藤田 順之

INTRODUCTION/AIMS: T2 magnetic resonance imaging (MRI) mapping has been applied to carpal tunnel syndrome (CTS) for quantitative assessment of the median nerve. However, quantitative changes in the median nerve before and after surgery using T2 MRI mapping remain unclear. We aimed to investigate whether pathological changes could be identified by pre- and postoperative T2 MRI mapping of the median nerve in CTS patients after open carpal tunnel release. METHODS: This was a prospective study that measured median nerve T2 and cross-sectional area (CSA) values at the distal carpal tunnel, hamate bone, proximal carpal tunnel, and forearm levels pre- and postoperatively. Associations between T2, CSA, and nerve conduction latency were also evaluated. RESULTS: A total of 36 patients with CTS (mean age, 64.5 ± 11.7 years) who underwent surgery were studied. The mean preoperative T2 values significantly decreased from 56.3 to 46.9 ms at the proximal carpal tunnel levels (p = .001), and from 52.4 to 48.7 ms at the hamate levels postoperatively (p = .04). Although there was a moderate association between preoperative T2 values at the distal carpal tunnel levels and distal motor latency values (r = -.46), other T2 values at all four carpal tunnel levels were not significantly associated with CSA or nerve conduction latency pre- or postoperatively. DISCUSSION: T2 MRI mapping of the carpal tunnel suggested a decrease in nerve edema after surgery. T2 MRI mapping provides quantitative information on the median nerve before and after surgery.

Hand osteoarthritis (HOA), characterized by an earlier onset age and reduced susceptibility to mechanical stress compared with knee and hip osteoarthritis, is considered a suitable disease for identifying predictive biomarkers of osteoarthritis. In particular, DNA methylation variants, expected to contribute to HOA susceptibility, hold potential as osteoarthritis biomarkers. In this study, leukocyte DNA methylation patterns were analyzed in blood samples from patients with HOA, aiming to identify disease-specific biomarkers for osteoarthritis. Using DNA methylation microarrays, we analyzed samples from three subjects with HOA and three age- and gender-matched healthy individuals. For validation, pyrosequencing analysis was conducted using samples from 16 to 9 subjects with and without HOA, respectively. From 735,026 probes in the DNA methylation array, the Top 100 CpG sites associated with HOA, based on low adjusted P-values, including those targeting bone morphogenetic protein 7 (BMP7), SBF2-AS1, PLOD2, ICOS, and CSF1R were identified. Validation analysis revealed significantly higher methylation levels in the BMP7-related site in the HOA group compared with the control group, even after adjusting for age, gender, and body mass index (p = 0.037). In contrast, no significant difference was observed in the other selected CpG sites between the HOA and control groups. This study highlights the significantly increased frequency of methylation at the specific BMP7 site in leukocytes of patients with HOA, suggesting its potential as a biomarker for HOA. Measurement of methylation levels at the CpG sites identified in this study offers a potential approach to prevent future osteoarthritis progression, providing valuable insights into disease management.

BACKGROUND: Managing medication use in older orthopedic patients is imperative to extend their healthy life expectancy in an aging society. However, the actual situation regarding polypharmacy, the intake of potentially inappropriate medications (PIMs), and fall risk-increasing drugs (FRIDs) among older orthopedic patients is not well characterized. This study aimed to investigate the medication-based profiles of older orthopedic patients to highlight the critical points of concern. METHODS: We retrospectively reviewed the clinical data of consecutive patients aged ≥ 65 years who underwent orthopedic surgery at two acute care hospitals between April 2020 and March 2021. The cutoff number of prescribed drugs for polypharmacy was set at 6. According to the specified guidelines, 19 categories of drugs were identified as PIMs, and 10 categories were classified as FRIDs. RESULTS: A total of 995 older patients with orthopedic surgery were assessed, of which 57.4% were diagnosed with polypharmacy, 66.0% were receiving PIMs, and 41.7% were receiving FRIDs. The prevalence of FRID intake did not significantly differ among patients with degenerative spinal disease (n = 316), degenerative disease of extremities (n = 331), and fractures (n = 272). Compared with patients with degenerative disease of the extremities, the multivariable-adjusted prevalence ratios (PRs) of polypharmacy and PIM intake were significantly higher in patients with degenerative spinal disease (1.26 [confidence intervals (CI): 1.11-1.44] and 1.12 [CI: 1.00-1.25]), respectively. Use of antiemetic drugs (adjusted PR, 13.36; 95% CI: 3.14-56.81) and nonsteroidal anti-inflammatory drugs (adjusted PR, 1.37; 95% CI: 1.05-1.78) was significantly higher in patients with degenerative spinal disease. Among patients with degenerative spinal disease, the prevalence of antiemetic drug intake was 8.7% in lumbar spinal patients and 0% in cervical spinal patients. CONCLUSIONS: More than half of the orthopedic patients in this study were affected by polypharmacy, and approximately two-thirds were prescribed some form of PIMs. Patients with degenerative spinal disease showed a significantly higher prevalence of polypharmacy and PIM use compared with other orthopedic diseases. Particular attention should be paid to the high frequency of antiemetic drugs and nonsteroidal anti-inflammatory drugs intake among patients with degenerative lumbar spine conditions.

