Dataset Information

The temporal and spatial expression of sclerostin and Wnt signaling factors during the maturation of posterolateral lumbar spine fusions.

ABSTRACT: The bone healing environment in the posterolateral spine following arthrodesis surgery is one of the most challenging in all of orthopedics and our understanding of the molecular signaling pathways mediating osteogenesis during spinal fusion is limited. In this study, the spatial and temporal expression pattern of Wnt signaling factors and inhibitors during spinal fusion was assessed for the first time. Bilateral posterolateral spine arthrodesis with autologous iliac crest bone graft was performed on 21 New Zealand White rabbits. At 1-, 2-, 3-, 4-, and 6-weeks, the expression of sclerostin and a variety of canonical and noncanonical Wnts signaling factors was measured by qRT-PCR from tissue separately collected from the transverse processes, the Outer and Inner Zones of the fusion mass, and the adjancent paraspinal muscle. Immunohistochemistry for sclerostin protein was also performed. Sclerostin and many Wnt factors, especially Wnt3a and Wnt5a, were found to have distinct spatial and temporal expression patterns. For example, harvesting ICBG caused a significant increase in sclerostin expression. Furthermore, the paraspinal muscle immediately adjacent to the transplanted ICBG also had significant increases in sclerostin expression at 3 weeks, suggesting new potential mechanisms for pseudarthroses following spinal arthrodesis. The presented work is the first description of the spatial and temporal expression of sclerostin and Wnt signaling factors in the developing spine fusion, filling an important knowledge gap in the basic biology of spinal fusion and potentially aiding in the development of novel biologics to increase spinal fusion rates.

SUBMITTER: Rodriguez-Feo J

PROVIDER: S-EPMC7984013 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundLumbar interbody fusion is among the most common types of spinal surgery performed. Over time, the term has evolved to encompass a number of different approaches to the intervertebral space, as well as differing implant materials. Questions remain over which approaches and materials are best for achieving fusion and restoring disc height.Questions/purposesWe reviewed the literature on the advantages and disadvantages of various methods and devices used to achieve and augment fusion between the disc spaces in the lumbar spine.MethodsUsing search terms specific to lumbar interbody fusion, we searched PubMed and Google Scholar and identified 4993 articles. We excluded those that did not report clinical outcomes, involved cervical interbody devices, were animal studies, or were not in English. After exclusions, 68 articles were included for review.ResultsPosterior approaches have advantages, such as providing 360° support through a single incision, but can result in retraction injury and do not always restore lordosis or correct deformity. Anterior approaches allow for the largest implants and good correction of deformities but can result in vascular, urinary, psoas muscle, or lumbar plexus injury and may require a second posterior procedure to supplement fixation. Titanium cages produce improved osteointegration and fusion rates but also increase subsidence caused by the stiffness of titanium relative to bone. Polyetheretherketone (PEEK) has an elasticity closer to that of bone and shows less subsidence than titanium cages, but as an inert compound PEEK results in lower fusion rates and greater osteolysis. Combination PEEK-titanium coating has not yet achieved better results. Expandable cages were developed to increase disc height and restore lumbar lordosis, but the data on their effectiveness have been inconclusive. Three-dimensionally (3D)-printed cages have shown promise in biomechanical and animal studies at increasing fusion rates and reducing subsidence, but additive manufacturing options are still in their infancy and require more investigation.ConclusionsAll of the approaches to spinal fusion have plusses and minuses that must be considered when determining which to use, and newer-technology implants, such as PEEK with titanium coating, expandable, and 3D-printed cages, have tried to improve upon the limitations of existing grafts but require further study.

Project description:Study Design Randomized controlled trial. Objective Despite a large number of publications of outcomes after spinal fusion surgery, there is still no consensus on the efficacy of the several different fusion methods. The aim of this study was to determine whether transforaminal lumbar interbody fusion (TLIF) results in an improved clinical outcome compared with uninstrumented posterolateral fusion (PLF) in the surgical treatment for chronic low back pain. Methods This study included 135 patients with degenerative disk disease (n = 96) or postdiskectomy syndrome (n = 39). Inclusion criteria were at least 1 year of back pain with or without leg pain in patients aged 20 to 65 with one- or two-level disease. Exclusion criteria were sequestration of disk hernia, psychosocial instability, isthmic spondylolisthesis, drug abuse, and previous spine surgery other than diskectomy. Pain was assessed by visual analog scale (pain index). Functional disability was quantified by the disability rating index and Oswestry Disability Index. The global outcome was assessed by the patient and classified as much better, better, unchanged, or worse. The patients were randomized to conventional uninstrumented PLF (n = 67) or TLIF (n = 68). PLF was performed in a standardized fashion using autograft. TLIF was performed with pedicle titanium screw fixation and a porous tantalum interbody spacer with interbody and posterolateral autograft. The clinical outcome measurements were obtained preoperatively and at 12 and 24 months postoperatively. The 2-year follow-up rate was 98%. Results The two treatment groups improved significantly from preoperatively to 2 years' follow-up. At final follow-up, the results in the TLIF group were significantly superior to those in the PLF group in pain index (2.0 versus 3.9, p = 0.007) and in disability rating index (22 versus 36, p = 0.003). The Oswestry Disability Index was better in the TLIF group (20 versus 28, p = 0.110, not significant). The global assessment was clearly superior in the TLIF group: 63% of patients scored "much better" in the TLIF group as compared with 48% in the PLF group (p = 0.017). Conclusions The results of the current study support the use of TLIF rather than uninstrumented PLF in the surgical treatment of the degenerative lumbar spine. The less optimal outcome after uninstrumented PLF may be explained by the much higher reoperation rate.

