Hasil untuk "Diseases of the musculoskeletal system"

Jürgen Braun, Björn Bühring

Osteoporosis is a systemic skeletal disease characterized by low bone mineral density (BMD) and poor bone quality, leading to reduced bone strength and increased risk of fracture. In rheumatic and musculoskeletal diseases (RMD), including rheumatoid arthritis (RA) and spondyloarthritides (SpA), such as axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), generalized bone loss associated with traumatic and non-traumatic fractures, such as insufficiency fractures (IF), is known to occur with the RANK-RANKL-osteoprotegerin axis and the Wnt-β-catenin signalling pathway playing a pathogenetic role. RA has been included in the Fracture Risk Assessment Tool (FRAX) system to be able to more precisely calculate the 10-year fracture risk associated with the disease. Various definitions for IF have been proposed; a recent paper by the EMA has defined fragility fractures as fractures occurring with low trauma at the hip, spine, pelvis, distal femur, proximal tibia, humerus, forearm, and multiple ribs. However, IF of the feet are currently not considered osteoporotic fractures. So-called stress fractures, which are known to often occur in athletes, have a similar MRI appearance. However, these are rather due to repetitive strain than to minor trauma. Also, based on recent data, this manuscript concentrates on the significance of fragility fractures in RMD.

Xenofon Baraliakos, Ye Eun Lee, Soyeon Park et al.

Abstract Background CT-P13 SC, a new subcutaneous (SC) formulation of biosimilar infliximab (IFX), was approved by the European Medicines Agency in 2020 for the treatment of radiographic axial spondyloarthritis (axSpA) in adult patients. The present study aimed to assess the real-world outcomes of CT-P13 SC (SC IFX) as a treatment for both radiographic and non-radiographic axSpA. Methods Data were drawn from the Adelphi Real World axSpA Disease Specific Programme™, a cross-sectional survey with retrospective data collection in France, Germany, Italy, Spain, and the UK between June 2023 and June 2024. Rheumatologists and their patients with axSpA completed questionnaires on patient demographics, clinical characteristics, and treatment satisfaction. Outcomes for patients on SC IFX were analyzed, with additional evaluations based on baseline characteristics and treatment patterns. Such outcomes were also compared with patients receiving other advanced therapies, including biologics and Janus kinase inhibitors. Results In total, 191 patients were evaluated. The mean patient age was 44.5 years, and most were male (117 [61.3%]). Baseline characteristics were similar between radiographic and non-radiographic axSpA patients, with a higher proportion of patients in the radiographic group (116 [60.7%] vs. 75 [39.3%]). Significant improvements in disease severity were observed with SC IFX from treatment initiation to data collection (severe disease: 37.4% to 3.2%), along with significantly lower levels of pain and fatigue, and fewer tender entheseal points and affected joints (all p < 0.0001). SC IFX treatment was also associated with improvements in musculoskeletal, extra-articular, systemic, and functional symptoms, and inflammatory imaging features. Subgroup analysis showed that SC IFX was effective across various patient populations with differing characteristics such as age, prior experience with advanced therapies, or coexisting conditions. SC IFX showed high treatment satisfaction for both physicians and patients. No new safety signals were reported. Conclusions In this real-world study, SC IFX demonstrated clinical effectiveness in both radiographic and non-radiographic axSpA, with consistent results across diverse patient characteristics. Both physicians and patients reported high satisfaction with no new safety concerns. This analysis suggests that SC IFX can be an effective, convenient, and well-tolerated treatment option for diverse axSpA patient populations.

Gongan Jiang, Weijun Wang, Yuhao Yang et al.

