Long-Term Follow-Up of a Person-Centered Prehabilitation Program Based on Cognitive-Behavioral Physical Therapy for Patients Scheduled for Lumbar Fusion.

OBJECTIVE: Long-term follow-ups of prehabilitation programs for lumbar spine surgery are lacking, and more comprehensive evaluations are needed. In the current study, we evaluated the long-term effects of a prehabilitation program compared with conventional care in relation to lumbar fusion surgery in patients with degenerative disc disease. METHODS: Patients (n = 118) receiving lumbar fusion surgery were included in a multicenter randomized controlled trial, involving 1 university hospital and 2 spine clinics. The intervention was a person-centered prehabilitation program based on cognitive-behavioral physical therapy that targeted psychological presurgical risk factors, physical activity, and overall health. The control group received conventional preoperative care. Patient-reported outcome measures (PROMs) included assessments at 8 time-points: Low back disability (primary outcome), back pain intensity, leg pain intensity, pain catastrophizing, fear of movement, anxiety and depressive mood, health-related quality of life, and patient-specific functioning. Physical activity and physical capacity were assessed at 5 time points. Linear mixed models were used to analyze the effects of the intervention. RESULTS: There were no significant differences between groups at the 12- and 24-month follow-ups for any outcome, except for the One Leg Stand test 1 year following surgery, in favor of the control group. There were significant improvements for both groups, from baseline to the 12- and 24-month follow-ups for all physical capacity test and PROMs, except for leg pain and self-efficacy for exercise. CONCLUSIONS: No long-term effects were found for the prehabilitation program compared to conventional care. Physical activity did not improve over time, despite significantly improved self-reported functioning and physical capacity measurements. IMPACT: These findings have implications for the current understanding of the long-term effects of prehabilitation and suggest that future research should focus on programs promoting physical activity both before and after lumbar spine surgery to decrease the risk of long-term adverse health outcomes.

MRI evaluation of foraminal changes in the cervical spine with assistance of a novel compression device.

Standard supine Magnetic Resonance Imaging (MRI) does not acquire images in a position where most patients with intermittent arm radiculopathy have symptoms. The aim of this study was to test the feasibility of a new compression device and to evaluate image quality and foraminal properties during a Spurling test under MRI acquisition. Ten asymptomatic individuals were included in the study (6 men and 4 women; age range 27 to 55 years). First, the subjects were positioned in the cervical compression device in a 3 T MRI scanner, and a volume T2 weighted (T2w) sequence was acquired in a relaxed supine position (3 min). Thereafter, the position and compressive forces on the patient's neck (provocation position) were changed by maneuvering the device from the control room, with the aim to simulate a Spurling test, causing a mild foraminal compression, followed by a repeated image acquisition (3 min). A radiologist measured the blinded investigations evaluating cervical lordosis (C3-C7), foraminal area on oblique sagittal images and foraminal cross-distance in the axial plane. A total of three levels (C4-C7) were measured on the right side on each individual. Measurements were compared between the compressed and relaxed state. Reliability tests for inter- and intraclass correlation were performed. The device was feasible to use and well tolerated by all investigated individuals. Images of adequate quality was obtained in all patients. A significant increase (mean 9.4, p = 0.013) in the cervical lordosis and a decreased foraminal cross-distance (mean 32%, p < 0.001) was found, during the simulated Spurling test. The area change on oblique sagittal images did not reach a statistically significant change. The reliability tests on the quantitative measures demonstrated excellent intraobserver reliability and moderate to good interobserver reliability. Applying an individualized provocation test on the cervical spine, which simulates a Spurling test, during MRI acquisition was feasible with the novel device and provided images of satisfactory quality. MRI images acquired with and without compression showed changes in cervical lordosis and foraminal cross distance indicating the possibility of detecting changes of the foraminal properties. As a next step, the method is to be tested on symptomatic patients.

Characteristics and predicted outcome of patients lost to follow-up after degenerative lumbar spine surgery.

