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author:("egun, Niels")
1.  Spondyloarthritis-related and degenerative MRI changes in the axial skeleton - an inter- and intra-observer agreement study 
The Back Pain Cohort of Southern Denmark (BaPa Cohort) was initiated with the aim of evaluating the clinical relevance of magnetic resonance imaging (MRI) in the diagnosis of early spondyloarthritis (SpA). In order to facilitate the collection of MRI data for this study, an electronic evaluation form was developed including both SpA-related and degenerative axial changes. The objective of the current study was to assess the intra- and inter-observer agreement of the MRI changes assessed.
Three radiologists evaluated 48 MRI scans of the whole spine and the sacroiliac joints from a subsample of the BaPa Cohort, consisting of patients with non-specific low back pain and patients with different stages of SpA features. The spine was evaluated for SpA-related and degenerative MRI changes and the SIJ for SpA-related changes. Inter- and intra-observer agreements were calculated with kappa statistics. In the interpretation of the kappa coefficient, the standards for strength of agreement reported by Landis and Koch were followed.
A total of 48 patients, 40% men and mean age of 31 years (range 18 – 40 years), were evaluated once by all three readers and re-evaluated by two of the readers after 4-12 weeks. For MRI changes in the spine, substantial to almost perfect observer agreement was found for the location and the size of vertebral signal changes and for disc degeneration and disc contour. For the sacroiliac joints, substantial or almost perfect observer agreement was found for the grading of bone marrow oedema and fatty marrow deposition, the depth of bone marrow oedema and for subchondral sclerosis. Global assessment of the SpA diagnosis had substantial to almost perfect observer agreements.
The acceptable agreement for key MRI changes in the spine and sacroiliac joints makes it possible to use these MRI changes in the BaPa Cohort study and other studies investigating MRI changes in patients with non-specific low back pain and suspected SpA.
PMCID: PMC3848902  PMID: 24060355
Agreement; Ankylosing spondylitis; Arthritis; Diagnosis; Kappa; Low back pain; Magnetic resonance imaging; Sacroiliac joint; Sacroiliitis; Spine; Spondyloarthropathy; Spondylarthritis
2.  Degenerative Spondylolisthesis Is Associated with Low Spinal Bone Density: A Comparative Study between Spinal Stenosis and Degenerative Spondylolisthesis 
BioMed Research International  2013;2013:123847.
Spinal stenosis and degenerative spondylolisthesis share many symptoms and the same treatment, but their causes remain unclear. Bone mineral density has been suggested to play a role. The aim of this study was to investigate differences in spinal bone density between spinal stenosis and degenerative spondylolisthesis patients. 81 patients older than 60 years, who underwent DXA-scanning of their lumbar spine one year after a lumbar spinal fusion procedure, were included. Radiographs were assessed for disc height, vertebral wedging, and osteophytosis. Pain was assessed using the Low Back Pain Rating Scale pain index. T-score of the lumbar spine was significantly lower among degenerative spondylolisthesis patients compared with spinal stenosis patients (−1.52 versus −0.52, P = 0.04). Thirty-nine percent of degenerative spondylolisthesis patients were classified as osteoporotic and further 30% osteopenic compared to only 9% of spinal stenosis patients being osteoporotic and 30% osteopenic (P = 0.01). Pain levels tended to increase with poorer bone status (P = 0.06). Patients treated surgically for symptomatic degenerative spondylolisthesis have much lower bone mass than patients of similar age treated surgically for spinal stenosis. Low BMD might play a role in the development of the degenerative spondylolisthesis, further studies are needed to clarify this.
