Zguro Batalov

Late diagnosis of osteoporosis with already existing low-energy fractures, often incorrect reassessment of fracture risk and suboptimal therapy is associated with significant unmet needs in high-risk patients. Predictors for fracture risk assessment are the basis of the long-term strategy for monitoring, stratifying patients and treating osteoporosis. To evaluate whether changes in total bone mineral density (BMD) of the lumbar spine and BMD of the femoral neck over 36 months were associated with transition to a lower estimated fracture risk category after adjustment for baseline patient characteristics and treatment type. Retrospective observational cohort study including 298 participants with postmenopausal and senile osteoporosis with and without low-energy fractures undergoing antiresorptive therapy. Data were followed for a period of 3 years and were collected at baseline and at a 1-year follow-up period. Multivariable logistic regression identified denosumab therapy (OR = 4.21, p = 0.003), percentage gain in BMD of the femoral neck (OR = 1.05, p = 0.004), and postmenopausal osteoporosis (OR = 9.37, p = 0.009) as independent predictors of lower fracture risk transition at 36 months. Transition rates were higher with denosumab than bisphosphonates (79.5% vs. 29.6%) and in postmenopausal vs. senile osteoporosis (61.6% vs. 5.7%). The reduced model showed good discrimination (AUC = 0.803), remaining stable on 10-fold cross-validation (AUC = 0.780). Given existing gaps in risk stratification and management of high risk patients, these findings highlight the clinical value of targeting BMD of the femoral neck improvements, optimizing therapeutic choices, and individualizing treatment.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease of the sacroiliac joints (SIJs) and spine, encompassing non-radiographic axSpA (nr-axSpA) and radiographic axSpA (r-axSpA) or ankylosing spondylitis (AS). Early diagnosis is challenging, particularly in nr-axSpA, due to the absence of radiographic sacroiliitis and overlap with nonspecific back pain. Imaging plays a pivotal role in disease classification and monitoring. To synthesize current evidence on inflammatory and structural facet joint involvement in axSpA, with particular emphasis on MRI characterization, available scoring approaches, differentiation from degenerative abnormalities, and the current limitations of facet joint assessment as a potential imaging biomarker. A review of current evidence regarding imaging modalities in axSpA, including conventional radiography, computed tomography (CT), MRI, radionuclide techniques, and musculoskeletal ultrasound (US), was performed. Particular emphasis was placed on ASAS/OMERACT MRI definitions and facet joint assessment. MRI enables early detection of inflammatory lesions such as bone marrow edema (BME), spondylitis, and enthesitis before structural damage becomes visible on radiographs. It also identifies structural changes including fat metaplasia, erosions, syndesmophytes, and ankylosis. Increasing evidence supports the clinical relevance of facet and costovertebral joint inflammation, which correlates with impaired spinal mobility and functional disability. However, inflammatory facet joint changes remain underreported in routine practice despite the development of semiquantitative scoring systems. Ultrasound complements MRI in assessing enthesitis but is limited in evaluating deep axial structures. MRI has become indispensable in axSpA diagnosis and monitoring. Standardized imaging definitions and structured reporting are essential to improve clinical integration and patient outcomes.

Janus kinase (JAK) inhibitors have become an important therapeutic option for a wide range of immune-mediated inflammatory diseases. By targeting intracellular cytokine signaling through inhibition of the JAK–STAT pathway, these agents provide effective suppression of multiple inflammatory cascades. Alongside their growing clinical use, changes in body weight—particularly weight gain—have recently been reported in clinical practice. Although this phenomenon has not consistently emerged as a prominent adverse event in randomized clinical trials, observational studies and real-world data suggest that weight gain may occur in some of the treated patients. The mechanisms underlying these changes remain barely understood and are likely multifactorial. Effective suppression of systemic inflammation may reverse inflammation-driven catabolism and restore metabolic balance, contributing to increases in body weight and lean body mass. In addition, experimental evidence indicates that JAK–STAT signaling participates in adipocyte differentiation, lipid metabolism, and energy regulation. Pharmacologic inhibition of this pathway may therefore influence adipose tissue biology, thermogenic activity, and appetite regulation through leptin-dependent signaling pathways. This review summarizes current evidence regarding weight and body composition changes associated with JAK inhibitor therapy, integrating findings from experimental studies, clinical trials, and real-world observations. Potential biological mechanisms are discussed alongside patient-related and disease-related factors that may modify the risk of weight gain. A better understanding of these immune–metabolic interactions may help guide clinical monitoring and future research on the metabolic consequences of JAK inhibition.

