Bone marrow mesenchymal stem cells (BMSCs) are multipotent progenitor cells with the capacity to differentiate into various mesenchymal lineages, including osteogenic, chondrogenic, and adipogenic tissues, rendering them promising candidates for regenerative medicine. This review delves into current foundational and preclinical research concerning BMSCs, with a particular emphasis on the use of genetically modified rat-derived BMSCs expressing green fluorescent protein (GFP) to facilitate in vivo cell tracking during tissue repair. It also examines various administration strategies, including intra-articular injections and magnetically guided cell targeting, to evaluate their therapeutic efficacy. Emerging evidence highlights the pivotal role of BMSCs in regenerating musculoskeletal tissues, including muscle, meniscus, and cartilage. Notably, the application of external magnetic fields (EMF) to direct magnetically labeled BMSCs to injury sites has demonstrated encouraging outcomes in cartilage repair. Furthermore, advances in BMSC culture techniques, single-cell genetic analysis, and tissue engineering methodologies may further augment their therapeutic potential. Preclinical and early-phase clinical studies underscore the promise of BMSCs as a minimally invasive therapeutic modality in orthopedic and regenerative medicine. Further research is essential to refine their applications and optimize delivery strategies, such as the use of internal magnetic fields generated by magnetized material implanted in damaged knee cartilage, to ensure long-term efficacy and safety.

Gout is the most common inflammatory arthritis, and its prevalence is increasing in part due to the rise in chronic kidney disease (CKD). Guidelines for managing gout from the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) provide limited guidance for patients with advanced renal disease, partly due to the exclusion of this group of from clinical trials. This, along with concerns about adverse drug reactions contributes to the undertreatment of gout in advanced CKD. Gout management involves different phases: treatment of acute gout flares, implementing prophylaxis to prevent attacks and urate-lowering therapy (ULT). In this review, we examine the management of gout, with particular attention to recommended adjustments for patients with advanced CKD, those undergoing dialysis, or individuals who have received renal transplants. We review the medications used in the management of gout and suggest adjustments for their selection and dose in patients with advanced CKD. The article discusses colchicine, glucocorticoids, and IL1-β inhibitors for acute gout treatment and provides recommendations for flare prophylaxis. We review the use of xanthine oxidase inhibitors (allopurinol, febuxostat) and pegloticase as urate-lowering therapies for patients with advanced CKD, on dialysis, or with renal transplants. The possible side effects of gout treatments in patients with CKD and the suggested monitoring protocols are discussed. The potential impact of allopurinol, colchicine, and IL1-β inhibitors on cardiovascular disease outcomes are reviewed. Finally, new targets and drugs being explored for treating gout in patients with advanced CKD are discussed.

Fracture non-union remains a significant clinical challenge despite considerable advances in diagnostic imaging and treatment modalities. Unpredictable healing, repeated interventions, and prolonged disability contribute to high patient morbidity and increased healthcare costs. Early and reliable prediction of non-union is therefore essential for timely intervention. This review discusses traditional radiographic assessment using the Radiologic Union Scale for the Tibia (RUST), its inherent limitations, and the emerging role of artificial intelligence (AI) and deep learning in fracture analysis. In addition, we review recent studies—including Bayesian classifiers and simulation models—that integrate AI for early prediction of non-union, and we provide an updated summary table of key studies.

Primary care physicians (PCPs) play a critical role in the management of gout worldwide. However, significant gaps in gout care persist, underscoring the need for improved approaches to its management. While some guidelines, such as those from the American College of Physicians (ACP) published in 2016, support a more reactive treat-to-symptoms approach, others from the American College of Rheumatology (ACR) and the European Alliance Of Associations For Rheumatology advocate for a proactive treat-to-target (TTT) strategy—focused on achieving optimal serum urate levels through urate lowering therapy (ULT). This divergence reflects differing clinical priorities and differential interpretation of the evidence and it may contribute to variability in care delivery. Improving gout management requires greater engagement from both patients and healthcare providers, with particular emphasis on increasing adherence to ULT. Patients need enhanced support to better understand the importance of sustained urate lowering treatment, while healthcare providers may benefit from clearer guidance aligned with evidence-based strategies to foster greater patient trust and confidence. This article provides an overview of the current state of guidelines, highlights areas of agreement and discordance between them, and identifies key areas for improving care delivery. It additionally offers insight into alternative care delivery strategies, such as those involving non-physician health professionals, which have shown promise in enhancing patient outcomes. Future research should focus on continued development of innovative, multi-modal interventions to improve ULT adherence, including health system-based initiatives and collaborative care models.

