Ajoy Prasad Shetty

Go Kubota,Hiroto Kamoda,Sumihisa Orita,Kazuhidee Inage,Michihiro Ito,Masaomi Yamashita,Takeo Furuya,Tsutomu Akazawa,Yasuhiro Shiga,Seiji Ohtori 대한척추외과학회 2018 Asian Spine Journal Vol.12 No.1

Study Design: Retrospective case series. Purpose: To examine the efficacy of platelet-rich plasma (PRP) for bone fusion in transforaminal lumbar interbody fusion (TLIF) using local bone grafting. Overview of Literature: Several authors have reported the efficacy of PRP for bone union in animal models. However, the use of PRP for bone fusion in TLIF surgery has not been fully explored. Methods: Twenty patients underwent single-level TLIF surgery because of L4 spondylolisthesis. An interbody fusion cage and local bone were used in nine patients (control group) and an interbody fusion cage, local bone, and PRP were used in 11 patients (PRP group). PRP was prepared from the patients’ blood samples (400 mL) immediately before surgery. The duration of bone union and postoperative bone fusion rate were assessed using plain radiography at every 3 months postoperatively and computed tomography at 12 or 24 months postoperatively, respectively. Lower back pain, leg pain, and leg numbness were evaluated using the visual analog scale preoperatively and at 3, 6, 12, and 24 months postoperatively. Results: The platelet count was 8.7 times higher in PRP than in blood. The bone union rate was significantly superior in the PRP group than in the control group (91% and 77%, respectively; p =0.035), whereas the average duration of bone union was not significantly different between the groups (7.7±0.74 and 10.0±2.00 months, respectively; p =0.131). There was no significant difference in lower back pain, leg pain, and leg numbness in both groups during follow-up (p >0.05). Conclusions Our study suggests that the use of PRP in TLIF surgery increases bone fusion rate.

Freeze-Dried Human Platelet-Rich Plasma Retains Activation and Growth Factor Expression after an Eight-Week Preservation Period

Yasuhiro Shiga,Go Kubota,Sumihisa Orita,Kazuhide Inage,Hiroto Kamoda,Masaomi Yamashita,Toru Iseki,Michihiro Ito,Kazuyo Yamauchi,Yawara Eguchi,Takeshi Sainoh,Jun Sato,Kazuki Fujimoto,Koki Abe,Hirohito 대한척추외과학회 2017 Asian Spine Journal Vol.11 No.3

Study Design: Controlled laboratory study. Purpose: This study aimed to evaluate the efficacy of platelet-rich plasma (PRP) stored at room temperature (RT), frozen, or after freeze-drying. Overview of Literature: PRP enriches tissue repair and regeneration, and is a novel treatment option for musculoskeletal pathologies. However, whether biological activity is preserved during PRP storage remains uncertain. Methods: PRP was prepared from blood of 12 healthy human volunteers (200 mL/person) and stored using three methods: PRP was stored at RT with shaking, PRP was frozen and stored at –80°C, or PRP was freeze-dried and stored at RT. Platelet counts and growth factor content were examined immediately after preparation, as well as 2, 4, and 8 weeks after storage. Platelet activation rate was quantified by flow cytometry. Results: Platelet counts were impossible to determine in many RT samples after 2 weeks, but they remained at constant levels in frozen and freeze-dried samples, even after 8 weeks of storage. Flow cytometry showed approximately 80% activation of the platelets regardless of storage conditions. Almost no growth factors were detected in the RT samples after 8 weeks, while low but significant expression was detected in the frozen and freeze-dried PRP. Over time, the mean relative concentrations of various growth factors decreased significantly or disappeared in the RT group. In the frozen group, levels were maintained for 4 weeks, but decreased significantly by 8 weeks (p <0.05). The freeze-dried group maintained baseline levels of growth factors for the entire 8-week duration. Conclusions: Freeze-drying enables PRP storage while maintaining bioactivity and efficacy for extended periods.

