Academic Engagement of Women as Orthopaedic Surgeons at the Annual Meetings of the Japanese Orthopaedic Association From 2012 to 2022.

BACKGROUND: Higher gender diversity correlates with higher patient satisfaction, higher-quality medical education, increased research productivity, and higher revenues. Although the field of Japanese orthopaedic surgery includes the lowest proportion of women and lags in gender diversity, reports on the current gender diversity status in academic activities are scarce. We investigated changes in women's participation in academic activities at the Japanese Orthopaedic Association (JOA) annual meetings over the past 11 years. METHODS: Data on the percentage of women in the JOA membership during 2012-2022 were analyzed to ascertain the proportion of women as first authors of oral and poster presentations, abstract reviewers, invited lecturers, seminar lecturers, general abstract oral chairpersons, symposium chairpersons, and speakers. Regarding the ratio of women among the JOA members during 2012-2022, we relied on data provided by the JOA. Data related to other categories were collected from the abstract book presented at the JOA Annual Meetings between 2012 and 2022. We analyzed the time trend for women's proportions using the Cochran-Armitage trend test. A p-value < 0.05 was considered statistically significant. RESULTS: During 2012-2022, the percentage of female members (4.9-6.7%), poster first authors (2.7-4.3%), abstract reviewers (0-1.5%), general abstract oral chairpersons (0-2.3%), symposium chairpersons (0-3.6%), and symposium speakers (1.6-6.8%) had increased significantly (p < 0.05). Oral first authors (2.2-4.1%), invited lecturers (0-6.8%), or seminar lecturers (0%-6.7%) showed no trend. Women engaged in academic activities at all annual association meetings did not exceed the women's proportion among the association members. CONCLUSION: Although the proportion of women members of the JOA has gradually increased and more women are involved in its annual meetings, the proportion of female presenters, invited speakers, symposiasts, and chairpersons of oral and poster presentations is generally lower than that of women as JOA members. Members should be asked to raise awareness, including more active education of women as physicians in educational institutions and the creation of positive actions to select women as physicians for more important roles (chairpersons, educational speakers, and symposiasts) in the organization of annual meetings.

Gender Diversity of the Japanese Society for Spine Surgery and Related Research Annual Meetings from 2013 to 2022.

Introduction: There are no reports that have examined the annual trends of the percentage of women who are members of the Japanese Society for Spine Surgery and Related Research (JSSR) or their roles at annual meetings. Furthermore, the status of gender diversity in the JSSR remains unclear. This study aims to identify gender diversity in the JSSR by quantifying the role of women at annual meetings over the past decade. Methods: We performed a retrospective review to explore gender role in the JSSR annual meeting by examining the meeting programs for 2013-2022. The gender ratios were surveyed each year for the following: (1) first authors of general application abstracts (oral and poster), (2) meeting guest speakers, (3) meeting moderators, and (4) program editors of the abstracts. We also investigated the availability of gender equality symposiums. Results: The percentage of women applying (1.1%-2.1%) and those who were invited as participants [guest speaker (0%-0.9%), moderator (0%-5.8%), and program editor (0%-0.6%)] at the annual JSSR meetings was low, with no significant increase over the past decade. In addition, there has never been a symposium promoting gender equality at the annual JSSR meeting. Conclusions: Our findings suggest that a strong and active role for institutional leaders and senior members to support the scholarly activities of women spine surgeons is important for adopting gender diversity in the JSSR academia. The absence of gender equality symposiums and the few invited women participants at the JSSR annual meeting may be due to a lack of gender diversity awareness among conference organizers or unconscious gender bias. Monitoring the role of women in the JSSR annual meetings may solve the gender diversity problem.

Developing Medical Education Curriculum Reform Strategies to Address the Impact of Generative AI: Qualitative Study.

