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Bone & Joint Research
Vol. 9, Issue 10 | Pages 653 - 666
7 Oct 2020
Li W Li G Chen W Cong L

Aims. The aim of this study was to systematically compare the safety and accuracy of robot-assisted (RA) technique with conventional freehand with/without fluoroscopy-assisted (CT) pedicle screw insertion for spine disease. Methods. A systematic search was performed on PubMed, EMBASE, the Cochrane Library, MEDLINE, China National Knowledge Infrastructure (CNKI), and WANFANG for randomized controlled trials (RCTs) that investigated the safety and accuracy of RA compared with conventional freehand with/without fluoroscopy-assisted pedicle screw insertion for spine disease from 2012 to 2019. This meta-analysis used Mantel-Haenszel or inverse variance method with mixed-effects model for heterogeneity, calculating the odds ratio (OR), mean difference (MD), standardized mean difference (SMD), and 95% confidence intervals (CIs). The results of heterogeneity, subgroup analysis, and risk of bias were analyzed. Results. Ten RCTs with 713 patients and 3,331 pedicle screws were included. Compared with CT, the accuracy rate of RA was superior in Grade A with statistical significance and Grade A + B without statistical significance. Compared with CT, the operating time of RA was longer. The difference between RA and CT was statistically significant in radiation dose. Proximal facet joint violation occurred less in RA than in CT. The postoperative Oswestry Disability Index (ODI) of RA was smaller than that of CT, and there were some interesting outcomes in our subgroup analysis. Conclusion. RA technique could be viewed as an accurate and safe pedicle screw implantation method compared to CT. A robotic system equipped with optical intraoperative navigation is superior to CT in accuracy. RA pedicle screw insertion can improve accuracy and maintain stability for some challenging areas. Cite this article: Bone Joint Res 2020;9(10):653–666


Bone & Joint Research
Vol. 9, Issue 5 | Pages 225 - 235
1 May 2020
Peng X Zhang C Bao J Zhu L Shi R Xie Z Wang F Wang K Wu X

Aims. Inflammatory response plays a pivotal role in the pathophysiological process of intervertebral disc degeneration (IDD). A20 (also known as tumour necrosis factor alpha-induced protein 3 (TNFAIP3)) is a ubiquitin-editing enzyme that restricts nuclear factor-kappa B (NF-κB) signalling. A20 prevents the occurrence of multiple inflammatory diseases. However, the role of A20 in the initiation of IDD has not been elucidated. The aim of the study was to investigate the effect of A20 in senescence of TNF alpha (TNF-α)-induced nucleus pulposus cells (NPCs). Methods. Immunohistochemical staining was performed to observe the expression of A20 in normal and degenerated human intervertebral discs. The NPCs were dissected from the tail vertebrae of healthy male Sprague-Dawley rats and were cultured in the incubator. In the experiment, TNF-α was used to mimic the inflammatory environment of IDD. The cell viability and senescence were examined to investigate the effect of A20 on TNF-α-treated NPCs. The expression of messenger RNA (mRNA)-encoding proteins related to matrix macromolecules (collagen II, aggrecan) and senescence markers (p53, p16). Additionally, NF-κB/p65 activity of NPCs was detected within different test compounds. Results. The expression of A20 was upregulated in degenerate human intervertebral discs. The A20 levels of NPCs in TNF-α inflammatory microenvironments were dramatically higher than those of the control group. TNF-α significantly decreased cell proliferation potency but increased senescence-associated beta-galactosidase (SA-β-Gal) activity, the expression of senescence-associated proteins, the synthesis of extracellular matrix, and G1 cycle arrest. The senescence indicators and NF-κB/p65 expression of A20 downregulated group treated with TNF-α were significantly upregulated compared to TNF-α-treated normal NPCs. Conclusion. A20 has a self-protective effect on the senescence of NPCs induced by TNF-α. The downregulation of A20 in NPCs exacerbated the senescence of NPCs induced by TNF-α. Cite this article:Bone Joint Res. 2020;9(5):225–235


Bone & Joint Research
Vol. 7, Issue 2 | Pages 124 - 130
1 Feb 2018
Coric D Bullard DE Patel VV Ryaby JT Atkinson BL He D Guyer RD

