Treatment Of Musculoskeletal Diseases Research Articles

NSAID use in orthopedic surgery:A review of current evidence and clinical practice guidelines.

Nonsteroidal anti-inflammatory drugs (NSAIDs)are a valuable class of medications for orthopedic surgeons and often play a pivotal role in pain control. However, there are many common stipulations resulting in avoidance of its use in the treatment of musculoskeletal disease. This review summarizes the mechanism of action of NSAIDs as well as provides an overview of commonly used NSAIDs and the differences between them. It provides a concise summary on the osseous effects of NSAIDs with regard to bone healing and heterotopic ossification. Most of all, it serves as a guide or reference for orthopedic providers when counseling patients on the risks and benefits of NSAID use, as it addresses the common stipulations encountered: "It irritates my stomach," "I have a history of bariatric surgery," "I'm already on a blood thinner," "I've had a heart attack," and "I've got kidney problems" and synthesizes both current research and society recommendations regarding safe use and avoidance of NSAIDs.

Expanding the therapeutic potential of Salvia miltiorrhiza: a review of its pharmacological applications in musculoskeletal diseases.

Musculoskeletal diseases (MSDs) present significant challenges to healthcare systems worldwide. Previous studies have demonstrated the high efficacy and prospects of Salvia miltiorrhiza and its active ingredients for treatment of MSDs. This review aims to illuminate the newfound applications of Salvia miltiorrhiza and its active ingredients in the treatment of various MSDs, effectively bridging the gap between an established medicine and an emerging field. In this review, previous studies related to Salvia miltiorrhiza and its active ingredients on the treatment of MSD were collected, the specific active ingredients of Salvia miltiorrhiza were summarized, the effects of Salvia miltiorrhiza and its active ingredients for the treatment of MSDs, as well as their potential molecular mechanisms were reviewed and discussed. Based on previous publications, Salvianolic acid A, salvianolic acid B, tanshinone IIA are the representative active ingredients of Salvia miltiorrhiza. Their application has shown significant beneficial outcomes in osteoporosis, fractures, and arthritis. Salvia miltiorrhiza and its active ingredients protect against MSDs by regulating different signaling pathways, including ROS, Wnt, MAPK, and NF-κB signaling. Salvia miltiorrhiza and its active ingredients demonstrate promising potential for bone diseases and have been explored across a wide variety of MSDs. Further exploration of Salvia miltiorrhiza's pharmacological applications in MSDs holds great promise for advancing therapeutic interventions and improving the lives of patients suffering from these diseases.

Causal effects of specific gut microbiota on musculoskeletal diseases: a bidirectional two-sample Mendelian randomization study.

Recent observational studies and clinical trials demonstrated an association between gut microbiota and musculoskeletal (MSK) diseases. Nonetheless, whether the gut microbiota composition has a causal effect on the risk of MSK diseases remains unclear. Based on large-scale genome-wide association studies (GWAS), we performed a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between gut microbiota and six MSK diseases, namely osteoporosis (OP), fracture, sarcopenia, low back pain (LBP), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). Instrumental variables for 211 gut microbiota taxa were obtained from the largest available GWAS meta-analysis (n = 18,340) conducted by the MiBioGen consortium. And the summary-level data for six MSK diseases were derived from published GWAS. The inverse-variance weighted (IVW) method was conducted as a primary analysis to estimate the causal effect, and the robustness of the results was tested via sensitivity analyses using multiple methods. The Bonferroni-corrected test was used to determine the strength of the causal relationship between gut microbiota and various MSK diseases. Finally, a reverse MR analysis was applied to evaluate reverse causality. According to the IVW method, we found 57 suggestive causal relationships and 3 significant causal relationships between gut microbiota and MSK diseases. Among them, Genus Bifidobacterium (β: 0.035, 95% CI: 0.013-0.058, p = 0.0002) was associated with increased left handgrip strength, Genus Oxalobacter (OR: 1.151, 95% CI: 1.065-1.245, p = 0.0003) was correlated with an increased risk of LBP, and Family Oxalobacteraceae (OR: 0.792, 95% CI: 0.698-0.899, p = 0.0003) was linked with a decreased risk of RA. Subsequently, sensitivity analyses revealed no heterogeneity, directional pleiotropy, or outliers for the causal effect of specific gut microbiota on MSK diseases (p > 0.05). Reverse MR analysis showed fracture may result in a higher abundance of Family Bacteroidales (p = 0.030) and sarcopenia may lead to a higher abundance of Genus Sellimonas (p = 0.032). Genetic evidence suggested a causal relationship between specific bacteria taxa and six MSK diseases, which highlights the association of the "gut-bone/muscle" axis. Further exploration of the potential microbiota-related mechanisms of bone and muscle metabolism might provide novel insights into the prevention and treatment of MSK diseases.