BACKGROUND: Generative artificial intelligence (GAI), represented by large language models, have the potential to transform health care and medical education. In particular, GAI's impact on higher education has the potential to change students' learning experience as well as faculty's teaching. However, concerns have been raised about ethical consideration and decreased reliability of the existing examinations. Furthermore, in medical education, curriculum reform is required to adapt to the revolutionary changes brought about by the integration of GAI into medical practice and research. OBJECTIVE: This study analyzes the impact of GAI on medical education curricula and explores strategies for adaptation. METHODS: The study was conducted in the context of faculty development at a medical school in Japan. A workshop involving faculty and students was organized, and participants were divided into groups to address two research questions: (1) How does GAI affect undergraduate medical education curricula? and (2) How should medical school curricula be reformed to address the impact of GAI? The strength, weakness, opportunity, and threat (SWOT) framework was used, and cross-SWOT matrix analysis was used to devise strategies. Further, 4 researchers conducted content analysis on the data generated during the workshop discussions. RESULTS: The data were collected from 8 groups comprising 55 participants. Further, 5 themes about the impact of GAI on medical education curricula emerged: improvement of teaching and learning, improved access to information, inhibition of existing learning processes, problems in GAI, and changes in physicians' professionality. Positive impacts included enhanced teaching and learning efficiency and improved access to information, whereas negative impacts included concerns about reduced independent thinking and the adaptability of existing assessment methods. Further, GAI was perceived to change the nature of physicians' expertise. Three themes emerged from the cross-SWOT analysis for curriculum reform: (1) learning about GAI, (2) learning with GAI, and (3) learning aside from GAI. Participants recommended incorporating GAI literacy, ethical considerations, and compliance into the curriculum. Learning with GAI involved improving learning efficiency, supporting information gathering and dissemination, and facilitating patient involvement. Learning aside from GAI emphasized maintaining GAI-free learning processes, fostering higher cognitive domains of learning, and introducing more communication exercises. CONCLUSIONS: This study highlights the profound impact of GAI on medical education curricula and provides insights into curriculum reform strategies. Participants recognized the need for GAI literacy, ethical education, and adaptive learning. Further, GAI was recognized as a tool that can enhance efficiency and involve patients in education. The study also suggests that medical education should focus on competencies that GAI hardly replaces, such as clinical experience and communication. Notably, involving both faculty and students in curriculum reform discussions fosters a sense of ownership and ensures broader perspectives are encompassed.

The influence of Gamification on medical students' diagnostic decision making and awareness of medical cost: a mixed-method study.

BACKGROUND: The gamification of learning increases student enjoyment, and motivation and engagement in learning tasks. This study investigated the effects of gamification using decision-making cards (DMCs) on diagnostic decision-making and cost using case scenarios. METHOD: Thirty medical students in clinical clerkship participated and were randomly assigned to 14 small groups of 2-3 medical students each. Decision-making was gamified using DMCs with a clinical information heading and medical cost on the front, and clinical information details on the back. First, each team was provided with brief clinical information on case scenarios. Subsequently, DMCs depending on the case were distributed to each team, and team members chose cards one at a time until they reached a diagnosis of the case. The total medical cost was then scored based on the number and contents of cards drawn. Four case scenarios were conducted. The quantitative outcomes including confidence in effective clinical decision-making, motivation to learn diagnostic decision-making, and awareness of medical costs were measured before and after our gamification by self-evaluation using a 7-point Likert scale. The qualitative component consisted of a content analysis on the benefits of learning clinical reasoning using DMCs. RESULT: Confidence in effective clinical decision-making, motivation to learn diagnostic decision-making, and awareness of medical cost were significantly higher after the gamification. Furthermore, comparing the clinical case scenario tackled last with the one tackled first, the average medical cost of all cards drawn by students decreased significantly from 11,921 to 8,895 Japanese yen. In the content analysis, seven advantage categories of DMCs corresponding to clinical reasoning components were extracted (information gathering, hypothesis generation, problem representation, differential diagnosis, leading or working diagnosis, diagnostic justification, and management and treatment). CONCLUSION: Teaching medical students clinical reasoning using DMCs can improve clinical decision-making confidence and learning motivation, and reduces medical cost in clinical case scenarios. In addition, it can help students to acquire practical knowledge, deepens their understanding of clinical reasoning, and identifies several important clinical reasoning skills including diagnostic decision-making and awareness of medical costs. Gamification using DMCs can be an effective teaching method for improving medical students' diagnostic decision-making and reducing costs.

How long will it take to reach the gender diversity goal for orthopaedics in Japan?

