Potential of whole-body dual-energy X-ray absorptiometry to predict muscle size of psoas major, gluteus maximus and back muscles.

BACKGROUND: Measurement of trunk muscle cross-sectional area (CSA) using axial magnetic resonance imaging (MRI) is considered clinically meaningful for understanding several spinal pathologies, such as low back pain and spinal sagittal imbalance. However, it remains unclear whether trunk muscle mass (TMM) measured using dual-energy X-ray absorptiometry (DXA) can predict the trunk muscle CSA. The aim of this study is to determine if DXA-derived TMM is associated and predicts with CSA of paraspinal muscles and gluteus maximus measured using MRI in healthy volunteers. METHODS: A total of 48 healthy volunteers underwent whole-body DXA and MRI of the spinopelvic region. The CSA of the psoas major, back muscles, and gluteus maximus were measured on axial MRI. Correlations and linear regressions between the TMM measured using DXA and the CSA of each musculature were investigated. RESULTS: There was a weak correlation between TMM and CSA of the psoas major in men (r = 0.39, P = 0.0678), and the linear regression was y = 301.74x - 401.24 (R2 = 0.2976, P = 0.0070). A moderate correlation was found in women (r = 0.58, P = 0.0021), and the linear regression was y = 230.21x - 695.29 (R2 = 0.4445, P = 0.0003). Moderate correlations were observed between TMM and CSA of the back muscles in both men (r = 0.63, P = 0.0012) and women (r = 0.63, P = 0.0007), the linear regression was y = 468.52x + 3688.5 (R2 = 0.5505, P < 0.0001) in men and y = 477.39x + 2364.1 (R2 = 0.564, P < 0.0001) in women. There was a strong correlation between TMM and CSA of the gluteus maximus in men (r = 0.72, P < 0.0001), and the linear regression was y = 252.69x - 880.5 (R2 = 0.6906, P < 0.0001). A moderate correlation was found in women (r = 0.69, P < 0.0001), and the linear regression was y = 230.74x - 231.32 (R2 = 0.6542, P < 0.0001). CONCLUSIONS: The DXA-derived TMM was able to predict the CSA of the psoas major, back muscles, and gluteus maximus, and significantly correlated with the CSA of the back muscles and gluteus maximus. It might be a safer and cheaper alternative for evaluating the size of the back muscles and gluteus maximus.

Effect of pre-operative HbA1c and blood glucose level on the surgical site infection after lumbar instrumentation surgery.

BACKGROUND: This study aims to investigate the effect of pre-operative hemoglobin A1c (HbA1c) and pre-operative blood glucose control on the rate of surgical site infection (SSI) after posterior lumbar instrumentation surgery in diabetes mellitus (DM) patients. METHODS: A total of 1046 patients who had undergone posterior lumbar instrumentation surgery were reviewed. Based on pre-operative HbA1c, patients were divided into three groups: non-DM group, low HbA1c group (HbA1c < 7.0 % in DM) and high HbA1c group (≥7.0). As well, based on the status of blood glucose control in DM patients immediately before surgery, patients were divided into two groups: good control group (post-prandial blood glucose [PBG] < 200 mg/dl) and poor control group (≥200). The rate of SSI was compared among these groups. RESULTS: SSI occurred in 1.9 % in non-DM group, 2.4 % in low HbA1c group, and 9.3 % in high HbA1c group. Compared with non-DM group, high HbA1c group had significantly higher rate of SSI (p = 0.001). There was not statistically different between non-DM and low HbA1c groups (p = 0.550). SSI occurred in 2.2 % in good control group, and 10.2 % in poor control group. The rate of SSI was significantly lower in good control group (p = 0.013). CONCLUSION: This study showed that the rate of SSI after posterior lumbar instrumentation surgery tend to be higher in DM patients with high HbA1c. However, the rate might be reduced to the same level as that of non-DM group by lowering PBG to <200 mg/dl immediately before surgery.

Posterior lumbar fusion surgery doesn't change sexual activities in patients with lumbar degenerative disease: an observational study.

