{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:14:37Z","timestamp":1786119277721,"version":"build-2736575974"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","license":[{"start":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T00:00:00Z","timestamp":1535760000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Communications"],"published-print":{"date-parts":[[2018,9]]},"abstract":"\n Bone loss is common in advanced cirrhosis, although the precise mechanisms underlying bone loss in cirrhosis are unknown. We studied the profile and functionality of bone\u2010forming cells and bone\u2010building proteins in bone marrow (BM) of individuals with cirrhosis (n = 61) and individuals without cirrhosis as normal controls (n = 50). We also performed dual energy X\u2010ray absorptiometry for clinical correlation. BM mesenchymal cells (MSCs) were analyzed for colony\u2010forming units\u2010fibroblasts and their osteogenic (fibronectin\u20101 [\n FN1<\/jats:italic>\n ]\n ,<\/jats:italic>\n insulin\u2010like growth factor binding protein 3 [\n IGFBP3<\/jats:italic>\n ]\n ,<\/jats:italic>\n collagen type 1 alpha 1 chain [\n COL1A1<\/jats:italic>\n ]\n ,<\/jats:italic>\n runt\u2010related transcription factor 2 [\n RUNX2<\/jats:italic>\n ], and alkaline phosphatase, liver [\n ALPL<\/jats:italic>\n ]) and adipogenic ( adiponectin, C1Q, and collagen domain containing [\n ADIPOQ<\/jats:italic>\n ]\n ,<\/jats:italic>\n peroxisome proliferator\u2010activated receptor gamma [\n PPAR\u03b3<\/jats:italic>\n ]\n ,<\/jats:italic>\n and fatty acid binding protein 4 [\n FABP4<\/jats:italic>\n ]) potentials. Colony\u2010forming units\u2010fibroblasts were lower in patients with cirrhosis (\n P =<\/jats:italic>\n 0.002) than in controls. Cirrhotic BM\u2010MSCs showed >2\u2010fold decrease in osteogenic markers. Compared to controls, patients with cirrhosis showed fewer osteocytes (\n P =<\/jats:italic>\n 0.05), osteoblasts, chondroblasts, osteocalcin\u2010positive (osteocalcin+) area, clusters of differentiation (CD)169+ macrophages (\n P <<\/jats:italic>\n 0.001, each), and nestin+ MSCs (\n P =<\/jats:italic>\n 0.001); this was more apparent in Child\u2010Turcotte\u2010Pugh (CTP) class C than A (\n P <<\/jats:italic>\n 0.001). Multivariate logistic regression showed low nestin+ MSCs (\n P =<\/jats:italic>\n 0.004) as a predictor of bone loss. Bone\u2010resolving osteoclasts were comparable among CTP groups, but >2\u2010fold decreased anti\u2010osteoclastic and increased pro\u2010osteoclastic factors were noted in patients with CTP C compared to CTP A. Bone\u2010building proteins (osteocalcin [\n P =<\/jats:italic>\n 0.008], osteonectin [\n P <<\/jats:italic>\n 0.001], and bone morphogenic protein 2 [\n P =<\/jats:italic>\n 0.001]) were decreased while anti\u2010bone repair factors (fibroblast growth factor 23 [\n P =<\/jats:italic>\n 0.015] and dipeptidyl peptidase 4 [\n P <<\/jats:italic>\n 0.001]) were increased in BM and peripheral blood; this was more apparent in advanced cirrhosis. The dual energy X\u2010ray absorptiometry scan T score significantly correlated with the population of osteoblasts, osteocytes, MSCs, and CD169+ macrophages.\n Conclusion:<\/jats:italic>\n Osteoprogenitor cells are substantially reduced in patients with cirrhosis and more so in advanced disease. Additionally, increased anti\u2010bone repair proteins enhance the ineffective bone repair and development of osteoporosis in cirrhosis.\n Hepatology Communications<\/jats:italic>\n 2018;0:0\u20100)\n <\/jats:p>","DOI":"10.1002\/hep4.1234","type":"journal-article","created":{"date-parts":[[2018,9,4]],"date-time":"2018-09-04T10:23:08Z","timestamp":1536056588000},"page":"1095-1110","source":"Crossref","is-referenced-by-count":20,"title":["Suboptimal Level of Bone\u2010Forming Cells in Advanced Cirrhosis are Associated with Hepatic Osteodystrophy"],"prefix":"10.1097","volume":"2","author":[{"given":"Chhagan","family":"Bihari","sequence":"first","affiliation":[{"name":"Department of Pathology,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepika","family":"Lal","sequence":"additional","affiliation":[{"name":"Department of Pathology,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Thakur","sequence":"additional","affiliation":[{"name":"Department of Pathology,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukriti","family":"Sukriti","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhananjay","family":"Mathur","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupama G.","family":"Patil","sequence":"additional","affiliation":[{"name":"Department of Pathology,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lovkesh","family":"Anand","sequence":"additional","affiliation":[{"name":"Department of Hepatology,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guresh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shvetank","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Thapar","sequence":"additional","affiliation":[{"name":"Department of Radiology,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apurba","family":"Rajbongshi","sequence":"additional","affiliation":[{"name":"Department of Pathology,Satyavadi Raja Harish Chandra Hospital,Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana","family":"Rastogi","sequence":"additional","affiliation":[{"name":"Department of Pathology,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupam","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiv K.","family":"Sarin","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"},{"name":"Department of Hepatology,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2018,9,4]]},"reference":[{"key":"hep41234-bib-0001-20240114","doi-asserted-by":"crossref","first-page":"15499","DOI":"10.3748\/wjg.v20.i42.15499","article-title":"Extrahepatic complications to cirrhosis and portal hypertension: haemodynamic and homeostatic aspects","volume":"20","year":"2014","journal-title":"World J Gastroenterol"},{"key":"hep41234-bib-0002-20240114","doi-asserted-by":"crossref","first-page":"9427","DOI":"10.3748\/wjg.v20.i28.9427","article-title":"Osteoporosis and fractures in liver disease: relevance, pathogenesis and therapeutic implications","volume":"20","year":"2014","journal-title":"World J Gastroenterol"},{"key":"hep41234-bib-0003-20240114","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/S0016-5085(03)01062-X","article-title":"Leboff MS; American Gastroenterological Association Clinical Practice Commitee. 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