PURPOSE: The relatively large number of participants lost to follow-up (attrition) in spinal registers calls for studies that investigate the features of these individuals and their possible outcome. The aim was to explore the effect of attrition on patient-reported outcome in patients undergoing degenerative lumbar spine surgery. Three groups were studied: spinal stenosis (LSS), disc herniation (LDH) and degenerative disc disorder (DDD). METHODS: Patients who underwent surgery for degenerative lumbar spine conditions during 2008-2012 according to registration in the Swespine national register were eligible for the study. Non-respondents were registered in Swespine prior to surgery, but not at follow-up. Swespine data were merged with hospital data from seven Swedish regions (65% of the population), Statistics Sweden, the National Patient Register and the Social Insurance Agency. Baseline characteristics of non-respondents were described and compared to those of the respondents. Coefficients from regression analyses on PROM values for respondents were used to estimate the levels of PROM values for non-respondents, assuming the same effects of baseline characteristics for the two subgroups. Regression analyses were then conducted to identify variables associated with non-response. The results from the regression analyses were used to predict outcomes for patients with the characteristics of a non-respondent. Primary outcome variable in LSS and LDH was Global Assessment for leg pain, and in DDD, Global Assessment for back pain. RESULTS: Age, sex, educational level, smoking, living alone, being born outside the EU, previous spine surgery and unexpected events before follow-up were factors that were significantly associated with non-response. Being born inside, the EU was important in all of the studied groups (LSS: OR 0.61 p = < 0.000; LDH: OR 0.68 p = 0.001; DDD: OR 0.58 p = 0.04). For spinal stenosis patients, an unexpected event appeared particularly important (OR 3.40, p = 0.000). The predicted outcome of non-respondents was significantly worse than for respondents (LSS: 75.4% successful outcome vs. 78.7%; LDH: 53.9% vs. 58.2%; DDD: 62.7% vs. 67.5%. P-value in all groups = < 0.000). CONCLUSION: Attrition in Swespine cannot be ignored, as non-respondents were predicted to have worse outcome. The effect of attrition bias should always be considered when contemplating outcome recorded in a quality register with patients lost to follow-up.

ISSLS prize in clinical science 2020: the reliability and interpretability of score change in lumbar spine research.

PURPOSE: A statistically significant score change of a PROM (Patient-Reported Outcome Measure) can be questioned if it does not exceed the clinically Minimal Important Change (MIC) or the SDC (Smallest Detectable Change) of the particular measure. The aim of the study was to define the SDC of three common PROMs in degenerative lumbar spine surgery: Numeric Rating Scale (NRSBACK/LEG), Oswestry Disability Index (ODI) and Euroqol-5-Dimensions (EQ-5DINDEX) and to compare them to their MICs. The transition questions Global Assessment (GABACK/LEG) were also explored. METHODS: Reliability analyses were performed on a test-retest population of 182 symptomatically stable patients, with similar characteristics as the Swespine registry population, who underwent surgery for degenerative lumbar spine conditions 2017-2018. The MIC values were based on the entire registry (n = 98,732) using the ROC curve method. The ICC for absolute agreement was calculated in a two-way random-effects single measures model. For categorical variables, weighted kappa and exact agreement were computed. RESULTS: For the NRS, the SDC exceeded the MIC (NRSBACK:3.6 and 2.7; NRSLEG: 3.7 and 3.2, respectively), while they were of an equal size of 18 for the ODI. The gap between the two estimates was remarkable in the EQ-5DINDEX, where SDC was 0.49 and MIC was 0.10. The GABACK/LEG showed an excellent agreement between the test and the retest occasion. CONCLUSION: For the tested PROM scores, the changes must be considerable in order to distinguish a true change from random error in degenerative lumbar spine surgery research. These slides can be retrieved under Electronic Supplementary Material.

Innominate Salter osteotomy using resorbable screws: a retrospective case series and presentation of a new concept for fixation.

PURPOSE: The Salter innominate osteotomy (SIO) in children is traditionally stabilized by Kirschner-wires, which have issues regarding stability, infection and the need to be extracted. To counter these disadvantages, we present a surgical method to stabilize SIO with modern resorbable poly lactic-co-glycolic acid screws. Using a case series of 21 patients treated with SIO for developmental dysplasia of the hip or Legg-Calvé-Perthes disease we evaluate the feasibility of the method. METHODS: The integrity of the osteotomy was interpreted by radiological measurements of acetabular index, centre-edge angle and Reimer's index. Perioperative and postoperative complications were evaluated. RESULTS: Radiographic evaluation revealed a stable osteotomy and favourable development in all measured parameters with the exception of one patient who fell out of bed the first day postoperatively. No other perioperative surgical complications were observed and there were no local reactions to the resorbable screws. CONCLUSION: Modern resorbable screws carry multiple benefits both for the patient and the surgeon. In our case series the implants provided sufficient stability and the implants caused no local reactions. The use of resorbable implants gave the surgeon a wider range of possible screw placements and avoided the need for implant removal. LEVEL OF EVIDENCE: Level IV - Case series.

