Effect of ibandronate on mitogen-activated protein kinase signaling pathway in rat models of osteoarthritis / 中国组织工程研究

BACKGROUND: Mitogen-activated protein kinase signaling pathway participates in the differentiation of osteoblasts and osteoclasts, closely related to subchondral bone reconstruction and play a key role in the occurrence and development of osteoarthritis. Bisphosphonates as bone resorption inhibitor is used to treat osteoporosis. OBJECTIVE: To observe the effect of sodium ibandronate on the knee osteoarthritis in rats, and changes of mitogen-activated protein kinase signaling pathway. METHODS: The study was approved by the Laboratory Animal Ethical Committee of the First Affiliated Hospital of South China University. Thirty female Sprague-Dawley rats were randomly divided into sham, model, and treatment groups. The rats in the latter two groups underwent ovariectomy bilaterally, and anterior cruciate ligament resection, and rats in the sham group received the fatty tissue surrounding the ovaries removed only. After 1 week of surgery, the rats in the treatment group were given intraperitoneal injection of 10 pg/kg sodium ibandronate, rats in the model group were injected with normal saline, and the sham group received no intervention. Twelve weeks late, the rats were killed to perform histological examination of cartticular cartilage and Mankin scores were detected. Micro-CT of subchondral bone and quantitative analysis of the bone microstructure were conducted. The protein and mRNA expression levels of extracellular signal regulated protein kinase and c-Jun N-terminal kinase in mitogen-activated protein kinase signaling pathway were measured. RESULTS AND CONCLUSION: (1) The cartilage structure in the model group was significantly damaged, the Mankin score was significantly higher than that in the sham group, and the Mankin score in the treatment group was significantly lower than that in the model group (P < 0.01). (2) The bone mineral density, trabecular bone volume ratio, trabecular number in the model group were significantly lower than those in the sham group (P < 0.01), and trabecular separation was higher than that in the sham group (P < 0.01). Compared with the model group, the treatment group had higher bone mineral density, trabecular bone volume ratio, trabecular number, and lower trabecular separation (P < 0.01). (3) The mRNA and protein expression levels of extracellular signal regulated protein kinase and c-Jun N-terminal kinase in the model group were significantly higher than those in the sham group (P < 0.05, P < 0.01), and the levels in the treatment group were significantly lower than those in the model group (P < 0.05). (4) To conclude, sodium ibandronate may inhibit subchondral bone loss and articular cartilage degeneration in rat models of osteoarthritis by inhibiting extracellular signal regulated protein kinase and c-Jun N-terminal kinase in mitogen-activated protein kinase signaling pathway.

Effects and mechanisms of sodium ibandronate in ovariectomy-induced osteoporosis rats / 中国组织工程研究

BACKGROUND: Bisphosphonates are a novel inhibitor of bone resorption that can inhibit the activity and function of osteoclasts. OBJECTIVE: To observe the effects of sodium ibandronate on the expression of dentin matrix protein 1, Caspace3, Bcl-2 and Bax in condylar cartilage in osteoporosis rats. METHODS: Thirty-six female rats were randomly divided into sham group, osteoporosis group and sodium ibandronate group, twelve in each group. The sham group did not excise ovaries during surgery. Bilateral ovaries of rats were removed in the osteoporosis and sodium ibandronate groups. On the 7th day after operation, rats in the sodium ibandronate group were intraperitoneally given sodium ibandronate 10 µg/kg, once every 7 days. After 90 days, the rat ovaries were taken. Bone mineral density was measured in each group. The changes of condylar cartilage were observed by toluidine blue staining and TUNEL staining. The expression of dentin matrix protein 1 protein was detected by immunohistochemistry. The levels of Caspase3, Bcl-2 and Bax were detected by western blot assay. The study protocol was approved by the Animal Ethics Committee of Nanhua Hospital in China with the approval No. SLXD_201804010. RESULTS AND CONCLUSION: Compared with the sham group or sodium ibandronate group, the bone mineral density in the osteoporosis group was significantly decreased (P < 0.05). The results of toluidine blue staining showed that the hypertrophic layer of condylar cartilage in the sodium ibandronate group was significantly thicker than that in the osteoporosis group. Compared with the sham group or sodium ibandronate group, the number of apoptotic cells in condylar cartilage and subchondral bone increased significantly in the osteoporosis group (P < 0.05). The expression of dentin matrix protein 1 protein was significantly lower in the osteoporosis group than the sham group, but it increased after treatment with sodium ibandronate (P < 0.05). Compared with the sham group, the expression of Caspase 3 and Bax in the osteoporosis group increased significantly, and the expression of Bcl-2 decreased. However, treatment with sodium ibandronate decreased the expression of Caspase 3 and Bax and increased the expression of Bcl-2 significantly. Overall, our findings reveal that sodium ibandronate can inhibit the apoptosis of condylar chondrocytes and the number of osteoclasts in osteoporotic state, which may be related to the regulation of Caspase 3, Bcl-2, Bax and dentin matrix protein 1 expression.