The Time Course Changes in Bone Metabolic Markers after Administering the Anti-Receptor Activator of Nuclear Factor-Kappa B Ligand Antibody and Drug Compliance among Patients with Osteoporosis

Kazuhide Inage,Sumihisa Orita,Kazuyo Yamauchi,Yoshihiro Sakuma,Go Kubota,Yasuhiro Oikawa,Takeshi Sainoh,Jun Sato,Kazuki Fujimoto,Yasuhiro Shiga,Kazuhisa Takahashi,Seiji Ohtori 대한척추외과학회 2015 Asian Spine Journal Vol.9 No.3

Study Design: Retrospective study. Purpose: We conducted a study to investigate the time course changes in bone metabolic markers after the administration of the anti-receptor activator of nuclear factor-kappa B ligand (RANKL) antibody and to assess drug compliance among osteoporotic patients. Overview of Literature: The anti-RANKL antibody is expected to provide an improvement in those with a bone metabolism disorder. However there are only a few clinical reports available on the effect of treatment. Methods: We included 40 post-menopausal osteoporotic patients who received the anti-RANKL antibody. To determine the time course changes in the bone metabolic markers, we measured the serum tartrate-resistant acid phosphatase 5b (TRACP 5b; a bone resorption marker) and the serum N-terminal propeptide of type 1 collagen (P1NP; a bone formation marker) levels prior to and 1 month after administrating the anti-RANKL antibody. To evaluable drug compliance, we assessed the dropout rate during treatment and at 6 months after treatment. Results: The average TRACP 5b level significantly decreased from 574.8 mU/dL before treatment to 153.2 mU/dL 1 month after treatment (p <0.05). There was no significant difference in the average P1NP level, which was 56.9 μG/L and 35.1 μG/L before and 1 month after treatment, respectively (p >0.05). As for drug compliance, we did not have any dropouts during the treatment or after 6 months (dropout rate: 0%). Conclusions: Our study suggests that anti-RANKL antibody treatment suppresses bone resorption and maintains bone formation.

Long-Term Outcomes of In Situ Fusion for Treating Dysplastic Spondylolisthesis

Kazuhide Inage,Sumihisa Orita,Kazuyo Yamauchi,Miyako Suzuki,Yoshihiro Sakuma,Go Kubota,Yasuhiro Oikawa,Takeshi Sainoh,Jun Sato,Kazuki Fujimoto,Yasuhiro Shiga,Koki Abe,Hirohito Kanamoto,Masahiro Inoue 대한척추외과학회 2017 Asian Spine Journal Vol.11 No.2

Study Design: Retrospective, observational, single-center study. Purpose: To investigate the long-term outcomes of in situ fusion procedures for treating dysplastic spondylolisthesis. Overview of Literature: In situ fusion performed in patients with dysplastic spondylolisthesis avoids the development of nerve complications. Methods: In total, 12 of 28 patients who underwent in situ fusion for treating dysplastic spondylolisthesis at Chiba University Hospital from 1974 to 2004 were followed up in August 2013. Surgical complications were evaluated. Low back pain and leg pain were assessed using a visual analog scale (VAS). Vertebral alignment, including the lumbosacral angle and lumbar lordosis angle measurement on radiographic images (profile view in the neutral standing position), was evaluated during preoperative, postoperative, and final examinations. Results: The mean follow-up duration, patient age at the final examination, and patient age at operation were 20.0±7.2, 42.3±13.3, and 22.3±11.4 years, respectively. No complications were reported. Mean VAS scores for low back pain and leg pain were significantly lower at the final examination than at the preoperative examination (p <0.05). At the preoperative, postoperative, and final examinations, the mean lumbosacral angle was 32.3°±14.2°, 33.7°±11.8°, and 36.5°±16.4°, while the mean lumbar lordosis angle was 51.0°±14.8°, 48.6°±18.8°, and 49.6°±15.5°, respectively. No significant differences were noted among these values across the different time periods (p <0.05). Conclusions: In situ fusion performed in patients with dysplastic spondylolisthesis avoids the development of nerve complications such as nerve paralysis that may occur after repositioning operation and maintains appropriate long-term sagittal alignment, even 20 years after operation.

