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.

Advanced glycation end products are associated with sarcopenia in older women: aging marker dynamics.

The aim of this study was to determine whether advanced glycation end products (AGEs) revealed by skin autofluorescence (SAF), serum and urine pentosidine level, and serum homocysteine level can serve as a biomarker for sarcopenia in older women. The participants were 70 elderly women. The AGEs pentosidine, homocysteine, and SAF were measured as aging markers. This study shows that among the biomarkers for aging, serum pentosidine correlates with a loss of appendicular lean mass and can serve as a biomarker for sarcopenia. Moreover, SAF and homocysteine values exhibited a positive correlation with age and correlated with each other.Abbreviations: AGEs: advanced glycation end products; BIA: bioelectrical impedance analyzer; BMD: bone mineral density; DLS: degenerative lumbar scoliosis; DXA: dual-energy X-ray absorptiometry; ELISA: enzyme-linked immunoassay; HHcy: hyperhomocysteinemia; RIA: radioimmunoassay; SAF: skin autofluorescence; SMI: skeletal muscle mass index; T2DM: type 2 diabetes patients.

Frequency of Adverse Drug Reactions and Analgesic Effects of Mirogabalin during Treatment of Peripheral Neuropathic Pain: A Retrospective Clinical Investigation.

INTRODUCTION: Mirogabalin should be equivalent to pregabalin, but with fewer incidences of adverse drug reactions (ADRs). To verify these benefits in actual clinical trials, our study investigated the frequency of ADRs and mirogabalin's analgesic effects during treatment of peripheral neuropathic pain. METHODS: This study included 74 patients with lower limb pain. We surveyed patient reports of ADRs during the follow-up period as the primary endpoint and examined the visual analog scale (VAS) reported for lower limb pain as the secondary endpoint (before administration, and two and four weeks after administration). RESULTS: The occurrence of ADR was 27.0%, like the frequency of ADRs in the clinical trials for other disorders. However, the discontinuation rate of administration was 10.8%, which was significantly lower than the frequency of ADR occurrences. When the analgesic effect was assessed, a significant decrease in the temporal change of VAS for lower limb pain was observed before administration, and two and four weeks after administration. CONCLUSIONS: In this study, the occurrence of ADRs reported by the patients was like the frequency of ADRs reported in the clinical trials for other disorders. When assessing the analgesic effect, the temporal change of VAS for lower limb pain was found to decrease significantly before administration, and two and four weeks after administration.

Ablation of Iah1, a candidate gene for diet-induced fatty liver, does not affect liver lipid accumulation in mice.

Nonalcoholic fatty liver disease (NAFLD) is a pathological condition caused by excess triglyceride deposition in the liver. The SMXA-5 severe fatty liver mouse model has been established from the SM/J and A/J strains. To explore the genetic factors involved in fatty liver development in SMXA-5 mice, we had previously performed quantitative trait locus (QTL) analysis, using (SM/J×SMXA-5)F2 intercross mice, and identified Fl1sa on chromosome 12 (centromere-53.06 Mb) as a significant QTL for fatty liver. Furthermore, isoamyl acetate-hydrolyzing esterase 1 homolog (Iah1) was selected as the most likely candidate gene for Fl1sa. Iah1 gene expression in fatty liver-resistant A/J-12SM mice was significantly higher than in fatty liver-susceptible A/J mice. These data indicated that the Iah1 gene might be associated with fatty liver development. However, the function of murine Iah1 remains unknown. Therefore, in this study, we created Iah1 knockout (KO) mice with two different backgrounds [C57BL/6N (B6) and A/J-12SM (A12)] to investigate the relationship between Iah1 and liver lipid accumulation. Liver triglyceride accumulation in Iah1-KO mice of B6 or A12 background did not differ from their respective Iah1-wild type mice under a high-fat diet. These results indicated that loss of Iah1 did not contribute to fatty liver. On the other hands, adipose tissue dysfunction causes lipid accumulation in ectopic tissues (liver, skeletal muscle, and pancreas). To investigate the effect of Iah1 deficiency on white adipose tissue, we performed DNA microarray analysis of epididymal fat in Iah1-KO mice of A12 background. This result showed that Iah1 deficiency might decrease adipokines Sfrp4 and Metrnl gene expression in epididymal fat. This study demonstrated that Iah1 deficiency did not cause liver lipid accumulation and that Iah1 was not a suitable candidate gene for Fl1sa.

