Impending Atypical Femoral Fracture on the Contralateral Side Progressed to a Complete Fracture Early after Surgery for an Atypical Femoral Fracture: A Case Report.

Introduction: Long-term bisphosphonate (BP) administration may cause an atypical femoral fracture that is occasionally bilateral. We encountered a case of an impending atypical femoral fracture on the contralateral side that progressed to a complete fracture early after surgery for an atypical femoral fracture. Case Report: An 83-year-old woman who had received long-term BP therapy developed a right femoral atypical incomplete fracture that progressed to a complete fracture 5 days after surgery for an atypical complete left femoral fracture. Conclusion: The findings from this case suggest that when an atypical femoral fracture occurs in patients receiving long-term BP therapy, the possibility of an impending atypical femoral fracture on the contralateral side should be considered, and radiographs or CT images should be obtained for both legs. To prevent long-term bed rest in older adults, one- or two-stage bilateral surgery should be considered when imaging reveals bilateral atypical femoral fractures.

Clinical Efficacy of Neurotropin for Lumbar Spinal Stenosis with Low Back Pain.

PURPOSE: We compared the clinical effects of Neurotropin, limaprost alfadex, and a combination of both drugs for lumbar spinal stenosis (LSS) with low back pain (LBP). METHODS: We conducted a multicenter, randomized, active-controlled, open-label trial from March 2021 to May 2022. Participants were patients diagnosed with LSS by MRI and were randomly assigned to three groups: Neurotropin/limaprost combination (NL group), Neurotropin (N group), and limaprost group (L group). Participants received the drugs administered orally for 12 weeks, and each examination and observation was performed before any drug administration and every 2 weeks thereafter. We recorded age, sex, height, weight, duration of symptoms, intermittent claudication distance, level of stenosis in MRI, and concomitant analgesics as examination items in the trial period. Items measured during the trial were visual analog scale (VAS) score (mm) for LBP, leg pain and numbness, walking activity (walking speed, stride length), standing balance (3 m Timed Up-and-Go (TUG) Test results, Five Times Sit-to-Stand Test (FTSST) results), LBP/Quality of Life (QOL)-related scores (Oswestry Disability Index (ODI), Euro QOL 5-Dimensions 5-Level (EQ-5D-5L), Roland-Morris Disability Questionnaire (RDQ)), psychological factors (Pain catastrophizing scale (PCS) and Pain Self-Efficacy Questionnaire (PSEQ) scores), and adverse events. Each item was evaluated using changes at each visit (weeks 2-12) from baseline value before drug administration (week 0), and changes were considered significant when p < 0.05. RESULTS: We included results from 64 patients in the present study; 24 were assigned to the NL group (mean age 71.2 years), 20 to the N group (mean age 76.2 years), and 20 to the L group (mean age 74.4 years). There were no significant differences between the three groups in patient characteristics, concomitant analgesics, or baseline VAS score, gait balance, or QOL-related scores (p ≥ 0.05). The VAS and leg pain scores were significantly improved in Group L, and LBP was improved significantly in Group N. QOL and ODI scores improved significantly in the NL and L groups, EQ-5D score improved significantly in the L group, and RDQ score improved significantly in all groups (p < 0.05). Psychological factor and PCS scores improved significantly in the NL and L groups (p < 0.05). Walking speed and stride length were improved significantly in the NL and N groups (p < 0.05). TUG/FTSST scores were improved significantly in all groups (p < 0.05). Leg pain VAS score was improved significantly (p < 0.05) in the L group compared with the NL group after 6 and 12 weeks of administration, and LBP VAS was improved significantly in the N group after 6 weeks compared with the NL group (p < 0.05). Walking speed was significantly improved in the NL group after 2 weeks compared with the N group and improved significantly in the NL group after 6 weeks (p < 0.05) compared with the L group. RDQ was decreased significantly in the L group compared with the NL group after 8 weeks (p < 0.05). CONCLUSIONS: Combined use of Neurotropin and limaprost showed an additional effect on walking speed compared with single drug administration. Neurotropin may contribute to the improvement of low back pain, walking speed/stride length, and standing balance. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTs031200282).

Effect of romosozumab in premenopausal women with severe osteoporosis and anorexia nervosa.

