Age-related and menopause-related changes of urinary excretion of C- and N-terminal cross-linked telopeptides of type I collagen and the relationships thereof with menopause-related bone loss

Abstract

To study the age-related and menopause-related changes of urinary excretion of C- and N-terminal cross-linked telopeptides of type I collagen (uCTX/Cr and uNTX/Cr) and the relationships thereof with menopause state, years after menopause, bone mineral density (BMD), and menopause-related bone loss in healthy women. ELISA was used to examine the uCTX/Cr and uNTX/Cr of 659 female volunteers aged 20 - 80 in Changsha. Dual energy X-ray absorptiometry (DXA) was used to measure the BMD of various skeletal sites, including the lumbar vertebrae (L1 - L4) at anteroposterior (AP) position, L(2) - L(4) at lateral (LAT) position, hip, and forearm. 339 postmenopausal women among the 659 subjects were divided into 3 groups, osteoporotic, osteopenic, and normal groups according to the WHO criteria of osteoporosis diagnosis. (1) Both the curves of uCTX/Cr and uNTX/Cr with age were fit the best by regression analysis of cubic equation. The coefficients of determination (R(2)) were 0.139 for uCTX/Cr and 0.149 for uNTX/Cr. The levels of uCTX/Cr and uNTX/Cr of the women aged > 35 increased with age. (2) The values of uCTX/Cr and uNTX/Cr were 253 mg/mol +/- 101 mg/mol Cr and 63 nmol +/- 34 nmol BCE/mmol Cr respectively in the postmenopausal women, remarkably higher than those of the premenopausal women (149 mg/mol +/- 80 mg/mol Cr and 33 nmol +/- 17 nmol BCE/mmol Cr respectively), increased by 69.5% and 93.4% respectively. The annual change rates of uCTX/Cr and uNTX/Cr were the highest within the first 5 years after menopause, and these increases were in agreement with the significant decrease of BMD at most skeletal sites by 10.8% approximately 27.6%. (3) After controlled for age and body weight, both uCTX/Cr and uNTX/Cr showed significant negative correlation with BMD (r = -0.078 to -0.283, P < 0.05 or 0.01), and there was a significant positive correlation between uCTX/Cr and uNTX/Cr. (4) The elevation of the levels of uCTX/Cr and uNTX/Cr in the osteoporotic and osteopenic postmenopausal subgroups were significantly higher than those in the postmenopausal women with normal BMD (P < 0.05 or 0.01). For example, the uCTX/Cr levels of the osteoporotic, osteopenic, and normal BMD subgroups according to the DXA results at the anteroposterior lumbar spine were 189 +/- 87, 272 +/- 108, and 366 +/- 135 mg/mol Cr respectively, while the uNTX/Cr levels were 52 +/- 22, 68 +/- 34 and 108 +/- 41 nmol BCE/mmol Cr respectively. uCTX/Cr and uNTX/Cr can be used as sensitive markers to determine the bone turnover status, which is changeable with age and menopausal status in women. They present a significantly negative correlation with BMD, and increase significantly in the postmenopausal women with osteopenia or osteoporosis, which indicates that measuring uCTX/Cr and uNTX/Cr can predict age-related and menopause-related bone loss in women.