Effects of zoledronate versus placebo on spine bone mineral density and microarchitecture assessed by the trabecular bone score in postmenopausal women with osteoporosis: a three-year study

The trabecular bone score (TBS) is an index of bone microarchitectural texture calculated from anteroposterior dual-energy X-ray absorptiometry (DXA) scans of the lumbar spine (LS) that predicts fracture risk, independent of bone mineral density (BMD). The aim of this study was to compare the effects of yearly intravenous zoledronate (ZOL) versus placebo (PLB) on LS BMD and TBS in postmenopausal women with osteoporosis. Changes in TBS were assessed in the subset of 107 patients recruited at the Department of Osteoporosis of the University Hospital of Berne, Switzerland, who were included in the HORIZON trial. All subjects received adequate calcium and vitamin D3. In these patients randomly assigned to either ZOL (n = 54) or PLB (n = 53) for 3 years, BMD was measured by DXA and TBS assessed by TBS iNsight (v1.9) at baseline and 6, 12, 24, and 36 months after treatment initiation. Baseline characteristics (mean ± SD) were similar between groups in terms of age, 76.8 ± 5.0 years; body mass index (BMI), 24.5 ± 3.6 kg/m(2) ; TBS, 1.178 ± 0.1 but for LS T-score (ZOL-2.9 ± 1.5 versus PLB-2.1 ± 1.5). Changes in LS BMD were significantly greater with ZOL than with PLB at all time points (p < 0.0001 for all), reaching +9.58% versus +1.38% at month 36. Change in TBS was significantly greater with ZOL than with PLB as of month 24, reaching +1.41 versus-0.49% at month 36; p = 0.031, respectively. LS BMD and TBS were weakly correlated (r = 0.20) and there were no correlations between changes in BMD and TBS from baseline at any visit. In postmenopausal women with osteoporosis, once-yearly intravenous ZOL therapy significantly increased LS BMD relative to PLB over 3 years and TBS as of 2 years.

Sensory innervation of the dorsal longitudinal ligament and the meninges in the lumbar spine of the dog

Although intervertebral disc herniation is a well-known disease in dogs, pain management for this condition has remained a challenge. The goal of the present study is to address the lack of information regarding the innervation of anatomical structures within the canine vertebral canal. Immunolabeling was performed with antibodies against protein gene product 9.5, Tuj-1 (neuron-specific class III β-tubulin), calcitonin gene-related peptide, and neuropeptide Y in combination with the lectin from Lycopersicon esculentum as a marker for blood vessels. Staining was indicative of both sensory and sympathetic fibers. Innervation density was the highest in lateral areas, intermediate in dorsal areas, and the lowest in ventral areas. In the dorsal longitudinal ligament (DLL), the highest innervation density was observed in the lateral regions. Innervation was lower at mid-vertebral levels than at intervertebral levels. The presence of sensory and sympathetic fibers in the canine dura and DLL suggests that pain may originate from both these structures. Due to these regional differences in sensory innervation patterns, trauma to intervertebral DLL and lateral dura is expected to be particularly painful. The results ought to provide a better basis for the assessment of medicinal and surgical procedures.

An image-based method to automatically propagate bony landmarks: application to computational spine biomechanics.

In attempts to elucidate the underlying mechanisms of spinal injuries and spinal deformities, several experimental and numerical studies have been conducted to understand the biomechanical behavior of the spine. However, numerical biomechanical studies suffer from uncertainties associated with hard- and soft-tissue anatomies. Currently, these parameters are identified manually on each mesh model prior to simulations. The determination of soft connective tissues on finite element meshes can be a tedious procedure, which limits the number of models used in the numerical studies to a few instances. In order to address these limitations, an image-based method for automatic morphing of soft connective tissues has been proposed. Results showed that the proposed method is capable to accurately determine the spatial locations of predetermined bony landmarks. The present method can be used to automatically generate patient-specific models, which may be helpful in designing studies involving a large number of instances and to understand the mechanical behavior of biomechanical structures across a given population.

Development and validation of a quantitative method to assess pedicle screw loosening in posterior spine instrumentation on plain radiographs.

