Thorsten Guehring

Effects of controlled dynamic disc distraction on degenerated intervertebral discs: An in vivo study on the rabbit lumbar spine model

Study Design. An in vivo study on the rabbit lumbar spine model. Objectives. Effects of temporary dynamic distraction on intervertebral discs were studied on the lumbar spine rabbit model to characterize the changes associated with disc distraction and to evaluate feasibility of temporary disc distraction to previously compressed discs in order to stimulate disc regeneration. Summary of Background Data. Studies have shown that accelerated degeneration of the intervertebral disc results from altered mechanical loading conditions. The development of methods for the prevention of disc degeneration and the restoration of disc tissue that has already degenerated are needed. Methods. New Zealand white rabbits (n = 32) were used for this study. The rabbits were randomly assigned to one of five groups. In 12 animals, the discs were first loaded for 28 days using a custom-made external loading device to stimulate disc degeneration. After 28 days loading time, the discs in six animals were distracted for 7 days and in six animals for 28 days using the same external device, however, modified as dynamic distraction device. In six animals, the discs were distracted for 28 days without previous loading; and in six animals, the discs were loaded for 28 days and afterwards the loading device removed for 28 days for recovery without distraction. Six animals were sham operated. The external device was situated; however, the discs remained undistracted and they also served as controls. After 28 to 56 days loading and distraction time, the animals were killed and the lumbar spine was harvested for examination. Disc height, disc morphology, cell viability, relative neutral zone, and tangent modulus were measured. Results. After 28 days of loading, the discs demonstrated a significant decrease in disc space. Histologically, disorganization of the architecture of the anulus occurred. The number of dead cells increased significantly in the anulus and cartilage endplate. These changes were re-versible after 28 days of distraction. The disc thickness increased significantly as compared with the specimens from the 28 days loading group without distraction. Histologically, the discs showed signs of tissue regeneration after 28 days of distraction. The number of dead cells decreased significantly in comparison with the loaded discs without distraction. The flexibility of compressed discs was higher than of compressed/distracted discs. Conclusions. The results of this study suggest that disc regeneration can be induced by axial dynamic distraction in the rabbit intervertebral disc. The decompressed rabbit intervertebral discs showed signs of tissue recovery on a biologic, cellular, and a biomechanical level after 28 days of distraction.

Stimulation of gene expression and loss of anular architecture caused by experimental disc degeneration--an in vivo animal study.

Study Design. An external compression model was used to evaluate gene and protein expression in intervertebral discs with moderate disc degeneration. Objective. To determine messenger ribonucleic acid and protein expression levels of relevant disc components. Summary of Background Data. An animal model of mechanically induced disc degeneration was developed and characterized histologically. However, little is known at the molecular level in moderate disc degeneration. Methods. There were 8 New Zealand white rabbits subjected to monosegmental posterior compression to induce moderate disc degeneration. Twelve animals served as controls or sham controls. Discs were analyzed using immunohistochemistry for collagen type 1 (COL1), COL2, aggrecan, and bone morphogenetic protein-2/4 (BMP-2/4). For gene analysis, conventional and quantitative polymerase chain reactions were used for COL1A2, COL2A1, aggrecan, BMP-2, biglycan, decorin, osteonectin, fibromodulin, fibronectin, matrix metalloproteinase-13 (MMP-13), and tissue inhibitor of MMP-1. Gene expression for nontreated, sham-treated, and compressed discs was quantified in relation to the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase. Results. Immunohistochemistry of compressed discs showed a loss of anular architecture, and a significant reduction of BMP-2/4 and COL2 positive cells. Gene expression analysis showed a significant up-regulation of COL1A2, osteonectin, decorin, fibronectin, tissue inhibitor of MMP-1, BMP-2, and MMP-13 in compressed discs. Conclusions. Experimental moderate disc degeneration is characterized by a loss of BMP-2/4 and COL2 positive cells, although gene expression of disc constituents, catabolic enzymes, and growth factors is stimulated to reestablish disc integrity.

Disc distraction shows evidence of regenerative potential in degenerated intervertebral discs as evaluated by protein expression, magnetic resonance imaging, and messenger ribonucleic acid expression analysis.

