Zoledronic Acid In Patients Research Articles

Progression-Free Survival Subset Analysis - Denosumab Vs Zoledronic Acid in Bone Disease Treatment of Newly Diagnosed Multiple Myeloma: An International, Double-Blind, Double-Dummy, Randomized Controlled Phase 3 Study

Introduction: The full primary analysis of the international, double-blind, double-dummy, randomized controlled phase 3 study (20090482) that assessed the efficacy and safety of denosumab vs zoledronic acid for preventing skeletal-related events (SREs) in newly diagnosed patients with multiple myeloma (NDMM) met the primary noninferiority endpoint of time to first on-study SRE (Raje N, et al. Lancet Oncol. 2018). Overall survival, a secondary endpoint, was similar in both arms; however, this result was based on a limited number of events having occurred (denosumab 14.1% vs zoledronic acid 15.0%), which might have affected the ability to detect a difference and also may have been further diluted by multiple subsequent lines of therapy. In addition, results from an exploratory endpoint, progression-free survival (PFS), demonstrated a clinically meaningful 10.7 months median PFS benefit (hazard ratio [HR], 0.82; 95% CI, 0.68-0.99; descriptive P=0.036; Table 1) of denosumab versus zoledronic acid on top of standard of care first-line anti-myeloma treatment. This result provided suggestive clinical evidence of a potential anti-myeloma effect based on RANKL inhibition. Here we present further analysis of PFS according to prespecified subgroups of patients from the 20090482 study.Methods: Adult NDMM patients with ≥1 documented lytic bone lesion were included in this study. Patients received subcutaneous denosumab (120 mg) plus intravenous placebo or intravenous zoledronic acid (4 mg) plus subcutaneous placebo every 4 weeks. Both groups also received investigators' choice of first-line anti-myeloma therapy. The exploratory endpoint PFS (time from randomization to date of first overall disease progression or death due to any cause, investigator identified) was estimated using the Kaplan-Meier method and analyzed using a Cox proportional hazards model stratified by randomization stratification factors and adjusted for baseline covariates. PFS subgroup analyses were conducted according to the novel first-line therapy use (proteasome inhibitor [PI] use, immunomodulatory drug [IMiD] use, PI and IMiD use) and the intent to receive an autologous stem cell transplant (ASCT; yes, no).Results: Overall, 1718 patients (denosumab, n=859; zoledronic acid, n=859) were included in the primary analysis. By the time of the primary analysis cut-off, 219 patients (25.5%) in the denosumab group and 260 patients (30.3%) in the zoledronic acid group had a PFS event. The percentages of patients receiving novel first-line therapy were balanced between the two groups (see Table 1). For patients who had received first-line PI-based therapy, PFS favored denosumab vs zoledronic acid (median, 40.0 vs 35.4 months; HR, 0.74; 95% CI, 0.58-0.95; descriptive P=0.019; Table 1). For patients who had received first-line IMiD only-based therapy, median PFS was not reached with denosumab therapy and was 34.3 months with zoledronic acid therapy (HR, 0.85; 95% CI, 0.53-1.35; descriptive P=0.49). Median PFS was also not reached for either denosumab or zoledronic acid for patients who had received first-line PI plus IMiD therapy (HR, 0.95; 95% CI, 0.62-1.46; descriptive P=0.82). For patients with the intent at baseline to receive an ASCT (54% in each treatment group; Table 1), PFS favored denosumab vs zoledronic acid (median, 46.1 vs 35.7 months; HR, 0.65; 95% CI, 0.49-0.85; descriptive P=0.002).Conclusion: Overall results from this subanalysis indicated PFS impact and benefit of denosumab on top of anti-myeloma therapy, independent from first-line novel therapy which was balanced among treatment arms, mainly in the subgroup of patients receiving PI only-based first-line therapy. In addition, benefit was observed in patients with the intent to receive ASCT, described with an impressive HR of 0.65. [Display omitted] DisclosuresTerpos:Amgen Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, steering committee member, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: member of steering committee, Research Funding; Genesis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: member of DMC, Research Funding; BMS: Consultancy; Novartis: Consultancy. Willenbacher:Amgen: Honoraria, Other: Steering board, Research Funding; Celgene: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Roche: Honoraria, Research Funding; BMS: Honoraria; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Merck: Honoraria. Shimizu:Daiichi-Sankyo, Co., Ltd: Consultancy; Fujimoto Pharmacuetical Corp: Consultancy; Amgen Inc.: Other: Non-remunerative Position of Influence, Denosumab 20090482 Global Steering Committee Member. García-Sanz:Hospira: Research Funding; Pharmacyclics: Research Funding; Spanish Government: Research Funding; Gilead: Research Funding; Amgen Inc.: Research Funding; Incyte: Consultancy; BMS: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses. Glennane:Amgen: Employment, Equity Ownership. Guan:Amgen: Employment, Equity Ownership. Niepel:Amgen Inc.: Employment, Equity Ownership. Raje:BMS: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Merck: Consultancy; Takeda: Consultancy; AstraZeneca: Research Funding; Research to Practice: Honoraria; Medscape: Honoraria; Amgen Inc.: Consultancy.