Abstract Objective Information on pathogens and sensitive antibiotics is crucial for treating periprosthetic joint infection (PJI), one of the most severe complications of joint arthroplasty. Lacking this information is not uncommon, and empirical antibiotic treatment should be adopted as a compromise. This study aimed to develop regional-specific antimicrobial regimens and provide a reference for empirical antibiotic treatment for PJI by retrospectively analyzing the pathogen profiles of PJI patients treated in our center and their antibiotic sensitivities. Methods PJI patients treated at our center from January 2018 to December 2024 were retrospectively recruited. Joint aspiration was performed preoperatively to collect synovial fluid for culture and differential cell counting, and synovial tissue samples were obtained intraoperatively from at least three different sites for culture. Patients were diagnosed according to the guidelines of the 2018 International Consensus Meeting and the European Bone and Joint Infection Society. The culture-positive rate, distribution of gram-positive pathogens, methicillin resistance, mixed infections, and multidrug resistance were analyzed. The effective coverage rates of antibiotics were determined, and appropriate empirical antibiotic regimens were proposed. Results A total of 255 PJI patients, comprising 104 males and 151 females, were included; 141 patients had hip PJI, and 114 had knee PJI. Among them, 224 patients (87.8%) had positive culture results. We isolated 335 pathogens, including 218 coagulase-negative staphylococcal infections (65.1%). Staphylococcus epidermidis was the most prevalent pathogen, with 86 isolates (25.7%), followed by Staphylococcus aureus, with 45 isolates (13.4%), and Streptococci, with 20 isolates (6.0%). In hip PJI, the most common pathogens were Staphylococcus epidermidis (50 isolates, 26.6%) and Staphylococcus aureus (30 isolates, 16.0%), and in knee PJI, Staphylococcus epidermidis was predominant (36 isolates, 24.5%). In terms of drug resistance, 48.1% of the staphylococcal strains were methicillin resistant, and 57.6% of the pathogens were multidrug resistant. Staphylococci showed 100% sensitivity to vancomycin and linezolid but were highly resistant to β-lactams and quinolones. In patients with acute postoperative PJI, the combination of vancomycin combined with ceftazidime was 98.4% effective. In patients with chronic PJI, vancomycin combined with imipenem and meropenem achieved effective coverage rates of 94.4% and 95.5%, respectively. The combination of linezolid with meropenem also achieved a 95.5% effective coverage rate. Conclusion Gram-positive bacteria were the predominant pathogens associated with PJI, with high rates of methicillin resistance and multidrug resistance. The combination of vancomycin and meropenem is an empirical antibiotic regimen for culture-negative chronic PJI patients in this region, with the combination of linezolid and meropenem as an alternative. For patients with culture-negative acute postoperative PJI, vancomycin combined with ceftazidime is suggested as the preferred empirical therapy.

Caroline J. Cushman, Andrew F. Ibrahim, Alexander D. Smith et al.

Background: The musculoskeletal system, due to inherent structure and function, lends itself to contributing toward joint pain, whether from inflammatory disorders such as rheumatoid arthritis, degenerative diseases such as osteoarthritis, or trauma causing soft tissue injury. Administration of peptides for treatment of joint pain or inflammation is an emerging line of therapy that seeks to offer therapeutic benefits while remaining safe and relatively non-invasive. Purpose: The purpose of this study is to review the current literature on existing oral peptide agents, intra-articular peptide agents, and new developments in human trials to assess route of administration (RoA) for drug delivery in terms of soft tissue regeneration. Study Design: Narrative Review. Methods: A comprehensive literature search was conducted using the PubMed database. The search included medical subject headings (MeSH) terms related to peptide therapy, soft tissue regeneration, and RoA. Inclusion criteria comprised articles focusing on the mechanisms of action of peptides, clinical or biochemical outcomes, and review articles. Exclusion criteria included insufficient literature or studies not meeting the set evidence level. Conclusion: The review identified various peptides demonstrating efficacy in soft tissue repair. Oral and intra-articular peptides showed distinct advantages in soft tissue regeneration, with intra-articular routes providing localized effects and oral routes offering systemic benefits. However, both routes have limitations in bioavailability and absorption. Still in their infancy, further inquiries/research into the properties and efficacy of emerging peptides will be necessary before widespread use. As a viable alternative prior to surgical intervention, peptide treatments present as promising candidates for positive outcomes in soft tissue regeneration.

Tian-Liang, Qiaohui Xie, Ribu Shama et al.

