Discussion
RA, OA, pain
MINOR, DISEASE, BONE EROSION, BONE DESTRUCTION, OSTEOPOROSIS, RADON EXPOSURE
The aim of this study was to investigate the effect of radon spa treatment on osteoclastogenesis and to compare the observed effects with thermal spa treatment. So far, previous studies have shown, that MSD patients show long-lasting pain reduction and a decrease of bone erosion markers such as CTX after radon spa treatment (Based on this, our hypothesis was that radon as well as thermal spa treatments inhibit the differentiation and bone resorbing activity of OCs, which in turn leads to pain relief. More pronounced effects are expected after radon spa treatment. To investigate this in patients that underwent either radon or thermal spa treatment in two consecutive years (with a crossover of the treatment modalities in the second year), we performed an To the best of our knowledge, this is the first study assessing osteoclastogenesis on bone slices after radon therapy The comparison between radon and LDRT treatment is very complex, although both are considered low-dose irradiations. Radon spa is applied as a whole-body exposure, whereas LDRT is only applied locally on the affected joint. Also, the physical doses delivered are in different orders of magnitudes, i.e. 10 x 1-10 µGy for radon spa (However, both LDRT and radon treatment are used to treat MSDs and lead to significant pain reduction (However, for X-ray exposure our own previously reported results obtained In the here presented results obtained in the frame of the RAD-ON02 study, we quantified in addition to the resorption activity and the fraction of mOCs, markers for bone resorption and formation in serum and plasma of MSD patients. We observed that RANKL was significantly decreased after radon spa treatment (These latter results are not in agreement with the respective results obtained in the preceding RAD-ON01 trial, where RANKL levels were not modified and the OPG concentration was decreased after radon spa treatment (The minor comparability of cohorts is a general problem when comparing with other studies. Further indication for a decrease of RANKL after treatment in a radon spa was reported for persons, which were healthy and at the risk age for developing osteoporosis. Moreover, in parallel to the spa treatment, they underwent physical activity. It is clear, that the inflammatory status of the individuals (healthy or suffering from MSD) and the physical activity in this study have a major influence on bone metabolism (In line with our own results, for OA patients a significant reduction of RANKL and no change of OPG after radon treatments in gallery was observed compared to before treatment, whereas in RA patients in the same study, a significant increase in OPG concentration was observed after radon spa treatment (However, CTX is mostly measured in urine. Gaisberger et al. measured the urinary CTX level in OA patients, which slightly declined both with and without radon treatment, indicating slight changes of CTX, independent of radon exposure. Both groups of patients received the same basis therapies (massage, physical training). Unfortunately, the study was not blinded and performed in a small cohort of patients, therefore the significance of the results is limited (We also investigated markers for bone formation in the plasma of patients in this study. The OCN concentration did not change after both treatments (To investigate whether radon treatment has an influence on cartilage-degrading enzymes such as MMP, we examined MMP3 and MMP9 in the serum of the patients. Radon and thermal spa treatment showed no effect on MPP3 and MPP9 concentrations in this patient cohort (As already mentioned, the solubility of radon in fat is higher than in water (A complex interaction between bone and immune cells results in the regulation of bone resorption and formation (In conclusion, we could demonstrate that radon spa treatment has an effect on the fraction and resorbing activity of mOCs, the RANKL concentration in serum, and on the T cell subtypes, which are abundant in the peripheral blood, i.e. the fraction of Treg cells that inhibits immune activity and osteoclastogenesis. However, we could not confirm previous results on other markers of bone resorption (CTX) and adipokines (visfatin), indicating the importance of a well-characterized patient cohort. These markers and markers of cartilage destruction, i.e. MMP3 and 9, were in the MSD cohorts investigated at levels of healthy individuals and therefore most likely only slightly changed, independent of radon exposure, or not changed at all.Taken together, our results showed that the observed influence on bone destruction and immune suppression are not based on radon exposure alone, but are probably more pronounced for radon spa treatment. This highlight the importance of a placebo control in a trial. In order to investigate the osteo-immunological influence of radon therapy on MSD patients, the patient collective should be defined more precisely (disease status) in future studies.