Medical Care Use Among Patients with Monogenic Osteoporosis Due to Rare Variants in LRP5, PLS3, or WNT1.

Pathogenic variants in the LRP5, PLS3, or WNT1 genes can significantly affect bone mineral density, causing monogenic osteoporosis. Much remains to be discovered about the phenotype and medical care needs of these patients. The purpose of this study was to examine the use of medical care among Dutch individuals identified between 2014 and 2021 with a pathogenic or suspicious rare variant in LRP5, PLS3, or WNT1. In addition, the aim was to compare their medical care utilization to both the overall Dutch population and the Dutch Osteogenesis Imperfecta (OI) population. The Amsterdam UMC Genome Database was used to match 92 patients with the Statistics Netherlands (CBS) cohort. Patients were categorized based on their harbored variants: LRP5, PLS3, or WNT1. Hospital admissions, outpatient visits, medication data, and diagnosis treatment combinations (DTCs) were compared between the variant groups and, when possible, to the total population and OI population. Compared to the total population, patients with an LRP5, PLS3, or WNT1 variant had 1.63 times more hospital admissions, 2.0 times more opened DTCs, and a greater proportion using medication. Compared to OI patients, they had 0.62 times fewer admissions. Dutch patients with an LRP5, PLS3, or WNT1 variant appear to require on average more medical care than the total population. As expected, they made higher use of care at the surgical and orthopedic departments. Additionally, they used more care at the audiological centers and the otorhinolaryngology (ENT) department, suggesting a higher risk of hearing-related problems.

Estimated cumulative radiation exposure in patients treated for adolescent idiopathic scoliosis.

PURPOSE: Adolescent idiopoathic scoliosis (AIS) is a progressive spinal deformity, most often observed in female patients of pubescent age. The deformity's severity, its progression through time, its treatment and subsequent follow-up are assessed with routine radiological evaluation of the patient's full spine. This study aimed to determine the cumulative radiation exposure in average patients with AIS treated by brace or surgery throughout their treatment. METHODS: The average number of imaging procedures and corresponding radiation doses were retrospectively obtained from the medical charts of AIS patients treated conservatively and/or surgically at our institution. The median radiation exposure of all imaging modalities was stated in effective dose (mSv). The estimated cumulative effective radiation dose of the each treatment group was determined by multiplication of the average number of imaging conducted, and the median effective radiation dose per imaging modality. RESULTS: In total, 73 AIS patients were included (28 brace, 45 surgically). Patients treated with a brace were subjected to an average of 9.03 full spine radiographs, resulting in an estimated effective cumulative dose of 0.505 mSv over a median treatment period of 3.23 years. Patients treated surgically received an average of 14.29 full spine radiographs over a median treatment period of 2.76 years. The estimated effective cumulative dose amounted from 0.951 to 1.841 mSv, depending on the surgical technique. CONCLUSION: The cumulative effective radiation doses rendered to AIS patients as part of their treatment and follow-up were relatively low. However, every exposure to ionising radiation for medical imaging purposes should be minimised.

Understanding the Lenke Classification for Adolescent Idiopathic Scoliosis (AIS).

For over 20 years, the Lenke classification has been used as a standard to describe and classify scoliosis patterns in patients with adolescent idiopathic scoliosis (AIS). Based on this classification, patients are given a treatment recommendation, which is usually surgical. The Lenke classification has proven to be a reliable and reproducible classification for patients with AIS; however, it still proves to be complex in daily clinical practice. This study presents a simple approach to the Lenke classification for AIS patients that is easier to understand and to apply.

Current models to understand the onset and progression of scoliotic deformities in adolescent idiopathic scoliosis: a systematic review.