BACKGROUND: In Japan, orthopaedics is one of the medical fields with the lowest proportion of women. This study analyses the change in gender diversity over the past decade and estimates the time required to achieve the 30% gender diversity goal, according to the critical mass in Japan in 2020. METHODS: We investigated the demographic composition of orthopaedic surgeons in 2020 by age group, the gender ratio of the main clinical fields from 2010 to 2020, and estimated the time required for the bottom 10 (i.e., least diverse) medical departments in Japan to reach the proportion of 30% women. We used simple linear regression analyses to clarify the number of years. RESULTS: In 2020, the population pyramid of orthopaedic surgeons showed that those in their 50s were the largest component with 24.1%, followed by those in their 40s and 30s with 22.3% and 19.4%, respectively. The percentage of women orthopaedic surgeons increased slightly from 4.1% in 2010 to 5.7% in 2020. This means that to achieve the proportion of 30% women at the current annual increase rate, orthopaedics would require up to 160 years, cardiovascular 149 years, and neurosurgery 135 years. CONCLUSION: Contrary to the recent increase in the number of women physicians, there has been only a slight increase in the number of women orthopaedic surgeons over the past decade. Moreover, the number of young male orthopaedic surgeons has decreased. As current orthopaedic surgeons age and retire, Japan will soon face an overall shortage of orthopaedic surgeons. Issues that must still be addressed in Japanese orthopaedics include educating men and women about gender diversity and bias, changing stereotypes about surgical lifestyles, improving work-life balance, and diligent and collaborative efforts at both the individual and community levels.

Nerve Growth Factor in Breast Cancer Cells Promotes Axonal Growth and Expression of Calcitonin Gene-related Peptide in a Rat Model of Spinal Metastasis.

BACKGROUND/AIM: Bone metastasis commonly causes severe pain. Nerve growth factor (NGF) contributes to pain, and promotes the production of pain-associated neuropeptides, such as calcitonin gene-related peptide (CGRP), from sensory nerve endings. We hypothesized that breast cancer cells have NGF levels that promote axonal growth from dorsal root ganglia (DRGs) neurons, and increase their CGRP production associated with pain from spinal metastases. MATERIALS AND METHODS: Expression of NGF by the cultured rat breast adenocarcinoma cell line CRL-1666 was determined using an enzyme-linked immunosorbent assay (ELISA). We constructed a rat model of spinal metastasis by implanting CRL-1666 into L6 vertebrae and determined the change in CGRP expression in DRG neurons innervating vertebrae immunohistochemically. RESULTS: NGF was expressed by CRL-1666. When DRG cells were co-cultured with CRL-1666, there were more CGRP-ir neurons and with a greater average length of axon growth than in cultures without CRL-1666 (p<0.05). In the rat model of metastasis, there were more CGRP-ir DRG neurons innervating vertebra treated with CRL-1666 than in vertebrae from sham surgery control rats (p<0.05). CONCLUSION: NGF from breast cancer may mediate spinal bone pain from metastasis via axonal growth and up-regulation of pain-associated neuropeptides.

Neural crest stem cells can be induced in vitro from human-induced pluripotent stem cells using a novel protocol free of feeder cells.

Objective: Our knowledge of human neural crest stem cells (NCSCs) is expanding, owing to recent advances in technologies utilizing human-induced pluripotent stem cells (hiPSCs) that generate NCSCs. However, the clinical application of these technologies requires the reduction of xeno-materials. To overcome this significant impediment, this study aimed to devise a novel method to induce NCSCs from hiPSCs without using a feeder cell layer. Materials and Methods: hiPSCs were cultured in feeder-free maintenance media containing the Rho-associated coiled-coil forming kinase inhibitor Y-27632. When the cells reached 50-70% confluence, differentiation was initiated by replacing the medium with knockout serum replacement (KSR) medium containing Noggin and SB431542. The KSR medium was then gradually replaced with increasing concentrations of Neurobasal medium from day 5 to 11. Results: Immunocytochemistry and flow cytometry were performed 12 days after induction of differentiation and revealed that the cells generated from hiPSCs expressed the NCSC markers p75 and HNK-1, but not the hiPSC marker SOX2. Conclusion: These findings demonstrate that hiPSCs were induced to differentiate into NCSCs in the absence of feeder cells.

Using peer role-playing to improve students' clinical skills for musculoskeletal physical examinations.