PMCID: PMC3760191  PMID: 24024179
3.  MR Imaging of Intra- and Periarticular Cyst-Like Lesions of the Knee Joint in Workers with Occupational Kneeling 
Objective. To determine the risk of intra- and periarticular cyst-like lesions of the knee joint in occupational kneeling. Methods. Magnetic resonance imaging of both knees (n = 282) was conducted in 92 male floor layers and 49 male graphic designers (referents), with a mean age of 55.6 years (range 42–70 years). The prevalence of cyst-like lesions was computed among floor layers and graphic designers, respectively, and associations with occupation summarized by odds ratio (OR) with 95% confidence intervals (CIs). Using logistic regression, models were adjusted for age, body mass index, knee injuries, and knee-straining sports. Results. Floor layers had a significantly higher prevalence of cyst-like lesions in the posterior part of the knee joint compared to graphic designers (OR 2.70, 95% CI 1.50–4.84). Floor layers also had a higher prevalence of fluid collections in the popliteus tendon recess (OR 2.17, 95% CI 0.99–4.77) and large cystic lesions of the popliteus muscle (OR 3.83, 95% CI 0.78–18.89). The prevalence of cystic lesions in the anterior part of the knee joint was low among floor layers (8.7%) and there was no significant difference between the two trade groups (P = 0.34). Conclusions. Occupational kneeling increases the risk of cyst-like lesions in the posterior part of the knee joint.
PMCID: PMC3380240  PMID: 22737172
4.  Fusion mass bone quality after uninstrumented spinal fusion in older patients 
European Spine Journal  2010;19(12):2200-2208.
Older people are at increased risk of non-union after spinal fusion, but little is known about the factors determining the quality of the fusion mass in this patient group. The aim of this study was to investigate fusion mass bone quality after uninstrumented spinal fusion and to evaluate if it could be improved by additional direct current (DC) electrical stimulation. A multicenter RCT compared 40 and 100 μA DC stimulation with a control group of uninstrumented posterolateral fusion in patients older than 60 years. This report comprised 80 patients who underwent DEXA scanning at the 1 year follow-up. The study population consisted of 29 men with a mean age of 72 years (range 62–85) and 51 women with a mean age of 72 years (range 61–84). All patients underwent DEXA scanning of their fusion mass. Fusion rate was assessed at the 2 year follow-up using thin slice CT scanning. DC electrical stimulation did not improve fusion mass bone quality. Smokers had lower fusion mass BMD (0.447 g/cm2) compared to non-smokers (0.517 g/cm2) (P = 0.086). Women had lower fusion mass BMD (0.460 g/cm2) compared to men (0.552 g/cm2) (P = 0.057). Using linear regression, fusion mass bone quality, measured as BMD, was significantly influenced by gender, age of the patient, bone density of the remaining part of the lumbar spine, amount of bone graft applied and smoking. Fusion rates in this cohort was 34% in the control group and 33 and 43% in the 40 and 100 μA groups, respectively (not significant). Patients classified as fused after 2 years had significant higher fusion mass BMD at 1 year (0.592 vs. 0.466 g/cm2, P = 0.0001). Fusion mass bone quality in older patients depends on several factors. Special attention should be given to women with manifest or borderline osteoporosis. Furthermore, bone graft materials with inductive potential might be considered for this patient population.
PMCID: PMC2997208  PMID: 20429017
Spinal fusion; Randomised clinical trial; Bone mineral density; Electrical stimulation; Bone graft; Age; Smoking
5.  Occupational kneeling and radiographic tibiofemoral and patellofemoral osteoarthritis 
The objective of our study was to evaluate the association between occupational kneeling and compartment specific radiographic tibiofemoral (TF) and patellofemoral (PF) osteoarthritis (OA).
Questionnaire data and bilateral knee radiographs were obtained in 134 male floor layers and 120 male graphic designers (referents). Weight-bearing radiographs in three views (postero-anterior, lateral and axial) were classified according to joint space narrowing. After the exclusion of subjects with reports of earlier knee injuries the odds ratio (OR) with 95% confidence intervals (CI) of TF and PF OA was computed among floor layers compared to graphic designers in three age groups (≤ 49; 50–59; ≥ 60 years). Using logistic regression, estimates were adjusted for body mass index and knee-straining sports. In addition, the association between trade seniority and TF OA was assessed in age-adjusted test for trend analyses.