Biosimilars are biologic products that provide equal mechanisms and efficacy to that of their original biologic references. This paper aims to provide a comprehensive overview of the numerous ways biosimilars are improving care for individuals living with rheumatoid arthritis (RA), from the effective application of biosimilars in treatment-naive RA patients, switching from an original biologic to a biosimilar, to the ability to tailor biologic therapy in respect to mechanisms provided by different biologic classes. Biosimilars provide a significant reduction in cost and provide patients with treatment options that do not exhibit adverse drug reactions (ADRs) as exhibited with methotrexate and other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Understanding mechanisms to discern patient response to biologic therapies will gain increasing importance as biosimilars with different targeted mechanisms enter the market. Patients who do not respond to one class of biologic medicine now have alternative biosimilars available to support their care. Study results support that patients initiated on biosimilars stay on biosimilars, so it is prudent to remain aware of the biosimilars available and candidates in development.

Calcium pyrophosphate deposition (CPPD) disease is the most prevalent crystal related arthropathy in the older-aged population. The clinical spectrum of CPPD arthropathy can include asymptomatic, acute, and chronic inflammatory disease that primarily results in irreversible structural joint damage. The manifestations and impact of structural damage that result from other inflammatory non-degenerative features of chronic CPP crystal inflammatory arthritis are often underrecognized and may lead to an inaccurate perception of disease severity. This pictorial essay sought to display the disease burden and various presentations of chronic inflammatory CPP crystal arthritis. Sonographic imaging of cases with chronic CPP arthritis was presented for diagnostic considerations and to demonstrate the extent of irreversible articular and peri-articular damage occurring at a structural level. Evolving understanding of the imaging characteristics of CPPD disease will provide a better appreciation of disease morbidity caused by this condition and stress the need to expand efforts to find effective treatments to dissolve crystal deposition and targeted therapies that will contain the inflammatory response to crystals. Recognizing the anatomic consequences of tissue damage that arise from CPPD disease should also help reflect on potential surgical alternatives to mitigate the progression of structural complications until effective disease modifying agents for this condition emerge.

The temporomandibular joint (TMJ) involvement is an underestimated feature of juvenile idiopathic arthritis (JIA) since it is usually asymptomatic at presentation for an undeterminable time. Late diagnosis of TMJ arthritis in JIA patients leads to delayed treatment, long-term orofacial disturbances, and impaired health-related quality of life (HRQOL). Therefore, the detection of TMJ involvement is fundamental and represents a challenge. This perspective presents state-of-the-art current initiatives and available tools for early diagnosis of TMJ arthritis in children with JIA. Standardized protocols and multidisciplinary efforts for improving clinical skills in the assessment of TMJ in JIA are presented and commented on. An overview of imaging efforts for early detection of TMJ involvement in JIA is also provided, with a critical review of the advantages and limitations of different techniques, imaging protocols, and scoring systems. The perspective offers insights into the correct use and improvement of available and potential tools for early identification of TMJ arthritis in JIA subjects who deserve timely multidisciplinary treatment, avoiding both underestimation and over-diagnosis of TMJ arthritis in routine clinical practice.

This sub-analysis of the PROPER study aimed to evaluate outcomes following the transition from reference adalimumab (ADL) to SB5 (Imraldi^™) in routine clinical practice in Spanish patients with rheumatoid arthritis (RA). Adult Spanish patients (n = 73) with RA who initiated SB5 as part of routine clinical practice following treatment with reference ADL were recruited. Outcome measures included persistence on SB5, clinical characteristics, and disease activity scores at the time of transition to SB5 treatment, clinical management over time, and safety. At Week 48, the Kaplan-Meier [95% confidence interval (CI)] estimate of the probability of persistence on SB5 after switching from reference ADL was 0.84 (0.73–0.90) and 83.6% (46/55) of patients were in remission or had low disease activity. The majority of patients [83.6% (61/73)] experienced no disease flare during the study period and reported that the injection was “simple or very simple” to administer (baseline: 66.7%; Week 48: 69.0%) and were generally “satisfied or very satisfied” with the duration of the injection. In total, 21 patients (21/73, 28.8%) reported at least one drug-related adverse event, which were mild in most cases (17/21, 80.9%). In a Spanish cohort of patients with RA transitioning from reference ADL to SB5, the probability of SB5 persistence was high and treatment effectiveness was maintained for up to 48 weeks. There were no new safety signals and SB5 was well tolerated. These findings suggest that there is no evidence to mitigate against transition from reference ADL to SB5 in patients with RA (Clinicaltrials.gov listing: NCT04089514).

