Bone microarchitecture in patients with autoimmune hepatitis

Abstract

In patients with autoimmune hepatitis (AIH), osteoporosis represents a common extrahepatic complication, which we recently demonstrated by an assessment of areal bone mineral density (aBMD) via dual-energy X-ray absorptiometry (DXA). However, it is well established that bone quality and fracture risk does not solely depend on aBMD, but also on bone microarchitecture. It is currently not known whether AIH patients exhibit a site-or compartment-specific deterioration in the skeletal microarchitecture. In order to assess potential geometric, volumetric, and microarchitectural changes, high-resolution peripheral quantitative computed tomography (HR-pQCT) measurements were performed at the distal radius and distal tibia in female patients with AIH (n=51) and compared to agematched female healthy controls (n=32) as well as AIH/primary biliary cholangitis (PBC) overlap syndrome (n=25) and PBC alone (PBC, n=36). DXA at the lumbar spine and hip, clinical characteristics, transient elastography (FibroScan) and laboratory analyses were also included in this analysis. AIH patients showed a predominant reduction of cortical thickness (Ct.Th) in the distal radius and tibia compared to heathy controls (p<0.0001 and p=0.003, respectively). In contrast, trabecular parameters such as bone volume per tissue volume (BV/TV) did not differ significantly at the distal radius (p=0.453) or tibia (p=0.508). Linear regression models revealed significant negative associations of Ct.Th with age (95% CI:-14 to-5 µm / year, p<0.0001) but not liver stiffness, cumulative prednisolone dose (even after an adjustment for age) or disease duration. The duration of high dose prednisolone (≥7.5mg) was negatively associated with trabecular thickness (Tb.Th) at the distal radius but none of the other microarchitectural parameters. No differences in bone microarchitecture parameters between AIH, AIH/PBC and PBC could be detected. In conclusion, AIH patients showed a severe age-dependent deterioration of the cortical bone microarchitecture, which is most likely the major contribution to the observed increased fracture risk in these patients.

The altered osteocytic expression of connexin 43 and sclerostin in human cadaveric donors with alcoholic liver cirrhosis: Potential treatment targets

“…Our histomorphometric analysis showed a significant association between the severity of liver tissue disturbance associated with ALC and osteocytic Cx43 and sclerostin expression levels in investigated femoral and vertebral bone samples (Figure 4). These findings suggest that the staging of liver disease could significantly contribute to ALC‐induced bone loss (Figure 5), which was previously indicated by various studies dealing with individuals with alcoholic and nonalcoholic liver disease (Culafić et al, 2014; Jadzic, Cvetkovic, Tomanovic, et al, 2020; Jadzic, et al, 2021; Schmidt et al, 2021). However, the assessed osteocytic lacunar network parameters and bone marrow adiposity parameters in lumbar vertebrae did not significantly correlate with the HAI values of the ALC group.…”

“…However, the assessed osteocytic lacunar network parameters and bone marrow adiposity parameters in lumbar vertebrae did not significantly correlate with the HAI values of the ALC group. Results of other research teams that used peripheral quantitative CT to assess bone deterioration in alcoholic and nonalcoholic liver cirrhosis patients did not show significant correlations between micro-structural bone loss and clinical stages (Schmidt et al, 2021;Wakolbinger et al, 2019), suggesting that the clinical utility of our findings requires further confirmation in large prospective studies in controlled clinical settings.…”

Increased Risk of Osteoporotic Fracture in Patients With Autoimmune Hepatitis

“…However, patients with AIH without glucocorticoid use also had an increased risk of osteoporotic fracture. Recently, possible associations between AIH and osteoporosis have been reported in small-scale studies (16)(17)(18). Notably, patients with AIH have a severe age-dependent deterioration of the cortical bone microarchitecture exceeding the age-associated bone loss in healthy controls.…”

“…Notably, patients with AIH have a severe age-dependent deterioration of the cortical bone microarchitecture exceeding the age-associated bone loss in healthy controls. This may contribute to an increased risk of osteoporotic fractures (18). Cortical bone loss is known to be a significant contributor to bone strength, and the majority of bone loss after age $65 years is cortical (19).…”

Autoimmune Lebererkrankungen – ein Update (Teil 1)

“…Dies gilt insbesondere für Patient*innen unter Steroidtherapie. Zudem sollte bei Erstdiagnose einer autoimmunen Lebererkrankung eine Knochendichtemessung (mittels Dual Energy X-Ray Absorptiometrie = DXA) veranlasst und im Verlauf je nach Befund und Therapie, spätestens jedoch alle 5 Jahre, wiederholt werden 49 – 51 .…”