The prevalence of TF OA was significantly higher among floor layers aged 50–59 years compared to graphic designers (OR = 3.6, 95% CI = 1.1–12.0) while non-significant estimates were found in the young and elderly age groups. Furthermore, the adjusted OR of TF OA increased with trade seniority among floor layers (test for trend, OR = 2.2, 95% CI = 1.0–5.1), but not among graphic designers (OR = 1.2, 95% CI = 0.4–3.5). There were no significant differences regarding PF OA between the two occupational groups.
Results corroborate the existence of a causal relationship between occupational kneeling and radiographic TF OA and suggest a dose-response association with trade seniority. An association between kneeling and PF OA was however doubtful. Apparent discrepancies between findings in different age groups are most likely reflecting selection bias.
PMCID: PMC2726153  PMID: 19594940
6.  Healing properties of allograft from alendronate-treated animal in lumbar spine interbody cage fusion 
European Spine Journal  2004;14(3):222-226.
This study investigated the healing potential of allograft from bisphosphonate-treated animals in anterior lumbar spine interbody fusion. Three levels of anterior lumbar interbody fusion with Brantigan cages were performed in two groups of five landrace pigs. Empty Brantigan cages or cages filled with either autograft or allograft were located randomly at different levels. The allograft materials for the treatment group were taken from the pigs that had been fed with alendronate, 10 mg daily for 3 months. The histological fusion rate was 2/5 in alendronate-treated allograft and 3/5 in non-treated allograft. The mean bone volume was 39% and 37.2% in alendronate-treated or non-treated allograft (NS), respectively. No statistical difference was found between the same grafted cage comparing two groups. The histological fusion rate was 7/10 in all autograft cage levels and 5/10 in combined allograft cage levels. No fusion was found at all in empty cage levels. With the numbers available, no statistically significant difference was found in histological fusion between autograft and allograft applications. There was a significant difference of mean bone volume between autograft (49.2%) and empty cage (27.5%) (P<0.01). In conclusion, this study did not demonstrate different healing properties of alendronate-treated and non-treated allograft for anterior lumbar interbody fusion in pigs.
PMCID: PMC3476744  PMID: 15248057
Anterior lumbar interbody fusion (ALIF); Bisphosphonate; Bone graft; Cage; CT
7.  Anterior lumbar interbody fusion with carbon fiber cage loaded with bioceramics and platelet-rich plasma. An experimental study on pigs 
European Spine Journal  2004;13(4):354-358.
Platelet-rich plasma (PRP) is an autogenous source of growth factor and has been shown to enhance bone healing both in clinical and experimental studies. PRP in combination with porous hydroxyapatite has been shown to increase the bone ingrowth in a bone chamber rat model. The present study investigated whether the combination of beta tricalcium phosphate (β-TCP) and PRP may enhance spinal fusion in a controlled animal study. Ten Danish Landrace pigs were used as a spinal fusion model. Immediately prior to the surgery, 55 ml blood was collected from each pig for processing PRP. Three-level anterior lumbar interbody fusion was performed with carbon fiber cages and staples on each pig. Autogenous bone graft, β-TCP, and β-TCP loaded with PRP were randomly assigned to each level. Pigs were killed at the end of the third month. Fusion was evaluated by radiographs, CT scanning, and histomorphometric analysis. All ten pigs survived the surgery. Platelet concentration increased 4.4-fold after processing. Radiograph examination showed 70% (7/10) fusion rate in the autograft level. All the levels with β-TCP+PRP showed partial fusion, while β-TCP alone levels had six partial fusions and four non-fusions (P=0.08). CT evaluation of fusion rate demonstrated fusion in 50% (5/10) of the autograft levels. Only partial fusion was seen at β-TCP levels and β-TCP+PRP levels. Histomorphometric evaluation found no difference between β-TCP and β-TCP+PRP levels on new bone volume, remaining β-TCP particles, and bone marrow and fibrous tissue volume, while the same parameters differ significantly when compared with autogenous bone graft levels. We concluded from our results in pigs that the PRP of the concentration we used did not improve the bone-forming capacity of β-TCP biomaterial in anterior spine fusion. Both β-TCP and β-TCP+PRP had poorer radiological and histological outcomes than that of autograft after 3 months.