PURPOSE: To create an updated and comprehensive overview of the modeling studies that have been done to understand the mechanics underlying deformities of adolescent idiopathic scoliosis (AIS), to predict the risk of curve progression and thereby substantiate etiopathogenetic theories. METHODS: In this systematic review, an online search in Scopus and PubMed together with an analysis in secondary references was done, which yielded 86 studies. The modeling types were extracted and the studies were categorized accordingly. RESULTS: Animal modeling, together with machine learning modeling, forms the category of black box models. This category is perceived as the most clinically relevant. While animal models provide a tangible idea of the biomechanical effects in scoliotic deformities, machine learning modeling was found to be the best curve-progression predictor. The second category, that of artificial models, has, just as animal modeling, a tangible model as a result, but focusses more on the biomechanical process of the scoliotic deformity. The third category is formed by computational models, which are very popular in etiopathogenetic parameter-based studies. They are also the best in calculating stresses and strains on vertebrae, intervertebral discs, and other surrounding tissues. CONCLUSION: This study presents a comprehensive overview of the current modeling techniques to understand the mechanics of the scoliotic deformities, predict the risk of curve progression in AIS and thereby substantiate etiopathogenetic theories. Although AIS remains to be seen as a complex and multifactorial problem, the progression of its deformity can be predicted with good accuracy. Modeling of AIS develops rapidly and may lead to the identification of risk factors and mitigation strategies in the near future. The overview presented provides a basis to follow this development.

Total knee arthroplasty improves gait adaptability in osteoarthritis patients; a pilot study.

Background: Gait adaptability is of utmost importance for keeping balance during gait in patients with knee osteoarthritis, also after total knee arthroplasty (TKA). The aims of this explorative study are: (1) assess the effect of age, knee osteoarthritis and TKA on gait adaptability; (2) assess changes in gait adaptability pre-to post-TKA and (3) their relation to functional outcomes. Methods: Gait adaptability was measured using a Target Stepping Test (TST) in knee osteoarthritis patients before (preTKA) and 12 months after TKA (postTKA) and compared to asymptomatic old (AsOld) and young adults (AsYng). TST imposed an asymmetrical gait pattern with projected stepping targets at high walking speed. Gait adaptability was determined through stepping accuracy on the targets. The Oxford Knee Score (OKS) and Timed-Up-and-Go test (TUG) measured patients' physical function. Results: 12 preTKA, 8 postTKA, 18 AsYng, 21 AsOld were tested. Age showed no effect on TST-stepping accuracy. PreTKA showed worse TST-stepping accuracy compared to AsYng and AsOld (7.7; 6.2 cm difference). PostTKA showed an improvement of 52% in TST-stepping accuracy compared to preTKA (3.2 cm).Higher stepping accuracy preTKA predicted higher stepping accuracy post-TKA. In addition, low preTKA stepping accuracy predicted more improvement postTKA. Pre-to post-TKA improvement of stepping accuracy was related to improvement on the TUG (Beta = 0.17, p = 0.024), but not to OKS. Conclusions: Gait adaptability is improved following TKA in knee osteoarthritis patients and no longer significantly worse than asymptomatic adults. The relation of gait adaptability to function is shown by its relation to the TUG and shows to have predictive value pre-to post-TKA.

Patient-Reported Long-Term Outcomes After Free Vascularized Fibula Graft in Spinal Reconstruction: a 24-year Cohort.

PURPOSE: The use of free vascularized fibula grafts (FVFG) in complex spinal deformity surgery intends to allow for life-long stability of the spine with good long-term clinical outcome. However, these long-term outcomes of this technique are still lacking. The objective of this study is to report the long-term postoperative outcomes and establish the long-term viability of this method for spinal reconstruction. METHODS: A retrospective cohort study was conducted in all patients who underwent spinal reconstructive surgery utilizing a FVFG at a tertiary medical centre. Questionnaires taken from the participants were the Numeric Pain Rating Scale (NPRS), Oswestry Low Back Pain Disability (also known as Oswestry Disability Index (ODI)), Scoliosis Research Society 22r (SRS-22), the EQ-5D-5L and a self-assembled questionnaire regarding donor site comorbidities and patient satisfaction. RESULTS: Over a period of 24 years (1995-2019), we used FVFG for spinal reconstruction in 31 patients. A total of 25 patients were included in this study, 8 patients were deceased at the time of this study, and sixteen patients responded to the questionnaires. Patient satisfaction was rated 6.8 out of 10, the average SRS-22r score was 3.6, EQ-5D-5L score was 0.725, and the ODI score showed a minimal disability (0-20%) postoperatively. Overall complication-free survival was 8.9 years. Nine patients underwent a re-operation in the spinal area; five for the removal of the spinal instrumentation. CONCLUSION: Patients reported satisfied and good long-term outcomes following FVFG surgical procedure for complex spinal deformities. Therefore, considering the alternatives, this procedure provides a good long-term solution for complex spinal deformity surgery.

