Attempted Suicide Is Independently Associated with Increased In-Hospital Mortality and Hospital Length of Stay among Injured Patients at Community Tertiary Hospital in Japan: A Retrospective Study with Propensity Score Matching Analysis.

Suicide is an increasingly important public healthcare concern worldwide. Studies examining the effect of attempted suicide on clinical outcomes among patients with trauma are scarce. We conducted a retrospective cohort study at a community emergency department in Japan. We included all severely injured patients with an Injury Severity Score > 15 from January 2002 to December 2021. The primary outcome measure was in-hospital mortality. The other outcome of interest was hospital length of stay. One-to-one propensity score matching was performed to compare these outcomes between suicide attempt and no suicide attempt groups. Of the 2714 eligible patients, 183 (6.7%) had trauma caused by a suicide attempt. In the propensity score-matched analysis with 139 pairs, the suicide attempt group showed a significant increase in-hospital mortality (20.9% vs. 37.4%; odds ratio 2.27; 95% confidence intervals 1.33-3.87) compared with the no suicide attempt group. Among survivors, the median hospital length of stay was significantly longer in the suicide attempt group than that in the no suicide attempt group (9 days vs. 12 days, p = 0.0076). Because of the unfavorable consequences and potential need for additional healthcare, increased attention should be paid to patients with trauma caused by a suicide attempt.

Ultrasound-based upper limb muscle thickness is useful for screening low muscularity during intensive care unit admission: A retrospective study.

BACKGROUND & AIMS: Malnutrition is associated with poor outcomes. Muscle mass is an important malnutrition indicator included in Global Leadership Initiative on Malnutrition (GLIM) criteria. Although bioelectrical impedance analysis and dual-energy X-ray absorptiometry are common muscle mass assessment methods, they are unreliable during intensive care unit (ICU) admission due to the influence of dynamic fluid changes. We hypothesized that ultrasound-based upper limb muscle assessment would be useful for assessing muscularity at ICU admission. METHODS: We retrospectively analyzed prospectively obtained ultrasound data from patients admitted to an ICU. We excluded patients without computed tomography (CT) imaging of the third lumbar vertebra within 2 days of ICU admission. Primary outcomes were the diagnostic utility of ultrasound-based upper limb muscle thickness for assessing low muscularity by CT. Low muscularity was defined as a skeletal muscle index of 36.0 cm2/m2 for males and 29.0 cm2/m2 for females at the cross-sectional area of the third lumbar vertebrae. Secondary outcomes of this study included the relationships between upper limb muscle thickness and biceps brachii muscle cross-sectional area, quadriceps femoris thickness, rectus femoris cross-sectional area. RESULTS: Among 64 patients assessed by ultrasound, 52 had CT examination records and were included in the analysis. The mean age was 70 ± 13 years, and the mean body mass index was 23.3 ± 4.2 kg/m2. Upper limb muscle thickness had the discriminative power to assess low muscularity at an area under the curve of 0.77 (95% CI [confidence interval], 0.63-0.91); the cutoff value (26.8 cm) had 84.6% sensitivity and 66.7% specificity. The upper limb muscle index had the discriminative power to assess low muscularity at an area under the curve of 0.80 (95% CI, 0.68-0.93); the cutoff value (9.9 mm/m2) had 76.9% sensitivity and 71.8% specificity. Upper limb muscle thickness was correlated with upper limb muscle cross-sectional area, quadriceps femoris muscle thickness, rectus femoris muscle cross-sectional area (r = 0.39-0.76, p < 0.01, n = 52). CONCLUSIONS: Ultrasound-based upper limb muscle thickness assessments can screen for low muscularity upon ICU admission.

Risk factors of the poor long-term prognosis of osteoporotic vertebral fractures: A multicenter cohort study.

INTRODUCTION: The presence of existing osteoporotic vertebral fracture (OVF) increases the mortality risk. However, the influence of the characteristics of OVF is unclear. This study aimed to investigate the influence of new OVF on patients' long-term prognosis using our past cohort study. METHOD: This is an extension study of our cohort study carried out between 2005 and 2007. In the present extension study, of 420 patients, 197 whose contact information was available at the 6-month follow-up were included in the telephone survey in 2018. Five patients refused to participate in the survey, and 82 could not be contacted. Eventually, 110 patients were enrolled. Of the Demographic data, radiological findings, medical history, and clinical outcome were investigated at injury onset and at the 6-month follow-up. A proportional hazard model was used to investigate the risk factors for mortality. RESULTS: Among 110 patients, 33 died. Male sex and low body mass index (BMI <18.5 kg/m2) were significant risk factors for mortality [hazard ratio (HR) = 6.40, 1.01-40.50; 5.24, 1.44-19.04, respectively]. The history of stroke and liver disease increased the risk of mortality (HR = 13.37, 1.93-92.7; 6.62, 1.15-38.14, respectively). As regards radiological findings, local kyphosis progression per 1° or ≥7° were significant risk factors of mortality (HR = 1.20, 1.06-1.36; 5.38, 1.81-16.03, respectively). CONCLUSIONS: A telephone survey at 12 years after the occurrence of OVF analyzed risk factors for mortality and showed that a progression of local kyphosis in fractures between injury onset and 6 months after injury was a risk factor of poor prognosis.