Objectives. Pulsed electromagnetic field (PEMF) stimulation was evaluated after anterior cervical discectomy and fusion (ACDF) procedures in a randomized, controlled clinical study performed for United States Food and Drug Administration (FDA) approval. PEMF significantly increased fusion rates at six months, but 12-month fusion outcomes for subjects at elevated risk for pseudoarthrosis were not thoroughly reported. The objective of the current study was to evaluate the effect of PEMF treatment on subjects at increased risk for pseudoarthrosis after ACDF procedures. Methods. Two evaluations were performed that compared fusion rates between PEMF stimulation and a historical control (160 subjects) from the FDA investigational device exemption (IDE) study: a post hoc (PH) analysis of high-risk subjects from the FDA study (PH PEMF); and a multicentre, open-label (OL) study consisting of 274 subjects treated with PEMF (OL PEMF). Fisher’s exact test and multivariate logistic regression was used to compare fusion rates between PEMF-treated subjects and historical controls. Results. In separate comparisons of PH PEMF and OL PEMF groups to the historical control group, PEMF treatment significantly (p < 0.05, Fisher’s exact test) increased the fusion rate at six and 12 months for certain high-risk subjects who had at least one clinical risk factor of being elderly, a nicotine user, osteoporotic, or diabetic; and for those with at least one clinical risk factor and who received at least a two- or three-level arthrodesis. Conclusion. Adjunctive PEMF treatment can be recommended for patients who are at high risk for pseudoarthrosis. Cite this article: D. Coric, D. E. Bullard, V. V. Patel, J. T. Ryaby, B. L. Atkinson, D. He, R. D. Guyer. Pulsed electromagnetic field stimulation may improve fusion rates in cervical arthrodesis in high-risk populations. Bone Joint Res 2018;7:124–130. DOI: 10.1302/2046-3758.72.BJR-2017-0221.R1


Bone & Joint Research
Vol. 7, Issue 1 | Pages 28 - 35
1 Jan 2018
Huang H Nightingale RW Dang ABC

Objectives. Loss of motion following spine segment fusion results in increased strain in the adjacent motion segments. However, to date, studies on the biomechanics of the cervical spine have not assessed the role of coupled motions in the lumbar spine. Accordingly, we investigated the biomechanics of the cervical spine following cervical fusion and lumbar fusion during simulated whiplash using a whole-human finite element (FE) model to simulate coupled motions of the spine. Methods. A previously validated FE model of the human body in the driver-occupant position was used to investigate cervical hyperextension injury. The cervical spine was subjected to simulated whiplash exposure in accordance with Euro NCAP (the European New Car Assessment Programme) testing using the whole human FE model. The coupled motions between the cervical spine and lumbar spine were assessed by evaluating the biomechanical effects of simulated cervical fusion and lumbar fusion. Results. Peak anterior longitudinal ligament (ALL) strain ranged from 0.106 to 0.382 in a normal spine, and from 0.116 to 0.399 in a fused cervical spine. Strain increased from cranial to caudal levels. The mean strain increase in the motion segment immediately adjacent to the site of fusion from C2-C3 through C5-C6 was 26.1% and 50.8% following single- and two-level cervical fusion, respectively (p = 0.03, unpaired two-way t-test). Peak cervical strains following various lumbar-fusion procedures were 1.0% less than those seen in a healthy spine (p = 0.61, two-way ANOVA). Conclusion. Cervical arthrodesis increases peak ALL strain in the adjacent motion segments. C3-4 experiences greater changes in strain than C6-7. Lumbar fusion did not have a significant effect on cervical spine strain. Cite this article: H. Huang, R. W. Nightingale, A. B. C. Dang. Biomechanics of coupled motion in the cervical spine during simulated whiplash in patients with pre-existing cervical or lumbar spinal fusion: A Finite Element Study. Bone Joint Res 2018;7:28–35. DOI: 10.1302/2046-3758.71.BJR-2017-0100.R1


Bone & Joint Research
Vol. 6, Issue 5 | Pages 337 - 344
1 May 2017
Kim J Hwang JY Oh JK Park MS Kim SW Chang H Kim T

