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Reviews

Low-dose radiation therapy for osteoarthritis and enthesopathies: a review of current data

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Pages 1352-1367 | Received 15 Jan 2021, Accepted 09 Jul 2021, Published online: 29 Jul 2021

References

  • Afolabi HA, Zakaria ZB, Hashim MNM, Vinayak CR, Ahmed Shokri AB. 2019. Body mass index and predisposition of patients to knee osteoarthritis. Obesity Med. 16:100143.
  • Ahmed SMU, Luo L, Namani A, Wang XJ, Tang X. 2017. Nrf2 signaling pathway: pivotal roles in inflammation. Biochim Biophys Acta. 1863(2):585–597.
  • Allen KD, Coffman CJ, Golightly YM, Stechuchak KM, Keefe FJ. 2009. Daily pain variations among patients with hand, hip, and knee osteoarthritis. Osteoarthr Cartil. 17(10):1275–1282.
  • Álvarez B, Montero Á, Aramburu F, Calvo E, Ángel de la Casa M, Valero J, Hernando O, López M, Ciérvide R, García-Aranda M, et al. 2020. Radiotherapy for ostheoarticular degenerative disorders: when nothing else works. Osteoarthr Cartil Open. 1(3–4):100016.
  • Ameri A, Ameri P, Rahnama N, Mokhtari M, Sedaghat M, Hadavand F, Taghizadeh-Hesary F. 2020. Low-dose whole-lung irradiation for COVID-19 pneumonia: what is the optimal dose? Final results of a pilot study. Int J Radiat Oncol Biol Phys. 109(4):859–866.
  • Arenas M, Gil F, Gironella M, Hernández V, Biete A, Piqué JM, Panés J. 2008. Time course of anti-inflammatory effect of low-dose radiotherapy: correlation with TGF-beta(1) expression. Radiother Oncol. 86(3):399–406.
  • Arenas M, Gil F, Gironella M, Hernández V, Jorcano S, Biete A, Piqué JM, Panés J. 2006. Anti-inflammatory effects of low-dose radiotherapy in an experimental model of systemic inflammation in mice. Int J Radiat Oncol Biol Phys. 66(2):560–567.
  • Arenas M, Sabater S, Hernández V, Rovirosa A, Lara PC, Biete A, Panés J. 2012. Anti-inflammatory effects of low-dose radiotherapy. Indications, dose, and radiobiological mechanisms involved. Strahlenther Onkol. 188(11):975–981.
  • Borzì RM, Mazzetti I, Cattini L, Uguccioni M, Baggiolini M, Facchini A. 2000. Human chondrocytes express functional chemokine receptors and release matrix-degrading enzymes in response to C-X-C and C-C chemokines. Arthritis Rheum. 43(8):1734–1741.
  • Brown W, Doll R. 1965. Mortality from cancer and other causes after radiotherapy for ankylosing spondylitis. Br Med J. 2(5474):1327–1332.
  • Calabrese EJ. 2013. X-Ray treatment of carbuncles and furuncles (boils): a historical assessment. Hum Exp Toxicol. 32(8):817–827.
  • Calabrese EJ, Calabrese V. 2013. Reduction of arthritic symptoms by low dose radiation therapy (LD-RT) is associated with an anti-inflammatory phenotype. Int J Radiat Biol. 89(4):278–286.
  • Calabrese EJ, Dhawan G. 2012. The role of x-rays in the treatment of gas gangrene: a historical assessment. Dose Response. 10(4):626–643.
  • Calabrese EJ, Dhawan G. 2013. How radiotherapy was historically used to treat pneumonia: could it be useful today? Yale J Biol Med. 86(4):555–570.
  • Calabrese E, Dhawan G. 2014. Historical use of x-rays: treatment of inner ear infections and prevention of deafness. Hum Exp Toxicol. 33(5):542–553.
  • Calabrese EJ, Dhawan G, Kapoor R. 2014. Use of X-rays to treat shoulder tendonitis/bursitis: a historical assessment. Arch Toxicol. 88(8):1503–1517.