PURPOSE Currently, the diagnosis of pedicle screw (PS) loosening is based on a subjectively assessed halo sign, that is, a radiolucent line around the implant wider than 1 mm in plain radiographs. We aimed at development and validation of a quantitative method to diagnose PS loosening on radiographs. METHODS Between 11/2004 and 1/2010 36 consecutive patients treated with thoraco-lumbar spine fusion with PS instrumentation without PS loosening were compared with 37 other patients who developed a clinically manifesting PS loosening. Three different angles were measured and compared regarding their capability to discriminate the loosened PS over the postoperative course. The inter-observer invariance was tested and a receiver operating characteristics curve analysis was performed. RESULTS The angle measured between the PS axis and the cranial endplate was significantly different between the early and all later postoperative images. The Spearman correlation coefficient for the measurements of two observers at each postoperative time point ranged between 0.89 at 2 weeks to 0.94 at 2 months and 1 year postoperative. The angle change of 1.9° between immediate postoperative and 6-month postoperative was 75% sensitive and 89% specific for the identification of loosened screws (AUC = 0.82). DISCUSSION The angle between the PS axis and the cranial endplate showed good ability to change in PS loosening. A change of this angle of at least 2° had a relatively high sensitivity and specificity to diagnose screw loosening.

Image-based biomechanical assessment of vertebral body and intervertebral disc in the human lumbar spine

Life expectancy continuously increases but our society faces age-related conditions. Among musculoskeletal diseases, osteoporosis associated with risk of vertebral fracture and degenerative intervertebral disc (IVD) are painful pathologies responsible for tremendous healthcare costs. Hence, reliable diagnostic tools are necessary to plan a treatment or follow up its efficacy. Yet, radiographic and MRI techniques, respectively clinical standards for evaluation of bone strength and IVD degeneration, are unspecific and not objective. Increasingly used in biomedical engineering, CT-based finite element (FE) models constitute the state-of-art for vertebral strength prediction. However, as non-invasive biomechanical evaluation and personalised FE models of the IVD are not available, rigid boundary conditions (BCs) are applied on the FE models to avoid uncertainties of disc degeneration that might bias the predictions. Moreover, considering the impact of low back pain, the biomechanical status of the IVD is needed as a criterion for early disc degeneration. Thus, the first FE study focuses on two rigid BCs applied on the vertebral bodies during compression test of cadaver vertebral bodies, vertebral sections and PMMA embedding. The second FE study highlights the large influence of the intervertebral disc’s compliance on the vertebral strength, damage distribution and its initiation. The third study introduces a new protocol for normalisation of the IVD stiffness in compression, torsion and bending using MRI-based data to account for its morphology. In the last study, a new criterion (Otsu threshold) for disc degeneration based on quantitative MRI data (axial T2 map) is proposed. The results show that vertebral strength and damage distribution computed with rigid BCs are identical. Yet, large discrepancies in strength and damage localisation were observed when the vertebral bodies were loaded via IVDs. The normalisation protocol attenuated the effect of geometry on the IVD stiffnesses without complete suppression. Finally, the Otsu threshold computed in the posterior part of annulus fibrosus was related to the disc biomechanics and meet objectivity and simplicity required for a clinical application. In conclusion, the stiffness normalisation protocol necessary for consistent IVD comparisons and the relation found between degeneration, mechanical response of the IVD and Otsu threshold lead the way for non-invasive evaluation biomechanical status of the IVD. As the FE prediction of vertebral strength is largely influenced by the IVD conditions, this data could also improve the future FE models of osteoporotic vertebra.

Comparative effects of teriparatide and ibandronate on spine bone mineral density (BMD) and microarchitecture (TBS) in postmenopausal women with osteoporosis: a 2-year open-label study