Background: Distinguishing between osteoarthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis (PsA) remains challenging despite different underlying mechanisms. Synovial fluid reflects metabolic changes within affected joints, yet comprehensive metabolomic comparisons across these conditions are limited. We aimed to identify disease-specific metabolic signatures in synovial fluid that could improve differential diagnosis and reveal therapeutic targets. Methods: We collected synovial fluid from 39 patients (20 OA, 5 RA, and 14 PsA) during routine knee arthrocentesis between January 2023 and February 2024. Following metabolite extraction, we performed untargeted metabolomic profiling using quadrupole time-of-flight liquid chromatography–mass spectrometry (Q-TOF LC/MS). Data underwent multivariate statistical analysis, including principal component analysis (PCA) and partial least squares–discriminant analysis (PLS-DA), to identify discriminatory metabolites. Results: While unsupervised analysis showed overlap between groups, supervised PLS-DA achieved clear metabolic separation. RA samples showed elevated itaconic acid, indicating inflammatory macrophage activation, and increased O-acetylserine, suggesting altered one-carbon metabolism. Hypoxanthine was decreased, which reflected severe metabolic stress. PsA exhibited the unique elevation of 4,4-dimethylcholestane and 2-oxoarginine. These metabolites have previously been unreported in this disease. OA demonstrated increased hippuric acid and indoleacetic acid, which are both gut microbiota products, supporting the gut–joint axis hypothesis. Conclusions: Each arthritis type displayed distinct metabolic fingerprints in synovial fluid. Candidate discriminatory metabolites, including gut-derived metabolites in OA and specific lipid alterations in PsA, open new diagnostic and therapeutic avenues. Given the limited RA sample size (n = 5), RA-related results should be viewed as exploratory and requiring validation in larger independent cohorts. These metabolites may, after rigorous validation in larger and independent cohorts, contribute to multi-metabolite biomarker panels for earlier diagnosis and to the rational design of targeted therapeutics addressing disease-specific metabolic disruptions.

Background/Objectives: Rheumatoid arthritis is an autoimmune disease that induces joint deformity and disability. There are great expectations for biomarkers that would predict the response to treatment. CHI3L1 and CHI3L2 are chitinase-like proteins (CLPs) which lack enzymatic activity. CHI3L1 is expressed by a variety of cells, while reports on CHI3L2 are limited. The aim of the current study is to evaluate gene and protein CHI3L1 and CHI3L2 expressions before and after treatment of patients with RA and to search for correlations with ultrasonography and conventional laboratory parameters. Methods: Twenty-four newly diagnosed RA patients (19 females and five males) were enrolled in the study. Fourteen patients were treated with tofacitinib (TOFA) and 10 patients with methotrexate (MTX) for twenty-four weeks. Conventional biochemical and immunological markers were examined at the start of the treatment and after the follow-up period. The activity of RA was assessed via the Disease Activity Score 28 (DAS28). Gene expression and protein analysis were performed. Results: Ultrasonographic and clinical laboratory parameters showed improvement after therapy in both groups. A decrease in plasma levels of CHI3L1 (p = 0.04 *) and CHI3L2 (p = 0.03 *) were found after treatment with TOFA. No changes in either protein level were detected after MTX therapy, nor were any differences discovered in the gene expression of CLPs after treatment with both therapeutics. Strong correlations between CRP, GUS7 and CLPs were also established. Conclusions: The similar dynamics of CLPs expression in naïve RA patients and their distinct interplay with disease-related parameters after therapy suggest that both proteins may display different functions in RA pathophysiology.