  • Calabrese EJ, Dhawan G, Kapoor R, Kozumbo WJ. 2019. Radiotherapy treatment of human inflammatory diseases and conditions: optimal dose. Hum Exp Toxicol. 38(8):888–898.
  • Calabrese EJ, Giordano JJ, Kozumbo WJ, Leak RK, Bhatia TN. 2018. Hormesis mediates dose-sensitive shifts in macrophage activation patterns. Pharmacol Res. 137:236–249.
  • Calabrese EJ, Kozumbo WJ. 2021. The hormetic dose-response mechanism: Nrf2 activation. Pharmacol Res. 167:105526.
  • Calabrese EJ, Kozumbo WJ, Kapoor R, Dhawan G, Lara PC, Giordano J. 2021. NRF2 activation putatively mediates clinical benefits of low-dose radiotherapy in COVID-19 pneumonia and acute respiratory distress syndrome (ARDS): novel mechanistic considerations. Radiother Oncol. 160:125–131.
  • Cannon B, Randolph JG, Murray JE. 1959. Malignant irradiation for benign conditions. N Engl J Med. 260(5):197–202.
  • Chu M, Zhu X, Wang C, Rong J, Wang Y, Wang S, Xing B, Tao Y, Zhuang X, Jiang L. 2017. The rs4238326 polymorphism in ALDH1A2 gene potentially associated with non-post traumatic knee osteoarthritis susceptibility: a two-stage population-based study. Osteoarthr Cartil. 25(7):1062–1067.
  • Cimmino MA, Sarzi-Puttini P, Scarpa R, Caporali R, Parazzini F, Zaninelli A, Marcolongo R. 2005. Clinical presentation of osteoarthritis in general practice: determinants of pain in Italian patients in the AMICA study. Semin Arthritis Rheum. 35(1):17–23.
  • Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, Bridgett L, Williams S, Guillemin F, Hill CL, et al. 2014. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 73(7):1323–1330.
  • Ćwikła JB, Żbikowski P, Kwiatkowska B, Buscombe JR, Sudoł-Szopińska I. 2014. Radiosynovectomy in rheumatic diseases. J Ultrason. 14(58):241–251.
  • Deloch L, Derer A, Hueber AJ, Herrmann M, Schett GA, Wölfelschneider J, Hahn J, Rühle P-F, Stillkrieg W, Fuchs J, et al. 2018. Low-dose radiotherapy ameliorates advanced arthritis in hTNF-α tg mice by particularly positively impacting on bone metabolism. Front Immunol. 9:1834–1834.
  • Donaubauer A-J, Zhou J-G, Ott OJ, Putz F, Fietkau R, Keilholz L, Gaipl US, Frey B, Weissmann T. 2020. Low dose radiation therapy, particularly with 0.5 Gy, improves pain in degenerative joint disease of the fingers: results of a retrospective analysis. IJMS. 21(16):5854.
  • DosReis GA, Lopes MF. 2009. The importance of apoptosis for immune regulation in Chagas disease. Mem Inst Oswaldo Cruz. 104(suppl 1):259–262. Retrieved from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762009000900033&nrm=iso.
  • Dray A, Read SJ. 2007. Arthritis and pain. Future targets to control osteoarthritis pain. Arthritis Res Ther. 9(3):212.
  • Esmann L, Idel C, Sarkar A, Hellberg L, Behnen M, Möller S, van Zandbergen G, Klinger M, Köhl J, Bussmeyer U, et al. 2010. Phagocytosis of apoptotic cells by neutrophil granulocytes: diminished proinflammatory neutrophil functions in the presence of apoptotic cells. J Immunol. 184(1):391–400.
  • Felson DT, Neogi T. 2018. Osteoarthritis. In Jameson JL, Fauci A, Kasper D, Hauser S, Longo D, Loscalzo J, editors. Harrison's principles of internal medicine. 19th ed. New York (NY): McGraw-Hill Education.
  • Ferri LA, Maugeri N, Rovere-Querini P, Calabrese A, Ammirati E, Cianflone D, Maseri A, Manfredi AA. 2009. Anti-inflammatory action of apoptotic cells in patients with acute coronary syndromes. Atherosclerosis. 205(2):391–395.
