Collagen-Related Markers of Bone Turnover Reflect the Severity of Liver Fibrosis in Patients with Primary Biliary Cirrhosis

Abstract

The influence of a nonskeletal disease with increased connective tissue synthesis or degradation in the collagenrelated markers of bone turnover has been evaluated in 34 women with primary biliary cirrhosis (PBC; age range 41-81 years), a disease with increased hepatic fibrosis, often associated with osteoporosis. Serum osteocalcin (BGP), and carboxy-terminal (PICP) and amino-terminal (PINP) propeptides of type I collagen were assessed as indexes of bone formation, whereas serum tartrate-resistant acid phosphatase (TRAP), and cross-linked carboxyterminal telopeptide of type I collagen (ICTP), and urinary hydroxyproline (HYP), pyridinoline (PYR), deoxypyridinoline (DPYR), and type I collagen cross-linked N-(NTX) and C-telopeptide (CTX) were measured as markers of bone resorption. The histologic stage of the disease and serum amino-terminal propeptide of type III collagen (PIIINP) as an index of liver fibrogenesis were also evaluated. BGP levels were significantly lower, whereas PICP and PINP levels were higher in patients than in controls. Among the bone resorption markers, serum ICTP and urinary PYR, DPYR, HYP, NTX, and CTX levels were significantly higher in patients than in controls. Serum PIIINP levels were also increased in PBC patients. BGP did not correlate with PICP and PINP, but these markers of bone formation as well as ICTP, PYR, DPYR, and NTX correlated with serum PIIINP levels. Serum TRAP did not correlate with collagen-related markers of bone resorption. Moreover, patients with PIIINP and bilirubin above normal levels had higher PICP, PINP, ICTP PYR, DPYR, CTX, and NTX. These markers correlated with the histologic stage of the disease, but not with osteopenia measured by densitometric procedures in 22 patients. In conclusion, collagen-related markers of bone turnover do not reflect bone remodeling in PBC. The close association of these markers with PIIINP and the clinical and histologic stage of the liver disease suggests that they are influenced by liver collagen metabolism. (J Bone Miner Res 1998;13:731-738)

Alendronate Improves Bone Mineral Density in Primary Biliary Cirrhosis: A Randomized Placebo-Controlled Trial * #

“…22 It has been shown that in patients with PBC, NTx levels do not accurately correlate with bone turnover. 39 Collagen-derived markers of bone turnover are influenced by liver collagen metabolism, and appear to be affected in the setting of extensive liver fibrosis. 39 Almost half of the patients in the alendronate group in our study had histologically advanced liver disease (stages 3-4); therefore, the measured markers were probably affected by histological stage and did not adequately reflect changes in bone turnover.…”

“…39 Collagen-derived markers of bone turnover are influenced by liver collagen metabolism, and appear to be affected in the setting of extensive liver fibrosis. 39 Almost half of the patients in the alendronate group in our study had histologically advanced liver disease (stages 3-4); therefore, the measured markers were probably affected by histological stage and did not adequately reflect changes in bone turnover. Furthermore, it is known that NTx levels are lower in postmenopausal women receiving hormone replacement therapy compared with those not receiving hormones, 40 and a large percent of our study patients were on concomitant estrogen therapy.…”

Biochemical Markers of Bone Resorption and Hormonal Regulation of Bone Metabolism Following Liver Transplantation

“…У реципиентов после ОТП большинство исследователей анализи-руют изменения продуктов деградации коллагена 1-го типа, определяемые в моче или в сыворотке крови [4,9,11,17]. Вместе с тем имеются данные, что при патологических условиях в печени акти-визируются процессы отложения неспецифиче-ских фибриллярных коллагенов 1, 3 и 5-го типов [18,33], и следовательно, деградация некостного коллагена может явиться причиной завышенной оценки деградации костного коллагена 1-го типа, в частности бета-изомера С-терминального тело-пептида коллагена 1-го типа (бета-кросслапсов). В последнее время появились работы о высокой прогностической значимости сывороточной кост-ной фракции 5б тартрат-резистентной кислой фос-фатазы (КТРКФ-5б) -маркера остеокластической активности, который имеет низкую дневную ва-риабельность и не накапливается в циркулирую-щей крови в случае почечной или печеночной па-тологии [23].…”

“…С другой стороны, тепловая и хо-лодовая ишемия могут привести к дегенеративным изменениям клеток донорской печени и развитию миофибробласт-зависимому синтезу коллагена 1-го типа [32]. Хирургическое вмешательство и неполное восстановление функции трансплантата могли явиться причинами выработки фибробласта-ми печени неспецифических коллагенов, и в част-ности, коллагена 1-го типа, как это было отмечено у больных с хроническими заболеваниями пече-ни [18,31]. Более того, гистоморфометрическая оценка процессов резорбции и костеобразования у реципиентов через 4 месяца после ОТП показа-ла, что на фоне выраженного усиления процессов формирования кости (увеличение числа остео-бластов и объема вновь минерализованной кости) число клеток остеокластического ряда и площадь зоны резорбции практически не изменились [20].…”

Serum Markers of Liver Fibrosis: Combining the BIPED Classification and the Neo-Epitope Approach in the Development of New Biomarkers

“…Guañabens N et al [40] evaluated the bone turnover markers N-telopeptide of type I collagen (NTX), C-telopeptide of type I collagen (CTX) and N-terminal pro-peptide of collagen type I (PINP) in 34 women with primary biliary cirrhosis, a disease with increased liver fibrosis. The aim was to evaluate the influence of a nonskeletal disease with increased connective tissue synthesis or degradation on the levels of the bone turnover markers.…”