Astrocyte-neuron lactate transport is required for long-term memory formation.

We report that, in the rat hippocampus, learning leads to a significant increase in extracellular lactate levels that derive from glycogen, an energy reserve selectively localized in astrocytes. Astrocytic glycogen breakdown and lactate release are essential for long-term but not short-term memory formation, and for the maintenance of long-term potentiation (LTP) of synaptic strength elicited in vivo. Disrupting the expression of the astrocytic lactate transporters monocarboxylate transporter 4 (MCT4) or MCT1 causes amnesia, which, like LTP impairment, is rescued by L-lactate but not equicaloric glucose. Disrupting the expression of the neuronal lactate transporter MCT2 also leads to amnesia that is unaffected by either L-lactate or glucose, suggesting that lactate import into neurons is necessary for long-term memory. Glycogenolysis and astrocytic lactate transporters are also critical for the induction of molecular changes required for memory formation, including the induction of phospho-CREB, Arc, and phospho-cofilin. We conclude that astrocyte-neuron lactate transport is required for long-term memory formation.

Periostin increased by mechanical stress upregulates interleukin-6 expression in the ligamentum flavum.

Ligamentum flavum (LF) hypertrophy is a major cause of lumbar spinal canal stenosis. Although mechanical stress is thought to be a major factor involved in LF hypertrophy, the exact mechanism by which it causes hypertrophy has not yet been fully elucidated. Here, changes in gene expression due to long-term mechanical stress were analyzed using RNA-seq in a rabbit LF hypertrophy model. In combination with previously reported analysis results, periostin was identified as a molecule whose expression fluctuates due to mechanical stress. The expression and function of periostin were further investigated using human LF tissues and primary LF cell cultures. Periostin was abundantly expressed in human hypertrophied LF tissues, and periostin gene expression was significantly correlated with LF thickness. In vitro, mechanical stress increased gene expressions of periostin, transforming growth factor-ß1, α-smooth muscle actin, collagen type 1 alpha 1, and interleukin-6 (IL-6) in LF cells. Periostin blockade suppressed the mechanical stress-induced gene expression of IL-6 while periostin treatment increased IL-6 gene expression. Our results suggest that periostin is upregulated by mechanical stress and promotes inflammation by upregulating IL-6 expression, which leads to LF degeneration and hypertrophy. Periostin may be a pivotal molecule for LF hypertrophy and a promising therapeutic target for lumbar spinal stenosis.

Impact of surgical treatment on patient reported outcome in patients with spinal metastases from prostate cancer.

OBJECTIVE: This study aimed to elucidate postoperative outcomes in patients with spinal metastases of prostate cancer, with a focus on patient-oriented assessments. METHODS: This was a prospective multicenter registry study involving 35 centers. A total of 413 patients enrolled in the Japanese Association for Spine Surgery and Oncology Multicenter Prospective Study of Surgery for Metastatic Spinal Tumors were evaluated for inclusion. The eligible patients were followed for at least 1 year after surgery. The Frankel Classification, Eastern Cooperative Oncology Group Performance Status, visual analog scale for pain, face scale, Barthel Index, vitality index, indications for oral pain medication, and the EQ-5D-5L questionnaire were used for evaluating functional status, activities of daily living, and patient motivation. RESULTS: Of the 413 eligible patients, 41 with primary prostate cancer were included in the study. The patient-oriented assessments indicated that the patients experienced postoperative improvements in quality of life and motivation in most items, with the improvements extending for up to 6 months. More than half of the patients with Frankel classifications B or C showed improved neurological function at 1 month after surgery, and most patients presented maintained or improved their classification at 6 months. CONCLUSION: Surgical intervention for spinal metastases of prostate cancer significantly improved neurological function, quality of life, and motivation of the patients. Consequently, our results support the validity of surgical intervention for improving the neurological function and overall well-being of patients with spinal metastases of prostate cancer.