Prediction of pathological response to neoadjuvant chemotherapy in breast cancer patients by imaging

BackgroundDiagnostic imaging is important for predicting the pathological response to chemotherapy during neoadjuvant chemotherapy (NAC) and for considering the surgical management with appropriate resection after NAC. This study was performed to examine the accuracy of the present radiological imaging for predicting the pathological complete response (pCR). MethodsFrom 188 patients in our previous JONIE1 Study, a randomized controlled trial comparing chemotherapy with and without zoledronic acid for patients with human epidermal growth factor receptor 2-negative breast cancer, we evaluated 122 patients whose tumor size was examined by magnetic resonance imaging or ultrasound at three points: before NAC; after administering fluorouracil, epirubicin, and cyclophosphamide; and after NAC. The maximum tumor diameter was evaluated by magnetic resonance imaging or ultrasound. Tumor reduction ratios were calculated at the same three points. The association between the radiological clinical response and the pCR was examined. ResultsAmong the 122 patients evaluated, there were 98 and 24 patients with luminal (Lum) and triple-negative (TN) subtypes, respectively. There were no patients who showed tumor progression after treatment. The radiological size of the tumors was finally reduced by an average of 58.4%. Clinical complete response and pCR were achieved in 22 (18.0%) and 15 (12.3%) patients, respectively. In the overall population (n = 122), the accuracy, sensitivity, and specificity for predicting pCR were 86.1%, 88.8%, and 66.7%, respectively. The negative predictive value and false-negative rate were 45.5% and 11.2%, respectively. According to subtypes, the accuracies were 83.7% and 95.8% in Lum and TN, respectively. Negative predictive value and false-negative rate were markedly different between the Lum (29.4% and 13.5%) and TN subtypes (100% and 0%), respectively. ConclusionsThis randomized clinical trial demonstrated that NAC was safe for operable breast cancer patients with appropriate radiological monitoring. Radiological evaluation after NAC may be a reliable method for predicting pathological response in the TN subtype, but not in the Lum subtype.

Bone-targeted therapies to reduce skeletal morbidity in prostate cancer.

Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer (mCRPC). Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.

РАСПРОСТРАНЕННОСТЬ И КЛИНИЧЕСКИЕ ОСОБЕННОСТИ МЕДИКАМЕНТОЗНО АССОЦИИРОВАННЫХ ОСТЕОНЕКРОЗОВ ЧЕЛЮСТЕЙ

Subject of study. Bisphosphonate - related osteonecrosis of the jaw (BRONJ) is a severe complication, which may arise in patients, receiving BP therapy and also in patients taking designer drugs (desomorphine, methamphetamine). Urgency of the study is caused by broad bisphosphonate administration in patients with the proved bone metastasises, myelomatosis, Paget disease. Use of red phosphorus at clandestine production of desomorphine and methamphetamine in patients with drug abuse. Atypical forms of osteomyelitis develop at these two categories of people. Purpose - to study the prevalence and features of clinical and X-ray picture of the drug-related osteonecrosis. Methodology. The study is based on retrospective survey of records and X-ray examination of patients being on treatment in maxillofacial surgery’s unit in MAU “CGKB” (Central Clinical City Hospital) #23 in 2013-2017. Results. Drug - related osteonecrosis was diagnosed in 31.2% hospitalization cases with jaw osteomyelitis. In 50% designer drugs taking (desomorphine, methamphetamine) was the reason. In 50% was the administration of bisphosphonates therapy at bone metastasises in patients with malignant neoplasms and myelomatosis. The clinical picture is characterized by protracted disease course with frequent relapses. At X-ray examination the lack of sequesters with an accurate demarcation zone is characteristic. Conclusions. Prevalence of drug-related osteonecrosis is increasing due to widespread use of drugs called Zoledronic acid in patients with cancer. Detailed history taking on the outpatient reception hours plays the leading role at osteonecrosis diagnostics. Chemotherapy as well as continuing of designer drugs taking promotes progressing of osteonecrosis of a jaw and its relapses in spite of the treatment. Relapses nascency is the reason for rehospitalizations.