The importance of level stratification for quantitative MR studies of lumbar intervertebral discs: a cross-sectional analysis in 101 healthy adults.

PURPOSE: To investigate whether quantitative T2-times depend on lumbar intervertebral disc (IVD) level. METHODS: The lumbar spine (Th12/L1-L5/S1) of 101 participants (53.5% female, 30.0[± 3.6]years, 173.5[± 9.6]cm and 69.9[± 13.4]kg), without history of back pain, was examined on a 3T scanner with sagittal T2-mapping. All IVDs were stratified according to Pfirrmann grade and lumbar level, with mean T2-time determined for the entire IVD volume and in five subregions of interests. RESULTS: Significant level-dependent T2-time differences were detected, both for the entire IVD volume and its subregions. For the entire IVD volume, Pfirrmann grade 2 IVDs displayed 9-18% higher T2-times in Th12/L1 IVDs compared to L2/L3-L5/S1 IVDs (0.001 > p < 0.004) and significantly different T2-times in L1/L2-L2/L3 IVDs compared to most of the IVDs in the lower lumbar spine. In Pfirrmann grades 1, 3 and 4 IVDs, no significant level-dependent T2-time differences were observed for the entire IVD. More pronounced results were observed when comparing IVD subregions, with significant level-dependent differences also within Pfirrmann grade 1 and grade 3 IVDs. For example, in posterior IVD subregions mean T2-time was 80-82% higher in Th12/L1 compared to L3/L4-L4/L5 Pfirrmann grade 1 IVDs (p < 0.05) and 10-14% higher in L5/S1 compared to L3/L4-L4/L5 Pfirrmann grade 3 IVDs (0.02 > p < 0.001). DISCUSSION: Significant level-dependent T2-time differences within several Pfirrmann grades, both for the entire IVD volume and for multiple IVD subregions, were shown in this large cohort study. The T2-time differences between levels existed in both non-degenerated and degenerated IVDs. These findings show the importance of stratifying for lumbar level when quantitative IVD studies are performed using T2-mapping. These slides can be retrieved under Electronic Supplementary Material.

Follow-up of degenerative lumbar spine surgery-PROMs stabilize after 1 year: an equivalence study based on Swespine data.

PURPOSE: To evaluate the outcome of degenerative lumbar spine surgery in a credible way, patient-reported outcome measures (PROMs) should be assessed after an adequate follow-up period. Most authors/journals consider a follow-up period of less than two years to be too short. The purpose of this study was to explore the possibility of restricting follow-up to one year. METHODS: Adult patients operated between 1998 and 2017 were retrieved from Swespine (Lumbar Disc Herniation n = 31,314, Lumbar Spinal Stenosis n = 53,043 and Degenerative Disc Disease n = 14,375). The proportion reaching the minimal important change (MIC) in Visual Analogue Scale for pain (VASBACK/LEG), Oswestry Disability Index (ODI) and the quality-of-life measure EQ-5DINDEX at 1 and 2 years, respectively, was calculated. The single-item questions such as Global Assessment (GABACK/LEG) and Satisfaction were analysed by the McNemar test. Threshold values for a successful outcome based on the final scores of each PROM at 1 and 2 years post-surgery were also defined. RESULTS: For all the three diagnostic groups, the differences in proportions reaching MIC of each PROM at 1 and 2 years were below 2%. Global Assessment and Satisfaction with outcome at one year remained at 2 years. There were no important differences of threshold values of treatment success based on final scores CONCLUSION: No clinically important changes in PROMs appeared between 1 and 2 years after surgery for degenerative lumbar conditions, demonstrating that a follow-up period of 1 year as opposed to 2 years is sufficient in effectiveness studies if PROMs are to be used as outcome variables. These slides can be retrieved under Electronic Supplementary Material.

Determination of mechanical and rheological properties of a cell-loaded peptide gel during ECM production.