Advanced glycation end products in musculoskeletal system and disorders.

The human population is ageing globally, and the number of old people is increasing yearly. Diabetes is common in the elderly, and the number of diabetic patients is also increasing. Elderly and diabetic patients often have musculoskeletal disorder, which are associated with advanced glycation end products (AGEs). AGEs are heterogeneous molecules derived from non-enzymatic products of the reaction of glucose or other sugar derivatives with proteins or lipids, and many different types of AGEs have been identified. AGEs are a biomarker for ageing and for evaluating disease conditions. Fluorescence, spectroscopy, mass spectrometry, chromatography, and immunological methods are commonly used to measure AGEs, but there is no standardized evaluation method because of the heterogeneity of AGEs. The formation of AGEs is irreversible, and they accumulate in tissue, eventually causing damage. AGE accumulation has been confirmed in neuromusculoskeletal tissues, including bones, cartilage, muscles, tendons, ligaments, and nerves, where they adversely affect biomechanical properties by causing charge changes and forming cross-linkages. AGEs also bind to receptors, such as the receptor for AGEs (RAGE), and induce inflammation by intracellular signal transduction. These mechanisms cause many varied aging and diabetes-related pathological conditions, such as osteoporosis, osteoarthritis, sarcopenia, tendinopathy, and neuropathy. Understanding of AGEs related pathomechanism may lead to develop novel methods for the prevention and therapy of such disorders which affect patients' quality of life. Herein, we critically review the current methodology used for detecting AGEs, and present potential mechanisms by which AGEs cause or exacerbate musculoskeletal disorders.

Less-invasive decompression procedures can reduce risk of reoperation for lumbar spinal stenosis with diffuse idiopathic skeletal hyperostosis extended to the lumbar segment: analysis of two retrospective cohorts.

PURPOSE: Clinical outcomes after decompression procedures are reportedly worse for lumbar spinal stenosis (LSS) with diffuse idiopathic skeletal hyperostosis (DISH), especially DISH extended to the lumbar segment (L-DISH). However, no studies have compared the effect of less-invasive surgery versus conventional decompression techniques for LSS with DISH. The purpose of this study was to compare the long-term risk of reoperation after decompression surgery focusing on LSS with L-DISH. METHODS: This study compared open procedure cohort (open conventional fenestration) and less-invasive procedure cohort (bilateral decompression via a unilateral approach) with ≥ 5 years of follow-up. After stratified analysis by L-DISH, patients with L-DISH were propensity score-matched by age and sex. RESULTS: There were 57 patients with L-DISH among 489 patients in the open procedure cohort and 41 patients with L-DISH among 297 patients in the less-invasive procedure cohort. The reoperation rates in L-DISH were higher in the open than less-invasive procedure cohort for overall reoperations (25% and 7%, p = 0.026) and reoperations at index levels (18% and 5%, p = 0.059). Propensity score-matched analysis in L-DISH demonstrated that open procedures were significantly associated with increased overall reoperations (hazard ratio [HR], 6.18; 95% confidence interval [CI], 1.37-27.93) and reoperations at index levels (HR, 4.80; 95% CI, 1.04-22.23); there was no difference in reoperation at other lumbar levels. CONCLUSIONS: Less-invasive procedures had a lower risk of reoperation, especially at index levels for LSS with L-DISH. Preserving midline-lumbar posterior elements could be desirable as a decompression procedure for LSS with L-DISH.

Machine-learning-based approach for nonunion prediction following osteoporotic vertebral fractures.

