Original ArticlesCircadian Variation of Urinary Type I Collagen Crosslinked C-Telopeptide and Free and Peptide-Bound Forms of Pyridinium Crosslinks
Introduction
Diurnal rhythm in bone turnover has been reported, as assessed by several bone metabolic markers. So far, urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr), urinary hydroxyproline, serum osteocalcin, the carboxyterminal propeptide of type I procollagen (PICP), the carboxyterminal pyridinoline crosslinked telopeptide of type I collagen (ICTP), and urinary excretion of crosslinked N-telopeptides of type I collagen (NTx) were reported to undergo circadian periodicities with higher values at night.2, 4, 13, 21, 24, 25, 26, 29, 34
Urinary Pyr and Dpyr are two mature crosslinking amino acids that form covalent crosslinks between adjacent collagen chains in extracellular matrix.3, 15They have been reported to be sensitive markers in assessing bone metabolic diseases.11, 22, 23, 27, 28, 33They are released from mature collagen during bone resorption and excreted in the urine in the free (∼40%–50%) or peptide-bound (50%–60%) form.16, 31, 35Using high-performance liquid chromatography (HPLC), total and free pyridinium crosslinks can be measured.[16]Several recent clinical studies disclosed that changes in the free fraction of Pyr or Dpyr might not reflect changes in the excretion of total Pyr or Dpyr.6, 17, 19Therefore, the variation of each form of urinary pyridinium crosslinks needs to be evaluated.
A direct immunoassay, using antibodies that recognize urinary type I C-telopeptide breakdown products [CrossLaps (CTx)] is now available.[8]CTx showed greater response to bisphosphonate therapy and discriminated postmenopausal status or bone metabolic diseases from premenopausal status or normals, respectively.1, 7, 18Urinary CTx was reported to undergo circadian variation in early postmenopausal women and in men.[36]
The aims of this study were: (1) to compare the circadian rhythm of bone collagen degradation as determined by urinary excretion of Pyr or Dpyr using HPLC and CTx in premenopausal women and osteoporotic women, and (2) to assess the circadian variation of free or peptide-bound forms of pyridinium crosslinks.
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Subjects
Nine healthy women aged 22–40 years [mean ± standard deviation (SD) 30.6 ± 6.7 years] and nine osteoporotic women aged 65–83 years (75.5 ± 7.5 years) were recruited. None had been treated with calcitonin or bisphosphonates in the past 6 months. All osteoporotic women had a femoral neck fracture and/or vertebral fractures, but none of the vertebral fractures had occurred during the 6 months prior to this study. Since we found that the values of the urinary biochemical markers do not change
Pyridinium Crosslinks and CTx in Premenopausal Women and Osteoporotic Women
The study population and mean assay results are shown in Table 1. Mean urinary concentrations of all pyridinium crosslinks measured by HPLC and CTx measured by ELISA were significantly higher in osteoporotic than in premenopausal women (p < 0.05, unpaired t test) (Table 1). The values of all parameters of urinary Pyr and Dpyr in osteoporotic women were approximately two- and threefold higher, respectively, than those in premenopausal women. When the values of free crosslinks measured by HPLC
Discussion
In this study, urinary CTx showed significant circadian variation with a peak value at night and a nadir during daytime. The pattern of the circadian variation of urinary CTx was congruent with those in other metabolic bone markers.2, 4, 13, 21, 24, 25, 26, 29, 34Alexandersen et al.[1]reported that urinary CTx underwent circadian variation in postmenopausal women and in men. In this study, urinary CTx underwent circadian variation in both premenopausal and osteoporotic women. Furthermore, we
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