Adjuvant-induced autoimmune/ autoinflammatory syndrome (ASIA) is a group of symptoms that are often found in other systemic, autoimmune diseases, which makes its recognition and diagnosis a growing problem in modern clinical practice. Although not completely clear, the genesis is associated with adjuvants - substances found in implants, vaccines, substances external to the body that lead to an exaggerated immune response. Key points of the clinical and paraclinical specificity of the disease are arthralgias, myalgias, cognitive disorders, and positivity of various autoimmune and inflammatory markers. The objectives of this report are to summarize current information about the disease, discuss diagnostic criteria, and review therapeutic options, placing special interest on the ultrasound findings. The presented case outlines the diagnostic difficulty even with the various clinical, imaging, and laboratory findings. Directing clinical thought towards this syndrome is of utmost importance for its easier recognition in practice and achieving favorable outcomes in the treatment of affected patients.

Osteoporosis is among the leading socially significant diseases, with potential for early diagnosis and effective treatment. Appropriate selection of therapy, particularly after reassessment of ongoing antiosteoporotic therapy, can reduce both fracture risk and healthcare system costs. To evaluate strategies for reassessing antiosteoporotic therapy on the grounds of changes in fracture risk among women in the Bulgarian population. We conducted a retrospective observational cohort study including 300 participants women with postmenopausal, senile osteoporosis or low-energy fractures undergoing antiresorptive therapy. Data were collected at the time of discharge and during a 1-year follow-up period, covering a total monitoring period of 3 years. The FRAX score based on hip fracture (HF), proved to be a more sensitive predictor of future fractures ( HF > 4.5% in 65.22% with postmenopausal osteoporosis and in 100% with senile). In the bisphosphonate treatment group, total bone mineral density (BMD) of the lumbar spine (VL) and BMD оf the femoral neck (FN) demonstrated a clearer trend of BMD improvement (month 36: 0.838 g/cm² ± 0.01 SD and 0.622 g/cm² ± 0.04 SD ) compared to T-scores. BMD —particularly of the FN—and FN T-scores in patients at very high fracture risk were significant indicators for therapy reassessment. BMD of the FN consistently predicted changes in fracture risk across all monitoring periods. Implementing national strategies for the reassessment of antiosteoporotic therapy, on the grounds of evolving fracture risk, could enhance clinical decision-making and address existing gaps in the treatment of high-risk patients.

Rheumatoid arthritis (RA) is an autoimmune disease affecting the synovium. Mitochondrial dysfunction is considered a critical factor in the pathogenesis of RA. The aim of the study was to determine the effect of methotrexate and tofacitinib on mitochondrial function and oxidative stress in an in vitro study on the model synovial cell line SW982. TNF-alpha-stimulated SW982 cells, as well as control untreated cells, were incubated with methotrexate and tofacitinib. A metabolic test was performed to assess mitochondrial function. The oxidative stress generated after the application of the therapeutics was determined by a chromatographic analysis. The results obtained showed an increase in ATP levels (p < 0.0001) and a decrease in proton leak (p < 0.0003) after treatment with tofacitinib. The opposite trend was observed—reduced ATP production (p < 0.0096) and increased levels of proton leak (p < 0.0001)—after treatment with methotrexate. A two-fold increase in 8-ISOPGF2A was measured in comparison to TNF-alpha-stimulated and untreated cells. The dynamics of mitochondrial activity and oxidative stress were monitored in a certified RA model cell line after the administration of two different therapeutics. Methotrexate was found to induce mitochondrial dysfunction and oxidative stress in vitro, while tofacitinib partially improved mitochondrial parameters.