Use of Bioelectrical Impedance Analysis for the Measurement of Appendicular Skeletal Muscle Mass/Whole Fat Mass and Its Relevance in Assessing Osteoporosis among Patients with Low Back Pain: A Comparative Analysis Using Dual X-ray Absorptiometry

Kazuki Fujimoto,Kazuhide Inage,Yawara Eguchi,Sumihisa Orita,Miyako Suzuki,Go Kubota,Takeshi Sainoh,Jun Sato,Yasuhiro Shiga,Koki Abe,Hirohito Kanamoto,Masahiro Inoue,Hideyuki Kinoshita,Masaki Norimoto 대한척추외과학회 2018 Asian Spine Journal Vol.12 No.5

Study Design: Cross-sectional observational study. Purpose: To compare measurements of appendicular skeletal muscle mass (ASMM) and whole fat mass (WFM) obtained using dualenergy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) among patients with low back pain (LBP). Moreover, the study investigated the correlation between BIA-based ASMM and DXA-based bone mineral density (BMD). Overview of the Literature: If reliable, BIA may be a useful alternative to DXA as a screening tool for sarcopenia and osteoporosis among patients with LBP. Methods: Measurements were performed in 130 patients, including BMD of the lumbar spine and femoral neck. The correlation between DXA and BIA as well as between BIA-ASMM and BMD were evaluated. Results: BIA and DXA were highly correlated in both male and female patients (r =0.73–0.90, p <0.0001). However, BIA consistently overestimated ASMM by 1.5–2.5 kg on an average (p <0.0001) and underestimated WFM (−4.0 to −2.7 kg) on an average (p <0.0001). BIA-based ASMM correlated with BMD of the lumbar spine in both male and female patients (r =0.28–0.37, p ≤0.02) and that of the femoral neck (r =0.34–0.51, p ≤0.005). Regarding the calculated skeletal muscle index (SMI: ASMM/height [m2]) used as a criterion for sarcopenia, BIA-based SMI correlated with BMD of the lumbar spine in male patients (r =0.44, p =0.0004) and that of the femoral neck in female patients (r =0.33, p =0.009). Conclusions: BIA may be a favorable alternative to DXA as a screening tool for sarcopenia and osteoporosis among patients with LBP. Considering the overestimation of BIA-based ASMM and SMI, we recommend using the cutoff values for sarcopenia of 7.9 kg/m2 for males and 6.1 kg/m2 for females.

Dose Optimization for Single Intradiscal Administration of the Tumor Necrosis Factor-α Inhibitor, Etanercept, in Rat Disc Injury Models

Kazuhide Inage,Sumihisa Orita,Kazuyo Yamauchi,Takane Suzuki,Miyako Suzuki,Yoshihiro Sakuma,Go Kubota,Yasuhiro Oikawa,Takeshi Sainoh,Jun Sato,Kazuki Fujimoto,Yasuhiro Shiga,Koki Abe,Hirohito Kanamoto,M 대한척추외과학회 2016 Asian Spine Journal Vol.10 No.4

Study Design: Experimental animal study. Purpose: We aimed to determine the optimal dose of a single direct injection of the tumor necrosis factor (TNF)-α inhibitor, etanercept, by using the rat model of degenerative intervertebral disc from injury. Overview of Literature: The pain-related peptide expression was suppressed in the etanercept (100 μg and 1,000 μg)-administered groups in a dose-dependent manner. Methods: The neurotracer FluoroGold (FG) was applied to the surfaces of L4/5 discs to label their innervating dorsal root ganglion (DRG) neurons (n=50). Ten rats were included in the nonpunctured disc sham surgery control group, whereas the other 40 were included in the experimental group in which intervertebral discs were punctured with a 23-gauge needle. Saline or etanercept (10 μg, 100 μg, or 1,000 μg) was injected into the punctured discs (n=10 for each treatment). After 14 days of surgery, DRGs from L1 to L6 were harvested, sectioned, and immunostained for calcitonin gene-related peptide (CGRP). The proportion of FG-labeled CGRPimmunoreactive DRG neurons was evaluated in all the groups. Results: There were no significant differences between the puncture+saline group and the puncture+10-μg etanercept group (p >0.05). However, a significant decrease in the percentage of FG and CGRP double-positive cells in FG-positive cells was observed in the etanercept (100 μg and 1,000 μg)-administered groups in a dose-dependent manner (p <0.05). Conclusions: When a low dose of the TNF-α inhibitor (10 μg of etanercept) was directly administered to the rat intervertebral disc in the rat model of degenerative intervertebral disc from injury, no suppressive effect on the pain-related peptide expression was observed. However, when a higher dose of etanercept (100 μg and 1,000 μg) was administered, the pain-related peptide expression was suppressed in a dose-dependent manner.