Objective evaluation of postoperative changes in real-life activity levels in the postoperative course of lumbar spinal surgery using wearable trackers.

BACKGROUND: Lumbar spinal disease causes disabilities in performing daily activities. Operative treatments are aimed at pain relief and rapid return to routine activity. Patient-based outcome measures are used to evaluate pathologies and therapeutic effects associated with lumbar spinal disease. Nevertheless, it remains unknown as to how much such treatment improves activity levels. The purpose of the current study was to measure changes in activity levels before and after lumbar spinal surgery using a wearable activity tracker and to analyze the differences between results and patient-based outcomes. METHODS: Sixty patients who underwent lumbar surgery were studied. The physical activity of participants was objectively evaluated using a wearable Micro-Motion logger system (Actigraph). We measured the amount of activity before and at 1, 3, 6, and 12 months after the surgery to evaluate postoperative changes. The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, Oswestry Disability Index, Roland-Morris Disability Questionnaire and visual analog scale were used to assess patient-based outcomes of pain and activities of daily living-related scores; we analyzed the relationships between scores and actual activity levels. RESULTS: The amount of actual activity decreased significantly 1 month after the surgery compared to that during the preoperative period, which then improved after 3 months postoperatively (p < 0.01). Furthermore, there was a significant improvement 6 months after the surgery compared to that during the preoperative period (p < 0.05). The changes in activity for each period were strongly correlated, regardless of the period. In contrast, a significant improvement was observed at 1 month after the surgery in almost all items of the patient-based questionnaires (p < 0.05). CONCLUSIONS: The objective activity tracker demonstrated that lumbar surgery results in the amount of activity decreasing 1 month just after surgery followed by gradual postoperative recovery within 3 months. By contrast, patient-based outcomes showed improvement in 1 month that was significantly different from the change in actual activity, indicating a gap between patient-oriented clinical scores and their actual activities.

Simultaneous MR neurography and apparent T2 mapping of cervical nerve roots before microendoscopic surgery to treat patient with radiculopathy due to cervical disc herniation: Preliminary results.

There is no imaging modality to quantitatively evaluate compressed cervical nerve roots in cervical radiculopathy. Here we sought to evaluate the usefulness of simultaneous apparent T2 mapping and neurography with nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation-enhancement imaging (SHINKEI-Quant) to evaluate compressed nerves quantitatively in patients with cervical radiculopathy due to cervical disc hernia before microendoscopic surgery. One patient with cervical radiculopathy due to cervical disc hernia before microendoscopic surgery and 5 healthy subjects underwent simultaneous apparent T2 mapping and neurography with SHINKEI-Quant. The patient was a 49-year-old man with severe right upper arm pain and numbness. Based on MRI images, we suspected right C7 radiculopathy due to C6-7 cervical disc hernia. The T2 relaxation times of the cervical dorsal root ganglia of the brachial plexus bilaterally at C5-C8 were measured. We observed no significant differences in T2 relaxation times between the nerve roots on the left and right at each spinal level with values in healthy subjects. In our patient, neurography revealed swelling of the right C7 nerve, and a prolonged T2 relaxation time compared with that of the contralateral, unaffected C7 nerve. We performed microendoscopic surgery and the symptoms improved. We were able to evaluate the injured nerve root quantitatively in a patient with cervical radiculopathy using the SHINKEI-Quant technique, being the first study to our knowledge to show the usefulness of this technique to evaluate cervical radiculopathy quantitatively before microendoscopic surgery.

Analgesic Effect of Duloxetine on an Animal Model of Monosodium Iodoacetate-Induced Hip Osteoarthritis.