PURPOSE: An osteoporotic vertebral fracture (OVF) is a common disease that causes disabilities in elderly patients. In particular, patients with nonunion following an OVF often experience severe back pain and require surgical intervention. However, nonunion diagnosis generally takes more than six months. Although several studies have advocated the use of magnetic resonance imaging (MRI) observations as predictive factors, they exhibit insufficient accuracy. The purpose of this study was to create a predictive model for OVF nonunion using machine learning (ML). METHODS: We used datasets from two prospective cohort studies for OVF nonunion prediction based on conservative treatment. Among 573 patients with acute OVFs exceeding 65 years in age enrolled in this study, 505 were analyzed. The demographic data, fracture type, and MRI observations of both studies were analyzed using ML. The ML architecture utilized in this study included a logistic regression model, decision tree, extreme gradient boosting (XGBoost), and random forest (RF). The datasets were processed using Python. RESULTS: The two ML algorithms, XGBoost and RF, exhibited higher area under the receiver operating characteristic curves (AUCs) than the logistic regression and decision tree models (AUC = 0.860 and 0.845 for RF and XGBoost, respectively). The present study found that MRI findings, anterior height ratio, kyphotic angle, BMI, VAS, age, posterior wall injury, fracture level, and smoking habit ranked as important features in the ML algorithms. CONCLUSION: ML-based algorithms might be more effective than conventional methods for nonunion prediction following OVFs.

A nationwide multicenter study of the cost effectiveness of five leading drugs for pharmacological management of cervicobrachial symptoms.

BACKGROUND: Cervicobrachial pain frequently affects the quality of life (QOL) of the general public and has a significant economic impact on the health care systems of various countries. There are a number of treatment options for this disease, including widely-used drug therapy, but the effectiveness of each option is indeterminate, and there have been no published cost-effectiveness analysis studies so far. This prospective observational study aimed to examine the cost-effectiveness of drug treatment for cervicobrachial symptoms. METHODS: A 6-month medication regimen for each of five frequently-prescribed drugs for cervicobrachial symptoms was administered to 322 patients at 24 centers in Japan. Outcome measures, including of the EuroQol Group 5D, Short Form-8, and Visual Analog Scale (VAS), were investigated at baseline and every month thereafter. Incremental cost-effectiveness ratios (ICERs) of the drug cost to quality-adjusted life years (QALYs) were calculated. A stratified analysis of patient characteristics was also performed to identify baseline factors potentially affecting cost-effectiveness. RESULTS: The ICER of entire drug treatment for cervicobrachial symptoms was 7,491,640 yen. Compared with the reference willingness-to-pay, the ICER was assumed to not be cost-effective. A certain number of QALYs were gained during the first 3 months after the treatment intervention, but almost no QALYs were gained during the following 3 months. Stratified analysis showed that cost-effectiveness was extremely low for patients with high baseline VAS and high QOL. CONCLUSIONS: The available medications for cervicobrachial symptoms did not have excellent cost-effectiveness. Although a certain number of QALYs were gained during the first 3 months after medication, no QALYs were gained in the latter half of the study period, suggesting that it is not advisable to continue the medication needlessly. LEVEL OF EVIDENCE: II, prospective cohort study.

Neck pain and related factors in patients with rheumatoid arthritis.

OBJECTIVES: In rheumatoid arthritis, neck pain can be caused by inflammatory reactions or cervical lesions, but the prevalence and associated factors have not been well studied. This study aimed to investigate the prevalence of neck pain in patients with rheumatoid arthritis and elucidate the related factors. METHODS: This study included 146 patients with rheumatoid arthritis. Neck pain, quality of life, and levels of anxiety and depression were evaluated using a questionnaire. Cervical lesions and spinal alignment were evaluated using plain radiograph and magnetic resonance imaging. Factors associated with neck pain were analysed using a logistic regression model. RESULTS: Fifty-six per cent of the patients had neck pain, and the quality of life scores were significantly worse in these patients. Multivariate analysis revealed age, C7 sagittal vertical axis, upper cervical lesion, and endplate erosion as factors associated with neck pain in patients with rheumatoid arthritis. CONCLUSIONS: More than half the patients with rheumatoid arthritis suffer from neck pain, and neck pain affects the quality of life and activities of daily living. Neck pain was associated with upper cervical lesion and endplate erosion suggesting the importance of radiological examination in patients with rheumatoid arthritis and neck pain.