Evaluation of Histological Changes in Back Muscle Injuries in Rats over Time

Koki Abe,Kazuhide Inage,Yoshihiro Sakuma,Sumihisa Orita,Kazuyo Yamauchi,Miyako Suzuki,Go Kubota,Yasuhiro Oikawa,Takeshi Sainoh,Jun Sato,Kazuki Fujimoto,Yasuhiro Shiga,Hirohito Kanamoto,Kazuhisa Takaha 대한척추외과학회 2017 Asian Spine Journal Vol.11 No.1

Study Design: Animal model study. Purpose: The purpose of this study was to evaluate the histological variation in the injured muscle and production of calcitonin generelated peptide in rats over time. Overview of Literature: Vertebral surgery has been reported to cause atrophy of the back muscles, which may result in pain. However, few reports have described the time series histological variation in the injured muscle and changes in the dominant nerve. Methods: We used 30 male, 8-week-old Sprague-Dawley rats. The right and left sides of the paravertebral muscle were considered as the injured and uninjured sides, respectively. A 115 g weight was dropped from a height of 1 m on the right paravertebral muscle. Hematoxylin and eosin (H&E) staining of the muscle was performed 1–3 weeks after injury for histological evaluation. Fluoro-Gold (FG) was injected into the paravertebral muscle. The L2 dorsal root ganglia on both sides were resected 1, 2, and 3 weeks after injury, and immunohistochemical staining for calcitonin gene-related peptide was performed. Results: H&E staining of the paravertebral muscle showed infiltration of inflammatory cells and the presence of granulation tissue in the injured part on the ipsilateral side 1 week after injury. Muscle atrophy occurred 3 weeks after injury, but was repaired via spontaneous replacement of muscle cells/fibers. In contrast, compared with the uninjured side, the percentage of cells double-labeled with FG and calcitonin gene-related peptide in FG-positive cells in the dorsal root ganglia of the injured side was significantly increased at each time point throughout the study period. Conclusions: These results suggest that sensitization of the dominant nerve in the dorsal root ganglia, which may be caused by cicatrix formation, can protract injured muscle pain. This information may be helpful in elucidating the underlying mechanism of persistent pain after back muscle injury.

Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain

Kazuhide Inage,Sumihisa Orita,Kazuyo Yamauchi,Takane Suzuki,Miyako Suzuki,Yoshihiro Sakuma,Go Kubota,Yasuhiro Oikawa,Takeshi Sainoh,Jun Sato,Kazuki Fujimoto,Yasuhiro Shiga,Koki Abe,Hirohito Kanamoto,M 대한척추외과학회 2016 Asian Spine Journal Vol.10 No.4

Study Design: Retrospective study. Purpose: To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Overview of Literature: Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Methods: Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. Results: No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p <0.001). Conclusions: Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent the transition of acute low back pain to chronic low back pain.

Correlation among Inflammatory Cytokine Expression Levels, Degree of Disk Degeneration, and Predominant Clinical Symptoms in Patients with Degenerated Intervertebral Discs

Takeshi Sainoh,Kazuhide Inage,Sumihisa Orita,Masao Koda,Takeo Furuya,Kazuyo Yamauchi,Miyako Suzuki,Yoshihiro Sakuma,Go Kubota,Yasuhiro Oikawa,Jun Sato,Kazuki Fujimoto,Yasuhiro Shiga,Koki Abe,Hirohito 대한척추외과학회 2017 Asian Spine Journal Vol.11 No.3