BACKGROUND: There are few studies about sexual function in the patient with posterior lumbar spinal fusion for degenerative lumbar disease. The aim of this study is to investigate sexual activities in patients with lumbar degenerative disease before and after lumbar fusion surgery. METHODS: We recruited 35 patients who underwent lumbar spinal fusion at the age of 55 years or younger. They were 17 men and 18 women with a mean age of 47.4 years. After informed consent, the patients were asked to complete anonymous questionnaire concerning sexual desire, activity, and satisfaction before and after surgery. RESULTS: In the presick period, 69% of the patients had sexual desire, and 79% achieved satisfaction during sexual activity. Lumbar degenerative disease decreased sexual desire and frequency of sexual activity in 40%, and 74% respectively. Before surgery, satisfaction in sexual activities decreased in 53%, and 55% of the patients felt discomfort during sexual activity. Adjustment in sexual position was required in 44% of man and 54% of woman. After surgery, Sexual desire, frequency of sexual activity and satisfaction did not regain after surgery in 94%, 93% and 92%, respectively. Those who did not feel discomfort after surgery was significantly lower VAS in both low back pain and leg pain than the patients felt discomfort (low back pain; p = 0.024, leg pain; p = 0.046). CONCLUSION: This study demonstrated that lumbar degenerative diseases decreased sexual desire, frequency of sexual activity and satisfaction, and little of the patients regained their sexual activities after posterior lumbar fusion surgery in the middle-aged patients.

Characteristics of older patients with postmenopausal osteoporosis who developed loss of muscle mass during the COVID-19 pandemic - a case-control study.

BACKGROUND: Under the restriction of social activities during the coronavirus disease 2019 (COVID-19) pandemic, there was concern about the loss of muscle mass due to a decrease in physical activity for the elderly. The purpose of this study was to investigate the characteristics of older patients with postmenopausal osteoporosis who developed loss of muscle mass during the COVID-19 pandemic in Japan. METHODS: A total of 54 patients with postmenopausal osteoporosis were evaluated in this study. Whole-body dual-energy X-ray absorptiometry was performed pre- and post-COVID-19 pandemic to measure trunk and lower limb muscle mass. At the time of the post-COVID-19 pandemic, we conducted a survey to compare lifestyle before pandemic (the frequency of going out, the frequency of meeting acquaintances or families living apart, regular exercise habits, walking time, family structure), and comorbidities between the muscle mass loss (ML) group and the muscle mass maintenance (MM) group. The ML group consisted of patients with at least a 5% decrease in lower limb muscle mass or trunk muscle mass. RESULTS: A significant difference was found only for the family structure (P = 0.0279); in the ML group, those living alone were the largest group, while in the MM group they were the smallest group. CONCLUSIONS: The ML group was significantly more likely to live alone than the MM group. The current study showed that loss of muscle mass was more common in patients living alone.

Dyslipidemia as a novel risk for the development of symptomatic ossification of the posterior longitudinal ligament.

BACKGROUND CONTEXT: Obesity and visceral fat have been implicated as potential factors in the pathogenesis of the ossification of the posterior longitudinal ligament (OPLL); the details of the factors involved in OPLL remain unclear. PURPOSE: We aimed to determine the association between dyslipidemia and symptomatic OPLL. STUDY DESIGN: Single institution cross-sectional study. PATIENT SAMPLE: Data were collected from Japanese patients with OPLL (n=92) who underwent whole-spine computed tomography scanning. Control data (n=246) without any spinal ligament ossification were collected from 627 Japanese participants who underwent physical examination. OUTCOME MEASURES: Baseline information and lipid parameters, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) from fasting blood samples were collected to assess the comorbidity of dyslipidemia. METHODS: Patient data were collected from 2020 to 2022. Patients with dyslipidemia were defined as those who were taking medication for dyslipidemia and who met one of the following criteria: TG ≥150 mg/dL, LDL-C ≥140 mg/dL, and/or HDL-C <40 mg/dL. The factors associated with OPLL development were evaluated using multivariate logistic regression analysis. RESULTS: The comorbidity of dyslipidemia in the OPLL group was more than twice that in the control group (71.7% and 35.4%, respectively). The mean body mass index (BMI) of the OPLL group was significantly higher than that of the control group (27.2 kg/m2 and 23.0 kg/m2). Multivariate logistic regression analysis revealed that dyslipidemia was associated with the development of OPLL (regression coefficient, 0.80; 95% confidence interval, 0.11-1.50). Additional risk factors included age, BMI, and diabetes mellitus. CONCLUSIONS: We demonstrated a novel association between dyslipidemia and symptomatic OPLL development using serum data. This suggests that visceral fat obesity or abnormal lipid metabolism are associated with the mechanisms of onset and exacerbation of OPLL as well as focal mechanical irritation due to being overweight.

Clinical outcomes of short-segment lumbar fusion in patients older than 85 years with a minimum 2-year follow-up.