UNLABELLED Treatment effects over 2 years of teriparatide vs. ibandronate in postmenopausal women with osteoporosis were compared using lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). Teriparatide induced larger increases in BMD and TBS compared to ibandronate, suggesting a more pronounced effect on bone microarchitecture of the bone anabolic drug. INTRODUCTION The trabecular bone score (TBS) is an index of bone microarchitecture, independent of bone mineral density (BMD), calculated from anteroposterior spine dual X-ray absorptiometry (DXA) scans. The potential role of TBS for monitoring treatment response with bone-active substances is not established. The aim of this study was to compare the effects of recombinant human 1-34 parathyroid hormone (teriparatide) and the bisphosphonate ibandronate (IBN), on lumbar spine (LS) BMD and TBS in postmenopausal women with osteoporosis. METHODS Two patient groups with matched age, body mass index (BMI), and baseline LS BMD, treated with either daily subcutaneous teriparatide (N = 65) or quarterly intravenous IBN (N = 122) during 2 years and with available LS BMD measurements at baseline and 2 years after treatment initiation were compared. RESULTS Baseline characteristics (overall mean ± SD) were similar between groups in terms of age 67.9 ± 7.4 years, body mass index 23.8 ± 3.8 kg/m(2), BMD L1-L4 0.741 ± 0.100 g/cm(2), and TBS 1.208 ± 0.100. Over 24 months, teriparatide induced a significantly larger increase in LS BMD and TBS than IBN (+7.6 % ± 6.3 vs. +2.9 % ± 3.3 and +4.3 % ± 6.6 vs. +0.3 % ± 4.1, respectively; P < 0.0001 for both). LS BMD and TBS were only weakly correlated at baseline (r (2) = 0.04) with no correlation between the changes in BMD and TBS over 24 months. CONCLUSIONS In postmenopausal women with osteoporosis, a 2-year treatment with teriparatide led to a significantly larger increase in LS BMD and TBS than IBN, suggesting that teriparatide had more pronounced effects on bone microarchitecture than IBN.

Necessary or unnecessary? a critical glance on spine surgery

Patients with complaints and symptoms caused by spinal degenerative diseases demonstrate a high rate of spontaneous improvement. Except of severe neurological symptoms such as high grade motor deficits, medically intractable pain and vegetative symptoms (cauda syndrome) operations require 1) symptoms, 2) a mechanical cause visible on imaging that sufficiently explains the symptoms, 3) a completed conservative treatment protocol performed over a 4) 6-12 week period. According to the evidence found in the literature, patients with lumbar disk herniation significantly benefit from surgery by a faster relieve of pain and return to social and professional activity, however, the results are converging after a period of 1-2 years. Surgery of lumbar spinal stenosis is considered a gold standard and superior to conservative care when symptoms are severe and leg pain is present. Bilateral microsurgical decompression using a bilateral or a unilateral approach with over-the-top decompression of the contralateral nerve root are superior to laminectomy as the decompression procedure. Lumbar fusion is only indicated in patients with spinal stenosis when a major or mobile spondylolisthesis is diagnosed. There is no indication of prophylactic surgery to avoid a "dangerous" deficit that might develop in the future.

Patient-rated Outcomes of Lumbar Fusion in Patients with Degenerative Disease of the Lumbar Spine: Does Age Matter?

Introduction: Current demographic changes are characterized by population aging, such that the surgical treatment of degenerative spine conditions in the elderly is gaining increasing relevance. However, there is a general reluctance to consider spinal fusion procedures in this patient age group due to the increased likelihood of complications. The aim of this study was to assess the patient-rated outcome and complication rates associated with lumbar fusion procedures in three different age groups. Methods: This was a retrospective analysis of prospectively collected data from consecutive patients who underwent first-time, one to three level posterior instrumented fusion between 2004 and 2011, due to degenerative disease of the lumbar spine. Data were obtained from our Spine Surgery Outcomes Database (linked to the International Spine Tango Register). Before surgery, patients completed the multidimensional Core Outcome Measures Index (COMI), and at 3 and 12 months after surgery they completed the COMI and rated the Global Treatment Outcome (GTO) and their satisfaction with care. Patients were divided into three groups according to their age: younger (≥50y <65y; n = 317), older (≥65y <80y; n = 350), and geriatric (≥ 80y; n = 40). Results: 707 consecutive patients were included. The preoperative comorbidity status differed significantly (p < 0.0001) between the age groups, with the highest scores in the geriatric group. General medical complications during surgery were lower in the younger age group (7%) than in the older (13.4%; p = 0.006) and geriatric groups (17.5%; p = 0.007). Duration of hospital stay was longer (p = 0.006) in the older group (10.8 ± 3.7 days) than the younger (10.0 ± 3.6 days) group. There were no significant group differences (p>0.05) for any of the COMI domains covering pain, function, symptom specific well-being, general quality of life, and social and work disability at either 3 months’ or 12 months’ follow-up. Similarly, there were no differences (p>0.05) between the age groups for GTO and patient-rated satisfaction at either follow-up. Conclusions: Preoperative comorbidity and general medical complications during lumbar fusion for degenerative disorders of the lumbar spine are both greater in geriatric patients than in younger patients. However, patient-rated outcome is as good in the elderly as it is in younger age groups. These data suggest that geriatric age per se is not a contraindication to instrumented fusion for lumbar degenerative disease.

