Osteo-immunological impact of radon spa treatment: due to radon or spa alone? Results from the prospective, thermal bath placebo-controlled RAD-ON02 trial

Musculoskeletal disorders (MSDs) are associated with pain and lead to reduced mobility and quality of life for patients. Radon therapy is used as alternative or complementary to pharmaceutical treatments. According to previous reports, radon spa leads to analgesic and anti-inflammatory effects, but...

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Main Authors: Denise Eckert, Megi Evic, Jasmin Schang, Maike Isbruch, Melissa Er, Lea Dörrschuck, Felicitas Rapp, Anna-Jasmina Donaubauer, Udo S. Gaipl, Benjamin Frey, Claudia Fournier
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-01-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1284609/full
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author Denise Eckert
Megi Evic
Jasmin Schang
Maike Isbruch
Melissa Er
Lea Dörrschuck
Felicitas Rapp
Anna-Jasmina Donaubauer
Udo S. Gaipl
Benjamin Frey
Claudia Fournier
author_facet Denise Eckert
Megi Evic
Jasmin Schang
Maike Isbruch
Melissa Er
Lea Dörrschuck
Felicitas Rapp
Anna-Jasmina Donaubauer
Udo S. Gaipl
Benjamin Frey
Claudia Fournier
author_sort Denise Eckert
collection DOAJ
description Musculoskeletal disorders (MSDs) are associated with pain and lead to reduced mobility and quality of life for patients. Radon therapy is used as alternative or complementary to pharmaceutical treatments. According to previous reports, radon spa leads to analgesic and anti-inflammatory effects, but the cellular and molecular mechanisms are widely unknown. A previous study (RAD-ON01) revealed, that bone erosion markers like collagen fragments (C-terminal telopeptide, CTX) are reduced after radon spa treatment in serum of patients with degenerative MSDs. Within the scope of the prospective, placebo-controlled RAD-ON02 trial presented here, we analyzed the influence of radon and thermal spa treatment on osteoclastogenesis. From patient blood, we isolate monocytes, seeded them on bone slices and differentiated them in the presence of growth factors into mature osteoclasts (mOCs). Subsequent analysis showed a smaller fraction of mOCs after both treatments, which was even smaller after radon spa treatment. A significantly reduced resorbed area on bone slices reflects this result. Only after radon spa treatment, we detected in the serum of patients a significant decrease of receptor activator of NF-κB ligand (RANKL), which indicates reduced differentiation of OCs. However, other markers for bone resorption (CTX) and bone formation (OPG, OCN) were not altered after both treatments. Adipokines, such as visfatin and leptin that play a role in some MSD-types by affecting osteoclastogenesis, were not changed after both treatments. Further, also immune cells have an influence on osteoclastogenesis, by inhibiting and promoting terminal differentiation and activation of OCs, respectively. After radon treatment, the fraction of Treg cells was significantly increased, whereas Th17 cells were not altered. Overall, we observed that both treatments had an influence on osteoclastogenesis and bone resorption. Moreover, radon spa treatment affected the Treg cell population as well as the Th17/Treg ratio were affected, pointing toward a contribution of the immune system after radon spa. These data obtained from patients enrolled in the RAD-ON02 trial indicate that radon is not alone responsible for the effects on bone metabolism, even though they are more pronounced after radon compared to thermal spa treatment.