Determination of Stability Constants of Ibandronate Complexes with Ca(II), Mg(II) and Sr(II)

An abnormal condition which troubles a living organism is called a disease. Nowadays, the most common problems thepeople are affected by are the heart problems. Several times, they lead to death in most cases due to the lack of correctdiagnosis. The volume of data has been increasing rapidly in the area of health care. Predicting the heart problems is verydifficult for the physicians. It is intractable to find the interesting patterns among enormous volumes of data. To find those,pattern recognition can be used, and to discover the hidden knowledge, data mining can be used. There have been a largenumber of medical data sets available in the market. Among all types of heart diseases, Cardio Vascular Disease is a type.So, many researchers carried out their works in heart disease dataset with 13 attributes, and 15 attributes with various datamining methods. In this study, ranking method was used in preprocessing a stage with total of 17 attributes for strengtheningthe rate of accuracy. The Zero R and J48 algorithms from NN and Multilayer Perceptron & decision tree were appliedrespectively on the dataset. The classifiers’ performance was analyzed by error rate and time complexity with accuracy. Inthis research, Multilayer perceptron classifier showed high accuracy results with 13 attributes. Out of these three classifiers,J48 classifier gave high accuracy, minimum error rate and less time while using 17 attributes. Hence, these approaches canbe very useful to the physicians to take decisions at the proper time. This research work was entirely carried out by WEKA(Waikato Environment Knowledge Analysis) data mining tool.

Effectiveness of monthly intravenous ibandronate injections in a real-world setting: Subgroup analysis of a postmarketing observational study

OBJECTIVES: The favorable safety and consistent effectiveness of monthly intravenous (IV) ibandronate injections was demonstrated in a prospective, postmarketing, observational study in Japanese patients with osteoporosis. Here, we present subgroup analyses from the study. METHODS: Lumbar spine (L2–4) bone mineral density (BMD) gains were assessed in the following subgroups: aged <75 or ≥75 years, absence or presence of vertebral fractures, previous bisphosphonate (BP) treatment, and concomitant versus naïve osteoporosis drug treatment. The cumulative incidence of fractures and relative change in bone turnover markers were also examined. RESULTS: Of 1062 enrolled patients, 1025 received monthly IV ibandronate 1 mg and were assessed for 12 months. BMD gains with ibandronate were comparable, irrespective of older age or prevalent fractures. Overall, 515 patients (50.2%) had previously received osteoporosis treatment; of these, 166 (16.1%) received other BPs. Mean BMD changes were 3.69% (95% confidence interval [CI], 0.89%–6.50%) in patients previously treated with other BPs, and 4.26% (95% CI, 2.88%–5.64%) in patients who had not received prior osteoporosis treatment. Among the 510 patients (49.7%) concomitantly prescribed active vitamin D drugs, mean BMD changes were 5.74% (95% CI, 2.53%–8.95%) with eldecalcitol versus 3.54% (95% CI, 1.98%–5.10%) with ibandronate alone. The lowest fracture incidence was observed with the combination of ibandronate and eldecalcitol, but differences between the subgroups were not statistically significant. CONCLUSIONS: Monthly IV ibandronate demonstrated comparable BMD gains in the patient subgroups analyzed. Concomitant use of ibandronate with eldecalcitol showed a trend of higher BMD gains and lower fracture incidence than ibandronate alone.

