{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T19:34:04Z","timestamp":1780342444619,"version":"3.54.1"},"reference-count":47,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Osteoporotic hip fractures are a considerable cause of pain and disability particularly among the elderly. Osteoporosis causes loss of bone stability, which in turn leads to an increased risk of fractures especially in metaphyseal bone. Moreover, the body\u2032s capacity for healing is diminished, resulting in prolonged recovery times following these fractures. The underlying mechanisms are not fully elucidated yet. Therefore, the aim of the current study was to determine the influence of age on a murine proximal femur fracture model in young and middle\u2010aged mice and whether the model could be suitable to study the molecular mechanisms of age\u2010related delayed fracture healing. A proximal femur fracture was performed in 12\u2010 and 52\u2010week\u2010old male C57BL\/6\u2009J mice. Multiplex cytokine analysis was conducted at 6\u2009h and 24\u2009h after fracture. \u00b5CT analysis, histomorphometry and immunostainings were performed at 14 and 21 days. Furthermore, spatial transcriptomics was performed at 14 days after fracture. Our data revealed an osteopenic phenotype in intact tibiae in middle\u2010aged animals. Moreover, fracture callus size, cartilage formation, expression of late chondrogenic factors and osteoblast and osteoclast numbers were significantly decreased in the fracture callus of middle\u2010aged mice. This resulted in less bone formation. Our data further suggested increased presence of p21\n                    <jats:sup>+<\/jats:sup>\n                    senescent cells and a higher expression of senescence\u2010associated secretory phenotype (SASP, e.g.: IL\u20106, CCL\u20105 and CCL\u20102) in older mice, whereas CXCL12 expression was reduced in these animals. In conclusion, we could confirm a diminished healing capacity of metaphyseal hip fractures in mice that were 52 weeks old. This was accompanied by differences in gene and protein expression including SASP\u2010factors.\n                  <\/jats:p>","DOI":"10.1002\/jor.70063","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T03:30:38Z","timestamp":1757561438000},"page":"2233-2246","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Influence of Age on Fracture Healing in Young and Middle\u2010Aged Mice in a Proximal Femur Fracture Model"],"prefix":"10.1002","volume":"43","author":[{"given":"Tabea","family":"Schmid","sequence":"first","affiliation":[{"name":"Institute of Orthopaedic Research and Biomechanics University Medical Center Ulm Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kanewska","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic and Trauma Surgery University Hospital Erlangen, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6897-2549","authenticated-orcid":false,"given":"Charles","family":"Lam","sequence":"additional","affiliation":[{"name":"Orthopaedic Trauma Institute, Department of Orthopaedic Surgery University of California San Francsisco USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Kalbitz","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic and Trauma Surgery University Hospital Erlangen, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Dieterich","sequence":"additional","affiliation":[{"name":"Institute of Orthopaedic Research and Biomechanics University Medical Center Ulm Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Ignatius","sequence":"additional","affiliation":[{"name":"Institute of Orthopaedic Research and Biomechanics University Medical Center Ulm Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Riegger","sequence":"additional","affiliation":[{"name":"Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopedics Ulm University Medical Center Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico Valerio","family":"Giger","sequence":"additional","affiliation":[{"name":"AO Research Institute Davos Davos Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2723-7342","authenticated-orcid":false,"given":"Esther","family":"Wehrle","sequence":"additional","affiliation":[{"name":"AO Research Institute Davos Davos Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph S.","family":"Marcucio","sequence":"additional","affiliation":[{"name":"Orthopaedic Trauma Institute, Department of Orthopaedic Surgery University of California San Francsisco USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore","family":"Miclau","sequence":"additional","affiliation":[{"name":"Orthopaedic Trauma Institute, Department of Orthopaedic Surgery University of California San Francsisco USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3333-2613","authenticated-orcid":false,"given":"Melanie","family":"Haffner\u2010Luntzer","sequence":"additional","affiliation":[{"name":"Institute of Orthopaedic Research and Biomechanics University Medical Center Ulm Ulm Germany"},{"name":"AO Research Institute Davos Davos Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"Osteoporosis: Assessing the Risk of Fragility Fracture. London;2017."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11657-013-0144-1"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60320-0"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.48"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2008.10.035"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12287"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI148073"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI179834"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2892"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32552-1"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2021.08.004"},{"key":"e_1_2_8_13_1","first-page":"162","article-title":"Electron Microscopic and Histologic Studies on Fracture Repair in Old and Young Rats","volume":"357","author":"Aho A. J.","year":"1966","journal-title":"Acta Chirurgica Scandinavica Supplementum"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0736-0266(00)90034-2"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.orthres.2005.04.003.1100230610"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.80B2.0800243"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1302\/2046-3758.71.BJR-2016-0334.R2"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.1"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2007.08.048"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/17453674.2016.1205172"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v040a11"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2012.04.007"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24677"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3791\/58122"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.883707"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2008.10.039"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116282"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2024.102986"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-021-02584-9"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adp8496"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101608"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/jbmrpl\/ziae023"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1239145"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-017-0413-9"},{"key":"e_1_2_8_36_1","first-page":"391","article-title":"Senile and Postmenopausal Osteoporosis","volume":"21","author":"Avioli L. V.","year":"1976","journal-title":"Advances in Internal Medicine"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13112"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.25439"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-023-00309-1"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-014-3829-x"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3801"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3579"},{"key":"e_1_2_8_43_1","doi-asserted-by":"crossref","unstructured":"D.Saul D.Jurk M. L.Doolittle et al. Distinct Secretomes in p16\u2010 and p21\u2010 Positive Senescent Cells Across Tissues.bioRxiv. 2023.","DOI":"10.1101\/2023.12.05.569858"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2019.154783"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-019-00545-7"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2015.10.025"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012369454-6\/50074-1"},{"key":"e_1_2_8_48_1","unstructured":"Of Mice and Men: Translating Mouse Age to Human Age accessed 09.03.2025."}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.70063","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:04:05Z","timestamp":1762866245000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.70063"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,10]]},"references-count":47,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/jor.70063"],"URL":"https:\/\/doi.org\/10.1002\/jor.70063","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,10]]},"assertion":[{"value":"2025-04-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}