Study Design. An animal model of degeneration was used to determine the effects of disc distraction, and was evaluated with magnetic resonance imaging (MRI) as well as gene and protein expression levels. Objective. To investigate gene expression and MRI effects of distraction. Summary of Background Data. Disc degeneration can result from hyper-physiologic loading. Distracted discs with degeneration showed histologic signs of tissue recovery. Methods. There were 18 rabbits that underwent 28 days of compression (200 N) to induce moderate disc degeneration followed by 28 days of distraction (120 N; attached and loaded distraction device) or sham distraction (attached but unloaded distraction device). Comparison was performed with 56 days of compressed discs without distraction. Quantitative outcome measures were MRI signal intensity and gene expression analysis to determine: messenger ribonucleic acid levels for extracellular matrix genes, including collagen 1, collagen 2, biglycan, decorin, aggrecan, fibromodulin, and osteonectin; and matrix-regulative genes, including matrix metalloproteinase-13, tissue-inhibitor of matrix metalloproteinase-1, and bone morphogenetic protein (BMP)-2. Immunohistology was performed for collagen 2 and BMP-2 to label cells semiquantitatively by staining of the cell-surrounding matrix. Results. A total of 28 days of compression decreased signal intensity. Distraction over the same period reestablished physiologic signal intensity, however, a persistent reduction was found in sham distraction. Distraction resulted in gene expression up-regulation of collagen 1 (5.4-fold), collagen 2 (5.5-fold), biglycan (7.7-fold), and decorin (3.4-fold), while expression of fibromodulin (0.16-fold), tissue-inhibitor of matrix metalloproteinase-1 (0.05-fold), and BMP-2 (0.15-fold) was decreased, as compared with 56 days compression. Distracted discs showed more BMP-2 (19.67 vs. 3.67 in 56 days compression) and collagen 2 (18.67 vs. 11.33 in 56 days compression) positive cells per field. Conclusions. Distraction results in disc rehydration, stimulated extracellular matrix gene expression, and increased numbers of protein-expressing cells.

A new porcine in vivo animal model of disc degeneration: response of anulus fibrosus cells, chondrocyte-like nucleus pulposus cells, and notochordal nucleus pulposus cells to partial nucleotomy.

Study Design. In vivo animal study. Objectives. To describe a new porcine disc degeneration model, and to analyze disc remodeling and degeneration after nucleotomy with special view to the different nucleus pulposus (NP) cell types. Summary of Background Data. Thus far, predominantly smaller animals were used for disc degeneration models; however, such small discs were inappropriate to investigate cell implementation therapies. Though notochordal cells (NCs) are important for disc formation and maintenance, differences in the amount of NCs between human and animal discs have often been neglected. Methods. Twenty-four Goettingen minipigs underwent partial nucleotomy with a 16G biopsy cannula, to remove ∼10% of total NP volume. Animals were followed up for 3, or 24 weeks and analyzed by radiographs, MRIs, (immuno)histology, gene expression analysis, and biomechanical testing. Results. Three weeks after nucleotomy disc height was reduced by 26%, and magnetic resonance imaging signal intensity by 40%. At 24 weeks disc height was decreased by 32%. Increased degenerative changes were found in a histodegeneration score 3 and 24 weeks after nucleotomy, as well as considerable NP scarification after 3 weeks. In controls, cytokeratin-8 immunohistochemistry identified NCs in proximity to chondrocyte-like NP cells at approximately equal ratio. After nucleotomy, NCs were considerably reduced to <10% of total NP cells. Matrix genes were upregulated, except for aggrecan that decreased to 35% of initial values 3 weeks after nucleotomy. Matrix degrading factors (matrix metalloproteinases 13 and 3) were continuously upregulated, whereas transcripts of their inhibitors (tissue inhibitors of matrix metalloproteinase 2 and 3) were downregulated. No significant changes in segmental spinal flexibility or bone density were found after nucleotomy. Conclusion. We introduced a new disc degeneration model with relatively large discs that could be used for cell therapeutic approaches. The study gives further information about disc remodeling after nucleotomy and indicates the relevance of an altered cellular composition for the development of disc degeneration.

Quality of Reduction Influences Outcome After Locked-Plate Fixation of Proximal Humeral Type-C Fractures.