OBJECTIVES This study aimed to systematize the Zhuang medicinal herbs of Ardisia (ZMHA) in China, to clarify the traditional use in Zhuang medicine and the dynamics of international research on phytochemistry, pharmacology, clinical application, and toxicity. KEY FINDINGS There are 25 species of ZMHA, approximately 938 compounds from the different part, including triterpenoids, phenolics, volatile oils, etc. Pharmacological activity studies have also shown that this genus has anti-tumour, anti-inflammatory, anti-oxidant, anti-bacterial, anti-microbial, etc., and significant effects on respiratory, digestive, urinary, and musculoskeletal system diseases without toxic side effects. SUMMARY The Ardisia has a medicinal history of nearly a thousand years, mainly for treating diseases of the injuries, musculoskeletal, and symptomatic system in Zhuang medicine. Some plants, such as A. crenata, A. gigantifolia, and A. japonica, are also commonly used in folk Zhuang medicine formulas, to treat musculoskeletal, injury, respiratory, and urinate systems disease. These diseases are related to inflammation. These could provide a new direction for future new drug development research. Therefore, species identification and resource investigation should be strengthened, and conducted in vitro mechanism, in vivo pharmacology, clinical efficacy, and toxicology studies and establish a perfect quality standard system.

Randhir Singh, Gagandeep Singh

D. Bikle

Abstract The interest in vitamin D continues unabated with thousands of publications contributing to a vast and growing literature each year. It is widely recognized that the vitamin D receptor (VDR) and the enzymes that metabolize vitamin D are found in many cells, not just those involved with calcium and phosphate homeostasis. In this mini review I have focused primarily on recent studies that provide new insights into vitamin D metabolism, mechanisms of action, and clinical applications. In particular, I examine how mutations in vitamin D metabolizing enzymes—and new information on their regulation—links vitamin D metabolism into areas such as metabolism and diseases outside that of the musculoskeletal system. New information regarding the mechanisms governing the function of the VDR elucidates how this molecule can be so multifunctional in a cell-specific fashion. Clinically, the difficulty in determining vitamin D sufficiency for all groups is addressed, including a discussion of whether the standard measure of vitamin D sufficiency, total 25OHD (25 hydroxyvitamin) levels, may not be the best measure—at least by itself. Finally, several recent large clinical trials exploring the role of vitamin D supplementation in nonskeletal diseases are briefly reviewed, with an eye toward what questions they answered and what new questions they raised.

Nitchanant Kitcharanant, Prangmalee Leurcharusmee, Pichitchai Atthakomol et al.

Abstract Background Even with the great advancements in recent years in total knee arthroplasty (TKA), some patients continue to have persistent postsurgical pain (PPSP). The advantages of systemic corticosteroids in the perioperative context have been further supported by previously published trials. However, the impact of dexamethasone on the intensity of post-TKA PPSP is still unclear. We aimed to investigate its effect on the degree of PPSP and compare that with a placebo. Methods In this randomized, double-blind, placebo-controlled study, 48 patients undergoing unilateral TKA were given intravenous dexamethasone 10 mg or saline just before spinal anesthesia was induced, and they also received two additional doses of dexamethasone 10 mg or saline 24 and 48 h after surgery. A standardized, multimodal analgesic regimen was administered to each patient. The modified WOMAC pain scores at 12 weeks postoperative were the main outcome. The secondary outcomes included pain during a walk of five meters, pain during active knee flexion at 45 degrees, maximum pain at rest during the previous 24 h, nausea visual analogue scale values, and use of rescue opioid and antiemetic medications. Results There was no difference in modified WOMAC pain scores 12 weeks after surgery between patients who received and did not receive perioperative dexamethasone. At 24, 30, 48, 54, and 72 h following surgery, the dexamethasone group experienced considerably less pain during a five-meter walk and during 45 degrees active knee flexion (p < 0.01). At postoperative 0–24, 24–48, and 48–72 h, the dexamethasone group experienced less maximal pain at rest (p < 0.01). The dexamethasone group also had less visual analogue scale scores for nausea at 6, 24, 30, 48, and 54 h after surgery (p < 0.02). During the first 0–24 and 24–48 h, the dexamethasone group consumed fewer opioids and antiemetic medications (p < 0.01). All patients showed no signs of wound complications. Conclusions When compared to a placebo at 12 weeks after TKA, intravenous dexamethasone did not reduce PPSP. Nevertheless, early postoperative pain was relieved by perioperative intravenous dexamethasone, which also decreased the need for opioid and antiemetic medications and decreased postoperative nausea and vomiting. Trial registration NCT02760459.

