URINARY-EXCRETION OF PYRIDINIUM CROSS-LINKS IN HEALTHY WOMEN - THE LONG-TERM EFFECTS OF MENOPAUSE AND OESTROGEN PROGESTERONE THERAPY/

OBJECTIVES We investigated the effect of the menopause when followed l ongitudinally for a decade to evaluate whether women with an increased bone loss continue to have elevated urinary excretion of pyridinium c ross-links later in menopause. Furthermore, we investigated the effect of oestrogen/progesterone therapy on the urinary excretion of pyridin ium cross-links. PARTICIPANTS In the cross-sectional study: 18 healthy premenopausal, 142 healthy post-menopausal women and 41 osteopenic po st-menopausal women. In the longitudinal study: 45 healthy post-menopa usal women followed up for 7-10 years after the menopause; these women were further divided into two equal groups, according to their loss o f forearm bone mineral content over 2 years. In the oestradiol/progest erone double-blind, placebo-controlled P-year trial: early post-menopa usal women were given either hormone replacement therapy (n = 38) or p lacebo (n = 16). MEASUREMENTS The urinary excretion of pyridinoline/ c reatinine (Pyr/Cr) and urinary deoxypyridinoline/creatinine (D-Pyr/Cr) , two new markers of bone resorption. RESULTS Pyr/Cr and D-Pyr/Cr incr eased significantly after the menopause (Pyr/Cr, 77%; D-Pyr/Cr, 98%, P < 0.001). Hormone replacement therapy reversed this increase towards premenopausal levels. Both pyridinium cross-links remained fairly cons tant during the first decade of the menopause, when measured in the lo ngitudinal study. When the women were divided according to loss in for earm BMC, those with a loss greater than 3.5%/2 years had significantl y higher levels of pyridinium cross-links (P < 0.05-0.01). Furthermore , both Pyr/Cr and D-Pyr/Cr were significantly higher in elderly osteop enic women (aged 68-72 years) than in age-matched non-osteopenic women (P < 0.01-0.001). CONCLUSIONS Both Pyr/Cr and D-Pyr/Cr, two new marke rs of bone resorption, increased significantly at the time of the meno pause, thereafter remaining fairly constant during the first post-meno pausal decade. Women with increased bone loss continue to have elevate d urinary excretion of pyridinium cross-links during the first decade of the menopause. This post-menopausal change is reversed by hormone r eplacement therapy to the premenopausal level.