PMCID: PMC3468048  PMID: 14730438
Spinal fusion; Bone substitute; Platelet-rich plasma; Tricalcium phosphate; Pig
8.  Inhibition of spinal fusion by use of a tissue ingrowth inhibitor 
European Spine Journal  2003;13(2):157-163.
“Spinal instrumentation without fusion” techniques, which do not interfere with spinal growth, have been used extensively in the treatment of progressive spinal scoliosis in very young children. Due to subperiosteal exposure, the process of spinal instrumentation may induce spontaneous bony fusion. Instrumentation and surgical techniques have been modified in order to prevent spontaneous posterior fusion from occurring in children. An absorbable ADCON-L gel has been shown to inhibit scar and epidural adhesions following spinal surgeries. However, little is known about its influence on spinal fusion. In the present study, a single-level intertransverse arthrodesis at L4-5 on both sides was performed on each of nine pigs. Each side was randomly designed to receive autogenous bone graft with or without ADCON-L gel. The animals were followed for 10 weeks postoperatively. A fusion rate of 78% (7/9) was obtained in the autograft treatment by plain X-ray and CT evaluation, while the autograft/ADCON-L treatment yielded a 0% (0/9) fusion rate (p=0.001). Histomorphometric evaluation revealed that the addition of ADCON-L gel to bone graft decreased bone and bone marrow formation and significantly increased fibrous tissue formation. No statistical difference between the two treatments was found in cartilage, bone surface density, osteoid surfaces or osteoclast-covered surfaces in any zone. We conclude that ADCON-L gel mixed into autogenous bone graft can delay or decrease bone formation at spinal arthrodesis sites, thus influencing the extent of spinal fusion. This accords with our hypothesis that the use of ADCON-L gel can prevent not only the occurrence of spontaneous fusion in very young scoliosis patients after instrumentation without fusion, but also re-ossification of a decompressed spinal canal.
PMCID: PMC3476572  PMID: 14618383
Spinal fusion; ADCON-L; Bone regeneration; Pig
9.  The influence of intervertebral disc tissue on anterior spinal interbody fusion: an experimental study on pigs 
European Spine Journal  2002;11(5):476-481.
Intervertebral disc has been shown to be related to low back pain and nerve root injury in pathologic conditions. However, little is known about its influence on spinal fusion. With the development of minimal invasive operations, such as laparoscopic anterior spinal fusion with cages, insufficient discectomy may occur. With its inflammatory properties, the residue nucleus pulposus may have an effect on spinal fusion. In this study, a two-level lumbar spine interbody fusion (L3/4, L5/6) with a Brantigan cage was performed on ten Danish Landrace pigs. Each level was randomly assigned to one of the following methods: (1) implantation of Brantigan cage filled with autogenous iliac crest bone graft, or (2) implantation of Brantigan cage filled with a mixture of autograft and the nucleus pulposus tissue harvested from the disc level in which it was to be inserted. Each level was stabilized with two staples. The pigs were followed for 12 weeks in the same standardized condition. After sacrifice, the lumbar spines were taken out, and plain X-ray, computed tomographic (CT) scanning and histomorphometry were performed to study the fusion mass inside the cages. From plain radiographs, new bone formation could be seen inside and around the cage. CT evaluation showed that the nucleus pulposus level had a 20% (2/10) fusion rate, while the pure autograft level had a 70% (7/10) fusion rate (P=0.07). The histological fusion rate was even lower in the nucleus pulposus level (10%), and was significantly different from the autograft level (70%, P=0.02). Histomorphometric parameters of new bone formation, bone marrow space and fibrous tissue differed significantly between the two levels (P=0.04; P=0.02; P=0.04 respectively). We conclude that when nucleus pulposus is mixed with the autogenous bone graft, it can delay or decrease the bone formation inside the cage, thus influencing the final fusion.
PMCID: PMC3611310  PMID: 12384757
Spine fusion Interbody fusion Nucleus pulposus Pig

Results 1-9 (9)