Protective Attitudes toward Occupational Radiation Exposure among Spine Surgeons in Japan: An Epidemiological Description from the Survey by the Society for Minimally Invasive Spinal Treatment.

Background and Objectives: The global trend toward increased protection of medical personnel from occupational radiation exposure requires efforts to promote protection from radiation on a societal scale. To develop effective educational programs to promote radiation protection, we clarify the actual status and stage of behavioral changes of spine surgeons regarding radiation protection. Materials and Methods: We used a web-based questionnaire to collect information on the actual status of radiation protection and stages of behavioral change according to the transtheoretical model. The survey was administered to all members of the Society for Minimally Invasive Spinal Treatment from 5 October to 5 November 2020. Results: Of 324 members of the Society for Minimally Invasive Spinal Treatment, 229 (70.7%) responded. A total of 217 participants were analyzed, excluding 12 respondents who were not exposed to radiation in daily practice. A trunk lead protector was used by 215 (99%) participants, while 113 (53%) preferred an apron-type protector. Dosimeters, thyroid protector, lead glasses, and lead gloves were used by 108 (50%), 116 (53%), 82 (38%), and 64 (29%) participants, respectively. While 202 (93%) participants avoided continuous irradiation, only 120 (55%) were aware of the source of the radiation when determining their position in the room. Regarding the behavioral change stage of radiation protection, 134 (62%) participants were in the action stage, while 37 (17%) had not even reached the contemplation stage. Conclusions: We found that even among the members of the Society for Minimally Invasive Spinal Treatment, protection of all vulnerable body parts was not fully implemented. Thus, development of educational programs that cover the familiar risks of occupational radiation exposure, basic protection methods in the operating room, and the effects of such protection methods on reducing radiation exposure in actual clinical practice is warranted.

Incidence of and risk factors for spondylolisthesis, scoliosis, and vertebral fracture in rheumatoid arthritis.

INTRODUCTION: Although lumbar lesions such as spondylolisthesis, scoliosis, and vertebral fracture are not specific to rheumatoid arthritis (RA), the prevalence is high in RA patients. However, no longitudinal study has evaluated lumbar lesions in RA. This study aimed to investigate the incidence of and risk factors for lumbar lesions in RA by a prospective longitudinal cohort study. MATERIALS AND METHODS: The study cohort comprised 110 patients with RA from the 'analysis of factors for RA spinal disorders (AFFORD)' study who completed the secondary survey at a single orthopaedic outpatient RA clinic. Radiological examination included standing radiographs and magnetic resonance imaging (MRI) of the lumbar spine. New development of spondylolisthesis, scoliosis, and vertebral fracture were assessed between baseline and secondary survey. RESULTS: The incidences of spondylolisthesis, scoliosis, and vertebral fracture were 42%, 16%, and 12%, respectively, during a mean follow-up of 7 years. The independent risk factor for de novo scoliosis was poor control of RA (adjusted odds ratio [aOR] 4.81, p = 0.011), while the independent risk factors for new vertebral fracture was use of glucocorticoid at secondary survey (aOR 14.87, p = 0.012). Patients with de novo scoliosis exhibited more severe low back pain and lower quality of life than those without. CONCLUSION: The incidence of scoliosis was related in patients with poor control of RA, while new vertebral fracture was more common in patients with use of glucocorticoid. Control of disease activity might be important in preventing radiological lumbar disorders in RA.

Delayed aortic injury after thoracic corrective osteotomy: a case report.

