Association between Osteoporosis and Skeletal Muscle Mass in Men.

STUDY DESIGN: Cross-sectional study. PURPOSE: This cross-sectional study aimed to investigate the risk factors for osteoporosis in men by assessing bone mineral density (BMD), skeletal muscle mass, body fat mass, grip strength, and advanced glycation end products (AGEs). OVERVIEW OF LITERATURE: Fewer studies have reported the correlation between BMD and skeletal muscle mass in women. Moreover, a few studies have examined the relationship between osteoporosis and skeletal muscle mass. METHODS: This study included 99 men (mean age, 74.9 years; range, 28-93 years) who visited Qiball Clinic for BMD and body composition examinations. The osteoporosis group consisted of 24 patients (mean age, 72.5 years; range, 44-92 years), and the control group consisted of 75 individuals (mean age, 74.9 years; range, 28-93 years). Whole-body skeletal muscle mass was measured using a bioelectrical impedance analyzer. BMD was measured by dual X-ray absorptiometry. Skin autofluorescence (SAF), a marker of dermal AGE accumulation, was measured using a spectroscope. Osteoporosis was defined as a bone density T score of -2.5 or less. Physical findings, skeletal muscle mass, BMD, grip strength, and SAF were compared between the osteoporosis and control groups. RESULTS: The osteoporosis group had significantly lower trunk muscle mass (23.1 kg vs. 24.9 kg), lower leg muscle mass (14.4 kg vs. 13.0 kg), and skeletal mass index (7.1 kg/m2 vs. 6.7 kg/m2) than the control group (all p<0.05). Lower limb muscle mass was identified as a risk factor for osteoporosis in men (odds ratio, 0.64; p=0.03). CONCLUSIONS: Conservative treatment of osteoporosis in men will require an effective approach that facilitates the maintenance or strengthening of skeletal muscle mass, including exercise therapy with a focus on lower extremities and nutritional supplementation.

New treatment strategy for chronic low back pain with alpha wave neurofeedback.

The lifetime prevalence of low back pain is 83%. Since there is a lack of evidence for therapeutic effect by cognitive behavioral therapy (CBT) or physical therapy (PT), it is necessary to develop objective physiological indexes and effective treatments. We conducted a prospective longitudinal study to evaluate the treatment effects of CBT, PT, and neurofeedback training (NFT) during alpha wave NFT. The early-chronic cases within 1 year and late-chronic cases over 1 year after the diagnosis of chronic low back pain were classified into six groups: Controls, CBTs, PTs, NFTs, CBT-NFTs, PT-NFTs. We evaluated the difference in EEG, psychosocial factors, scores of low back pain before/after the intervention. Therapeutic effect was clearly more effective in the early-chronic cases. We found that the intensity of alpha waves increased significantly after therapeutic intervention in the NFT groups, but did not have the main effect of reducing low back pain; the interaction between CBT and NFT reduced low back pain. Factors that enhance therapeutic effect are early intervention, increased alpha waves, and self-efficacy due to parallel implementation of CBT/PT and NFT. A treatment protocol in which alpha wave neurofeedback training is subsidiarily used with CBT or PT should be developed in the future.

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.

Risk Factors for Proximal Junctional Fracture Following Fusion Surgery for Osteoporotic Vertebral Collapse with Delayed Neurological Deficits: A Retrospective Cohort Study of 403 Patients.

INTRODUCTION: Approximately 3% of osteoporotic vertebral fractures develop osteoporotic vertebral collapse (OVC) with neurological deficits, and such patients are recommended to be treated surgically. However, a proximal junctional fracture (PJFr) following surgery for OVC can be a serious concern. Therefore, the aim of this study is to identify the incidence and risk factors of PJFr following fusion surgery for OVC. METHODS: This study retrospectively analyzed registry data collected from facilities belonging to the Japan Association of Spine Surgeons with Ambition (JASA) in 2016. We retrospectively analyzed 403 patients who suffered neurological deficits due to OVC below T10 and underwent corrective surgery; only those followed up for　≥2 years were included. Potential risk factors related to the PJFr and their cut-off values were calculated using multivariate logistic regression analysis and receiver operating characteristic (ROC) analysis. RESULTS: Sixty-three patients (15.6%) suffered PJFr during the follow-up (mean 45.7 months). In multivariate analysis, the grade of osteoporosis (grade 2, 3: adjusted odds ratio (aOR) 2.92; p=0.001) and lower instrumented vertebra (LIV) level (sacrum: aOR 6.75; p=0.003) were independent factors. ROC analysis demonstrated that lumbar bone mineral density (BMD) was a predictive factor (area under curve: 0.72, p=0.035) with optimal cut-off value of 0.61 g/cm2 (sensitivity, 76.5%; specificity, 58.3%), but that of the hip was not (p=0.228). CONCLUSIONS: PJFr was found in 16% cases within 4 years after surgery; independent risk factors were severe osteoporosis and extended fusion to the sacrum. The lumbar BMD with cut-off value 0.61 g/cm2 may potentially predict PJFr. Our findings can help surgeons select perioperative adjuvant therapy, as well as a surgical strategy to prevent PJFr following surgery.