We investigated the efficacy of duloxetine on hyperalgesia, histopathological and radiographic findings, pain-related sensory innervation of dorsal-root ganglia (DRG), and spinal changes in a rat model of induced hip osteoarthritis (OA). The right hip joints of male Sprague-Dawley rats (n = 6 rats/group) in the Sham group were injected with 25 µl of sterile saline and 25 µl of sterile saline with 2 mg of monosodium iodoacetate (MIA) were injected to the MIA + Vehicle and MIA + Duloxetine groups. We injected duloxetine 20 mg/kg intraperitoneally in the MIA + Duloxetine group 28 days after injection, whereas rats in the MIA + Vehicle group were injected with 0.5 ml of 20% dimethyl sulfoxide. We assessed hyperalgesia, histopathological changes, immunoreactive (-ir) neurons for calcitonin gene-related peptide and activating transcription factor 3 in DRG, and immunoreactive neurons for ionized-calcium-binding adaptor molecule 1 (Iba1) in the dorsal horn of the spinal cord. MIA administration into the hip joint let to mechanical hyperalgesia of the ipsilateral hind paw (p < 0.05). A single injection of duloxetine significantly attenuated it in induced hip OA (p < 0.05) and suppressed the number of Iba1-ir microglia of the ipsilateral dorsal horn (p < 0.05). These results suggest that a single injection of duloxetine suppressed mechanical hyperalgesia and may influence the expression of Iba1 in the microglia of the ipsilateral dorsal horn in the MIA-induced hip OA. This finding implies the inhibitory effects of duloxetine against neuropathic pain, which may lead to a change of microglial activities. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:422-430, 2020.

Reduced leg muscle mass and lower grip strength in women are associated with osteoporotic vertebral compression fractures.

Lower limb muscle mass and grip loss may be risk factors for vertebral compression fractures in women. PURPOSE: We examined the relationship between bone mineral density, bone strength, skeletal muscle mass, grip strength, and skin autofluorescence (SAF) in women with osteoporotic vertebral compression fractures (VCF). METHODS: A total of 1039 women (mean age 73.3 years) were included in our study. These included 222 cases of VCF (mean 77.8 years) and 817 controls (mean 72.0 years). Lumbar and femur BMD were measured for all participants using dual-energy X-ray absorptiometry (DXA). Bone strength surrogates, such as cross-sectional area (CSA) of the proximal femur, were evaluated using Advanced Hip Assessment software. SAF was measured with an autofluorescence reader. We used a bioelectrical impedance analyzer (BIA) to analyze body composition, including appendicular skeletal muscle mass index (SMI; appendicular lean mass (kg)/(height (m))2. We measured bone density, geometric parameters related to bone strength, skeletal muscle mass, grip strength, and SAF in both groups. We also examined factors related to vertebral fracture using multiple logistic regression analysis. RESULTS: Women with vertebral fractures had lower SMI (5.55 vs 5.76 kg/m2, p = 0.0006), smaller femoral cross-sectional area (97.20 vs 100.09, p = 0.014), lower grip strength (16.81 vs 19.16 kg, p < 0.0001), and increased skin autofluorescence (2.38 vs 2.25, p = 0.0002) compared to women without fractures. The prevalence of sarcopenia (SMI < 5.75) was 63.51% in VCF subjects and 52.02% in controls, revealing a high prevalence in VCF (p = 0.002). Skeletal muscle mass and grip strength were not significantly different between patients with acute and old VCF, suggesting that low skeletal muscle mass and muscle weakness may exist before fracture. From the multiple logistic regression analysis, lower femoral density (p = 0.0021), CSA (p = 0.0166), leg muscle mass (p = 0.0127), and left arm grip strength (p = 0.0255) were risk factors for vertebral compression fractures; all were negatively correlated with increased vertebral fractures. CONCLUSIONS: Lower limb muscle mass and grip loss may be closely related to the onset of vertebral compression fracture.

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.

Comparison of the Activity Level of the Upper Limbs and Trunk in Patients with Low Back Pain Evaluated Using a Wearable Accelerometer: A Validation Study.