OBJECTIVE: Although the number of elderly patients requiring lumbar fusion for lumbar degenerative disorders has increased over time, the postoperative outcomes of lumbar fusion in very elderly patients (> 85 years) remains unknown. This study aimed to evaluate the comprehensive outcomes of lumbar fusion in elderly patients older than 85 years with mid-term follow-up. METHODS: The authors retrospectively researched patients older than 85 years who underwent single- or double-level posterior lumbar interbody fusion or transforaminal lumbar interbody fusion from 2012 to 2019. Twenty-nine patients who had at least 2 years of follow-up were included in this study. The average age was 86.4 years, and the average follow-up period was 42.2 months. Each patient was matched with 60- to 75-year-old controls. The Oswestry Disability Index (ODI) score; Roland-Morris Disability Questionnaire (RMDQ) score; Japanese Orthopaedic Association (JOA) score; JOA recovery rate; and low-back pain (LBP), leg pain, and leg numbness visual analog scale (VAS) scores were obtained. The spinopelvic parameters were measured using lateral standing radiographs of the whole spine. RESULTS: Although there were no significant differences in the ODI, RMDQ, JOA recovery rate, and leg pain and leg numbness VAS scores at 2 years postoperatively between the very elderly and control groups, the VAS LBP score was significantly lower in the very elderly group than in the control group. Preoperative and postoperative sagittal vertical axes were significantly higher and sacral slopes were significantly lower in the very elderly group than in the control group. The incidences of postoperative delirium and new lumbar vertebral fracture were significantly higher in the very elderly group (17.2%) than in the control group (4.6%). CONCLUSIONS: This study showed that lumbar fusion could be performed in patients older than 85 years with satisfactory postoperative outcomes at the 2-year follow-up. In contrast, progressive spinopelvic sagittal imbalance, the incidence of lumbar vertebral fracture up to the final follow-up, and postoperative delirium were greater in the very elderly group than in the control group.

Patterns of Vertebral Bone Marrow Edema in the Normal Healing Process of Lumbar Interbody Fusion: Baseline Data for Diagnosis of Pathological Events.

STUDY DESIGN: Retrospective investigation using a prospectively collected database. OBJECTIVE: To examine the appearance and characteristics of vertebral bone marrow edema (BME) in the normal healing of lumbar interbody fusion. SUMMARY OF BACKGROUND DATA: Although BME in pathological spinal conditions has been well-documented, the patterns and characteristics of BME in the normal healing process of spinal fusion remains unexplored. MATERIALS AND METHODS: We reviewed imaging from 225 patients with normal healing following posterior lumbar interbody fusion or transforaminal lumbar interbody fusion. BME was identified on magnetic resonance imaging at the third postoperative week and categorized with respect to its appearance, including assessment of area and extension within the relevant vertebrae. RESULTS: Three hundred eighty-nine of the 450 instrumented vertebrae (86.4%) displayed evidence BME. All instances of BME were associated with the area of contact with the endplate. The average extent of BME was 32.7±1.0%. BME within normal healing following interbody fusion could be categorized into four types: no edema (13.6%), anterior corner (36.6%), around-the-cage focal (48.0%), and diffuse (1.8%). Anterior corner BME was significantly associated with instances of single cage placement than in dual cages (42.6% vs. 24.7%, P =0.0002). Single cages had a significantly higher rate of BME than dual cages (92.0% vs. 75.3%, P <0.0001). The extent of BME was significantly greater in the single cage cohort (36.9% vs. 24.2% in dual cages, P <0.0001). CONCLUSIONS: This serves as the first study demonstrating the patterns of BME associated with normal healing following lumbar interbody fusion procedures. Anterior corner BME and around-the-cage focal BME were the most common patterns encountered, with diffuse BME a relatively rare pattern. These findings might contribute to the better differentiation of postoperative pathological events from normal healing following lumbar interbody fusion. LEVEL OF EVIDENCE: 4.

Characteristics of the Patients with Poor Clinical Outcomes After Symptomatic Postoperative Lumbar Epidural Hematoma.

