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• W2073644019 abstract "Pyridinoline (Pyr) and deoxypyridinoline (DPyr) are two cross-links of collagen molecules that are present in the extracellular matrix and released during its degradation. In contrast to the wide distribution of collagen, Pyr is present in bone and cartilage, but not in significant amounts in other connective tissues, and D-Pyr appears to be specific for bone tissue. Therefore, the urinary excretion of Pyr and D-Pyr might be a sensitive marker of bone matrix degradation. Using a specific high pressure liquid chromatography assay we have measured Pyr and D-Pyr cross-links in a 24-h and a fasting urine sample in 60 early postmenopausal women and 19 premenopausal women matched for age. Menopause induced a 62% increase in Fu Pyr (49.8 ± 18.7 vs. 30.8 ± 8.0 pmol//imol creatinine; P < 0.001) and an 82% increase in Fu D-Pyr (8.2 ± 3.4 vs. 4.5 ± 1.4 pmol/Vmol creatinine; P < 0.001). In 20 postmenopausal women on hormone replacement therapy, urinary Pyr and D-Pyr returned to premenopausal levels within 6 months, contrasting with unchanged levels during placebo treatment. The 24-h excretion of Pyr and D-Pyr was significantly lower than the fasting excretion, but was similarly decreased after hormone replacement therapy. Pyr and D-Pyr excretion measured in the same urinary sample were highly correlated (r = 0.85 for fasting and 0.83 for 24-h sampling), but correlations between fasting and 24-h values were weak (D-Pyr, r = 0.30; Pyr, r= 0.29; P < 0.05 for both). Correlations between urinary cross-links and other markers of bone turnover (Fu hydroxyproline/creatinine and plasma osteocalcin) were significant but low (Pyr vs. osteocalcin, r = 0.29, P < 0.05; Pyr vs. hydroxyproline, r = 0/.34; P < 0.01; D-Pyr vs. osteocalcin, r = 0.39; P < 0.01), except for D-Pyr us. hydroxyproline (r = 0.24; P = 0,07), suggesting that these markers reflect different events of bone metabolism. Finally, a single measurement of the fasting excretion, but not of the 24-h excretion, of cross-links was significantly correlated (Pyr, r = 0.34; P < 0.05; D-Pyr, r = -0.46; P < 0.01), with the subsequent spontaneous rate of bone loss assessed by repeated measurements of the radial bone mineral content in 37 postmenopausal women. The correlation with the rate of bone loss was improved when the simultaneous measurement of plasma osteocalcin and urinary hydroxyproline/creatinine was combined (Pyr, r = 0.75; P < 0.001; D-Pyr, r = 0.77; P < 0.001). We conclude that the fasting excretion of Pyr and D-Pyr reflects bone turnover changes at the menopause and the effects of hormone replacement therapy. The combination of cross-links, hydroxyproline, and osteocalcin measurement seems promising to evaluate the rate of bone loss in postmenopausal women. (J Clin Endocrinol Metab 72: 367-373, 1991) A EFFECTIVE prevention of osteoporosis can be achieved at the time of menopause with long term hormone replacement therapy. Because of the constraints, the cost, and the potential side-effects of such treatment, it is generally accepted that intervention should be targeted at women who present a high risk of osteoporosis. The two main factors responsible for that risk are represented by a low peak bone mass and a high rate of bone loss at the time of hormone replacement therapy deprivation (1, 2). The postmenopausal rate of bone loss is related to an overall increase in bone turnover, which can be assessed by several biochemical markers. Serum alkaline phosphatase and urinary hydroxyproline are commonly used to assess bone formation and Received April 15,1990. Address all correspondence and requests for reprints to: Dr. P. D. Delmas, Hopital E. Herriot, Pav. F, 69437 Lyon Cedex 03, France. resorption, respectively, but their sensitivity and specificity are limited (3). Other markers of bone formation include the bone-specific alkaline phosphatase, serum osteocalcin, also called bone gla protein (4, 5), and the carboxy-terminal propeptide of type 1 procollagen. All of these markers are increased at the time of menopause, and we have recently shown that serum osteocalcin is significantly correlated with the spontaneous rate of bone loss in recently menopausal women (6). Similarly, serum osteocalcin was reported to be the best single predictor of the rate of bone loss in a large cohort of periand postmenopausal women followed prospectively during 4 yr (7). Because an increase in bone resorption is the primary event following estrogen deficiency, a sensitive marker of bone resorption would be valuable to analyze the effects of menopause on bone turnover. As stated above, urinary hydroxyproline is not specific for bone collagen" @default.
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• W2073644019 date "1991-12-01" @default.
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• W2073644019 title "91140954 Effect of menopause and hormone replacement therapy on the urinary excretion of pyridinium cross-links" @default.
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