  • Fransen M, Bridgett L, March L, Hoy D, Penserga E, Brooks P. 2011. The epidemiology of osteoarthritis in Asia. Int J Rheum Dis. 14(2):113–121.
  • Frey B, Gaipl US, Sarter K, Zaiss MM, Stillkrieg W, Rödel F, Schett G, Herrmann M, Fietkau R, Keilholz L. 2009. Whole body low dose irradiation improves the course of beginning polyarthritis in human TNF-transgenic mice. Autoimmunity. 42(4):346–348.
  • Genard G, Lucas S, Michiels C. 2017. Reprogramming of tumor-associated macrophages with anticancer therapies: radiotherapy versus chemo- and immunotherapies. Front Immunol. 8:828.
  • Glatzel M, Frohlich D, Kraub A, Basecke S. 2002. Results of radiotherapy for. gonarthrosis. Benign News. 3:9–11.
  • Goldie I, Rosengren B, Moberg E, Hedelin E. 1970. Evaluation of radiation treatment of painful conditions of the locomotor system. A double blind study. Acta Radiol Ther Phys Biol. 9(4):311–322.
  • Grässel S, Muschter D. 2017. Peripheral nerve fibers and their neurotransmitters in osteoarthritis pathology. Int J Mol Sci. 18(5):931.
  • Hautmann MG, Hipp M, Neumaier U, Steger F, Brockmann S, Treutwein M, Ernstberger A, Ettl T, Kölbl O, Süß C. 2020. Radiotherapy for osteoarthritis of the ankle and tarsal joints-analysis of 66 joints. Strahlenther Onkol. 196(6):569–575.
  • Hautmann MG, Rechner P, Hipp M, Neumaier U, Steger F, Pohl F, Weber M, Kölbl O, Süß C. 2019. Re-irradiation for osteoarthritis-retrospective analysis of 217 joints. Strahlenther Onkol. 195(12):1060–1067.
  • Hautmann MG, Rechner P, Neumaier U, Süß C, Dietl B, Putz FJ, Behr M, Kölbl O, Steger F. 2020. Radiotherapy for osteoarthritis-an analysis of 295 joints treated with a linear accelerator. Strahlenther Onkol. 196(8):715–724.
  • Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, Liang MH, Kremers HM, Mayes MD, Merkel PA, National Arthritis Data Workgroup, et al. 2008. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 58(1):15–25.
  • Hildebrandt G, Seed MP, Freemantle CN, Alam CA, Colville-Nash PR, Trott KR. 1998. Mechanisms of the anti-inflammatory activity of low-dose radiation therapy. Int J Radiat Biol. 74(3):367–378.
  • Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, Towheed T, Welch V, Wells G, Tugwell P, et al. 2012. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res. 64(4):465–474.
  • Huynh M-LN, Fadok VA, Henson PM. 2002. Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. J Clin Invest. 109(1):41–50.
  • Jevsevar DS. 2013. Treatment of osteoarthritis of the knee: evidence-based guideline, 2nd edition. J Am Acad Orthop Surg. 21(9):571–576.
  • Johnson VL, Hunter DJ. 2014. The epidemiology of osteoarthritis. Best Pract Res Clin Rheumatol. 28(1):5–15.
  • Juniku N, Micke O, Seegenschmiedt MH, Muecke R. 2019. Radiotherapy for painful benign skeletal disorders: results of a retrospective clinical quality assessment. [Radiotherapie bei schmerzhaften benignen muskuloskeletalen Erkrankungen: Ergebnisse einer retrospektiven klinischen Qualitätskontrolle]. Strahlenther Onkol. 195(12):1068–1073.
  • Kaltenborn A, Bulling E, Nitsche M, Carl UM, Hermann RM. 2016. The field size matters: low dose external beam radiotherapy for thumb carpometacarpal osteoarthritis: importance of field size. Strahlenther Onkol. 192(8):582–588.
  • Kandahari AM, Yang X, Dighe AS, Pan D, Cui Q. 2015. Recognition of immune response for the early diagnosis and treatment of osteoarthritis. J Immunol Res. 2015:192415.
  • Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. 2011. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 7(1):33–42.
  • Keilholz L, Seegenschmiedt MH, Sauer R 1998. Radiotherapie bei schmerzhaften degenerativ-entzündlichen Gelenkerkrankungen [Radiotherapy of degenerative joint disorders. Indication, technique and clinical results]. Strahlenther Onkol 174(5):243–250.
  • Keilholz L, Seegenschmiedt H, Sauer R. 1998. Radiotherapy for painful degenerative joint disorders. Indications, technique and clinical results. Strahlenther Onkol. 174(5):243–250.
  • Keinert K, Schumann E. 1982. Ergebnisse der strahlentherapie der arthrosis deformans des kniegelenks. Dt Gesundh-Wesen. 10:445–447.
  • Keller S, Müller K, Kortmann R-D, Wolf U, Hildebrandt G, Liebmann A, Micke O, Flemming G, Baaske D. 2013. Efficacy of low-dose radiotherapy in painful gonarthritis: experiences from a retrospective East German bicenter study. Radiat Oncol. 8(1):29.
  • Kern P, Keilholz L, Forster C, Seegenschmiedt MH, Sauer R, Herrmann M. 1999. In vitro apoptosis in peripheral blood mononuclear cells induced by low-dose radiotherapy displays a discontinuous dose-dependence. Int J Radiat Biol. 75(8):995–1003.
  • Knut L. 2015. Radiosynovectomy in the therapeutic management of arthritis. World J Nucl Med. 14(1):10–15.
  • Koc BB, Schotanus MGM, Borghans R, Jong B, Maassen ME, Buijsen J, Jansen EJP. 2019. Short-term pain reduction after low-dose radiotherapy in patients with severe osteoarthritis of the hip or knee joint: a cohort study and literature review. Eur J Orthop Surg Traumatol. 29(4):843–847.
  • Kriz J, Seegenschmiedt HM, Bartels A, Micke O, Muecke R, Schaefer U, Haverkamp U, Eich HT. 2018. Updated strategies in the treatment of benign diseases-a patterns of care study of the german cooperative group on benign diseases. Adv Radiat Oncol. 3(3):240–244.
  • Kumar PG, Anand SS, Singh J, Chawla ML. 2005. Radiosynoviorthesis in the treatment of disabling arthritis. Med J Armed Forces India. 61(4):367–368.
  • Kye SY, Park K. 2017. Suicidal ideation and suicidal attempts among adults with chronic diseases: a cross-sectional study. Compr Psychiatry. 73:160–167.
  • Laba T-L, Brien J-a, Fransen M, Jan S. 2013. Patient preferences for adherence to treatment for osteoarthritis: the MEdication Decisions in Osteoarthritis Study (MEDOS). BMC Musculoskelet Disord. 14(1):160.
  • Lana JFSD, Rodrigues BL. 2019. Osteoarthritis as a chronic inflammatory disease: a review of the inflammatory markers. In Toumi H, Mazor M, editors. Osteoarthritis biomarkers and treatments. London, UK: IntechOpen.
  • Lane NE, Shidara K, Wise BL. 2017. Osteoarthritis year in review 2016: clinical. Osteoarthr Cartil. 25(2):209–215.
  • Long H, Zeng X, Liu Q, Wang H, Vos T, Hou Y, Lin C, Qiu Y, Wang K, Xing D, et al. 2020. Burden of osteoarthritis in China, 1990–2017: findings from the Global Burden of Disease Study 2017. Lancet Rheumatol. 2(3):e164–e172.
  • Ma L-L, Wang Y-Y, Yang Z-H, Huang D, Weng H, Zeng X-T. 2020. Methodological quality (risk of bias) assessment tools for primary and secondary medical studies: what are they and which is better? Mil Med Res. 7(1):7.
  • Magnusson K, Turkiewicz A, Englund M. 2019. Nature vs nurture in knee osteoarthritis – the importance of age, sex and body mass index. Osteoarthr Cartil. 27(4):586–592.