The development of an injectable biomaterial that supports cell survival and maintains or promotes nucleus pulposus (NP) phenotype could aid delivery of cells to degenerated NPs causing low back pain. Mesenchymal cells were loaded and grown in a synthetic peptide gel, PuraMatrix®. Cells were observed within the gels over 0-28 days, and accumulation of glycosaminoglycans were detected by histological staining. The mechanical properties of the cell-loaded constructs, and the change of the mechanical properties were studied using stress relaxation of the gels under compression and confinement. The PuraMatrix® gel was shown to relax fast on compression indicating that the fluid could easily flow out of the gel, and thus indicating the presence of large pores/voids. The presence of these pores/voids was further supported by high mobility of dextran molecules, determined using fluorescence recovery after photo bleaching. The stress required to deform the cell-loaded constructs to a specific strain increases at day 21, at which point the presence of glycosaminoglycans within the cell-loaded constructs was also observed. The results provide evidence of changes in mechanical properties of the PuraMatrix® matrix upon excretion of the extracellular matrix by the cells.

Low back pain patients and controls display functional differences in endplates and vertebrae measured with T2-mapping.

PURPOSE: The aim was to (1) verify our previous finding that endplates (EPs) display load-induced T2-changes, (2) investigate whether vertebrae display load-induced T2-changes and (3) investigate whether EPs and vertebrae in LBP patients and controls display T2-differences during conventional unloaded MRI and axial loaded MRI (alMRI). METHODS: Twenty-seven patients (mean 39 years) and 12 (mean 38 years) controls were examined with T2-mapping on a 1.5 T scanner during conventional unloaded MRI and subsequently during alMRI (Dynawell® loading device), separated by approximately 20 min. For determination of EP and vertebral T2-values, volumetric regions of interest were manually segmented. Each vertebra was then divided into half to obtain superior and inferior units. The presence of EP changes (visual inhomogeneity in the EP zone), Schmorl's nodules and Modic changes were registered. RESULTS: For conventional unloaded MRI, the T2-values in the superior and inferior vertebral units and the EPs were significantly higher in the patients compared with controls (p < 0.03, p < 0.006) even when adjusted for the presence of Modic changes, Schmorl's nodules and EP signal changes. alMRI induced significant changes in the superior EPs of the patients (p < 0.001). Additionally, the T2-value differed significantly between the superior and inferior EP, as well as between the superior and inferior vertebra with higher values in the inferior units (p < 0.001). CONCLUSION: This study demonstrated significantly higher EP and vertebral T2-values in LBP patients in comparison with controls. In addition, alMRI induced significant T2-changes in the superior EPs for patients but not for controls. Importantly, the T2-differences between the groups may indicate that EPs and vertebrae in LBP patients have altered biodynamical characteristics compared to controls and the higher T2-values measured in patients may represent early inflammation or impaired nutritional transport. These slides can be retrieved from electronic supplementary material.

Axial loading during MRI reveals deviant characteristics within posterior IVD regions between low back pain patients and controls.

PURPOSE: To investigate differences in functional intervertebral disk (IVD) characteristics between low back pain (LBP) patients and controls using T2-mapping with axial loading during MRI (alMRI). METHODS: In total, 120 IVDs in 24 LBP patients (mean age 39 years, range 25-69) were examined with T2-mapping without loading of the spine (uMRI) and with alMRI (DynaWell® loading device) and compared with 60 IVDs in 12 controls (mean age 38 years, range 25-63). The IVD T2-value was acquired after 20-min loading in five regions of interests (ROI), ROI1-5 from anterior to posterior. T2-values were compared between loading states and cohorts with adjustment for Pfirrmann grade. RESULTS: In LBP patients, mean T2-value of the entire IVD was 64 ms for uMRI and 66 ms for alMRI (p = 0.03) and, in controls, 65 ms and 65 ms (p = 0.5). Load-induced T2-differences (alMRI-uMRI) were seen in all ROIs in both patients (0.001 > p < 0.005) and controls (0.0001 > p < 0.03). In patients, alMRI induced an increase in T2-value for ROI1-3 (23%, 18% and 5%) and a decrease for ROI4 (3%) and ROI5 (24%). More pronounced load-induced decrease was detected in ROI4 in controls (9%/p = 0.03), while a higher absolute T2-value was found for ROI5 during alMRI in patients (38 ms) compared to controls (33 ms) (p = 0.04). CONCLUSION: The alMRI-induced differences in T2-value in ROI4 and ROI5 between patients and controls most probably indicate biomechanical impairment in the posterior IVD regions. Hence, alMRI combined with T2-mapping offers an objective and clinical feasible tool for biomechanical IVD characterization that may deepen the knowledge regarding how LBP is related to altered IVD matrix composition. These slides can be retrieved under Electronic Supplementary Material.

