BACKGROUND: A prolonged-release formulation of oxycodone/naloxone has been shown to be effective in European populations for the management of chronic moderate to severe pain. However, no clinical data exist for its use in Korean patients. The objective of this study was to assess efficacy and safety of prolonged-release oxycodone/naloxone in Korean patients for management of chronic moderate-to-severe pain. METHODS: In this multicenter, single-arm, open-label, phase IV study, Korean adults with moderate-to-severe spinal disorder-related pain that was not satisfactorily controlled with weak opioids and nonsteroidal anti-inflammatory drugs received prolonged-release oral oxycodone/naloxone at a starting dose of 10/5 mg/day (maximum 80/40 mg/day) for 8 weeks. Changes in pain intensity and quality of life (QoL) were measured using a numeric rating scale (NRS, 0–10) and the Korean-language EuroQol-five dimensions questionnaire, respectively. RESULTS: Among 209 patients assessed for efficacy, the mean NRS pain score was reduced by 25.9% between baseline and week 8 of treatment (p < 0.0001). There was also a significant improvement in QoL from baseline to week 8 (p < 0.0001). The incidence of adverse drug reactions was 27.7%, the most common being nausea, constipation, and dizziness; 77.9% of these adverse drug reactions had resolved or were resolving at the end of the study. CONCLUSIONS: Prolonged-release oxycodone/naloxone provided significant and clinically relevant reductions in pain intensity and improved QoL in Korean patients with chronic spinal disorders. (ClinicalTrials.gov identifier: NCT01811238)
Adult ; Analgesia ; Analgesics, Opioid ; Chronic Pain* ; Constipation ; Dizziness ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Incidence ; Nausea ; Quality of Life ; Spine

PURPOSE: To compare the effects of alendronate and raloxifene on lumbar bone mineral density (BMD), bone turnover, and lipid metabolism in elderly women with osteoporosis. Subjects and Methods: One hundred twenty-two postmenopausal women with osteoporosis (mean age: 69.4 years) were randomly divided into 2 groups of 61 patients: the alendronate group and the raloxifene group. BMD of the lumbar spine, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of alkaline phosphatase (ALP), total cholesterol (TC), high and low density lipoprotein cholesterols (LDL-C and HDL-C, respectively), and triglycerides (TG) were measured during the 12-month-treatment period. RESULTS: The trial in 50 patients in the alendronate group and 52 patients in the raloxifene group could be completed. Both alendronate and raloxifene increased lumbar BMD (+8.0% and +2.4% at 12 months, respectively), followed by reductions of urinary NTX level and serum ALP level; however, the effects of alendronate were more pronounced than those of raloxifene. Only raloxifene reduced the serum levels of TC and LDL-C (-3.9% and -7.7% at 12 months, respectively), without any significant effect on the serum HDL-C and TG levels. CONCLUSION: The present study confirmed the efficacy of alendronate greater than raloxifene in increasing lumbar BMD through its effect on marked reduction of the bone turnover more than by raloxifene, and some beneficial effects of raloxifene on lipid metabolism in elderly women with osteoporosis.
Aged ; Alendronate/adverse effects/pharmacology/*therapeutic use ; Biological Markers/blood ; Bone Density/*drug effects ; Calcium/blood ; Female ; Fractures, Bone/prevention & control ; Humans ; Lipid Metabolism/*drug effects ; Osteoporosis/*drug therapy/*metabolism ; Phosphorus/blood ; Raloxifene/adverse effects/pharmacology/*therapeutic use ; Spine/drug effects

