Prevalence and effects of Vitamin D receptor polymorphism on bone mineral density and metabolism in patients with systemic sclerosis: a preliminary study.

Patients with systemic sclerosis (SSc) have a disproportionately high prevalence of reduced bone mineral density (BMD). Polymorphisms of the vitamin D receptor (VDR) gene have been associated with osteoporosis in patients with autoimmune diseases. The aim of this study was to investigate the prevalence and possible effects of VDR polymorphism on BMD and bone metabolism in patients with SSc. In patients with SSc measurement of BMD was performed using dual-energy X-ray absorptiometry. VDR polymorphisms (FokI, BsmI) were genotyped using restriction fragment length polymorphism analysis. Markers of bone metabolism (calcium, osteocalcin, ß-crosslaps) were determined. Primary endpoint was the prevalence of VDR gene polymorphisms and the association with reduced BMD. Secondary endpoints included associations between bone metabolism and VDR gene polymorphism. 79 Caucasian patients with SSc were included. Overall, 83.5% had reduced BMD (51.9% osteopenia, 31.6% osteoporosis). The prevalence of VDR gene polymorphism (73% BsmI, 77% FokI) was comparable to studies in healthy and rheumatic populations. The homozygous presence of FokI polymorphism, but not BsmI, was significantly associated with reduced axial BMD. Fokl polymorphism was significantly associated with reduced CTX levels, although changes remained within the reference limits. VDR polymorphisms can frequently be found in patients with SSc in comparable prevalence to healthy and rheumatic populations. The homozygous presence of FokI polymorphism, but not BsmI, was significantly associated with reduced axial BMD. This could be a possible contributor for the high prevalence of reduced BMD in 83.5% of patients with SSc in this study.Trial registration. DRKS00032768, date: 05.10.2023, retrospectively registered.

Whole-body cryotherapy for the treatment of rheumatoid arthritis: a monocentric, single-blinded, randomised controlled trial.

OBJECTIVES: To evaluate effects of whole-body cryotherapy (WBC) in rheumatoid arthritis (RA). METHODS: Patients with active RA undergoing a 16-day multimodal rheumatologic complex treatment were randomly assigned to either WBC (6 applications in 14 days at -130°C for 3 min) or no treatment. The primary outcome was the difference between groups in pain on a numerical rating scale after intervention. Secondary outcomes assessed effects on i) disease activity, ii) functional capacity, iii) cytokine levels, and iv) use of analgesics. RESULTS: A total of 56 RA patients completed the trial (intervention group [IG]: 31 patients, control group [CG]: 25 patients). The mean change (± standard error) in pain after intervention was -2 in the IG (95% confidence interval [CI] -2.75 to -1.31, p<0.001) and -0.88 (95% CI -1.43 to -0.33, p=0.003) in the CG, with a baseline-adjusted between-group difference of -1.31 ± 0.4 (95% CI -2.1 to -0.53; p=0.002). Pain at the 12-week follow-up visit remained significantly below baseline values in the IG. Disease activity and functional capacity showed statistically and clinically meaningful improvement after intervention but were not significant at the 12-week follow up. TNF and IL-6 levels changed significantly in the IG. Eighteen of 31 (58%) patients of the IG reduced or discontinued analgesics at the 12-week follow-up. No WBC-related side effects were reported. CONCLUSIONS: WBC in RA reduces pain and disease activity significantly and in a clinically meaningful manner, resulting in a reduction of analgesics. These effects are potentially based on a change in cytokine levels.

[Pain reduction through physical medicine : Update on the evidence]. / Schmerzreduktion durch physikalische Medizin : Update zur Evidenz.

Epidemiological data from the core documentation of the regional cooperative rheumatism centers in Germany confirm that the symptom of pain is an immense problem in both active inflammatory rheumatic diseases and when in remission. By definition pain is an unpleasant sensory and emotional experience. In the context of inflammatory rheumatic diseases, nociceptive pain is triggered by inflammatory mediators or structurally mechanical distress via activation of the nociceptors. In addition, inflammation is also locally enhanced by the release of proinflammatory substances, such as substance P or calcitonin gene-related peptide (CGRP) from activated nociceptors. The phenomena of inflammation and pain are linked in a self-reinforcing mechanism, which explains why pain can be effectively controlled by inhibiting inflammation and, conversely, why inhibiting pain also has positive effects on the inflammatory response. This review focuses on publications on multimodal rheumatological complex treatment and thermotherapy, which, under evidence-based study criteria, showed a reduction in pain and a partial influencing of molecular markers with a subsequent influence on the development of pain and the inflammatory process. The results are presented in the context of current physiological knowledge on the development of pain.

Serial whole-body cryotherapy in fibromyalgia is effective and alters cytokine profiles.