BACKGROUND: In total knee arthroplasty (TKA), cementless fixation is initially weaker than cement fixation. This study aimed to examine whether filling the tibial peg holes with bone improves initial fixation strength in cementless TKA. METHODS: This prospective, comparative study examined 88 joints in 66 patients randomized to the bone filling (48 joints) or conventional group (no bone filling; 40 joints). All patients underwent TKA with the NexGen® trabecular metal modular tibial component. In the bone filling group, resected cancellous bone was filled into the peg holes before insertion of the tibial component. We performed clinical and plain radiographic evaluations after the operation and measured bone mineral density (BMD) at five sites below the component at 1, 3, 6, and 12 months postoperatively. RESULTS: Operative time and clinical evaluations were not significantly different. Plain radiography showed significant longitudinal thickening of the trabecula below the peg (P<0.05) and decreased occurrence of reactive lines (P=0.07) in the bone filling group compared with the conventional group. BMD was significantly higher in the bone filling group in the medial region below the peg at 1, 3, and 6 months and in the central region at 1 and 3 months (all P<0.05). CONCLUSIONS: When using the NexGen trabecular metal modular tibial component, concurrent peg hole bone filling increases the initial component fixation strength. Possible effects on long-term stabilization warrant further study.

BACKGROUND: The management of degenerative cervical myelopathy (DCM), which often impairs lower extremity function and increases the risk of falls, is gaining recognition for its importance in an aging society. Despite the significant overlap between frailty and locomotive syndrome (LS) in older adults, their interaction in older DCM patients remains unclear. We aimed to determine the characteristics of older DCM patients with frailty, focusing on the association between frailty and LS. METHODS: We retrospectively examined the clinical records and imaging data of consecutive patients aged 65 years and above who underwent surgery for DCM at a single facility. Frailty and LS stage were diagnosed using the modified frailty index-11 and the 25-question Geriatric Locomotive Function Scale (GLFS-25), respectively. RESULTS: A total of 114 subjects were analyzed, among whom approximately 30% were diagnosed with frailty. DCM patients with frailty had significantly worse Japanese Orthopaedic Association Cervical Myelopathy Assessment Questionnaire (JOACMEQ) and GLFS-25 scores at baseline than did those without frailty. Moreover, DCM patients with frailty had significantly more advanced LS stage at baseline than did those without frailty. Meanwhile, no significant difference in the improvement in JOACMEQ and GLFS-25 scores were observed between those with and without frailty after surgery. More precisely, DCM patients with frailty experienced better improvement in lower extremity function based on the JOACMEQ than did those without frailty. CONCLUSIONS: Our results demonstrated that older DCM patients had favorable outcomes following surgery regardless of frailty. Despite the significant association between frailty and LS in DCM patients, frailty did not negatively impact the improvement in LS in older DCM patients. These findings provide valuable information for both older DCM patients and their attending physicians that would help guide decisions about cervical spine surgery for DCM.

Bone fractures represent a common health problem, particularly in an increasingly aging population. Bioresorbable magnesium (Mg) alloy-based implants offer promising alternatives to traditional metallic implants for the treatment of bone fractures because they eliminate the need for implant removal after healing. The Mg-Y-rare-earth (RE)-Zr alloy WE43, designed for orthopedic implants, has received European Conformity mark approval. However, currently, WE43 is not clinically used in certain countries possibly because of concerns related to RE metals. In this study, we investigated the use of a RE-free alloy, namely, Mg-Zn-Zr alloy (ZK30), as an implant for bone fractures. Hydrofluoric acid (HF) treatment was performed to improve the corrosion resistance of ZK30. HF-treated ZK30 (HF-ZK30) exhibited lower corrosion rate and higher biocompatibility than those of WE43 in in vitro experiments. After implanting a rod of HF-ZK30 into the fractured femoral bones of mice, HF-ZK30 held the bones and healed the fracture without deformation. Treatment results of HF-ZK30 were comparable to those of WE43, indicating the potential of HF-ZK30 as a bioresorbable and safe implant for bone repair.

INTRODUCTION: Recently, patient satisfaction has gained prominence as a crucial measure for ensuring patient-centered care. Furthermore, patient satisfaction after lumbar spinal canal stenosis (LCS) surgery is an important metric for physician's decision of surgical indication and informed consent to patient. This study aimed to elucidate how patient satisfaction changed after LCS surgery to identify factors that predict patient dissatisfaction. METHODS: We retrospectively reviewed time-course data of patients aged ≥40 years who underwent LCS surgery at multiple hospitals. The participants completed the Zurich Claudication Questionnaire (ZCQ) and the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) before surgery and then 6 months and 1 year postsurgery. Patient satisfaction was categorized according to the postoperative score of the satisfaction domain of the ZCQ: satisfied, score ≤2.0; moderately satisfied, 2.0< score ≤2.5; and dissatisfied, score >2.5. RESULTS: The study enrolled 241 patients. Our data indicated a satisfaction rate of around 70% at 6 months and then again 1 year after LCS surgery. Among those who were dissatisfied 6 months after LCS surgery, 47.6% were more satisfied 1 year postsurgery. Furthermore, 86.2% of those who were satisfied 6 months after LCS surgery remained satisfied at 1 year. Multivariable analysis revealed that age (relative risk, 0.5; 95% confidence interval, 0.2-0.8) and preoperative score of psychological disorders on the JOABPEQ (relative risk, 0.2; 95% confidence interval, 0.03-0.08) were significantly associated with LCS surgery dissatisfaction. In addition, the receiver operating characteristic curve analysis revealed that the cutoff value for the preoperative score of psychological disorder of the JOABPEQ was estimated at 40 for LCS surgery dissatisfaction. CONCLUSIONS: Age and psychological disorders were identified as significant predictors of dissatisfaction, with a JOABPEQ cutoff value providing potential clinical applicability.