  • Mahler EAM, Minten MJ, Leseman-Hoogenboom MM, Poortmans PMP, Leer JWH, Boks SS, van den Ende CHM. 2019. Effectiveness of low-dose radiation therapy on symptoms in patients with knee osteoarthritis: a randomised, double-blinded, sham-controlled trial. Ann Rheum Dis. 78(1):83–90.
  • Maicas N, Ferrándiz ML, Brines R, Ibáñez L, Cuadrado A, Koenders MI, van den Berg WB, Alcaraz MJ. 2011. Deficiency of Nrf2 accelerates the effector phase of arthritis and aggravates joint disease. Antioxid Redox Signal. 15(4):889–901.
  • McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM, Hawker GA, Henrotin Y, Hunter DJ, Kawaguchi H, et al. 2014. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr Cartil. 22(3):363–388.
  • Micke O, Seegenschmiedt MH, Adamietz IA, Kundt G, Fakhrian K, Schaefer U, Muecke R. 2017. Low-dose radiation therapy for benign painful skeletal disorders: the typical treatment for the elderly patient? Int J Radiat Oncol Biol Phys. 98(4):958–963.
  • Micke O, Ugrak E, Bartmann S, Adamietz IA, Schaefer U, Bueker R, Kisters K, Heinrich Seegenschmiedt M, Fakhrian K, Muecke R. 2018. Radiotherapy for calcaneodynia, achillodynia, painful gonarthrosis, bursitis trochanterica, and painful shoulder syndrome - Early and late results of a prospective clinical quality assessment. Radiat Oncol. 13(1):71–71.
  • Minten MJM, Leseman-Hoogenboom MM, Kloppenburg M, Kortekaas MC, Leer JW, Poortmans PMP, van den Hoogen FHJ, den Broeder AA, van den Ende CHM. 2018. Lack of beneficial effects of low-dose radiation therapy on hand osteoarthritis symptoms and inflammation: a randomised, blinded, sham-controlled trial. Osteoarthr Cartil. 26(10):1283–1290.
  • Mistry JB, Jackson DJ, Bukhari M, Taylor AM. 2016. A role for interleukins in ochronosis in a chondrocyte in vitro model of alkaptonuria. Clin Rheumatol. 35(7):1849–1856.
  • Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. 2010. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 8(5):336–341.
  • Montero A, Sabater S, Rödel F, Gaipl US, Ott OJ, Seegenschmiedt MH, Arenas M. 2020. Is it time to redefine the role of low-dose radiotherapy for benign disease? Ann Rheum Dis. 79(3):e34.
  • Mücke R, Seegenschmiedt MH, Heyd R, Schäfer U, Prott FJ, Glatzel M, Micke O, German Cooperative Group on Radiotherapy for Benign Diseases (GCG-BD). 2010. Radiotherapy in painful gonarthrosis. Results of a national patterns-of-care study. Strahlenther Onkol. 186(1):7–17.
  • Murphy L, Schwartz TA, Helmick CG, Renner JB, Tudor G, Koch G, Dragomir A, Kalsbeek WD, Luta G, Jordan JM. 2008. Lifetime risk of symptomatic knee osteoarthritis. Arthritis Rheum. 59(9):1207–1213.
  • Nakatsukasa H, Tsukimoto M, Ohshima Y, Tago F, Masada A, Kojima S. 2008. Suppressing effect of low-dose gamma-ray irradiation on collagen-induced arthritis. J Radiat Res. 49(4):381–389.
  • Nakatsukasa H, Tsukimoto M, Tokunaga A, Kojima S. 2010. Repeated gamma irradiation attenuates collagen-induced arthritis via up-regulation of regulatory T cells but not by damaging lymphocytes directly. Radiat Res. 174(3):313–324.
  • Neogi T, Zhang Y. 2013. Epidemiology of osteoarthritis. Rheum Dis Clin North Am. 39(1):1–19.
  • Niewald M, Fleckenstein J, Naumann S, Ruebe C. 2007. Long-term results of radiotherapy for periarthritis of the shoulder: a retrospective evaluation. Radiat Oncol. 2(1):34.