With axial loading during MRI diurnal T2-value changes in lumbar discs are neglectable: a cross sectional study.

BACKGROUND: Axial loading during MRI (alMRI) combined with T2 mapping recently was shown as a promising method to reveal biomechanical intervertebral disc (IVD) characteristics. This feasibility study aims to investigate whether there is a diurnal variation in the IVD T2-value when using alMRI. This is of importance for the planning of when to perform alMRI investigations and for interpretations of alMRI findings in relation to clinical symptoms. METHODS: Six healthy volunteers (30 lumbar discs), were examined with alMRI at three different sessions during 1 day. To be representative for a low back pain cohort in terms of age and IVD degeneration the included participants had a wide age range (27-63y) and all Pfirrmann grades represented. The T2-values were measured in five IVD regions of interest (ROI). The ROIs were equally large in sagittal plane with ROI1 representing anterior parts of the IVD, ROI5 posterior IVD parts and ROI2-4 the parts in between. RESULTS: T2-values of the entire IVD varied between 38 and 138 ms at 7 am, 33-143 ms at 11.30 am, and 31-147 ms at 4 pm with large regional IVD variations at all time points. No significant alterations of the T2-values over the day were found, neither for the entire IVD (p = 0.4) nor for the various ROIs (p = 0.2-1.0). Neither when correlated to Pfirrmann grade, any significant diurnal T2-value changes were found. CONCLUSIONS: With alMRI, only minor diurnal T2-value changes were found in the lumbar discs. Nonsignificant and neglectable diurnal changes are advantageous both for research purposes, as well as in the clinical setting, giving comparable and robust data regardless of at what time-point the alMRI is performed.

The value of patient global assessment in lumbar spine surgery: an evaluation based on more than 90,000 patients.

PURPOSE: There are two, principally different ways to obtain patient opinions regarding the outcome of spine surgery: using prospective multi-item questionnaires preoperatively and at follow-up, and using a retrospective single-item question at follow-up-both methods have distinct advantages and limitations. The purpose of the study was to explore the utility of using the simple transition question global assessment, GA, ("How is your back/leg pain today as compared to before the surgery?") as an overall patient-reported outcome measure (PROM) based on the large real-life database in the Swedish spine registry (Swespine). METHODS: The correlation between GA and the score-changes and the final scores at 1 year of follow-up for the PROMs VAS, ODI, and EQ-5D was examined. The correlations between GA and item-specific domains within the ODI, EQ-5D and SF-36 as well as the discriminative ability of PROMs with GA as reference criterion were also analysed. The cohort consisted of 94,132 patients registered in Swespine who were surgically treated for disc herniation, spinal stenosis or degenerative disc disease. RESULTS: The correlation coefficients for GA vs. the score-changes were lower than for GA vs final scores. For VAS they ranged for the different diagnosis groups from 0.33 to 0.61 and from 0.50 to 0.79, respectively. For ODI, the corresponding values ranged from 0.43 to 0.65 and 0.63 to 0.76; for the EQ-5D from 0.32 to 0.45 and 0.54 to 0.71. Further, GA showed a somewhat stronger correlation to pain-specific PROMs than to quality-of-life PROMs. CONCLUSIONS: The single-item outcome measure global assessment (GA) appears to be a feasible overall patient-reported outcome measure (PROM) and a useful reference for interpreting the scores of patient-reported outcome measures.

Lumbar surgery prior to total hip arthroplasty is associated with worse patient-reported outcomes.