BACKGROUND The aim of this study was to determine if fracture reduction, fracture pattern, and patient-related factors influence clinical outcome after locked-plate fixation of displaced proximal humeral fractures. METHODS Ninety-eight patients (mean age, 61.1 ± 11.2 years) with a proximal humeral fracture involving the anatomical neck (type C according to the OTA/AO classification system) were included. Clinical outcome was determined by age and sex-adjusted Constant score (CS%) and the Disabilities of the Arm, Shoulder and Hand (DASH) score. Fracture reduction was quantitatively determined by 3 parameters (head-shaft displacement, head-shaft alignment, and cranialization of the greater tuberosity), and patients were divided into groups according to anatomical reduction, acceptable reduction, or malreduction. Relative risk (RR) for complications, revision surgery, and inferior clinical outcome (CS of <50%) was determined according to the quality of fracture reduction and fracture pattern (disruption of the medial hinge; type-C3 fracture) and patient-related factors (age; comorbidities). RESULTS After a mean of 3.1 ± 1.5 years, the mean CS% and DASH score were 54.8% ± 28.0% and 31.9 ± 24.8, respectively. The complication rate was 32.7% (n = 32), and 27 patients (27.6%) required revision surgery. Anatomical or acceptable fracture reduction was achieved in 40 (40.8%) of the patients. This resulted in a significantly lower complication rate (20.0% compared with 41.4% among the patients with malreduction; p = 0.027), a trend of lower revision rate (20% compared with 32.8%; p = 0.165), and better clinical outcome (mean CS% of 65.4% ± 28.2% compared with 47.6% ± 25.7%; p = 0.002) without a higher risk for osteonecrosis of the humeral head (5% compared with 10.3%). Cranialization of the greater tuberosity of >5 mm (n = 25), head-shaft displacement of >5 mm (n = 50), and valgus head-shaft alignment (n = 12) all increased the RR for inferior clinical outcome by twofold to threefold. Conversely, a patient age of >65 years (n = 31) and an OTA/AO type-C3 fracture pattern (n = 38) were not significantly associated with complications and inferior clinical outcome (RR, 0.9 to 1.8). CONCLUSIONS Anatomical fracture reduction with a locked plate significantly improved the clinical outcome of unstable and displaced proximal humeral fractures involving the anatomical neck. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Increased bone formation in a rabbit long-bone defect model after single local and single systemic application of erythropoietin.

Background and purpose — Delayed bone healing with non-union is a common problem. Further options to increase bone healing together with surgery are needed. We therefore evaluated a 1-dose single application of erythropoietin (EPO), applied either locally to the defect or systemically during surgery, in a critical-size rabbit long-bone defect. Material and methods — 19 New Zealand White rabbits received a 15-mm defect in the radius diaphysis. An absorbable gelatin sponge was soaked with saline (control group and systemic treatment group) or EPO (local treatment group) and implanted into the gap. The systemic treatment group received EPO subcutaneously. In vivo micro-CT analysis was performed 4, 8, and 12 weeks postoperatively. Vascularization was evaluated histologically. Results — Semiquantitative histomorphometric and radiological evaluation showed increased bone formation (2.3- to 2.5-fold) in both treatment groups after 12 weeks compared to the controls. Quantitative determination of bone volume and tissue volume showed superior bone healing after EPO treatment at all follow-up time points, with the highest values after 12 weeks in locally treated animals (3.0- to 3.4-fold). More vascularization was found in both EPO treatment groups. Interpretation — Initial single dosing with EPO was sufficient to increase bone healing substantially after 12 weeks of follow-up. Local application inside the defect was most effective, and it can be administered directly during surgery. Apart from effects on ossification, systemic and local EPO treatment leads to increased callus vascularization.

Outcome of Early and Late Diagnosed Essex-Lopresti Injury.