Wrapping With Basic Fibroblast Growth Factor-Impregnated Collagen Sheet Reduces Rat Sciatic Nerve Allodynia.

Autologous vein wrapping is used to treat recurrent chronic constriction neuropathy and traumatic peripheral nerve injury. However, its use is restricted due to the inability to obtain sufficiently long veins for larger grafts. We previously reported that vein-derived basic fibroblast growth factor (bFGF) promotes heme oxygenase-1 (HO-1), which reduces allodynia via its anti-inflammatory properties. To mimic vein wrapping, we developed a collagen sheet impregnated with bFGF. Chronic constriction injury (CCI) was induced in male Wistar rats as a model of sciatic nerve injury, and the rats were divided into three groups: (i) untreated after CCI surgery (control group), (ii) treated with a collagen sheet wrap impregnated with phosphate-buffered saline (PBS/CS group), and (iii) treated with a collagen sheet wrap impregnated with bFGF (bFGF/CS group). Pain behavior (von Frey test) was evaluated on postoperative days (PODs) 1, 5, 7, and 14. Quantitative polymerase chain reaction was conducted on sciatic nerve RNA to quantify HO-1 gene, Hmox1, expression. Enzyme-linked immunosorbent assay were used to determine HO-1 protein levels on POD 1. von Frey testing showed significantly greater pain hypersensitivity in the control and PBS/CS groups than the bFGF/CS group. In the bFGF/CS group, Hmox1 messenger RNA and HO-1 protein levels were significantly increased in the sciatic nerve compared with the control and PBS/CS groups on PODs 1 and 5 and POD 1, respectively. The bFGF/CS group showed decreased allodynia and HO-1 induction, as observed with vein wrapping. Therefore, local application of bFGF may be an alternative treatment strategy for compressive neuropathy and peripheral nerve trauma in clinical settings. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2258-2263, 2019.

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.

Changes in proinflammatory cytokines, neuropeptides, and microglia in an animal model of monosodium iodoacetate-induced hip osteoarthritis.

The aim of this study was to investigate the local production of proinflammatory cytokines, pain-related sensory innervation of dorsal-root ganglia (DRG), and spinal changes in a rat model of induced hip osteoarthritis (OA). Seventy-five Sprague-Dawley rats were used, including 25 controls and 50 injected into the right hip joints (sham group, injected with 25 µl of sterile saline: N = 25; and monosodium iodoacetate (MIA) group, injected with 25 µl of sterile saline with 2 mg of MIA: N = 25). We measured the local production of TNF-α, immunoreactive (-ir) neurons for calcitonin gene-related peptide (CGRP), and growth associated protein-43 (GAP-43) in DRG, and immunoreactive neurons for ionized-calcium-binding adaptor molecule-1 (Iba-1) in the dorsal horn of spinal cord, on post-induction days 7, 14, 28, 42, and 56 (N = 5 rats/group/time point). For post-induction days 7-42, the MIA group presented significantly elevated concentrations of TNF-α than the other groups (p < 0.01), and a higher expression of CGRP-ir in FG-labeled DRG neurons than the sham group (p < 0.01). MIA rats also presented significantly more FG-labeled GAP-43-ir DRG neurons than the sham group on post-induction days 28, 42, and 56 (p < 0.05), and a significantly higher number of Iba-1-ir microglia in the ipsilateral dorsal horn than the other groups, on post-induction days 28, 42, and 56. The results suggest that in rat models, pain-related pathologies due to MIA-induced hip OA, originate from inflammation caused by cytokines, which leads to progressive, chronic neuronal damage that may cause neuropathic pain. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2978-2986, 2018.

Efficacy of nerve growth factor antibody in a knee osteoarthritis pain model in mice.

BACKGROUND: Nerve growth factor (NGF) is not only an important factor in nerve growth but also a major contributor to the production of inflammation. It has been reported that inhibiting NGF could reduce several types of pain in several animal models. Here, we aimed to clarify the efficacy of NGF antibody in a knee osteoarthritis (OA) pain model in mice. METHOD: Six-week-old male C57BR/J mice were used (n = 30). Ten mice comprised the control group, which received saline injection into the right knee joints; the other 20 mice comprised the experimental group, which received monoiodoacetate (MIA) injection into the right knee joints. Three weeks after surgery, the 20 experimental mice were randomly placed into treatment groups which received either sterile saline (non-treat group: 10 mg/kg, i.p.) or an anti-NGF antibody (anti-NGF group: 10 mg/kg, i.p.). Simultaneously, all mice received fluorogold (FG) retrograde neurotracer injection into their right joints. In a behavioral study, we evaluated gait using the CatWalk quantitative gait analysis system before surgery, 3 weeks after surgery (before treatment), 4 weeks after surgery (one week after surgery), and 5 weeks after surgery (2 weeks after surgery). In immunohistochemical analysis, the right dorsal root ganglia (DRGs) from the L4-L6 levels were resected 5 weeks after surgery (2 weeks after surgery). They were immunostained for calcitonin gene-related peptide (CGRP), and the number of FG-labeled or CGRP-immunoreactive (IR) DRG neurons was counted. RESULTS: On gait analysis using the CatWalk system, duty cycle, swing speed, and print area were decreased in non-treat group compared with those in control group and improved in the anti-NGF group compared with those in non-treat group. CGRP expression in DRGs was up-regulated in non-treat group compared with that in control group and suppressed in the anti-NGF group compared with that in non-treat group (both p < 0.05). CONCLUSIONS: MIA injection into the knee joint induced gait impairment and the up-regulation of CGRP in DRG neurons in a knee OA pain model in mice. Intraperitoneal injection of anti-NGF antibody suppressed this impairment of gait and up-regulation of CGRP in DRG neurons. These finding suggest that anti-NGF therapy might be valuable in the treatment of OA pain in the knee.