INTRODUCTION: Locomotive syndrome caused by degenerative musculoskeletal diseases is reported to improve with surgical treatment. However, it is unclear whether surgical treatment is effective for the locomotive syndrome developing in patients with degenerative cervical myelopathy (DCM). Thus, this study primarily aimed to longitudinally assess the change in locomotive syndrome stage before and after cervical spinal surgery for patients with DCM using the 25-question geriatric locomotive function scale (GLFS-25). A secondary objective was to identify factors associated with the postoperative improvement in the locomotive syndrome stage. METHODS: We retrospectively reviewed clinical data of patients undergoing cervical spine surgery at our institution from April 2020 to May 2022 who had answered the Japanese Orthopaedic Association Cervical Myelopathy Assessment Questionnaire, visual analog scale, and GLFS-25 preoperatively and at 6 months and 1 year postoperatively. We collected demographic data, medical history, preoperative radiographic parameters, presence or absence of posterior longitudinal ligament ossification, and surgical data. RESULTS: We enrolled 115 patients (78 men and 37 women) in the present study. Preoperatively, using the GLFS-25, 73.9% of patients had stage 3, 10.4% had stage 2, 9.6% had stage 1, 6.1% had no locomotive syndrome. The stage distribution of locomotive syndrome improved significantly at 6-months and 1-year postoperatively. The multivariable Poisson regression analysis revealed that better preoperative lower extremity function (relative risk: 3.0; 95% confidence interval: 1.01-8.8) was significantly associated with postoperative improvement in the locomotive syndrome stage. CONCLUSIONS: This is the first study to longitudinally assess the locomotive syndrome stage in patients with DCM using GLFS-25. Our results indicated that patients with DCM experienced significant improvement in the locomotive syndrome stage following cervical spine surgery. Particularly, the preoperative lower extremity function was significant in postoperative improvement in the locomotive syndrome stage.

INTRODUCTION: Frailty is an important factor in surgical outcomes. The current study aimed to evaluate the effect of preoperative frailty on postoperative outcomes in older patients with lumbar spinal canal stenosis (LSCS). METHODS: We retrospectively examined 209 patients aged ≥65 years who underwent surgery for LSCS. Health-related quality-of-life (HRQOL) tools, including the Roland-Morris Disability Questionnaire (RDQ), Zurich Claudication Questionnaire (ZCQ), and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), were used in the assessment conducted before surgery and at 6 months and 1 year after surgery. Frailty was categorized based on the 11-item modified frailty index (mFI-11). Patients with mFI-11 of 0, <0.21, and >0.21 were classified under the robust (R), pre-frailty (P), and frailty (F) groups, respectively. RESULTS: According to the mFI-11, 24, 138, and 47 patients were included in the R, P, and F groups, respectively. Regarding preoperative radiographic parameters, there was a remarkable increase in the sagittal vertical axis and a significant decrease in the development of lumbar lordosis with frailty progression. The preoperative scores of RDQ and ZCQ, and lumbar function, walking ability, social life, and psychological disorder domain scores of JOABPEQ differed significantly among these groups. The frequency of revision surgery was not higher in the F group than in the other groups. After adjustment for factors have shown different distributions among the three groups, the frequency of effective surgical cases did not show a clear trend among the three groups in all domains of the JOABPEQ. CONCLUSIONS: The preoperative HRQOL scores and the radiographic parameters of patients with LSCS worsened with frailty severity. However, frailty did not affect the rate of revision surgery and surgical efficacy in patients with LSCS. Although this study has limitations, our findings indicated that even LSCS patients with frailty can be considered for surgery if they have an indication for LSCS surgery.

BACKGROUND: Various treatments for chronic low back pain (LBP) have been reported; among them, platelet-rich plasma (PRP) as a regenerative medicine has attracted much attention. Although Modic type 1 change (MC1) is associated with LBP, no treatment has been established so far. In addition, no studies have administered PRP to intervertebral discs (IVDs) in patients with LBP, targeting MC1 only. Thus, the purpose of this study was to determine the safety and efficacy of PRP administration to the IVDs in patients with MC1 experiencing LBP. METHODS: PRP was injected intradiscally to 10 patients with MC1 experiencing LBP. Patients were followed prospectively for up to 24 weeks after primary administration. Physical condition, laboratory data, and lumbar x-ray images were evaluated for safety assessment. Furthermore, to evaluate the effectiveness of PRP, patient-reported outcomes were considered. In addition, changes in MC1 were assessed using magnetic resonance imaging (MRI). RESULTS: There were no adverse events in the laboratory data or lumbar X-ray images after administration. The mean visual analog scale, which was 70.0 ± 13.3 before the treatment, significantly decreased 1 week after PRP administration and was 39.0 ± 28.8 at the last observation. Oswestry disability index and Roland Morris disability questionnaire scores promptly improved after treatment, and both improved significantly 24 weeks after PRP administration. Follow-up MRI 24 weeks after treatment showed a significant decrease in the mean high-signal intensity of fat-suppressed T2-weighted imaging from 10.1 to 7.90 mm2 compared with that before PRP administration. CONCLUSIONS: The safety and efficacy of PRP administration to the IVDs of patients with MC1 experiencing LBP were identified. Post-treatment MRI suggested improvement in inflammation, speculating that PRP suppressed inflammation and consequently relieved the patient's symptoms. Despite the small number of patients, this treatment is promising for patients with MC1 experiencing LBP. The study protocol has been reviewed and approved by the Certified Committee for Regenerative Medicine and the Japanese Ministry of Health, Labor and Welfare (Japan Registry of Clinical Trials [jRCT] No. jRCTb042210159).