PURPOSE: To present a case of delayed aortic perforation due to a nondisplaced fracture of the 9th rib after vertebral osteotomy for degenerative kyphoscoliosis in patients with osteoporosis. METHODS: A 78-year-old female patient with osteoporosis had undergone T9-iliac correction surgery for degenerative kyphoscoliosis. After 2 years, the patient underwent T10 pedicle subtraction osteotomy for a T10 vertebral fracture and progression of kyphosis. Postoperatively, the patient had been doing well for 3 weeks; however, just before the day of discharge, she died following a cardiopulmonary arrest. An autopsy was performed with the consent of her family. RESULTS: Autopsy revealed a large amount of blood and a clot in the left thoracic cavity. Aortic perforation was found just in front of a nondisplaced fracture of the left 9th rib. CONCLUSION: This report describes a new critical complication after spinal correction surgery. Even without pedicle screw malposition, aortic injuries can happen to patients with osteoporosis after corrective osteotomy for degenerative kyphoscoliosis due to positional change of aorta and fragility of the ribs. The spine surgeon should be aware of this type of complication, and rib fractures around the aorta after vertebral osteotomy should not be neglected even when there is no displacement.

Decreased muscle mass and strength affected spinal sagittal malalignment.

PURPOSE: Correction surgeries for spinal malalignment showed good clinical outcomes; however, there were concerns including increased invasiveness, complications, and impact on medico-economics. Ideally, an early intervention is needed. To better understand the patho-mechanism and natural course of spinal alignment, the effect of factors such as muscle mass and strength on spinal sagittal imbalance were determined in a multicenter cross-sectional study. METHODS: After excluding metal implant recipients, 1823 of 2551 patients (mean age: 69.2 ± 13.8 years; men 768, women 1055) were enrolled. Age, sex, past medical history (Charlson comorbidity index), body mass index (BMI), grip strength (GS), and trunk muscle mass (TM) were reviewed. Spinal sagittal imbalance was determined by the SRS-Schwab classification. Multiple comparison analysis among four groups (Normal, Mild, Moderate, Severe) and multinomial logistic regression analysis were performed. RESULTS: On multiple comparison analysis, with progressing spinal malalignment, age in both sexes tended to be higher; further, TM in women and GS in both sexes tended to be low. On multinomial logistic regression analysis, age and BMI were positively associated with spinal sagittal malalignment in Mild, Moderate, and Severe groups. TM in Moderate and Severe groups and GS in the Moderate group were negatively associated with spinal sagittal malalignment. CONCLUSION: Aging, obesity, low TM, and low GS are potential risk factors for spinal sagittal malalignment. Especially, low TM and low GS are potentially associated with more progressed spinal sagittal malalignment. Thus, early intervention for muscles, such as exercise therapy, is needed, while the spinal sagittal alignment is normal or mildly affected.

Expression and function of fibroblast growth factor 1 in the hypertrophied ligamentum flavum of lumbar spinal stenosis.

BACKGROUND: Fibrosis is one of the main pathologies caused by hypertrophy of the ligamentum flavum (LF), which leads to lumbar spinal stenosis (LSS). The fibroblast growth factor (FGF) family is a key mediator of fibrosis. However, acidic fibroblast growth factor (FGF-1) expression and function are not well understood in LF. This study sought to evaluate FGF-1 expression in the hypertrophied and non-hypertrophied human LF, and to investigate its function using primary human LF cell cultures. METHODS: We obtained hypertrophied lumbar LF from LSS patients and non-hypertrophied lumbar LF from control patients during surgery. Immunohistochemistry and qPCR were performed to evaluate FGF-1 expression in LF tissue. The function of FGF-1 and transforming growth factor beta 1 (TGF-ß1) was also investigated using primary LF cell culture. The effects on cell morphology and cell proliferation were examined using a crystal violet staining assay and MTT assay, respectively. Immunocytochemistry, western blotting, and qPCR were performed to evaluate the effect of FGF-1 on TGF-ß1-induced myofibroblast differentiation and fibrosis. RESULTS: Immunohistochemistry and qPCR showed higher FGF-1 expression in hypertrophied LF compared to control LF. Crystal violet staining and MTT assay revealed that FGF-1 decreases LF cell size and inhibits their proliferation in a dose-dependent manner, whereas TGF-ß1 increases cell size and promotes proliferation. Immunocytochemistry and western blotting further demonstrated that TGF-ß1 increases, while FGF-1 decreases, α-SMA expression in LF cells. Moreover, FGF-1 also caused downregulation of collagen type 1 and type 3 expression in LF cells. CONCLUSION: FGF-1 is highly upregulated in the LF of LSS patients. Meanwhile, in vitro, FGF-1 exhibits antagonistic effects to TGF-ß1 by inhibiting cell proliferation and decreasing LF cell size as well as the expression of fibrosis markers. These results suggest that FGF-1 has an anti-fibrotic role in the pathophysiology of LF hypertrophy.