Corticosteroids and low bone mineral density affect hip cartilage in systemic lupus erythematosus patients: Quantitative T2 mapping.

BACKGROUND: The purpose of this diagnostic study was to quantify the effect of high-dose corticosteroid treatment on hip joint cartilage degeneration in patients with systemic lupus erythematosus (SLE), with and without osteonecrosis, using magnetic resonance imaging (MRI). METHODS: T2 mapping, with a 3.0 Tesla Discovery MR750 (GE Healthcare) MRI scanner, was performed in 12 volunteers without hip pathology (control group, 12 hips), in 11 patients with SLE without osteonecrosis, who were receiving corticosteroid therapy (corticosteroid-ON group, 17 hips), and in 15 patients with SLE receiving corticosteroids, who had noncollapsed and asymptomatic osteonecrosis (corticosteroid+ON group, 26 hips). The distribution of T2 values in the femoral head and acetabular cartilage were compared among the three groups. Step-wise multiple regression analysis was performed to determine the prognostic factors for T2 values indicative of femoral head cartilage degeneration. RESULTS: Mean T2 values of femoral head cartilage were significantly higher in the corticosteroid-ON (40.3 ms) and corticosteroid+ON (35.2 ms) groups than in the control group (30.1 ms, P = 0.001). T2 values of acetabular cartilage were significantly higher in the corticosteroid-ON group (41.8 ms) versus the control (33.4 ms) and the corticosteroid+ON groups (37.0 ms; P = 0.001). Low bone mineral density was a significant prognostic factor for high T2 values of cartilage at the femoral head in patients treated with corticosteroids, regardless of whether they had osteonecrosis. CONCLUSION: T2 mapping suggests that corticosteroid therapy and osteoporosis are independent risk factors for cartilage degeneration at the femoral head in patients with SLE.

Effectiveness of L2 spinal nerve infiltration for selective discogenic low back pain patients.

BACKGROUND: It has been reported that rat L5/6 lumbar discs are innervated mainly by L2 dorsal root ganglion neurons. We previously reported that L2 spinal nerve infiltration was effective for discogenic low back pain (DLBP) patients, although the diagnosis was based only on the results of physical examination, plain films, and magnetic resonance imaging (MRI). The purpose of the current study was to evaluate L2 spinal nerve block for DLBP patients retrospectively based on MRI findings and surgical results. METHODS: A total of 62 patients with only LBP and no accompanying radicular pain were investigated. Patients had only one level of disc degeneration on MRI. When pain was provoked during discography, we performed surgery at the next stage (40 patients). In all, 22 patients were excluded owing to negative discography results. Of the 40 patients, we evaluated 25 strictly selected patients suffering from DLBP. DLBP was diagnosed when the patient experienced pain relief at least 2 years after anterior lumbar interbody fusion. Fifteen patients who did not show pain relief after surgery were used for the non-DLBP group. L2 spinal nerve infiltration using 1.5 ml of lidocaine was performed in all 40 patients before surgery. The visual analogue scale (VAS) score after L2 spinal nerve infiltration was recorded, and an association of L2 spinal nerve infiltration and DLBP was explored. RESULTS: Low back pain scores assessed using the VAS score, the Japanese Orthopedic Association score, and the Oswestry Disability Index score in the two groups were not significantly different. L 2 spinal nerve infiltration was effective for 27 patients but not effective for 13 patients; the VAS score after 15 min and 2 h improved in the DLBP group compared with that of the non-DLBP group (P < 0. 05). L2 spinal nerve infiltration was more effective in DLBP patients (21 patients, 84%) than in the non-DLBP group (6 patients, 40%) (P < 0.05). CONCLUSIONS: In the current study, L2 spinal nerve infiltration was effective in 84% of selected DLBP patients and is thought to be a useful tool for diagnosing DLBP. However, we should take into consideration that the L2 spinal nerve infiltration was effective in 40% of non-DLBP patients as well.