Urinary hydroxypyridinium crosslinks of collagen as markers of bone resorption and estrogen efficacy in postmenopausal osteoporosis

Abstract

Estrogen deficiency‐induced bone loss has been associated with accelerated bone turnover. Levels of some biochemical markers, such as serum osteocalcin (BGP), tartrate‐resistant acid phosphatase (TRAP), and urinary hydroxyproline (OHP), have been shown to be related to the rate of bone turnover. They may therefore be useful in identifying the individual at risk for osteoporosis and monitoring the efficacy of the treatment. Two recently discovered markers, urinary pyridinoline (PYD) and deoxypyridinoline (DPD), are apparently directly related to bone matrix degradation and may be more accurate markers of bone resorption than OHP or TRAP. To evaluate the effects of menopause, osteoporosis, and estrogen replacement on the excretion of these new markers, we measured the levels of PYD and DPD and other biochemical markers of bone turnover in four groups of women, premenopausal healthy (PRE), postmenopausal healthy (POST), postmenopausal osteoporotic (UTO), and postmenopausal osteoporotic with estrogen treatment (ETO). Significant increases in PYD, DPD, BGP, TRAP, and OHP were found in POST and UTO groups compared with PRE. These increases were blunted by estrogen treatment when the levels of each of the markers returned to PRE levels. When comparing POST and UTO groups, significant increases were observed in UTO only for PYD, DPD, and urinary calcium but not for OHP, BGP, or TRAP. With subgroups matched for age and years from menopause, only DPD discriminated between POST and UTO. Indices of bone formation co‐varied with markers of bone resorption in the total population. Although this held true in PRE and ETO groups, the bone resorption markers were not well correlated with bone formation markers in POST or UTO groups when they were analyzed individually. None of the markers correlated with bone mineral density measurements. Our results suggest that (1) urinary pyridinium crosslinks are significantly elevated after menopause, and estrogen replacement reverses the increase in osteoporotic patients; (2) DPD may be the most discriminating marker of bone turnover; and (3) the lack of correlation between bone resorption and formation markers found in estrogen‐deficient groups indicates the possibility of an imbalance in bone remodeling.