The objective of this study was to analyze the effect of surgical menopause and
Paget's disease of bone, as well as the influence of
therapy, on the isomerization of the carboxyterminal telopeptide of
type I collagen (CTX). Fourteen women who had undergone surgical menopause and had begun
hormone replacement therapy (HRT) after surgery were recruited. Results for these women were compared with those of 29 patients with
Paget's disease of bone treated with
tiludronate (400 mg/day) for 3 months, and with those of a group of 21 healthy premenopausal women (control group I). In addition, 14 healthy individuals with an age range similar to that of the pagetic patients (control group II) were included in the study. Urine samples were analyzed for levels of nonisomerized and beta-isomerized CTX (alpha-CTX and beta-CTX). Biochemical determinations were performed 3 months after surgical menopause and after 3 and 9 months of HRT, and at baseline, and 1 and 6 months after
tiludronate treatment in the pagetic patients. The average levels of alpha-CTX and beta-CTX were higher in patients than in controls. In patients after surgical menopause, because of their greater increase of beta-CTX, the alpha-CTX/beta-CTX ratio was lower than that of control group I (0.881 +/- 0.3 vs 1.515 +/- 0.8; P < 0.05). In contrast, at baseline, pagetic patients showed marked increases in alpha-CTX levels, resulting in a higher alpha-CTX/beta-CTX ratio than that of control group II (2.879 +/- 1.3 vs 0.96 +/- 0.25; P < 0.0001). The average percent decrease in both markers after
therapy was similar in both conditions (-60% for alpha-CTX and -44% for beta-CTX after 3 months of HRT in the surgical menopause group, vs -66% for alpha-CTX and -41% for beta-CTX in the pagetic group, 1 month after finishing
tiludronate therapy; P, NS), resulting in a significant decrease of the alpha-CTX/beta-CTX ratio in pagetic patients (2.879 +/- 1.3 vs. 1.614 +/- 0.8; P < 0.001). In conclusion, surgical menopause is associated with a decrease in the urinary alpha-CTX/beta-CTX ratio because of the higher increase in the beta-CTX level after menopause. Pagetic patients show an increase in this ratio, compared with the control value, and the ratio decreases after
bisphosphonate treatment. The response to
therapy was similar in both conditions, with a comparable decrease of both markers. These findings show how bone markers may contribute to the understanding of pathophysiologic mechanisms in
bone diseases.