Objectives: This study aims to investigate the effects of romosozumab on bone mineral density (BMD) and bone metabolism. Methods: In this retrospective case series, romosozumab was administered to 5 premenopausal female patients with osteoporosis and anorexia nervosa with fragility fractures. BMD and bone turnover marker changes were investigated at 6 months and 1 year after administering romosozumab. Results: BMD increased and high-turnover bone metabolism decreased 6 months and 1 year after administering romosozumab. Conclusions: Romosozumab is useful for treating osteoporosis in patients with anorexia nervosa.

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.

Improvements in Intractable Lumbar and LowerExtremity Symptoms after Systemic Administration of Tocilizumab, an Anti-interleukin-6 Receptor Antibody.

STUDY DESIGN: Prospective cohort study (open-label, single-arm, and non-blinded). PURPOSE: This study aims to determine the effects of systemic administration of tocilizumab, an anti-interleukin-6 (IL-6) receptor antibody on refractory low back pain and leg symptoms. OVERVIEW OF LITERATURE: IL-6 overexpression is associated with neuropathic pain pathogenesis, which is potentially followed by chronic low back pain, including leg pain and numbness. This finding suggest that inhibition of IL-6 at the site of pain or in the transmission pathway could provide novel therapeutic targets for chronic low back pain. METHODS: This prospective, single-arm study included 11 patients (eight men; mean age, 62.7 years) with ≥3-months' chronic pain history due to lumbar disease. Subcutaneous TCZ injections were administered twice, at a 2-week interval. We evaluated low back pain, leg pain, and leg numbness using numeric rating scales and the Oswestry Disability Index (ODI; baseline and 6 months postinjection); serum IL-6 and tumor necrosis factor-α levels (baseline and 1 month postinjection); and clinical adverse events. RESULTS: Intractable symptoms reduced after TCZ administration. Low back pain improved for 6 months. Improvements in leg pain and numbness peaked at 4 and 1 month, respectively. Improvements in ODI were significant at 1 month and peaked at 4 months. Serum IL-6 was increased at 1 month. IL-6 responders (i.e., patients with IL-6 increases >10 pg/mL) showed particularly significant improvements in leg pain at 2 weeks, 1 month, and 2 months compared with nonresponders. We observed no apparent adverse events. CONCLUSIONS: Systemic TCZ administration improved symptoms effectively for 6 months, with peak improvements at 1-4 months and no adverse events. Changing serum IL-6 levels correlated with leg pain improvements; further studies are warranted to elucidate the mechanistic connections between lumbar disorders and inflammatory cytokines.

Japanese translation and linguistic validation of the Prosthetic Limb Users Survey of Mobility (PLUS-M).

BACKGROUND: Self-report survey instruments can be used to improve clinical care for lower-limb prosthesis users on a global scale by pooling comparable health outcomes data from multiple countries. The language translation process is critical to the quality and comparability of a translated survey instrument. OBJECTIVES: The goals of this research were to translate the Prosthetic Limb Users Survey of Mobility (PLUS-M) item bank from English to Japanese using established guidelines, and linguistically validate the translated instrument by assessing its clarity, comprehension, and cultural applicability with Japanese prosthesis users. STUDY DESIGN: Instrument translation and qualitative interviews. METHODS: The translation process included two forward translations, reconciliation, backward translation, and review by clinical experts in Japan. Adult lower-limb prosthesis users participated in a linguistic validation study by responding to translated survey items and providing item-by-item feedback through cognitive interviews. RESULTS: Following expert reviews, translated items were classified as grammatically and contextually unchanged (n = 21), minor revision required (n = 19), major revision required (n = 3), or removed (n = 1). Cognitive interviews with 10 participants indicated that additional revisions were required (n = 4). Items were revised and retested until it was determined that they were clear, well understood, and culturally applicable. CONCLUSIONS: Use of a multistep translation and linguistic validation processes resulted in a linguistically comparable Japanese translation of the PLUS-M item bank. Japanese translations of the PLUS-M 7- and 12-item short forms were created for use in clinical practice and research. Availability of these linguistically comparable instruments is expected to facilitate opportunities for international comparison of prosthetic mobility data.

Assessment of locomotive syndrome in patients with visceral cancer, the comparison with non-cancer patients using propensity score matching.