Efficacy, safety, and compliance of ibandronate treatment for 3 years in postmenopausal Japanese women with primary osteoporosis

OBJECTIVES: The aim of this study was to examine the efficacy, safety, and adherence of ibandronate (IBN) treatment with or without vitamin D supplementation for 3 years in Japanese women with postmenopausal osteoporosis. METHODS: This prospective investigation included 27 patients treated with IBN alone (monotherapy group) and 29 patients receiving IBN and alfacalcidol (ALF) (combination group). Bone metabolism and bone mineral density (BMD) were measured before and at 18, 24, 30, and 36 months of therapy. Treatment discontinuation and fracture occurrence were assessed as well. RESULTS: Lumbar 1–4 BMD (L-BMD) was significantly increased in the monotherapy and combination groups by 3.9% and 7.2%, respectively, at 36 months, with significant gains in total hip BMD (H-BMD) of 3.7% and 4.9%, respectively. There were significant differences in L-BMD improvement between the groups at 18, 24, and 30 months (P < 0.05) and at 36 months (P < 0.01). Compared with pretreatment levels, the percentage changes of L-BMD and H-BMD were significant at all time points in the combination group and at all points apart from L-BMD at 36 months in the monotherapy group. In the monotherapy group, 14 patients dropped out during 3 years and 2 vertebral fractures occurred during the first year. In the combination group, 16 cases dropped out during 3 years and 1 nonvertebral fracture was noted during the first year. CONCLUSIONS: Our findings suggest that combination therapy of IBN and vitamin D is superior to monotherapy with regard to L-BMD improvements for 3 years, with both groups showing comparable safety and adherence to treatment.

Safety and effectiveness of monthly intravenous ibandronate injections in a prospective, postmarketing, and observational study in Japanese patients with osteoporosis

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.

Comparison of effectiveness and safety of ibandronate and minodronate combined with eldecalcitol in primary osteoporosis of women: A 1-year follow-up study

OBJECTIVES: This is an open labeled and retrospective cohort study which compared the effectiveness and safety of ibandronate (IBN) and minodronate (MIN) combined with eldecalcitol (ELD) in primary osteoporosis of women. METHODS: One hundred and forty-eight primary osteoporotic women were classified into 3 groups; 1) intravenous IBN combined with oral ELD (IBN + ELD group, N = 50; 81.8 ± 6.2 years), 2) oral MIN combined with oral ELD (MIN + ELD group, N = 50; 77.2 ± 6.9 years) and 3) oral ELD alone (ELD group, N = 48; 75.0 ± 8.3 years). For statistical analysis, L-BMD, H-BMD, serum corrected Ca, serum iP, intact-PTH, TRACP-5b, BAP, serum Hcy, eGFR and urine Ca/Cr ratio were measured until 12 months after the start of therapy. RESULTS: L-BMD values increased significantly in both IBN + ELD and MIN + ELD group, however, H-BMD increased significantly in the IBN + ELD group only. TRACP-5b values decreased rapidly during the first 6 months in both IBN + ELD and MIN + ELD group. However, BAP value in the IBN + ELD group decreased more gradually compared with that in the MIN + ELD group. Both serum Ca value and urine Ca/Cr ratio tended to increase, and the eGFR value decreased significantly in each group. CONCLUSIONS: IBN combined with ELD administration can act more effectively to increase BMD compared with MIN combined with ELD administration. Differences of decreasing rate in TRACP-5b and BAP value may lead to differences of increased rate of BMD in the IBN + ELD and MIN + ELD group. Because many cases of osteoporosis are elderly persons associated with chronic kidney disease, monitoring of kidney function and concentration of Ca in blood and urine is essential.

