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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 microG/L and 35.1 microG/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.
Acid Phosphatase ; Bone Resorption ; Collagen Type I ; Compliance* ; Humans ; Metabolism ; Osteogenesis ; Osteoporosis* ; Patient Dropouts ; RANK Ligand ; Retrospective Studies

STUDY DESIGN: Retrospective cohort study. PURPOSE: To assess bone mineral density (BMD) and bone metabolism ≥27 years after surgery in female patients who underwent spinal fusion for adolescent idiopathic scoliosis (AIS) during adolescence and to determine their associations with physical performance. OVERVIEW OF LITERATURE: There are no studies investigating postsurgical BMD in middle-aged AIS patients. METHODS: This study included 23 patients who provided informed consent among 229 female patients with AIS who underwent spinal fusion from 1968 until 1988. Average age at the time of observation was 48.8 years. BMD was measured at the left femoral neck, and the levels of two bone metabolism markers–procollagen type 1 N-terminal propeptide (P1NP) and tartrate-resistant acid phosphatase 5b (TRACP-5b)–were measured from blood samples. Physical performance was measured using grip strength, sit-ups, sit-and-reach, side step, and standing long jump. RESULTS: Mean BMD was 0.784 g/cm2. According to the World Health Organization diagnostic criteria, one subject (4.3%) had osteoporosis, whereas nine subjects (39.1%) had osteopenia. In patients with osteoporosis or osteopenia, P1NP and TRACP-5b levels were high, and BMD loss was because of high metabolic turnover. All calculated standard scores for physical performance were lower in the study cohort than in healthy individuals. There was a positive correlation between BMD and the standard score for grip strength, whereas there were weak positive correlations between BMD and the standard scores for side step and standing long jump. CONCLUSIONS: In female AIS patients who underwent spinal fusion in adolescence, 4.3% and 39.1% had osteoporosis and osteopenia, respectively, ≥27 years after surgery. Exercise performance of these patients was poor compared with the national standards. In these patients, increased physical activity should be encouraged to prevent BMD loss in middle age.
Acid Phosphatase ; Adolescent* ; Bone Density* ; Bone Diseases, Metabolic ; Cohort Studies ; Female* ; Femur Neck ; Hand Strength ; Humans ; Informed Consent ; Metabolism ; Middle Aged ; Motor Activity ; Osteoporosis ; Retrospective Studies ; Scoliosis* ; Spinal Fusion ; World Health Organization

PURPOSE: Opioids improve pain from knee and hip osteoarthritis (OA) and decrease the functional impairment of patients. However, there is a possibility that opioids induce analgesia and suppress the physiological pain of OA in patients, thereby inducing the progression of OA changes in these patients. The purpose of the current study was to investigate the possibility of progressive changes in OA among patients using opioids. MATERIALS AND METHODS: Two hundred knee or hip OA patients were evaluated in the current prospective, randomized, active-controlled study. Patients were randomized 1:1:1 into three parallel treatment groups: loxoprofen, tramadol/acetaminophen, and transdermal fentanyl groups. Medication was administered for 12 weeks. Pain scores and progressive OA changes on X-ray films were evaluated. RESULTS: Overall, pain relief was obtained by all three groups. Most patients did not show progressive OA changes; however, 3 patients in the transdermal fentanyl group showed progressive OA changes during the 12 weeks of treatment. These 3 patients used significantly higher doses than others in the transdermal fentanyl group. Additionally, the average pain score for these 3 patients was significantly lower than the average pain score for the other patients in the transdermal fentanyl group. CONCLUSION: Fentanyl may induce progressive changes in knee or hip OA during a relatively short period, compared with oral Non-Steroidal Anti-Inflammatory Drugs or tramadol.
Aged ; Aged, 80 and over ; Analgesics, Opioid/*adverse effects/therapeutic use ; Disease Progression ; Female ; Fentanyl/*adverse effects/therapeutic use ; Humans ; Male ; Middle Aged ; Osteoarthritis, Hip/*drug therapy/radiography ; Osteoarthritis, Knee/*drug therapy/radiography ; Pain/drug therapy

PURPOSE: Bupivacaine is commonly used for the treatment of back pain and the diagnosis of its origin. Nonunion is sometimes observed after spinal fusion surgery; however, whether the nonunion causes pain is controversial. In the current study, we aimed to detect painful nonunion by injecting bupivacaine into the disc space of patients with nonunion after anterior lumbar interbody fusion (ALIF) surgery for discogenic low back pain. MATERIALS AND METHODS: From 52 patients with low back pain, we selected 42 who showed disc degeneration at only one level (L4-L5 or L5-S1) on magnetic resonance imaging and were diagnosed by pain provocation on discography and pain relief by discoblock (the injection of bupivacaine). They underwent ALIF surgery. If the patients showed low back pain and nonunion 2 years after surgery, we injected bupivacaine into the nonunion disc space. Patients showing pain relief after injection of bupivacaine underwent additional posterior fixation using pedicle screws. These patients were followed up 2 years after the revision surgery. RESULTS: Of the 42 patient subjects, 7 showed nonunion. Four of them did not show low back pain; whereas 3 showed moderate or severe low back pain. These 3 patients showed pain reduction after injection of bupivacaine into their nonunion disc space and underwent additional posterior fixation. They showed bony union and pain relief 2 years after the revision surgery. CONCLUSION: Injection of bupivacaine into the nonunion disc space after ALIF surgery for discogenic low back pain is useful for diagnosis of the origin of pain.
Back Pain ; Bupivacaine* ; Diagnosis ; Humans ; Intervertebral Disc ; Intervertebral Disc Degeneration ; Low Back Pain* ; Magnetic Resonance Imaging ; Methods ; Spinal Fusion ; Spine

PURPOSE: Sacroiliac fixation using iliac screws for highly unstable lumbar spine has been reported with an improved fusion rate and clinical results. On the other hand, there is a potential for clinical problems related to iliac fixation, including late sacroiliac joint arthritis and pain. MATERIALS AND METHODS: Twenty patients were evaluated. Degenerative scoliosis was diagnosed in 7 patients, failed back syndrome in 6 patients, destructive spondyloarthropathy in 4 patients, and Charcot spine in 3 patients. All patients underwent posterolateral fusion surgery incorporating lumbar, S1 and iliac screws. We evaluated the pain scores, bone union, and degeneration of sacroiliac joints by X-ray imaging and computed tomography before and 3 years after surgery. For evaluation of low back and buttock pain from sacroiliac joints 3 years after surgery, lidocaine was administered in order to examine pain relief thereafter. RESULTS: Pain scores significantly improved after surgery. All patients showed bone union at final follow-up. Degeneration of sacroiliac joints was not seen in the 20 patients 3 years after surgery. Patients showed slight low back and buttock pain 3 years after surgery. However, not all patients showed relief of the low back and buttock pain after injection of lidocaine into the sacroiliac joint, indicating that their pain did not originate from sacroiliac joints. CONCLUSION: The fusion rate and clinical results were excellent. Also, degeneration and pain from sacroiliac joints were not seen within 3 years after surgery. We recommend sacroiliac fixation using iliac screws for highly unstable lumbar spine.
Aged ; Arthritis/*surgery ; Bone Screws ; Female ; Humans ; Low Back Pain/diagnosis/epidemiology ; Lumbar Vertebrae/*surgery ; Male ; Middle Aged ; Pain/diagnosis/*epidemiology ; Sacroiliac Joint/*immunology/*pathology

STUDY DESIGN: Case series. PURPOSE: To determine the utility of "PainVision" apparatus for the assessment of low back pain. OVERVIEW OF LITERATURE: A newly developed device, the PainVision PS-2100 (Nipro, Osaka, Japan), has been used to assess the perception of pain in a quantitative manner. In the current study, we aimed to evaluate the efficacy of PainVision for the assessment of low back pain. METHODS: We assessed 89 patients with low back pain. The numeric rating scale (NRS) score, McGill Pain Questionnaire (MPQ) score and the degree of pain calculated by PainVision were measured twice at 4-week intervals in each patient. An electrode was patched on the forearm surface of the patients and the degree of pain was automatically calculated (degree of pain=100x[current producing pain comparable with low back pain-current at perception threshold/current at perception threshold]). Correlations between NRS and MPQ scores and the degree of pain were determined using Spearman's rank correlation test. RESULTS: There was a strong correlation between the NRS and MPQ scores at each time point (rs =0.60, p<0.0001). The degree of pain also showed a moderate correlation with NRS and MPQ scores at each time point (rs =0.40, p<0.03). The change in the degree of pain over 4 weeks showed a moderate correlation with changes in the NRS and MPQ scores (rs =0.40, p<0.01). CONCLUSIONS: PainVision as self-reported questionnaires is a useful tool to assess low back pain.
Electrodes ; Forearm ; Humans ; Low Back Pain* ; Pain Measurement ; Surveys and Questionnaires

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 gene-related 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.
Animals ; Back Pain ; Calcitonin Gene-Related Peptide ; Cytokines ; Diagnosis-Related Groups ; Endothelial Growth Factors ; Ganglia ; Ganglia, Spinal* ; Humans ; Intervertebral Disc* ; Low Back Pain ; Models, Animal ; Needles ; Neuropeptides* ; Punctures ; Rats* ; Rats, Sprague-Dawley ; Sodium ; Sodium Chloride ; Spinal Nerve Roots* ; Vascular Endothelial Growth Factor A*

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 gene-related 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.
Animals ; Atrophy ; Back Muscles* ; Calcitonin Gene-Related Peptide ; Cicatrix ; Eosine Yellowish-(YS) ; Ganglia, Sensory ; Ganglia, Spinal ; Granulation Tissue ; Hematoxylin ; Humans ; Male ; Models, Animal ; Muscular Atrophy ; Myalgia ; Rats* ; Rats, Sprague-Dawley ; Spine

PURPOSE: Pain from vertebral or femoral neck fractures is a particularly important problem in clinical orthopaedics. Transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated nonselective cation channel, and there are recent reports on an association between bone pain and TRPV1. However, an increase in TRPV1 activity has not been reported following femoral fracture. MATERIALS AND METHODS: We applied a neurotracer [Fluoro-gold (FG)] onto femur to detect dorsal root ganglia (DRGs) innervating the cortex of the femur in 30 Sprague Dawley rats. Seven days after application, a closed mid-diaphyseal fracture of the femur was performed. FG labeled TRPV1-immunoreactive (ir) DRGs innervating the femur were examined in nonfractured controls, and 3 days, 1 week, 2 weeks, and 4 weeks after fracture. We evaluated bone healing of the femur and compared the ratio of TRPV1-ir DRG neurons innervating the femur at the time points. RESULTS: Four weeks after fracture, complete bone union was observed. There was no significant difference in the ratio of FG labeled DRG neurons to total DRG neurons at each time point. The percentages of TRPV1-ir neurons in DRGs innervating the femur at 3 days and 1 week after fracture were significantly higher than those in control, 2 weeks, and 4 weeks after fracture (p<0.05). CONCLUSION: Fracture induced an increase of TRPV1-ir neurons in DRGs innervating the fractured femur within 3 days, and decreased during bone healing over 4 weeks. These findings show that TRPV1 may play a role in sensory sensation of bone fracture pain.
Animals ; Female ; Femur/*innervation/*metabolism ; Immunohistochemistry ; Rats ; Rats, Sprague-Dawley ; TRPV Cation Channels/*metabolism