New biochemical markers of bone resorption derived from collagen breakdown in the study of postmenopausal osteoporosis.

The aim of this work was to perform a comparative study between three recently developed biochemical markers of bone resorption derived from collagen metabolism--(1) total urinary free pyridinolines (Pyr), (2) serum pyridinoline cross-linked carboxy-terminal telopeptides of type I collagen (ICTP) and (3) a urinary-specific sequence for a part of the C-telopeptide of the alpha 1 chain of type I collagen (CTX)--in the diagnosis and follow-up of postmenopausal osteoporosis. Results were also evaluated relative to the classical biochemical marker urinary hydroxyproline (Hyp). The study included 20 untreated osteoporotic postmenopausal women (OSP), age 60 +/- 6 years, range 46-69 years; 27 osteoporotic postmenopausal women treated (OSP-T) by cyclic therapy with disodium etidronate, 25-hydroxyvitamin D and calcium for a period between 3 months and 4 years (25 +/- 15 months), age 59 +/- 7 years, range 41-67 years; 17 osteopenic postmenopausal women, age 57 +/- 6 years, range 46 +/- 68 years; and 29 healthy control postmenopausal women, age 56 +/- 7 years, range 41-70 years. The diagnostic criterion for postmenopausal osteoporosis was a bone mineral density (BMD) (Hologic QDR-1000) in lumbar spine and/or femoral neck more than 2 SD below the mean value corresponding to an age- and sex-matched healthy control group. For inclusion in the osteopenic group BMD values had to be between 1 and 2 SD below the mean BMD value corresponding to the control group. We found a significant increase (p < 0.01) in the levels of Pyr/Cr and CTX/Cr (Cr = creatinine) in OSP patients with respect to the control group and we did not observe any significant difference between control and OSP-T or osteopenic women. It is interesting to note that there was a mean increase in CTX/Cr in OSP patients of 101% of the control values, while the mean increase found in Pyr/Cr concentration was only 33%. However, we did not find significant differences in the concentrations of ICTP and Hyp/Cr between groups. In a comparison of Pyr/Cr and CTX/Cr, urinary CTX showed the higher diagnostic accuracy, as can be deduced from the receiver operating characteristic (ROC) curves. CTX sensitivity was 40% with a specificity of 100%, whereas the sensitivity was 25% for urinary Pyr/Cr. In conclusion, the results of the present work suggest that in osteoporotic women CTX has the highest diagnostic accuracy among the markers of bone resporption studied.