Background: The aim of this study was to investigate the outcomes in a large series of Essex-Lopresti injuries (ELIs) and to compare patients with early and late diagnoses. Methods: Thirty-one patients with an ELI (average age and standard deviation [SD], 46 ± 10 years) who were followed for a minimum of 2 years were included in the study. Patients were grouped according to whether the ELI had been diagnosed early (on the day of the injury) or late (>4 weeks after the radial head injury). Acute treatment of early-diagnosed ELI included temporary stabilization of the distal radioulnar joint (DRUJ) by Kirschner wires with the forearm in supination for 6 weeks. Clinical outcomes were assessed on the basis of the range of motion, Mayo Elbow Performance Score (MEPS), Mayo Wrist Score (MWS), visual analog scale (VAS) score for wrist and elbow pain, and Disabilities of the Arm, Shoulder and Hand (DASH) score. Results: The ELI was diagnosed on the day of the injury in 16 patients (52%; the early group) and late (at a mean of 7 ± 7 months; range, 1 to 24 months) in 15 (48%; the late group). After a mean duration of follow-up of 5.3 ± 3.0 years (range, 2.0 to 13.1 years), patients with an early diagnosed ELI had significantly better clinical outcomes, compared with those with a late diagnosis, with regard to the MEPS (91.3 ± 8.7 versus 74.7 ± 15.3, p = 0.003), MWS (81.3 ± 16.5 versus 66.3 ± 17.6, p = 0.019), DASH score (12.5 ± 8.7 versus 45.3 ± 23.5, p = 0.001), VAS elbow pain score (0.7 ± 1.1 versus 3.3 ± 2.1, p = 0.001), and VAS wrist pain score (0.9 ± 1.2 versus 3.9 ± 1.7, p < 0.001). The ranges of motion of the elbow and wrist did not differ significantly between the early and late groups (p > 0.05). A significantly lower percentage of patients had complications or subsequent surgical procedures in the early than in the late group (38% [6 of 16] versus 93% [14 of 15], p < 0.001). Conclusions: Early diagnosis of an ELI with temporary stabilization of the DRUJ leads to satisfactory clinical mid-term results, whereas late diagnosis of an ELI is associated with a deteriorated outcome. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Bursitis olecrani@@@Olecranon bursitis: Diagnostisches und therapeutisches Vorgehen@@@Diagnostic workup and treatment

ZusammenfassungDie Bursitis olecrani ist ein häufiges Krankheitsbild, dennoch ist die Behandlung nicht trivial und wird in der Literatur uneinheitlich dargestellt. Die akute, traumatisch bedingte Bursitis olecrani beim jungen Patienten ist in der Regel harmlos und selbstlimitierend. Die eitrige Bursitis ist dagegen rezidivträchtig und komplikationsbehaftet. Die Unterscheidung zwischen der eitrigen und nicht-eitrigen Bursitis olecrani ist grundlegend für eine erfolgreiche Behandlung. Das Ziel der Arbeit ist es daher, die wesentlichen Differenzierungsmerkmale zwischen der eitrigen und der nicht-eitrigen Bursitis darzulegen und einen Therapiealgorithmus vorzustellen, der die gängigen Behandlungskonzepte der jeweiligen Formen beinhaltet.AbstractOlecranon bursitis is a common medical condition. However, treatment is sometimes challenging and the recommendations in the literature are heterogeneous. Acute, posttraumatic olecranon bursitis in the young adult is usually uncomplicated and self-limited. In contrast, the course of septic bursitis can be complicated. Differentiation between septic and aseptic types of olecranon bursitis is fundamental for successful treatment. Therefore, the aim of this review is to present the main characteristics of septic and aseptic olecranon bursitis and to propose a treatment algorithm, which contains the currently accepted treatment recommendations.

Development and validation of a novel questionnaire for self-determination of the range of motion of wrist and elbow

BackgroundThe aim of this study was to develop and validate a novel self-administered questionnaire for assessing the patient’s own range of motion (ROM) of the wrist and the elbow.MethodsIn a prospective clinical study from January 2015 to June 2015, 101 consecutive patients were evaluated with a novel, self-administered, diagram-based, wrist motion assessment score (W-MAS) and elbow motion assessment score (E-MAS). The questionnaire was statistically evaluated for test-retest reliability, patient-physician agreement, comparison with healthy population, and influence of covariates (age, gender, affected side and involvement in workers’ compensation cases).ResultsAssessment of patient-physician agreement demonstrated almost perfect agreement (k > 0.80) with regard to six out of eight items. There was substantial agreement with regard to two items: elbow extension (k = 0.76) and pronation (k = 0.75). The assessment of the test-retest reliability revealed at least substantial agreement (k = 0.70). The questionnaire revealed a high discriminative power when comparing the healthy population with the study group (p = 0.007 or lower for every item). Age, gender, affected side and involvement in workers’ compensation cases did not in general significantly influence the patient-physician agreement for the questionnaire.ConclusionThe W-MAS and E-MAS are valid and reliable self-administered questionnaires that provide a high level of patient-physician agreement for the assessments of wrist and elbow ROM.Level of evidence: Diagnostic study, Level II