Elisa Cassart, Joan Miquel, Fernando Santana et al.

Xin Yang, Yimurang Hamiti, Kai Liu et al.

Abstract Background The management of docking site healing in bone transport remains a significant challenge in orthopedic surgery. Traditional assessment methods rely heavily on qualitative radiographic evaluations. This study investigates the utility of pixel value ratio (PVR), an objective quantitative measure, in assessing bone healing at the docking site during bone transport. Methods This retrospective study included 47 patients who underwent bone transport for lower limb reconstruction between January 2015 and January 2020. Patients were categorized into bone union (n = 35) and nonunion (n = 12) groups based on docking site outcomes. PVR was calculated using two methods (PVR1 and PVR2) at six time points over 24 months post-docking. Subgroup analyses were performed based on gender, age, and surgical site. Results Of 47 patients, 35 achieved bone union and 12 experienced nonunion. Both PVR1 and PVR2 were consistently lower in the union group compared to the nonunion group at all time points (p < 0.001). In the union group, PVR1 ranged from 1.064 ± 0.050 to 1.108 ± 0.062, while PVR2 ranged from 0.926 ± 0.079 to 0.946 ± 0.062. In the nonunion group, PVR1 ranged from 1.204 ± 0.057 to 1.273 ± 0.020, and PVR2 from 1.039 ± 0.060 to 1.148 ± 0.022. Subgroup analyses revealed that males had significantly lower PVR values compared to females, and tibial cases had lower PVR values compared to femoral cases in both union and nonunion groups (p < 0.05). All juvenile patients achieved union, compared to 71.4% of adults (p < 0.01). Conclusion PVR demonstrates significant potential as an objective tool for assessing docking site healing in bone transport procedures. The distinct patterns observed between union and nonunion cases provide a foundation for developing clinical guidelines to monitor and predict healing outcomes. Integration of PVR assessment into clinical practice could improve decision-making and optimize treatment protocols in bone transport procedures.

Kanehiro Hiyama, MD, PhD, Takuya Takakuwa, MD, Reiko Yamaguchi, MD et al.

S. Yadav, S. Bonnes, Elizabeth A. Gilman et al.

Case series Patients: Female, 45-year-old • Female, 46-year-old • Female, 54-year-old • Female, 61-year-old • Female, 19-year-old Final Diagnosis: Arthritis • rheumatoid arthritis Symptoms: Fatigue • joint pain • swelling Clinical Procedure: — Specialty: General and Internal Medicine • Rheumatology Objective: Rare coexistence of disease or pathology Background: Some patients who have recovered from acute infection with SARS-CoV-2 develop persistent symptoms that have been termed post-COVID syndrome (PoCoS). PoCoS can affect the musculoskeletal system, with arthralgia and myalgia being common. Preliminary evidence suggests that PoCoS is an immune-mediated condition that not only predisposes but also precipitates pre-existing inflammatory joint diseases such as rheumatoid arthritis and reactive arthritis. Here, we describe a series of patients who presented to our Post-COVID Clinic and were found to have inflammatory arthritis (reactive and rheumatoid arthritis). Case Reports: We present 5 patients who developed joint pain several weeks after recovery from acute SARS-CoV-2 infection. These patients were seen in our Post-COVID Clinic and came from locations across the United States. All 5 patients were women, with age of diagnosis of COVID-19 disease between 19 and 61 years (mean 37.8 years). All patients presented with joint pain as the primary concern to the Post-COVID Clinic. Abnormal joint imaging was present in all patients. Treatments varied and included non-steroidal anti-inflammatory drugs, acetaminophen, corticosteroids, immunomodulators (golimumab), methotrexate, leflunomide, and hydroxychloroquine. Conclusions: COVID-19 disease is a potential cause of inflammatory arthritis, with both rheumatoid arthritis and reactive arthritis demonstrated in our PoCoS population. Care must be taken to identify these conditions, as there are treatment ramifications.