AIMS: The aims of this study were to describe the prevalence of previous lumbar surgery in patients who undergo total hip arthroplasty (THA) and to investigate their patient-reported outcomes (PROMs) one year post-operatively. PATIENTS AND METHODS: Data from the Swedish Hip Arthroplasty Register and the Swedish Spine Register gathered between 2002 and 2012 were merged to identify a group of patients who had undergone lumbar surgery before THA (n = 997) and a carefully matched one-to-one control group. We investigated differences in the one-year post-operative PROMs between the groups. Linear regression analyses were used to explore the associations between previous lumbar surgery and these PROMs following THA. The prevalence of prior lumbar surgery was calculated as the ratio of patients identified with previous lumbar surgery between 2002 and 2012, and divided by the total number of patients who underwent a THA in 2012. RESULTS: The prevalence of lumbar surgery prior to THA in 2012 was 3.5% (351 of 10 082). Linear regression analyses showed an association with more pain (B = 4.35, 95% confidence interval (CI) 2.57 to 6.12), worse EuroQol (EQ)-5D index, (B = -0.089, 95% CI -0.112 to -0.066), worse EQ VAS (B = -6.75, 95% CI -8.58 to -4.92), and less satisfaction (B = 6.04, 95% CI 4.05 to 8.02). CONCLUSION: Lumbar spinal surgery prior to THA is associated with less reduction of pain, worse health-related quality of life, and less satisfaction one year after THA. This is useful information to share in the decision-making process and may help establish realistic expectations of the outcomes of THA in patients who also have previously undergone lumbar spinal surgery. Cite this article: Bone Joint J 2017;99-B:759-65.

The direction of human mesenchymal stem cells into the chondrogenic lineage is influenced by the features of hydrogel carriers.

Low back pain is a major public health issue in the Western world, one main cause is believed to be intervertebral disc (IVD) degeneration. To halt/diminish IVD degeneration, cell therapy using different biomaterials e.g. hydrogels as cell carriers has been suggested. In this study, two different hydrogels were examined (in vitro) as potential cell carriers for human mesenchymal stem cells (hMSCs) intended for IVD transplantation. The aim was to investigate cell-survival and chondrogenic differentiation of hMSCs when cultured in hydrogels Puramatrix® or Hydromatrix® and potential effects of stimulation with growth hormone (GH). hMSCs/hydrogel cultures were investigated for cell-viability, attachment, gene expression of chondrogenic markers SOX9, COL2A1, ACAN and accumulation of extracellular matrix (ECM). In both hydrogel types, hMSCs were viable for 28days, expressed integrin ß1 which indicates adhesion of hMSCs. Differentiation was observed into chondrocyte-like cells, in a higher extent in hMSCs/Hydromatrix® cultures when compared to hMSCs/Puramatrix® hydrogel cultures. Gene expression analyses of chondrogenic markers verified results. hMSCs/hydrogel cultures stimulated with GH displayed no significant effects on chondrogenesis. In conclusion, both hydrogels, especially Hydromatrix® was demonstrated as a promising cell carrier in vitro for hMSCs, when directed into chondrogenesis. This knowledge could be useful in biological approaches for regeneration of degenerated human IVDs.

Axial loading during MRI influences T2-mapping values of lumbar discs: a feasibility study on patients with low back pain.

PURPOSE: To investigate whether axial loading of the spine during MRI (alMRI) instantaneously induces changes in biochemical disc features as reflected by altered quantitative T2 values in patients with chronic low back pain (LBP). METHODS: T2 mapping was performed on 11 LBP patients (54 lumbar discs) during the conventional unloaded MRI and subsequent alMRI. Each disc was divided into five volumetric regions of interests (ROIs), anterior annulus fibrosus (AF) (ROI 1), the interface anterior AF-nucleus pulposus (NP) (ROI 2), NP (ROI 3), the interface NP-posterior AF (ROI 4), and the posterior AF (ROI 5). The mean T2 values for each ROI were compared between MRI and alMRI and correlated with degeneration grade (Pfirrmann), disc angle, and disc level. RESULTS: With alMRI, T2 values increased significantly in the whole disc as well as in various parts of the disc with an increase in ROI 1-3 and a decrease in ROI 5. The changes in T2 values correlated to degeneration grade, changes in disc angle, and lumbar level. CONCLUSION: alMRI instantaneously induces T2-value changes in lumbar discs and is, thus, a feasible method to reveal dynamic, biochemical disc features in patients with chronic LBP.

Bone material strength is associated with areal BMD but not with prevalent fractures in older women.

