Miyako Suzuki

Comparison of teriparatide and bisphosphonate treatment to reduce pedicle screw loosening after lumbar spinal fusion surgery in postmenopausal women with osteoporosis from a bone quality perspective.

Study Design. Prospective study. Objective. To examine the efficacy of teriparatide or bisphosphonate treatment to reduce pedicle screw (PS) loosening after instrumented lumbar posterolateral fusion in postmenopausal women with osteoporosis. Summary of Background Data. Failure of fixation caused by loosening of PSs in osteoporosis is a problem in spinal surgery. Oral administration of bisphosphonate or intermittent injection of parathyroid hormone treatment increases bone mass and reduces the risk of osteoporotic vertebral fractures. Although these treatments may be factor in improving bone quality, a clinical study of the efficacy of bisphosphonate or parathyroid hormone for reducing PS loosening that addresses the quality of the bone marrow and pedicle cortex has not yet been reported. Methods. Sixty-two women with osteoporosis diagnosed with degenerative spondylolisthesis were divided into 3 groups: a teriparatide group (daily subcutaneous injection of 20 &mgr;g of teriparatide, n = 20), a bisphosphonate group (daily oral administration 2.5 mg of risedronate, n = 20), and a control group (without medication for osteoporosis, n = 22). All patients underwent decompression and 1- or 2-level instrumented posterolateral fusion with a local bone graft. Loosening of PSs and surgical outcome were evaluated radiographically, clinically, and by computed tomography 12 months after surgery. Results. At 12-month follow-up, the incidence of PS loosening was 7% to 13% in the teriparatide group, 13% to 26% in the risedronate group, and 15% to 25% in the control group. The incidence of PS loosening in the teriparatide group was significantly lower than that in the risedronate or the control group (P < 0.05). In contrast, the extent of PS loosening in the risedronate group was not significantly different from that in the control group (P > 0.05). Conclusion. Our findings suggest that administration of teriparatide increased the quality of the lumbar spine bone marrow and pedicle cortex. Level of Evidence: 3

Epidural administration of spinal nerves with the tumor necrosis factor-alpha inhibitor, etanercept, compared with dexamethasone for treatment of sciatica in patients with lumbar spinal stenosis: a prospective randomized study.

Study Design. Prospective randomized trial. Objective. To examine the effect of the tumor necrosis factor alpha (TNF-&agr;) inhibitor, etanercept, on radicular pain by its epidural administration onto spinal nerves in patients with lumbar spinal stenosis. Summary of Background Data. TNF-&agr; is thought to play a crucial role in the radicular pain caused by lumbar disc herniation and spinal stenosis. Intravenous infusion of infliximab for sciatica has been examined in 2 studies; however, the results were equivocal. Methods. Eighty patients with low back and radicular leg pain were investigated. We diagnosed the patients by physical examination, and X-ray and magnetic resonance imaging. In 40 patients, we epidurally administered 2.0 mL of lidocaine and 10 mg of etanercept onto the affected spinal nerve, and 2.0 mL of lidocaine and 3.3 mg of dexamethasone was used in 40 patients. Low back pain, leg pain, and leg numbness were evaluated using a visual analogue scale (VAS) and Oswestry Disability Index (ODI) score before and for 1 month after epidural administration. Results. Low back pain, leg pain, and leg numbness in the 2 groups were not significantly different before epidural administration. Epidural administration of etanercept was more effective than dexamethasone for leg pain (3 days, and 1, 2, and 4 weeks: P < 0.05), low back pain (3 days, and 1 and 2 weeks: P < 0.05), and leg numbness (3 days, and 1 and 2 weeks: P < 0.05). No adverse event was observed in either group. Conclusion. Our results indicate that epidural administration of a TNF-&agr; inhibitor onto the spinal nerve produced pain relief, but no adverse event. TNF-&agr; inhibitors may be useful tools for the treatment of radicular pain caused by spinal stenosis.

Teriparatide accelerates lumbar posterolateral fusion in women with postmenopausal osteoporosis: prospective study.