  • Norouzbeigi N, Zakavi SR, Ayati N-K, Farahati J, Sadeghi R, Mirfeizi Z. 2015. Efficacy of radiosynovectomy in the treatment of chronic knee synovitis: Systematic review and meta-analysis. Iran J Nucl Med. 23(2):59–64. Retrieved from http://irjnm.tums.ac.ir/article_13269_8da6587182d18fa05e649be727559c4a.pdf.
  • Orlowsky EW, Kraus VB. 2015. The role of innate immunity in osteoarthritis: when our first line of defense goes on the offensive. J Rheumatol. 42(3):363–371.
  • Ott OJ, Hertel S, Gaipl US, Frey B, Schmidt M, Fietkau R. 2014. The Erlangen Dose Optimization Trial for radiotherapy of benign painful shoulder syndrome. Long-term results. Strahlenther Onkol. 190(4):394–398.
  • Ott OJ, Jeremias C, Gaipl US, Frey B, Schmidt M, Fietkau R. 2015. Radiotherapy for benign achillodynia. Long-term results of the Erlangen Dose Optimization Trial. Strahlenther Onkol. 191(12):979–984.
  • Ott OJ, Micke O, Mücke R, Niewald M, Rödel F, Schäfer U, Seegenschmiedt MH, Arenas M, Frey B, Gaipl US, et al. 2019. Low-dose radiotherapy: Mayday, mayday. We've been hit!. Strahlenther Onkol. 195(4):285–288.
  • Pal CP, Singh P, Chaturvedi S, Pruthi KK, Vij A. 2016. Epidemiology of knee osteoarthritis in India and related factors. Indian J Orthop. 50(5):518–522.
  • Perruche S, Saas P, Chen W. 2009. Apoptotic cell-mediated suppression of streptococcal cell wall-induced arthritis is associated with alteration of macrophage function and local regulatory T-cell increase: a potential cell-based therapy? Arthritis Res Ther. 11(4):R104.
  • Petri S, Körner S, Kiaei M. 2012. Nrf2/ARE signaling pathway: key mediator in oxidative stress and potential therapeutic target in ALS. Neurol Res Int. 2012:878030.
  • Ren Y, Xie Y, Jiang G, Fan J, Yeung J, Li W, Tam PKH, Savill J. 2008. Apoptotic cells protect mice against lipopolysaccharide-induced shock. J Immunol. 180(7):4978–4985.
  • Rödel F, Frey B, Manda K, Hildebrandt G, Hehlgans S, Keilholz L, Seegenschmiedt MH, Gaipl US, Rödel C. 2012. Immunomodulatory properties and molecular effects in inflammatory diseases of low-dose x-irradiation. Front Oncol. 2:120.
  • Rödel F, Keilholz L, Herrmann M, Sauer R, Hildebrandt G. 2007. Radiobiological mechanisms in inflammatory diseases of low-dose radiation therapy. Int J Radiat Biol. 83(6):357–366.
  • Rogers S, Eberle B, Vogt DR, Meier E, Moser L, Gomez Ordoñez S, Desborough S, Riesterer O, Takacs I, Hasler P, et al. 2020. Prospective evaluation of changes in pain levels, quality of life and functionality after low dose radiotherapy for epicondylitis, plantar fasciitis, and finger osteoarthritis. Front Med. 7:195–195.
  • Rühle PF, Wunderlich R, Deloch L, Fournier C, Maier A, Klein G, Fietkau R, Gaipl US, Frey B. 2017. Modulation of the peripheral immune system after low-dose radon spa therapy: Detailed longitudinal immune monitoring of patients within the RAD-ON01 study. Autoimmunity. 50(2):133–140.
  • Ruppert R, Seegenschmiedt MH, Sauer R. 2004. Radiotherapy of osteoarthritis. Indication, technique and clinical results. Orthopade. 33(1):56–62.
  • Ruppert R, Seegenschmiedt M, Sauer R. 2004. Radiotherapie von ArthrosenIndikation, Technik, klinische. Ergebnisse Orthopäde. 1(33):56–62.
  • Saklatvala J. 1986. Tumour necrosis factor alpha stimulates resorption and inhibits synthesis of proteoglycan in cartilage. Nature. 322(6079):547–549.