Risk factors for low back pain increase in rheumatoid arthritis: Analysis of a 7-year follow-up study.

OBJECTIVE: Several studies have demonstrated that low back pain (LBP) is related to disease activity in patients with rheumatoid arthritis (RA). However, there is no longitudinal research. This study aimed to determine the impacts and risk factors for LBP increase in RA in a longitudinal cohort study. METHODS: The study evaluated 113 patients with RA who completed the secondary survey. LBP increase was defined as ≥1 standard deviation of mean change in visual analogue scale (VAS) between the baseline and secondary surveys. The impacts of LBP increase on quality of life (QOL) and psychological status were evaluated. Risk factors were assessed among patient demographic characteristics and radiological changes. RESULTS: Mean change in VAS for LBP was -0.8 ± 30.4 mm during a mean 7-year follow-up. LBP increase was defined as ≥30-mm increase in VAS for LBP. Patients with LBP increase had significantly lower QOL and worse mental status than patients without it. Poor control of RA was identified as an independent risk factor for LBP increase (odds ratio, 9.82, p = .001). CONCLUSION: Patients with poor control of RA were likely to experience LBP increase in the long term. Control of RA disease activity is important for control of LBP, QOL, and mental status.

Microendoscopic Lumbar Posterior Decompression Surgery for Lumbar Spinal Stenosis: Literature Review.

Lumbar spinal stenosis (LSS) is a common disease in the elderly, mostly due to degenerative changes in the lumbar spinal complex. Decompression surgery is the standard surgical treatment for LSS. Classically, total laminectomy-which involves resection of the spinous process, entire laminae and medial facet-has been the standard decompression technique; however, it can cause post-surgical instability. To overcome this disadvantage, various minimally invasive techniques that preserve the stabilization structures of the spine have been developed, and surgeons have begun to re-evaluate decompression surgery from the standpoint of reduced invasiveness and cost. More than two decades have passed since the introduction of microendoscopic spine surgery, and studies continue to shed light on its advantages and limitations as new knowledge becomes available. This article is a narrative review of the available literature, along with authors' experience, regarding the indications, surgical techniques, clinical outcomes, and limitations/complications of microendoscopic decompression for LSS.

Association of occupational direct radiation exposure to the hands with longitudinal melanonychia and hand eczema in spine surgeons: a survey by the society for minimally invasive spinal treatment (MIST).

PURPOSE: To investigate the association between occupational direct radiation exposure to the hands and longitudinal melanonychia (LM) and hand eczema in spine surgeons. METHODS: A web-based questionnaire survey of the Society for Minimally Invasive Spinal Treatment (MIST) in Japan was conducted. The proportion of LM and hand eczema in hands with high and low-radiation exposure was compared using Fisher's exact test. The odds ratios (ORs) and their 95% confidence intervals (CIs) for the prevalence of LM and hand eczema in the high-radiation exposure hands were calculated using generalized estimating equations for logistic regression as control for the correlation of observations among the same individuals and possible confounders. RESULTS: Among 324 members of the society, responses were received from 229 members (70.7%). A total of 454 hands from 227 participants were analysed. The prevalence of LM and hand eczema was 43% and 29%, respectively. In a hand-by-hand comparison, more hands had LM in the high-radiation exposure group than the low-radiation exposure group (90 [40%] vs. 39 [17%], respectively, p < 0.001). A similar trend was observed for hand eczema (63 [28%] vs. 33 [15%], respectively, p = 0.001). The adjusted OR for high-radiation exposure hands was 3.18 (95% CI: 2.24-4.52). Consistent results were obtained for hand eczema, with an adjusted OR of 2.26 (95% CI: 1.67-3.06). CONCLUSION: The present study suggests that direct radiation exposure to physician's hands is associated with LM and hand eczema. Those with LM and radially biased hand eczema may have had high direct radiation exposure.