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spelling doaj.art-79be77218d03441186137aa86ce20f962024-01-16T04:22:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-01-011410.3389/fimmu.2023.12846091284609Osteo-immunological impact of radon spa treatment: due to radon or spa alone? Results from the prospective, thermal bath placebo-controlled RAD-ON02 trialDenise Eckert0Megi Evic1Jasmin Schang2Maike Isbruch3Melissa Er4Lea Dörrschuck5Felicitas Rapp6Anna-Jasmina Donaubauer7Udo S. Gaipl8Benjamin Frey9Claudia Fournier10Department of Biophysics, GSI Helmholtzzentrum Für Schwerionenforschung, Darmstadt, GermanyDepartment of Biophysics, GSI Helmholtzzentrum Für Schwerionenforschung, Darmstadt, GermanyDepartment of Biophysics, GSI Helmholtzzentrum Für Schwerionenforschung, Darmstadt, GermanyDepartment of Biophysics, GSI Helmholtzzentrum Für Schwerionenforschung, Darmstadt, GermanyDepartment of Biophysics, GSI Helmholtzzentrum Für Schwerionenforschung, Darmstadt, GermanyDepartment of Biophysics, GSI Helmholtzzentrum Für Schwerionenforschung, Darmstadt, GermanyDepartment of Biophysics, GSI Helmholtzzentrum Für Schwerionenforschung, Darmstadt, GermanyTranslational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyTranslational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyTranslational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyDepartment of Biophysics, GSI Helmholtzzentrum Für Schwerionenforschung, Darmstadt, GermanyMusculoskeletal disorders (MSDs) are associated with pain and lead to reduced mobility and quality of life for patients. Radon therapy is used as alternative or complementary to pharmaceutical treatments. According to previous reports, radon spa leads to analgesic and anti-inflammatory effects, but the cellular and molecular mechanisms are widely unknown. A previous study (RAD-ON01) revealed, that bone erosion markers like collagen fragments (C-terminal telopeptide, CTX) are reduced after radon spa treatment in serum of patients with degenerative MSDs. Within the scope of the prospective, placebo-controlled RAD-ON02 trial presented here, we analyzed the influence of radon and thermal spa treatment on osteoclastogenesis. From patient blood, we isolate monocytes, seeded them on bone slices and differentiated them in the presence of growth factors into mature osteoclasts (mOCs). Subsequent analysis showed a smaller fraction of mOCs after both treatments, which was even smaller after radon spa treatment. A significantly reduced resorbed area on bone slices reflects this result. Only after radon spa treatment, we detected in the serum of patients a significant decrease of receptor activator of NF-κB ligand (RANKL), which indicates reduced differentiation of OCs. However, other markers for bone resorption (CTX) and bone formation (OPG, OCN) were not altered after both treatments. Adipokines, such as visfatin and leptin that play a role in some MSD-types by affecting osteoclastogenesis, were not changed after both treatments. Further, also immune cells have an influence on osteoclastogenesis, by inhibiting and promoting terminal differentiation and activation of OCs, respectively. After radon treatment, the fraction of Treg cells was significantly increased, whereas Th17 cells were not altered. Overall, we observed that both treatments had an influence on osteoclastogenesis and bone resorption. Moreover, radon spa treatment affected the Treg cell population as well as the Th17/Treg ratio were affected, pointing toward a contribution of the immune system after radon spa. These data obtained from patients enrolled in the RAD-ON02 trial indicate that radon is not alone responsible for the effects on bone metabolism, even though they are more pronounced after radon compared to thermal spa treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1284609/fullosteoclastogenesisradon and thermal spa treatmentbone metabolismTh17/Treg cellsbiomarker and degenerative musculoskeletal diseases
spellingShingle Denise Eckert
Megi Evic
Jasmin Schang
Maike Isbruch
Melissa Er
Lea Dörrschuck
Felicitas Rapp
Anna-Jasmina Donaubauer
Udo S. Gaipl
Benjamin Frey
Claudia Fournier
Osteo-immunological impact of radon spa treatment: due to radon or spa alone? Results from the prospective, thermal bath placebo-controlled RAD-ON02 trial
Frontiers in Immunology
osteoclastogenesis
radon and thermal spa treatment
bone metabolism
Th17/Treg cells
biomarker and degenerative musculoskeletal diseases
title Osteo-immunological impact of radon spa treatment: due to radon or spa alone? Results from the prospective, thermal bath placebo-controlled RAD-ON02 trial
title_full Osteo-immunological impact of radon spa treatment: due to radon or spa alone? Results from the prospective, thermal bath placebo-controlled RAD-ON02 trial
title_fullStr Osteo-immunological impact of radon spa treatment: due to radon or spa alone? Results from the prospective, thermal bath placebo-controlled RAD-ON02 trial
title_full_unstemmed Osteo-immunological impact of radon spa treatment: due to radon or spa alone? Results from the prospective, thermal bath placebo-controlled RAD-ON02 trial
title_short Osteo-immunological impact of radon spa treatment: due to radon or spa alone? Results from the prospective, thermal bath placebo-controlled RAD-ON02 trial
title_sort osteo immunological impact of radon spa treatment due to radon or spa alone results from the prospective thermal bath placebo controlled rad on02 trial
topic osteoclastogenesis
radon and thermal spa treatment
bone metabolism
Th17/Treg cells
biomarker and degenerative musculoskeletal diseases
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1284609/full
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