Introduction/Objectives: Osteoarthritis (OA) is a chronic systemic disease that affects the entire array of joint structures. It is one of the most common chronic, socially significant diseases, associated with a decline in the quality of life of patients and constantly increasing the cost of treatment. Clinical trial outcomes are largely inconclusive, and OA remains one of the few musculoskeletal diseases without an established disease-modifying therapy. One potential explanation is the use of ineffective tools for OA classification, patient stratification, and the assessment of disease progression. There is growing interest in musculoskeletal ultrasonography (MSK US), as it enables the dynamic visualization of the examined structures and gives information about both inflammatory and structural changes that have occurred. Determining the leading ultrasound phenotype, which depends on the most damaged tissue at a given time (bone, cartilage, synovial membrane, joint capsule, ligaments, tendons, menisci, etc.), can rationalize therapy use by selecting patients more suitable for specific treatments. This article aims to evaluate and summarize the potential of MSK US in the process of determining the clinical phenotype of OA and to emphasize the importance of this imaging modality in evaluating further therapeutic strategies. Method: A single-center prospective study conducted in the period of September 2023–June 2024 enrolled 259 consecutive patients with proven OA. The statistical program Minitab version 22.2.1 (2025) was used to analyze the data. The predominant and secondary phenotypes were tabulated for each OA localization and were presented numerically and as relative proportions (%). The rate of the most frequently occurring phenotypes was compared against that of the less frequent ones through paired z-tests. The initially acceptable type I error was set at 5%; it was further adjusted for the number of comparisons (Bonferroni). Results: The most frequent and predominant US phenotype for patients with knee OA was intra-articular effusion (n = 47, 37.90%). It was significantly higher compared to the rest of the US phenotypes: synovial proliferation (n = 22, 17.70%; p < 0.001), cartilage destruction (n = 26, 21%; p = 0.001), altered subchondral bone (n = 8, 6.50%; p < 0.001), extra-articular soft tissue changes (n = 12, 9.70%; p < 0.001), crystal deposits (n = 6, 4.8%; p < 0.001), and post-traumatic (n = 3, 2.40%; p < 0.001). The most common US phenotype for hip OA was altered subchondral bone (n = 32, 47.1%), with significant differences from intra-articular effusion (n = 12, 17.60%; p = 0.001), synovial proliferation (n = 5, 7.40; p = 0.001), cartilage destruction (n = 12, 17.60%; p = 0.001), extra-articular soft tissue changes (n = 3, 4.40%; p = 0.001), crystal deposits (n = 3, 4.40%; p = 0.001), and post-traumatic (n = 0). Altered subchondral bone was also the leading US phenotype for hand OA (n = 31, 55.40%), with significant differences compared to intra-articular effusion (n = 1, 1.80%; p < 0.001), synovial proliferation (n = 7, 12.50%; p < 0.001), cartilage destruction (n = 11, 19.60%; p < 0.001), extra-articular soft tissue changes (n = 2, 3.60%; p < 0.001), crystal deposits (n = 3, 5.40%; p < 0.001), and post-traumatic (n = 1, 1.80%, p < 0.001). For shoulder OA, extra-articular soft tissue changes were the most frequent (n = 8, 46.20%), followed by post-traumatic (n = 4, 30.70%), as the rate of both phenotypes was significantly higher compared to that of intra-articular effusion (n = 0), synovial proliferation (n = 0), cartilage destruction (n = 1, 7.70%; p = 0.003), and crystal deposits (n = 0). Conclusions: The therapeutic approach for OA is a dynamic and intricate process, for which the type of affected joint and the underlying pathogenetic mechanism at a specific stage of the disease’s evolution is essential. MSK US is one of the options for the clinical phenotyping of OA. Some of the suggested ultrasound subtypes may serve as the rationale for selecting a particular treatment.