OBJECTIVES: Bee venom contains a potent antiinflammatory peptide 401 as well as mellitin. The purpose of this study was to see the efficacy and safety of purified bee venom injection therapy for knee or spinal osteoarthritis patients. METHODS: One hundred and one osteoarthritis patients were randomly assigned to bee venom injection therapy or oral nabumetone medication group. Bee venom injection group was subdivided into 3 groups according to different dosing schedule(group A: gradual increase up to 0.7mg, group B: up to 1.5mg and group C: up to 2.0mg). Control group patients(group D) were given 1000mg nabumetone daily for 6 weeks. There were 25, 26, 25, and 26 patients assigned to A, B, C, or D group. The efficacy of treatment was evaluated by measuring instruments developed by authors, and the safety of bee venom injection was evaluated by hematology and chemistry laboratory examination. RESULTS: Among 101 patients, eighty-one patients completed the study, but twenty patients were dropped out and two of these patients were dropped out due to adverse drug reaction. The efficacy in bee venom group showed better improvement than nabumetone group(p<0.01). Within bee venom group, group B and C showed better improvement than group A(p<0.01). Itching around injection site occurred in most patients, and bodyache occurred in 49 patients (81.7%). Hemoglobin was decreased(0.3g/dl) in group C, but no significant changes were observed in other laboratory values. CONCLUSION: The efficacy of bee venom injection in the control of knee or back pain in osteoarthritis patients was better than nabumetone medication. No severe allergic or adverse reaction was observed in bee venom treatment patients, but problems related with bee venom injection, such as pruritis, bodyache, and the possibility of anaphylaxis, should be considered for the use of bee venom injection.
Anaphylaxis ; Back Pain ; Bee Venoms* ; Bees* ; Chemistry ; Drug-Related Side Effects and Adverse Reactions ; Hematology ; Humans ; Knee ; Melitten ; Osteoarthritis* ; Osteoarthritis, Spine ; Pruritus

The purpose of this study was to investigate the treatment efficacies of salmon calcitonin (SC) and estrogen in a type-I osteoporotic rat model. Sixty, 3-month-old, female Wistar rats were divided into six groups. The first group was used as the control, and the second a sham, the other four were surgically ovariectomized. 24 hours after the ovariectomy, they were either left untreated (OVX), or treated with an injection of either 17-beta estradiol (E2) 30 mcg/kg/24 hours, low-dose calcitonin (LDC) 10 IU/ kg/48 hours or high-dose calcitonin (HDC) 20 IU/kg/48 hours. 6 weeks later, the bone densities were measured by DEXA, the animals sacrificed and the femurs harvested for histomorphometric evaluation. The bone mineral densities (BMD) of the spine and proximal femur were lower in the OVX group, but only the values of the spine BMD were statistically significant. The BMD of the spine seemed to be preserved with all the treatments. The histomorphometric evaluation revealed that after the OVX the decrease in the trabecular volume was prevented by all the treatments. However, significant changes in the indices of bone formation were not shown. In conclusion, all the treatments prevented bone lost in the ovariectomized rats. Histopathological measurements of bone formation are unlikely to provide any evidence for the effects of these agents on the osteoblastic function. In the animal model of estrogen depletion, our results suggest that the calcitonin provides an important alternative therapy for postmenopausal osteoporosis.
Animals ; Bone Density/drug effects ; Calcitonin/*administration & dosage ; Comparative Study ; Dose-Response Relationship, Drug ; Estradiol/*therapeutic use ; Female ; Osteoporosis/*drug therapy/pathology/physiopathology ; Ovariectomy ; Rats ; Rats, Wistar ; Salmon ; Spine/physiopathology

BACKGROUNDAlendronate, a nitrogen-containing bisphosphonate is a specific inhibitor of bone resorption and now in the forefront of treatment of osteoporosis. In this study, we reported a significant increase in bone mineral density (BMD) of the spine and the hip in postmenopausal women taking alendronate at 10 mg/d for 1, 2 and 3 years.

METHODSParticipants had received daily, oral, 10 mg dose of alendronate for one to three years and placed into one of three groups according to alendronate treatment duration: 41 women received alendronate for 1 year (group I), 46 received alendronate for 2 years (group II), and 30 received alendronate for 3 years (group III). Measurements of bone density had been made by dual energy X-ray absorbtiometry once each year.

RESULTSThe differences in L2-L4, L2, L4, femoral neck and trochanter BMD values before and after treatment for first group were significantly different. In second group, significant differences between initial and after treatment were found at the other sites except at the Ward's triangle. In the third group, only a significant increase in the L2-L4, L2, L3, L4, trochanter BMD values between before treatment and at the end of third year was found. Comparisons between groups were performed with Student's t test. ANOVA was used to test the age, menopause age, menopause duration and initial BMD values between the three groups. Calculated P values of less than 0.05 were considered statistically significant.

CONCLUSIONSAlendronate had increased BMD significantly at the spine and hip in postmenopausal women over three years. Increases of BMD in third group were significant during the first and second years. However, continued therapy with alendronate had been required to maintain the gain in BMD over the third year.

Absorptiometry, Photon ; Adult ; Aged ; Alendronate ; therapeutic use ; Analysis of Variance ; Bone Density ; drug effects ; Bone Resorption ; prevention & control ; Female ; Hip ; physiopathology ; Humans ; Middle Aged ; Osteoporosis, Postmenopausal ; drug therapy ; Spine ; physiopathology

Autophagy acts as an important homoeostatic mechanism by degradation of cytosolic constituents and plays roles in many physiological processes. Recent studies demonstrated that autophagy can also regulate the production and secretion of the proinflammatory cytokine interleukin-1β (IL-1β), which plays a critical role in the development and maintenance of neuropathic pain. In the present study, the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were significantly decreased after spinal nerve ligation (SNL), and the changes were accompanied by inhibited autophagy in the spinal microglia and increased mRNA and protein levels of IL-1β in the ipsilateral spinal cord. We then investigated the antinociceptive effect of rapamycin, a widely used autopahgy inducer, on SNL-induced neuropathic pain in rats and found that treatment with intrathecal rapamycin significantly attenuated the mechanical allodynia and thermal hyperalgesia. Moreover, rapamycin significantly enhanced autophagy in the spinal microglia, whereas it reduced the mRNA and protein levels of IL-1β in the ipsilateral spinal cord. Our results showed that rapamycin could ameliorate neuropathic pain by activating autophagy and inhibiting IL-1β in the spinal cord.
Animals ; Autophagy ; drug effects ; Immunosuppressive Agents ; Interleukin-1beta ; antagonists & inhibitors ; metabolism ; Male ; Neuralgia ; drug therapy ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Sirolimus ; pharmacology ; Spine ; metabolism ; pathology

STUDY DESIGN: Retrospective patient data collection and investigator survey. PURPOSE: To investigate patterns of opioid treatment for pain caused by spinal disorders in Korea. OVERVIEW OF LITERATURE: Opioid analgesic prescription and adequacy of consumption measures in Korea have markedly increased in the past decade, suggesting changing patterns in pain management practice; however, there is lack of integrated data specific to Korean population. METHODS: Patient data were collected from medical records at 34 university hospitals in Korea. Outpatients receiving opioids for pain caused by spinal disorders were included in the study. Treatment patterns, including opioid types, doses, treatment duration, outcomes, and adverse drug reactions (ADRs), were evaluated. Investigators were interviewed on their perceptions of opioid use for spinal disorders. RESULTS: Among 2,468 analyzed cases, spinal stenosis (42.8%) was the most common presentation, followed by disc herniation (24.2%) and vertebral fracture (17.5%). In addition, a greater proportion of patients experienced severe pain (73.9%) rather than moderate (19.9%) or mild (0.7%) pain. Oxycodone (51.9%) and fentanyl (50.8%) were the most frequently prescribed opioids; most patients were prescribed relatively low doses. The median duration of opioid treatment was 84 days. Pain relief was superior in patients with longer treatment duration (≥2 months) or with nociceptive pain than in those with shorter treatment duration or with neuropathic or mixed-type pain. ADRs were observed in 8.6% of cases. According to the investigators' survey, "excellent analgesic effect" was a perceived advantage of opioids, while safety concerns were a disadvantage. CONCLUSIONS: Opioid usage patterns in patients with spinal disorders are in alignment with international guidelines for spinal pain management. Future prospective studies may address the suitability of opioids for spinal pain treatment by using appropriate objective measurement tools.
Analgesics, Opioid ; Chronic Pain ; Data Collection ; Drug-Related Side Effects and Adverse Reactions ; Fentanyl ; Hospitals, University ; Humans ; Korea* ; Medical Records ; Nociceptive Pain ; Outpatients ; Oxycodone ; Pain Management ; Prescriptions ; Prospective Studies ; Research Personnel ; Retrospective Studies* ; Spinal Diseases ; Spinal Stenosis ; Spine

PURPOSE: Quadriplegic children with cerebral palsy are more susceptible to osteoporosis because of various risk factors that interfere with bone metabolism. Pamidronate is effective for pediatric osteoporosis, but there are no guidelines for optimal dosage or duration of treatment in quadriplegic children with osteoporosis. We aimed to evaluate the efficacy of low-dose pamidronate treatment in these patients. METHODS: Ten quadriplegic patients on antiepileptic drugs (6 male, 4 female patients; mean age, 10.9±5.76 years), with osteoporosis and gross motor function classification system level V, were treated with pamidronate (0.5–1.0 mg/kg/day, 2 consecutive days) every 3–4 months in a single institution. The patients received oral supplements of calcium and vitamin D before and during treatment. The lumbar spine bone mineral density (BMD) z score and biochemical markers of bone metabolism were measured regularly during treatment. RESULTS: The main underlying disorder was perinatal hypoxic brain damage (40%, 4 of 10). The mean cumulative dose of pamidronate was 4.49±2.22 mg/kg/yr, and the mean treatment period was 10.8±3.32 months. The BMD z score of the lumbar spine showed a significant increase from −4.22±1.24 before treatment to −2.61±1.69 during treatment (P=0.008). Alkaline phosphatase decreased during treatmentn (P=0.037). Significant adverse drug reactions and new fractures were not reported. CONCLUSION: Low-dose pamidronate treatment for quadriplegic children with cerebral palsy increased lumbar BMD and reduced the incidence of fracture.
Alkaline Phosphatase ; Anticonvulsants ; Biomarkers ; Bone Density ; Calcium ; Cerebral Palsy* ; Child* ; Classification ; Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Hypoxia, Brain ; Incidence ; Male ; Metabolism ; Osteoporosis* ; Quadriplegia ; Risk Factors ; Spine ; Vitamin D

OBJECTIVETo study the regulatory effect of Ligustrazine Injection (LI) on the cellular immune function in patients undergoing autologous blood transfusion (ABT).

METHODSEnrolled were 60 patients scheduled for receiving selective lumbar surgery at the Department of Spinal Orthopedics, First Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine during October 2009 to June 2010. They were equally randomized into two groups, the trial group and the control group. LI was given to patients in the trial group by intravenous dripping at the dose of 2 mg/kg 30 min before autologous blood collection. The LI (at the final concentration of 0.005%) was added in the heparin saline solution and the washing saline for recycle blood. No LI was given to patients in the control group. They received the same treatment of the trial group. The operation time, the amount of blood loss and blood transfusion were recorded. Patients' venous blood samples were collected for determining cytokines including interleukin-2 (IL-2), interleukin-10 (IL-10), interferon-gamma (IFN-gamma) by ELISA and calculating IL-2/IL-10 ratio before surgery (T1), 1 h (T2), 1 day (T3), and 5 days (T4) after ABT.

RESULTSThere was no statistical difference in the amount of blood loss and blood transfusion, the levels of IL-2, IL-10, IFN-gamma, or IL-2/IL-10 at T1 between the two groups (P>0.05). Compared with T1 of the same group, the level of IL-2 decreased at T(2-4), IL-10 increased and IL-2/IL-10 decreased at T(2-3) in the two groups. The level of IFN-gamma decreased at T(2-4), IL-2/IL-10 increased at T4, the level of IL-10 decreased at T4 in the control group (P<0.05, P<0.01). The level of IL-10 decreased at T4 in the trial group with statistical difference (P<0.05, P<0.01). Compared with the control group, the level of IL-2, IFN-gamma, and IL-2/IL-10 at T(2-4) were obviously higher in the trial group. But the IL-10 level was lower in the trial group than in the control group at T(2-4) (P<0.05, P<0.01).

CONCLUSIONThe application of LI in ABT had regulatory effects on the balance of cytokines.

Adult ; Aged ; Blood Transfusion, Autologous ; Female ; Humans ; Immunity, Cellular ; drug effects ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Interleukin-2 ; blood ; Male ; Middle Aged ; Postoperative Period ; Pyrazines ; therapeutic use ; Spine ; surgery ; Young Adult

The cuttlebones, harvested from cuttles, undergo the chemical reaction in high temperature and high pressure for a certain time. The products are qualitatively analysed, and spacial structure observation and cytocompatibility are tested. The results show that the chemical component of the cuttlebone is CaCO3 and the crystal type is aragonite. Cuttlebones undergo a hydro-thermal reaction, and thus transform into hydroxyapatite-that is, the cuttlebone-transformed hydroxyapatite(CBHA). The CBHA materials have the interconnected microporous network structures. Under the high magnification, CBHAs appear to have many micro-spheres, thus construct a new self-assembled nano-material system. The marrow stromal osteoblasts can adhere to and proliferate well on the surface of the CBHAs. These results show that CBHAs have good biocompatibility. Therefore, it can be a potential candidate scaffold for bone tissue engineering.
Animals ; Bone Substitutes ; chemical synthesis ; chemistry ; toxicity ; Cells, Cultured ; Durapatite ; chemical synthesis ; chemistry ; toxicity ; Materials Testing ; Osteoblasts ; cytology ; drug effects ; Rabbits ; Sepia ; anatomy & histology ; Spine ; anatomy & histology ; chemistry ; Tissue Engineering