Bone microarchitecture in patients with autoimmune hepatitis

Schmidt, Constantin; Stürznickel, Julian; Strahl, André; Oheim, Ralf; Weiler-Normann, Christina; Sebode, Marcial; Barvencik, Florian; Lohse, Ansgar W.; Schinke, Thorsten; Amling, Michael; Schramm, Christoph; Rolvien, Tim

Affiliations

¹Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

²Division of Orthopaedics, Department of Trauma and Orthopaedic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

³Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

⁴1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Abstract and keywords

In patients with autoimmune hepatitis (AIH), osteoporosis represents a common extrahepatic complication, which we recently showed 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-specific 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 age-matched female healthy controls (n = 32) as well as to female patients with AIH/primary biliary cholangitis (PBC) overlap syndrome (n = 25) and female patients with 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 healthy controls (p < .0001 and p = .003, respectively). In contrast, trabecular parameters such as bone volume fraction (BV/TV) did not differ significantly at the distal radius (p = .453) or tibia (p = .508). Linear regression models revealed significant negative associations between age and Ct.Th (95% confidence interval [CI], −14 to −5 μm/year, p < .0001), but not between liver stiffness, cumulative prednisolone dose (even after an adjustment for age), or disease duration with bone microarchitecture. The duration of high-dose prednisolone (≥7.5 mg) was negatively associated with trabecular thickness (Tb.Th) at the distal radius. 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.

Keywords: AUTOIMMUNE HEPATITIS; AUTOIMMUNE LIVER DISEASE; BONE MICROARCHITECTURE; HR-pQCT; OSTEOPOROSIS

Links

DOI: 10.1002/jbmr.4289

PubMed: 33724539

WoS: 000634881000001

History

Received: 2020-11-21

Revised: 2021-02-22

Accepted: 2021-03-11

Online: 2021-03-16

Cited Works (10)

Year	Entry
2007	Sornay‐Rendu E, Boutroy S, Munoz F, Delmas PD. Alterations of cortical and trabecular architecture are associated with fractures in postmenopausal women, partially independent of decreased BMD measured by DXA: the OFELY study. J Bone Miner Res. March 2007;22(3):425-433.
2016	Burt LA, Liang Z, Sajobi TT, Hanley DA, Boyd SK. Sex‐ and site‐specific normative data curves for HR‐pQCT. J Bone Miner Res. 2016;31(11):2041-2047.
2003	Stone KL, Seeley DG, Lui L-Y, Cauley JA, Ensrud K, Browner WS, Nevitt MC, Cummings SR; The Study of Osteoporotic Fractures research group. BMD at multiple sites and risk of fracture of multiple types: long-term results from the study of osteoporotic fractures. J Bone Miner Res. November 2003;18(11):1947-1954.
2020	Xi L, Song Y, Wu W, Qu Z, Wen J, Liao B, Tao R, Ge J, Fang D. Investigation of bone matrix composition, architecture and mechanical properties reflect structure-function relationship of cortical bone in glucocorticoid induced osteoporosis. Bone. July 2020;136:115334.
2010	Zebaze RMD, Ghasem-Zadeh A, Bohte A, Iuliano-Burns S, Mirams M, Price RI, Mackie EJ, Seeman E. Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study. Lancet. May 15, 2010;375(9727):1729-1736.
2010	Kendler DL, Roux C, Benhamou CL, Brown JP, Lillestol M, Siddhanti S, Man H-S, San Martin J, Bone HG. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res. January 2010;25(1):72-81.
2018	Chiba K, Okazaki N, Kurogi A, Isobe Y, Yonekura A, Tomita M, Osaki M. Precision of second-generation high-resolution peripheral quantitative computed tomography: intra- and intertester reproducibilities and factors involved in the reproducibility of cortical porosity. J Clin Densitom. April–June 2018;21(2):295-302.
2013	Nishiyama KK, Shane E. Clinical imaging of bone microarchitecture with HR-pQCT. Curr Osteoporos Rep. June 2013;11(2):147-155.
2012	Pialat JB, Burghardt AJ, Sode M, Link TM, Majumdar S. Visual grading of motion induced image degradation in high resolution peripheral computed tomography: impact of image quality on measures of bone density and micro-architecture. Bone. January 2012;50(1):111-118.
2020	Whittier DE, Boyd SK, Burghardt AJ, Paccou J, Ghasem-Zadeh A, Chapurlat R, Engelke K, Bouxsein ML. Guidelines for the assessment of bone density and microarchitecture in vivo using high-resolution peripheral quantitative computed tomography. Osteoporos Int. September 2020;31(9):1607-1627.