Routine regulatory requirements for large comparative efficacy trials (CETs) to support marketing approval of monoclonal antibody (mAb) biosimilars have been the focus of extensive debate in the last few years. This review examines the mounting evidence, accumulated over the past decade, focusing on relevant literature and data published in the European Product Assessment Reports (EPARs) for the fifteen anti-TNFα biosimilars approved to date. The potential for residual uncertainties that may require resolution through CETs following comparative physico-chemical, in-vitro potency, and single dose studies in healthy subjects is examined. It is noted that structural and physicochemical differences between biosimilars and reference products are detectable using modern analytical methods at levels well below those that could impact clinical outcomes, and that in vitro potency testing is fully capable of revealing clinically relevant differences. Additionally, comparative pharmacokinetic studies in healthy participants provide a sensitive assessment of potential differences in drug exposure and immunogenicity. The added value of CETs is further questioned in the light of the fact that anti-TNFα’s display a flat dose-response relationship, meaning that unlike cell-based assays, CETs have limited sensitivity to detect potency differences. Initial concerns about extrapolating data from rheumatoid arthritis studies to support marketing approval of other indications such as inflammatory bowel disease for which not all anti-TNFα’s are effective have been alleviated by post-approval studies. Additionally, as of the end of 2024, no cases where clinical efficacy data were necessary to resolve residual quality concerns have arisen following regulatory assessment of 56 mAb biosimilars and fusion proteins. CETs add significant cost and delay to the development of biosimilars and the time is now ripe to re-examine the need for these CET’s and for further evolution in regulatory thinking.

Pyogenic arthritis (PA) related mortality trends have not been studied well across various demographics in the United States (US). This cross-sectional study aimed to evaluate these trends among the US population aged ≥ 25 years from 1999–2020 using data from the CDC WONDER database. We identified all the deaths where PA was listed as the underlying or contributing cause of death, using the ICD-10 code M00. Age-adjusted mortality rates (AAMRs) were calculated per 1 million US population and the Joinpoint regression model was used to assess the annual mortality trends by calculating the annual percent change (APC) in AAMRs. Between 1999 and 2020, 13,965 total deaths occurred among US adults aged ≥ 25 years with an AAMR of 2.94. The overall AAMR of PA increased significantly from 1999 to 2020 with an APC of 2.01 (p < 0.01). Males and older adults had consistently higher AAMRs than their respective counterparts. Non-Hispanic (NH) American Indians/Alaska Natives and NH Blacks/African Americans had higher mortality rates compared with other racial groups. The Midwest had the highest overall AAMR, followed by the West, Northeast, and South regions. In conclusion, PA mortality has been on the rise and targeted interventions are warranted to reduce disproportionate mortality rates among vulnerable populations.

Chronic pain is a common problem in rheumatology. A distinction is made between nociceptive pain and nociplastic pain. Nociceptive pain is, for example, mechanistically explained by persistent inflammation. Neuropathic pain is caused by nerve damage of various possible causes. In contrast, nociplastic pain is not due to tissue damage or a lesion in the somatosensory nervous system—at least not with the currently available techniques. Nociplastic pain is based on an altered perception of pain through modulation of stimulus processing. The concept of central sensitization, together with other neurobiological and psychosocial mechanisms, is considered to be the best explanation for such pain conditions. The syndrome of fibromyalgia (FM), considered to be due to central sensitization, plays a major role in rheumatology—both in terms of differential diagnosis and because the management of inflammatory rheumatic diseases can be made more difficult by the simultaneous presence of FM. During the coronavirus pandemic, persistent pain syndromes with similarities to FM were described following a COVID-19 infection. There is a growing scientific controversy as to whether the so-called long COVID syndrome (LCS) is a separate entity or just a variant of FM.

Musculoskeletal ultrasound has become a valuable imaging tool in the diagnosis and management of rheumatologic disorders. Expertise in recognizing sonographic findings of pathology is the basis for its successful application in clinical use. This article will provide descriptions and a pictorial essay of ultrasound findings in common musculoskeletal manifestations of rheumatologic disorders.