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Molecular and Genetic Mechanisms of Spinal Stenosis Formation: Systematic Review.

ABSTRACT: Spinal stenosis (SS) is a multifactorial polyetiological condition characterized by the narrowing of the spinal canal. This condition is a common source of pain among people over 50 years old. We perform a systematic review of molecular and genetic mechanisms that cause SS. The five main mechanisms of SS were found to be ossification of the posterior longitudinal ligament (OPLL), hypertrophy and ossification of the ligamentum flavum (HLF/OLF), facet joint (FJ) osteoarthritis, herniation of the intervertebral disc (IVD), and achondroplasia. FJ osteoarthritis, OPLL, and HLF/OLFLF/OLF have all been associated with an over-abundance of transforming growth factor beta and genes related to this phenomenon. OPLL has also been associated with increased bone morphogenetic protein 2. FJ osteoarthritis is additionally associated with Wnt/β-catenin signaling and genes. IVD herniation is associated with collagen type I alpha 1 and 2 gene mutations and subsequent protein dysregulation. Finally, achondroplasia is associated with fibroblast growth factor receptor 3 gene mutations and fibroblast growth factor signaling. Although most publications lack data on a direct relationship between the mutation and SS formation, it is clear that genetics has a direct impact on the formation of any pathology, including SS. Further studies are necessary to understand the genetic and molecular changes associated with SS.

SUBMITTER: Byvaltsev VA

PROVIDER: S-EPMC9658491 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Molecular and Genetic Mechanisms of Spinal Stenosis Formation: Systematic Review.

Byvaltsev Vadim A VA Kalinin Andrei A AA Hernandez Phillip A PA Shepelev Valerii V VV Pestryakov Yurii Y YY Aliyev Marat A MA Giers Morgan B MB

International journal of molecular sciences 20221103 21

Spinal stenosis (SS) is a multifactorial polyetiological condition characterized by the narrowing of the spinal canal. This condition is a common source of pain among people over 50 years old. We perform a systematic review of molecular and genetic mechanisms that cause SS. The five main mechanisms of SS were found to be ossification of the posterior longitudinal ligament (OPLL), hypertrophy and ossification of the ligamentum flavum (HLF/OLF), facet joint (FJ) osteoarthritis, herniation of the i ...[more]

PMID: 36362274

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Project description:BackgroundThe management of spinal stenosis by surgery has increased rapidly in the past two decades, however, there is still controversy regarding the efficacy of surgery for this condition. Our aim was to investigate the efficacy and comparative effectiveness of surgery in the management of patients with lumbar spinal stenosis.MethodsElectronic searches were performed on MEDLINE, EMBASE, AMED, CINAHL, Web of Science, LILACS and Cochrane Library from inception to November 2014. Hand searches were conducted on included articles and relevant reviews. We included randomised controlled trials evaluating surgery compared to no treatment, placebo/sham, or to another surgical technique in patients with lumbar spinal stenosis. Primary outcome measures were pain, disability, recovery and quality of life. The PEDro scale was used for risk of bias assessment. Data were pooled with a random-effects model, and the GRADE approach was used to summarise conclusions.ResultsNineteen published reports (17 trials) were included. No trials were identified comparing surgery to no treatment or placebo/sham. Pooling revealed that decompression plus fusion is not superior to decompression alone for pain (mean difference -3.7, 95% confidence interval -15.6 to 8.1), disability (mean difference 9.8, 95% confidence interval -9.4 to 28.9), or walking ability (risk ratio 0.9, 95% confidence interval 0.4 to 1.9). Interspinous process spacer devices are slightly more effective than decompression plus fusion for disability (mean difference 5.7, 95% confidence interval 1.3 to 10.0), but they resulted in significantly higher reoperation rates when compared to decompression alone (28% v 7%, P < 0.001). There are no differences in the effectiveness between other surgical techniques for our main outcomes.ConclusionsThe relative efficacy of various surgical options for treatment of spinal stenosis remains uncertain. Decompression plus fusion is not more effective than decompression alone. Interspinous process spacer devices result in higher reoperation rates than bony decompression.

Project description:BackgroundLumbar spinal stenosis (LSS) is caused by neural compression due to narrowing of the lumbar spinal canal or neural foramen. Surgical intervention is a standard treatment for LSS; however, the steep increase in the surgical rate, post-operative complications, and comparatively low long-term satisfaction are considered to be limitations of this surgical approach. Conversely, acupotomy is a minimally invasive technique that combines the effects of conventional acupuncture with micro-incision, which may offer an alternative to surgery for the treatment of LSS. This review was conducted to investigate and critically review the current evidence on the efficacy and safety of acupotomy for LSS.MethodsEleven databases were searched from their respective inception dates to December 28, 2018. Randomized controlled trials (RCTs) comparing acupotomy and wait-list, sham treatment, or active controls were included. The quality of the included studies was assessed using risk-of-bias tool.ResultsSeven RCTs were included in this review and meta-analysis. The methodological quality of the included studies was generally poor. The acupotomy treatment group was associated with significantly lower visual analogue scale scores (range 0∼10) (5 RCTs; mean difference [MD] -1.55, 95% confidence interval [CIs] -2.60 to -0.50; I = 94%) and higher Japanese Orthopedic Association Score (3 RCTs; MD 4.70, 95% CI 3.73 to 5.68; I = 0%) compared to the active control group. In subgroup analysis based on the type of active controls, acupotomy retained significant benefits over lumbar traction and acupuncture, as well as over lumbar traction, spinal decompression, and acupuncture. Safety data were reported in only 1 study, and no adverse events occurred in either the acupotomy or the acupuncture control group.ConclusionAccording to current evidence, acupotomy might be beneficial for treating LSS. Acupotomy showed consistent superiority over lumbar traction, but the results were mixed in comparisons with other interventions, such as spinal decompression and acupuncture. However, the findings should be interpreted cautiously, given the poor methodological quality of the included studies, and potential small-study effects. Further larger, high-quality, rigorous RCTs should be conducted on this topic and rigorous reporting of acupotomy procedures and safety data should be encouraged.