BACKGROUND: When treating cancer patients, the progression of symptoms is accompanied by the deterioration of systemic conditions and motor function. From a risk-benefit perspective, a certain level of physical function must be maintained to continue cancer treatment. Recently, outpatient cancer treatment has become more common. Motor function is important to determine the feasibility of continuing cancer treatment. The study aimed to evaluate the motor function of patients with visceral cancer using locomo tests established by Japanese Orthopaedic Association. METHODS: Locomo tests were performed, and the results were compared with data from non-cancer individuals. Background data were matched by propensity score matching. Data from 53 cancer patients (group C) were compared with that of 75 non-cancer patients (group N). RESULTS: The average score in the two-step test of group C was lower than that of group N (1.27: 1.37, p = 0.004). The average function in the stand-up test of group C was worse than that of group N (p = 0.001). The average score in the 25-question geriatric locomotive function scale (GLFS) of group C was significantly higher than that of group N (19.92: 5.29, SE 2.21, p < 0.001). Higher 25-question GLFS scores indicate reduced mobility. The proportion of the locomo stage 2 in group C was significantly higher than in group N (51%: 13%, p < 0.001). The results of the two field tests revealed a clinically minimal difference between the two groups, but a statistically significant difference. Locomo tests may be detect potential motor dysfunction in outpatient cancer patients with apparently maintained motor function. CONCLUSIONS: Even in cancer patients who attend outpatient clinics, their motor functions could be potentially impaired. Therapeutic interventions to maintain and enhance motor function for cancer patients could be useful for continuing cancer treatment, and furthermore, improving prognosis.

Structure-Based Approaches to Improving Selectivity through Utilizing Explicit Water Molecules: Discovery of Selective ß-Secretase (BACE1) Inhibitors over BACE2.

BACE1 is an attractive target for disease-modifying treatment of Alzheimer's disease. BACE2, having high homology around the catalytic site, poses a critical challenge to identifying selective BACE1 inhibitors. Recent evidence indicated that BACE2 has various roles in peripheral tissues and the brain, and therefore, the chronic use of nonselective inhibitors may cause side effects derived from BACE2 inhibition. Crystallographic analysis of the nonselective inhibitor verubecestat identified explicit water molecules with different levels of free energy in the S2' pocket. Structure-based design targeting them enabled the identification of propynyl oxazine 3 with improved selectivity. Further optimization efforts led to the discovery of compound 6 with high selectivity. The cocrystal structures of 7, a close analogue of 6, bound to BACE1 and BACE2 confirmed that one of the explicit water molecules is displaced by the propynyl group, suggesting that the difference in the relative water displacement cost may contribute to the improved selectivity.

Pulmonary Function Improves in Patients with Adolescent Idiopathic Scoliosis who Undergo Posterior Spinal Fusion Regardless of Thoracoplasty: A Mid-Term Follow-Up.

INTRODUCTION: The purpose of the present study was to determine, in a mid-term follow-up 5 years or more after surgery, the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and expiratory flow in patients with adolescent idiopathic scoliosis (AIS) who underwent posterior spinal fusion (PSF) with or without thoracoplasty. METHODS: The subjects were 134 patients with AIS who underwent PSF between 2004 and 2013. Forty-five patients agreed to participate in the study. We divided the patients into two groups as follows: 24 patients who underwent PSF with thoracoplasty from 2004 to 2010 in the TP group and 21 patients who underwent PSF without thoracoplasty from 2011 to 2013 in the non-TP group. We evaluated whole spine X-ray imaging and pulmonary function tests (PFTs) in these patients. PFTs measured FVC, FEV1, peak expiratory flow (PEF), maximum expiratory flow at 50% FVC (V50), maximum expiratory flow at 25% FVC (V25), and the ratio of V50 to V25 (V50/V25). RESULTS: The main thoracic curves were 53.6 ± 10.1° before surgery, 19.8 ± 7.6° 1 week after surgery, 22.3 ± 8.3° 2 years after surgery, and 23.3 ± 7.6° at the most recent observation. Compared with preoperative values, FVC, FEV1, and % FEV1 were improved significantly at the most recent observation. No significant difference was observed between % FVC before surgery and at the most recent observation. Compared with preoperative values, PEF, V50, and V25 were improved significantly at the most recent observation. V50/V25 did not change significantly. The changes in PFT values in the TP group and the non-TP group were compared. No significant differences were observed in FVC, % FVC, FEV1, % FEV1, PEF, V50, or V25. CONCLUSIONS: Regardless of whether thoracoplasty was performed or not, FVC, FEV1, and expiratory flow were improved 5 years or later after PSF.