UNLABELLED: Reference point indentation is a novel method to assess bone material strength index (BMSi) in vivo. We found that BMSi at the mid-tibia was weakly associated with spine and hip areal bone mineral density but not with prevalent fracture in a population-based cohort of 211 older women. INTRODUCTION: Reference point indentation is a novel method to assess BMSi in vivo. Lower BMSi has been observed in patients with prior fracture than in controls, but no association between BMSi and areal bone mineral density (aBMD) has been found. Population-based association studies and prospective studies with BMSi and fractures are lacking. We hypothesized that BMSi would be associated with prevalent fractures in older Swedish women. The aim was to investigate the associations between BMSi, aBMD, and prevalent fracture in older women. METHODS: Two hundred eleven women, mean age 78.3 ± 1.1 years, were included in this cross-sectional, population-based study. BMSi was assessed using the OsteoProbe device at the mid-tibia. Areal BMD of the hip, spine, and non-dominant radius was measured using dual-energy X-ray absorptiometry (DXA). Fracture history was retrieved using questionnaires, and vertebral fractures were identified using vertebral fracture assessment (VFA) by DXA. RESULTS: One hundred ninety-eight previous fractures in 109 subjects were reported. A total of 106 women had a vertebral fracture, of which 58 women had moderate or severe fractures. An inverse correlation between BMSi and weight (r = -0.14, p = 0.04) was seen, and BMSi differed according to operator (ANOVA p < 0.01). Adjusting for weight and operator in a linear regression model, we found that BMSi was positively associated with aBMD of the total hip (ß = 0.14, p = 0.04), non-dominant radius (ß = 0.17, p = 0.02), and lumbar spine (L1-L4) (ß = 0.14, p < 0.05). Using logistic regression, we could not find any association in crude or adjusted BMSi (for age, weight, height, walking speed, calcium intake, smoking, bisphosphonate and glucocorticoid use, and operator) with prevalent fractures. CONCLUSION: We conclude that BMSi is associated with aBMD but not with prevalent fracture in a population-based cohort of 211 older women.

Indications of that migration of stem cells is influenced by the extra cellular matrix architecture in the mammalian intervertebral disk region.

Disk-degeneration is believed a major cause for lumbar pain. Previously, potential stem cell niches in the intervertebral disk (IVD) region, located adjacent to epiphyseal plate, was reported. The aim of the study was to examine migration of mesenchymal stem cells (MSCs), extracellular matrix (ECM) architecture in a potential cellular migration route (CMR; area located between the niche and IVD) and in the IVD in non-degenerated lapine- and in human degenerated IVD tissues. Human MSCs (n=3), human degenerated IVD tissues (n=10) and lapine IVDs (n=10) were collected. The samples were examined by immunohistochemistry for stem cell markers; CD90, OCT3/4, pre-chondrocytic marker; GDF5, catabolic markers; MMP9, MMP13, inflammatory marker; IL1R, cellular migration markers; SNAI1, SNAI2, adhesion markers; ß1-INTEGRIN and DDR2. In addition, gene-expression analyses (Real time PCR) were performed on additional samples. Further, time lapse studies were performed with hMSCs cultured on aligned COLL-I-fibers-coated glass-slides in DMEM-LG, 10% human serum containing fibroblast growth factor (bFGF). Presence of stem cells (CD90+, OCT3/4+), pre-chondocytic cells (GDF5+) and cells positive for migration markers (SNAI1+, SNAI2+), catabolic markers (MMP9+, MMP13+), inflammatory marker (IL1R+), adhesion markers (DDR2+, B1-INTEGRIN+) were detected (gene- and protein level) in investigated CMR and IVD regions. In the time lapse studies, MSCs alignment and protrusions were observed orientated in the same direction as collagen fibers. Results display influence of ECM collagen architecture and collagen fiber spatial direction on migration of stem cells. The results can be useful when developing tissue-engineering strategies for disk-degeneration.

Moderate physical exercise results in increased cell activity in articular cartilage of the knee joint in rats.