Study Design. Prospective trial. Objective. To examine the clinical efficacy of teriparatide for bone union after instrumented lumbar posterolateral fusion using local bone grafting in women with postmenopausal osteoporosis. Summary of Background Data. Intermittent parathyroid hormone (PTH) treatment increases bone mass and reduces the risk for osteoporotic vertebral fractures. Recombinant human PTH (1–34) has already been approved as a treatment for severe osteoporosis. Preclinical data support the efficacy of PTH for lumbar spinal fusion. However, clinical results of PTH for spinal fusion have not yet been reported. Methods. Fifty-seven women with osteoporosis diagnosed with degenerative spondylolisthesis were divided into 2 treatment groups, a teriparatide group (n = 29; daily subcutaneous injection of 20 &mgr;g of teriparatide) and a bisphosphonate group (n = 28; weekly oral administration of 17.5 mg of risedronate). All patients underwent decompression and 1- or 2-level instrumented posterolateral fusion with a local bone graft. Fusion rate, duration of bone union, and pain scores were evaluated 1 year after surgery. Results. Pain scores improved after surgery; however, no significant difference was noted between the groups after surgery. The rate of bone union was 82% in the teriparatide group and 68% in the bisphosphonate group. Average duration of bone union was 8 months in the teriparatide group and 10 months in the bisphosphonate group. The rate of bone union and average of duration of bone union in the teriparatide group patients were significantly superior to those in the bisphosphonate group. Conclusion. Daily subcutaneous injection of teriparatide for bone union using local bone grafting after instrumented lumbar posterolateral fusion in women with postmenopausal osteoporosis was more effective than oral administration of bisphosphonate.

Disk injury in rats produces persistent increases in pain-related neuropeptides in dorsal root ganglia and spinal cord glia but only transient increases in inflammatory mediators: pathomechanism of chronic diskogenic low back pain.

Study Design. Immunohistological analysis in an injured intervertebral disk (IVD) model. Objective. To elucidate and compare in rats the behavior of the sensory nervous system and inflammatory mediators in experimentally injured IVDs. Summary of Background Data. Multiple human and animal studies have verified the presence of sensory nerve fibers in IVDs or investigated the behavior of inflammatory mediators in injured IVDs, but no in vivo study to date has examined the relationship between the 2. Methods. Eight-week-old female rats were used. In the disk-injured group, L5/L6 disks were injured with a 24-gauge needle; simultaneously, the neurotracer Fluoro-gold was injected into the L5/L6 IVD. The L5/L6 IVD dorsal root ganglia (DRGs) from the L1 to L6 levels, and the spinal cord was resected at several time points after surgery. Nerve growth factor, tumor necrosis factor (TNF)-&agr; and interleukin (IL)-6 production in the IVDs were quantified using enzyme-linked immunosorbent assay. DRGs were immunostained for calcitonin gene-related peptide, and spinal cord sections were immunostained for ionized calcium-binding adaptor molecule-1 and glial fibrillary acidic protein. Results. Nerve growth factor, and TNF-&agr; levels (through 1 week) and IL-6 levels (through 4 days) were significantly higher in the disk-injured group than in the noninjured group (P < 0.05). However, starting at 2 weeks (nerve growth factor and TNF-&agr;) or 1 week (IL-6), the differences in inflammatory mediator levels between the 2 groups no longer were significant. In contrast, the percentage of calcitonin gene-related peptide-immunoreactive neurons among Fluoro-gold–labeled DRG neurons, and the numbers of ionized calcium-binding adaptor molecule-1-immunoreactive microglia and glial fibrillary acidic protein-immunoreactive astrocytes in the spinal dorsal horn remained significantly higher in the injured group than in the noninjured group at all-time points (P < 0.05). Conclusion. Disk injury in rats produces persistent increases in neuropeptides in DRGs and glia in the spinal cord, but only transient increases in inflammatory mediators in IVDs.

Surgical versus nonsurgical treatment of selected patients with discogenic low back pain: a small-sized randomized trial.

Low back pain (LBP) is a common clinical problem and is of major socioeconomic importance. Although any of the spinal structures (intervertebral discs, facet joints, vertebral bodies, ligaments, and muscles) may be a source of LBP, the most likely cause is a lumbar intervertebral disc.1–3 Many autho

Evaluation of low back pain using the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire for lumbar spinal disease in a multicenter study: differences in scores based on age, sex, and type of disease

BackgroundThe Japanese Orthopaedic Association (JOA) has investigated the JOA Back Pain Evaluation Questionnaire (JOABPEQ) to evaluate several aspects of low back pain in patients. The score includes five categories (25 items) selected from the Roland Morris Disability Questionnaire and Short Form 36, and a visual analogue scale. Japanese physicians have recently used these scores to evaluate back pain; however, the efficacy has not been fully explored in large-scale studies. In the current study, we used the JOABPEQ to evaluate lumbar spinal disease in 555 patients (with lumbar disc herniation, lumbar spinal stenosis, and lumbar disc degeneration/spondylosis) in multiple spine centers and compared the results based on age, sex, and type of disease.MethodsA total of 555 patients who had low back or leg pain were selected in 22 hospitals in Chiba Prefecture. Spine surgeons diagnosed their disease type based on symptoms, physical examination, radiography images, and magnetic resonance imaging. In all, 486 patients were diagnosed with spinal stenosis (239 patients), disc degeneration/spondylosis (143 patients), or disc herniation (104 patients). The other 69 patients were diagnosed with spondylolysis (16 patients) or other diseases (53 patients). The pain score in all patients was evaluated using the JOABPEQ (from 0 to 100, with 0 indicating the worst pain).ResultsThe age of the patients was 56.1 ± 13.3 years (mean ± SD); the age of patients in the disc herniation and disc degeneration/spondylosis group was significantly lower than that in the spinal stenosis group. The average JOABPEQ scores in all patients were, for low back pain, 47.1; lumbar function, 53.6; walking ability, 54.8; social life function, 48.7; and mental health, 48.3. The low back pain score in men was significantly worse than that in women. In contrast, the mental health score in women was significantly higher than that in men. The low back pain score in patients <40 years old and the walking ability score in patients >65 years old were significantly lower than those scores in other patients. Based on the disease type, low back pain, lumbar function, social life function, and mental health scores for patients with disc herniation were significantly worse than for those with spinal stenosis.ConclusionJOABPEQ scores were evaluated for several lumbar diseases. The average of five categories of JOABPEQ scores in all patients was similarly distributed. However, the average scores in the five categories were significantly different depending on age, sex, and type of disease. Compared with prior mass data (baseline data on the observational cohort of the Spine Patient Outcomes Research Trial in the United States), many data were similar based on the type of disease in the current study. Furthermore, the JOABPEQ is easy to use compared with the SF-36. Hence, we concluded that the JOABPEQ could be used worldwide as a tool for evaluating low back pain.

Difficulty of Diagnosing the Origin of Lower Leg Pain in Patients With Both Lumbar Spinal Stenosis and Hip Joint Osteoarthritis

Study Design. Case series. Objective. To present the difficulty of diagnosing the origin of lower leg pain in patients with lumbar spinal stenosis and hip joint arthritis. Summary of Background Data. Pain arising from a degenerated hip joint is sometimes localized to the lower leg. Patients with lumbar spinal disease may also show radicular pain corresponding to the lower leg area. If patients present with both conditions and only pain at the lower leg, it is difficult to determine the origin of the pain. Methods. We reviewed 420 patients who had leg pain with lumbar spinal stenosis diagnosed by myelography, computed tomography after myelography, or magnetic resonance imaging. Pain only at the ipsilateral lateral aspect of the lower leg but slight low back pain or pain around the hip joint was shown in 4 patients who had lumbar spinal stenosis and hip osteoarthritis. The symptoms resolved after L5 spinal nerve block, but remained after lidocaine infiltration into the hip joint. We performed decompression and posterolateral fusion surgery for these 4 patients. Results. Leg pain did not resolve after lumbar surgery in all patients. Conservative treatment was not effective from 6 to 12 months, so ultimately we performed ipsilateral total hip replacement for all patients and they became symptom-free. Conclusion. It is difficult to determine the origin of lower leg pain by spinal nerve block and hip joint block in patients with lumbar spinal stenosis and hip osteoarthritis. We take this into consideration before surgery.

18F-fluorodeoxyglucose-PET for patients with suspected spondylitis showing Modic change.

Study Design. Prospective cohort study. Objective. To examine the utility of 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) to diagnose pyogenic spondylitis in patients showing Modic change. Summary of Background Data. Vertebral bone marrow infection may appear as Modic type 1 signal on magnetic resonance imaging, so it is difficult to distinguish between common Modic change and infection. In the current study, we aimed to examine the utility of 18F-FDG-PET to diagnose pyogenic spondylitis in patients showing Modic change. Methods. In a prospective assessment of 312 patients showing low back pain, 18 patients were suspected of having pyogenic vertebral osteomyelitis because of their symptoms, biopsy results, blood analysis, x-ray examination, magnetic resonance imaging, and FDG-PET during a 1-year follow-up. Results. Observers ultimately diagnosed 11 patients with pyogenic spondylitis (group 1 observers). FDG-PET evaluation by 2 radiologists (group 2 observers) showed isotope accumulation in the lumbar spine in 11 patients, and no accumulation in 7 patients. The evaluation by group 1 observers, who did not see the FDG-PET findings, was compared with the evaluation by group 2 observers. No patients were evaluated differently by group 1 and group 2 observers. Conclusion. In conclusion, the rate of detecting spondylodiscitis infection was very high if FDG-PET was additionally used. FDG-PET is recommended to distinguish between common Modic change and spinal infection.

ISSLS prize winner: disc dynamic compression in rats produces long-lasting increases in inflammatory mediators in discs and induces long-lasting nerve injury and regeneration of the afferent fibers innervating discs: a pathomechanism for chronic discogenic low back pain.

Study Design. Animal model of intravertebral disc (IVD) degeneration. Objective. To examine production of inflammatory mediators in IVDs and neuropeptides in dorsal root ganglia (DRGs) in rat models of IVD compression and injury. Summary of Background Data. Sensory nerve fibers in IVDs and inflammatory mediator responses have been verified in animal models of IVD injury. However, the IVD injury in animals incompletely models degenerated human IVDs causing discogenic low back pain, because human IVDs are also subject to compression. Methods. Experimental groups (controls, IVD injury, IVD compression, and their combination) of Sprague Dawley rats were prepared. Fluoro-Gold (FG; Fluorochrome, Denver, CO) was applied into coccygeal IVDs. Inflammatory mediators in IVDs, including nerve growth factor, tumor necrosis factor &agr;, interleukin 1&bgr;, and interleukin 6, were quantified using enzyme-linked immunosorbent assays. DRGs were immunostained for calcitonin gene-related peptide, activating transcription factor 3, and growth-associated phosphoprotein 43. Results. The upregulation of inflammatory mediators was transient in the IVD injury group but delayed and long-lasting in the IVD compression group. When the IVD injury and compression were combined, the upregulation of inflammatory mediators was long-lasting through 8 weeks. The proportion of calcitonin gene-related peptide–immunoreactive neurons among Fluoro-Gold–labeled neurons remained significantly higher in the IVD injury, compression, and combination groups than in the controls. In contrast, increases in the proportions of activating transcription factor 3–immunoreactive or growth-associated phosphoprotein 43–immunoreactive neurons in the IVD injury group animals were transient but long-lasting in the compression and combination groups compared with controls. Conclusion. Disc injury in rats produces persistent increases in neuropeptides in DRGs but only transient increases in inflammatory mediators in IVDs. On the contrary, disc compression in rats produces a long-lasting increase in inflammatory mediators in IVDs and neuropeptides in DRGs. Moreover, disc compression induces persistent nerve injury and regeneration of the afferent fibers innervating IVDs.

Assessment of pain behavior in a rat model of intervertebral disc injury using the CatWalk gait analysis system.

Study Design. Pain behavior and immunohistological analysis in intervertebral disc (IVD) injury model. Objective. To investigate pain behavior in a rat model of IVD injury using the CatWalk system. Summary of Background Data. There are few reports examining low back pain behavior in animal models. The CatWalk is a computer-assisted gait analysis system that provides an automated way to assess gait function and pain-related alterations of this behavior. Methods. In the IVD injury group, L5–L6 IVDs were injured with a 24-gauge needle. Simultaneously, the neurotracer Fluoro-Gold (FG; Fluorochrome, Denver, CO) was injected into the L5–L6 IVDs. In the sham group, FG was injected into the L5–L6 IVDs only. Animals in the control group received no operation. One, 2, 3, and 4 weeks after surgery, the gait of rats in the 3 groups was investigated using the CatWalk system. One, 2, and 4 weeks after surgery, in IVD injury and sham groups, dorsal root ganglions from the L1 to L6 levels were resected. Dorsal root ganglions were immunostained for calcitonin gene-related peptide. Results. In the IVD injury group, the mean stands of hind paws and the mean duty cycle of front paws at some time points were significantly higher than those in the sham group. Furthermore, the mean stride length of the front and hind paws and the mean swing speed of the front and hind paws at some time points were significantly shorter than those in the sham group. The proportion of calcitonin gene-related peptide-immunoreactive, FG-labeled neurons among all FG-labeled dorsal root ganglion neurons in the IVD injury group was significantly higher than the corresponding proportion in the sham group. Conclusion. These results suggest that IVD injury produced significant changes in rat gait, including longer stance phases and shorter strides. In the future, we may be able to apply the CatWalk system to the evaluation of behavior associated with pain in models of low back pain. Level of Evidence: N/A