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.

Anchor type at upper instrumented vertebra and postoperative shoulder imbalance in patients with Lenke type 1 adolescent idiopathic scoliosis.

PURPOSE: To clarify the impact of anchor type at upper instrumented vertebra (UIV) on postoperative shoulder imbalance in patients with Lenke type 1 adolescent idiopathic scoliosis (AIS) who underwent posterior spinal fusion. METHODS: Subjects were 81 patients with Lenke type 1 AIS who underwent posterior spinal fusion between 2004 and 2013. Twenty-five patients agreed to participate in the study. We divided the patients into two groups: Hook group (15 patients with hooks at UIV who underwent surgery between 2004 and 2011) and PS group (ten patients with pedicle screws at UIV who underwent surgery between 2012 and 2013). To evaluate shoulder balance, first thoracic vertebra tilt angle (T1 tilt), clavicle angle (CA), and radiographic shoulder height (RSH) were measured. RESULTS: There were no significant differences in preoperative T1 tilt, CA, or RSH between the both groups. The postoperative 1-week, 2-year, and most recently observed T1 tilts were significantly smaller in the Hook group than in the PS group. There were no significant differences in postoperative 1-week, 2-year, and most recently observed CAs between the two groups. Although there were no significant differences in 1-week postoperative RSH between the groups, the 2-year postoperative RSH was significantly smaller in the Hook group than in the PS group. The most recently observed RSH tended to be smaller in the Hook group than in the PS group, but the difference was not significant. CONCLUSIONS: In the PS group, poor shoulder balance remained over the long term. The hooks at UIV adjusted postoperative shoulder balance.

Radiological Assessment of Damage to the Iliopsoas Muscle by the Oblique Lateral Interbody Fusion Approach.

INTRODUCTION: There are several reports about invasive muscle injury during posterior spinal surgery. However, few reports have evaluated the association between the clinical symptoms and changes in the physical properties of the psoas major after oblique lateral interbody fusion (OLIF). Therefore, the current study aimed to investigate the relationship between the clinical symptoms and changes in the psoas major muscle before and after OLIF. METHODS: Twenty-seven patients who underwent single-level OLIF following the diagnosis of degenerative lumbar disease were included in the study. The cross-sectional areas (CSAs) of the psoas major on the approaching and contralateral sides were measured in the axial computed tomography view of the surgical intervertebral space preoperatively and postoperatively at 1 week and 3, 6, and 12 months. The preoperative and postoperative changes in the CSAs were compared. Muscle degeneration was evaluated using axial magnetic resonance images at the same level as that in the CSA evaluation preoperatively and at 12 months postoperatively. Additionally, the relationship between these parameters and postoperative lower limb symptoms was investigated. RESULTS: Significant swelling of the psoas major on the approach side was observed 1 week postoperatively (p < 0.05). No postoperative muscle degeneration was observed. Three cases of paresthesia in the front of the thigh were observed, but no association was found with changes in CSA in any of the cases. CONCLUSIONS: The OLIF approach caused swelling of the psoas major 1 week postoperatively with no more muscle degeneration in the mid-term. Although numbness of the lower limbs was found in some cases, no association was found with changes in CSA. Our study findings suggest that the OLIF approach causes temporary injury or swelling of the psoas major, but the long-term damage to the muscle is not significant.

Spinal Alignments of Residual Lumbar Curve Affect Disc Degeneration after Spinal Fusion in Patients with Adolescent Idiopathic Scoliosis: Follow-up after 5 or More Years.

