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The impact of serial radon and hyperthermia exposure in a therapeutic adit on pivotal cytokines of bone metabolism in rheumatoid arthritis and osteoarthritis

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Abstract

Secondary osteoporosis is a frequent complication of rheumatoid arthritis (RA) and the result of an imbalance of catabolic and anabolic mechanisms of bone metabolism. The effects of serial low-dose radon and hyperthermia (LDRnHT) exposure in a therapeutic adit (12 applications in 3 weeks) on the serum levels of the cytokines osteoprotegerin (OPG), receptor activator of NF kappa-B ligand (RANKL), tumor necrosis factor-α (TNF-α), and also on the RANKL/OPG ratio were investigated in 25 RA patients and an age-matched control of 24 patients with osteoarthritis (OA). Cytokine measurements were performed at baseline and after completion of LDRnHT. Anti-CCP antibodies (ACPA) were measured in RA patients in parallel. Medication in both groups was limited to non-steroidal anti-inflammatory drugs, and low-dose prednisolone (16 of 24 RA patients) as needed. RA and OA patients showed a significant decrease of TNF-α levels (p < 0.001). Both groups showed significantly decreased levels of RANKL (RA: p < 0.001, OA: p < 0.01). Only the RA patients presented a significant increase of OPG (p < 0.01) and decrease of the RANKL/OPG ratio (p < 0.01), and the ACPA levels (p < 0.001). LDRnHT results in a reduction of osteocatabolic and an increase of osteoanabolic cytokines, which represents the molecular basis for inhibiting osteoclastic activity in secondary osteoporosis and explains in part the effect of LDRnHT this physical therapy modality in a key inflammatory disease. Although reduced ACPA levels were observed under the therapy and although this could potentially contribute to an osteoprotective effect, in this case, it is rather uncertain as the reduction was only minor in magnitude.

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Acknowledgments

We thank the Gasteiner Kur, REHA- and HeilstollenbetriebsgesmbH for the possibility to carry out the study, and Angelika Moder from the Gastein Research Institute for advice. They had no role in the study design, data collection and analysis, data interpretation, the writing of the manuscript, or the decision to submit the manuscript for publication.

Authors’ contributions

UL and BK conceived and designed the study. UL, KF, and EN carried out the ELISA assays. UL, GD, and IT performed the statistical analysis. UL, GD, KF, and UML interpreted the data. UL, KF, and UML drafted the manuscript. All authors revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Rheumatology, Osteology and Physical Medicine, Kerckhoff-Klinik, University of Gießen, Bad Nauheim, Germany

    Uwe Lange, Gabriel Dischereit, Ingo Tarner, Klaus Frommer, Elena Neumann & Ulf Müller-Ladner

  2. Kurhaus Hanusch, Bad Hofgastein, Austria

    Bernhard Kürten

Authors
  1. Uwe Lange
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  2. Gabriel Dischereit
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  3. Ingo Tarner
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  4. Klaus Frommer
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  5. Elena Neumann
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  6. Ulf Müller-Ladner
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  7. Bernhard Kürten
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Correspondence to Uwe Lange.

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Ethical standards

The study was conducted in cooperation with the Gastein Research Institute and was carried out in parallel following a recently published pilot study [9] approved by the ethics committee of the state of Salzburg, Austria, and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its alter amendments. Owing to the Salzburg ethics committee, approval needed to be given on oral basis as no medication was needed. However, according to data recording rules all patients submitted written consent forms, and all patients screened for participation in the study agreed to take part and fully completed the study.

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Lange, U., Dischereit, G., Tarner, I. et al. The impact of serial radon and hyperthermia exposure in a therapeutic adit on pivotal cytokines of bone metabolism in rheumatoid arthritis and osteoarthritis. Clin Rheumatol 35, 2783–2788 (2016). https://doi.org/10.1007/s10067-016-3236-7

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  • DOI: https://doi.org/10.1007/s10067-016-3236-7

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