OBJECTIVE: Symptomatic postoperative lumbar epidural hematoma (PLEH) may lead to poor outcomes even after evacuation. This study aimed to verify the short-term clinical outcomes after the evacuation of PLEH and to clarify the characteristics of the patients with poor postoperative outcomes. METHODS: Twenty-five patients (average age; 70.4 years) underwent PLEH evacuation after lumbar spine surgery. The mean follow-up period was 12.0 (range 3-37) months. Pre and postoperative Japanese Orthopedic Association scores and visual analog scale (VAS) of low back pain (LBP), leg pain, and leg numbness were retrospectively collected. The dural sac cross-sectional area at the most compressed level was measured on magnetic resonance imaging. The patients were classified into 2 groups: poor outcome group (P group) had less than 50% of Japanese Orthopedic Associationrecovery rate and good group (G group) with 50% or more recovery rate. RESULTS: The rate of delayed evacuation (over 24 hours of onset) was significantly higher in P group than in G group (P = 0.027). There was no significant difference in dural sac cross-sectional areabetween the 2 groups (P = 0.438). VAS of LBP, leg pain, and leg numbness in G group significantly improved postoperatively. Although VAS of LBP and leg pain in P group significantly improved postoperatively, there was no significant difference between the pre and postoperative VAS of leg numbness. CONCLUSIONS: Delayed evacuation of PLEH can lead to poor postoperative outcomes after lumbar spine surgery. Moreover, patients with poor outcomes remained with postoperative leg numbness. Early evacuation of symptomatic PLEH is key to avoid poor outcomes and persistent leg numbness.

Pre-existing adjacent level foraminal stenosis does not affect the outcome of a single level lumbar interbody fusion.

BACKGROUND: The aim of this study was to investigate whether or not pre-existing asymptomatic neuroforaminal stenosis adjacent to the fusion level develops adjacent segment disease (ASD) after single-level lumbar interbody fusion. SUMMARY AND BACKGROUND DATA: Risk factors of ASD after spinal fusion have been well investigated, but there have been few studies focused on the relationship between ASD and pre-existing asymptomatic neuroforaminal stenosis. METHODS: A total of 302 patients who had undergone a single-level lumbar interbody fusion were reviewed at a minimum of 2 year follow-up. They were 109 men and 193 women with a mean age of 68.8 years. Follow-up periods was averaged 53.5 months. ASD was defined as neurological deterioration related to adjacent segment pathologies which required an additional surgery. Based on the pathologies, patients were divided into three categories: ASD due to foraminal stenosis (ASD-FS), ASD due to central stenosis (ASD-CS), and ASD due to herniated disc (ASD-HD). Measured variables were age, gender, diagnosis, BMI, decompression procedures at adjacent segments, preoperative anterior/posterior slip, asymptomatic neuroforaminal stenosis, facet tropism, and postoperative spinopelvic parameters. RESULTS: Thirty-eight patients (12.6%) developed ASD. There were 15 patients with ASD-FS, 18 patients with ASD-CS, and five patients with ASD-HD. Lumbar lordosis (LL) and sacral slope (SS) were significantly smaller and pelvic tilt (PT) was significantly larger in ASD-FS. Asymptomatic neuroforaminal stenosis was detected preoperatively in 33.3% of the ASD-FS group, and 18.6% of non-ASD group; the incidence was not significantly different. CONCLUSIONS: Adjacent-level neuroforaminal stenosis was not a significant risk of ASD after single-level lumbar interbody fusion, and might not need to be fused if asymptomatic.

Perioperative Complications of Open Spine Surgery in Older Adults over 90 Years of Age.

Introduction: Despite perioperative risks in nonagenarian patients who undergo open spine surgery for degeneration disorder or spinal trauma being of great interest, the prevalence of complications in this group remains unclear. This study aims to examine the perioperative complications of open spine surgery in the elderly over 90 years of age. Methods: Preoperative and intraoperative characteristics including the American Society of Anesthesiologists Physical Status (ASA-PS) class, type of surgery, and complications within 30 postoperative days were retrospectively collected from the medical records of nonagenarians who underwent open spine surgery between April 2004 and July 2019 at our spine centers. Results: A total of 48 patients met the inclusion criteria of this study. All belong to ASA-PS class 2 (69%) or 3. Preoperative American Spinal Injury Association Impairment Scale grades in trauma group were grade A in 4 cases, B in 1 case, C in 5 cases, D in 11 cases, and E in 1 case. Major complications (deep surgical site infection, cardiac event, respiratory disorder, gastrointestinal hemorrhage, and renal failure) occurred in 13 cases, and the rate of overall perioperative complications was 45.8%. One patient who underwent cervical stabilization for cervical fracture dislocation died at postoperative 13 days due to respiratory disorder. The rates of major complications and overall perioperative complications were 3.6% and 14.3% in the degenerative group and 45.5% and 81.8% in the trauma group, respectively. Especially in the trauma group, respiratory disorder occurred in 7 cases, delirium in 11 cases, and urinary tract infection in 5 cases. Conclusions: Although the perioperative complication rate reached 81.8% in spinal trauma cases, the complication rate in degenerative disorders was relatively low as 14.3%. Open spine surgery for degenerative disorders can be relatively safe even in nonagenarians, whereas the risks of perioperative complications, including respiratory disorder and delirium, were high in spinal trauma cases.

