best at discriminating osteoporotic postmenopausal women from aged-matched control postmenopausal women.