Bone microarchitecture and bone turnover in hepatic cirrhosis

Abstract

Summary Liver cirrhosis leads to bone loss. To date, information on bone quality (three-dimensional microarchitecture) and, thus, bone strength is scarce. We observed decreased bone quality at both assessed sites, independent of disease severity. Therefore, all patients should undergo early-stage screening for osteoporosis. Introduction Recent studies found low bone mineral density in cirrhosis, but data on bone microstructure are scarce. This study assessed weight-bearing and non-weight-bearing bones in patients with cirrhosis and healthy controls. The primary objective was to evaluate trabecular and cortical microarchitecture. Methods This was a single-center study in patients with recently diagnosed hepatic cirrhosis. Thirty-two patients and 32 controls participated in this study. After determining the type of cirrhosis, the parameters of bone microarchitecture were assessed by high-resolution peripheral quantitative computed tomography. Results Both cortical and trabecular microarchitectures showed significant alterations. At the radius, trabecular bone volume fraction was 17% lower (corrected p = 0.028), and, at the tibia, differences were slightly more pronounced. Trabecular bone volume fraction was 19% lower ( p = 0.024), cortical bone mineral density 7% ( p = 0.007), and cortical thickness 28% ( p = 0.001), while cortical porosity was 32% higher ( p = 0.023), compared to controls. Areal bone mineral density was lower (lumbar spine − 13%, total hip − 11%, total body − 9%, radius − 17%, and calcaneus − 26%). There was no correlation between disease severity and microarchitecture. Areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry (DXA) correlated well with parameters of cortical and trabecular microarchitecture. Conclusions Hepatic cirrhosis deteriorates both trabecular and cortical microarchitecture, regardless of disease severity. Areal bone mineral density is diminished at all sites as a sign of generalized affection. In patients with hepatic cirrhosis, regardless of its origin or disease severity, aBMD measurements are an appropriate tool for osteologic screening.

The severity of hepatic disorder is related to vertebral microstructure deterioration in cadaveric donors with liver cirrhosis

“…Even though some studies indicated that the etiology of LC could be an important etiopathogenetic factor in bone turnover imbalance (Beck et al, 2018; Jeong & Kim, 2019), other studies claimed the opposite. For instance, a recently published microstructural analysis of tibia and radius did not reveal any significant differences among LC of various etiology (viral, autoimmune, alcoholic, and hemochromatosis‐induced LC) (Wakolbinger et al, 2019), which is in line with our findings of lumbar vertebrae. Additionally, the same group did not observe differences in bone biomarkers, bone microstructure, and BMD between patients with alcoholic and non‐alcoholic CLD (Wakolbinger et al, 2019).…”

“…For instance, a recently published microstructural analysis of tibia and radius did not reveal any significant differences among LC of various etiology (viral, autoimmune, alcoholic, and hemochromatosis‐induced LC) (Wakolbinger et al, 2019), which is in line with our findings of lumbar vertebrae. Additionally, the same group did not observe differences in bone biomarkers, bone microstructure, and BMD between patients with alcoholic and non‐alcoholic CLD (Wakolbinger et al, 2019). Our findings support the previous observations, suggesting that the ALC‐induced negative effects on bone status originate from CLD rather than alcohol intake per se.…”

“…Based on the observed deterioration of trabecular micro‐architecture, we may assume reduced vertebral strength and increased vertebral fragility in individuals with LC, which is in line with previous findings of various clinical studies (Alcalde Vargas et al, 2012; Bang et al, 2015; Crawford et al, 2003; Wibaux et al, 2011). Importantly, our first time reported findings on cardiac cirrhosis‐induced bone loss are comparable with previously observed bone microstructural alteration in patients with biliary, autoimmune, viral, and alcoholic LC (Crilly et al, 1988; Guichelaar et al, 2002; Jadzic et al, 2020; Schmidt et al, 2018; Wakolbinger et al, 2019). To our knowledge, specific epidemiological studies regarding vertebral fracture incidence in cardiac cirrhosis are absent in the current literature, but considering our finding of reduced trabecular bone quantity microstructural parameters, it is indicative that cardiac cirrhosis could significantly contribute to an age‐associated reduction in vertebral strength.…”

“…Considering that BMD of LC patients with non‐traumatic vertebral fractures is not always in osteoporotic range (López‐Larramona, Lucendo, & González‐Delgado, 2013), a 3D microstructural analysis could provide a significant contribution to the understanding of the increased vertebral fragility in this population. To date, some bone microstructural analyses were performed in LC patients (Guichelaar, Malinchoc, Sibonga, Clarke, & Hay, 2002; Jorge‐Hernandez et al, 1988; Schmidt et al, 2018; Wakolbinger et al, 2019), but these studies varied in etiology of LC, assessed skeletal site, and applied methodology. In addition, a limited number of studies considering the particular effect of chronic alcohol consumption on human bone microstructure is available (Crilly, Anderson, Hogan, & Delaquerrière‐Richardson, 1988; Ulhøi, Meldgaard, Steiniche, Odgaard, & Vesterby, 2017), so further investigation is needed.…”

Compromised bone strength in patients with alcoholic liver cirrhosis

“…Prethodna histomorfometrijska studija, sprovedena na biopsijama ilijačne kosti pacijenata sa bilijarnom cirozom jetre, pokazala je značajan gubitak trabekularne kosti usled smanjenja debljine i broja trabekula (slika 2) (36), što je potvrđeno i kod pacijenata sa alkoholnom cirozom i hroničnim alkoholnim pankreatitisom (37,38). Slično tome, nedavno publikovana pQCT analiza je pokazala ne samo oštećenje trabekularne već i značajno propadanje kortikalne kosti tibije i radijusa (slika 2) kod bolesnika sa cirozom različitih uzroka, uključujuči alkoholom indukovanu cirozu jetre (39,40). U prilog značajnijem propadanju trabekularne kosti govore i rezultati naše prethodne studije o značajnom smanjenju ukupne koštane mase, broja, debljine i stepena povezanosti trabekula u telima lumbalnih kičmenih pršljenova kod pacijenata sa ACJ (slika 2) (41).…”