Relationship between number of radiological risk factors for delayed union after osteoporotic vertebral fracture and clinical outcomes.

This study demonstrated that number of three specific radiological risk factors (MR T2WI confined high-intensity pattern and diffuse low-intensity pattern, thoracolumbar vertebrae involvement, middle column injury) added prognostic information for delayed union, kyphotic deformity, and prolonged pain. PURPOSE: Delayed union after osteoporotic vertebral fracture (OVF) causes prolonged pain, QOL impairment, progression of collapse, kyphotic deformity, and neurologic impairment. Some specific radiological findings can be useful for predicting delayed union. We aimed to explore the prevalence and concomitance of various types of radiological risk factors for delayed union after osteoporotic vertebral fracture (OVF) and to assess the impact of risk factor number on clinical outcomes. METHODS: A total of 508 patients with fresh OVF from 25 institutes were evaluated. All patients were treated conservatively without surgical interventions. At the 6-month follow-up, the patients were classified into bone union and delayed union groups based on plain X-ray findings. We examined the presence and absence of three specific radiological risk factors (MR T2WI confined high-intensity pattern and diffuse low-intensity pattern, thoracolumbar vertebrae involvement, middle column injury) and analyzed clinical outcomes according to numbers of radiological risk factors. RESULTS: Delayed union was observed in 101 patients (19.9%) at the 6-month follow-up. The most common radiological risk factor was thoracolumbar vertebrae involvement (73.8%), followed by middle column injury (33.9%) and specific MRI findings (T2WI confined high-intensity pattern and diffuse low-intensity pattern) (29.7%). Overall, 85 (16.7%) patients had zero radiological risk factors, 212 (42.7%) had one, 137 (27.0%) had two, and 69 (13.6%) had three. When assessing the number of radiographic risk factors which included the MRI findings (the 3-risk factor method), the odds ratio for delayed union after acute OVF was 5.8 in the 2/3-risk factor group and 13.1 in the 3/3-risk factor group. Even when assessing the number of radiographic risk factors without MRI findings (2-risk factor method), the odds ratio was 3.2 in the 1/2-risk factor group and 10.2 in the 2/2-risk factor group. CONCLUSION: Number of radiological risk factors added prognostic information for delayed union, kyphotic deformity, and prolonged pain.

Impact of paravertebral muscle in thoracolumbar and lower lumbar regions on outcomes following osteoporotic vertebral fracture: a multicenter cohort study.

We investigated the effect of paravertebral muscle (PVM) on poor prognosis in osteoporotic vertebral fracture (OVF) and remaining lower back pain (LBP) in the thoracolumbar and lower lumbar regions. Additional OVF occurrence in the thoracolumbar and remaining LBP in the lumbar region was significantly related to PVM fat infiltration percentage. PURPOSE: Paravertebral muscle (PVM) is an important component of the spinal column. However, its role in the healing process after osteoporotic vertebral fracture (OVF) is unclear. This study aimed to clarify the effect of PVM in thoracolumbar and lower lumbar regions on OVF clinical and radiological outcomes. METHODS: This was a multicenter prospective cohort study from 2012 to 2015. Patients ≥ 65 years old who presented within 2 weeks after fracture onset were followed up for 6 months. PVM was measured at the upper edge of the L1 and L5 vertebral body in the magnetic resonance imaging (MRI) T2-axial position at registration. The cross-sectional area (CSA), relative CSA (rCSA), and fat infiltration percentage (FI%) were measured. Severe vertebral compression, delayed union, new OVF, and remaining low back pain (LBP) were analyzed. RESULTS: Among 153 patients who were followed up for 6 months, 117 with measurable PVM were analyzed. Their average age was 79.1 ± 7.2 years, and 94 were women (80.3%). There were 48 cases of severe vertebral compression, 21 delayed unions, 11 new OVF, and 27 remaining LBP. Among all poor prognoses, only the FI% of the PVM was significantly associated with new OVF (p = 0.047) in the thoracolumbar region and remaining LBP (p = 0.042) in the lumbar region. CONCLUSION: The occurrence of additional OVF in the thoracolumbar region and remaining LBP in the lumbar region was significantly related to the FI% of the PVM. Physicians should be aware that patients with such fatty degeneration shown in acute MRI may require stronger treatment.