Factor analysis of the North American Spine Society outcome assessment instrument: a study based on a spine registry of patients treated with lumbar and cervical disc arthroplasty.

Background context Studies involving factor analysis (FA) of the items in the North American Spine Society (NASS) outcome assessment instrument have revealed inconsistent factor structures for the individual items. Purpose This study examined whether the factor structure of the NASS varied in relation to the severity of the back/neck problem and differed from that originally recommended by the developers of the questionnaire, by analyzing data before and after surgery in a large series of patients undergoing lumbar or cervical disc arthroplasty. Study design/setting Prospective multicenter observational case series. Patient sample Three hundred ninety-one patients with low back pain and 553 patients with neck pain completed questionnaires preoperatively and again at 3 to 6 and 12 months follow-ups (FUs), in connection with the SWISSspine disc arthroplasty registry. Outcome measures North American Spine Society outcome assessment instrument. Methods First, an exploratory FA without a priori assumptions and subsequently a confirmatory FA were performed on the 17 items of the NASS-lumbar and 19 items of the NASS-cervical collected at each assessment time point. The item-loading invariance was tested in the German version of the questionnaire for baseline and FU. Results Both NASS-lumbar and NASS-cervical factor structures differed between baseline and postoperative data sets. The confirmatory analysis and item-loading invariance showed better fit for a three-factor (3F) structure for NASS-lumbar, containing items on “disability,” “back pain,” and “radiating pain, numbness, and weakness (leg/foot)” and for a 5F structure for NASS-cervical including disability, “neck pain,” “radiating pain and numbness (arm/hand),” “weakness (arm/hand),” and “motor deficit (legs).” Conclusions The best-fitting factor structure at both baseline and FU was selected for both the lumbar- and cervical-NASS questionnaires. It differed from that proposed by the originators of the NASS instruments. Although the NASS questionnaire represents a valid outcome measure for degenerative spine diseases, it is able to distinguish among all major symptom domains (factors) in patients undergoing lumbar and cervical disc arthroplasty; overall, the item structure could be improved. Any potential revision of the NASS should consider its factorial structure; factorial invariance over time should be aimed for, to allow for more precise interpretations of treatment success.

Influencing factors on the length of stay in lumbar spine surgery: analysis of the German spine registry

INTRODUCTION Spinal disc herniation, lumbar spinal stenosis and spondylolisthesis are known to be leading causes of lumbar back pain. The cost of low back pain management and related operations are continuously increasing in the healthcare sector. There are many studies regarding complications after spine surgery but little is known about the factors predicting the length of stay in hospital. The purpose of this study was to identify these factors in lumbar spine surgery in order to adapt the postoperative treatment. MATERIAL AND METHODS The current study was carried out as a post hoc analysis on the basis of the German spine registry. Patients who underwent lumbar spine surgery by posterior surgical access and with posterior fusion and/or rigid stabilization, whereby procedures with dynamic stabilization were excluded. Patient characteristics were tested for association with length of stay (LOS) using bivariate and multivariate analyses. RESULTS A total of 356 patients met the inclusion criteria. The average age of all patients was 64.6 years and the mean LOS was 11.9 ± 6.0 days with a range of 2-44 days. Independent factors that were influencing LOS were increased age at the time of surgery, higher body mass index, male gender, blood transfusion of 1-2 erythrocyte concentrates and the presence of surgical complications. CONCLUSION Identification of predictive factors for prolonged LOS may allow for estimation of patient hospitalization time and for optimization of postoperative care. In individual cases this may result of a reduction in the LOS.

Dendritic spine morphology determines membrane-associated protein exchange between dendritic shafts and spine heads.