Project description:ObjectivesNeurogenic claudication due to lumbar spinal stenosis (LSS) is a growing health problem in older adults. We updated our previous Cochrane review (2013) to determine the effectiveness of non-operative treatment of LSS with neurogenic claudication.DesignA systematic review.Data sourcesCENTRAL, MEDLINE, EMBASE, CINAHL and Index to Chiropractic Literature databases were searched and updated up to 22 July 2020.Eligibility criteriaWe only included randomised controlled trials published in English where at least one arm provided data on non-operative treatment and included participants diagnosed with neurogenic claudication with imaging confirmed LSS.Data extraction and synthesisTwo independent reviewers extracted data and assessed risk of bias using the Cochrane Risk of Bias Tool 1. Grading of Recommendations Assessment, Development and Evaluation was used for evidence synthesis.ResultsOf 15 200 citations screened, 156 were assessed and 23 new trials were identified. There is moderate-quality evidence from three trials that: Manual therapy and exercise provides superior and clinically important short-term improvement in symptoms and function compared with medical care or community-based group exercise; manual therapy, education and exercise delivered using a cognitive-behavioural approach demonstrates superior and clinically important improvements in walking distance in the immediate to long term compared with self-directed home exercises and glucocorticoid plus lidocaine injection is more effective than lidocaine alone in improving statistical, but not clinically important improvements in pain and function in the short term. The remaining 20 new trials demonstrated low-quality or very low-quality evidence for all comparisons and outcomes, like the findings of our original review.ConclusionsThere is moderate-quality evidence that a multimodal approach which includes manual therapy and exercise, with or without education, is an effective treatment and that epidural steroids are not effective for the management of LSS with neurogenic claudication. All other non-operative interventions provided insufficient quality evidence to make conclusions on their effectiveness.Prospero registration numberCRD42020191860.

Project description:BackgroundSeveral surgical options for degenerative lumbar spinal stenosis (LSS) are available, but current guidelines do not recommend which one should be prioritized. Although previous network meta-analyses (NMAs) have been performed on this topic, they have major methodological problems and could not provide the convincing evidence and clinical practical information required.MethodsRandomized controlled trials (RCTs) comparing at least two surgical interventions were included by searching AMED, CINAHL, EMBASE, the Cochrane Library, and MEDLINE (inception to August 2023). A frequentist random-effects NMA was performed for physical function and adverse events due to any reason. For physical function, three follow-up time points were included: short-term (< 6 months post-intervention), mid-term (≥ 6 months but < 12 months), and long-term (≥ 12 months). Laminectomy was the reference comparison intervention.ResultsA total of 43 RCTs involving 5017 participants were included in the systematic review and 28 RCTs encompassing 14 types of surgical interventions were included in the NMA. For improving physical function (scale 0-100), endoscopic-assisted laminotomy (mean difference: - 8.61, 95% confidence interval: - 10.52 to - 6.69; moderate-quality evidence), laminectomy combined with Coflex (- 8.41, - 13.21 to - 3.61; moderate quality evidence), and X-stop (- 6.65, - 8.60 to - 4.71; low-quality evidence) had small effects at short-term follow-up; no statistical difference was observed at mid-term follow-up (very low- to low-quality evidence); at long-term follow-up, endoscopic-assisted laminotomy (- 7.02, - 12.95 to - 1.08; very low-quality evidence) and X-stop (- 10.04, - 18.16 to - 1.93; very low-quality evidence) had a small and moderate effect, respectively. Compared with laminectomy, endoscopic-assisted laminotomy was associated with fewer adverse events due to any reason (odds ratio: 0.27, 0.09 to 0.86; low-quality evidence).ConclusionsFor adults with degenerative LSS, endoscopic-assisted laminotomy may be the safest and most effective intervention in improving physical function. However, the available data were insufficient to indicate whether the effect was sustainable after 6 months.Trial registrationPROSPERO (CRD42018094180).

Dataset Information

Molecular and Genetic Mechanisms of Spinal Stenosis Formation: Systematic Review.

Publications

Molecular and Genetic Mechanisms of Spinal Stenosis Formation: Systematic Review.

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