Patient-reported outcomes for cervical disease in end-stage renal disease patients: Propensity matching analysis using volunteer data.

As the number of patients with end-stage renal disease (ESRD) has been increasing, the number of cervical spine surgeries for the patients with ESRD has also been increasing. The purpose is to identify the differences in cervical disease-specific patient-reported outcomes (PROs) between a healthy population and patients with ESRD, adjusting for subjects' age and physical activity. METHODS: The ESRD group included patients with ESRD who were treated with hemodialysis in our outpatient clinic and healthy volunteers were individuals who attended public health lectures. Volunteers with a history of cervical disease were excluded. All participants answered the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) and questionnaires that evaluate the disability in performing physical activities. RESULTS: A total of 111 participants were enrolled and divided into the ESRD group (n = 40) and the control group (n = 71). After adjusting for age and sex using propensity score, cervical function (p = 0.008), lower-extremity function (p = 0.007), and QOL (p < 0.001) in patients in the adjusted ESRD group were significantly lower than those in the control group. In multivariate linear regression, the use of hemodialysis was a significant variable that was negatively related to lower-extremity function (p = 0.004) and QOL (p = 0.011) independent of age and disability in performing physical activity. CONCLUSION: The ESRD was a significant negative factor of lower-extremity function and QOL, independent of age, sex, and disability in performing physical activity. These results can help understand the cervical status of patients with ESRD and adjust the goal for such patients after cervical surgery.

Association between MRI findings and back pain after osteoporotic vertebral fractures: a multicenter prospective cohort study.

BACKGROUND CONTEXT: Osteoprotic vertebral fractures (OVFs) are common in elderly people. The association between back pain due to OVF with magnetic resonance imaging (MRI) signal change is unclear. In this study we hypothesized that MRI findings would be a predictive factor for back pain measured by visual analogue scale (VAS) at 6 months follow-up. PURPOSE: The aim was to study the MRI findings that predict back pain after OVF and the association between radiological findings and scores of back pain. STUDY DESIGN: Multicenter prospective cohort study. PATIENT SAMPLE: A total of 153 OVF patients. OUTCOME MEASURE: The outcome measures were VAS back pain and MRI signal change. METHODS: This study was performed from 2012 to 2015. Consecutive patients with less than 2-week-old OVFs at 11 institutions were enrolled prospectively. MRI was performed at enrollment and at 1, 3, and 6 months follow-up. T1- and T2-weighted images (T1WI and T2W1) were obtained at each time point and their association with VAS scores of back pain at 6 months were investigated. Anterior compression ratio, posterior compression ratio, and angular motion of vertebral bodies were also measured on X-rays at each follow-up. This research had no financial support. There are no conflicts of interest. RESULT: The 6 months follow-up was completed by 153 patients. At enrollment, the average VAS score of back pain was 75 mm, and it had improved at the 6-month follow-up to an average score of 20 mm. There was a significant correlation between T1 diffuse low signal change and VAS scores at the 6-month follow-up (p<.01). T2 high signal changes (odds ratio; 4.01, p<.01) and old vertebral fractures (odds ratio; 2.47, p=.04) were independent risk factors for back pain. The correlation between angular motion of vertebrae on X-rays and the VAS score of back pain was significant at all time points. CONCLUSION: This study demonstrates the radiological factors associated with persistent back pain after an OVF and the association between the VAS score of back pain and radiological findings. In addition, T2 high signal changes in acute phase and old vertebral fractures were independent risk factors for residual back pain.

The degeneration of adjacent intervertebral discs negatively influence union rate of osteoporotic vertebral fracture: A multicenter cohort study.

BACKGROUND: With the increasing aging population in developed countries, there has been an associated increased prevalence of osteoporotic vertebral fracture (OVF). Many previous reports have attempted to predict the risk of delayed union associated with OVF. However, the role of endplate failure and the degeneration of adjacent intervertebral discs, and their association with delayed union has received little attention. The aim of this study was to evaluate the endplate fracture and disc degeneration rank as risk factors for delayed union. MATERIALS AND METHODS: Two hundred and eighteen consecutive patients with fresh OVF were enrolled in the study. MRI and X-ray were performed at the time of enrollment and at the 6 months follow-up. The MR images were used to assess the degeneration grade of adjacent intervertebral discs (using the modified Pfirrmann grading system), and endplate failure. Supine and weight-bearing radiographs were used to define angular motion and compression ratio of the anterior vertebral body wall. RESULTS: A total of 139 patients (112 female, 27 male) completed the 6 month follow-up (a 65.1% follow-up rate). The study revealed 27 cases of delayed union (19.4%). A healthier adjacent caudal disc with low grade degeneration was found to be associated with an increased risk of delayed union (P = 0.008). Bi-endplate injury and significant compression of the anterior vertebral body wall were significantly associated with delayed union (P = 0.019, and P = 0.001 respectively). Rapid progression of the adjacent cranial disc degeneration was observed at the end of the 6 month follow-up period (P = 0.001). CONCLUSION: Modified Pfirrmann grading system revealed that a healthier adjacent intervertebral disc at the caudal level and bi-endplate fracture were significantly associated with an increased risk of delayed union. These findings may influence the management strategy for patients with OVF.