BACKGROUND: Moderate exercise regimens have shown minor positive effects on matrix turnover in articular cartilage (AC), while effects at cellular level, e.g. proliferation, are scarcely described. AIM: The aim of this study was to investigate the effects of moderate exercise on cell proliferation and recruitment of cells possibly active in regeneration in different regions of cartilage in the rat knee joint. METHODS: Eighteen rats were orally given 5-bromo-2-deoxyuridine (BrdU) for 14 days for in vivo DNA labeling. Nine rats underwent treadmill training for 50 min/day, 5 days/week (exercise group), and 9 rats served as controls (no exercise). Animals were sacrificed after 14, 56 and 105 days, and knee joints were harvested. BrdU+ cells were visualized immunohistochemically (IHC) and counted in AC, posterior stem cell niche (PN), potential migration route (PMR; area between PN and the AC border), potential migration area (PMA; region between PN and AC including PN) and epiphyseal cartilage plate (EP) of the tibia and femur. RESULTS: Compared to controls, in the exercise group BrdU+ cells/mm(2) were increased on days 14 (p = 0.022) and 105 (p = 0.045) in AC of the tibia and on day 105 (p = 0.014) in AC of the femur. BrdU+ cell numbers were increased in the PMR region of the tibia on days 14 (p = 0.023) and 105 (p = 0.0018) and in the PMR region of the femur on day 105 (p = 0.0099) as well as in the PMA region of the tibia (p = 0.0008) and femur (p = 0.0080) on day 105. No significant differences in BrdU+ cells/mm(2) were seen in PN or EP between the groups at any time point. Regarding collagen 2A1 expression and proteoglycan accumulation, no significant differences between groups were detected. CONCLUSIONS: The results indicate increased cell activity in AC in response to physical exercise and may help to understand the complexity of AC regeneration in the normal mammal knee joint.

Evoked thalamic neuronal activity following DRG application of two nucleus pulposus derived cell populations: an experimental study in rats.

PURPOSE: To investigate the effects on evoked thalamic neuronal activity of application of notochordal cells and chondrocyte-like cells derived from nucleus pulposus (NP) onto a dorsal root ganglion (DRG) and to compare these effects with a previously reported increased thalamic activity induced by NP. METHODS: Nucleus pulposus was harvested from tail discs of adult rats and the disc cells were separated into two cell populations, notochordal cells and chondrocyte-like cells. The two cell populations were applied separately, or in combination, to the L4 DRG of anaesthetised female Sprague-Dawley rats during acute electrophysiological experiments. In control experiments, cell suspension medium was applied on the DRG. Recordings from the contralateral thalamus were sampled for 40 min while electrically stimulating the ipsilateral sciatic nerve at above Aδ-fibre thresholds. RESULTS: Application of notochordal cells resulted in a decrease in evoked thalamic activity within 10 min while chondrocyte-like cells did not induce any changes during the 40 min of recording. The difference in evoked thalamic activity 40 min after notochordal and chondrocyte-like cell application, respectively, was statistically significant. Neither an increased concentration of chondrocyte-like cells alone nor a combination of the two cell populations induced any changes in thalamic activity. CONCLUSIONS: Separate exposure of the DRG to the two NP-derived cell populations induced different effects on evoked thalamic activity, but none of the tested cell samples induced an increase in neuronal activity similar to that previously observed with NP. This indicates a high complexity of the interaction between NP and nervous tissue.

Biocompatibility and resorption of a radiopaque premixed calcium phosphate cement.

Calcium phosphate cements (CPC) are used as bone void filler in various orthopedic indications; however, there are some major drawbacks regarding mixing, transfer, and injection of traditional CPC. By using glycerol as mixing liquid, a premixed calcium phosphate cement (pCPC), some of these difficulties can be overcome. In the treatment of vertebral fractures the handling characteristics need to be excellent including a high radio-opacity for optimal control during injection. The aim of this study is to evaluate a radiopaque pCPC regarding its resorption behavior and biocompatibility in vivo. pCPC and a water-based CPC were injected into a Ø 4-mm drilled femur defect in rabbits. The rabbits were sacrificed after 2 and 12 weeks. Cross sections of the defects were evaluated using histology, electron microscopy, and immunohistochemical analysis. Signs of inflammation were evaluated both locally and systemically. The results showed a higher bone formation in the pCPC compared to the water-based CPC after 2 weeks by expression of RUNX-2. After 12 weeks most of the cement had been resorbed in both groups. Both materials were considered to have a high biocompatibility since no marked immunological response was induced and extensive bone ingrowth was observed. The conclusion from the study was that pCPC with ZrO(2) radiopacifier is a promising alternative regarding bone replacement material and may be suggested for treatment of, for example, vertebral fractures based on its high biocompatibility, fast bone ingrowth, and good handling properties.