Accuracy assessment of pedicle screw insertion with patient specific 3D­printed guides through superimpose CT-analysis in thoracolumbar spinal deformity surgery.

PURPOSE: In order to avoid pedicle screw misplacement in posterior spinal deformity surgery, patient specific 3D­printed guides can be used. An accuracy assessment of pedicle screw insertion can be obtained by superimposing CT-scan images from a preoperative plan over those of the postoperative result. The aim of this study is to report on the accuracy of drill guide assisted pedicle screw placement in thoracolumbar spinal deformity surgery by means of a superimpose CT-analysis. METHODS: Concomitant with the clinical introduction of a new technique for drill guide assisted pedicle screw placement, the accuracy of pedicle screw insertion was analyzed in the first patients treated with this technique by using superimpose CT-analysis. Deviation from the planned ideal intrapedicular screw trajectory was classified according to the Gertzbein scale. RESULTS: Superimpose CT-analysis of 99 pedicle screws in 5 patients was performed. The mean linear deviation was 0.92 mm, the mean angular deviation was 2.92° with respect to the preoperatively planned pedicle screw trajectories. According to the Gertzbein scale, 100% of screws were found to be positioned within the "safe zone". CONCLUSION: The evaluated patient specific 3D-printed guide technology was demonstrated to constitute a safe and accurate tool for precise pedicle screw insertion in spinal deformity surgeries. Superimpose CT-analysis showed a 100% accuracy of pedicle screw placement without any violation of the pedicle wall or other relevant structures. We recommend a superimpose CT-analysis for the first consecutive patients when introducing new technologies into daily clinical practice, such as intraoperative imaging, navigation or robotics.

Gel-type autologous chondrocyte implantation for cartilage repair in patients with prior ACL reconstruction: A retrospective two year follow-up.

PURPOSE: To describe the early patient-reported outcomes of articular cartilage repair in patients with pain due to grade III or IV articular cartilage defects after prior anterior cruciate ligament (ACL) reconstruction. METHODS: Nineteen patients underwent a gel-type autologous chondrocyte implantation (GACI) procedure after ACL reconstruction. Median timeframe between ACL reconstruction and GACI procedure was 52 months (range 16 to 369). The average age at chondrocyte implantation was 35 (standard deviation (SD) eight) years and average cumulative articular cartilage defect size was nine (SD four) square centimeter. Outcome was assessed prior to the GACI procedure and two years after GACI using the International Knee Documentation Committee (IKDC) score and the Knee injury and Osteoarthritis Outcome Score (KOOS). RESULTS: Two year post-GACI scores showed a statistically significant improvement of IKDC (13, SD 22, p=.02) and KOOS quality of life (18, SD 27, p=.01) compared to the pre-GACI scores. The other KOOS domains did improve, but not statistically significant. Seven (37%) patients underwent reoperation after the GACI. CONCLUSION: Patients with prior ACL reconstruction and suffering from ongoing pain associated with cartilage defects can benefit from cartilage repair with GACI.

Mechanics and biology in intervertebral disc degeneration: a vicious circle.

Intervertebral disc degeneration is a major cause of low back pain. Despite its long history and large socio-economical impact in western societies, the initiation and progress of disc degeneration is not well understood and a generic disease model is lacking. In literature, mechanics and biology have both been implicated as the predominant inductive cause; here we argue that they are interconnected and amplify each other. This view is supported by the growing awareness that cellular physiology is strongly affected by mechanical loading. We propose a vicious circle of mechanical overloading, catabolic cell response, and degeneration of the water-binding extracellular matrix. Rather than simplifying the disease, the model illustrates the complexity of disc degeneration, because all factors are interrelated. It may however solve some of the controversy in the field, because the vicious circle can be entered at any point, eventually leading to the same pathology. The proposed disease model explains the comparable efficacy of very different animal models of disc degeneration, but also helps to consider the consequences of therapeutic interventions, either at the cellular, material or mechanical level.