Difference of clinical course between cases with bone union and those with delayed union following osteoporotic vertebral fractures.

In this prospective multicenter study of osteoporotic vertebral fractures (OVFs), delayed union of OVF at 6-month follow-up caused prolonged pain, QOL impairment, ADL impairment, cognitive status deterioration, and vertebral collapse progression. PURPOSE: Delayed union following osteoporotic vertebral fracture displayed as an intravertebral cleft on plain X-rays was reported to be a factor for prolonged severe pain. However, the difference of clinical course between bone union and delayed union cases still remains unclear. The purpose of this study was to identify how OVF delayed union following conventional conservative treatment influences the clinical course with a prospective multicenter study. METHODS: A total of 324 OVF patients from 25 institutes in Osaka, Japan, were included in the study. At the 6-month follow-up after initial visit to each institute, the patients were classified into bone union and delayed union groups based on plain X-ray findings. The outcome assessments included a VAS for back pain, SF-36 for quality of life (QOL), severity of bed-ridden state for activities of daily living (ADL), MMSE for cognitive functions, and degree of vertebral collapse on plain X-rays. RESULTS: Overall, 280 patients were included into the union group and 44 into the delayed union group. The VAS score at 6 months was significantly worse in the delayed union group (p = 0.01). The scores for the SF-36 scales of physical functioning and bodily pain at 6 months were significantly lower in the delayed union group (p = 0.019, p = 0.01, respectively). The percentage of nearly or completely bed-ridden patients was significantly higher in the delayed union group. The percentage of newly developed cognitive impairment was significantly higher in the delayed union group (p = 0.02). Progression of vertebral collapse during the 6-month follow-up was more pronounced in the delayed union group (p < 0.01). CONCLUSION: The present results revealed that delayed union following OVF causes prolonged pain, QOL impairment, ADL impairment, cognitive status deterioration, and vertebral collapse progression.

Characterizing the course of back pain after osteoporotic vertebral fracture: a hierarchical cluster analysis of a prospective cohort study.

This study demonstrated four distinct patterns in the course of back pain after osteoporotic vertebral fracture (OVF). Greater angular instability in the first 6 months after the baseline was one factor affecting back pain after OVF. PURPOSE: Understanding the natural course of symptomatic acute OVF is important in deciding the optimal treatment strategy. We used latent class analysis to classify the course of back pain after OVF and identify the risk factors associated with persistent pain. METHODS: This multicenter cohort study included 218 consecutive patients with ≤ 2-week-old OVFs who were enrolled at 11 institutions. Dynamic x-rays and back pain assessment with a visual analog scale (VAS) were obtained at enrollment and at 1-, 3-, and 6-month follow-ups. The VAS scores were used to characterize patient groups, using hierarchical cluster analysis. RESULTS: VAS for 128 patients was used for hierarchical cluster analysis. Analysis yielded four clusters representing different patterns of back pain progression. Cluster 1 patients (50.8%) had stable, mild pain. Cluster 2 patients (21.1%) started with moderate pain and progressed quickly to very low pain. Patients in cluster 3 (10.9%) had moderate pain that initially improved but worsened after 3 months. Cluster 4 patients (17.2%) had persistent severe pain. Patients in cluster 4 showed significant high baseline pain intensity, higher degree of angular instability, and higher number of previous OVFs, and tended to lack regular exercise. In contrast, patients in cluster 2 had significantly lower baseline VAS and less angular instability. CONCLUSIONS: We identified four distinct groups of OVF patients with different patterns of back pain progression. Understanding the course of back pain after OVF may help in its management and contribute to future treatment trials.

Risk factors for cognitive decline following osteoporotic vertebral fractures: A multicenter cohort study.