Determination of Related Substances in Ibandronate Sodium Raw Materials by Ion Suppression Chromatography / 中国药房

OBJECTIVE:To adopt ion suppression chromatography to determine related substance in ibandronate sodium raw materials.METHODS:The separation was performed on a Dionex IonPac AS11-HC column with mobile phase consisted of potassium hydroxide (gradient elution) at the flow rate of 1.1 mL/min.The column temperature was set at 45 ℃,and sample size was 20 μL.Suppressed conductivity detector was adopted with temperature of 35 ℃.RESULTS:The linear ranges of phosphite,impurity Ⅰ and phosphate were 3.08-30.83 μg/mL(r=0.999 9),2.84-28.43 μg/mL(r=0.999 1),2.95-29.52 μg/mL(r=0.999 9),respectively.The limits of quantitation were 2.47,56.7,3.31 ng,and the limits of detection were 0.75,17.2,1.0 ng.RSDs of precision,stability and reproducibility tests were all lower than 4.0％.The recoveries were 101.49％-103.57％ (RSD=0.7％,n=9),100.00％-104.85％ (RSD=1.8％,n=9),101.35％-104.08％ (RSD=0.9％,n=9),respectively.CONCLUSIONS:The method is simple,accurate and sensitive,and is suitable for the determination of related substance in ibandronate sodium raw materials.

Retrospective study for the change of bone density over 2 years in patients at Sorokdo hospital / 나학회지

INTRODUCTION: Author investigated the baseline of BMD and T-score through analysis of bone density for 254 ex-hansen patients in 2014. This study aims to evaluate the change of BMD and T-score after two years of medication to improve the BMD of those patients. MATERIALS AND METHODS: The 144 subjects received the tests for bone density at 2015 and 2016 consecutively and have taken medication since 2014. DXA machine was used on L1–L4 and femur neck and the results of BMD and T-score were compared with those in 2014. RESULTS: The rate of male to female was 1:1.08, their mean age was 77.3 years old. In comparison with the results of 2014, the change of BMDs(g/cm2) at femur neck were −0.08 in 60s, −0.11 in 70s, and −0.09 in 80s and older. For the change of T-score, they showed −0.70 in 60s, −0.81 in 70s, and −1.30 in 80s and older. But the BMDs at femur neck in 2016 increased by 0.04 in 60s and 0.01 in 80s and older. CONCLUSION: Both of the bone densities and T-scores at femur neck were decreased comparing with those of 2014. But the change of BMDs between 2015 and 2016 was almost absent. So, the effect of long term medication with bisphosphonate was thought to be effective for improving BMDs in old ex-hansen patients at national Sorokdo hospital.

Ibandronate in the Treatment of Pediatric Osteoporosis.

We administered oral ibandronate (once a month) to 7 children (6 boys) with low bone mineral density and prevalent low energy fractures. We observed a significant increase (17%) in bone density after one year and additional 3% increase after second year. No further fractures occurred.

Knowledge, Attitude and Practices Concerning Cosmetic Surgery among Female Medical Students at the University Hospital, King Saud University, Riyadh, Saudi Arabia.

Background: This study investigates the knowledge, attitudes and practices of cosmetic surgery among female medical students at King Saud University (KSU). Methods: A quantitative observational cross-sectional approach was used to carry out the study at the KSU College of Medicine. A web-based questionnaire was first developed to collect the data necessary to fulfill the objectives of the research. The population under study included a random sample in which the questionnaire was sent to all female medical students at KSU. The sample size was estimated by using a single proportion formula with an acceptable margin of error at 5%. The sample size obtained was 384. Results: A response rate of 99% was achieved. The mean age of the participants was 20.9±1.48.Out of 381 KSU female medical students in our study, almost all participants (360, 94.5%) have heard about cosmetic surgery. Television was the source of knowledge for more than one third (38%) of participants who had already heard about cosmetic surgery. Just over half (51.4%) of surveyed KSU female medical students recognized the best definition of cosmetic surgery as “a surgery that modifies or improves the appearance of a physical feature electively”. A great majority of participants (86%) reported knowing of a particular type of cosmetic surgery, namely breast augmentation. Almost all participants (92.4%) agreed that “women perform more cosmetic surgery than men”. Only 9% of participants reported undergoing cosmetic surgery, where most of them (19 out of 35) went through laser treatment for the skin and almost the same number had a cosmetic surgery for personal satisfaction. Conclusion: From this research, we recommend further studies to go beyond educational institutions to the public at large, and to study different sub-populations.

The Burden of Respiratory Syncytial Virus Disease in Pre-Term Infants.

This mini-review summarises the risk factors for acquiring Respiratory Syncitial Virus (RSV) infection, and describes the harmful effects of the infection in pre-term infants. Moreover, theoretical considerations are discussed for the prevention of RSV infection in high-risk infant categories, such as pre-term infants. Background: Neonates positive for RSV are more prone to severe infection than neonates infected with other common respiratory viruses. Despite RSV infection being more common in late neonates than in early ones, pre-term infants ≤ 35 wk gestational age (GA) are at high risk for developing severe RSV disease. Efforts to prevent infection include case management, vaccination and the identification of risk factors. The morbidity and mortality risks of RSV disease are highest in pre-term newborns with other underlying disease, such as bronchopulmonary dysplasia (BPD) or hemodynamically significant congenital heart disease (hsCHD). Associations between RSV-positive neonates and climate factors are also discussed. Nosocomial-acquired respiratory syncytial virus infections in pre-term infants in Neonatal Intensive Care Units (NICUs) are reported. The development of an RSV vaccine has been challenging, and vaccine in pre-term infants is currently unavailable. Palivizumab, a monoclonal antibody licensed for the prevention of RSV, lowers respiratory tract disease in pre-term infants. The home healthcare nurse can play an important role. By developing patient and caregiver trust, the nurse can implement an RSV prevention plan, leading to a decrease in the hospitalization of premature infants with RSV. Conclusions: Commercially-insured late pre-term infants with RSV infection are at high risk of recurrent wheezing and infantile asthma for 1 year after the initial episode, and pose a significant economic burden on the healthcare system. Education is critical for the continuing development of clinical NICU nursing practice.

Efficacy of a Once-Monthly Pill Containing Ibandronate and Cholecalciferol on the Levels of 25-Hydroxyvitamin D and Bone Markers in Postmenopausal Women with Osteoporosis

BACKGROUND: The present study evaluated the efficacy of a combination of ibandronate and cholecalciferol on the restoration of the levels of 25-hydroxyvitamin D (25[OH]D) and various bone markers in postmenopausal women with osteoporosis. METHODS: This was a randomized, double-blind, active-controlled, prospective 16-week clinical trial conducted in 20 different hospitals. A total of 201 postmenopausal women with osteoporosis were assigned randomly to one of two groups: the IBN group, which received a once-monthly pill containing 150 mg ibandronate (n=99), or the IBN+ group, which received a once-monthly pill containing 150 mg ibandronate and 24,000 IU cholecalciferol (n=102). Serum levels of 25(OH)D, parathyroid hormone (PTH), and various bone markers were assessed at baseline and at the end of a 16-week treatment period. RESULTS: After 16 weeks of treatment, the mean serum levels of 25(OH)D significantly increased from 21.0 to 25.3 ng/mL in the IBN+ group but significantly decreased from 20.6 to 17.4 ng/mL in the IBN group. Additionally, both groups exhibited significant increases in mean serum levels of PTH but significant decreases in serum levels of bone-specific alkaline phosphatase and C-telopeptide of type 1 collagen (CTX) at 16 weeks; no significant differences were observed between the groups. However, in subjects with a vitamin D deficiency, IBN+ treatment resulted in a significant decrease in serum CTX levels compared with IBN treatment. CONCLUSION: The present findings demonstrate that a once-monthly pill containing ibandronate and cholecalciferol may be useful for the amelioration of vitamin D deficiency in patients with postmenopausal osteoporosis. Moreover, this treatment combination effectively decreased serum levels of resorption markers, especially in subjects with a vitamin D deficiency, over the 16-week treatment period.

Scurvy Induced Hemodynamic Instability.

Aim: Our case report aims to inform practicing clinicians of an unusual presentation of vitamin C deficiency in the setting of a developed nation where this illness is rare and underappreciated. Case Presentation: We present the case of a noncompliant 16-year-old African American female with vertically transmitted human immunodeficiency virus/acquired immune deficiency syndrome who presented to the emergency department (ED) with a CD4 count of 4 and a hemoglobin level of 5.7 g/dL. In the ED, she was found to have persistent low-grade bleeding initially believed to be of an upper gastrointestinal origin, but which was later found come from the oral mucosa. Her stools were dark in color and guaiac positive. She was hemodynamically unstable, for which she was transfused with packed red blood cells and briefly treated with continuous norepinephrine infusion. Her initial coagulation studies were noncontributory with an international normalized ratio of 1.1, a prothrombin time of 35, and a platelet count that was also within normal limits. Esophagogastroduodenoscopy and a colonoscopy were both unremarkable. Bone marrow biopsy showed normocellular marrow with 80% cellularity and trilinear hematopoiesis. Her vitamin C level was zero. She was diagnosed with scurvy and treated with vitamin C supplementation. Discussion and Conclusion: Vitamin C deficiency can lead to an often-forgotten medical condition called scurvy. It can cause defective collagen synthesis leading to fragile capillaries, gingival bleeding, and cutaneous changes. Unrecognized, this condition can lead to significant bleeding and can be lethal in select patient populations. Our case is unique in that it shows that vitamin C deficiency can masquerade as upper gastrointestinal bleeding and may present with significant hemodynamic instability requiring blood transfusions and vasopressor support. It is therefore imperative to keep in mind the diagnosis of scurvy as a potential cause of hemodynamic instability even in an industrialized nation such as the United States. Vitamin C deficiency is a rare and underdiagnosed medical entity in the hospital setting that can lead to hemodynamic instability. Scurvy patients can present with melena and oral bleeding, mimicking hematemesis.

Estudo de biodisponibilidade relativa de ibandronato de sódio após administração oral de dose única em voluntários sadios / Bioavailability study of sodium ibandronate after single oral dose in health volunteers

O objetivo do estudo foi verificar a biodisponibilidade de duas formulações de ibandronato de sódio, comprimidos de 150 mg, com base em comparações estatísticas dos parâmetros farmacocinéticos urinários, quantidade total excretada na urina (Ae), velocidade de excreção máxima (Rmax) e tempo médio em que o Rmax foi observado (tmax). O estudo foi cruzado, aberto, aleatório, com dois tratamentos, dois períodos, duas sequências com administração de dose única de ibandronato de sódio após jejum de 10 horas, em 70 voluntários sadios do sexo masculino. O intervalo entre os períodos (washout) foi de 21 dias. As amostras de urina foram obtidas por um período de 48 horas após a administração dos medicamentos. O ibandronato foi quantificado em urina por LC-MS-MS após extração em fase sólida, seguida de um procedimento de derivatização. Os parâmetros farmacocinéticos Ae, Rmax e tmax foram calculados e a média da razão teste/referência e os IC90% para Ae e Rmax foram obtidos. O Rmax médio dos medicamentos teste e referência foi, respectivamente, de 496.374,11 ng/h e 467.524,28 ng/h, ambos atingidos em 1,5 hora. O Ae médio foi de 1.996,29 µg para o medicamento teste e de 1.870,37 µg para o referência. Os IC90% para Rmax e Ae estão dentro dos limites de 80% a 125%, portanto, podemos concluir que os medicamentos teste e referência são bioequivalentes de acordo com os critérios da ANVISA.

Long-term risks of bisphosphonate therapy / Riscos do tratamento a longo prazo com bisfosfonatos

The objective this study was to summarize long-term risks associated with bisphosphonate therapy. Search of relevant medical publications for data from clinical trials, trial extensions, observational studies and post-marketing reports. Trial extensions and modifications did not reveal significant long-term safety issues. Observational data suggest at least as many benefits as risks. Post-marketing reports of musculoskeletal pain, osteonecrosis of the jaw and atypical femur fractures have been widely circulated in the lay press. Most focus on long-terms risks has been on osteonecrosis of the jaw and atypical femur fractures which occur in patients who have not received bisphosphonate therapy but may be more frequent (though still uncommon) in patients who have been on treatment for 5 years or longer. Lower-risk patients may be able to stop treatment after 3-5 years for a “drug holiday,” which mitigates these long-term risks; for higher risk patients, therapy through 6-10 years appears to be advisable and offers more benefits than risks.

O objetivo deste estudo foi resumir os riscos associados ao tratamento a longo prazo com bisfosfonatos. Foram pesquisadas as publicações médicas relevantes incluindo ensaios clínicos, extensões de ensaios clínicos, estudos observacionais e relatórios pós-comercialização (vigilância farmacológica). As extensões e modificações de ensaios clínicos não indicaram nenhuma situação de alarme quanto à segurança dos bisfosfonatos a longo prazo. Dados observacionais sugerem pelo menos tantos benefícios quanto riscos. Entretanto, relatos pós-comercialização de dor musculoesquelética, osteonecrose da mandíbula e fraturas de fêmur atípicas foram amplamente divulgados na imprensa leiga. O foco nos riscos a longo prazo do tratamento com bisfosfonatos tem sido pincipalmente a osteonecrose da mandíbula e as fraturas atípicas de fêmur. Essas últimas, embora mais frequentes (ainda que pouco comuns) em pacientes que receberam tratamento com bisfosfonatos por 5 anos ou mais, podem ocorrer em indivíduos não tratados com esses medicamentos. Pacientes com baixo risco de fratura podem potencialmente parar o tratamento depois de 3 a 5 anos (“drug holiday”). Esse procedimento reduz os riscos desses medicamentos a longo prazo. Não obstante, nos pacientes de maior risco a terapia por 6 a 10 anos parece ser aconselhável e oferece mais benefícios do que riscos.

Estradiol and/or Ibandronate Therapy Ameliorates Oxidative Status in Livers of Ovariectomized Rats.

Background: Overiectomized rats suffer from osteoporosis that mainly results from oxidative stress (OS). Studies revealed that the levels of antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-S-transferase, catalase (CAT), and glutathione reductase could be used to determine and follow-up OP. The anti-oxidant activity of anti-osteoporotic drugs needs further investigations to be proved to add more confidence in the ability of these drugs to control the disease. Objective: To investigate the possible anti-oxidant effect of treatment with ibandronate, a highly potent nitrogen-containing bisphosphonate, on activities of catalase and glutathione peroxidase anti-oxidant enzymes, thiobarbituric reactive substance (TBARS), as a marker of lipid peroxidation and DEPPD free radicals in liver homogenates of ovariectomized rats. Methods: Fifty adult female albino rats were divided into five equal groups ( n=10 rats): Group (1): served as control injected with saline, 2nd group: rats were subjected to ovariectomy, 3rd group: rats were exposed to ovariectomy and treated with estradiol, 4th group: were ovariectomized and treated with ibandronate and 5th group: were ovariectomized and treated with both estradiol and ibandronate. Duration of therapy with either drug was 12 weeks. Results: Estradiol alone or in combination with ibandronate to ovariectomized rats showed significant increase in activities of anti-oxidant enzymes. Both drugs reduces hepatic TBARS and DEPPD free radicals in hepatic homogenates in this model of OP. Conclusion: The present study can conclude that ovariectomy leading to oxidative changes liver of tested rats. Co-administration of estradiol and ibandronate provides a kind of protection against alterations in anti-oxidative/oxidative balance. The results support the hypothesis stated by experimental studies that anti-osteoporotic treatment could also possess anti-oxidative protective property.

Evaluation of Osseointegration around Tibial Implants in Rats by Ibandronate-Treated Nanotubular Ti-32Nb-5Zr Alloy

Materials with differing surfaces have been developed for clinical implant therapy in dentistry and orthopedics. This study was designed to evaluate bone response to titanium alloy containing Ti-32Nb-5Zr with nanostructure, anodic oxidation, heat treatment, and ibandronate coating. Rats were randomly assigned to two groups for implantation of titanium alloy (untreated) as the control group and titanium alloy group coated with ibandronate as the experimental group. Then, the implants were inserted in both tibiae of the rats for four weeks. After implantation, bone implant interface, trabecular microstructure, mechanical fixation was evaluated by histology, micro-computed tomography (microCT) and the push-out test, respectively. We found that the anodized, heat-treated and ibandronate-coated titanium alloy triggered pronounced bone implant integration and early bone formation. Ibandronate-coated implants showed elevated values for removal torque and a higher level of BV/TV, trabecular thickness and separation upon analysis with microCT and mechanical testing. Similarly, higher bone contact and a larger percentage bone area were observed via histology compared to untreated alloy. Furthermore, well coating of ibandronate with alloy was observed by vitro releasing experiment. Our study provided evidences that the coating of bisphosphonate onto the anodized and heat-treated nanostructure of titanium alloy had a positive effect on implant fixation.