STUDY DESIGN: Multicenter case-control study. OBJECTIVE: To identify imaging characteristics of the cervical spine in patients with retro-odontoid pseudotumor (ROP) without rheumatoid arthritis (RA) and determine the pathogenesis of ROP. SUMMARY OF BACKGROUND DATA: ROP results from proliferative changes in the soft tissue of the atlantoaxial junction surrounding the region of the transverse ligament, and is commonly seen in RA patients. However, the pathogenesis of ROP caused by mechanical instability of the upper cervical spine in patients without RA is yet to be explained. METHODS: We collected imaging data (preoperative radiographs, magnetic resonance imaging [MRI], and computed tomography [CT]) of patients who underwent surgery between April 2011 and March 2022 at the three university hospitals for ROP (cases) and cervical spondylotic myelopathy (as age, sex, and institution matched controls). The two groups were compared for different parameters on cervical dynamic radiographs, MRI, and CT. RESULTS: The ROP group consisted of 42 patients, and the control group comprised 168 patients. C2-C7 range of motion was significantly smaller in the ROP group (25.8 ± 2.6°) compared to the control group (33.0 ± 1.0°). C2-C7 sagittal vertical axis was significantly larger in the ROP group than the control group (39.3 ± 3.6 mm versus 32.2 ± 1.3 mm). MRI and CT assessment showed progressive degeneration at all intervertebral levels in the ROP group. A significant positive correlation was observed between the thickness of the soft tissue posterior to the dental process and the atlantodental interval in the flexion position (r = 0.501). CONCLUSION: The development of ROP was associated with degeneration of facet joints and intervertebral discs in the middle and lower cervical spine. Our findings suggest that decreased mobility of the middle and lower cervical spine may cause instability in the upper cervical spine, leading to the formation of ROP.

AIMS: With the aging society worldwide, lumbar spinal stenosis (LSS) has become common, and its incidence has been increasing worldwide. Frailty and locomotive syndrome significantly overlap as disorders in older people. The current study aimed to validate the association between frailty and locomotive syndrome in patients with LSS. In particular, the involvement of frailty in locomotive syndrome following surgery was examined. METHODS: We retrospectively reviewed the time-course data of consecutive patients aged ≥65 years who underwent lumbar spinal surgery for LSS. The locomotive syndrome stages were determined using the 25-Question Geriatric Locomotive Function Scale: stage 0, score ≤6; stage 1, score ≥7; stage 2, score ≥16; and Stage 3, score ≥24. Robust, pre-frailty, and frailty were defined as a modified frailty index-11 score of 0, <0.21, and >0.21, respectively. RESULTS: This study included 234 patients. All patients except one were diagnosed with locomotive syndrome preoperatively. Approximately 24.8% of participants were diagnosed with frailty. LSS surgery improved locomotive syndrome regardless of frailty severity. Meanwhile, multivariable analysis indicated that frailty could significantly inhibit improvement in locomotive syndrome after surgery in old patients with LSS (estimated relative risk: 0.6; 95% confidence interval: 0.4-0.9). CONCLUSIONS: This study first assessed the association between locomotive syndrome and frailty in patients with LSS. Locomotive syndrome could be managed effectively with surgery regardless of frailty severity in old patients with LSS. However, our findings emphasize the need to screen for frailty preoperatively in this patient group. Geriatr Gerontol Int 2024; 24: 116-122.

CASE: An 85-year-old woman was transported to our institution due to difficulty in walking. Preoperative imaging showed spinal cord lesions indicative of spinal cord tumor at the T7-8 level, accompanied by T8 vertebral fracture. Intraoperatively, the spinal lesion was suspected to be an epidural abscess; therefore, the capsule was resected, and the abscess was drained. We added pedicle screw fixation at the T6-10 level. Postoperatively, the spinal cord lesion was definitively diagnosed as spinal epidural tuberculoma. CONCLUSION: Spinal epidural tuberculomas should be considered in the treatment of spinal cord lesions causing paralysis attributed to spinal cord compression.

INTRODUCTION: Fractures are often caused by falls in older people. Among various causes of falls, polypharmacy is known to be a risk of falls. Furthermore, potentially inappropriate medicines (PIMs), which interact with polypharmacy, include the drugs involved in falls. Here, we primarily aimed to investigate the prescribed drugs in older surgical patients with extremity fractures to determine the frequency of polypharmacy and identify PIMs. The second aim was to clarify the characterization of prescribed drugs of older patients with hip fracture. MATERIALS AND METHODS: We retrospectively collected the following clinical data of consecutive patients aged ≥65 years who underwent surgery for extremity fractures at our hospital between April 2019 and March 2021. A total of 19 categories were considered as PIMs. The Poisson regression models were used to examine the association between the number of prescribed drugs and hip fracture prevalence. RESULTS: A total of 590 patients were reviewed. Our data showed that 55% of older patients with extremity fractures took ≥6 prescription drugs. The frequency of prescription of hypnotics, antithrombotic drugs, diuretics, and non-steroidal anti-inflammatory drugs was comparatively high among the 19 categories of PIMs. Multivariable analysis revealed that polypharmacy was significantly associated with hip fractures. Among PIMs, antithrombotic drugs and diuretics were significantly associated with the prevalence of hip fractures. Finally, we found a significant positive association between the prevalence of hip fracture and the number of drug categories of PIMs among older patients with extremity fractures. CONCLUSIONS: The present study clarified the characterization of the prescribed drugs in older surgical patients with extremity fractures. Special attention should be paid to hip fractures of older patients with polypharmacy or prescribed with many drugs categories of PIMs, particularly antithrombotic drugs and diuretics.

PURPOSE: It is still unclear how lumbar spinal surgery affects the lipid metabolism of patients with lumbar spinal disorders (LSDs) such as lumbar spinal canal stenosis and lumbar disk herniation. The present study aimed to assess the impact of lumbar spinal surgery on lipid metabolism in patients with LSDs and clarify the factors associated with changes in visceral fat (VF) accumulation before and after lumbar spinal surgery. METHODS: Consecutive patients with lumbar spinal surgery for LSDs were prospectively included. Abdominal computed tomography images and blood examination of the participants were evaluated before surgery and at 6 months and 1 year after surgery. The cross-sectional VF area (VFA) was measured at the level of the navel using computed tomography images. Blood examination items included triglycerides and high-density lipoprotein (HDL). RESULTS: The study enrolled a total of 138 patients. Female patients with LSDs had significantly increased VFA and serum triglyceride levels after lumbar spinal surgery. On multivariable analysis, the group with > 100 cm2 of preoperative VFA and a postoperative decrease in VFA had a significantly worse preoperative walking ability based on the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (relative risk 2.1; 95% confidence intervals 1.1-4.1). CONCLUSIONS: The present study demonstrated that patients with LSDs did not necessarily improve their lipid metabolism after lumbar spinal surgery. Instead, female patients with LSDs had significantly deteriorated lipid metabolism after lumbar spinal surgery. Finally, a worse preoperative walking ability was associated with the improvement in excess VF accumulation after lumbar spinal surgery.