BACKGROUND: The traditional curriculum for medical students in Japan does not include sufficient opportunities for students to develop their skills for musculoskeletal (MSK) examination and clinical reasoning and diagnosis. Therefore, an effective programme is required to help medical students and residents improve their clinical skills in MSK. This paper aims to assess the clinical skills of medical students who have participated in a peer role-playing simulation programme using a mini clinical evaluation exercise (mini-CEX). METHODS: Participants were 90 female medical students who were completing their first orthopaedic clinical clerkship. They were divided into two groups. The simulation group participated in a role-play focussed on MSK cases as low-fidelity simulation, a structured debriefing with the course supervisor, and a self-reflection on Day 1 (n = 64). The control group did not participate in the role-play due to randomised clerkship schedules (n = 26). On Day 2 of the intervention, we observed and assessed all participants' performances during MSK outpatient encounters using the mini-CEX. We compared the mini-CEX score between the simulation group and the control group; the Wilcoxon rank-sum test was used for statistical analysis. RESULTS: The mini-CEX scores for physical examination, clinical reasoning and diagnosis, and overall clinical competency were significantly higher in the simulation group than in the control group (p < .05, physical examination: p = .014, clinical reasoning: p = .042, overall: p = .016). These findings suggest that medical students who partake in a peer role-playing simulation programme could experience improved clinical skills for physical examination, clinical reasoning and diagnosis, and overall clinical competency in real-life MSK outpatient encounters. CONCLUSIONS: Through a mini-CEX assessment, our findings indicate that medical students who participated in our peer role-playing simulation programme have improved clinical skills. Peer role-playing as a low-fidelity simulation and practical educational opportunity will enable educators to polish the competency of medical students in musculoskeletal physical examinations and clinical reasoning and diagnosis in a clinical setting.

Dual-Energy X-ray Absorptiometry and Bioelectrical Impedance Analysis are Beneficial Tools for Measuring the Trunk Muscle Mass of Patients with Low Back Pain.

INTRODUCTION: Limb muscle mass measurement using dual-energy X-ray absorptiometry (DXA) is considered the gold standard for the diagnosis of sarcopenia. Moreover, bioelectrical impedance analysis (BIA) is also recognized as a beneficial tool considering its high correlation with DXA. However, it remains to be elucidated whether DXA and BIA can accurately measure trunk lean mass. The aim of this study was to investigate the correlation between DXA and BIA measurements of trunk muscle mass and the cross-sectional area (CSA) of trunk muscles measured using magnetic resonance imaging (MRI) and to compare measures of trunk muscle mass obtained using DXA and BIA in patients with low back pain (LBP). METHODS: In total, 65 patients participated in the study. The correlation between DXA and BIA measurements and the CSA of trunk and paraspinal muscles at the L4-5 level were calculated. In addition, the correlation between DXA and BIA measurements of trunk muscle mass and the differences between these two measurements were determined. RESULTS: The correlation coefficient between DXA and BIA trunk muscle mass measurement and trunk muscle CSA was 0.74 and 0.56 for men and 0.69 and 0.44 for women, respectively. DXA and BIA measurement values showed a significantly moderate correlation with the CSA of the erector spinae (ES) and psoas major (PM). The multifidus (MF) CSA did not correlate with measurements of DXA and BIA in both men and women. Although DXA and BIA measurements were significantly correlated, a significant difference between these two measurements was found. BIA overestimated the trunk muscle mass significantly compared with DXA. CONCLUSIONS: Trunk muscle mass measured with DXA and BIA was correlated with the CSA of most trunk muscles. Although the measurement of DXA and BIA showed a high correlation, BIA overestimated trunk muscle mass compared with DXA. Both DXA and BIA are beneficial for measuring trunk muscle mass.

Tumor Necrosis Factor-α Produced by Osteoclasts Might Induce Intractable Pain in a Rat Spinal Metastasis Model of Breast Cancer.