Classification and prognostic factors of residual symptoms after minimally invasive lumbar decompression surgery using a cluster analysis: a 5-year follow-up cohort study.

PURPOSE: Residual symptoms indicating incomplete remission of lower leg numbness or low back pain may occur after spine surgery. The purpose was to elucidate the pattern of residual symptoms 5 years after minimally invasive lumbar decompression surgery using a cluster analysis. METHODS: The study comprised 193 patients with lumbar spinal stenosis (LSS) (108 men, 85 women) ranging in age from 40 to 86 years (mean, 67.9 years). Each patient underwent 5-year follow-up. The Japanese Orthopedic Association score and visual analog scale scores for low back pain, leg pain, and leg numbness at 5 years were entered into the cluster analysis to characterize postoperative residual symptoms. Other clinical data were analyzed to detect the factors significantly related to each cluster. RESULTS: The analysis yielded four clusters representing different patterns of residual symptoms. Patients in cluster 1 (57.0%) were substantially improved and had few residual symptoms of LSS. Patients in cluster 2 (11.4%) were poorly improved and had major residual symptoms. Patients in cluster 3 (17.6%) were greatly improved but had mild residual low back pain. Patients in cluster 4 (14.0%) were improved but had severe residual leg numbness. Prognostic factors of cluster 2 were a short maximum walking distance, motor weakness, resting lower leg numbness, cofounding scoliosis, and high sagittal vertical axis. CONCLUSIONS: This is the first study to identify specific patterns of residual symptoms of LSS after decompression surgery. Our results will contribute to acquisition of preoperative informed consent and identification of patients with the best chance of postoperative improvement.

Topical co-administration of zoledronate with recombinant human bone morphogenetic protein-2 can induce and maintain bone formation in the bone marrow environment.

BACKGROUND: Bone morphogenetic proteins (BMPs) induce osteogenesis in various environments. However, when BMPs are used alone in the bone marrow environment, the maintenance of new bone formation is difficult owing to vigorous bone resorption. This is because BMPs stimulate the differentiation of not only osteoblast precursor cells but also osteoclast precursor cells. The present study aimed to induce and maintain new bone formation using the topical co-administration of recombinant human BMP-2 (rh-BMP-2) and zoledronate (ZOL) on beta-tricalcium phosphate (ß-TCP) composite. METHODS: ß-TCP columns were impregnated with both rh-BMP-2 (30 µg) and ZOL (5 µg), rh-BMP-2 alone, or ZOL alone, and implanted into the left femur canal of New Zealand white rabbits (n = 56). The implanted ß-TCP columns were harvested and evaluated at 3 and 6 weeks after implantation. These harvested ß-TCP columns were evaluated radiologically using plane radiograph, and histologically using haematoxylin/eosin (H&E) and Masson's trichrome (MT) staining. In addition, micro-computed tomography (CT) was performed for qualitative analysis of bone formation in each group (n = 7). RESULTS: Tissue sections stained with H&E and MT dyes revealed that new bone formation inside the ß-TCP composite was significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Micro-CT data also demonstrated that the bone volume and the bone mineral density inside the ß-TCP columns were significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). CONCLUSIONS: The topical co-administration of both rh-BMP-2 and ZOL on ß-TCP composite promoted and maintained newly formed bone structure in the bone marrow environment.