BACKGROUND: Posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) has a potential risk for postoperative pleural effusion. Although pleural effusion at an early period after PSF for AIS occurs with a relatively high frequency and occasionally requires some treatments, the impact of postoperative pleural effusion on future pulmonary function or lung volume (LV) has not been clarified to date. The aim of this study was to evaluate the effect of pleural effusion after PSF for AIS on the postoperative pulmonary function and LV. METHODS: A total of 114 consecutive patients who underwent PSF for AIS followed up greater than 2 years at our institute were retrospectively reviewed. We evaluated postoperative pleural effusion by computed tomography (CT) at the 1-week follow-up and divided patients into the pleural effusion (PF) and non-pleural effusion (NP) groups. We investigated spirometry parameters recorded for testing included vital capacity (VC), forced expiratory volume in the first second (FEV1), %VC, and FEV1% and measured the LV using CT images and a workstation at baseline and 2 years after surgery. RESULTS: A total of 87 (76.3%) patients with postoperative pleural effusion were identified, but all patients were asymptomatic and did not require additional treatment for postoperative pleural effusion. All pulmonary function parameters at the 2-year follow-up exhibited no significant differences between the two groups. Although preoperative left LV (1.21±0.30 L vs. 1.36±0.34 L; p=.022) and total LV (2.68±0.62 L vs. 2.99±0.73 L; p=.031) were significantly lower in the PF group than in the NP group, all postoperative LV parameters were similar between the two groups. CONCLUSIONS: Pleural effusion at an early period after PSF for AIS was a postoperative occurrence without an impact on future pulmonary function and LV.

Bone marrow endothelial cells (BMECs) play a key role in bone formation and haematopoiesis. Although recent studies uncovered the cellular taxonomy of stromal compartments in the bone marrow (BM), the complexity of BMECs is not fully characterized. In the present study, using single-cell RNA sequencing, we defined a spatial heterogeneity of BMECs and identified a capillary subtype, termed type S (secondary ossification) endothelial cells (ECs), exclusively existing in the epiphysis. Type S ECs possessed unique phenotypic characteristics in terms of structure, plasticity and gene expression profiles. Genetic experiments showed that type S ECs atypically contributed to the acquisition of bone strength by secreting type I collagen, the most abundant bone matrix component. Moreover, these cells formed a distinct reservoir for haematopoietic stem cells. These findings provide the landscape for the cellular architecture in the BM vasculature and underscore the importance of epiphyseal ECs during bone and haematopoietic development.

OBJECTIVE: To investigate the characteristics and symptoms of patients with hip osteoarthritis that are associated with spatiotemporal gait parameters, including their variability and asymmetry. DESIGN: A retrospective, cross-sectional study. SETTING: University hospital. PARTICIPANTS: The study analyzed the gait analysis data of 155 patients (N=155) with hip osteoarthritis who were admitted to a university hospital for total hip replacement and were able to walk on a treadmill without a handrail. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The dependent variables were gait parameters during treadmill walking. These included gait speed, stride length, cadence, coefficient of variation of stride length and stride time, swing time symmetry index, and step symmetry index. Single and multiple regression analyses were conducted using independent variables of the characteristics and symptoms of the patients, including age, sex, height, pain, leg-length discrepancy, and muscle strength of the affected and normal sides measured with a hand-held dynamometer (iliopsoas, gluteus medius, and quadriceps). RESULTS: In the analysis, gait speed and stride were the dependent variables, whereas age, height, and muscle strength on the affected side were the significant independent variables (P<.05). Additionally, pain demonstrated a marginal association with gait speed (P=.053). Only the leg-length discrepancy correlated with cadence. When the coefficient of variation of the stride length was the dependent variable, age and muscle strength on the affected side were significant. For the swing time symmetry index, only the muscle strength on the affected side was significant. Furthermore, the step symmetry index only correlated with leg-length discrepancy. The muscle strength on the affected side was the only significant independent variable for the coefficient of variation of the stride time. CONCLUSIONS: The results revealed that each of the frequent clinical symptoms of hip osteoarthritis, such as pain, muscle weakness, and leg-length discrepancy, can explain different aspects of gait performance.

Background and Objectives: There are several advantages of using lateral lumbar interbody fusion (LLIF) for correction surgeries for adult spinal deformity (ASD); however, we currently have unresolved new issues, including occasional anterior longitudinal ligament (ALL) rupture during the posterior correction procedure. When LLIF was initially introduced, only less lordotic cages were available and ALL rupture was more frequently experienced compared with later periods when more lordotic cages were available. We performed finite element analysis (FEA) regarding the mechanism of ALL rupture during a posterior correction procedure. Methods: A spring (which mimics ALL) was introduced at the location of ALL in the FEA and an LLIF cage with two different lordotic angles, 6 and 12 degrees (6DC/12DC), was employed. To assess the extent of burden on the ALL, the extension length of the spring during the correction procedure was measured and the location of the rotation center was examined. Results: We observed a significantly higher degree of length extension of the spring during the correction procedure in the FEA model with 6DC compared with that of 12DC. We also observed that the location of the rotation center was shifted posteriorly in the FEA model with 6DC compared with that of 12DC. Conclusions: It is considered that the posterior and rostral edge of the less lordotic angle cage became a hinge, and the longer lever arm increased the burden on ALL as the principle of leverage. It is important to use an LLIF cage with a sufficient lordotic angle, that is compatible with the degree of posterior osteotomy in ASD correction.