Long-Term Creep Behavior of the Intervertebral Disk: Comparison between Bioreactor Data and Numerical Results.

The loaded disk culture system is an intervertebral disk (IVD)-oriented bioreactor developed by the VU Medical Center (VUmc, Amsterdam, The Netherlands), which has the capacity of maintaining up to 12 IVDs in culture, for approximately 3 weeks after extraction. Using this system, eight goat IVDs were provided with the essential nutrients and submitted to compression tests without losing their biomechanical and physiological properties, for 22 days. Based on previous reports (Paul et al., 2012, 2013; Detiger et al., 2013), four of these IVDs were kept in physiological condition (control) and the other four were previously injected with chondroitinase ABC (CABC), in order to promote degenerative disk disease (DDD). The loading profile intercalated 16 h of activity loading with 8 h of loading recovery to express the standard circadian variations. The displacement behavior of these eight IVDs along the first 2 days of the experiment was numerically reproduced, using an IVD osmo-poro-hyper-viscoelastic and fiber-reinforced finite element (FE) model. The simulations were run on a custom FE solver (Castro et al., 2014). The analysis of the experimental results allowed concluding that the effect of the CABC injection was only significant in two of the four IVDs. The four control IVDs showed no signs of degeneration, as expected. In what concerns to the numerical simulations, the IVD FE model was able to reproduce the generic behavior of the two groups of goat IVDs (control and injected). However, some discrepancies were still noticed on the comparison between the injected IVDs and the numerical simulations, namely on the recovery periods. This may be justified by the complexity of the pathways for DDD, associated with the multiplicity of physiological responses to each direct or indirect stimulus. Nevertheless, one could conclude that ligaments, muscles, and IVD covering membranes could be added to the FE model, in order to improve its accuracy and properly describe the recovery periods.

The outcome and survival of palliative surgery in thoraco-lumbar spinal metastases: contemporary retrospective cohort study.

UNLABELLED: Purpose: To evaluate outcome and survival and to identify prognostic variables for patients surgically treated for spinal metastases. Methods: A retrospective study was performed on 86 patients, surgically treated for spinal metastases. Preoperative analyses of the ASIA and spinal instability neoplastic scores (SINS) were performed. Survival curves of different prognostic variables were made by Kaplan­Meier analysis and the variables entered in a Cox proportional hazards model to determine their significance on survival. The correlation between preoperative radiotherapy and postoperative wound infections was also evaluated. Results: Survival analysis was performed on 81 patients,37 women and 44 men. Five patients were excluded due to missing data. Median overall survival was 38 weeks [95 % confidence interval (CI) 27.5­48.5 weeks], with a 3-month survival rate of 81.5 %. Breast tumor had the best median survival of 127 weeks and lung tumor the worst survival of 18 weeks. Univariate analysis showed tumor type, preoperative ASIA score (p = 0.01) and visceral metastases(p = 0.18) were significant prognostic variables for survival.Colon tumors had 5.53 times hazard ratio compared to patients with breast tumor. ASIA-C score had more than 13.03 times the hazard ratio compared to patients with an ASIA-E score. Retrospective analysis of the SINS scores showed 34 patients with a score of 13­18 points, 44 patients with a score of 7­12 points, and 1 patient with a score of 6 points. Preoperative radiotherapy had no influence on the postoperative incidence of deep surgical wound infections (p = 0.37). CONCLUSIONS: Patients with spinal metastases had a median survival of 38 weeks postoperative. The primary tumor type and ASIA score were significant prognostic factors for survival. Preoperative radiotherapy neither had influence on survival nor did it constitute a risk for postoperative surgical wound infections.

Giant cell tumors of the sacrum--a nationwide study on midterm results in 26 patients after intralesional excision.