Objectives. The objective of this study was to assess the association between whole body sagittal balance and risk of falls in elderly patients who have sought treatment for back pain. Balanced spinal sagittal alignment is known to be important for the prevention of falls. However, spinal sagittal imbalance can be markedly compensated by the lower extremities, and whole body sagittal balance including the lower extremities should be assessed to evaluate actual imbalances related to falls. Methods. Patients over 70 years old who visited an outpatient clinic for back pain treatment and underwent a standing whole-body radiograph were enrolled. Falls were prospectively assessed for 12 months using a monthly fall diary, and patients were divided into fallers and non-fallers according to the history of falls. Radiological parameters from whole-body radiographs and clinical data were compared between the two groups. Results. A total of 144 patients (120 female patients and 24 male patients) completed a 12-month follow-up for assessing falls. A total of 31 patients (21.5%) reported at least one fall within the 12-month follow-up. In univariate logistic regression analysis, the risk of falls was significantly increased in older patients and those with more medical comorbidities, decreased lumbar lordosis, increased sagittal vertical axis, and increased horizontal distance between the C7 plumb line and the centre of the ankle (C7A). Increased C7A was significantly associated with increased risk of falls even after multivariate adjustment. Conclusion. Whole body sagittal balance, measured by the horizontal distance between the C7 plumb line and the centre of the ankle, was significantly associated with risk of falls among elderly patients with back pain. Cite this article: J. Kim, J. Y. Hwang, J. K. Oh, M. S. Park, S. W. Kim, H. Chang, T-H. Kim. The association between whole body sagittal balance and risk of falls among elderly patients seeking treatment for back pain. Bone Joint Res 2017;6:–344. DOI: 10.1302/2046-3758.65.BJR-2016-0271.R2


Bone & Joint Research
Vol. 6, Issue 4 | Pages 245 - 252
1 Apr 2017
Fu M Ye Q Jiang C Qian L Xu D Wang Y Sun P Ouyang J

Objectives. Many studies have investigated the kinematics of the lumbar spine and the morphological features of the lumbar discs. However, the segment-dependent immediate changes of the lumbar intervertebral space height during flexion-extension motion are still unclear. This study examined the changes of intervertebral space height during flexion-extension motion of lumbar specimens. Methods. First, we validated the accuracy and repeatability of a custom-made mechanical loading equipment set-up. Eight lumbar specimens underwent CT scanning in flexion, neural, and extension positions by using the equipment set-up. The changes in the disc height and distance between adjacent two pedicle screw entry points (DASEP) of the posterior approach at different lumbar levels (L3/4, L4/5 and L5/S1) were examined on three-dimensional lumbar models, which were reconstructed from the CT images. Results. All the vertebral motion segments (L3/4, L4/5 and L5/S1) had greater changes in disc height and DASEP from neutral to flexion than from neutral to extension. The change in anterior disc height gradually increased from upper to lower levels, from neutral to flexion. The changes in anterior and posterior disc heights were similar at the L4/5 level from neutral to extension, but the changes in anterior disc height were significantly greater than those in posterior disc height at the L3/4 and L5/S1 levels, from neutral to extension. Conclusions. The lumbar motion segment showed level-specific changes in disc height and DASEP. The data may be helpful in understanding the physiologic dynamic characteristics of the lumbar spine and in optimising the parameters of lumbar surgical instruments. Cite this article: M. Fu, Q. Ye, C. Jiang, L. Qian, D. Xu, Y. Wang, P. Sun, J. Ouyang. The segment-dependent changes in lumbar intervertebral space height during flexion-extension motion. Bone Joint Res 2017;6:245–252. DOI: 10.1302/2046-3758.64.BJR-2016-0245.R1


Bone & Joint Research
Vol. 5, Issue 11 | Pages 544 - 551
1 Nov 2016
Kim Y Bok DH Chang H Kim SW Park MS Oh JK Kim J Kim T

Objectives. Although vertebroplasty is very effective for relieving acute pain from an osteoporotic vertebral compression fracture, not all patients who undergo vertebroplasty receive the same degree of benefit from the procedure. In order to identify the ideal candidate for vertebroplasty, pre-operative prognostic demographic or clinico-radiological factors need to be identified. The objective of this study was to identify the pre-operative prognostic factors related to the effect of vertebroplasty on acute pain control using a cohort of surgically and non-surgically managed patients. Patients and Methods. Patients with single-level acute osteoporotic vertebral compression fracture at thoracolumbar junction (T10 to L2) were followed. If the patients were not satisfied with acute pain reduction after a three-week conservative treatment, vertebroplasty was recommended. Pain assessment was carried out at the time of diagnosis, as well as three, four, six, and 12 weeks after the diagnosis. The effect of vertebroplasty, compared with conservative treatment, on back pain (visual analogue score, VAS) was analysed with the use of analysis-of-covariance models that adjusted for pre-operative VAS scores. Results. A total of 342 patients finished the 12-week follow-up, and 120 patients underwent vertebroplasty (35.1%). The effect of vertebroplasty over conservative treatment was significant regardless of age, body mass index, medical comorbidity, previous fracture, pain duration, bone mineral density, degree of vertebral body compression, and canal encroachment. However, the effect of vertebroplasty was not significant at all time points in patients with increased sagittal vertical axis. Conclusions. For single-level acute osteoporotic vertebral compression fractures, the effect of vertebroplasty was less favourable in patients with increased sagittal vertical axis (> 5 cm) possible due to aggravation of kyphotic stress from walking imbalance. Cite this article: Y-C. Kim, D. H. Bok, H-G. Chang, S. W. Kim, M. S. Park, J. K. Oh, J. Kim, T-H. Kim. Increased sagittal vertical axis is associated with less effective control of acute pain following vertebroplasty. Bone Joint Res 2016;5:544–551. DOI: 10.1302/2046-3758.511.BJR-2016-0135.R1