INTRODUCTION: Causes of pain due to spinal metastases have been insufficiently investigated. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were the focus of this study. Both are known as proinflammatory cytokines associated with the pathophysiology of pain syndromes1 ). It is well known that cancer cells produce these cytokines, but whether osteoclasts produce them as well remains unclear. We hypothesize that osteoclasts produce these cytokines; in other words, pain from spinal metastasis is stronger than pain from the primary tumor. METHODS: We made a rat spinal metastasis model of breast cancer (metastasis group) and models with a hole in the vertebrae (puncture group) and resected the vertebrae. Tartrate-resistant acid phosphatase (TRAP) staining was performed to reconfirm that osteoclasts increase in vertebrae with spinal metastasis. We then evaluated TNF-α and IL-6 expression using immunohistochemistry and real-time polymerase chain reaction (PCR). RESULTS: The results of TRAP staining showed that osteoclasts increase in metastatic vertebrae. The osteoclasts in the puncture models were TNF-α negative but were TNF-α positive in the metastasis model. The osteoclasts in the puncture models and metastasis model were both IL-6 positive. According to the real-time PCR results, TNF-α in vertebrae increased in the metastasis model, but IL-6 did not increase in the metastasis model compared with in the puncture model. CONCLUSIONS: The number of osteoclasts is higher in the metastasis model. While TNF in the osteoclasts increased in the spinal metastasis model, IL-6 did not. This probably means that breast cancer affects TNF production in osteoclasts. This increase of TNF-α may lead to pain from spinal metastasis.

Skeletal Muscle Cell Oxidative Stress as a Possible Therapeutic Target in a Denervation-Induced Experimental Sarcopenic Model.

STUDY DESIGN: A basic study using a rodent model of sarcopenia. OBJECTIVE: To elucidate the contribution of oxidative stress to muscle degeneration and the efficacy of antioxidant treatment for sarcopenia using an animal model of neurogenic sarcopenia. SUMMARY OF BACKGROUND DATA: Oxidative stress has been reported to be involved in a number of pathologies, including musculoskeletal disorders. Its relationship with sarcopenia, one of the potential origins of lower back pain, however, is not yet fully understood. METHODS: Myoblast cell lines (C2C12) were treated with H2O2, an oxidative stress inducer, and N-acetyl-L-cysteine (NAC), an antioxidant. Apoptotic effects induced by oxidative stress and the antioxidant effects of NAC were assessed by western blotting, immunocytochemistry, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assays. An animal model of sarcopenia was produced via axotomy of the sciatic nerves to induce muscle atrophy. Twenty-four male Sprague-Dawley rats were divided into sham, sham+NAC, axotomy, and axotomy+NAC groups. Rats were provided water only or water containing NAC (1 g/L) for 4 weeks. The gastrocnemius muscle was isolated and stained with hematoxylin and eosin (H&E) 2 weeks after axotomy, from which muscle cells were harvested and protein extracted for evaluation. RESULTS: Mitogen-activated protein kinases (MAPKs) were significantly activated by H2O2 treatment in C2C12 cells, which was ameliorated by NAC pretreatment. Furthermore, H2O2 induced apoptosis and death of C2C12 cells, which was prevented by NAC pretreatment. The weight of the gastrocnemius muscle was reduced in the axotomy group, which was prevented by NAC administration. Lastly, although muscle specimens from the axotomy group showed greater reductions in muscle fiber, the oral administration of NAC significantly inhibited amyotrophy via antioxidant effects. CONCLUSION: The current in vitro and in vivo study demonstrated the possible involvement of oxidative stress in sarcopenic pathology. NAC represents a potential anti-sarcopenic drug candidate, preventing amyotrophy and fatty degeneration. LEVEL OF EVIDENCE: 4.

Platelet-rich plasma enhances bone union in posterolateral lumbar fusion: A prospective randomized controlled trial.