Effects on bone resorption markers of continuing pamidronate or switching to zoledronic acid in patients with high risk bone metastases from breast cancer

BackgroundSwitching patients who remain at high risk of skeletal related events (SREs) despite pamidronate to the more potent bisphosphonate zoledronate, may be an effective treatment strategy. As part of a previously reported clinic study in this setting, we evaluated whether biomarkers for bone resorption, such as Bone-Specific Alkaline Phosphatase (BSAP), bone sialoprotein (BSP), and N-terminal telopeptide (NTX) correlated with subsequent SRE risk. MethodsBreast cancer patients who remained at high risk of SREs despite at least 3 months of q.3–4 weekly pamidronate were randomized to either continue on pamidronate or to switch to zoledronate (4mg) once every 4 weeks for 12-weeks. High risk bone metastases were defined by either: occurrence of a prior SRE, bone pain, radiologic progression of bone metastases and/or serum C-terminal telopeptide (CTx) levels > 400ng/L despite pamidronate use. Serum samples were collected at baseline and weeks 1, 4, 8 and 12 (CTx and BSAP) and baseline and week 12 (NTx and BSP), and all putative biomarkers were measured by ELISA. Follow up was extended to 2 years post trial entry for risk of subsequent SREs. The Kaplan-Meier method was used to estimate time-to-event outcomes. Generalized estimating equations (GEE) were used to evaluate if laboratory values over time or the change in laboratory values from baseline were associated with having a SRE within the time frame of this study. ResultsFrom March 2012 to May 2014, 76 patients were screened, with 73 eligible for enrolment. All 73 patients were available for biochemical analysis, with 35 patients receiving pamidronate and 38 patients receiving zoledronate. The GEE analysis found that no laboratory value was associated with having a subsequent SRE. Interaction between visit and laboratory values was also investigated, but no interaction effect was statistically significant. Only increased number of lines of prior hormonal treatment was associated with subsequent SRE risk. ConclusionOur analysis failed to find any association between serum BSAP, BSP, CTx or NTx levels and subsequent SRE risk in this cohort of patients. This lack of correlation between serum biomarkers and clinical outcomes could be due to influences of prior bisphosphonate treatment or presence of extra-osseous metastases in a significant proportion of enrolled patients. As such, caution should be used in biomarker interpretation and use to direct decision making regarding SRE risk for high risk patients in this setting.

The skeletal-related events of denosumab versus zoledronic acid in patients with bone metastases: A meta-analysis of randomized controlled trials

ObjectiveThe meta-analysis was used to evaluate the skeletal-related events (SREs) and efficacy of denosumab versus zoledronic acid (ZA) in patients with bone metastases. MethodsThe data of this meta-analysis study were searched from PUBMED, EMBASE, Cochrane Library, Web of Science with Conference Proceedings, Elsevier and China National Knowledge Infrastructure (CNKI) databases till August 2017. Two independent reviewers reviewed the reference lists of relevant articles. The fixed-effects model and random-effects model were used to summarize relative estimates and 95% confidence intervals (CIs) according to the heterogeneity of the included studies. ResultsThree randomized controlled trials (RCTs) including 4050 patients were identified in this meta-analysis study. The pooled analysis showed that denosumab could significantly reduce SREs, series SREs [Odds Ratio (OR) = 0.84; 95% CI, 0.74–0.95, I2 = 0%, P = 0.008] in patients with bone metastases as compared with ZA. Similar results of spinal cord compression SRE and surgery to bone SRE were obtained with (OR = 0.84; 95% CI, 0.70–1.01, I2 = 0%, P = 0.07) and (OR = 0.92; 95% CI, 0.78–1.08, I2 = 0%, P = 0.28) separately, radiation to bone SRE (OR = 0.72; 95% CI, 0.46–1.10, I2 = 11%, P = 0.13) and pathological fracture SRE (OR = 0.78; 95% CI, 0.35–1.73, I2 = 25%, P = 0.54) showed similar results, there were no significant difference between denosumab and ZA in patients with bone metastases. ConclusionDenosumab was more effective than ZA in reducing the incidence of SRE in patients with bone metastases.

Safety of Zoledronic Acid in Patients with Thalassemia Associated Low Bone Mineral Density.

Safety of Zoledronic Acid in Patients with Thalassemia Associated Low Bone Mineral Density.