Fernando Perez-Ruiz

Bedros Taslakian, Larry E. Miller, Tarub S. Mabud et al.

Objective: Genicular artery embolization (GAE) is a novel, minimally invasive procedure for treatment of knee osteoarthritis (OA). This meta-analysis investigated the safety and effectiveness of this procedure. Design: Outcomes of this systematic review with meta-analysis were technical success, knee pain visual analog scale (VAS; 0–100 scale), WOMAC Total Score (0–100 scale), retreatment rate, and adverse events. Continuous outcomes were calculated as the weighted mean difference (WMD) versus baseline. Minimal clinically important difference (MCID) and substantial clinical benefit (SCB) rates were estimated in Monte Carlo simulations. Rates of total knee replacement and repeat GAE were calculated using life-table methods. Results: In 10 groups (9 studies; 270 patients; 339 knees), GAE technical success was 99.7%. Over 12 months, the WMD ranged from −34 to −39 at each follow-up for VAS score and −28 to −34 for WOMAC Total score (all p ​< ​0.001). At 12 months, 78% met the MCID for VAS score; 92% met the MCID for WOMAC Total score, and 78% met the SCB for WOMAC Total score. Higher baseline knee pain severity was associated with greater improvements in knee pain. Over 2 years, 5.2% of patients underwent total knee replacement and 8.3% received repeat GAE. Adverse events were minor, with transient skin discoloration as the most common (11.6%). Conclusions: Limited evidence suggests that GAE is a safe procedure that confers improvement in knee OA symptoms at established MCID thresholds. Patients with greater knee pain severity may be more responsive to GAE.

Honor Morris, Cátia F. Gonçalves, M. Dudek et al.

Circadian clocks in the brain and peripheral tissues temporally coordinate local physiology to align with the 24 hours rhythmic environment through light/darkness, rest/activity and feeding/fasting cycles. Circadian disruptions (during ageing, shift work and jet-lag) have been proposed as a risk factor for degeneration and disease of tissues, including the musculoskeletal system. The intervertebral disc (IVD) in the spine separates the bony vertebrae and permits movement of the spinal column. IVD degeneration is highly prevalent among the ageing population and is a leading cause of lower back pain. The IVD is known to experience diurnal changes in loading patterns driven by the circadian rhythm in rest/activity cycles. In recent years, emerging evidence indicates the existence of molecular circadian clocks within the IVD, disruption to which accelerates tissue ageing and predispose animals to IVD degeneration. The cell-intrinsic circadian clocks in the IVD control key aspects of physiology and pathophysiology by rhythmically regulating the expression of ~3.5% of the IVD transcriptome, allowing cells to cope with the drastic biomechanical and chemical changes that occur throughout the day. Indeed, epidemiological studies on long-term shift workers have shown an increased incidence of lower back pain. In this review, we summarise recent findings of circadian rhythms in health and disease, with the IVD as an exemplar tissue system. We focus on rhythmic IVD functions and discuss implications of utilising biological timing mechanisms to improve tissue health and mitigate degeneration. These findings may have broader implications in chronic rheumatic conditions, given the recent findings of musculoskeletal circadian clocks.

