Urinary excretion of pyridinium cross‐links in healthy women; the long‐term effects of menopause and oestrogen/progesterone therapy

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Abstract
Summary: 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 (PPCONCLUSIONS 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.