OBJECTIVES: Although cervical spondylotic myelopathy (CSM) has a marked impact on locomotive function, few studies have evaluated this relationship in terms of locomotive syndrome. Thus, we assessed (i) the stages of locomotive syndrome in preoperative CSM patients using the 25-question geriatric locomotive function scale (GLFS-25), (ii) the correlation between GLFS-25 scores and the Japanese orthopaedic association (JOA) scores or the JOA cervical myelopathy evaluation questionnaire (JOACMEQ) scores, and (iii) the factors associated with stage 3 locomotive syndrome in preoperative CSM patients. METHODS: We used clinical data from 107 patients scheduled for cervical spinal surgery for CSM. Data were collected prior to surgery, and included age, gender, body mass index, medical history, JOA score, and JOACMEQ and GLFS-25 scores. RESULTS: Of the included CSM patients, 93.5% were diagnosed with locomotive syndrome, of whom 77.6% were stage 3 according to GLFS-25 evaluation. For the correlation between GLFS-25 and JOA or JOACMEQ, the upper and lower extremity function scores of JOACMEQ and the JOA were strongly inversely correlated with the GLFS-25 score. Finally, multivariate analysis suggested that severe lower extremity status in the JOACMEQ was significantly associated with stage 3 locomotive syndrome in preoperative CSM patients. CONCLUSIONS: Using the GLFS-25, we found that lower extremity status had the strongest association with stage 3 locomotive syndrome in preoperative CSM patients. These findings are useful for preventing CSM patients from requiring future nursing care.

BACKGROUND: To investigate the possibility of silver (Ag)-induced adverse events and the degree of bone fusion in posterior lumbar interbody fusion surgery using an Ag-containing hydroxyapatite (HA) lumbar interbody cage. METHODS: An Ag-HA cage consisting of highly osteoconductive HA interfused with Ag was developed, and we applied it clinically at three university-affiliated hospitals from April 2020 to December 2020. During the 12-month postoperative observation period, Ag-related adverse events, neuropathy, and postoperative complications were investigated as indicators of safety, while clinical improvement and the fusion status were investigated as indicators of efficacy. Clinical improvement was defined as improvement beyond the minimum clinically important difference (MCID) in the numerical rating scale (NRS; 1.6) for low back and lower limb pain and the Oswestry Disability Index (ODI; 12.8). RESULTS: We performed lumbar interbody fusion using an Ag-HA cage for 48 patients (female, n = 25; mean age, 67.5 years). The mean preoperative NRS was 6.4 (standard deviation, 1.9), while the mean preoperative ODI was 44 [12]. No adverse effects (i.e., argyria) were identified during the 12-month observation period. Surgical site infection occurred in one case, although the implant was preserved via immediate debridement. In total, 39 (81%) participants showed clinical improvement beyond MCID for both NRS and ODI. Bone fusion was achieved at 45 levels (88%) at 6 months and 48 levels (91%) at 12 months postoperatively. CONCLUSIONS: The results of this study suggest that Ag-HA cages can be safely used in spinal fusion procedures and have the potential to prevent postoperative infections, prevent deterioration of the quality of life, and result in favorable outcomes. Larger-scale and longer-term follow-up studies will be required to corroborate these conclusions. Trial registration UMIN 000039964 (date: April 01, 2020).

INTRODUCTION: Lateral lumbar interbody fusion (LLIF) has been introduced in Japan in 2013. Despite the effectiveness of this procedure, several considerable complications have been reported. This study reported the results of a nationwide survey performed by the Japanese Society for Spine Surgery and Related Research (JSSR) on the complications associated with LLIF performed in Japan. METHODS: JSSR members conducted a web-based survey following LLIF between 2015 and 2020. Any complications meeting the following criteria were included: (1) major vessel, (2) urinary tract, (3) renal, (4) visceral organ, (5) lung, (6) vertebral, (7) nerve, and (8) anterior longitudinal ligament injury; (9) weakness of psoas; (10) motor and (11) sensory deficit; (12) surgical site infection; and (13) other complications. The complications were analyzed in all LLIF patients, and the differences in incidence and type of complications between the transpsoas (TP) and prepsoas (PP) approaches were compared. RESULTS: Among the 13,245 LLIF patients (TP 6,198 patients [47%] and PP 7,047 patients [53%]), 389 complications occurred in 366 (2.76%) patients. The most common complication was sensory deficit (0.5%), followed by motor deficit (0.43%) and weakness of psoas muscle (0.22%). Among the patient cohort, 100 patients (0.74%) required revision surgery during the survey period. Almost half of the complications developed in patients with spinal deformity (183 patients [47.0%]). Four patients (0.03%) died from complications. Statistically more frequent complications occurred in the TP approach than in the PP approach (TP vs. PP, 220 patients [3.55%] vs. 169 patients [2.40%]; p<0.001). CONCLUSIONS: The overall complication rate was 2.76%, and 0.74% of the patients required revision surgery because of complications. Four patients died from complications. LLIF may be beneficial for degenerative lumbar conditions with acceptable complications; however, the indication for spinal deformity should be carefully determined by the experience of the surgeon and the extent of the deformity.