BACKGROUND CONTEXT: Platelet-rich plasma (PRP) accelerates bone union in vivo in a rodent model of spinal fusion surgery. However, PRP's effect on bone union after spinal surgery remains unclear. PURPOSE: The objective of this study was to evaluate the efficacy of PRP after posterolateral lumbar fusion (PLF) surgery. STUDY DESIGN/SETTING: Single-center prospective randomized controlled clinical trial with 2-year follow-up. PATIENT SAMPLE: The patient sample included a total 62 patients (31 patients in the PRP group or 31 patients in the control group). OUTCOME MEASURES: The outcome measures included the bone fusion rate, the area of bone fusion mass, the duration of bone fusion, and the clinical score using the visual analog scale (VAS). MATERIALS AND METHODS: We randomized 62 patients who underwent one- or two-level instrumented PLF for lumbar degenerative spondylosis with instability to either the PRP (31 patients) or the control (31 patients) groups. Platelet-rich plasma-treated patients underwent surgery using an autograft bone chip (local bone), and PRP was prepared from patient blood samples immediately before surgery; patients from the control group underwent PLF without PRP treatment. We assessed platelet counts and growth factor concentrations in PRP prepared immediately before surgery. The duration of bone union, the postoperative bone fusion rate, and the area of fusion mass were assessed using plain radiography every 3 months after surgery and by computed tomography at 12 or 24 months. The duration of bone fusion and the clinical scores for low back pain, leg pain, and leg numbness before and 3, 6, 12, and 24 months after surgery were evaluated using VAS. RESULTS: Data from 50 patients with complete data were included. The bone union rate at the final follow-up was significantly higher in the PRP group (94%) than in the control group (74%) (p=.002). The area of fusion mass was significantly higher in the PRP group (572 mm2) than in the control group (367 mm2) (p=.02). The mean period necessary for union was 7.8 months in the PRP group and 9.8 months in the control group (p=.013). In the PRP, the platelet count was 7.7 times higher and the growth factor concentrations were 50 times higher than those found in plasma (p<.05). There was no significant difference in low back pain, leg pain, and leg numbness in either group at any time evaluated (p>.05). CONCLUSIONS: Patients treated with PRP showed a higher fusion rate, greater fusion mass, and more rapid bone union after spinal fusion surgery than patients not treated with PRP.

Elevated Levels of Serum Pentosidine Are Associated with Dropped Head Syndrome in Older Women.

STUDY DESIGN: A retrospective observational study was performed. PURPOSE: We investigated the prevalence of sarcopenia in dropped head syndrome (DHS), and the relationship between biochemical markers, including major advanced glycation end products (AGEs), pentosidine, and DHS in older women. OVERVIEW OF LITERATURE: AGEs have been implicated in the pathogenesis of sarcopenia. METHODS: We studied 13 elderly women with idiopathic DHS (mean age, 77.2 years) and 20 healthy volunteers (mean age, 74.8 years). We used a bioelectrical impedance analyzer to analyze body composition, including appendicular skeletal muscle mass index (SMI; appendicular lean mass [kg]/[height (m)]2). Cervical sagittal plane alignment, including C2-C7 sagittal vertical axis (C2-C7SVA), C2-C7 angle, and C2 slope (C2S), was measured. Biochemical markers, such as serum and urinary pentosidine, serum homocysteine, 1, 25-dihydroxyvitamin D, and 25-hydroxyvitamin D, were measured. The level of each variable was compared between DHS and controls. The relationship between biochemical markers and DHS was examined. RESULTS: Sarcopenia (SMI <5.75) was observed at a high prevalence in participants with DHS (77% compared to 22% of healthy controls). Height, weight, femoral bone mineral density, appendicular lean mass, total lean mass, and SMI all had significantly lower values in the DHS group. Serum and urinary pentosidine, and serum homocysteine were significantly higher in the DHS group compared to controls. Analysis of cervical alignment revealed a significant positive correlation of serum pentosidine with C2-C7SVA and C2S. CONCLUSIONS: Sarcopenia was involved in DHS, and high serum pentosidine levels are associated with severity of DHS in older women.

Influence of Skeletal Muscle Mass and Spinal Alignment on Surgical Outcomes for Lumbar Spinal Stenosis.

STUDY DESIGN: Retrospective observational study. PURPOSE: We considered the relationship between spinal alignment and skeletal muscle mass on clinical outcomes following a surgery for lumbar spinal stenosis (LSS). OVERVIEW OF LITERATURE: There are no reports of preoperative factors predicting residual low back pain following surgery for LSS. METHODS: Our target population included 34 women (mean age, 74.4 years) who underwent surgery for LSS. Prior to and 6 months after the surgery, systemic bone mineral density and lean soft tissue mass were measured using dual-energy X-ray absorptiometry. Skeletal muscle mass index (SMI) was calculated as the sum of the arm and leg lean mass in kilograms divided by height in meters squared. The spinal alignment was also measured. Clinical outcomes were evaluated using the Japanese Orthopedic Association scoring system, leg and low back pain Visual Analog Scale, and Roland-Morris Disability Questionnaire (RDQ). Additionally, we examined the bone mineral density, skeletal muscle mass, and spinal alignment before and after the surgery. We used the Spearman correlation coefficient to examine the associations among clinical outcomes, preoperative muscle mass, and spinal alignment. RESULTS: Sarcopenia (SMI <5.46) was observed in nine subjects (26.5%). Compared with normal subjects (SMI >6.12), RDQ was significantly higher in subjects with sarcopenia (p =0.04). RDQ was significantly negatively correlated with SMI (r =-0.42, p <0.05). There was a significant positive correlation between postoperative RDQ and pelvic tilt (PT; r =0.41, p <0.05). SMI and PT were significantly negatively correlated (r =-0.39, r <0.05). CONCLUSIONS: Good postoperative outcomes were negatively correlated with low preoperative appendicular muscle mass, suggesting that postoperative outcomes were inferior in cases of decreased appendicular muscle mass (sarcopenia). Posterior PT due to decreased limb muscle mass may contribute to postoperative back pain, showing that preoperatively reduced limb muscle mass and posterior PT are predictive factors in the persistence of postoperative low back pain.

