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Orthopaedic Surgery Sep 2023Knee osteoarthritis (KOA) is a chronic joint bone disease characterized by inflammatory destruction and hyperplasia of bone. Its main clinical symptoms are joint... (Review)
Review
Knee osteoarthritis (KOA) is a chronic joint bone disease characterized by inflammatory destruction and hyperplasia of bone. Its main clinical symptoms are joint mobility difficulties and pain, severe cases can lead to limb paralysis, which poses major pressure to the quality of life and mental health of patients, but also brings serious economic burden to society. The occurrence and development of KOA is influenced by many factors, including systemic factors and local factors. The joint biomechanical changes caused by aging, trauma and obesity, abnormal bone metabolism caused by metabolic syndrome, the effects of cytokines and related enzymes, genetic and biochemical abnormalities caused by plasma adiponectin, etc. all directly or indirectly lead to the occurrence of KOA. However, there is little literature that systematically and comprehensively integrates macro- and microscopic KOA pathogenesis. Therefore, it is necessary to comprehensively and systematically summarize the pathogenesis of KOA in order to provide a better theoretical basis for clinical treatment.
Topics: Humans; Osteoarthritis, Knee; Quality of Life; Bone and Bones; Pain; Knee Joint
PubMed: 37435789
DOI: 10.1111/os.13809 -
Frontiers in Public Health 2023Degeneration of the intervertebral disc (IVD) is a normal part of aging. Due to the spine's declining function and the development of pain, it may affect one's physical... (Review)
Review
Degeneration of the intervertebral disc (IVD) is a normal part of aging. Due to the spine's declining function and the development of pain, it may affect one's physical health, mental health, and socioeconomic status. Most of the intervertebral disc degeneration (IVDD) therapies today focus on the symptoms of low back pain rather than the underlying etiology or mechanical function of the disc. The deteriorated disc is typically not restored by conservative or surgical therapies that largely focus on correcting symptoms and structural abnormalities. To enhance the clinical outcome and the quality of life of a patient, several therapeutic modalities have been created. In this review, we discuss genetic and environmental causes of IVDD and describe promising modern endogenous and exogenous therapeutic approaches including their applicability and relevance to the degeneration process.
Topics: Humans; Intervertebral Disc Degeneration; Quality of Life; Intervertebral Disc; Low Back Pain; Aging
PubMed: 37483952
DOI: 10.3389/fpubh.2023.1156749 -
Osteoarthritis and Cartilage Feb 2024Great progress continues to be made in our understanding of the multiple facets of osteoarthritis (OA) biology. Here, we review the major advances in this field and... (Review)
Review
Great progress continues to be made in our understanding of the multiple facets of osteoarthritis (OA) biology. Here, we review the major advances in this field and progress towards therapy development over the past year, highlighting a selection of relevant published literature from a PubMed search covering the year from the end of April 2022 to the end of April 2023. The selected articles have been arranged in themes. These include 1) molecular regulation of articular cartilage and implications for OA, 2) mechanisms of subchondral bone remodelling, 3) role of synovium and inflammation, 4) role of age-related changes including cartilage matrix stiffening, cellular senescence, mitochondrial dysfunction, metabolic dysfunction, and impaired autophagy, and 5) peripheral mechanisms of OA pain. Progress in the understanding of the cellular and molecular mechanisms responsible for the multiple aspects of OA biology is unravelling novel therapeutic targets for disease modification.
Topics: Humans; Osteoarthritis; Inflammation; Cartilage, Articular; Bone and Bones; Biology
PubMed: 37944663
DOI: 10.1016/j.joca.2023.11.002 -
JAMA Oncology Jun 2023Spine metastasis can be treated with high-dose radiation therapy with advanced delivery technology for long-term tumor and pain control. (Randomized Controlled Trial)
Randomized Controlled Trial
Stereotactic Radiosurgery vs Conventional Radiotherapy for Localized Vertebral Metastases of the Spine: Phase 3 Results of NRG Oncology/RTOG 0631 Randomized Clinical Trial.
IMPORTANCE
Spine metastasis can be treated with high-dose radiation therapy with advanced delivery technology for long-term tumor and pain control.
OBJECTIVE
To assess whether patient-reported pain relief was improved with stereotactic radiosurgery (SRS) as compared with conventional external beam radiotherapy (cEBRT) for patients with 1 to 3 sites of vertebral metastases.
