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Over the decades, the scientific perception of OA has shifted from a\u00a0simple degeneration of cartilage and bone to a\u00a0multifactorial disease involving various cell types and immunomodulatory factors. Despite a\u00a0wide range of conventional treatment modalities available, a\u00a0significant proportion of patients remain treatment refractory. Low-dose radiotherapy (LDRT) has been used for decades in the treatment of patients with inflammatory and\/or degenerative diseases and has proven a\u00a0viable option even in cohorts of patients with a\u00a0rather poor prognosis. While its justification mainly derives from a\u00a0vast body of empirical evidence, prospective randomized trials have until now failed to prove the effectiveness of LDRT. Nevertheless, over the decades, adaptions of LDRT treatment modalities have evolved using lower dosages with establishment of different treatment schedules for which definitive clinical proof is still pending. Preclinical research has revealed that the immune system is modulated by LDRT and very recently osteoimmunological mechanisms have been described. Future studies and investigations further elucidating the underlying mechanisms are an essential key to clarify the optimal patient stratification and treatment procedure, considering the patients\u2019 inflammatory status, age, and sex. The present review aims not only to present clinical and preclinical knowledge about the mechanistic and beneficial effects of LDRT, but also to emphasize topics that will need to be addressed in future studies. Further, a\u00a0concise overview of the current status of the underlying radiobiological knowledge of LDRT for clinicians is given, while seeking to stimulate further translational research.<\/jats:p>","DOI":"10.1007\/s00066-022-02038-6","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T04:03:48Z","timestamp":1672891428000},"page":"1164-1172","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Low-dose radiotherapy of osteoarthritis: from biological findings to clinical effects\u2014challenges for future studies"],"prefix":"10.1007","volume":"199","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1443-5422","authenticated-orcid":false,"given":"Thomas","family":"Weissmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9605-4841","authenticated-orcid":false,"given":"Michael","family":"R\u00fcckert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3966-2872","authenticated-orcid":false,"given":"Florian","family":"Putz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1655-373X","authenticated-orcid":false,"given":"Anna-Jasmina","family":"Donaubauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2082-216X","authenticated-orcid":false,"given":"Markus","family":"Hecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0418-4401","authenticated-orcid":false,"given":"S\u00f6ren","family":"Schnellhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Schubert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Roesch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"H\u00f6fler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5806-6158","authenticated-orcid":false,"given":"Oliver J.","family":"Ott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlen","family":"Haderlein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Lettmaier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Fietkau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6743-3351","authenticated-orcid":false,"given":"Benjamin","family":"Frey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6375-5476","authenticated-orcid":false,"given":"Udo S.","family":"Gaipl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5577-2302","authenticated-orcid":false,"given":"Lisa","family":"Deloch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,5]]},"reference":[{"issue":"3","key":"2038_CR1","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.semarthrit.2013.07.003","volume":"43","author":"M Hiligsmann","year":"2013","unstructured":"Hiligsmann\u00a0M et\u00a0al (2013) Health economics in the field of osteoarthritis: an expert\u2019s consensus paper from the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO). 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R.\u00a0Fietkau: conflict of interest Astra-Zeneca and MSD as well as honoraria from Merck Serono, Astra-Zeneca, MSD, Novocure, and research funding from Fresenius Nutrition, Merck Oncology, MSD, Astra-Zeneca, Novocure, and Siemens AG. F.\u00a0Putz reports grants and speaker fees from Siemens Healthcare GmbH and Varian not related to the present work. T.\u00a0Weissmann, M.\u00a0R\u00fcckert, A.-J.\u00a0Donaubauer, S.\u00a0Schnellhardt, P.\u00a0Schubert, J.\u00a0Roesch, D.\u00a0H\u00f6fler, O.J.\u00a0Ott, M.\u00a0Haderlein, S.\u00a0Lettmaier, B.\u00a0Frey, U.S.\u00a0Gaipl, and L.\u00a0Deloch declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}