Vascular endothelial growth factor in degenerating intervertebral discs of rat caudal vertebrae.

INTRODUCTION: Discogenic back pain remains poorly understood with respect to etiopathogenesis, despite being a considerable burden. We sought to examine the expression of vascular endothelial growth factor in injured intervertebral discs in rat caudal vertebrae. METHODS: Forty-eight male Sprague Dawley rats were assigned to 2 groups according to disc puncture injury: puncture (n = 32) or non-puncture (n = 16). Disc puncture was performed percutaneously such that the incision would be in the primary plane of motion for the coccygeal discs 5-6, 6-7, and 7-8. A 26-gauge needle was used to puncture each disc 10 times. Punctured discs were examined histologically by hematoxylin and eosin staining at 1, 7, 14, and 28 days post-injury. RESULTS: Vascular endothelial growth factor was localized immunohistochemically, and determined quantitatively using an enzyme-linked immunosorbent assay. Peak inflammation occurred on the 7th day post-injury, but tissue degeneration continued until day 28. Local expression of vascular endothelial growth factor tended to be highest in the annulus fibrosus on the 7th and 14th days after puncture injury. The level of vascular endothelial growth factor was highest 1-day post-injury, and then gradually decreased thereafter. Furthermore, vascular endothelial growth factor levels in the puncture group were significantly higher than those in the non-puncture control group (p < 0.05). CONCLUSIONS: We found increased expression of the inflammatory cytokine vascular endothelial growth factor in injured intervertebral discs, suggesting that vascular endothelial growth factor may be clinically important in discogenic back pain.

The effects of minodronate and activated vitamin D on bone mineral density and muscle mass in postmenopausal women with osteoporosis.

INTRODUCTION: Osteoporosis and sarcopenia are said to be similar disorders. However, few reports have described the effects of anti-osteoporosis drugs on muscle mass in clinical practice. METHODS: We selected 150 postmenopausal women with osteoporosis treated by minodronate (osteoporosis medication [OM] group) and 50 postmenopausal women without osteoporosis who did not receive treatment (no osteoporosis [NO] group). The OM group was further divided into two treatment subgroups: a combination of monthly minodronate and daily activated vitamin D vs. monthly minodronate alone. We measured lumbar spine and femoral neck bone mineral density (BMD) with dual-energy X-ray absorptiometry and muscle mass of the upper limbs, lower limbs, and trunk with bioelectrical impedance analysis at baseline and after 6 months. RESULTS: The OM and NO groups contained 130 and 37 patients, respectively (mean age: 73.9 ± 8.3 and 74.1 ± 10.0 years, respectively). In the OM group, lumbar spine BMD significantly increased after 6 months, while lower limb muscle mass significantly decreased. In the NO group, lumbar spine BMD and lower limb muscle mass did not significantly change after 6 months. In the OM group, BMD of the lumbar spine significantly increased but the lower limb muscle mass significantly decreased after 6 months relative to the NO group. In the combination therapy subgroup of the OM group muscle mass decreased significantly less than in the minodronate-alone subgroup. CONCLUSIONS: In postmenopausal women with osteoporosis, minodronate can increase BMD but cannot increase muscle mass. However, simultaneous use of activated vitamin D can suppress muscle mass decrease. The combination of activated vitamin D and minodronate may be useful for treating osteoporosis in postmenopausal women.