DESIGN, SETTING, AND PARTICIPANTS
In this randomized clinical trial, patients with 1 to 3 vertebral metastases were randomized 2:1 to the SRS or cEBRT groups. This NRG 0631 phase 3 study was performed as multi-institutional enrollment within NRG Oncology. Eligibility criteria included the following: (1) solitary vertebral metastasis, (2) 2 contiguous vertebral levels involved, or (3) maximum of 3 separate sites. Each site may involve up to 2 contiguous vertebral bodies. A total of 353 patients enrolled in the trial, and 339 patients were analyzed. This analysis includes data extracted on March 9, 2020.
INTERVENTIONS
Patients randomized to the SRS group were treated with a single dose of 16 or 18 Gy (to convert to rad, multiply by 100) given to the involved vertebral level(s) only, not including any additional spine levels. Patients assigned to cEBRT were treated with 8 Gy given to the involved vertebra plus 1 additional vertebra above and below.
MAIN OUTCOMES AND MEASURES
The primary end point was patient-reported pain response defined as at least a 3-point improvement on the Numerical Rating Pain Scale (NRPS) without worsening in pain at the secondary site(s) or the use of pain medication. Secondary end points included treatment-related toxic effects, quality of life, and long-term effects on vertebral bone and spinal cord.
RESULTS
A total of 339 patients (mean [SD] age of SRS group vs cEBRT group, respectively, 61.9 [13.1] years vs 63.7 [11.9] years; 114 [54.5%] male in SRS group vs 70 [53.8%] male in cEBRT group) were analyzed. The baseline mean (SD) pain score at the index vertebra was 6.06 (2.61) in the SRS group and 5.88 (2.41) in the cEBRT group. The primary end point of pain response at 3 months favored cEBRT (41.3% for SRS vs 60.5% for cEBRT; difference, -19 percentage points; 95% CI, -32.9 to -5.5; 1-sided P = .99; 2-sided P = .01). Zubrod score (a measure of performance status ranging from 0 to 4, with 0 being fully functional and asymptomatic, and 4 being bedridden) was the significant factor influencing pain response. There were no differences in the proportion of acute or late adverse effects. Vertebral compression fracture at 24 months was 19.5% with SRS and 21.6% with cEBRT (P = .59). There were no spinal cord complications reported at 24 months.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, superiority of SRS for the primary end point of patient-reported pain response at 3 months was not found, and there were no spinal cord complications at 2 years after SRS. This finding may inform further investigation of using spine radiosurgery in the setting of oligometastases, where durability of cancer control is essential.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT00922974.
Topics: Humans; Male; Adolescent; Female; Radiosurgery; Spinal Fractures; Quality of Life; Fractures, Compression; Spine; Pain
PubMed: 37079324
DOI: 10.1001/jamaoncol.2023.0356 -
Redox Biology Jun 2023Increasing studies have reported that intervertebral disc degeneration (IVDD) is the main contributor and independent risk factor for low back pain (LBP), it would be,...
Increasing studies have reported that intervertebral disc degeneration (IVDD) is the main contributor and independent risk factor for low back pain (LBP), it would be, therefore, enlightening that investigating the exact pathogenesis of IVDD and developing target-specific molecular drugs in the future. Ferroptosis is a new form of programmed cell death characterized by glutathione (GSH) depletion, and inactivation of the regulatory core of the antioxidant system (glutathione system) GPX4. The close relationship of oxidative stress and ferroptosis has been studied in various of diseases, but the crosstalk between of oxidative stress and ferroptosis has not been explored in IVDD. At the beginning of the current study, we proved that Sirt3 decreases and ferroptosis occurs after IVDD. Next, we found that knockout of Sirt3 (Sirt3) promoted IVDD and poor pain-related behavioral scores via increasing oxidative stress-induced ferroptosis. The (immunoprecipitation coupled with mass spectrometry) IP/MS and co-IP demonstrated that USP11 was identified to stabilize Sirt3 via directly binding to Sirt3 and deubiquitinating Sirt3. Overexpression of USP11 significantly ameliorate oxidative stress-induced ferroptosis, thus relieving IVDD by increasing Sirt3. Moreover, knockout of USP11 in vivo (USP11) resulted in exacerbated IVDD and poor pain-related behavioral scores, which could be reversed by overexpression of Sirt3 in intervertebral disc. In conclusion, the current study emphasized the importance of the interaction of USP11 and Sirt3 in the pathological process of IVDD via regulating oxidative stress-induced ferroptosis, and USP11-mediated oxidative stress-induced ferroptosis is identified as a promising target for treating IVDD.