INTRODUCTION: Wearable accelerometers can be used to evaluate waking and sleeping movements. Although a correlation between accelerometer data captured at the wrist and waist has been reported, it has not been evaluated in patients with low back pain. Therefore, this study aimed to evaluate correlations between movement measured at the wrist and waist, using wearable accelerometers, in patients with low back pain. METHODS: Twenty patients with chronic low back pain and 20 healthy volunteers were enrolled. Two identical accelerometers were simultaneously worn by each participant, one on the nondominant wrist and the other at the waist, for 1 week. We compared the mean number of active movements and mean total amount of movement between the wrist and the waist to evaluate daytime and sleep activities. During sleep, we also evaluated sleep efficiency and time awake after sleep onset. RESULTS: In daytime activity, the mean number of active movements and mean total amount of movement was greater for the wrist than for the waist, and the amount of waist movements relative to wrist movements was significantly lower in patients with low back pain than in healthy volunteers (p < 0.05). Despite these differences, the mean number of active movements and mean total amount of movement at the wrist and waist were strongly correlated in both groups. During sleep, although there was no difference in either measured sleep efficiency at the wrist or waist or time awake after sleep onset, measurements were strongly correlated in both groups. CONCLUSIONS: A strong correlation between movement data at the wrist and waist during both daytime activities and sleep was identified in patients with low back pain. Therefore, a wearable accelerometer worn on the wrist can reliably measure the movement of patients with low back pain, simplifying data capture for clinical and research purposes and improving patient comfort.

Post-Operative Spinal Epidural Hematoma after Thoracic and Lumbar Spinous Process-Splitting Laminectomy for Thoracic and Lumbar Spinal Stenosis.

INTRODUCTION: To investigate the risk of epidural hematoma after spinous process-splitting laminectomy (SPSL). METHODS: A total of 137 cases (mean age, 72.4 years; 68 men) of SPSL were included. Of these, there were instances (3.7%; mean age, 70.5 years; all male) of postoperative development of new neurologic deficit due to epidural hematoma requiring reoperation. The 133 subjects (72.5 years; 64 men) with normal postoperative course were used as controls, and comparisons were made between both groups using chi-squared and Student's t-tests. Regarding our investigation of risk factors for epidural hematoma, logistic regression was conducted with presence or absence of hematoma as our primary outcome variable, and age, gender, disease duration, number of laminectomies, which levels were decompressed, blood loss, length of case, drain output, coagulopathy, and whether or not there was an intraoperative dural tear were our explanatory variables. RESULTS: All cases of hematoma were single-level laminectomies; there was one case of T9-10 and 3 cases of L2-3. In our direct comparison of both groups (hematoma versus control), the proportion of men was significantly higher in the hematoma group (100% versus 48%, p < 0.05); levels decompressed were also significantly higher (p < 0.05) in the hematoma group, and drain outputs were significantly lower (113 mL versus 234 mL, p < 0.05). From our logistic regression analysis, the levels were significantly higher (χ2 = 15, p = 0.0001) and the drain outputs were smaller (χ2 = 4.6, p = 0.03) in the hematoma group. CONCLUSIONS: Single-level decompression higher than the L2-3 level and reduced drain output were risk factors for spinal epidural hematoma. With this method of spinous process suturing and reconstruction there is less decompression compared with more conventional methods; therefore, the effect of hematoma may be more pronounced at higher vertebral levels with reduced canal width, and drain failure may also occur with this limited space.

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.

Relationship between patient-based scoring systems and the activity level of patients measured by wearable activity trackers in lumbar spine disease.

PURPOSES: To evaluate whether a relationship exists between patient-based scoring systems and the activity level of patients with low back pain (LBP) by using wearable activity trackers, and to determine whether activity level was affected by patient factors. METHODS: The subjects were 66 patients with LBP. The physical activity of participants was objectively evaluated using the Micro-Motion logger (Actigraph). The activity level was analyzed with the mean active count of the proportional-integrating mode (PMAC) and zero-crossing mode. Clinical symptoms were evaluated using the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Roland-Morris Disability Questionnaire, the Oswestry Disability Index, and visual analog scale (VAS). The relationships between each item of the patient-based questionnaire and activity level, and the influence of individual factors (age, sex, body mass index [BMI], low back pain, and muscle mass) on the activity level were evaluated. RESULTS: In each domain of the JOABPEQ, lumbar spine dysfunction and social life dysfunction were correlated with PMAC (r = 0.327 and 0.321, respectively). The low back pain VAS scores were correlated with PMAC (r = - 0.246). Multiple regression analysis shows that individual factors affecting the activity level of patients with LBP were sex, BMI, low back pain, and muscle mass in PMAC (p < 0.01). CONCLUSIONS: Some domains of the questionnaires were correlated with activity level, but others were not. Additionally, the activity level of patients with LBP was affected by sex, BMI, LBP, and skeletal muscle mass index. These slides can be retrieved under Electronic Supplementary Material.