Chemical and biological differences between original and mimetic pentosan polysulfates

Pentosan polysulfate sodium (PPS) is a semi-synthetic, heparin-like polysaccharide with manifold therapeutic actions. It is approved for treatment of bladder pain syndrome / interstitial cystitis in humans and treatment of musculoskeletal diseases in animals.PPS is produced by a complex procedure using beech wood as starting material. It consists of a mixture of sulfated glucuronoxylans, whose structural composition cannot be fully characterized by physicochemical analysis. The question arises whether PPS follow-on products are identical with the original and thus meet the requirement for generic drug application.The aim of this study was to investigate whether commercially available PPS products differ in physicochemical characteristics and biological effects from the original.Ten PPS preparations from different manufactures were analyzed using orthogonal analytical techniques including, inter alia, size exclusion chromatography with triple detection, nuclear magnetic resonance spectroscopy, and high-resolution mid-infrared spectroscopy in aqueous solution with chemometric evaluation. For functional analysis, we measured the plasma kallikrein generation in human plasma and FXII activation.The study revealed significant structural and biological differences between PPS from different sources. Therefore, follow-on products cannot be considered identical but at best similar to original PPS. However, their similar efficacy and safety have still to be proven by comprehensive studies.

Deep learning for the rapid automatic segmentation of forearm muscle boundaries from ultrasound datasets.

Ultrasound (US) is widely used in the clinical diagnosis and treatment of musculoskeletal diseases. However, the low efficiency and non-uniformity of artificial recognition hinder the application and popularization of US for this purpose. Herein, we developed an automatic muscle boundary segmentation tool for US image recognition and tested its accuracy and clinical applicability. Our dataset was constructed from a total of 465 US images of the flexor digitorum superficialis (FDS) from 19 participants (10 men and 9 women, age 27.4 ± 6.3years). We used the U-net model for US image segmentation. The U-net output often includes several disconnected regions. Anatomically, the target muscle usually only has one connected region. Based on this principle, we designed an algorithm written in C++ to eliminate redundantly connected regions of outputs. The muscle boundary images generated by the tool were compared with those obtained by professionals and junior physicians to analyze their accuracy and clinical applicability. The dataset was divided into five groups for experimentation, and the average Dice coefficient, recall, and accuracy, as well as the intersection over union (IoU) of the prediction set in each group were all about 90%. Furthermore, we propose a new standard to judge the segmentation results. Under this standard, 99% of the total 150 predicted images by U-net are excellent, which is very close to the segmentation result obtained by professional doctors. In this study, we developed an automatic muscle segmentation tool for US-guided muscle injections. The accuracy of the recognition of the muscle boundary was similar to that of manual labeling by a specialist sonographer, providing a reliable auxiliary tool for clinicians to shorten the US learning cycle, reduce the clinical workload, and improve injection safety.

Comparison of the Penetration Depth of 905 nm and 1064 nm Laser Light in Surface Layers of Biological Tissue Ex Vivo.