INTRODUCTION: Whole-body cryotherapy (WBC) has shown to be beneficial in the treatment of fibromyalgia (FM). There is cumulative evidence that cytokines play a crucial role in FM. It's unknown whether clinical effects of WBC can be demonstrated at the molecular level and how long the effects last. METHODS: We compared effects of serial WBC (6 sessions (- 130 °C in 6 weeks) in FM patients and healthy controls (HC). Primary outcome was the change in pain level (visual analogue scale 0-100 mm) after 6 sessions. Secondary outcomes were a change in disease activity (revised Fibromyalgia Impact Questionnaire) and pain after 3 sessions and 3 months after discontinued therapy and in cytokine levels (interleukin (IL-)1, IL-6, tumor necrosis factor α (TNF-α) and IL-10). The patients' opinions on the satisfaction, effectiveness and significance of WBC were evaluated. RESULTS: Twenty-three FM patients and 30 HC were enrolled. WBC resulted in a significant reduction in pain and disease activity after 3 and 6 sessions. No clinical benefit could be measured 3 months after discontinued treatment. Overall, probands were satisfied with WBC and considered WBC to be important and effective. FM patients had significantly different levels of IL-1, IL-6, TNF-α and IL-10 at each reading point compared to HC. Levels of IL-1, IL-6 and IL-10 were significantly altered over time in FM patients. Compared to HC FM patients showed a significantly different response of IL1, - 6 and - 10 to WBC. CONCLUSION: Serial WBC is a fast acting and effective treatment for FM. Proven effects of WBC may be explained by changes in cytokines.

Serial whole-body cryotherapy in fibromyalgia is effective and alters cytokine profiles

Abstract Introduction: Whole-body cryotherapy (WBC) has shown to be beneficial in the treatment of fibromyalgia (FM). There is cumulative evidence that cytokines play a crucial role in FM. It's unknown whether clinical effects of WBC can be demonstrated at the molecular level and how long the effects last. Methods: We compared effects of serial WBC (6 sessions (- 130 °C in 6 weeks) in FM patients and healthy controls (HC). Primary outcome was the change in pain level (visual analogue scale 0-100 mm) after 6 sessions. Secondary outcomes were a change in disease activity (revised Fibromyalgia Impact Questionnaire) and pain after 3 sessions and 3 months after discontinued therapy and in cytokine levels (interleukin (IL-)1, IL-6, tumor necrosis factor α (TNF-α) and IL-10). The patients' opinions on the satisfaction, effectiveness and significance of WBC were evaluated. Results: Twenty-three FM patients and 30 HC were enrolled. WBC resulted in a significant reduction in pain and disease activity after 3 and 6 sessions. No clinical benefit could be measured 3 months after discontinued treatment. Overall, probands were satisfied with WBC and considered WBC to be important and effective. FM patients had significantly different levels of IL-1, IL-6, TNF-α and IL-10 at each reading point compared to HC. Levels of IL-1, IL-6 and IL-10 were significantly altered over time in FM patients. Compared to HC FM patients showed a significantly different response of IL1, - 6 and - 10 to WBC. Conclusion: Serial WBC is a fast acting and effective treatment for FM. Proven effects of WBC may be explained by changes in cytokines.(AU)

Serial locally applied water-filtered infrared a radiation in axial spondyloarthritis - a randomized controlled trial.

INTRODUCTION: Aim of this randomized controlled trial was to evaluate the effects of serial locally applied water-filtered infrared A radiation (sl-wIRAR) in patients with axial spondyloarthritis (axSpA). METHODS: axSpA patients with active disease undergoing a 7-day multimodal rheumatologic complex treatment under non-steroidal anti-inflammatory drug (NSAID) therapy were eligible. Patients were randomly assigned in a 1:1 ratio. The intervention group (IG) received additional sl-wIRAR treatment of the back (2 treatments for 30 min per day for 6 days) to assess whether locally applied hyperthermia can i) reduce pain levels, ii) reduce disease activity and improve functionality and iii) whether an effect on tumor necrosis factor α (TNFα) levels is detectable. Additionally, it was examined whether a reduction in NSAID therapy could be achieved after trial completion. RESULTS: 71 patients completed the trial (IG: 36 patients, control group (CG) 35 patients). sl-wIRAR led to a significant pain reduction measured by a numeric rating scale (p < .0005) and in comparison, to the CG (p = .006). sl-wIRAR treatment resulted in a significant reduction in the Bath Anyklosing Spondylitis Disease Activity Index (BASDAI) (p = .004) and Bath Ankylosing Spondylitis Functional Index (p = .004) with no significant difference to the CG. TNF-α levels were significantly decreased (p = .001) only in the IG with a significant difference to the CG (p = .01). 26 (76%) of patients in the IC reduced their NSAID therapy after trial completion. CONCLUSION: sl-wIRAR treatment in axSpA leads to a rapid reduction in pain allowing NSAID dosage reduction. A reason for these desirable effects could be a change in TNFα levels.

Evaluation of a special concept of physical therapy in spondyloarthritis: German multimodal rheumatologic complex treatment for spondyloarthritis.