PURPOSE: Evaluation of recurrences, complications and function at mid-term follow-up after curettage for sacral giant cell tumor (GCT). METHODS: We retrospectively studied all 26 patients treated for sacral GCT in the Netherlands (from 1990 to 2010). Median follow-up was 98 (6-229) months. All patients underwent intralesional excision, 21 with local adjuvants, 5 radiotherapy, 3 IFN-α, 1 bisphosphonates. Functional outcome was assessed using Musculoskeletal Tumor Society (MSTS) score. Statistics were performed with Kaplan-Meier, Cox regression, log rank and Mann-Whitney U. RESULTS: Recurrence rate was 14/26 after median 13 (3-139) months and was highest after isolated curettage (4/5). Soft tissue masses >10 cm increased recurrence risk (HR = 3.3, 95 % CI = 0.81-13, p = 0.09). Complications were reported in 12/26 patients. MSTS was superior in patients without complications (27 vs. 21; p = 0.024). CONCLUSION: Recurrence rate for sacral GCT was highest after isolated curettage, indicating that (local) adjuvant treatment is desired to obtain immediate local control. Complications were common and impaired function.

Surface proteomic analysis of osteosarcoma identifies EPHA2 as receptor for targeted drug delivery.

BACKGROUND: Osteosarcoma (OS) is the most common bone tumour in children and adolescents. Despite aggressive therapy regimens, treatment outcomes are unsatisfactory. Targeted delivery of drugs can provide higher effective doses at the site of the tumour, ultimately improving the efficacy of existing therapy. Identification of suitable receptors for drug targeting is an essential step in the design of targeted therapy for OS. METHODS: We conducted a comparative analysis of the surface proteome of human OS cells and osteoblasts using cell surface biotinylation combined with nano-liquid chromatography - tandem mass spectrometry-based proteomics to identify surface proteins specifically upregulated on OS cells. This approach generated an extensive data set from which we selected a candidate to study for its suitability as receptor for targeted treatment delivery to OS. First, surface expression of the ephrin type-A receptor 2 (EPHA2) receptor was confirmed using FACS analysis. Ephrin type-A receptor 2 expression in human tumour tissue was tested using immunohistochemistry. Receptor targeting and internalisation studies were conducted to assess intracellular uptake of targeted modalities via EPHA2. Finally, tissue micro arrays containing cores of human OS tissue were stained using immunohistochemistry and EPHA2 staining was correlated to clinical outcome measures. RESULTS: Using mass spectrometry, a total of 2841 proteins were identified of which 156 were surface proteins significantly upregulated on OS cells compared with human primary osteoblasts. Ephrin type-A receptor 2 was highly upregulated and the most abundant surface protein on OS cells. In addition, EPHA2 was expressed in a vast majority of human OS samples. Ephrin type-A receptor 2 effectively mediates internalisation of targeted adenoviral vectors into OS cells. Patients with EPHA2-positive tumours showed a trend toward inferior overall survival. CONCLUSION: The results presented here suggest that the EPHA2 receptor can be considered an attractive candidate receptor for targeted delivery of therapeutics to OS.

Relation between radiological assessment and biomechanical stability of lumbar interbody fusion in a large animal model.

PURPOSE: To relate the progress of vertebral segmental stability after interbody fusion surgery with radiological assessment of spinal fusion. METHODS: Twenty goats received double-level interbody fusion and were followed for a period of 3, 6 and 12 months. After killing, interbody fusion was assessed radiographically by two independent observers. Subsequently, the lumbar spines were subjected to four-point bending and rotational deformation, assessed with an optoelectronic 3D movement registration system. In addition, four caprine lumbar spines were analysed in both the native situation and after the insertion of a cage device, as to mimic the direct post-surgical situation. The range of motion (ROM) in flexion/extension, lateral bending and axial rotation was analysed ex vivo using a multi-segment testing system. RESULTS: Significant reduction in ROM in the operated segments was already achieved with moderate bone ingrowth in flexion/extension (71 % reduction in ROM) and with only limited bone ingrowth in lateral bending (71 % reduction in ROM) compared to the post-surgical situation. The presence of a sentinel sign always resulted in a stable vertebral segment in both flexion/extension and lateral bending. For axial rotation, the ROM was already limited in both native and cage inserted situations, resulting in non-significant differences for all radiographic scores. DISCUSSION: In vivo vertebral segment stability, defined as a significant reduction in ROM, is achieved in an early stage of spinal fusion, well before a radiological bony fusion between the vertebrae can be observed. Therefore, plain radiography underestimates vertebral segment stability.

Incidence and gender differences of slipped capital femoral epiphysis in the Netherlands from 1998-2010 combined with a review of the literature on the epidemiology of SCFE.