The choice of parameters for laser beams used in the treatment of musculoskeletal diseases is of great importance. First, to reach high penetration depths into biological tissue and, secondly, to achieve the required effects on a molecular level. The penetration depth depends on the wavelength since there are multiple light-absorbing and scattering molecules in tissue with different absorption spectra. The present study is the first comparing the penetration depth of 1064 nm laser light with light of a smaller wavelength (905 nm) using high-fidelity laser measurement technology. Penetration depths in two types of tissue ex vivo (porcine skin and bovine muscle) were investigated. The transmittance of 1064 nm light through both tissue types was consistently higher than of 905 nm light. The largest differences (up to 5.9%) were seen in the upper 10 mm of tissue, while the difference vanished with increasing tissue thickness. Overall, the differences in penetration depth were comparably small. These results may be of relevance in the selection of a certain wavelength in the treatment of musculoskeletal diseases with laser therapy.

Fracture healing-orthobiologics: from basic science to clinical application.

Orthopaedics as a field and a profession is fundamentally concerned with the treatment of musculoskeletal disease, in all of its many forms. Our collective understanding of the cellular mechanisms underlying musculoskeletal pathology resulting from injury continues to evolve, opening novel opportunities to develop orthobiologic treatments to improve care. It is a long path to move from an understanding of cellular pathology to development of successful clinical treatment, and this article proposes to discuss some of the challenges to achieving translational therapies in orthopaedics. The article will focus on challenges that clinicians will likely face in seeking to bring promising treatments forward to clinical practice and strategies for improving success in translational efforts.

The Potential Roles of Ferroptosis in Pathophysiology and Treatment of Musculoskeletal Diseases-Opportunities, Challenges, and Perspectives.

Ferroptosis is different from other forms of cell death, such as apoptosis, autophagy, pyroptosis, and cuproptosis, mainly involving iron metabolism and lipid peroxidation. Ferroptosis plays an important role in various disease, such as malignant tumors, neuron-degenerative diseases, and cardiovascular diseases, and has become the focus of current research. Both iron overload and lipid peroxide accumulation contribute to the occurrence, development, and treatment of musculoskeletal diseases, such as osteoporosis, osteoarthritis, osteosarcoma, intervertebral disc degeneration, and spinal cord injury. For a better understanding of the potential roles ferroptosis may play in pathophysiology and treatment of common musculoskeletal disorders, this article briefly reviewed the relationship and possible mechanisms. Through an investigation of ferroptosis' role in musculoskeletal diseases' occurrence, development, and treatment, ferroptosis could offer new opportunities for clinical diagnosis and treatment.

Application and thinking of musculoskeletal ultrasound in diagnosis and treatment of musculoskeletal diseases with acupuncture and moxibustion.

Musculoskeletal ultrasound (MSUS) is characterized as the dynamic, real-time and continuous visualization, the quantitative and qualitative localization,the simple operation and the absence of use contraindication. As a tool for auxiliary examination, treatment, evaluation and research, in acupuncture and moxibustion, MSUS may improve the accuracy of acupoint location, guide the direction and depth of needle insertion, monitor the reactions of deqi, guarantee the safety of operation and quantify the effect evaluation. Hence, it may provide an objective basis for acupuncture and moxibustion research and be conductive to display the operation techniques of acupuncture and moxibustion by means of objective approaches such as imaging and data.

Transdermal drug delivery via microneedles for musculoskeletal systems.

As the population is ageing and lifestyle is changing, the prevalence of musculoskeletal (MSK) disorders is gradually increasing with each passing year, posing a serious threat to the health and quality of the public, especially the elderly. However, currently prevalent treatments for MSK disorders, mainly administered orally and by injection, are not targeted to the specific lesion, resulting in low efficacy along with a series of local and systemic adverse effects. Microneedle (MN) patches loaded with micron-sized needle array, combining the advantages of oral administration and local injection, have become a potentially novel strategy for the administration and treatment of MSK diseases. In this review, we briefly introduce the basics of MNs and focus on the main characteristics of the MSK systems and various types of MN-based transdermal drug delivery (TDD) systems. We emphasize the progress and broad applications of MN-based transdermal drug delivery (TDD) for MSK systems, including osteoporosis, nutritional rickets and some other typical types of arthritis and muscular damage, and in closing summarize the future prospects and challenges of MNs application.

