Rheumatic and musculoskeletal diseases (RMDs) usually lead to morphological and functional deficits of various extend, increased morbidity and a considerable loss of quality of life. Modern pharmacological treatment has become effective and can stop disease progression. Nonetheless, disease progression is often only slowed down. Moreover, pharmacological treatment does not improve functionality per se. Therefore, multimodal treatment of rheumatic disorders with physical therapy being a key element is of central importance for best outcomes. In recent years, research into physical medicine shifted from a sole investigation of its clinical effects to a combined investigation of clinical effects and potential changes in the molecular level (e.g., inflammatory cytokines and the cellular autoimmune system), thus offering new explanations of clinical effects of physical therapy. In this review we provide an overview of studies investigating different heat applications in RMDs, their effect on disease activity, pain and their influence on the molecular level.

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, β-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.

Rheumatoid arthritis (RA) is associated with systemic bone loss and thus an established risk factor for osteoporosis. Janus kinase inhibitors (JAKi) have shown osteo-protective effects. However, clinical data on the effects of baricitinib on bone mineral density (BMD) remain limited. Therefore, we investigated the effects of a 1-year treatment with baricitinib on BMD in RA patients. Patients with active RA beginning treatment with baricitinib were included. BMD was measured at the lumbar spine and femoral neck using Dual-Energy X-Ray Absorptiometry (DXA). Disease activity was assessed using DAS28-CRP and cDAI. The primary endpoint was the change in BMD after 12 months. Secondary endpoints evaluated changes in disease activity, prednisolone dose and alkaline phosphatase (AP) levels and its relation to BMD. A total of 46 RA patients were recruited, of whom 26 completed the study. Overall, BMD remained stable. Non-responders to baricitinib (based on DAS28-CRP) showed a significant decline in spine BMD (− 2.12%, p = 0.039), while responders showed stable BMD. The between-group difference in spine BMD ( p = 0.008) and T-score ( p = 0.012) was significant. Demographic and clinical characteristics did not differ significantly between groups. Disease activity (DAS28-CRP: p = 0.003; cDAI: p = 0.007), prednisolone dose ( p = 0.006), and AP levels ( p = 0.03) all improved significantly. Under baricitinib, BMD loss appeared stabilized in RA patients. Non-responders to baricitinib experienced a significant loss of BMD with a significant difference to responders raising the question if seen effects are achieved by controlling disease activity or if there is an additional explicit JAKi effect on bone metabolism. Trial registration number: DRKS00020780, date: 13.3.2020.

Hypervascularisation is a dominant feature of the inflamed synovium in rheumatoid arthritis (RA). As RA synovial fibroblasts (RASFs) are key cells of synovial pathophysiology and are located adjacent to the aberrant endothelial cells (ECs), we hypothesised that this interaction might be responsible for the pathological hypervascularisation. In the severe combined immunodeficiency (SCID) mouse model for RA, RASF-mediated helix-like vessel (HLV) formation was described and modulated by canstatin, an antiangiogenic collagen IV fragment that blocks the angiopoietin (ANGPT)/Tie2 pathway in EC. ANGPT2/CD31 and CXCL2 immunofluorescence on implants and human synovium was performed. RASF were stimulated with interleukin (IL)-1β once or repetitively and immunoassays, real-time polymerase chain reaction and RNA sequencing were performed. Two-dimensional (2D) tube formation and 3-dimensional spheroid-based assays using human umbilical vein ECs and fluorescent-stained RASF with/without canstatin, IL-11 and CXCL2 were evaluated. In SCID mice, RASF-specific HLV formation started early and increased until day 30. The number of HLV was significantly reduced by canstatin. Compared to osteoarthritis synovium, ANGPT2 was significantly upregulated in RA vessels. Repetitive RASF stimulation significantly decreased IL-6, IL-11 and CXCL-2 compared to RASF stimulated once with IL-1β. When RASF was stimulated once, CXCL2 and IL-11 were significantly reduced along with 2D tube formation, while repetitive stimulation significantly attenuated hypervascularisation. RNAseq revealed underlying pathways leading to altered tube formation. We showed that RASF affect vascularisation in vitro and in vivo. The results support the idea that canstatin is able to alter the RASF pathological HLV formation. In the SCID mouse model, this was regulated on a molecular level mediated by ANGPT2 in a vascular endothelial growth factor A-independent manner, contributing significantly to one of the central aspects of RA pathophysiology.

