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 longitudinally for a decade to evaluate whether women with an increased bone loss continue to have elevated urinary excretion of pyridinium cross-links later in menopause. Furthermore, we investigated the effect of oestrogen/progesterone therapy on the urinary excretion of pyridinium cross-links.

PARTICIPANTS: In the cross-sectional study: 18 healthy premenopausal, 142 healthy post-menopausal women and 41 osteopenic post-menopausal women. In the longitudinal study: 45 healthy post-menopausal women followed up for 7-10 years after the menopause; these women were further divided into two equal groups, according to their loss of forearm bone mineral content over 2 years. In the oestradiol/progesterone double-blind, placebo-controlled 2-year trial: early post-menopausal women were given either hormone replacement therapy (n = 38) or placebo (n = 16).

MEASUREMENTS: The urinary excretion of pyridinoline/creatinine (Pyr/Cr) and urinary deoxypyridinoline/creatinine (D-Pyr/Cr), two new markers of bone resorption.

RESULTS: Pyr/Cr and D-Pyr/Cr increased 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 constant during the first decade of the menopause, when measured in the longitudinal study. When the women were divided according to loss in forearm BMC, those with a loss greater than 3.5%/2 years had significantly higher levels of pyridinium cross-links (P < 0.05-0.01). Furthermore, both Pyr/Cr and D-Pyr/Cr were significantly higher in elderly osteopenic 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 markers of bone resorption, increased significantly at the time of the menopause, thereafter remaining fairly constant during the first post-menopausal decade. Women with increased bone loss continue to have elevated urinary excretion of pyridinium cross-links during the first decade of the menopause. This post-menopausal change is reversed by hormone replacement therapy to the premenopausal level.