Bone & Joint Research
Vol. 5, Issue 9 | Pages 419 - 426
1 Sep 2016
Leichtle CI Lorenz A Rothstock S Happel J Walter F Shiozawa T Leichtle UG

Objectives. Cement augmentation of pedicle screws could be used to improve screw stability, especially in osteoporotic vertebrae. However, little is known concerning the influence of different screw types and amount of cement applied. Therefore, the aim of this biomechanical in vitro study was to evaluate the effect of cement augmentation on the screw pull-out force in osteoporotic vertebrae, comparing different pedicle screws (solid and fenestrated) and cement volumes (0 mL, 1 mL or 3 mL). Materials and Methods. A total of 54 osteoporotic human cadaver thoracic and lumbar vertebrae were instrumented with pedicle screws (uncemented, solid cemented or fenestrated cemented) and augmented with high-viscosity PMMA cement (0 mL, 1 mL or 3 mL). The insertion torque and bone mineral density were determined. Radiographs and CT scans were undertaken to evaluate cement distribution and cement leakage. Pull-out testing was performed with a material testing machine to measure failure load and stiffness. The paired t-test was used to compare the two screws within each vertebra. Results. Mean failure load was significantly greater for fenestrated cemented screws (+622 N; p ⩽ 0.001) and solid cemented screws (+460 N; p ⩽ 0.001) than for uncemented screws. There was no significant difference between the solid and fenestrated cemented screws (p = 0.5). In the lower thoracic vertebrae, 1 mL cement was enough to significantly increase failure load, while 3 mL led to further significant improvement in the upper thoracic, lower thoracic and lumbar regions. Conclusion. Conventional, solid pedicle screws augmented with high-viscosity cement provided comparable screw stability in pull-out testing to that of sophisticated and more expensive fenestrated screws. In terms of cement volume, we recommend the use of at least 1 mL in the thoracic and 3 mL in the lumbar spine. Cite this article: C. I. Leichtle, A. Lorenz, S. Rothstock, J. Happel, F. Walter, T. Shiozawa, U. G. Leichtle. Pull-out strength of cemented solid versus fenestrated pedicle screws in osteoporotic vertebrae. Bone Joint Res 2016;5:419–426


Bone & Joint Research
Vol. 5, Issue 6 | Pages 239 - 246
1 Jun 2016
Li P Qian L Wu WD Wu CF Ouyang J

Objectives. Pedicle-lengthening osteotomy is a novel surgery for lumbar spinal stenosis (LSS), which achieves substantial enlargement of the spinal canal by expansion of the bilateral pedicle osteotomy sites. Few studies have evaluated the impact of this new surgery on spinal canal volume (SCV) and neural foramen dimension (NFD) in three different types of LSS patients. Methods. CT scans were performed on 36 LSS patients (12 central canal stenosis (CCS), 12 lateral recess stenosis (LRS), and 12 foraminal stenosis (FS)) at L4-L5, and on 12 normal (control) subjects. Mimics 14.01 workstation was used to reconstruct 3D models of the L4-L5 vertebrae and discs. SCV and NFD were measured after 1 mm, 2 mm, 3 mm, 4 mm, or 5 mm pedicle-lengthening osteotomies at L4 and/or L5. One-way analysis of variance was used to examine between-group differences. Results. In the intact state, SVC and NFD were significantly larger in the control group compared with the LSS groups (P<0.05). After lengthening at L4, the percentage increase in SCV (per millimetre) was LRS>CCS>FS>Control. After lengthening at L5 and L4-L5, the percentage increase in SCV (per millimetre) was LRS>FS>CCS>Control. After lengthening at L4 and L4-L5, the percentage increase in NFD (per millimetre) was FS>CCS>LRS>Control. After lengthening at L5, the percentage increase in NFD (per millimetre) was CCS>LRS>control>FS. Conclusions. LRS patients are the most suitable candidates for treatment with pedicle-lengthening osteotomy. Lengthening L4 pedicles produced larger percentage increases in NFD than lengthening L5 pedicles (p < 0.05). Lengthening L4 pedicles may be the most effective option for relieving foraminal compression in LSS patients. Cite this article: P. Li, L. Qian, W. D. Wu, C. F. Wu, J. Ouyang. Impact of pedicle-lengthening osteotomy on spinal canal volume and neural foramen size in three types of lumbar spinal stenosis. Bone Joint Res 2016;5:239–246. DOI: 10.1302/2046-3758.56.2000469