Extracorporeal Shock Wave Treatment for Calcifying Tendinitis of the Shoulder: A Case Report and Literature Review

Background: Calcifying tendinitis of the shoulder (CTS), also known as rotator cuff calcific tendinitis, is a self-limiting shoulder disorder primarily characterized by inflammation surrounding hydroxyapatite crystal deposits in the tendons of the rotator cuff. Given the specific characteristics of the shoulder joint and the uncertainty regarding the efficacy of various treatments for CTS, no standardized treatment protocol has been established. However, numerous studies have demonstrated that extracorporeal shock wave therapy (ESWT) is effective in alleviating pain and improving joint function in patients with calcifying tendinitis of the shoulder. The therapeutic process works using high-energy shock waves to break down deposits of calcification, reduce local inflammation, and promote tissue healing. The purpose of this article is to present a case of symptomatic calcifying tendinopathy involving the rotator cuff and further demonstrate that ESWT has good efficacy in the treatment of musculoskeletal diseases. Results: In this case, a 39-year-old woman with a 6-month history of shoulder pain and limited range of motion (ROM) was diagnosed with calcifying tendinitis of the shoulder. A single session of shock wave therapy resulted in the complete resolution of calcific deposits and the patient’s symptoms, leading to a return to her normal ROM and improved quality of life. Conclusion: ESWT has been shown to be a good alternative to surgery for the treatment of calcifying tendinitis of the shoulder (CTS). It can significantly alleviate pain, improve shoulder function, and reduce the average size of calcium deposits. It might be the first choice for treating shoulder tendinopathy due to its effectiveness and safety. Keywords: Calcifying tendinitis, Shoulder pain, Extracorporeal shock wave treatment, Case report

Secreted Factors and Extracellular Vesicles Account for the Immunomodulatory and Tissue Regenerative Properties of Bone-Marrow-Derived Mesenchymal Stromal Cells for Osteoarthritis.

Bone-marrow-derived mesenchymal stromal cells (BMSCs) showed therapeutic potential in the treatment of musculoskeletal diseases, including osteoarthritis (OA). Their soluble mediators and extracellular vesicles (EVs), which make up the secretome, suppress immune response, attenuate inflammation and promote cartilage repair. EVs, as well as the whole secretome, have been investigated as cell free approaches for OA although, to date, a disease-tailored molecular fingerprint is missing. In this study, soluble mediators and miRNAs were sifted in the BMSCs' secretome and EVs, respectively, and analyzed in the frame of cell types and factors involved in OA. The majority of identified molecules repress the activation of immune cells and the production of OA-related inflammatory mediators, as well as promote cartilage protection by acting on both chondrocytes homeostasis and extracellular matrix-degrading enzymes. These data provide the molecular ground for the therapeutic potential of BMSCs for regenerative applications for OA and support the use of secretome or EVs as cell-free applications in joint diseases.

Efficacy of Laser Therapy in the Treatment of Shoulder Impingement Syndrome: A Systematic Review and Meta-Analysis

Abstract Background Laser therapy is used as a noninvasive treatment for musculoskeletal diseases, including shoulder pain, but its efficacy in shoulder impingement syndrome remains controversial. This study aimed to systematically evaluate the efficacy and safety of laser therapy in shoulder impingement syndrome. Methods The PubMed, Embase, and Cochrane Library databases were searched from its establishment to June 2021. Randomized controlled trials (RCTs) in shoulder impingement syndrome were included. The primary outcome was pain, and the secondary outcomes were function and range of motion. Meta-analysis was performed with RevMan 5.3. Results A total of 12 RCTs and 669 participants were included. The results showed that laser therapy exhibited significant efficacy in shoulder impingement syndrome, especially in terms of pain release (MD=1.26, 95% CI=0.55–1.97, P=0.0005) and range of motion (MD=4.27, 95% CI=1.93–6.61, P=0.0003). However, the effect of shoulder function was uncertain (SMD=0.43, 95% CI=0–0.85, P=0.05). The subgroup analysis of pain showed that the efficacy of the laser therapy was related to the wavelength of the laser and the number of combined treatments. No adverse events were reported in the included trials. Conclusions Laser therapy can significantly relieve pain in shoulder impingement syndrome and has no adverse reactions.