Spinal diseases are commonly associated with pain and neurological symptoms, which negatively impact patients' quality of life. Platelet-rich plasma (PRP) is an autologous source of multiple growth factors and cytokines, with the potential to promote tissue regeneration. Recently, PRP has been widely used for the treatment of musculoskeletal diseases, including spinal diseases, in clinics. Given the increasing popularity of PRP therapy, this article examines the current literature for basic research and emerging clinical applications of this therapy for treating spinal diseases. First, we review in vitro and in vivo studies, evaluating the potential of PRP in repairing intervertebral disc degeneration, promoting bone union in spinal fusion surgeries, and aiding in neurological recovery from spinal cord injury. Second, we address the clinical applications of PRP in treating degenerative spinal disease, including its analgesic effect on low back pain and radicular pain, as well as accelerating bone union during spinal fusion surgery. Basic research demonstrates the promising regenerative potential of PRP, and clinical studies have reported on the safety and efficacy of PRP therapy for treating several spinal diseases. Nevertheless, further high-quality randomized controlled trials would be required to establish clinical evidence of PRP therapy.

Abstract Background Polypharmacy is a growing public health problem occurring in all healthcare settings worldwide. Elderly patients with lumbar spinal canal stenosis (LSS) who manifest low back and neuropathic pain and have a high frequency of comorbidity are predicted to take many drugs. However, no studies have reported polypharmacy in elderly patients with LSS. Thus, we aimed to review the polypharmacy among elderly LSS patients with elective surgeries and examine how the surgical treatment reduces the polypharmacy. Methods We retrospectively enrolled all the patients aged ≥ 65 years who underwent spinal surgery for LSS between April 2020 and March 2021. The prescribed drugs of participants were directly checked by pharmacists in the outpatient department preoperatively and 6-month and 1-year postoperatively. The baseline characteristics were collected beside the patient-based outcomes including Roland–Morris Disability Questionnaire, Zurich Claudication Questionnaire, and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ). The cutoff number of drugs for polypharmacy was defined as 6. The prescription drugs were divided into 9 categories: drugs for neuropsychiatric, cardiovascular, respiratory, digestive, endocrine metabolic, and urinary renal diseases; blood products; pain relief medication; and others. Results A total of 102 cases were finally analyzed, with a follow-up rate of 78.0%. Of the participants, the preoperative polypharmacy prevalence was 66.7%. The number of drugs 6-month and 1-year postoperatively was significantly less than the preoperative one. The proportions of polypharmacy at 6 months and 1 year after surgery significantly decreased to 57.8% and 55.9%, respectively. When the prescribed drugs were divided into 9 categories, the number of drugs for pain relief and digestive diseases was significantly reduced after surgery. The multi-variable analysis revealed that a higher score in the psychological disorder of JOABPEQ was associated with 3 or more drugs decreased 1-year postoperatively (OR, 2.5; 95% CI: 1.0–6.1). Conclusion Polypharmacy prevalence was high among elderly LSS patients indicated for lumbar spinal surgery. Additionally, our data showed that lumbar spinal surgery was effective in reducing polypharmacy among elderly LSS patients. Finally, the multi-variable analysis indicated that better psychological condition was associated with the reduction of prescribed drugs after lumbar spinal surgery.

Treatment for lumbar spinal canal stenosis (LSCS) is mainly classified into conservative and surgical therapies. Among conservative therapies, pharmacological treatment is commonly prescribed for LSCS. Meanwhile, surgical treatment is the last option for LSCS. This study aimed to examine the impact of lumbar surgery on pharmacological treatment for patients with LSCS. Consecutive patients aged ≥ 40 years who underwent lumbar surgery for LSCS were identified. A total of 142 patients were retrospectively reviewed for preoperative and 6-month and 1-year postoperative LSCS medications. The results showed that the number of LSCS medications significantly decreased after lumbar surgery. The proportion of the patients taking non-steroidal anti-inflammatory drugs, pregabalin/mirogabalin, opioids, prostaglandin E1 analogs, and neurotropin was significantly decreased after lumbar surgery, but that of the patients taking mecobalamin, acetaminophen, and serotonin-noradrenalin reuptake inhibitors was not significantly changed. Additionally, around 15% of the participants showed an increase in LSCS medications even after lumbar surgery. Multivariable analysis revealed that individuals without improvements in walking ability (RR: 2.7, 95% CI: 1.3–5.9) or social life (RR: 2.3, 95% CI: 1.1–5.0) had a greater risk of a postoperative increase in LSCS medications. The study results may provide physicians with beneficial information on treatment for LSCS.

Oxidative stress (OS) results in many disorders, of which degenerative musculoskeletal conditions are no exception. However, the interaction between OS and ligamentum flavum (LF) hypertrophy in lumbar spinal canal stenosis is not clearly understood. The first research question was whether OS was involved in LF hypertrophy, and the second was whether the antioxidant N-acetylcysteine (NAC) was effective on LF hypertrophy. In total, 47 LF samples were collected from patients with lumbar spinal disorders. The cross-sectional area of LF was measured on axial magnetic resonance imaging. Immunohistochemistry of 8-OHdG and TNF-α were conducted on human LF samples. A positive association was found between 8-OHdG or TNF-α expression and cross-sectional area of LF. Flow cytometry analysis showed that H2O2, buthionine sulfoximine, and TNF-α treatment significantly increased intracellular reactive oxygen species in primary LF cells. NAC inhibited the induction of LF hypertrophy markers by OS or TNF in a real-time reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. Western blotting analysis indicated that p38, Erk, and p65 phosphorylation were involved in intracellular OS signaling in LF cells. In conclusion, our results indicated that OS could be a therapeutic target for LF hypertrophy. Although this study included no in vivo studies to examine the longitudinal efficacy of NAC on LF hypertrophy, NAC may have potential as a therapeutic agent against lumbar spinal canal stenosis.