Radiobrominated probe targeting activated p38α in inflammatory diseases.

OBJECTIVE: p38α, a member of the mitogen-activated protein kinase superfamily, is activated by external stimuli, followed by nuclear translocation for the regulation of inflammatory responses at the transcriptional and translational levels in inflammatory diseases. Thus, activated p38α would be an appropriate target molecule for in vivo noninvasive imaging and targeted radionuclide therapy. For this purpose, we designed a radiobrominated compound, 6-(4-[77Br]bromo-2-fluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)-pyrido[2,3-d]pyrimidin-7(8H)-one ([77Br]4-BR), based on a potent p38α selective inhibitor, R1487, for use with single-photon emission computed tomography. We synthesized [77Br]4-BR and evaluated its effectiveness as an activated p38α imaging probe compared with our previous radioiodinated probe (6-(2-fluoro-4-[125I]iodophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)-pyrido[2,3-d]pyrimidin-7(8H)-one ([125I]4-IR)) in a mouse inflammatory model. METHODS: We designed [77Br]4-BR by replacing the radioiodine of [125I]4-IR or the fluorine of R1487 with radiobromine at the 4-position of the phenoxy ring. We synthesized 4-BR via a four-step process. The inhibitory potency of 4-BR was measured using an ADP-Glo™ kinase assay system. Radiosynthesis of [77Br]4-BR was performed via an organotin-radiobromine exchange reaction using the corresponding tributyltin precursor. Radioactivity biodistribution was evaluated in normal ddY mice and turpentine oil-induced inflammation model mice for 120 min after intravenous administration of [77Br]4-BR. The temporal changes in radioactivity in blood fractions were compared between [77Br]4-BR and [125I]4-IR. RESULTS: 4-BR was synthesized at a total yield of 9.1% and showed a p38α inhibitory potency similar to that of 4-IR. [77Br]4-BR was successfully obtained from a tributyltin precursor with high radiochemical yield (89.9%), purity (95.9%), and molar activity (2.0 TBq/µmol). [77Br]4-BR showed accumulation of high radioactivity in the inflamed tissue (3.4% ± 0.9% ID/g, peaking at 15 min), rapid delivery throughout the body, and rapid blood clearance with approximately half of the blood radioactivity existing as an intact form at 60 min. Although the maximum radioactivity accumulation in inflamed tissue after [77Br]4-BR administration was approximately half that of [125I]4-IR because of its faster blood clearance and lower free fraction in the input function, the inflamed tissue-to-blood ratio was comparable between [77Br]4-BR and [125I]4-IR. CONCLUSIONS: [77Br]4-BR would be a promising imaging agent for detecting activated p38α in inflammatory diseases.

Trends of Spine Surgeries during the First COVID-19 Semi-Lockdown: Survey in a Non-Epidemic Region in Japan.

Introduction: In the early phase of the coronavirus disease 2019 (COVID-19) pandemic, the importance of triaging surgeries was suggested to reduce burdens on the existing health system and maintaining service. The governor declared a state of emergency and requested that residents avoid going out unnecessarily (semi-lockdown) for the entire prefecture including our medical region from February 28 until May 25, 2020. However, for several spine patients, a significant delay in care may result in the progression of extremity weakness and pain. This study aimed to investigate trends of spine surgeries during the first COVID-19 semi-lockdown in the nonepidemic region in Japan. Methods: Spine surgeries performed in our institution from February 28 until May 25 between 2017 and 2020 were retrospectively reviewed and analyzed. We compared the number of spine surgeries and types of surgical spine pathologies between 2017 and 2019: previous years and 2020: a COVID-19 year. Results: The mean number of spine surgeries performed in previous years was 121 cases, and the number of spine surgeries performed in a COVID-19 year was 109 cases. The percentage of urgent surgeries was 19.6% in previous years versus 37.6% in a COVID-19 year; the difference was statistically significant (P<0.05). Among the urgent surgical spine pathologies, the prevalence of cauda equina or severe nerve root compression leading to progressive neurological deterioration or intractable pain was 20.2% in a COVID-19 year, which was significantly higher than 12.4% in previous years (P<0.05). Conclusions: The first COVID-19 semi-lockdown in Japan led to a decrease in elective cases and an increase in urgent cases and might affect progressive neurological deterioration for some spine patients even in a nonepidemic region.