Study Design: Observational study. Purpose: To assess the correlation among inflammatory cytokine expression levels, degree of intervertebral disk (IVD) degeneration, and predominant clinical symptoms observed in degenerative disk disease (DDD). Overview of Literature: Low back pain (LBP) is associated with inflammatory cytokine expression levels, including those of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and nerve growth factor (NGF). However, the association between cytokine expression levels and the physiological mechanisms of disk degeneration and clinical pain remain controversial. Methods: Using the enzyme-linked immunosorbent assay, TNF-α, IL-6, and NGF expression levels were analyzed in 58 IVD samples that were harvested from patients with lumbar DDD. Patient samples were grouped according to the degree of IVD degeneration using the Pfirrmann grading system and magnetic resonance imaging, and the correlations between the disease groups and each cytokine expression level were assessed. In addition, on the basis of their predominant preoperative symptoms, the patients were assigned to either an LBP or leg pain group to determine the correlation among these disease manifestations and individual cytokine expression levels. Results: A gradual increase in TNF-α (R=0.391) and IL-6 (R=0.388) expression levels correlated with the degree of IVD degeneration, whereas NGF (R=0.164) expression levels exhibited a minimal decrease with disease progression. Regarding the predominant clinical manifestation, only the LBP group exhibited a significant increase in TNF-α expression levels (p =0.002). Conclusions: These results suggested that TNF-α and IL-6 play an important role in the pathophysiology of IVD degeneration at any stage, whereas NGF plays an important role during the early disease stages. Moreover, because TNF-α expression levels were significantly high in the LBP group, we propose that they are involved in LBP onset or progression.

Inhibiting Vascular Endothelial Growth Factor in Injured Intervertebral Discs Attenuates Pain-Related Neuropeptide Expression in Dorsal Root Ganglia in Rats

Jun Sato,Kazuhide Inage,Masayuki Miyagi,Yoshihiro Sakuma,Kazuyo Yamauchi,Masao Koda,Takeo Furuya,Junichi Nakamura,Miyako Suzuki,Go Kubota,Yasuhiro Oikawa,Takeshi Sainoh,Kazuki Fujimoto,Yasuhiro Shiga 대한척추외과학회 2017 Asian Spine Journal Vol.11 No.4

Study Design: An experimental animal study. Purpose: To evaluate effects of anti-vascular endothelial growth factor (VEGF) on the content and distribution of the calcitonin generelated peptide (CGRP) in the dorsal ganglia in a rat model. Overview of Literature: Increased expression of VEGF in degenerative disc disease increases the levels of inflammatory cytokines and nerve ingrowth into the damaged discs. In animal models, increased levels of VEGF can persist for up to 2 weeks after an injury. Methods: Through abdominal surgery, the dorsal root ganglia (DRG) innervating L5/L6 intervertebral disc were labeled (FluoroGold neurotracer) in 24, 8-week old Sprague Dawley rats. The rats were randomly allocated to three groups of eight rats each. The anti- VEGF group underwent L5/6 intervertebral disc puncture using a 26-gauge needle, intradiscal injection of 33.3 μg of the pegaptanib sodium, a VEGF165 aptamer. The control-puncture group underwent disc puncture and intradiscal injection of 10 μL saline solution, and the sham-surgery group underwent labeling but no disc puncture. Two rats in each group were sacrificed on postoperative days 1, 7, 14, and 28 after surgery. L1–L6 DRGs were harvested, sectioned, and immunostained to detect the content and distribution of CGRP. Results: Compared with the control, the percentage of CGRP-positive cells was lower in the anti-VEGF group (p <0.05; 40.6% and 58.1% on postoperative day 1, 44.3% and 55.4% on day 7, and 42.4% and 59.3% on day 14). The percentage was higher in the control group compared with that of the sham group (p <0.05; sham group, 34.1%, 40.7%, and 33.7% on postoperative days 1, 7, and 14, respectively). Conclusions: Decreasing CGRP-positive cells using anti-VEGF therapy provides fundamental evidence for a possible therapeutic role of anti-VEGF in patients with discogenic lower back pain.