Osteoporotic Pain is Associated with Increased Transient Receptor Vanilloid 4 Expression in the Dorsal Root Ganglia of Ovariectomized Osteoporotic Rats: A Pilot Basic Study.

INTRODUCTION: Osteoporosis can produce a persistent state of pain known as osteoporotic pain. One proposed mechanism of this pathology is increased calcitonin gene-related peptide (CGRP; a marker related to inflammatory pain) expression in the dorsal root ganglia (DRG) innervating osteoporotic vertebrae. Alternatively, a previous study revealed that axial loading caused osteoporotic pain in a rodent model of coccygeal vertebrae compression. Because this compression model is associated with trauma, additional mechanistic studies of osteoporotic pain in the absence of trauma are required. The current study aimedto evaluate the expression and relative distribution of transient receptor potential vanilloid 4 (TRPV4), a pain-related mechanoreceptor, in ovariectomized (OVX) osteoporotic rats. METHODS: CGRP-immunoreactive (-ir) and TRPV4-ir DRG neurons innervating the L3 vertebrae of Sprague-Dawley rats were labeled with a neurotracer, FluoroGold. Intravertebral pH was also measured during the neurotracer procedure. TRPV4-ir/CGRP-ir FluoroGold-positive DRG neurons were quantified in sham control and OVX rats (n = 10, ea). The threshold for statistical significance was set at P < 0.05. RESULTS: There was no statistical difference in the number of FluoroGold-positive DRG neurons between groups; however, there were significantly more CGRP-ir/TRPV4-ir FluoroGold-positive DRG neurons in the OVX group compared with the sham control group (P < 0.05) as well as the significantly increased molecular production of each peptide. Intravertebral pH was also lower in the OVX group compared with the sham control group (P < 0.05). CONCLUSION: Sensory neurons innervating osteoporotic vertebrae exhibited increased expression of co-localized CGRP and TRPV4 in OVX osteoporotic rats. Additionally, intravertebral pH was low in the vicinity osteoporotic vertebrae. Considering that TRPV4 is a mechanosensitive nociceptor that is activated in acidic environments, its upregulation may be associated with the pathology of osteoporotic pain derived from microinflammation involved in osteoporosis.

Pentosidine concentration is associated with degenerative lumbar scoliosis in older women: preliminary results.

PURPOSE: Advanced glycation end products (AGEs) have been implicated in the pathogenesis of sarcopenia. The objective of the study was to investigate the prevalence of sarcopenia in degenerative lumbar scoliosis (DLS), and the relationship between biochemical markers including major AGEs, pentosidine, and DLS in older women. METHODS: Our study participants were 20 elderly women with idiopathic DLS (mean age 76.4 years, range 56-88). Nineteen age- and sex-matched volunteers (mean age 74.0 years, range 62-86) served as controls. Spinal and femoral BMD of all participants was measured using dual-energy X-ray absorptiometry. We used a bioelectrical impedance analyzer to analyze body composition, including appendicular skeletal muscle mass index [SMI; appendicular lean mass (kg)/(height (m)]2. SMI < 5.75 was considered diagnostic for sarcopenia. Coronal and sagittal spinal alignments were measured. The following biochemical markers were measured: serum and urinary pentosidine, serum homocysteine, 1,25(OA)2D, and 25(OH)D. The level of each variable was compared between DLS and controls. The relationship between biochemical markers including pentosidine and DLS was examined. RESULTS: Sarcopenia was observed at a high prevalence in participants with DLS: 50% compared with 15.8% of healthy controls. Height, weight, femoral BMI, appendicular lean mass, total lean mass, and SMI all had significantly lower values in the DLS group. Serum pentosidine was significantly higher for the DLS group compared with controls. Correlations with serum pentosidine revealed a significant positive correlation between lumbar scoliosis, pelvic tilt, and pelvic incidence-lumbar lordosis mismatch, and a significantly negative correlation between thoracic kyphosis (P < 0.05). CONCLUSIONS: We found that sarcopenia was involved in DLS, and high serum pentosidine levels are associated with severity of coronal and sagittal malalignment in older women, suggesting that high levels of AGEs are a potential biomarker for the progression of lumbar scoliosis and kyphotic deformity. Further studies are needed to clarify the pathogenesis of DLS.