PURPOSE: The incidence of slipped capital femoral epiphysis (SCFE) among children living in the Netherlands has never been published. METHODS: The national hospitalization registration system of the Netherlands was searched for the incidence of surgical procedures for SCFE in the Netherlands among different pediatric age groups between 1998 and 2010. International Classification of Diseases, 9th Revision codes were used. RESULTS AND CONCLUSION: The incidence of surgical procedures for SCFE during the last decade was 11.6 per 100,000 children aged 5 to 19 years. No statistical difference in the incidence of SCFE was found between boys and girls, although the incidence of SCFE did significantly increase in girls during the study period. Based on our analysis, the Netherlands appears to be the first country in which no difference in the incidence of SCFE among boys and girls has been reported. However, during the study period there has been a concomitant increase in the number of girls with SCFE.

Slipped capital femoral epiphysis and its association with endocrine, metabolic and chronic diseases: a systematic review of the literature.

PURPOSE: Puberty, obesity, endocrine and chronic systemic diseases are known to be associated with slipped capital femoral epiphysis (SCFE). The mechanical insufficiency of the physis in SCFE is thought to be the result of an abnormal weakening of the physis. However, the mechanism at the cellular level has not been unravelled up to now. METHODS: To understand the pathophysiology of endocrine and metabolic factors acting on the physis, we performed a systematic review focussing on published studies reporting on hormonal, morphological and cellular abnormalities of the physis in children with SCFE. In addition, we looked for studies of the effects of endocrinopathies on the human physis which can lead to cause SCFE and focussed in detail on hormonal signalling, hormone receptor expression and extracellular matrix (ECM) composition of the physis. We searched in the PubMed, EMBASE.com and The Cochrane Library (via Wiley) databases from inception to 11th September 2012. The search generated a total of 689 references: 382 in PubMed, 232 in EMBASE.com and 75 in The Cochrane Library. After removing duplicate papers, 525 papers remained. Of these, 119 were selected based on titles and abstracts. After excluding 63 papers not related to the human physis, 56 papers were included in this review. RESULTS: Activation of the gonadal axis and the subsequent augmentation of the activity of the growth hormone-insulin-like growth factor 1 (GH-IGF-1) axis are important for the pubertal growth spurt, as well as for cessation of the physis at the end of puberty. The effects of leptin, thyroid hormone and corticosteroids on linear growth and on the physis are also discussed. Children with chronic diseases suffer from inflammation, acidosis and malnutrition. These consequences of chronic diseases affect the GH-IGF-1 axis, thereby, increasing the risk of the development of SCFE. The risk of SCFE and avascular necrosis in children with chronic renal insufficiency, growth hormone treatment and renal osteodystrophy remains equivocal. CONCLUSIONS: SCFE is most likely the result of a multi-factorial event during adolescence when height and weight increase dramatically and the delicate balance between the various hormonal equilibria can be disturbed. Up to now, there are no screening or diagnostic tests available to predict patients at risk.

Validation of vibration testing for the assessment of the mechanical properties of human lumbar motion segments.

Experimental modal analysis is a non-destructive measurement technique, which applies low forces and small deformations to assess the integrity of a structure. It is therefore a promising method to study the mechanical properties of the spine in vivo. Previously, modal parameters successfully revealed artificially induced spinal injuries. The question remains however, whether experimental modal analysis can be applied successfully in human spinal segments with mechanical changes due to physiological processes. Since quasi-static mechanical testing is considered the "gold standard" for assessing intervertebral stiffness, the purpose of our study was to examine if the mechanical properties derived from vibration testing and quasi-static testing correlate. Six cadaver human spines (L1-L5) were loaded quasi-statically in bending and torsion, while an optical system measured the angular rotations of the individual motion segments. Subsequently, the polysegmental spines were divided into L2-L3 and L4-L5 segments and a shaker was used to vibrate the upper vertebra, while its response was obtained from accelerometers in anteroposterior and mediolateral directions. From the resulting frequency response function the eigenfrequencies (ratio between stiffness and mass) and vibration modes (pattern of motion) were determined. The vibration results showed clear eigenfrequencies for flexion-extension (mean 121.83Hz, SD 40.05Hz), lateroflexion (mean 132.17, SD 34.80Hz) and axial rotation (mean 236.17Hz, SD 81.45Hz). Furthermore, the correlation between static and dynamic tests was significant (r=0.73, p=0.01). In conclusion, the findings from this study show that experimental modal analysis is a valid method to assess the mechanical properties of human lumbar motion segments.

