Urinary Galactosyl-Hydroxylysine in Postmenopausal Osteoporotic Women: A Potential Marker of Bone Fragility

Abstract

Alterations of the collagen matrix, e.g., increased hydroxylation and glycosylation of lysyl residues in collagen I, were found in human osteoporotic bone, and it was suggested that they could alter the mechanical properties of skeleton. To test this hypothesis, we evaluated the content of galactosyl-hydroxylysine (GHYL) in bone collagen, as assessed by its urinary excretion, and related it to the occurrence of fracture. Two hundred and fifteen unselected postmenopausal women with osteoporosis were divided in two subgroups (comparable for age, age of menopause, bone mineral density, and biochemical parameters of bone turnover) on the basis of the history of fragility fracture; 115 patients had suffered no fracture and 100 patients had suffered one or more fractures 3 or more years before. Four urinary markers of bone turnover (hydroxyproline, cross-linked N-telopeptide, free deoxypyridoline, and GHYL) were evaluated in all patients. There was no difference between the two groups with regard to all the parameters studied except for GHYL, which was significantly higher in the group with a history of fracture (1.35 ± 0.82 mmol/mol of creatinine [Cr] versus 1.03 ± <0.48 mmol/mol Cr, p < 0.001); this marker did not correlate with other markers of bone remodeling in the fracture group, indicating a possible defect in bone collagen. In conclusion, provided that increased levels of urinary GHYL do reflect overglycosylation of hydroxylysine in bone collagen, the GHYL may be considered a marker of bone collagen quality. Our results, showing higher urinary GHYL in osteoporosis patients with fracture, seem to confirm this

Bone biomarker for the clinical assessment of osteoporosis: recent developments and future perspectives

“…Therefore, GHYL is considered as a better bone resorption biomarker than GGHYL and HYP. In previous work, the concentration of GHYL in urinary excretion has been applied to evaluate the occurrence of fracture in postmenopausal osteoporotic women without fragility fractures and postmenopausal osteoporotic women with fragility fractures [42]. The high levels of GHYL in fracture patients suggest a possible defect in bone collagen and the urinary GHYL may indeed identify such an abnormality.…”

Inflammation and arthritis: perspectives of the glycobiologist

“…However, in several affected RA patients, T cells were found to predominantly recognize the glycosylated version of the collagen II epitope [91]. In addition, increased concentrations of galactosylated HO-Lys were found in the urine of patients with a history of bone fractures and may be a marker for bone fragility [92]. Thus both glycosylated collagens and glycosylation-deficient collagen II may be involved in RA and OA.…”

Korrelieren biochemische Knochenstoffwechselmarker mit einer histologisch gesicherten High- bzw. Low-Turnover-Osteoporose?

“…Daraus ergibt sich die Frage, ob Bisphosphonate, Raloxifen und Parathormon immer gleich gut wirken und damit austauschbar sind oder ob es mög-lich sein wird, Subgruppen zu definieren, die von dem einen Wirkprinzip mehr profitieren als von dem anderen. Ein logischer Ansatz wäre die diagnostische Einteilung in High-Turnover-und Low-Turnover-Knochenstoffwechselsituationen mit dem differentialtherapeutischen Konzept, dass Patienten mit High Turnover mehr von einer antire- [27,48]. Da die Szintigraphie aufgrund der radioaktiven Belastung für die klinische Routine von den Patienten in der Regel nicht gewünscht wird, untersuchten wir bei Patienten ohne vorausgegangene Fraktur und ohne osteotrope Vorbehandlung, ob der histologische Befund mit einem bestimmten Spiegel der Knochenmarker assoziiert ist.…”