Autologous conditioned serum applications in the treatment of musculoskeletal diseases: a narrative review.

Aim:Autologous conditioned serum has been studied as a treatment option in musculoskeletal disorders and resulted in varying outcomes. This study aims to pool the current data on this matter.Materials & methods:Major databases were searched for the topics, and after screening the results, the final 21 papers (level of evidence I or II) were included.Results & conclusion:This study showed a major focus of the literature on the effectiveness of autologous conditioned serum in osteoarthritis, in which there is much high-quality evidence suggesting its safety and efficacy. Also, some of the available experiments are assessing its application in tendinopathies and radiculopathies which, despite positive results, recommend further evaluations on this topic.

Effect of hydrogen sulphide containing mineral water on experimental osteoporosis in rats

Background/Aim: Sulphur mineral water is widely used in the treatment of musculoskeletal diseases. Hydrogen sulphide is an important regulator of bone metabolism and its application in the treatment of osteoporosis is intensively researched. The aim of this study was to analyse biochemical and histological effects of H2S containing mineral water of "Mlječanica" spring on ovariectomy-induced experimental osteoporosis in rats. Methods: In this experiment a 14-week-old Wistar female rats were used. The animals undergone bilateral ovariectomy (OVX groups) as an experimental model for oestrogen-deficient osteoporosis. After six weeks, animals were divided into control and the experimental group. Rats from the experimental group treated with H2S (SW group) containing mineral water ad libitum during five weeks. Biochemical parameters for monitoring sulphur water effects were concentration in serum of osteocalcin, alkaline phosphatase, calcium and phosphorus. Histological analyses of the left tibia coloured with haematoxylin-eosin were carried out. Results: Regarding the biochemical parameters, a statistically significant increase was observed in the OVX group for osteocalcin, alkaline phosphatase calcium and phosphorus compared to the sham-operated (CNT) group (p < 0.01). In SW + OVX, alkaline phosphatase was statistically significantly decreased (p < 0.01) and serum osteocalcin and phosphorus increased (p < 0.01). Calcium values were increased without significance. In the OVX + SW group, histological analyses showed numerous osteoblasts along the trabecular endosteum and the growth of young chondrocytes in the central bone zone and their migration to the peripheral parts. Conclusion: Drinking the H2S containing "Mlječanica" mineral water has led to decreased alkaline phosphatase, increased osteocalcin and phosphorus concentration in serum and stimulated the bone reparation in osteoporotic rats.

Bioengineered optogenetic model of human neuromuscular junction

Functional human tissues engineered from patient-specific induced pluripotent stem cells (hiPSCs) hold great promise for investigating the progression, mechanisms, and treatment of musculoskeletal diseases in a controlled and systematic manner. For example, bioengineered models of innervated human skeletal muscle could be used to identify novel therapeutic targets and treatments for patients with complex central and peripheral nervous system disorders. There is a need to develop standardized and objective quantitative methods for engineering and using these complex tissues, in order increase their robustness, reproducibility, and predictiveness across users. Here we describe a standardized method for engineering an isogenic, patient specific human neuromuscular junction (NMJ) that allows for automated quantification of NMJ function to diagnose disease using a small sample of blood serum and evaluate new therapeutic modalities. By combining tissue engineering, optogenetics, microfabrication, optoelectronics and video processing, we created a novel platform for the precise investigation of the development and degeneration of human NMJ. We demonstrate the utility of this platform for the detection and diagnosis of myasthenia gravis, an antibody-mediated autoimmune disease that disrupts the NMJ function.

Stromal Vascular Fraction and Amniotic Epithelial Cells: Preclinical and Clinical Relevance in Musculoskeletal Regenerative Medicine.