The feasibility of modal testing for measurement of the dynamic characteristics of goat vertebral motion segments.

Structural vibration testing might be a promising method to study the mechanical properties of spinal motion segments as an alternative to imaging and spinal manipulation techniques. Structural vibration testing is a non-destructive measurement technique that measures the response of a system to an applied vibration as a function of frequency, and allows determination of modal parameters such as resonance frequencies (ratio between stiffness and mass), vibration modes (pattern of motion) and damping. The objective of this study was to determine if structural vibration testing can reveal the resonance frequencies that correspond to the mode shapes flexion-extension, lateroflexion and axial rotation of lumbar motion segments, and to establish whether resonance frequencies can discriminate specific structural alterations of the motion segment. Therefore, a shaker was used to vibrate the upper vertebra of 16 goat lumbar motion segments, while the response was obtained from accelerometers on the transverse and spinous processes and the anterior side of the upper vertebra. Measurements were performed in three conditions: intact, after dissection of the ligaments and after puncturing the annulus fibrosus. The results showed clear resonance peaks for flexion-extension, lateral bending and axial rotation for all segments. Dissection of the ligaments did not affect the resonance frequencies, but puncturing the annulus reduced the resonance frequency of axial rotation. These results indicate that vibration testing can be utilised to assess the modal parameters of lumbar motion segments, and might eventually be used to study the mechanical properties of spinal motion segments in vivo.

Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature.

Treating metastatic osteosarcoma (OS) remains a challenge in oncology. Current treatment strategies target the primary tumour rather than metastases and have a limited efficacy in the treatment of metastatic disease. Metastatic cells have specific features that render them less sensitive to therapy and targeting these features might enhance the efficacy of current treatment. A detailed study of the biological characteristics and behaviour of metastatic OS cells may provide a rational basis for innovative treatment strategies. The aim of this review is to give an overview of the biological changes in metastatic OS cells and the preclinical and clinical efforts targeting the different steps in OS metastases and how these contribute to designing a metastasis directed treatment for OS.

Posterior lumbar interbody fusion using non resorbable poly-ether-ether-ketone versus resorbable poly-L-lactide-co-D,L-lactide fusion devices. Clinical outcome at a minimum of 2-year follow-up.

Previous papers on resorbable poly-L-lactide-co-D,L-lactide (PLDLLA) cages in spinal fusion have failed to report adequately on patient-centred clinical outcome measures. Also comparison of PLDLLA cage with a traditionally applicable counterpart has not been previously reported. This is the first randomized prospective study that assesses clinical outcome of PLDLLA cage compared with a poly-ether-ether-ketone (PEEK) implant. Twenty-six patients were randomly assigned to undergo instrumented posterior lumbar interbody fusion (PLIF) whereby either a PEEK cage or a PLDLLA cage was implanted. Clinical outcome based on visual analogue scale scores for leg pain and back pain, as well as Oswestry Disability Index (ODI) and SF-36 questionnaires were documented and analysed. When compared with preoperative values, all clinical parameters have significantly improved in the PEEK group at 2 years after surgery with the exception of SF-36 general health, SF-36 mental health and SF-36 role emotional scores. No clinical parameter showed significant improvement at 2 years after surgery compared with preoperative values in the PLDLLA patient group. Only six patients (50%) in the PLDLLA group showed improvement in the VAS scores for leg and back pain as well as the ODI, as opposed to 10 patients (71%) in the PEEK group. One-third of the patients in the PLDLLA group actually reported worsening of their pain scores and ODI. Three cases of mild to moderate osteolysis were seen in the PLDLLA group. Following up on our preliminary report, these 2-year results confirm the superiority of the PEEK implant to the resorbable PLDLLA implant in aiding spinal fusion and alleviating symptoms following PLIF in patients with degenerative spondylolisthesis associated with either canal stenosis or foramen stenosis or both and emanating from a single lumbar segment.