Clinical Outcomes and Postoperative Radiographic Assessment of Osteoplastic Hemilaminectomy in the Treatment of Lumbar Foraminal Nerve Root Compression.

INTRODUCTION: Osteoplastic hemilaminectomy for the treatment of lumbar foraminal nerve root compression is a safe technique as the exiting nerve root can be directly observed during neuroforaminal decompression without spinal fusion. Moreover, this procedure allows anatomical reconstruction of the posterior elements. However, there might be a potential risk for the progression of lumbar segmental instability after performing this procedure. This study aimed to review the radiographic and clinical outcomes of osteoplastic hemilaminectomy for the treatment of lumbar foraminal nerve root compression. METHODS: We retrospectively reviewed 51 patients who underwent osteoplastic hemilaminectomy with a minimum follow-up of 2 years. The clinical outcomes were evaluated using the visual analog scale (VAS) for low back pain, leg pain, and numbness and the Japanese Orthopaedic Association (JOA) score. Lumbar segmental instability was evaluated as a radiographic assessment using functional radiography. The mean follow-up period was 65 months. RESULTS: The preoperative VASs for low back pain, leg pain, and numbness were 46±31, 72±26, and 43±34, respectively, which were improved to 24±23, 19±23, and 19±23, respectively. The JOA score was also improved from 14±5 to 22±4. Three patients (5.9%) were reoperated due to recurrent disc herniation within 2 years following surgery. In addition, three patients (5.9%) developed postoperative lumbar segmental instability but did not require additional surgery. CONCLUSIONS: The current study revealed that 94.1% of the patients who underwent osteoplastic hemilaminectomy achieved a significant improvement in the clinical outcomes and did not require additional surgery within 2 years following the procedure. Over a 5-year follow-up on average, 5.9% of the subjects developed postoperative lumbar segmental instability; however, they have maintained acceptable clinical conditions.

Close association between non-alcoholic fatty liver disease and ossification of the posterior longitudinal ligament of the spine.

Ossification of the posterior longitudinal ligament (OPLL) of the spine is a disease of unknown etiology occurring frequently in individuals with metabolic disturbances. Obesity has been suggested as a potential risk factor for the severity of OPLL. We aimed to investigate whether non-alcoholic fatty liver disease (NAFLD) is associated with OPLL severity. We assessed the severity of NAFLD by a liver-to-spleen (L/S) ratio on computed tomography (CT) scans of 85 symptomatic OPLL patients at a single institution in Japan. We also assessed the severity of OPLL by CT reconstruction sagittal and axial images. The prevalence of NAFLD in middle-aged patients (age < 70 years, n = 50) was 80.3%, which was 2.5-8 times higher than that in the general Japanese population (9-30%). The ossification index of the spinal ligaments increased in proportion to the severity of fatty liver. The L/S ratio was revealed as a significant risk factor associated with the total ossification index (standardized ß: -0.40, 95% confidence interval - 54.34 to - 4.22). This study suggests the potential contribution of NAFLD to the progression of OPLL. The close association between NAFLD and OPLL demonstrated in this study warrants further study to elucidate the causal nature of this relationship.

Development of radioiodinated pyrimidinopyridone derivatives as targeted imaging probes of activated p38α for single photon emission computed tomography.