A. Pilipenko, V. Mazurov, I. Gaydukova

Celiac disease (CD) is one of the most common gastrointestinal tract diseases, in adults and children. Prevalence of CD is 1-3% [2]. The most common symptoms of CD are gastrointestinal symptoms. At the same time, celiac disease may manifest with extraintestinal symptoms, including the musculoskeletal, nervous, reproductive system, and skin, especially when it debuts at a late age [1,2]. However, data about musculoskeletal manifestations of CD are limited.To show the frequency of musculoskeletal complaints and their peculiarities in patients with CD.Data from 94 patients with diagnosed by gastroenterologist celiac disease were collected with the on-lain survey. All the patients were positive in CD-related immunological and genetic tests and had biopsy established CD.Тhe average age of respondents is 37,52 ± 11,2 years, women 79 (84,1%), men 15 (15,9%). Among 94 respondents 0.1% do not follow a gluten-free diet, 10.6% 5 years, 14.9% – 10-15 years, 8.5% > 15 years. Gastrointestinal symptoms have started at the age 40 years old).Extraintestinal symptoms such as drowsiness were noted by 46.8 %, headaches by 40.4%, weakness by 59.6%, irritability by 57.4% of respondents. Lack of coordination was noticed in 18.1% of cases, dizziness in 22.3%, 57.4% have numbness, decreased sensitivity, and tingling feeling in the limbs. Joint pain had 54.3% of the patients with CD (Figure 1).Figure 1.Frequency of pain in different jointsThe maximal intensity of pain was noticed in the morning (8.5%) or late night (13.8%) times and fulfilled inflammatory pain criteria (ASAS). In 17% was noticed interrelation between gluten-free diet violation and the appearance of joint pain. In 26.6% was noticed signs of enthesitis. Weakness of arms was noticed by 39.4% of respondents. Non-steroidal anti-inflammatory drugs (NSAIDs) were started by 35.1% of patients, without any improvement in 66% of cases.Patients’ surveys showed that musculoskeletal symptoms in patients with celiac disease are not a rare problem and they are comparable with the frequency of neurological symptoms. Additional research is necessary for a better understanding of the nature of musculoskeletal involvement in celiac disease.[1]Admou, B., et al. https://doi.org/10.1155/2012/637187.[2]Laurikka P., et al. https://doi.org/10.3390/nu10081015None declared

C. Sánchez-Piedra, C. Díaz-Torné, J. Manero et al.

From the beginning of the COVID-19 pandemic, more than 4.7 million cases have been detected in the world, Spain being one of the countries hardest hit by the SARS-CoV-2.1 The role of the immune system and immunomodulatory therapies in the evolution of this infection is still controversial.2 The study of patients with rheumatic and musculoskeletal diseases (RMDs) such as rheumatoid arthritis (RA), spondyloarthropathies (SpA) or systemic lupus erythematosus, treated with immunomodulatory therapies is essential to understand the prognosis of COVID-19 in this specific population and to the management of these patients. BIOBADASER is a multicentre prospective observational registry promoted by the Spanish Society of Rheumatology (SER) and supported by the Spanish Agency of Drugs and Medical Devices. It is aimed at assessing safety in patients with RMDs starting treatment with any biological (bDMARD) or targeted synthetic disease-modifying antirheumatic drug (tsDMARD). More than 6600 patients are prospectively followed up in BIOBADASER 3.0. This report describes the clinical characteristics and outcomes of patients with COVID-19 in BIOBADASER. We have identified 41 patients with RMDs treated with bDMARD and …

Alex M Hollenberg, Charles O Smith, Laura C Shum et al.

ABSTRACT Cellular bioenergetics is a promising new therapeutic target in aging, cancer, and diabetes because these pathologies are characterized by a shift from oxidative to glycolytic metabolism. We have previously reported such glycolytic shift in aged bone as a major contributor to bone loss in mice. We and others also showed the importance of oxidative phosphorylation (OxPhos) for osteoblast differentiation. It is therefore reasonable to propose that stimulation of OxPhos will have bone anabolic effect. One strategy widely used in cancer research to stimulate OxPhos is inhibition of glycolysis. In this work, we aimed to evaluate the safety and efficacy of pharmacological inhibition of glycolysis to stimulate OxPhos and promote osteoblast bone-forming function and bone anabolism. We tested a range of glycolytic inhibitors including 2-deoxyglucose, dichloroacetate, 3-bromopyruvate, and oxamate. Of all the studied inhibitors, only a lactate dehydrogenase (LDH) inhibitor, oxamate, did not show any toxicity in either undifferentiated osteoprogenitors or osteoinduced cells in vitro. Oxamate stimulated both OxPhos and osteoblast differentiation in osteoprogenitors. In vivo, oxamate improved bone mineral density, cortical bone architecture, and bone biomechanical strength in both young and aged C57BL/6J male mice. Oxamate also increased bone formation by osteoblasts without affecting bone resorption. In sum, our work provided a proof of concept for the use of anti-glycolytic strategies in bone and identified a small molecule LDH inhibitor, oxamate, as a safe and efficient bone anabolic agent. © 2020 American Society for Bone and Mineral Research (ASBMR).

F. McQueen, N. Stewart, J. Crabbe et al.