Topics: Humans; Deubiquitinating Enzymes; Ferroptosis; Glutathione; Intervertebral Disc Degeneration; Nucleus Pulposus; Oxidative Stress; Pain; Sirtuin 3; Thiolester Hydrolases
PubMed: 37099926
DOI: 10.1016/j.redox.2023.102707 -
Musculoskeletal Science & Practice Aug 2023The concept that headaches may originate in the cervical spine has been discussed over decades and is still a matter of debate. The cervical spine has been traditionally...
INTRODUCTION
The concept that headaches may originate in the cervical spine has been discussed over decades and is still a matter of debate. The cervical spine has been traditionally linked to cervicogenic headache; however, current evidence supports the presence of cervical musculoskeletal dysfunctions also in tension-type headache.
PURPOSE
This position paper discusses the most updated clinical and evidence-based data about the cervical spine in tension-type headache.
IMPLICATIONS
Subjects with tension-type headache exhibit concomitant neck pain, cervical spine sensitivity, forward head posture, limited cervical range of motion, positive flexion-rotation test and also cervical motor control disturbances. In addition, the referred pain elicited by manual examination of the upper cervical joints and muscle trigger points reproduces the pain pattern in tension-type headache. Current data supports that the cervical spine can be also involved in tension-type headache, and not just in cervicogenic headache. Several physical therapies including upper cervical spine mobilization or manipulation, soft tissue interventions (including dry needling) and exercises targeting the cervical spine are proposed for managing tension-type headache; however, the effectiveness of these interventions depends on a proper clinical reasoning since not all will be equally effective for all individuals with tension-type headache. Based on current evidence, we propose to use the terms cervical "component" and cervical "source" when discussing about headache. In such a scenario, in cervicogenic headache the neck can be the cause (source) of the headache whereas in tension-type headache the neck will have a component on the pain pattern, but it will be not the cause since it is a primary headache.
Topics: Humans; Tension-Type Headache; Post-Traumatic Headache; Headache; Physical Examination; Cervical Vertebrae
PubMed: 37268552
DOI: 10.1016/j.msksp.2023.102780 -
Head & Face Medicine Sep 2023The limited number of randomized controlled trials (RCTs) comparing the efficacy of soft tissue manual therapy and self-therapy interventions prompted the authors to... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
The limited number of randomized controlled trials (RCTs) comparing the efficacy of soft tissue manual therapy and self-therapy interventions prompted the authors to focus on the analgesic and myorelaxant use of massage, post-isometric muscle relaxation (PIR) and therapeutic exercise in TMD patients.
OBJECTIVES
To evaluate the effectiveness of soft tissue therapy and therapeutic exercises in female patients with pain, increased masseter muscle tension and limited mandibular mobility.
MATERIAL AND METHODS
The study was conducted on a group of 82 women (G1) with the Ib disorder diagnosed in DC/TMD (Ib-myofascial pain with restricted mobility). The control group (G2) consisted of 104 women without diagnosed TMDs (normal reference values for TMJ ROM and masseter muscle sEMG bioelectric activity). Diagnostic procedures were performed in both groups (sEMG of the masseter muscles at baseline and during exercise, measurement of TMJ mobility, assessment of pain intensity-NRS scale). The G1 group was randomly divided into 3 therapeutic groups in which the therapy was carried out for 10 days: therapeutic exercises (TE), manual therapy - massage and therapeutic exercises (MTM_TE), manual therapy - PIR and therapeutic exercises (MTPIR_TE). Each time after therapy, the intensity of pain and TMJ mobility were assessed. Sealed, opaque envelopes were used for randomization. After 5 and 10 days of therapy, bilateral sEMG signals of the masseter muscles were acquired.
RESULTS
Massage, PIR and self-therapy led to a decrease in sEMG at rest as well as in exercise. After day 6 of therapy, the groups obtained a significant difference (p = 0.0001). Each of the proposed forms of therapy showed a minimal clinically significant difference (MID) in the sEMG parameter at the endpoint, with the most considerable difference in the MTM_TE group. The forms of MT used were effective in reducing the patients' pain intensity; however, a significant difference between therapies occurred after 4 treatments (p = 0.0001). Analyzing the MID between methods, it was observed that self-therapy had an analgesic effect only after 8 treatments, while PIR after 3 and massage after 1 treatment. After day 7, the mean pain score in the MTM_TE group was 0.889 and in the TMPIR_TE group was 3.44 on the NRS scale. In terms of MMO, a significant difference was obtained between monotherapy and each form of TM, i.e. massage (p = 0.0001) and PIR (p = 0.0001). Analyzing mandibular lateral movements, the authors got a significant difference in the proposed MT forms, of which massage treatments exceeded the effectiveness of PIR.
CONCLUSIONS
Soft tissue manual therapy and therapeutic exercise are simple and safe interventions that can potentially benefit patients with myogenic TMDs, with massage showing better analgesic effects than PIR.