OBJECTIVE: p38α, a member of the mitogen-activated protein kinase superfamily, is ubiquitously expressed in a variety of mammalian cells. Activated p38α induces inflammatory responses to external stimuli, suggesting that non-invasive detection of activated p38α would be valuable for diagnosing inflammatory diseases. For this purpose, we designed radiolabeled compounds [123I]2-IR and [123I]4-IR based on a potent p38α selective inhibitor R1487 for use with single photon emission computed tomography (SPECT). In this study, we used 125I instead of 123I due to its more usable radiochemical properties, synthesized [125I]2-IR and [125I]4-IR, and evaluated their effectiveness as activated p38α imaging probes. METHODS: [123I]2-IR and [123I]4-IR were designed by introduction of a 123I atom at the 2- or 4-ositions of the phenoxy ring, preserving the pyrimidinopyridone structure of R1487. We synthesized 2-IR and 4-IR via a 7-step process. The inhibitory potencies of 2-IR, 4-IR, and p38α inhibitors were measured using an ADP-Glo™ kinase assay system. Radioiodination of 2-IR and 4-IR was performed via an organotin-radioiodine exchange reaction using the corresponding tributyltin precursors. Biodistributions were evaluated by determining radioactivity in tissues of interest after intravenous administration of [125I]2-IR and [125I]4-IR in normal ddY mice and turpentine oil-induced inflammation model mice. In vivo inhibition study was also performed in inflammation model mice after intravenous administration of [125I]4-IR with pretreatment of p38α inhibitors. RESULTS: We synthesized 2-IR and 4-IR at total yields of 17.5% and 19.2%, respectively. 4-IR had higher p38α inhibitory potency than 2-IR; both compounds were significantly less potent than R1487. [125I]2-IR and [125I]4-IR were successfully obtained from tributyltin precursors with high radiochemical yield (> 65%), purity (> 97%), and molar activity (~ 81 GBq/µmol). [125I]4-IR showed high radioactivity accumulation in the inflamed tissue (7.0 ± 1.2%D/g), rapid delivery throughout the body, and rapid blood clearance, resulting in a high inflammation-to-blood ratio (6.2 ± 0.4) and a high inflammation-to-muscle ratio (5.2 ± 1.3) at 30 min, while [125I]2-IR showed low radioactivity accumulation in inflamed tissue over the experimental period. Further, radioactivity accumulation in inflamed tissue after [125I]4-IR administration was significantly decreased by pretreatment with selective inhibitors. CONCLUSIONS: [123I]4-IR would be a promising imaging agent for detection of activated p38α.

Bone Metabolism in the Healing Process of Lumbar Interbody Fusion: Temporal Changes of Bone Turnover Markers.

STUDY DESIGN: Prospective longitudinal study. OBJECTIVE: The aim of this study was to evaluate temporal changes of bone turnover markers (BTMs) after lumbar spinal fusion in patients without osteoporosis. SUMMARY OF BACKGROUND DATA: Radiological studies are the standard method to monitor bony fusion, but they do not allow a timely assessment of bone healing. BTMs react rapidly to changes in bone metabolism during fusion process and could be an additional tool to monitor this process. METHODS: A total of 78 nonosteoporosis patients who had undergone one- or two-level transforaminal lumbar interbody fusion were included. Fusion status was assessed using computed tomography sagittal and coronal images. Serum levels of bone-specific alkaline phosphatase (BAP), procollagen type 1 amino-terminal propeptide (P1NP), and osteocalcin (OC) were measured to assess bone formation, and tartrate-resistant acid phosphatase 5b (TRACP-5b) was measured to assess bone resorption. Serum samples were obtained before surgery and at 1, 2, 4, 8, 13, 26, 39, and 52 weeks after surgery. RESULTS: A solid fusion was achieved in 71 of 78 patients (91%), and seven patients resulted in pseudarthrosis. In the fusion group, the level of all BTMs once decreased at 1 postoperative week. Then, BAP and P1NP reached a peak at 4 weeks after surgery, and TRACP-5b and OC peaked at 8 weeks. Thereafter, the level of P1NP and TRACP-5b gradually got closer to the baseline over a year, and BAP kept high until 52 postoperative weeks. In the pseudarthrosis group, peak level of BTMs was significantly higher and the increased level of BAP and P1NP was kept until 52 weeks. CONCLUSION: The present study demonstrated dynamics of BTMs after lumbar spinal fusion in patients without osteoporosis. These normal population data contribute as a baseline to evaluate the effect of osteogenic agents on bone metabolism after spinal fusion.Level of Evidence: 2.

Is Bone Nonunion, Vertebral Deformity, or Spinopelvic Malalignment the Best Therapeutic Target for Amelioration of Low Back Pain After Osteoporotic Vertebral Fracture?