INTRODUCTION: Despite preserving lumbar disc mobility, spinal sagittal, and/or coronal alignment might ultimately impede surgical success. The purpose of this study was to elucidate the effects of spinal alignment on lumbar disc degeneration after 5 or more years in adolescent idiopathic scoliosis (AIS) patients who underwent spinal fusion. METHODS: Subjects were 49 AIS patients who underwent posterior spinal fusion without lumbar curve fusion. The inclusion criteria were the following: 1) Lenke type 1A, 1B, 2A or 2B, 2) age 10 to 19 years at the time of operation, and 3) minimum 5-year follow-up. The exclusion criteria were the following: 1) diagnosed as other than AIS, 2) history of lumbar disc herniation and spondylolysis, 3) subsequent surgery, and 4) history of surgery before AIS surgery. Nineteen patients agreed to participate in this research. X-rays, lumbar MRI, and questionnaires were evaluated. Disc degeneration in non-fused segments was defined as Pfirrmann grade 3 or higher. Patients with disc degenerations at the final observation (DD[+] group) were compared to those without disc degenerations (DD[-] group). RESULTS: There were no significant differences in the preoperative or postoperative 1-week X-ray parameters between both groups. The lumbar curve was significantly larger in the DD[+] group compared with the DD[-] group at the final observation (DD[+]: 16.8 degrees, DD[-]: 10.4 degrees, p = 0.035). The sagittal vertical axis (SVA) was significantly larger in the DD[+] group compared with the DD[-] group at the final observation (DD[+]: -4.4 mm, DD[-]: -34.3 mm, p = 0.006). SRS-22 function, self-image, and satisfaction scores were lower in the DD [+] group compared with the DD[-] group at the final observation. CONCLUSIONS: The patients with DD had significantly larger lumbar curve and SVA with lower SRS-22 function, self-image, and satisfaction scores at the final observation. Even though the non-fused segments were preserved, spinal alignments of non-fused lumbar curve affect the DDs.

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.

Freeze-Dried Platelet-Rich Plasma Induces Osteoblast Proliferation via Platelet-Derived Growth Factor Receptor-Mediated Signal Transduction.

STUDY DESIGN: Controlled laboratory study. PURPOSE: This study aimed to evaluate the in vitro pharmacological activity of growth factors (GFs) in freeze-dried platelet-rich plasma (FD-PRP) after storage for 4 weeks. OVERVIEW OF LITERATURE: Freshly prepared PRP is a rich source of many GFs. We reported that FD-PRP stored for 8 weeks accelerated bone union in a rat posterolateral fusion model equally well as fresh-PRP. However, the pharmacological activity of FD-PRP after longterm storage has not been shown in vitro. METHODS: Immediately after preparation, as well as 4 weeks after freeze-dried storage, the platelet count was measured. Human osteoblasts were treated with fresh-PRP and FD-PRP, respectively. Western blotting was used to assess the phosphorylation of the platelet-derived growth factor (PDGF) receptor (PDGFR) and its downstream target, extracellular signal-regulated kinase (ERK). The proliferation rates of osteoblasts were investigated by immunocytochemistry and MTT cell viability assays. Furthermore, we used western blotting to evaluate the effect of PDGFR knockdown on the phosphorylation of ERK stimulated with fresh-PRP and FD-PRP. RESULTS: Platelet counts in both the fresh-PRP and FD-PRP samples were approximately 10-fold higher than in peripheral blood samples. The phosphorylation and activation of the PDGFR and ERK were evenly induced by fresh-PRP and FD-PRP stimulation. Both freshPRP and FD-PRP significantly induced osteoblast proliferation in MTT cell viability assays. Furthermore, osteoblast PDGFR knockdown attenuated the downstream ERK activation by fresh PRP and FD-PRP. CONCLUSIONS: We demonstrated the pharmacological activity of PDGF in FD-PRP in vitro after 4 weeks of storage.

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.

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.

Discovery of an Extremely Potent Thiazine-Based ß-Secretase Inhibitor with Reduced Cardiovascular and Liver Toxicity at a Low Projected Human Dose.

Genetic evidence points to deposition of amyloid-ß (Aß) as a causal factor for Alzheimer's disease. Aß generation is initiated when ß-secretase (BACE1) cleaves the amyloid precursor protein. Starting with an oxazine lead 1, we describe the discovery of a thiazine-based BACE1 inhibitor 5 with robust Aß reduction in vivo at low concentrations, leading to a low projected human dose of 14 mg/day where 5 achieved sustained Aß reduction of 80% at trough level.