Three cases of adjacent segment disease post-posterior spinal fusion, treated successfully by oblique lateral interbody fusion: A clinical series.

The incidence of spinal fusion surgery and associated adjacent segment disease (ASD) is steadily increasing. We report three cases of ASD after posterior fixation, treated by oblique lateral interbody fusion (OLIF). All cases had a good postoperative course. Altogether, OLIF surgery may be a viable option for treating ASD.

Diffusion tensor tractography of the lumbar nerves before a direct lateral transpsoas approach to treat degenerative lumbar scoliosis.

OBJECTIVEThe purpose of this study was to determine the relationship between vertebral bodies, psoas major morphology, and the course of lumbar nerve tracts using diffusion tensor imaging (DTI) before lateral interbody fusion (LIF) to treat spinal deformities.METHODSDTI findings in a group of 12 patients (all women, mean age 74.3 years) with degenerative lumbar scoliosis (DLS) were compared with those obtained in a matched control group of 10 patients (all women, mean age 69.8 years) with low-back pain but without scoliosis. A T2-weighted sagittal view was fused to tractography from L3 to L5 and separated into 6 zones (zone A, zones 1-4, and zone P) comprising equal quarters of the anteroposterior diameters, and anterior and posterior to the vertebral body, to determine the distribution of nerves at various intervertebral levels (L3-4, L4-5, and L5-S1). To determine psoas morphology, the authors examined images for a rising psoas sign at the level of L4-5, and the ratio of the anteroposterior diameter (AP) to the lateral diameter (lat), or AP/lat ratio, was calculated. They assessed the relationship between apical vertebrae, psoas major morphology, and the course of nerve tracts.RESULTSAlthough only 30% of patients in the control group showed a rising psoas sign, it was present in 100% of those in the DLS group. The psoas major was significantly extended on the concave side (AP/lat ratio: 2.1 concave side, 1.2 convex side). In 75% of patients in the DLS group, the apex of the curve was at L2 or higher (upper apex) and the psoas major was extended on the concave side. In the remaining 25%, the apex was at L3 or lower (lower apex) and the psoas major was extended on the convex side. Significant anterior shifts of lumbar nerves compared with controls were noted at each intervertebral level in patients with DLS. Nerves on the extended side of the psoas major were significantly shifted anteriorly. Nerve pathways on the convex side of the scoliotic curve were shifted posteriorly.CONCLUSIONSA significant anterior shift of lumbar nerves was noted at all intervertebral levels in patients with DLS in comparison with findings in controls. On the convex side, the nerves showed a posterior shift. In LIF, a convex approach is relatively safer than an approach from the concave side. Lumbar nerve course tracking with DTI is useful for assessing patients with DLS before LIF.

Analysis of skeletal muscle mass in women over 40 with degenerative lumbar scoliosis.

PURPOSE: We investigated the involvement of sarcopenia in middle-aged and elderly women with degenerative lumbar scoliosis (DLS). METHODS: A total of 971 women (mean age 70.4 years) were included in our study. These included 87 cases of DLS (mean 73.8 years) and 884 controls (69.8). Lumbar and femur BMD was measured for all participants 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. We determined bone density and skeletal muscle mass in both groups and determined the prevalence of sarcopenia. We examined the correlation between bone density and appendicular muscle mass in both groups. We also examined factors related to scoliosis using logistic regression analysis. RESULTS: The DLS group showed significantly higher lumbar BMD, lower femur BMD, lower lean mass arm, and lower lean mass leg, and lower lean mass trunk (p < 0.05). Sarcopenia prevalence (SMI < 5.75) was 59.8% in DLS subjects and 42.8% in controls, revealing a high prevalence in DLS (p < 0.05). In both groups, lumbar and femur BMD were positively correlated with appendicular muscle mass. By logistic regression analysis, trunk muscle mass was detected as a risk factor for DLS independent of age (p < 0.05). CONCLUSIONS: In middle-aged and elderly women, prevalence of sarcopenia was 59.8% in DLS cases and 42.8% in controls, which revealed a high prevalence in DLS. A decrease in trunk muscle was a significant risk factor for DLS that was independent of age. These slides can be retrieved under Electronic Supplementary Material.

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.

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.