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Micro\u2013computed tomographic (\u00b5CT) and histomorphometric analyses showed reduced bone mass and higher osteoclast and bone resorption parameters in MDX mice compared with wild-type mice, whereas osteoblast parameters and mineral apposition rate were lower. In a panel of circulating pro-osteoclastogenic cytokines evaluated in the MDX sera, interleukin 6 (IL-6) was increased compared with wild-type mice. Likewise, DMD patients showed low bone mineral density (BMD) Z-scores and high bone-resorption marker and serum IL-6. Human primary osteoblasts from healthy donors incubated with 10% sera from DMD patients showed decreased nodule mineralization. Many osteogenic genes were downregulated in these cultures, including osterix and osteocalcin, by a mechanism blunted by an IL-6-neutralizing antibody. In contrast, the mRNAs of osteoclastogenic cytokines IL6, IL11, inhibin-\u03b2A, and TGF\u03b22 were increased, although only IL-6 was found to be high in the circulation. Consistently, enhancement of osteoclastogenesis was noted in cultures of circulating mononuclear precursors from DMD patients or from healthy donors cultured in the presence of DMD sera or IL-6. Circulating IL-6 also played a dominant role in osteoclast formation because ex vivo wild-type calvarial bones cultured with 10% sera of MDX mice showed increase osteoclast and bone-resorption parameters that were dampen by treatment with an IL-6 antibody. These results point to IL-6 as an important mediator of bone loss in DMD and suggest that targeted anti-IL-6 therapy may have a positive impact on the bone phenotype in these patients. \u00a9 2011 American Society for Bone and Mineral Research<\/jats:p>","DOI":"10.1002\/jbmr.410","type":"journal-article","created":{"date-parts":[[2011,4,20]],"date-time":"2011-04-20T19:44:55Z","timestamp":1303328695000},"page":"1891-1903","source":"Crossref","is-referenced-by-count":132,"title":["Mechanisms inducing low bone density in duchenne muscular dystrophy in mice and humans"],"prefix":"10.1093","volume":"26","author":[{"given":"Anna","family":"Rufo","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Del Fattore","sequence":"additional","affiliation":[{"name":"Ospedale Pediatrico \u201cBambino Ges\u00f9,\u201d Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy"},{"name":"Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Capulli","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Carvello","sequence":"additional","affiliation":[{"name":"Ospedale Pediatrico \u201cBambino Ges\u00f9,\u201d Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loredana","family":"De Pasquale","sequence":"additional","affiliation":[{"name":"Ospedale Pediatrico \u201cBambino Ges\u00f9,\u201d Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation and Geriatrics, University Hospital, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Pierroz","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation and Geriatrics, University Hospital, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Morandi","sequence":"additional","affiliation":[{"name":"Muscle Pathology and Immunology Unit, Istituto Neurologico \u201cC. 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