BACKGROUND: Osteoporotic vertebral fractures (OVFs) are the most common cause of intractable back pain and reduced activities of daily living (ADL), which may affect cognitive function. However, no previous studies have reported a change in cognitive function after OVFs. The purpose was to reveal cognitive function changes after OVFs and investigate the risk factors for cognitive decline. METHODS: Consecutive patients with symptomatic OVFs were enrolled in a prospective multicenter cohort study. The inclusion criteria were age >65 years, diagnosis of acute or subacute OVF, and back pain onset within 2 months prior to presentation. Cognitive function was assessed with the mini-mental state examination. Medical history, radiological findings, and ADL were investigated as risk factors for cognitive decline. RESULTS: We recruited a sample of 339 patients (58 men and 281 women) who met the inclusion criteria. Patients underwent examinations and completed questionnaires at both the time of enrollment and at 6-month follow-up. At 6-month follow-up, cognitive decline was observed in 26 (7.7%) patients. Medical history, including comorbidities and sports activities, did not affect odds ratios (ORs). However, elevated ORs were associated with delayed union (OR: 4.67, 95% Confidence interval: 1.22-17.87). In addition, significantly increased ORs were associated with reduced ADL at 6-month follow-up. CONCLUSIONS: The current results revealed the incidence of cognitive decline after the onset of OVF. Delayed union and reduced ADL at 6-month follow-up were associated with cognitive decline. Patients with cognitive decline experienced significantly reduced quality of life. These results highlight the importance of preventing cognitive impairment in patients with symptomatic OVF. Physical treatment or early surgical treatment may provide appropriate options, particularly for patients with suspected delayed union.

New Predictive Index for Lumbar Paraspinal Muscle Degeneration Associated With Aging.

STUDY DESIGN: A cross-sectional imaging study of paraspinal muscle degeneration using a new index for easy evaluation. OBJECTIVE: To examine the natural progression of age-related changes in the lumbar paraspinal muscles and to verify the validity of our new index for evaluating paraspinal muscle degenerationSUMMARY OF BACKGROUND DATA.: Measurement of paraspinal muscle morphology is an effective method for reflecting atrophy and fat infiltration, but it is complicated to perform. Therefore, we focused on the groove between lumbar paraspinal muscles as a simple index for evaluating paraspinal muscle degeneration. METHODS: A total of 160 subjects aged 10 to 88 years (10 male and 10 female subjects in each decade) with lumbar lordosis of more than 20° were included. Body mass index (BMI) was calculated. Sagittal T2-weighted magnetic resonance imaging (MRI) was used to measure lumbar lordosis, while axial T2-weighted MRI was used to measure cross-sectional area (CSA) and fat infiltration rate of the paraspinal muscles at the intervertebral disc level from L1 to L5. To quantify the depth of the groove between the paraspinal muscles, our own image index (lumbar indentation value (LIV): equal to the length of the bulge of the muscle to the attachment of the spinous process), also was measured. We then determined the correlation between LIV and paraspinal muscle degeneration. RESULTS: There were no significant differences in BMI and lumbar lordosis between age groups. CSA of the paraspinal muscles tended to decrease with age, and fat infiltration rate increased with age. There was a negative correlation between CSA and fat infiltration rate at all levels (r = -0.474 to -0.634). LIV decreased significantly with age and strongly correlated with CSA at all levels (r = 0.709-0.789). CONCLUSION: Our new index is a simple and effective parameter for evaluating paraspinal muscle degeneration associated with aging. LEVEL OF EVIDENCE: 4.

Impact of initial conservative treatment interventions on the outcomes of patients with osteoporotic vertebral fractures.

STUDY DESIGN: Prospective multicenter study. OBJECTIVE: To examine whether initial conservative treatment interventions for osteoporotic vertebral fractures (OVF) influence patient outcomes. SUMMARY OF BACKGROUND DATA: OVFs have been described as stable spinal injuries and, in most cases, are managed well with conservative treatment. However, systematic treatments for OVF have not been clearly established. METHODS: A total of 362 patients with OVF (59 males and 303 females; mean age, 76.3 yr) from 25 institutes were enrolled in this clinical study. All the patients were treated conservatively without any surgical interventions. The patient outcomes were evaluated 6 months after the fractures on the basis of Short Form-36 (SF-36) physical component summary (PCS) and mental component summary (MCS), activities of daily living (the Japanese long-term care insurance system), back pain (visual analogue scale), cognitive status (mini-mental state examination), and vertebral collapse, which were used as response variables. Furthermore, brace type, hospitalization, bisphosphonates after injury, and painkillers after injury were explanatory variables for the treatment interventions. To evaluate the independent effects of treatment interventions on patient outcomes, we performed multivariate logistic regression analyses and obtained odds ratios that were adjusted for the potential confounding effects of age, sex, level of fracture, presence of middle-column injury, pain visual analogue scale at enrollment, mini-mental state examination score at enrollment, and previous use of steroids. RESULTS: There was no significant difference for treatment intervention factors including brace type, hospitalization, bisphosphonates after injury, and painkillers after injury. For adjusting factors, the presence of middle-column injury was significantly associated with SF-36 PCS ≤ 40, reduced activities of daily living, prolonged back pain, and vertebral collapse. Female sex and advanced age were associated with SF-36 PCS ≤ 40. Low mini-mental state examination scores at enrollment were associated with SF-36 PCS ≤ 40 and reduced activities of daily living. The previous use of steroids was associated with SF-36 MCS ≤ 40, prolonged back pain, and vertebral collapse. No other examined variables were significant risk factors for patient outcomes. CONCLUSION: These results showed that treatment intervention factors did not affect patient outcomes 6 months after OVF. Middle-column injury was a significant risk factor for both clinical and radiological outcomes. In the future, establishing systematic treatments for cases with middle-column injuries is needed. LEVEL OF EVIDENCE: 2.