Sarcopenia is related to spinal sagittal imbalance in patients with spinopelvic mismatch.

PURPOSE: To clarify the relationship between sarcopenia and spinopelvic parameters. METHODS: Among outpatients of spine surgery department, 126 patients (mean age 77.2 years. M/F = 71/55) were included. We diagnosed patients with sarcopenia using the diagnostic algorithm of the Asian Working Group for Sarcopenia. Spinopelvic parameters and the prevalence of spinopelvic mismatch (pelvic incidence minus lumbar lordosis ≥ 10°) were investigated and compared between patients with and without sarcopenia. Furthermore, we compared the spinopelvic parameters between the Sarcopenia and No Sarcopenia groups under each condition of spinopelvic match and mismatch. RESULTS: The prevalence of sarcopenia in this study was 21.4%. Overall, the spinopelvic parameters except thoracic kyphosis (TK) (Sarcopenia: 34.7°, No Sarcopenia: 24.3°, p < 0.01) were not significantly different between the Sarcopenia and No Sarcopenia groups. Prevalence of patients with spinopelvic mismatch was also not significantly different between the Sarcopenia and No Sarcopenia groups (37.0% vs. 42.4%, p = 0.66). Among patients without spinopelvic mismatch, there was no spinopelvic parameter with a significant difference between the 2 groups. However, among patients with spinopelvic mismatch, sagittal vertebral axis (SVA) (115.7 mm vs. 58.7 mm, p < 0.01) and TK (36.6° vs. 21.3°, p < 0.01) of the Sarcopenia group were significantly larger than those of the No Sarcopenia group. Moreover, sarcopenia was independently related to a significant increase in SVA (ß = 50.7, p < 0.01) and TK (ß = 14.0, p < 0.01) in patients with spinopelvic mismatch, after adjustment for age. CONCLUSIONS: Sarcopenia is related to spinal sagittal imbalance because of insufficient compensation by flattening thoracic kyphosis in patients with spinopelvic mismatch. These slides can be retrieved under Electronic Supplementary Material.

The association of back muscle strength and sarcopenia-related parameters in the patients with spinal disorders.

PURPOSE: To evaluate the correlations between back muscle strength, trunk muscle mass, and sarcopenia-related parameters in patients with spinal disorders. METHODS: This cross-sectional observational study included 230 consecutive patients with spinal disorders who visited our outpatient clinic (age range 65-92 years). We measured back muscle strength, handgrip strength, gait speed, and appendicular and trunk skeletal muscle mass using bioimpedance analysis. We classified the subjects into the sarcopenia, dynapenia, or normal stages in accordance with the guidelines set by the European Working Group on Sarcopenia in Older People, and used the cutoff values reported in the guidelines set by the Asian Working Group for Sarcopenia. RESULTS: Back muscle strength was significantly correlated with trunk muscle mass (males: r = 0.47, P < 0.001; females: r = 0.39, P < 0.001), handgrip strength (males: r = 0.67, P < 0.001; females: r = 0.59, P < 0.001), and gait speed (males: r = 0.49, P < 0.001; females: r = 0.51, P < 0.001). The respective incidences of the sarcopenia, dynapenia, and normal stages were 16.4%, 26.7%, and 56.9% for males, and 23.7%, 50.9%, and 25.4% for females. Dynapenia was significantly more prevalent in females than in males. Back muscle strength in the normal group was significantly greater than that in the sarcopenic and dynapenic groups. CONCLUSION: Back muscle strength is significantly correlated with trunk muscle mass and sarcopenia-related parameters in patients with spinal disorders. Back muscle strength in the sarcopenic stage is significantly lesser than that in the normal stage. Although sarcopenia is a multifaceted geriatric syndrome, spinal disorders might be one of the risk factors for disease-related sarcopenia. These slides can be retrieved from Electronic Supplementary Material.