{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:24:05Z","timestamp":1786955045979,"version":"build-2736575974"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"7","funder":[{"DOI":"10.13039\/100002287","name":"The Progeria Research Foundation","doi-asserted-by":"publisher","award":["PRFCLIN2007-01"],"award-info":[{"award-number":["PRFCLIN2007-01"]}],"id":[{"id":"10.13039\/100002287","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002287","name":"The Progeria Research Foundation","doi-asserted-by":"publisher","award":["PRFCLIN2007-02"],"award-info":[{"award-number":["PRFCLIN2007-02"]}],"id":[{"id":"10.13039\/100002287","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002287","name":"The Progeria Research Foundation","doi-asserted-by":"publisher","award":["PRFCLIN2009-03"],"award-info":[{"award-number":["PRFCLIN2009-03"]}],"id":[{"id":"10.13039\/100002287","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002287","name":"The Progeria Research Foundation","doi-asserted-by":"publisher","award":["NIDDK T32DK007699-41"],"award-info":[{"award-number":["NIDDK T32DK007699-41"]}],"id":[{"id":"10.13039\/100002287","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002287","name":"The Progeria Research Foundation","doi-asserted-by":"publisher","award":["NIDDK K12DK133995"],"award-info":[{"award-number":["NIDDK K12DK133995"]}],"id":[{"id":"10.13039\/100002287","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pediatric Endocrine Society Fima Lifshitz Junior Faculty Clinical Research Grant"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ZIA HD009023"],"award-info":[{"award-number":["ZIA HD009023"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hutchinson-Gilford Progeria Syndrome (HGPS) is a devastating, ultrarare genetic premature aging disease resulting in early atherosclerosis and death during adolescence due to heart failure. Structures of mesenchymal origin, including bone, fat, and muscle, create a progressive skeletal dysplasia, lifelong failure to thrive, and a unique bone phenotype. Characterizing the interaction between muscle and bone has emerged as a powerful tool for defining drivers of bone disease in other conditions but has not been previously explored in HGPS. We examined the \u201cmuscle-bone unit\u201d using radial pQCT in youth with HGPS aged 2-18\u00a0yr before and after treatment with lonafarnib, a farnesyltransferase inhibitor that extends HGPS lifespan. Untreated radii displayed highly abnormal shapes in 70% of individuals spanning all ages. Compared to controls, HGPS forearm muscle and radial area were lower (p\u00a0&amp;lt;\u2009.001) and grew more slowly (muscle \u03b2\u00a0=\u20091.4\u00a0cm2\/yr vs 0.3\u00a0cm2\/yr in HGPS; radius \u03b2\u00a0=\u20095.8\u00a0mm2\/yr vs 0.5\u00a0mm2\/yr in HGPS). Fat area decreased with age (\u03b2\u00a0=\u2009\u2212.2\u00a0cm2\/yr, p\u00a0&amp;lt;\u2009.001) and muscle area, normalized for either BMI or radial length, was reduced in HGPS (p\u00a0=\u2009.02 and p\u2009\u2264\u2009.001, respectively). These normalized outcomes were similar to controls at younger ages but diverged as patients aged. Radial architectural changes were present even before changes in muscle area and represent a pattern distinct from the normal aging process and other muscle-wasting pediatric conditions. Lonafarnib therapy did not normalize the muscle-bone phenotype after 24 mo, although some individuals (25%) had partial normalization of radial shape. These results demonstrate that the muscle-bone unit is uncoupled in children with HGPS. Normal muscle mass for body size at younger ages implies that there is an opportunity for early treatment to avoid impending pathology. New strategies are needed to ameliorate this phenotype in HGPS, and this study provides a benchmark for gauging future therapies.<\/jats:p>","DOI":"10.1093\/jbmr\/zjaf184","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T13:05:11Z","timestamp":1764335111000},"page":"740-750","source":"Crossref","is-referenced-by-count":0,"title":["Lonafarnib clinical trials demonstrate uncoupling of the muscle-bone unit in Hutchinson-Gilford Progeria Syndrome"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1683-323X","authenticated-orcid":false,"given":"Raymond J","family":"Kreienkamp","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Endocrinology, Boston Children\u2019s Hospital , Boston, MA 02115,","place":["United States"]},{"name":"Programs in Metabolism and Medical and Population Genetics, The Broad Institute of MIT and Harvard , Cambridge, MA 02142,","place":["United States"]},{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie B","family":"Gordon","sequence":"additional","affiliation":[{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["United States"]},{"name":"Department of Pediatrics, Hasbro Children's Hospital , Providence, RI 02903,","place":["United States"]},{"name":"Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital , Boston, MA 02115 ,","place":["United States"]},{"name":"Department of Pediatrics, Boston Children\u2019s Hospital , Boston, MA 02115 ,","place":["United States"]},{"name":"The Progeria Research Foundation , Peabody, MA 01960 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Ehrbar","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Statistics, Boston University , Boston, MA 02215,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Pendleton","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Endocrinology, Boston Children\u2019s Hospital , Boston, MA 02115,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J","family":"Schiferl","sequence":"additional","affiliation":[{"name":"Bone Diagnostic LLC, Spring Branch , TX 78070,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asya","family":"Lyass","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Statistics, Boston University , Boston, MA 02215,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica E","family":"Kleinman","sequence":"additional","affiliation":[{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["United States"]},{"name":"Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital , Boston, MA 02115 ,","place":["United States"]},{"name":"Department of Pediatrics, Boston Children\u2019s Hospital , Boston, MA 02115 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian D","family":"Snyder","sequence":"additional","affiliation":[{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["United States"]},{"name":"Department of Orthopedics and Sports Medicine, Boston Children's Hospital , Boston, MA 02115,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8988-7186","authenticated-orcid":false,"given":"Catherine M","family":"Gordon","sequence":"additional","affiliation":[{"name":"Section on Adolescent Bone Health & Body Composition, Eunice Kennedy Shriver National Institute of Child Health and Human Development , Bethesda, MD 20892 ,","place":["United 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