Change of Lumbar Ligamentum Flavum after Indirect Decompression Using Anterior Lumbar Interbody Fusion

Seiji Ohtori,Sumihisa Orita,Kazuyo Yamauchi,Yawara Eguchi,Yasuchika Aoki,Junichi Nakamura,Masayuki Miyagi,Miyako Suzuki,Gou Kubota,Kazuhide Inage,Takeshi Sainoh,Jun Sato,Kazuki Fujimoto,Yasuhiro Shiga 대한척추외과학회 2017 Asian Spine Journal Vol.11 No.1

Study Design: Retrospective case series. Purpose: The purpose of this study was to examine changes in the ligamentum flavum thickness and remodeling of the spinal canal after anterior fusion during a 10-year follow-up. Overview of Literature: Extreme lateral interbody fusion provides minimally invasive treatment of the lumbar spine; this anterior fusion without direct posterior decompression, so-called indirect decompression, can achieve pain relief. Anterior fusion may restore disc height, stretch the flexure of the ligamentum flavum, and increase the spinal canal diameter. However, changes in the ligamentum flavum thickness and remodeling of the spinal canal after anterior fusion during a long follow-up have not yet been reported. Methods: We evaluated 10 patients with L4 spondylolisthesis who underwent stand-alone anterior interbody fusion using the iliac crest bone. Magnetic resonance imaging was performed 10 years after surgery. The cross-sectional area (CSA) of the dural sac and the ligamentum flavum at L1–2 to L5–S1 was calculated using a Picture Archiving and Communication System. Results: Spinal fusion with correction loss (average, 4.75 mm anterior slip) was achieved in all patients 10 years postsurgery. The average CSAs of the dural sac and the ligamentum flavum at L1–2 to L5–S1 were 150 mm2 and 78 mm2, respectively. The average CSA of the ligamentum flavum at L4–5 (30 mm2) (fusion level) was significantly less than that at L1–2 to L3–4 or L5–S1. Although patients had an average anterior slip of 4.75 mm, the average CSA of the dural sac at L4–5 was significantly larger than at the other levels. Conclusions: Spinal stability induced a lumbar ligamentum flavum change and a sustained remodeling of the spinal canal, which may explain the long-term pain relief after indirect decompression fusion surgery.

Efficacy of Direct Injection of Etanercept into Knee Joints for Pain in Moderate and Severe Knee Osteoarthritis

Seiji Ohtori,Sumihisa Orita,Kazuyo Yamauchi,Yawara Eguchi,Nobuyasu Ochiai,Shunji Kishida,Kazuki Kuniyoshi,Yasuchika Aoki,Junichi Nakamura,Tetsuhiro Ishikawa,Masayuki Miyagi,Hiroto Kamoda,Miyako Suzuki 연세대학교의과대학 2015 Yonsei medical journal Vol.56 No.5

Purpose: Osteoarthritic (OA) pain is largely considered to be inflammatory pain. However, during the last stage of knee OA, sensorynerve fibers in the knee are shown to be significantly damaged when the subchondral bone junction is destroyed, and this can induce neuropathic pain. Several authors have reported that tumor necrosis factor-α (TNFα) in a knee joint plays a crucial role in pain modulation. The purpose of the current study was to evaluate the efficacy of etanercept, a TNFα inhibitor, for pain in knee OA. Materials and Methods: Thirty-nine patients with knee OA and a 2–4 Kellgren-Lawrence grading were evaluated in this prospectivestudy. Patients were divided into two groups; hyaluronic acid (HA) and etanercept injection. All patients received a single injectioninto the knee. Pain scores were evaluated before and 4 weeks after injection using a visual analogue scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and they were compared between the groups. Results: Before injection, VAS and WOMAC scores were not significantly different between the groups (p>0.05). Significant pain relief was found in the etanercept group at 1 and 2 weeks by VAS, and at 4 weeks by WOMAC score, compared with the HA group (p<0.05). No adverse events were observed in either group. Conclusion: Direct injection of etanercept into OA knee joints was an effective treatment for pain in moderate and severe OA patients. Furthermore, this finding suggests that TNFα is one factor that induces OA pain.

Classification of Chronic Back Muscle Degeneration after Spinal Surgery and Its Relationship with Low Back Pain

Seiji Ohtori,Sumihisa Orita,Kazuyo Yamauchi,Yawara Eguchi,Yasuchika Aoki,Junichi Nakamura,Tetsuhiro Ishikawa,Masayuki Miyagi,Hiroto Kamoda,Miyako Suzuki,Gou Kubota,Kazuhide Inage,Takeshi Sainoh,Jun Sa 대한척추외과학회 2016 Asian Spine Journal Vol.10 No.3