  • Salaffi F, Ciapetti A, Carotti M. 2014. The sources of pain in osteoarthritis: a pathophysiological review. Reumatismo. 66(1):57–71.
  • Sautter-Bihl ML, Liebermeister E, Scheurig H, Heinze HG. 1993. [Analgetic irradiation of degenerative-inflammatory skeletal diseases. Benefits and risks]. Dtsch Med Wochenschr. 118(14):493–498.
  • Schaue D, Jahns J, Hildebrandt G, Trott KR. 2005. Radiation treatment of acute inflammation in mice. Int J Radiat Biol. 81(9):657–667.
  • Seegenschmiedt MH, Katalinic A, Makoski H-B, Haase W, Gademann G, Hassenstein E. 2000. Radiation therapy for benign diseases: patterns of care study in Germany. Int J Radiat Oncol Biol Phys. 47(1):195–202.
  • Seegenschmiedt MH, Micke O, Muecke R, & German Cooperative Group on Radiotherapy for Non-malignant, D. 2015. Radiotherapy for non-malignant disorders: state of the art and update of the evidence-based practice guidelines. Br J Radiol. 88(1051):20150080.
  • Seegenschmiedt MH, Micke O, Niewald M, Mücke R, Eich HT, Kriz J, Heyd R, German Cooperative Group on Radiotherapy of Benign Diseases (GCG-BD) 2015. DEGRO guidelines for the radiotherapy of non-malignant disorders: part III: hyperproliferative disorders. Strahlenther Onkol. 191(7):541–548.
  • Sokolove J, Lepus CM. 2013. Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations. Ther Adv Musculoskelet Dis. 5(2):77–94.
  • Torres M, Ayra E, Albuerne O, Montano Delgado MA. 2009. Absorbed dose profiles for 32P, 90Y, 188Re, 177Lu, 153Sm and 169Er: radionuclides used in radiosynoviortheses treatment. Rev Española Med Nucl. 28(4):188–192.
  • Trott K-R, Kamprad F. 2006. Estimation of cancer risks from radiotherapy of benign diseases. Strahlenther Onkol. 182(8):431–436.
  • van den Ende CHM, Minten MJM, Leseman-Hoogenboom MM, van den Hoogen FHJ, den Broeder AA, Mahler EAM, Poortmans PMP. 2020. Long-term efficacy of low-dose radiation therapy on symptoms in patients with knee and hand osteoarthritis: follow-up results of two parallel randomised, sham-controlled trials. Lancet Rheumatol. 2(1):e42–e49.
  • Veronese N, Stubbs B, Solmi M, Smith TO, Noale M, Cooper C, Maggi S. 2017. Association between lower limb osteoarthritis and incidence of depressive symptoms: data from the osteoarthritis initiative. Age Ageing. 46(3):470–476.
  • Vina ER, Kwoh CK. 2018. Epidemiology of osteoarthritis: literature update. Curr Opin Rheumatol. 30(2):160–167.
  • Warner SC, Valdes AM. 2017. Genetic association studies in osteoarthritis: is it fairytale? Curr Opin Rheumatol. 29(1):103–109.
  • Weng L, Williams RO, Vieira PL, Screaton G, Feldmann M, Dazzi F. 2010. The therapeutic activity of low-dose irradiation on experimental arthritis depends on the induction of endogenous regulatory T cell activity. Ann Rheum Dis. 69(8):1519–1526.
  • Wieland HA, Michaelis M, Kirschbaum BJ, Rudolphi KA. 2005. Osteoarthritis – an untreatable disease? Nat Rev Drug Discov. 4(4):331–344.
  • Woolf AD, Pfleger B. 2003. Burden of major musculoskeletal conditions. Bull World Health Organ. 81(9):646–656.
  • Wunderlich R, Ernst A, Rödel F, Fietkau R, Ott O, Lauber K, Frey B, Gaipl US. 2015. Low and moderate doses of ionizing radiation up to 2 Gy modulate transmigration and chemotaxis of activated macrophages, provoke an anti-inflammatory cytokine milieu, but do not impact upon viability and phagocytic function. Clin Exp Immunol. 179(1):50–61.

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