Project description:Background: T-score discordance is common in osteoporosis diagnosis and leads to problems for clinicians formulating treatment plans. Objectives: This study investigated the potential predictors of T-score discordance and compared fracture risk among individuals with varying T-score discordance status. Design: This was a single-center cross-sectional study conducted at Wan Fang Hospital, Taipei City, between 1 February 2020 and 31 January 2022. Methods: The present study enrolled patients aged ⩾50 years who received advanced bone health examination. Participants with a history of fracture surgery or underlying musculoskeletal diseases were excluded. Bioelectrical impedance analysis and dual-energy X-ray absorptiometry were used to determine the body composition and T-score, respectively. Discordance was defined as different T-score categories between the lumbar spine and hip. The impact of discordance on an individual’s fracture risk was assessed using the Fracture Risk Assessment Tool (FRAX). Results: This study enrolled 1402 participants (181 men and 1221 women). Of the 912 participants diagnosed with osteoporosis, 47 (5%) and 364 (40%) were categorized as having major and minor discordance, respectively. Multinomial logistic regression revealed that decreased walking speed was significantly correlated with major discordance but not osteoporosis in both the hip and lumbar spine (odds ratio of 0.25, p = 0.04). The adjusted FRAX scores for the major osteoporotic fracture risks of the major and minor discordance groups were approximately 14%, which was significantly lower than that of people having osteoporosis in both the hip and lumbar spine. Conclusions: Walking speed exhibited the most significant correlation with major discordance in patients with osteoporosis. Although adjusted major fracture risks were similar between the major and minor discordance groups, further longitudinal studies are warranted to confirm this finding. Registrations: This study was approved by the Ethics Committee of Taipei Medical University on 01/04/2022 (TMU-JIRB N202203088).

Project description:Background contextPseudarthrosis following spinal fusion remains problematic despite modern surgical and grafting techniques. In surgical spinal fusion, new bone forms via intramembranous and endochondral ossification, with endochondral ossification occurring in the hypoxic zones of the fusion bed. During bone development and fracture healing, the key cellular mediator of endochondral ossification is the hypertrophic chondrocyte given its ability to function in hypoxia and induce neovascularization and ossification. We therefore hypothesize that hypertrophic chondrocytes may be an effective bone graft alternative.PurposeSpinal fusion procedures have increased substantially; yet 5% to 35% of all spinal fusions may result in pseudoarthrosis. Pseudoarthrosis may occur because of implant failure, infection, or biological failure, among other reasons. Advances in surgical techniques and bone grafting have improved fusion; however pseudarthrosis rates remain unacceptably high. Thus, the goal of this study is to investigate hypertrophic chondrocytes as a potential biological graft alternative.MethodsUsing a validated murine fracture model, hypertrophic chondrocytes were harvested from fracture calluses and transplanted into the posterolateral spines of identical mice. New bone formation was assessed by X-ray, microcomputed tomography (μCT), and in vivo fluorescent imaging. Results were compared against a standard iliac crest bone graft and a sham surgery control group. Funding for this work was provided by the Department of Orthopaedics and Rehabilitation, the OREF (Grant #16-150), and The Caitlin Lovejoy Fund.ResultsRadiography, μCT, and in vivo fluorescent imaging demonstrated that hypertrophic chondrocytes promoted bone formation at rates equivalent to iliac crest autograft. Additionally, μCT analysis demonstrated similar fusion rates in a subset of mice from the iliac crest and hypertrophic chondrocyte groups.ConclusionsThis proof-of-concept study indicates that hypertrophic chondrocytes can promote bone formation comparable to iliac crest bone graft. These findings provide the foundation for future studies to investigate the potential therapeutic use of hypertrophic chondrocytes in spinal fusion.

Dataset Information

The temporal and spatial expression of sclerostin and Wnt signaling factors during the maturation of posterolateral lumbar spine fusions.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets