OBJECTIVES: To reassess the safety and efficacy of once-weekly teriparatide 56.5 mg in osteoporosis patients with a high fracture risk. METHODS: This postmarketing observational study was conducted at 72 weeks according to the package insert. Of the 3573 Japanese osteoporosis patients in the safety analysis set, 91.80% were women, the mean age was 78.1 years, and 69.89% had a history of prevalent fragility fractures, indicating that a high proportion of patients at high risk of fracture were enrolled. RESULTS: Persistence with weekly teriparatide treatment was 59.36%, and 38.95% at 24 and 72 weeks, respectively. Adverse drug reactions (ADRs) were reported in 898 patients (25.13%), and serious ADRs were reported in 26 patients (0.73%). The most frequent ADRs were nausea, vomiting, and headache. The cumulative incidence of new vertebral fractures 72 weeks after the start of treatment was 3.31%. Increases in the bone mineral density were observed in the lumbar spine, femoral neck, and proximal femur. The serum levels of the bone formation markers, procollagen type I N-terminal propeptide and bone-type alkaline phosphatase, increased slightly at 24 weeks and then decreased to baseline levels. At 24 and 72 weeks, the bone resorption markers, serum cross-linked N-terminal telopeptide of type I collagen and urinary cross-linked N-terminal telopeptide of type I collagen, were the same as or slightly lower than at baseline. Visual analogue scale scores for low back pain also decreased. CONCLUSIONS: The present results showed that once-weekly teriparatide may also be useful for osteoporosis patients with a high risk of fracture.
Alkaline Phosphatase ; Asian Continental Ancestry Group ; Biomarkers ; Bone Density ; Bone Resorption ; Collagen Type I ; Drug-Related Side Effects and Adverse Reactions ; Female ; Femur ; Femur Neck ; Headache ; Humans ; Incidence ; Low Back Pain ; Nausea ; Observational Study ; Osteogenesis ; Osteoporosis ; Product Labeling ; Spine ; Teriparatide ; Vomiting

BACKGROUND: Epidural steroid injections (ESIs) have been widely used in managing spinal pain. Dexamethasone has recently emerged as a useful drug in this setting, relative to particulate steroids, although the associated systemic effects have not been fully elucidated. This study aimed to investigate the incidences and types of systemic effects after fluoroscopically guided ESI with dexamethasone. METHODS: This retrospective study included 888 ESIs with dexamethasone (fluoroscopically guided at the cervical and lumbosacral levels) performed on 825 patients during January to June 2017. Data regarding systemic effects were collected via telephone interviews using a standardized questionnaire at 2 weeks after the procedure. Data on patient demographic, clinical, and procedural characteristics were collected and analyzed to identify factors that were associated with systemic effects. All statistical analyses were performed using the chi-squared test. RESULTS: Among the 825 patients, 40 patients (4.8%) experienced systemic effects during the 2-week follow-up period. The most common systemic effect was facial flushing (12 patients, 1.5%), which was followed by urticaria (7 patients, 0.8%) and insomnia (7 patients, 0.8%). A history of spine surgery was significantly associated with the occurrence of systemic effects (P = 0.036). Systemic effects were significantly more common for injections at the cervical level than at the lumbar level (P = 0.019). CONCLUSIONS: Approximately 4.8% of the patients who underwent ESI with dexamethasone experienced minor and transient systemic effects. These effects were more common in patients who had undergone a previous spine surgery or received a cervical ESI.
Dexamethasone ; Drug-Related Side Effects and Adverse Reactions ; Epidural Space ; Fluoroscopy ; Flushing ; Follow-Up Studies ; Humans ; Incidence ; Interviews as Topic ; Low Back Pain ; Retrospective Studies ; Sleep Initiation and Maintenance Disorders ; Spine ; Steroids ; Urticaria

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

OBJECTIVES: This postmarketing, observational study evaluated the safety and effectiveness of monthly intravenous (IV) ibandronate in Japanese patients with osteoporosis. METHODS: Eligible patients received monthly IV ibandronate 1mg for 12 months. Adverse drug reactions (ADRs) were evaluated. Changes in bone mineral density (BMD) and bone turnover markers (BTMs) were assessed using matched t-test analysis. Cumulative fracture rates were analyzed by Kaplan-Meier methodology. RESULTS: In total, 1062 patients were enrolled, of whom 1025 (n = 887 women, n = 138 men) were treated. Mean patient age was 77 years. Seventy-five ADRs were reported in 54 patients (5.26%). Four patients (0.39%) experienced serious ADRs, including one case of osteonecrosis of the jaw. Acute-phase reactions occurred in 21 patients (2.04%), and half of them arose after the first ibandronate injection. No new safety concerns were identified. Significant increases in BMD at 12 months relative to baseline were observed at the lumbar spine (4.84%, n = 187; 95% confidence interval [CI], 3.47%–6.21%), femoral neck (2.73%, n = 166; 95% CI, 1.46%–4.01%), and total hip (1.93%, n = 133; 95% CI, 0.80%–3.07%). Significant reductions were observed in all BTMs at 12 months (n = 174 in tartrate-resistant acid phosphatase-5b, n = 101 in procollagen type 1 N-terminal propeptide at baseline). The cumulative incidence of nontraumatic, new vertebral and nonvertebral fractures was 3.16% (95% CI, 2.12%–4.70%). Analyses in women only showed similar results to the overall population. CONCLUSIONS: These findings confirm the favorable safety and consistent effectiveness of ibandronate, and indicate that monthly IV ibandronate would be beneficial in daily practice for the treatment of Japanese patients with osteoporosis.
Asian Continental Ancestry Group ; Bone Density ; Bone Remodeling ; Drug-Related Side Effects and Adverse Reactions ; Female ; Femur Neck ; Hip ; Humans ; Incidence ; Japan ; Jaw ; Observational Study ; Osteonecrosis ; Osteoporosis ; Procollagen ; Prospective Studies ; 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

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

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

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

OBJECTIVETo study the curative effect of surgical treatment of drug-resistant spinal tuberculosis.

METHODSFrom March 2005 and April 2009, the clinical data of 60 patients with drug-resistant spinal tuberculosis were retrospectively analyzed. Including 36 males and 24 females; aged from 5 to 79 years with an average of 47.3 years. Thirty-four patients had neurological deficits, among them, 2 cases were grade A, 5 cases were grade B, 13 cases were grade C, 14 cases were grade D according to ASIA standard. According to the severity and location of the infection, the patients underwent anterior, posterolateral costotransversectomy or posterior debridement and bone grafting and internal fixation. The antituberculous chemotherapy for a total of 12 to 18 months was guided by conventional and genotypic drug susceptibility testing. Tubercular relapse, neurological function, spinal fusion were observed by ASIA grade, X-ray and CT scan.

RESULTSAll cases were followed up from 1 to 5 years with an average of 3.1 years. Recurrence was found in 2 cases who were cured after second operation. 34 cases with neurological deficits recovered totally or partially. X-ray or CT films showed spinal fusion in 57 patients.

CONCLUSIONThe therapeutic effect of individuall operative options is good in treating drug-resistant spinal tuberculosis after antituberculous chemotherapy based on conventional and genotypic drug susceptibility testing.

Adolescent ; Adult ; Aged ; Antitubercular Agents ; therapeutic use ; Child ; Child, Preschool ; Drug Resistance, Bacterial ; Female ; Humans ; Male ; Middle Aged ; Mycobacterium ; drug effects ; genetics ; Radiography ; Retrospective Studies ; Spine ; Tuberculosis, Multidrug-Resistant ; diagnostic imaging ; drug therapy ; microbiology ; surgery ; Tuberculosis, Spinal ; diagnostic imaging ; drug therapy ; microbiology ; surgery ; Young Adult

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