Study Design: Retrospective case series. Purpose: To classify back muscle degeneration using magnetic resonance imaging (MRI) and investigate its relationship with back pain after surgery. Overview of Literature: Back muscle injury and degeneration often occurs after posterior lumbar surgery, and the degeneration may be a cause of back pain. However, the relationship between back muscle degeneration and back pain remains controversial. Methods: A total of 84 patients (average age, 65.1 years; 38 men, 46 women) with lumbar spinal stenosis underwent posterior decompression surgery alone. MRI (1.5 tesla) was evaluated before and more than a year after surgery in all patients. Muscle on MRI was classified into three categories: low intensity in T1-weighted imaging, high intensity in T2-weighted imaging (type 1), high intensity in both T1- and T2-weighted images (type 2), and low intensity in both T1- and T2-weighted imaging (type 3). The prevalence of the types and their relationship with back pain (determined on a visual analog scale) were evaluated. Results: MRI revealed muscle degeneration in all patients after surgery (type 1, 6%; type 2, 82%; and type 3, 12%). Type 2 was significantly more frequent compared with types 1 and 3 (p <0.01). Low back pain was significantly improved after surgery (p <0.01). Low back pain was not associated with any MRI type of muscle degeneration after surgery (p >0.05). Conclusions: Various pathologies of back muscle degeneration after posterior lumbar surgery were revealed. Type 2 (fatty) change was most frequent, and other patients had type 3 (scar) or type 1 (inflammation or water-like) changes. According to the Modic classification of bone marrow changes, Modic type 1 change is associated with inflammation and back pain. However, no particular type of back muscle degeneration was correlated with back pain after surgery.

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

Hideyuki Kinoshita,Sumihisa Orita,Kazuhide Inage,Kazuki Fujimoto,Yasuhiro Shiga,Koki Abe,Masahiro Inoue,Masaki Norimoto,Tomotaka Umimura,Takeshi Ishii,Tsukasa Yonemoto,Hiroto Kamoda,Toshinori Tsukanis 대한척추외과학회 2020 Asian Spine Journal Vol.14 No.1

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 long-term 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 fresh-PRP 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.

Do Physical Symptoms Predict the Outcome of Surgical Fusion in Patients with Discogenic Low Back Pain?

Seiji Ohtori,Sumihisa Orita,Kazuyo Yamauchi,Yawara Eguchi,Yasuchika Aoki,Junichi Nakamura,Masayuki Miyagi,Miyako Suzuki,Gou Kubota,Kazuhide Inage,Takeshi Sainoh,Jun Sato,Yasuhiro Shiga,Koki Abe,Kazuki 대한척추외과학회 2016 Asian Spine Journal Vol.10 No.3

Study Design: Retrospective case series. Purpose: To determine whether symptoms predict surgical outcomes for patients with discogenic low back pain (DLBP). Overview of Literature: Specific diagnosis of DLBP remains difficult. Worsening of pain on flexion is a reported symptom of DLBP. This study sought to determine whether symptoms predict surgical outcomes for patients with DLBP. Methods: We investigated 127 patients with low back pain (LBP) and no dominant radicular pain. Magnetic resonance imaging was used to select patients with disc degeneration at only one level. If pain was provoked during discography, we performed fusion surgery (87 patients). Visual analogue scale score and responses to a questionnaire regarding symptoms including worsening of pain on flexion or extension were assessed. Symptom sites before surgery were categorized into LBP alone, or LBP plus referred inguinal or leg pain. We followed 77 patients (average 3.0 years) and compared symptoms before surgery with surgical outcome. Results: Sixty-three patients with a good outcome showed postsurgical pain relief (≥60% pain relief) and 14 patients with a poor outcome did not (<60% pain relief). In patients with good outcomes, worsening of LBP was evident in 65% of cases on flexion and in 35% on extension. However, these findings were not significantly different from those in patients with poor outcomes. The percentage of patients with LBP alone was significantly lower and the percentage of patients with LBP plus referred inguinal or leg pain was significantly higher in the group with good surgical outcome compared with patients in the group with poor surgical outcome (p <0.05). Conclusions: Worsening of pain on extension may be a symptom of DLBP. Surgical outcomes were superior in patients with both LBP and either referred inguinal or leg pain compared with those having LBP alone.

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.

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.

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.

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.

Time-Course Changes in Bone Metabolism Markers and Density in Patients with Osteoporosis Treated with Romosozumab: A Multicenter Retrospective Study

Kazuhide Inage,Sumihisa Orita,Yawara Eguchi,Yasuhiro Shiga,Masao Koda,Yasuchika Aoki,Toshiaki Kotani,Tsutomu Akazawa,Takeo Furuya,Junichi Nakamura,Hiroshi Takahashi,Miyako Suzuki-Narita,Satoshi Maki,S 연세대학교의과대학 2021 Yonsei medical journal Vol.62 No.9

Purpose: In this multicenter retrospective observational study, we examined the early effects of romosozumab in patients with severeosteoporosis in terms of time-course changes in bone metabolism marker, improvement in bone density, and adverse effects. Materials and Methods: Patients with severe osteoporosis were included. We investigated the progress of TRACP 5b and P1NPbefore and 1–2 months after the administration of romosozumab. We also investigated the bone density of lumbar spine, femoralneck, and the entire femur, measured by the DXA method, before and 5–7 months after the administration of romosozumab. Results: A total of 70 patients (7 males and 63 females, age 75.0±3.6 years) participated in this study. Significant improvements inTRACP 5b and P1NP levels were observed before and 1–2 months after romosozumab administration. The average bone densityof lumbar spine, femoral neck, and the entire femur were measured before and 5–7 months after romosozumab administration;and a significant increase only observed in the lumbar spine. Conclusion: Consistent with the findings of previous clinical studies, romosozumab has both bone formation-enhancing andbone resorption effects (dual effect). In addition, romosozumab also demonstrated improvement in bone density from the earlyphase after the administration, though the result was only seen in the lumbar spine.