Prognostic factors for reduction of activities of daily living following osteoporotic vertebral fractures.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: To elucidate the prognostic factors indicating reduced activities of daily living (ADL) at the time of the 6-month follow-up after osteoporotic vertebral fracture (OVF). SUMMARY OF BACKGROUND DATA: OVF has severe effects on ADL and quality of life (QOL) in elderly patients and leads to long-term deteriorations in physical condition. Many patients recover ADL with acceleration of bony union and spinal stability, but some experience impaired ADL even months after fracture. Identifying factors predicting reduced ADL after OVF may prove valuable. METHODS: Subjects in this prospective study comprised 310 OVF patients from 25 institutes. All patients were treated conservatively without surgery. Pain, ADL, QOL, and other factors were evaluated on enrollment and at 6 months. ADL were evaluated using the criteria of the Japanese long-term care insurance system to evaluate the degree of independence. We defined reduced ADL as a reduction of at least single grade at 6 months after fracture and investigated factors predicting reduced ADL after OVF, using uni- and multivariate regression analysis. RESULTS: ADL were reduced at 6 months after OVF in 66 of 310 patients (21.3%). In univariate analysis, age more than 75 years (P = 0.044), female sex (P = 0.041), 2 or more previous spine fractures (P = 0.009), presence of middle column injury (P = 0.021), and lack of regular exercise before fracture (P = 0.001) were significantly associated with reduced ADL. In multivariate analysis, presence of middle column injury (odds ratio [OR], 2.26; P = 0.022) and lack of regular exercise before fracture (OR, 2.49; P = 0.030) were significantly associated with reduced ADL. CONCLUSION: These results identified presence of middle column injury of the vertebral body and lack of regular exercise before fracture as prognostic factors for reduced ADL. With clarification and validation, these risk factors may provide crucial tools for determining subsequent OVF treatments. Patients showing these prognostic factors should be observed carefully and treated with more intensive treatment options.

Local delivery of siRNA using a biodegradable polymer application to enhance BMP-induced bone formation.

Small interfering RNA (siRNA) is useful tool for specific and efficient knockdown of disease-related genes. However, in vivo applications of siRNA are limited due to difficulty in its efficient delivery to target cells. In this study, we investigated the efficacy of a biodegradable hydrogel, poly-d,l-lactic acid-p-dioxanone-polyethylene glycol block co-polymer (PLA-DX-PEG), as a siRNA carrier. PLA-DX-PEG pellets with or without fluorescein-labeled dsRNA were implanted into mouse dosal muscle pouches. The cellular uptake of dsRNA surround the polymer was confirmed by fluorescent microscopy. The fluorescence intensity was dose-dependent of the dsRNA, and exhibited a time-dependent decrease. To investigate its biological efficiency, noggin (antagonoist to BMPs) gene-silencing with siRNA (siRNA/Noggin) was examined by the amount of suppression of BMP-2-induced noggin expression and the level of performance of BMP, indicated by ectopic bone formation. Noggin gene expression induced by BMP-2 was suppressed by addition of siRNA/Noggin to the implant, and the ectopic bone formation induced by implants with both BMP-2 and siRNA/Noggin was significantly greater than those induced by implants with BMP-2 alone. These results indicate the efficacy of local delivery of siRNAs by PLA-DX-PEG polymer, which intensified bone-inducing effects of BMP and promoted new bone formation by suppressing gene expression of Noggin.

Characteristic radiographic or magnetic resonance images of fresh osteoporotic vertebral fractures predicting potential risk for nonunion: a prospective multicenter study.