Bone & Joint Research
Vol. 5, Issue 4 | Pages 145 - 152
1 Apr 2016
Bodalia PN Balaji V Kaila R Wilson L

Objectives. We performed a systematic review of the literature to determine the safety and efficacy of bone morphogenetic protein (BMP) compared with bone graft when used specifically for revision spinal fusion surgery secondary to pseudarthrosis. Methods. The MEDLINE, EMBASE and Cochrane Library databases were searched using defined search terms. The primary outcome measure was spinal fusion, assessed as success or failure in accordance with radiograph, MRI or CT scan review at 24-month follow-up. The secondary outcome measure was time to fusion. Results. A total of six studies (three prospective and three retrospective) reporting on the use of BMP2 met the inclusion criteria (203 patients). Of these, four provided a comparison of BMP2 and bone graft whereas the other two solely investigated the use of BMP2. The primary outcome was seen in 92.3% (108/117) of patients following surgery with BMP2. Although none of the studies showed superiority of BMP2 to bone graft for fusion, its use was associated with a statistically quicker time to achieving fusion. BMP2 did not appear to increase the risk of complication. Conclusion. The use of BMP2 is both safe and effective within the revision setting, ideally in cases where bone graft is unavailable or undesirable. Further research is required to define its optimum role. Cite this article: Mr P. Bodalia. Effectiveness and safety of recombinant human bone morphogenetic protein-2 for adults with lumbar spine pseudarthrosis following spinal fusion surgery: A systematic review. Bone Joint Res 2016;5:145–152. DOI: 10.1302/2046-3758.54.2000418


Bone & Joint Research
Vol. 5, Issue 2 | Pages 46 - 51
1 Feb 2016
Du J Wu J Wen Z Lin X

Objectives. To employ a simple and fast method to evaluate those patients with neurological deficits and misplaced screws in relatively safe lumbosacral spine, and to determine if it is necessary to undertake revision surgery. Methods. A total of 316 patients were treated by fixation of lumbar and lumbosacral transpedicle screws at our institution from January 2011 to December 2012. We designed the criteria for post-operative revision scores of pedicle screw malpositioning (PRSPSM) in the lumbosacral canal. We recommend the revision of the misplaced pedicle screw in patients with PRSPSM = 5′ as early as possible. However, patients with PRSPSM < 5′ need to follow the next consecutive assessment procedures. A total of 15 patients were included according to at least three-stage follow-up. Results. Five patients with neurological complications (PRSPSM = 5′) underwent revision surgery at an early stage. The other ten patients with PRSPSM < 5′ were treated by conservative methods for seven days. At three-month follow-up, only one patient showed delayed onset of neurological complications (PRSPSM 7′) while refusing revision. Seven months later, PRSPSM decreased to 3′ with complete rehabilitation. Conclusions. This study highlights the significance of consecutively dynamic assessments of PRSPSMs, which are unlike previous implementations based on purely anatomical assessment or early onset of neurological deficits.and also confirms our hypothesis that patients with early neurological complications may not need revision procedures in the relatively broad margin of the lumbosacral canal. Cite this article: X-J. Lin. Treatment strategies for early neurological deficits related to malpositioned pedicle screws in the lumbosacral canal: A pilot study. Bone Joint Res 2016;5:46–51


Bone & Joint Research
Vol. 2, Issue 8 | Pages 169 - 178
1 Aug 2013
Rodrigues-Pinto R Richardson SM Hoyland JA

Mesenchymal stem-cell based therapies have been proposed as novel treatments for intervertebral disc degeneration, a prevalent and disabling condition associated with back pain. The development of these treatment strategies, however, has been hindered by the incomplete understanding of the human nucleus pulposus phenotype and by an inaccurate interpretation and translation of animal to human research. This review summarises recent work characterising the nucleus pulposus phenotype in different animal models and in humans and integrates their findings with the anatomical and physiological differences between these species. Understanding this phenotype is paramount to guarantee that implanted cells restore the native functions of the intervertebral disc. Cite this article: Bone Joint Res 2013;2:169–78