Background and Objectives: Modic type 1 is known to be associated with lower back pain (LBP), but at present, a treatment has not been fully established. Meanwhile, platelet-rich plasma (PRP) has been used for tissue regeneration and repair in the clinical setting. There is no clinical PRP injection trial for the intervertebral disc of LBP patients with Modic type 1. Thus, this study aimed to verify PRP injection safety and efficacy in LBP patients with Modic type 1. As a preliminary experiment, two LBP cases with Modic type 1 are presented. Materials and Methods: PRP was administered intradiscally to two LBP patients with Modic type 1. PRP was obtained from the patients' anticoagulated blood. Primary endpoints were physical condition, laboratory data, and X-ray for safety evaluation. Secondary endpoints were pain scores using the visual analog scale (VAS), the Oswestry Disability Index (ODI), and the Roland-Morris Disability Questionnaire (RDQ) to evaluate PRP efficacy. The observation period was 24 weeks after the PRP injection. In addition, changes in Modic type 1 using MRI were evaluated. Results: This study assessed two LBP patients with Modic type 1. There were no adverse events in physical condition, laboratory data, or lumbar X-rays after injection. Follow-up MRI showed a decrease of high signal intensity on T2WI compared to before PRP administration. The pain scores tended to improve after the injection. Conclusions: PRP injection into the intervertebral disc of LBP patients with Modic type 1 might be safe and effective. This analysis will be continued as a prospective study to establish the efficacy.

CASE: Patients with myelopathy due to narrowing of the spinal canal with ossification of the ligamentum flavum (OLF) generally require surgical intervention, but surgical methods for OLF remain controversial. We discuss our experience regarding posterior fusion surgery with instrumentation for a patient with recurrent OLF at the same level after decompression surgery as well as describe the preoperative and postoperative course of this rare case. CONCLUSION: Posterior decompression and fusion surgery is recommended as revision surgery for recurrent OLF at the same level after decompression surgery. A detailed surgical planning should be developed before surgery.

INTRODUCTION: Adolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated. MATERIAL AND METHODS: Mendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese. RESULTS: Significant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10-3), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10-3) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10-3), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI. CONCLUSIONS: Our Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS.

Objective: Although syringomyelia is considered a risk factor for neurological complications of correction surgery for scoliosis, only a few reports on the surgical results of the correction surgery complicated with associated syringomyelia are available. The purpose of this study is to verify the potential risk of neurological complications due to the presence of syringomyelia and explore the factors affecting the surgical outcomes of posterior correction surgery for scoliosis associated with syringomyelia. Methods: This is a retrospective observational study in a single university hospital setting. Among 754 consecutive patients who underwent posterior correction and fusion surgery for scoliosis from 2009 through 2018 in our institution, we identified 28 patients presenting with spinal syringomyelia on preoperative whole spine MRI. The identified cases comprised 14 males and 14 females aged 11 years to 23 years (14.0 ± 2.9 years), and those with wide-type syrinx within fused spinal levels had undergone surgery for syringomyelia beforehand. First, we investigated the occurrence rate of peri- and postoperative neurological complications. Then we explored the factors affecting the correction rate of the Cobb angle and the incidence of coronal decompensation. Results: Neurological complication (transient sensory deficits in bilateral legs) occurred in one case with thoracic single curve and narrow-type syrinx, disappearing spontaneously within several weeks postoperatively. The cases with an L4 long curve (n = 3, including L4 in thoracolumbar long C-shaped curve) showed a significantly poor correction rate (38.7%, p = 0.003) and developed postoperative coronal decompensation. Conclusions: Prior treatment for wide-type syrinx located within the spinal fusion level effectively prevented severe neurological complications, and when treating cases with long-curve L4 scoliosis associated with syringomyelia, the surgeons should note the occurrence of postoperative coronal decompensation.

Osteosarcoma is a malignant tumor that produces neoplastic bone or osteoid osteoma. In human multicentric osteosarcoma (HMOS), a unique variant of human osteosarcoma (HOS), multiple bone lesions occur simultaneously or asynchronously before lung metastasis. HMOS is associated with an extremely poor prognosis, and effective treatment options are lacking. Using the proteins in our previously generated HMOS cell lines as antigens, we generated antibodies using a human antibody phage library. We obtained antibody clones recognizing 95 independent antigens and developed a fluorescence probe-based enzyme-linked immunosorbent assay (ELISA) technique capable of evaluating the reactivity of these antibodies by fluorescence intensity, allowing simple, rapid, and high-throughput selection of antibody clones. These results were highly correlated with those using flow cytometry. Subsequently, the HMOS cell lysate was incubated with the antibody, the antigen-antibody complex was recovered with magnetic beads, and the protein bands from electrophoresis were analyzed using liquid chromatography-mass spectrometry (LC/MS). CAVIN1/polymerase I transcript release factor was specifically detected in the HMOS cells. In conclusion, we found via a novel high-throughput screening method that CAVIN1/PTRF is an HMOS-specific cell membrane biomarker and an antigen capable of producing human antibodies. In the future, antibody-drug conjugate targeting of these specific proteins may be promising for clinical applications.

Adolescent idiopathic scoliosis (AIS) is a serious health problem affecting 3% of live births all over the world. Many loci associated with AIS have been identified by previous genome wide association studies, but their biological implication remains mostly unclear. In this study, we evaluated the AIS-associated variants in the 7p22.3 locus by combining in silico, in vitro, and in vivo analyses. rs78148157 was located in an enhancer of UNCX, a homeobox gene and its risk allele upregulated the UNCX expression. A transcription factor, early growth response 1 (EGR1), transactivated the rs78148157-located enhancer and showed a higher binding affinity for the risk allele of rs78148157. Furthermore, zebrafish larvae with UNCX messenger RNA (mRNA) injection developed body curvature and defective neurogenesis in a dose-dependent manner. rs78148157 confers the genetic susceptibility to AIS by enhancing the EGR1-regulated UNCX expression. © 2022 American Society for Bone and Mineral Research (ASBMR).