STUDY DESIGN: Prospective multicenter study. OBJECTIVE: To identify radiographic or magnetic resonance (MR) images of fresh vertebral fractures that can predict a high risk for delayed union or nonunion of osteoporotic vertebral fractures (OVFs). SUMMARY OF BACKGROUND DATA: Vertebral body fractures are the most common fractures in osteoporosis patients. Conservative treatments are typically chosen for OVFs, and associated back pain generally subsides within several weeks with residual persistent deformity of the vertebral body. In some patients, OVF healing is impaired and correlated with prolonged back pain. However, assessments such as plain radiograph or MR images taken during the early phase to predict high risks for nonunions of OVFs and/or poor prognoses have not been identified. METHODS: A total of 350 OVF patients from 25 institutes were enrolled in this clinical study. Plain radiograph and MR images of the OVFs were routinely taken at enrollment at the respective institutes. The findings on the plain radiograph and MR images were classified after enrollment in the study. All the patients were treated conservatively without any surgical intervention. After a 6-month follow-up, the patients were classified into two groups, a union group and a nonunion group, depending on the presence of an intravertebral cleft on plain radiograph or MR images. The associations of the images from the first visit with those of the corresponding nonunions at the 6-month follow-up were analyzed by multivariate logistic regression to elucidate specific image characteristics that may predict a high risk for nonunion of OVFs. RESULTS: Forty-eight patients (49 vertebrae) among the 350 patients (363 vertebrae) were classified as nonunions, indicating a nonunion incidence of 13.5% for conventional conservative treatments for OVFs. The statistical analyses revealed that a vertebral fracture in the thoracolumbar spine, presence of a middle-column injury, and a confined high intensity or a diffuse low intensity area in the fractured vertebrae on T2-weighted MR images were significant risk factors for nonunion of OVFs. CONCLUSION: The results of this study revealed significant relationships between plain radiograph and MR images of acute phase OVFs and the incidence of nonunion. As these risk factors are defined more clearly and further validated, they may become essential assessment tools for determining subsequent OVF treatments. Patients with one or more of the earlier-described risk factors for nonunion should be observed carefully and provided with more intensive treatments.

Low back pain in patients treated surgically for scoliosis: longer than sixteen-year follow-up.

STUDY DESIGN: A retrospective study. OBJECTIVE: To evaluate long-term outcome regarding low back pain (LBP) in patients treated surgically for scoliosis. SUMMARY OF BACKGROUND DATA: Measures of long-term outcome after surgery for scoliosis have focused mainly on radiologic changes. However, subjective symptoms such as LBP after surgical treatment are of great concern to patients who undergo surgical treatment for scoliosis. METHODS: Thirty-two patients treated surgically for scoliosis between 1976 and 1989 were included in this study. The mean duration of follow-up was 21.1 years. Eighteen patients had adolescent idiopathic scoliosis, 8 had congenital scoliosis, and 6 had symptomatic scoliosis. We evaluated long-term outcome by direct interview. Degree of LBP was evaluated by visual analogue scale score and Moskowitz classification in addition to clinical and radiologic evaluation. Patients were also asked to complete the SF-36 questionnaire. RESULTS: Mean visual analogue scale score at the latest follow-up was 21 (0-80), and 15% of patients had occasional or frequent LBP in Moskowitz classification. On the SF-36, score for bodily pain was not markedly different from that for age-matched controls. Among radiologic findings, level of distal fusion had no effect on the incidence or severity of LBP. Furthermore, preoperative Cobb angle, latest Cobb angle, and degenerative changes of subjacent segment each exhibited no correlation with degree of LBP, either. On the other hand, sagittal balance was a factor affecting LBP following scoliosis surgery. CONCLUSION: We evaluated long-term outcomes regarding LBP following scoliosis surgery. Regardless of residual back deformity, LBP was found to be no more frequent than in the normal population in Japan. Positive sagittal balance at the latest follow-up was a factor significantly contributing to LBP following scoliosis surgery.

Quality of life in patients treated surgically for scoliosis: longer than sixteen-year follow-up.