Topics: Female; Humans; Mandible; Pain; Temporomandibular Joint; Therapy, Soft Tissue
PubMed: 37684652
DOI: 10.1186/s13005-023-00385-y -
Nature Medicine Dec 2023Various types of cellular injection have become a popular and costly treatment option for patients with knee osteoarthritis despite a paucity of literature establishing... (Randomized Controlled Trial)
Randomized Controlled Trial
Various types of cellular injection have become a popular and costly treatment option for patients with knee osteoarthritis despite a paucity of literature establishing relative efficacy to each other or corticosteroid injections. Here we aimed to identify the safety and efficacy of cell injections from autologous bone marrow aspirate concentrate, autologous adipose stromal vascular fraction and allogeneic human umbilical cord tissue-derived mesenchymal stromal cells, in comparison to corticosteroid injection (CSI). The study was a phase 2/3, four-arm parallel, multicenter, single-blind, randomized, controlled clinical trial with 480 patients with a diagnosis of knee osteoarthritis (Kellgren-Lawrence II-IV). Participants were randomized to the three different arms with a 3:1 distribution. Arm 1: autologous bone marrow aspirate concentrate (n = 120), CSI (n = 40); arm 2: umbilical cord tissue-derived mesenchymal stromal cells (n = 120), CSI (n = 40); arm 3: stromal vascular fraction (n = 120), CSI (n = 40). The co-primary endpoints were the visual analog scale pain score and Knee injury and Osteoarthritis Outcome Score pain score at 12 months versus baseline. Analyses of our primary endpoints, with 440 patients, revealed that at 1 year post injection, none of the three orthobiologic injections was superior to another, or to the CSI control. In addition, none of the four groups showed a significant change in magnetic resonance imaging osteoarthritis score compared to baseline. No procedure-related serious adverse events were reported during the study period. In summary, this study shows that at 1 year post injection, there was no superior orthobiologic as compared to CSI for knee osteoarthritis. ClinicalTrials.gov Identifier: NCT03818737.
Topics: Humans; Osteoarthritis, Knee; Pain; Single-Blind Method; Treatment Outcome
PubMed: 37919438
DOI: 10.1038/s41591-023-02632-w -
British Journal of Hospital Medicine... Jul 2023Hip pain in a child can pose a diagnostic conundrum. In most cases, the cause of a painful hip is often attributed to trauma, but a number of these cases will be... (Review)
Review
Hip pain in a child can pose a diagnostic conundrum. In most cases, the cause of a painful hip is often attributed to trauma, but a number of these cases will be atraumatic. The main entities to consider are inflammatory, infective and neoplastic causes. Pathologies such as avascular necrosis and slipped upper femoral epiphysis can also present in a similar manner. A detailed history and clinical examination are crucial in narrowing down the differential diagnosis. In addition, understanding the most appropriate imaging modalities and the characteristic radiological findings is key in ensuring timely treatment and management. This article reviews the various disease processes in children who present with hip pain and outlines the most appropriate assessment and imaging modalities that will aid diagnosis.
Topics: Child; Humans; Hip; Arthralgia; Pain; Femur
PubMed: 37490445
DOI: 10.12968/hmed.2023.0054 -
Current Osteoporosis Reports Dec 2023The purpose of this article is to review the current understanding of inflammatory processes on bone, including direct impacts of inflammatory factors on bone cells, the... (Review)
Review
PURPOSE OF REVIEW
The purpose of this article is to review the current understanding of inflammatory processes on bone, including direct impacts of inflammatory factors on bone cells, the effect of senescence on inflamed bone, and the critical role of inflammation in bone pain and healing.
RECENT FINDINGS
Advances in osteoimmunology have provided new perspectives on inflammatory bone loss in recent years. Characterization of so-called inflammatory osteoclasts has revealed insights into physiological and pathological bone loss. The identification of inflammation-associated senescent markers in bone cells indicates that therapies that reduce senescent cell burden may reverse bone loss caused by inflammatory processes. Finally, novel studies have refined the role of inflammation in bone healing, including cross talk between nerves and bone cells. Except for the initial stages of fracture healing, inflammation has predominately negative effects on bone and increases fracture risk. Eliminating senescent cells, priming the osteo-immune axis in bone cells, and alleviating pro-inflammatory cytokine burden may ameliorate the negative effects of inflammation on bone.
Topics: Humans; Bone Density; Bone and Bones; Osteoclasts; Bone Diseases; Inflammation
PubMed: 37759135
DOI: 10.1007/s11914-023-00824-4