OBJECTIVES: Multimodal rheumatologic complex treatment (MRCT) is a specific concept of German inpatient care focusing on physical therapy for patients with rheumatic diseases suffering from exacerbated pain and functional impairment. As physical therapy is a key concept in the treatment of spondyloarthritis (SpA), we conducted a monocentric retrospective analysis of the effects of MRCT on pain and functional status in patients with SpA including patients with axial spondyloarthritis (axSpA), non-radiographic axial spondyloarthritis (nr-axSpA) and psoriatic arthritis with axial involvement (axPsA). METHODS: 134 treatment episodes provided to 100 patients with SpA between 2014 and 2017 were analysed. We evaluated changes in pain intensity, in functional status and in disease activity before and after a treatment episode. In addition, we assessed potential influences of various patient characteristics, the course of the disease and comorbidities. RESULTS: Overall, MRCT resulted in significant amelioration of pain (NRS: p < 0.001), significant improvement of functional capacity (FFbH: p = 0.03; HAQ: p = 0.02; BASFI: p < 0.001) and significant reduction of disease activity (BASDAI p < 0.001; DAS28: p = 0.009). In general, treatment effects on axSpA, nr-axSpA and axPsA were comparable. Different aspects of the disease and its previous course did not have a significant effect on the outcome parameters. Comorbidities (e.g. fibromyalgia) did not significantly influence treatment response. CONCLUSION: MRCT not only decreases pain and improves function but also reduces disease activity in patients with axSpA, nr-axSpA and axPsA irrespective of the course of disease and comorbidities (e.g. fibromyalgia), thus underlining the importance of non-pharmacological and physical treatment in the treatment of SpA.Key Points• Physical treatment is a key component in treating SpA.• Multimodal rheumatologic complex treatment (MRCT) is a specific concept of German inpatient care focusing on physical therapy for patients with rheumatic diseases suffering from exacerbated pain and functional impairment.• MRCT not only decreases pain and improves function but also reduces disease activity in patients with axSpA, nr-axSpA and axPsA irrespective of the course of disease and comorbidities (e.g. fibromyalgia).• MRCT could be a role model of treating SpA by means of physical therapy as its effects are not influenced by therapy, disease duration or comorbidities and as it has no side effects.

Adult lactose intolerance, calcium intake, bone metabolism and bone density in German-Turkish immigrants.

INTRODUCTION: Adult lactose intolerance (ALI) significantly alters calcium intake and absorption, and thus may promote osteoporosis. ALI is a recessive condition with a geographical north-south gradient characterised by decreased levels of intestinal lactase. PCR-based genotyping of lactase (LCT) gene polymorphisms is a safe and easy way to diagnose ALI and may complement diagnostic procedures to identify individuals at risk for reduced calcium intake and subsequently osteoporosis due to lactose malabsorption. Therefore, we investigated the frequency of ALI and its influence on calcium intake, markers of bone metabolism and bone mineral density (BMD) in a cohort of Turkish immigrants living in Germany. MATERIALS AND METHODS: We investigated single nucleotide polymorphisms of the LCT gene, calcium intake, markers of bone metabolism and BMD in 183 Turkish immigrants. RESULTS: ALI was diagnosed in 154 out of 183 (81%) probands. ALI was significantly associated with self-reported lactose intolerance (p < 0.001) and dislike for dairy products (p < 0.01). Osteopenia was diagnosed in 59 out of 183 (32%) and osteoporosis in 15 out of 183 (8%) probands. Probands with reduced BMD had ALI in 86%. All probands had a decreased calcium intake [mg/week]. There was no significant association between ALI, calcium intake, markers of bone metabolism or BMD. CONCLUSION: Turkish immigrants mostly have ALI and overall show a reduced calcium intake per week. However, ALI did not significantly influence calcium intake, markers of bone metabolism or BMD in this cohort. Therefore, ALI in Turkish immigrants does not seem to be a risk factor for osteoporosis.

Potentials and Limits of Physiotherapy in Osteoarthritis.

BACKGROUND: In view of the already existing and the expected growing costs due to the pathological osteoarthritic joint alterations and the related consequences, preventive and conservative strategies which can avoid or delay osteoarthritic joint alterations are welcomed from a socioeconomical perspective. Here, it should be mentioned that corresponding primary prevention measures should take place early by already educating children about a healthy diet and motivating them to regular physical exercise. In overt or symptomatic osteoarthritis, a good joint function and reduction of disease-related pain as well as a delay in the progression of osteoarthritis should be the primary goals of non-surgical therapeutic approaches. OBJECTIVE: The current body of studies is already able to prove the effectiveness of differential indicative physiotherapeutic and physical measures and should be further developed in the future. Nevertheless, the implementation of the available knowledge from the studies under evidencebased medicine criteria proves difficult during the daily routine in clinics. On one hand, an assessment of the effectiveness of physical therapy within the framework of a multimodal treatment approach (e.g. thermotherapy in combination with manual therapy) is difficult to define. RESULT AND CONCLUSION: On the other hand, an objective assessment of treatment success, owing to the heterogeneity among the patients (above all varied disease activity, functional limitations, accompanying diseases and therapy) will also remain complicated.

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

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.