STUDY DESIGN: A retrospective study. OBJECTIVE: To evaluate the long-term quality of life (QOL) of patients treated surgically for scoliosis. SUMMARY OF BACKGROUND DATA: Measures of long-term outcome after surgery for scoliosis have focused mainly on radiologic changes. However, QOL issues such as working status and marital status are the subjects of greatest concern for patients who will undergo surgical treatment for scoliosis. METHODS: Thirty-two patients treated surgically for scoliosis between 1976 and 1989 were included in this study. The mean duration of follow-up was 21.1 years. Eighteen patients had adolescent idiopathic scoliosis, 8 congenital scoliosis, and 6 symptomatic scoliosis. We evaluated long-term outcome by direct interview with patients. Working status, marital status, and childbearing were determined in addition to clinical and radiologic evaluation. Patients were also asked to fill out the short form (SF)-36 and Scoliosis Research Society (SRS)-22 questionnaires. RESULTS: Twenty-seven patients (84.4%) were or had been engaged in various occupations without marked difficulty. Although none of the male patients was married, 62.5% of the female patients were married. Half of the female patients had delivered babies after surgery, and the mean number of such children was 1.83. On the SF-36, none of the scores for subjects with idiopathic or congenital scoliosis were markedly different from those for age-matched healthy controls. Multivariate logistic regression analysis revealed that marked preoperative Cobb angle and positive sagittal balance at the most recent follow-up were significantly associated with increased odds ratio for poor scores on the SRS-22. CONCLUSION: We evaluated long-term QOL in patients treated surgically for scoliosis, and found that it was not impaired, particularly in the case of patients with idiopathic or congenital scoliosis. Larger preoperative Cobb angle and positive sagittal balance at the most recent follow-up were related to poor outcome in QOL as assessed by the SRS-22.

Factors affecting neurological deficits and intractable back pain in patients with insufficient bone union following osteoporotic vertebral fracture.

The purpose of this study was to examine factors affecting the severity of neurological deficits and intractable back pain in patients with insufficient bone union following osteoporotic vertebral fracture (OVF). Reports of insufficient union following OVF have recently increased. Patients with this lesion have various degrees of neurological deficits and back pain. However, the factors contributing to the severity of these are still unknown. A total of 45 patients with insufficient union following OVF were included in this study. Insufficient union was diagnosed based on the findings of vertebral cleft on plain radiography or CT, as well as fluid collection indicating high-intensity change on T2-weighted MRI. Multivariate logistic regression analysis was performed to determine the factors contributing to the severity of neurological deficits and back pain in the patients. Age, sex, level of fracture, duration after onset of symptoms, degree of local kyphosis, degree of angular instability, ratio of occupation by bony fragments, presence or absence of protrusion of flavum, and presence or absence of ossification of the anterior longitudinal ligament (OALL) in the adjacent level were used as explanatory variables, while severity of neurological deficits and back pain were response variables. On multivariate analysis, factors significantly affecting the severity of neurological deficits were angular instability of more than 15 degrees [adjusted odds ratio (OR), 9.24 (95% confidence interval, CI 1.49-57.2); P < 0.05] and ratio of occupation by bony fragments in the spinal canal of more than 42% [adjusted OR 9.23 (95%CI 1.15-74.1); P < 0.05]. The factor significantly affecting the severity of back pain was angular instability of more than 15 degrees [adjusted OR 14.9 (95%CI 2.11-105); P < 0.01]. On the other hand, presence of OALL in the adjacent level reduced degree of back pain [adjusted OR 0.14 (95%CI 0.03-0.76); P < 0.05]. In this study, pronounced angular instability and marked posterior protrusion of bony fragments in the canal were factors affecting neurological deficits. In addition, marked angular instability was a factor affecting back pain. These findings are useful in determining treatment options for patients with insufficient union following OVF.

RNA interference for noggin enhances the biological activity of bone morphogenetic proteins in vivo and in vitro.

Noggin is a major extracellular antagonist to bone morphogenetic proteins (BMPs) which binds to BMPs and blocks binding of them to BMP-specific receptors and negatively regulates BMP-induced osteoblastic differentiation. In this study, we investigated the effect of noggin silencing by transfection of small interfering RNA (siRNA) on BMP-induced osteoblastic differentiation in vitro and ectopic bone formation in vivo induced by recombinant human BMP-2 (rhBMP-2). Noggin mRNA expression was up-regulated in response to rhBMP-2 in C2C12 cells, a myoblastic cell line, in dose- and time-dependent fashion as determined by real-time RT-PCR assay. Silencing of noggin expression by transfection of noggin siRNA suppressed BMP-stimulated noggin expression, resulting in acceleration of BMP-induced osteoblastic differentiation. For in vivo noggin silencing, siRNA was injected locally into back muscles and transfected into local cells by electroporation, where rhBMP-2-retaining (5 microg) collagen disks had been surgically placed. The implants were harvested at 2 weeks after surgery from experimental and control group mice and analyzed by radiological and histological methods. As a result, bone mineral content of ossicles ectopically induced by rhBMP-2 was significantly increased by silencing of noggin. Our findings suggest that silencing of noggin enhances the osteoblastic differentiation of BMP-responding cells in vitro and new bone formation induced by rhBMP-2 in vivo by eliminating negative regulation of the effects of BMP. RNA interference might be useful for intensifying the effects of BMP in promoting new bone (callus) formation in repair of damaged bone.