Musculoskeletal regenerative medicine is mainly based on the use of cell therapy to heal damaged tissues such as bone, cartilage, and tendons. Throughout the years, different cell types have been employed for the treatment of musculoskeletal diseases, in particular, mesenchymal stem cells (MSCs) derived from bone marrow (BMSCs) and adipose tissue (ADSCs). Though the results of these literature studies have been encouraging, there are some limitations, especially on long-term results. Recently, some interest has shifted towards new cell types such as the stromal vascular fraction (SVF) and amniotic endothelial cells (AECs). The aim of the present literature review is to evaluate preclinical and clinical studies that used SVF and AECs for musculoskeletal tissue regeneration. Forty-eight preclinical and clinical studies, performed in the last 10 years, were identified. Both SVF and AECs, injected or implanted with or without scaffolds, were shown to be valid alternatives, and in some ways superior, to ADSCs and BMSCs, being able to differentiate towards osteogenic, chondrogenic, and tenogenic lineages, and to promote cell and tissue regenerative potential. The use of SVF and AECs could represent a new regenerative treatment in several musculoskeletal pathologies, solving the problem of cell expansion in vitro.

Нейротропные витамины группы В: фокус на обезболивающий и противовоспалительный эффекты

Patients with musculoskeletal diseases (MSDs) constitute a heavy burden on the society. Therefore, there is a constant search for safe and efficient methods for treatment of such conditions, in which inflammation underlies the pathogenetic process. Chronic back pain is associated with physical inactivity and other lifestyle factors, such as tobacco consumption, poor dietary habits, overweight, poor sleep quality, and uncontrollable stress. For example, obesity is associated with low-grade chronic systemic inflammation, and is, therefore, a significant risk factor for occurrence and chronicity of back pain. The patient's lifestyle may contribute to MSDs, including chronic MSDs associated with inflammation and decreased functional capacity, both independently or in combination with other risk factors. The most common drugs used for treatment of MSDs are the non-steroidal anti-inflammatory drugs (NSAIDs). However, taking into account the possible NSAID-induced adverse events, the physicians are constantly thinking about ways to reduce the risks. В vitamins (B1, B6 and B12) possess analgesic and anti-inflammatory effects, which are discussed in the paper. When used in combination with NSAIDs, particularly in combination of diclofenac with vitamins B1, B6 and B12, the B vitamins possess some other positive effects contributing to restoration of mobility, pain relief and functional recovery in patients with low back pain. Such combination (diclofenac + vitamins B1, B6 and B12) is represented on the Russian market by Neurodiclovit, the successful use of which is discussed in the case report.

Injectable Biologics: What Is the Evidence?

Injectable biologics have attracted considerable interest in the field of musculoskeletal medicine. Biologics encompass a broad and diverse group of human tissue-derived therapeutics. The most commonly reported biologics for use in musculoskeletal conditions include platelet-rich plasma, bone marrow aspirate concentrate, mesenchymal stem cells, microfragmented fat, stromal vascular fraction, amniotic membrane-based products, and autologous conditioned serum. The benefits of biologics in tissue healing and regeneration are thought to be derived from their trophic, paracrine, and immunomodulatory functions. The purpose of this review is to define commonly used injectable biologics and to appraise current evidence on its efficacy in the treatment of musculoskeletal disease.

Extracellular Vesicles from Mesenchymal Stem Cells as Novel Treatments for Musculoskeletal Diseases

Mesenchymal stem/stromal cells (MSCs) represent a promising therapy for musculoskeletal diseases. There is compelling evidence indicating that MSC effects are mainly mediated by paracrine mechanisms and in particular by the secretion of extracellular vesicles (EVs). Many studies have thus suggested that EVs may be an alternative to cell therapy with MSCs in tissue repair. In this review, we summarize the current understanding of MSC EVs actions in preclinical studies of (1) immune regulation and rheumatoid arthritis, (2) bone repair and bone diseases, (3) cartilage repair and osteoarthritis, (4) intervertebral disk degeneration and (5) skeletal muscle and tendon repair. We also discuss the mechanisms underlying these actions and the perspectives of MSC EVs-based strategies for future treatments of musculoskeletal disorders.