Estudo replicado de biodisponibilidade relativa de duas formulações de ibandronato de sódio em voluntários sadios dos sexos feminino (pós-menopausa e não menopausa) e masculino / A replicated study of relative bioavailability of two formulations of sodium ibandronate in healthy female (postmenopausal and non-menopausal) and male volunteers

O estudo foi realizado para comparar a biodisponibilidade de duas formulações de ibandronato de sódio 150 mg comprimidos (Ibandronato de Sódio do Aché Laboratórios Farmacêuticos S/A formulação teste e Bonviva® da Produtos Roche Químicos e Farmacêuticos S.A formulação referência, Brasil) em 80 voluntários de ambos os sexos (20 voluntários do sexo feminino na pós-menopausa, 20 voluntários do sexo femino na não menopausa e 40 voluntários do sexo masculino). O estudo foi aberto, replicado, aleatorizado, 2-sequências, 4-períodos, cruzado com dois tratamentos, nos quais um grupo de voluntários recebeu a formulação teste e outro a formulação referência. As amostras de plasma foram obtidas ao longo de um intervalo de 72 horas. As concentrações de ibandronato de sódio foram determinadas através de espectrometria de mssa (UPLC-MS-MS), utilizando Ibandronato deuterado como padrão interno. A partir dos dados obtidos, calcularam-se os seguintes parâmetros farmacocinéticos: ASC0-t, ASC0-¥ e Cmax. A média geométrica de Ibandronato de Sódio/Bonviva® 150 mg foi de 102,18 % para ASC0-t, 102,14 % para ASC0-¥ e 100,64% para Cmax. Os intervalos de confiança de 90% foram de 94,89 - 110,03%, 94,92 - 109,91% e 91,88 - 110,23%, respectivamente. Uma vez que os intervalos de confiança de 90% para Cmax e ASC0-t estiveram dentro da faixa de 80% a 125% proposta pelo FDA e pela ANVISA (Agência Nacional de Vigilância Sanitária do Brasil), conclui-se que o comprimido de ibandronato de sódio de 150 mg foi bioequivalente ao comprimido de Bonviva® de 150 mg e, dessa forma, o produto teste pode ser considerado intercambiável na prática médica.

Comparative study on the efficacy and safety of zoledronic acid and sodium ibandronate in treating bone metastasis in breast cancer patients / 中华内分泌外科杂志

ObjectiveTo retrospectively evaluate the efficacy and safety of zoledronic acid and sodium ibandronate in treating bone metastasis in breast cancer patients.MethodsThe study included 47 patients who were treated with zoledronic acid and sodium ibandronate respectively from Aug.2006 to Mar.2011. KaplanMeier curve and Log rank test were adopted to detect the difference in survival time of skeletal related event (SRE) and survival rate between patients treated with different medicine,and x2 test was uscd to rcveal thc rate difference of pain killing effects and adverse effects.Results 1.The total effective rate of pain killing was 88.9％ and 85％ respectively.The difference had no statistical significance(P =0.467).2.The 1,2 and 3-year-survival rate in zoledronic acid group and sodium ibandronate group was 88.7％,44.4％,24.2％vs 94.7％,40.5％,5.8％.The difference had no statistical significance(P =0.744).3.The 2,3,and 4-year-survival rate in zoledronic acid group and sodium ibandronate group was 70.4％,40.7％,23.1％ vs 85％,46.7％,17.5％.The difference had no statistical significance( P =0.994).4.The 1,2 and 3-year SRE-free overall survival rate of the group with metastasis first to bone only was 92％,50.8％,and 23.8％,while the rate of the group with first metastasis to visceral organs was 85.4％,21.4％,and 5.3％ ( P =0.012).5.The 2 and 3-year overall survival rate of the group with metastasis first to bone only was 95.8％ and 74.2％ respectively,while the rate of the group with first metastasis to visceral organs was 56.5％ and 10.1％ ( P ＜0.001 ).The difference of 4 and 5 had statistical significance.The difference of zoledronic acid group and sodium ibandronate group in rate of adverse effects had no statistical significance.Conclusions Compared to sodium ibandronate,zoledronic acid has no superiority in either delaying the occurrence of SRE or improving overall survival rate.The -2are similar in incidence of adverse effects and pain control.The prognosis of patients whose first presentation is complicated by metastasis to other organs is poor.