Systemic sclerosis (SSc) is associated with an increased risk of osteoporosis. Gastrointestinal manifestations of SSc such as dysphagia and chronic gastritis affect up to 90% of patients and thus may impair the efficacy and safety of oral antiresorptive treatments. However, data on the comparative effectiveness and safety of antiresorptive therapies in SSc are lacking. Patients with SSc treated for osteoporosis at our rheumatology department between 2004 and 2024 were included if they had at least 2 dual-energy X-ray absorptiometry measurements 2 years apart (before and during antiresorptive therapy). Primary endpoint was the change in bone mineral density (BMD). Secondary endpoints assessed changes in BMD for individual drugs, with a specific focus on oral compared with parenterally administered drugs. Adverse events were documented descriptively. A total of 42 patients were included. Overall, antiresorptive therapy significantly improved axial BMD (+3.78%, p = .012), whereas femoral BMD remained unchanged. Subgroup analysis showed a significant axial BMD increase with parenteral therapy (+5.46%, p = .026, n = 21), but not with oral drugs (n = 21). Denosumab yielded the highest axial BMD gain (+7.51%). Overall, no new fractures occurred. One patient developed stage 1 osteonecrosis of the jaw (ONJ) under ibandronate. Three of 19 patients (16%) developed mild gastrointestinal symptoms. No severe gastrointestinal symptoms occurred. Antiresorptive therapies appear to be effective in patients with SSc. Subgroup analysis suggests that parenteral administration, particularly denosumab, may offer superior efficacy. Gastrointestinal adverse effects were mild and consistent with published rates in the general population, whereas ONJ could be more relevant than in the general population.

Zusammenfassung: Hintergrund: Die systemische Sklerose (SSc) ist eine komplexe Autoimmunerkrankung mit multiorganischer Manifestation und erheblicher Morbidität und Mortalität. Aufgrund dessen sind SSc-Patienten übermäßig häufig von Osteoporose betroffen, die im Kontext der SSc bislang unzureichend charakterisiert ist und im Praxisalltag oftmals untergeht. Ziel: Darstellung der aktuellen Evidenzlage zur Epidemiologie, pathophysiologischen Mechanismen, diagnostischen Besonderheiten sowie therapeutischen Herausforderungen der Osteoporose im Kontext der SSc. Methodik: Narrative Übersicht relevanter Primär- und Sekundärliteratur (2003–2025) aus PubMed, Embase und aktuellen Leitlinienquellen mit Fokus auf osteologische Aspekte bei SSc. Ergebnisse: Patienten mit SSc zeigen eine signifikant erhöhte Prävalenz von Osteoporose und Frakturen. Die SSc aggraviert über Vaskulopathie, Fibrose wie auch Autoimmunität/Entzündungsaktivität Risikofaktoren der Osteoporose wie postmenopausaler Status, Malnutrition und Untergewicht. Diagnostisch erweist sich der Trabecular Bone Score (TBS) als ergänzendes Verfahren zur Frakturrisikobeurteilung. Die SSc erschwert v. a. über die gastrointestinale Manifestation zudem die osteospezifische Therapie, insbesondere orale Bisphosphonate scheinen weniger gut zu wirken. Erste Hinweise auf die Wirksamkeit parenteraler Antiresorptiva liegen vor. Diskussion: Die Osteoporose bei SSc erfordert ein krankheitsspezifisches Risikomanagement und ein individualisiertes diagnostisches sowie therapeutisches Vorgehen. Weitere prospektive Studien sind notwendig, um evidenzbasierte Therapieempfehlungen zu etablieren.