STUDY DESIGN: Cohort study (level 3). OBJECTIVE: The aim of this study was to identify independent risk factors for residual low back pain (LBP) following osteoporotic vertebral fracture (OVF). SUMMARY OF BACKGROUND DATA: Nonunion has been proposed as the primary cause of residual LBP following OVF. However, LBP can occur even when union is maintained. Other reported causes of LBP after OVF include vertebral deformities and spinopelvic malalignment. METHODS: Sixty-seven patients with single-level thoracolumbar OVF who had not received previous osteoporotic treatment were enrolled. Conservative treatment was conducted using a soft lumbosacral orthosis plus osteoporosis drugs, either weekly alendronate (bisphosphonate) or daily teriparatide. Pain scores, kyphosis angle of fractured vertebra (VKA), and spinopelvic alignment, including pelvic incidence minus lumbar lordosis (PI-LL), were assessed periodically during treatment. Radiographic union was evaluated independently by three specialists at 24 weeks post-admission. Patients were divided by pain scores >40% at 24 weeks into the LBP (n = 36) and non-LBP (n = 31) groups. Temporal changes and statistical associations were examined to identify risk factors for LBP at 24 weeks. RESULTS: At 24 weeks, 25% of OVFs failed to achieve union. The LBP group consisted of 71% of nonunion and 48% of union cases. Stepwise multinomial regression analysis showed VKA at 24 weeks >25° was significant risk factor for the LBP group (odds ratio: 6.24, 95% confidence interval: 1.77-22.02, P = 0.004). Significant differences in VKA emerged during treatment in the LBP group, but PI-LL showed the tendency not to change throughout the treatment period. Non-union was correlated with VKA (area under the curve: 0.864). CONCLUSION: Although spinopelvic malalignment is considered as a preexisting factor for LBP, VKA exacerbated by nonunion predominantly led to LBP after a new OVF. Each incidence of OVF should be treated to limit further morphological changes to the fractured vertebra. LEVEL OF EVIDENCE: 3.

The efficacy of osteoporotic treatment in patients with new spinal vertebral compression fracture pain, ADL, QOL, bone metabolism and fracture-healing - In comparison with weekly teriparatide with bisphosphonate.

We conducted a randomized control study to compare the effects of pain, QOL, bone metabolism and fracture healing by administering bisphosphonate (BP) or weekly teriparatide preparation (W-TPTD) to 43 patients (5 males and 38 females) with fresh spinal vertebral compression fractures for osteoporosis. The patients were aged between 61 and 93 years old (mean 78.1 years). In principle, a MRI was used for any diagnosis of new vertebral fractures. From this study, lumbar spine bone mineral density (BMD), after 24 weeks of administration, showed a significant increase (p < 0.05) in both the BP group (mean 5.3%) and in the W-TPTD group (mean 4.9%). The W-TPTD group showed a better Roland-Morris disability Questionnaire (RDQ) improvement throughout the whole period of the study compared with the BP group, the difference was statistically significant after 24 weeks of administration (p < 0.05). The EuroQol 5 dimensions (EQ-5D) and visual analogue scale (VAS) score significantly improved over time in both groups (p < 0.05). The fracture-healing rate was observed in 45% of the BP group and 73% of the W-TPTD group at Week 12, and a statistically significant higher fracture-healing rate was obtained in the W-TPTD group compared to the BP group (p < 0.05). The mean time of fracture-healing was 3.9 months for the BP group and 2.8 months in the W-TPTD group. Statistically significant faster fracture-healing was observed in the W-TPTD group (p < 0.05). At Week 12 and Week 24, P1NP was significantly higher in the W-TPTD group compared to that of the BP group (p < 0.05). TRACP-5b showed no major fluctuations during the study period in either group. These results suggest that W-TPTD may promote better fracture healing of any new osteoporotic vertebral compression fractures compared with a BP.

Peri-operative complications of lumbar spine surgery in patients over eighty five years of age: a retrospective cohort study.

PURPOSE: To compare peri-operative complication rates in ≥ 85-year-old patients who underwent decompression surgery with or without instrumented fusion for degenerative disorders. METHODS: This study involved 907 patients who underwent lumbar spine surgery for degenerative disorders between January 2006 and June 2012. Of these, 33 patients (3.6% of the entire population) were over 85 years of age (85-94 years). Decompression-alone and instrumentation groups were compared in terms of comorbidities, American Society of Anesthesiologists (ASA)-physical status (PS) class, peri-operative complications, and Japanese Orthopedic Association (JOA) scores. RESULTS: Thirty-three ≥ 85-year-old patients underwent surgery. All were ASA-PS class 2 (94%) or 3. The decompression-alone (n = 19) and instrumentation (n = 14) groups did not differ in comorbidity (95 vs. 100%, P = 0.383) or ASA-PS class (P = 0.561). Both exhibited improved JOA scores (decompression-alone: 13.4/29 to 22.7/29; instrumentation: 8.6/29 to 17.9/29; P = 0.9068) and had similar peri-operative complication rates (21.0 vs. 28.5%, P = 0.374). CONCLUSIONS: Although instrumentation is considered more invasive than decompression, we detected no statistically significant differences in peri-operative complication rates between these two types of surgery in ≥ 85-year-old patients. Surgeons should perform instrumentation even in the patients over 85 years with ASA class 3 or less.