The purpose of this study was to examine whether variability in the shape of dendritic spines affects protein movement within the plasma membrane. Using a combination of confocal microscopy and the fluorescence loss in photobleaching technique in living hippocampal CA1 pyramidal neurons expressing membrane-linked GFP, we observed a clear correlation between spine shape parameters and the diffusion and compartmentalization of membrane-associated proteins. The kinetics of membrane-linked GFP exchange between the dendritic shaft and the spine head compartment were slower in dendritic spines with long necks and/or large heads than in those with short necks and/or small heads. Furthermore, when the spine area was reduced by eliciting epileptiform activity, the kinetics of protein exchange between the spine compartments exhibited a concomitant decrease. As synaptic plasticity is considered to involve the dynamic flux by lateral diffusion of membrane-bound proteins into and out of the synapse, our data suggest that spine shape represents an important parameter in the susceptibility of synapses to undergo plastic change.

Clinical Use of Quantitative Computed Tomography–Based Finite Element Analysis of the Hip and Spine in the Management of Osteoporosis in Adults: the 2015 ISCD Official Positions—Part II

The International Society for Clinical Densitometry (ISCD) has developed new official positions for the clinical use of quantitative computed tomography (QCT)-based finite element analysis of the spine and hip. The ISCD task force for QCT reviewed the evidence for clinical applications and presented a report with recommendations at the 2015 ISCD Position Development Conference. Here we discuss the agreed upon ISCD official positions with supporting medical evidence, rationale, controversy, and suggestions for further study. Parts I and III address the clinical use of QCT of the hip, and the clinical feasibility of existing techniques for opportunistic screening of osteoporosis using CT scans obtained for other diagnosis such as colonography was addressed.

The 100 Most Influential Publications in Cervical Spine Research

STUDY DESIGN Bibliometric study of current literature. OBJECTIVE To identify and analyze the 100 most cited publications in cervical spine research. SUMMARY OF BACKGROUND DATA The cervical spine is a dynamic field of research with many advances made within the last century. However, the literature has never been comprehensively analyzed to identify and compare the most influential articles as measured by the number of citations. METHODS All databases of the Thomson Reuters Web of Knowledge were utilized in a two-step approach. First, the 150 most cited cervical spine studies up to and including 2014 were identified using four keywords. Second, all keywords related to the cervical spine found in the 150 studies (n = 38) were used to conduct a second search of the database. The top 100 most cited articles were hereby selected for further analysis of current and past citations, authorship, geographic origin, article type, and level of evidence. RESULTS Total citations for the 100 studies identified ranged from 173 to 879. They were published in the time frame 1952 to 2008 in a total of 30 different journals. Most studies (n = 42) were published in the decade 1991 - 2000. Level of evidence ranged from 1 to 5 with 39 studies in the level 4 category. 13 researchers were first author more than once and 9 researchers senior author more than once. The two step approach with a secondary widening of search terms yielded an additional 27 studies, including the first ranking article. CONCLUSIONS This bibliometric study is likely to include some of the most important milestones in the field of cervical spine research of the last 100 years. LEVEL OF EVIDENCE 3.

Spine radiography in the evaluation of back and neck pain in an orthopaedic emergency clinic

BACKGROUND AND OBJECTIVES Despite the recommendations of national and international societies for the treatment of patients with acute neck and back pain, still too many radiologic examinations were performed. The purpose of this study was to analyze and optimize diagnostics and treatment of patients with acute back pain. METHODS The medical records of 484 patients presented to the emergency clinic with acute neck or back pain were analyzed for clinical history, physical examination, radiographic findings and therapy. RESULTS Radiographs of the lumbar, cervical, or thoracic spine were performed in 338 cases (70%). Radiographs were normal in 142 patients (42%) and degenerative changes were identified in 123 patients (36%). Only 2 patients (0.4%) had radiographic findings that had direct therapeutic relevance: 1 patient with metastatic disease and 1 patient with posttraumatic C1-C2 instability. For most patients without sensorimotor deficits and absent specific indications for radiography (“red flags”), therapy was not affected by the results of radiography. CONCLUSIONS Plain radiography of the spine was unnecessary in most patients initially evaluated with non-specific acute back pain and does not improve the clinical outcome. The implementation of national and international guidelines is a slow process, but helps to reduce costs and to protect patients from unnecessary ionizing radiation exposure.