Raynaud’s Phenomenon

Raynaud’s phenomenon (RP) is a clinical consequence of recurrent vasospasm of the small arteries and arterioles of the fingers and toes provoked by cold and emotional stress. RP is classified into two categories, i.e., primary and secondary RP. Primary RP is an isolated finding in the absence of an underlying pathology, while secondary RP is a syndrome in the context of another disease. The patients with primary RP have a younger age at onset, sparing of the thumb, and benign course without development of digital ulcers. Contrarily, secondary RP is characterized with later age of onset above 30 years, thumb involvement, and more severe course with possible development of trophic changes. In these cases, a focused, complaint-directed history and physical examination aim to reveal clinical symptoms and findings that confirm the presence of an underlying disorder, e.g., connective tissue disease (CTD) or other pathology. Together with clinical examination, laboratory, immunological, and capillaroscopic assessments facilitate the internal differential diagnosis of secondary RP. The capillaroscopic examination should be performed in all patients with symptoms of RP even in those cases without signs of systemic rheumatic disease, because the abnormal capillaroscopic picture inherits a high positive predictive value for the development of CTD

Pleiotropic Effects of Metformin in Osteoarthritis

The involvement of the knee joint is the most common localization of the pathological process in osteoarthritis (OA), which is associated with obesity in over 50% of the patients and is mediated by mechanical, inflammatory, and metabolic mechanisms. Obesity and the associated conditions (hyperglycemia, dyslipidemia, and hypertension) have been found to be risk factors for the development of knee OA, which has led to the emerging concept of the existence of a distinct phenotype, i.e., metabolic knee OA. Combined assessment of markers derived from dysfunctional adipose tissue, markers of bone and cartilage metabolism, as well as high-sensitivity inflammatory markers and imaging, might reveal prognostic signs for metabolic knee OA. Interestingly, it has been suggested that drugs used for the treatment of other components of the metabolic syndrome may also affect the clinical course and retard the progression of metabolic-associated knee OA. In this regard, significant amounts of new data are accumulating about the role of metformin—a drug, commonly used in clinical practice with suggested multiple pleiotropic effects. The aim of the current review is to analyze the current views about the potential pleiotropic effects of metformin in OA. Upon the analysis of the different effects of metformin, major mechanisms that might be involved in OA are the influence of inflammation, oxidative stress, autophagy, adipokine levels, and microbiome modulation. There is an increasing amount of evidence from in vitro studies, animal models, and clinical trials that metformin can slow OA progression by modulating inflammatory and metabolic factors that are summarized in the current up-to-date review. Considering the contemporary concept about the existence of metabolic type knee OA, in which the accompanying obesity and systemic low-grade inflammation are suggested to influence disease course, metformin could be considered as a useful and safe component of the personalized therapeutic approach in knee OA patients with accompanying type II diabetes or obesity

Microangiopathy in Rheumatic Diseases

Capillaries are part of the microcirculation, which consists of arterioles, capillaries, and venules and are the connecting link between the arterial and venous blood circulation [...

Knee Osteoarthritis—How Close Are We to Disease-Modifying Treatment: Emphasis on Metabolic Type Knee Osteoarthritis

Osteoarthritis (OA) is a whole-joint disease that affects cartilage, bone, and synovium as well as ligaments, menisci, and muscles [...

Knee Osteoarthritis—How Close Are We to Disease-Modifying Treatment: Emphasis on Metabolic Type Knee Osteoarthritis

Osteoarthritis (OA) is a whole-joint disease that affects cartilage, bone, and synovium as well as ligaments, menisci, and muscles [...

Microangiopathy in Rheumatic Diseases

Capillaries are part of the microcirculation, which consists of arterioles, capillaries, and venules and are the connecting link between the arterial and venous blood circulation [...

Pleiotropic Effects of Metformin in Osteoarthritis

The involvement of the knee joint is the most common localization of the pathological process in osteoarthritis (OA), which is associated with obesity in over 50% of the patients and is mediated by mechanical, inflammatory, and metabolic mechanisms. Obesity and the associated conditions (hyperglycemia, dyslipidemia, and hypertension) have been found to be risk factors for the development of knee OA, which has led to the emerging concept of the existence of a distinct phenotype, i.e., metabolic knee OA. Combined assessment of markers derived from dysfunctional adipose tissue, markers of bone and cartilage metabolism, as well as high-sensitivity inflammatory markers and imaging, might reveal prognostic signs for metabolic knee OA. Interestingly, it has been suggested that drugs used for the treatment of other components of the metabolic syndrome may also affect the clinical course and retard the progression of metabolic-associated knee OA. In this regard, significant amounts of new data are accumulating about the role of metformin—a drug, commonly used in clinical practice with suggested multiple pleiotropic effects. The aim of the current review is to analyze the current views about the potential pleiotropic effects of metformin in OA. Upon the analysis of the different effects of metformin, major mechanisms that might be involved in OA are the influence of inflammation, oxidative stress, autophagy, adipokine levels, and microbiome modulation. There is an increasing amount of evidence from in vitro studies, animal models, and clinical trials that metformin can slow OA progression by modulating inflammatory and metabolic factors that are summarized in the current up-to-date review. Considering the contemporary concept about the existence of metabolic type knee OA, in which the accompanying obesity and systemic low-grade inflammation are suggested to influence disease course, metformin could be considered as a useful and safe component of the personalized therapeutic approach in knee OA patients with accompanying type II diabetes or obesity

Disease-Modifying Potential of Metformin and Alendronate in an Experimental Mouse Model of Osteoarthritis

Osteoarthritis (OA) is the most common degenerative joint disease causing progressive damages of the cartilage and subchondral bone, synovial inflammation, and severe pain. Despite the complex pathomorphological changes that occur in OA, the approach to different forms of OA is standardized. The global results from pharmacological treatment are not satisfactory. Hence, this study aimed to explore the effects of metformin, alendronate, and their combination on OA development and progression in mice with collagenase-induced osteoarthritis (CIOA). Female ICR (CD-2) mice were randomized to five groups: control group, CIOA untreated, CIOA + metformin, CIOA + alendronate, and CIOA + metformin + alendronate. OA was induced by the intra-articular (i.a.) injection of collagenase. OA phenotype was analyzed by flow cytometry (bone marrow cell differentiation), ELISA (serum levels of the adipokines leptin and resistin), and histology (pathological changes of the knee joint). Treatment with metformin, alendronate, or their combination inhibited the expression of RANK and RANKL on osteoblasts and osteoclasts obtained by ex vivo cultivation of bone marrow cells in mineralization or osteoclastogenic media. In addition, metformin treatment was effective for the attenuation of fibroblast differentiation, but not of mesenchymal stem cells (MSCs), while alendronate had an opposite effect. The combination of metformin and alendronate had a suppressive effect on both MSCs and fibroblasts differentiation. Treatment with metformin, alendronate, and their combination decreased serum concentrations of leptin and resistin in the chronic phase of arthritis. The histopathological examination showed that compared with the untreated CIOA group (OA score 9), the groups treated with metformin (OA score 4) or alendronate (OA score 6) had lower scores for cartilage changes. Metformin combined with alendronate significantly decreased the degree of cartilage degeneration (OA score 2), suggesting that this combination might be a useful approach for the treatment of OA patients