Safety of Denosumab Versus Zoledronic Acid in Patients with Bone Metastases: A Meta-Analysis of Randomized Controlled Trials

Introduction: Bone metastases lead to local bone destruction and skeletal complications. Bisphosphonates, particlulaly zoledronic acid (ZA), play a central role in the treatment of bone metastases. Some studies have shown that denosumab may delay and prevent SREs in metastatic bone disease more effectively than ZA; therefore, we systematically reviewed and assessed the safety of denosumab and ZA. Methods: The PubMed, EMBASE, Cochrane Library, Web of Science with Conference Proceedings, Elsevier, and China National Knowledge Infrastructure (CNKI) databases were searched up to October 2015. 2 independent reviewers extracted data from each eligible study using a standard protocol, and both fixed-effects and random-effects models were used to analyze and evaluate the data extracted from eligible articles. Results: 6 randomized controlled trials enrolling 13,733 patients were included. Occurrences of adverse events were generally similar between the denosumab and ZA groups except anemia and anorexia in patients with bone metastases and back pain and bone pain. However, occurrences of serious adverse events such as hypocalcaemia , renal adverse events , and new primary malignancy were significantly different between the denosumab and ZA groups. Only the occurrence of osteonecrosis of the jaw showed no significant difference between the denosumab and ZA groups in patients with bone metastases. Conclusion: Denosumab was safer in delaying or preventing skeletal-related events in patients with bone metastases and prevented pain progression compared to ZA in this meta-analysis.

Efficacy and safety of denosumab from a phase III, randomized, active-controlled study compared with zoledronic acid in patients of Asian ancestry with bone metastases from solid tumors.

10116Background: This phase III double-blind study was conducted to provide bridging data to the available efficacy and safety data of denosumab (DmAb) from global skeletal-related events (SRE)-pre...

Efficacy of Zoledronic Acid in Patients with Systemic Osteoporosis and Problem of «Non Respondents» to the Treatment

Efficacy of Zoledronic Acid in Patients with Systemic Osteoporosis and Problem of «Non Respondents» to the Treatment

Efficacy of Zoledronic Acid in Patients with Systemic Osteoporosis and Problem of «Non Respondents» to the Treatment

Prospective study of zolendronic acid efficacy was performed in 112 patients with systemic osteoporosis. Study results confirmed the presence of patients who did not response to the treatment: in 15.7 % of observations reduction of mineral bone density (BMD) continued to progress. No significant differences in initial deviations of resorption and bone formation markers, peculiarities of calcium homeostasis were detected in “non respondents”. At the same time by the 12th month after treatment initiation the relationship between BMD increase with preservation of marked decrease of resorption marker (deoxypyridinoline) and bone formation marker (osteocalcin) was noted, that pointed out the expediency of prognostic model creation. Evaluation of the influence of certain risk factors (age, results of blood and urine biochemical tests, data of densitometry including the results of femoral neck BMD in some patients) using discriminant analysis showed that 81.5% of patients were correctly referred to the groups of patients who responded and not responded to treatment. Out of all initially studied parameters the most significant were 7 that in 78.6% of cases (method sensitivity) enabled to identify the patients with negative treatment effect and in 82.1% of cases (method specificity) - with positive treatment effect.

PCN298 - The Clinical and Economic Burden of Skeletal Related Events in Austria, Czech Republic, Germany, Greece, Italy, Spain and Switzerland: a Comparison Between the use of Denosumab and Zoledronic Acid In Patients with Prostate Cancer And Bone Metastases

PCN298 - The Clinical and Economic Burden of Skeletal Related Events in Austria, Czech Republic, Germany, Greece, Italy, Spain and Switzerland: a Comparison Between the use of Denosumab and Zoledronic Acid In Patients with Prostate Cancer And Bone Metastases

PCN299 - The Clinical and Economic Burden of Skeletal Related Events in Austria, Czech Republic, Germany, Greece, Italy, Spain and Switzerland: A Comparison Between the use of Denosumab and Zoledronic acid in Patients With Breast Cancer and Bone Metastases

To estimate the total number of skeletal-related events (SREs) prevented, related hospital burden and direct medical expenditure when denosumab is used instead of zoledronic acid for SRE prevention in seven European countries. A model was developed combining country-specific breast cancer mortality data from the World Health Organization or from local registries, the proportion of metastatic breast cancer patients with bone metastases (BMs) at high risk of developing SREs from published literature, the prevalence of breast cancer with BMs was derived assuming a steady state approach (with incidence equivalent to mortality of metastatic disease), and the average survival for metastatic breast cancer patients from published literature. Annual SRE rates from a European observational retrospective study and the treatment effect observed in a head-to-head clinical trial of denosumab versus zoledronic acid were used to estimate the total number of predicted SREs by treatment option. Country-specific findings from two retrospective studies were used to estimate the total number of hospitalisations, inpatient days and direct medical costs associated with the management of SREs. Across all countries, the estimated prevalence of breast cancer patients with BMs was 87,592 patients: Austria, 3,253; Czech Republic, 3,509; Germany, 37,895; Greece, 4,639; Italy, 27,767; Spain, 7,553; and Switzerland, 2,975. When denosumab was the selected treatment option, 36,324 SREs were estimated to be avoided per year compared with the use of zoledronic acid, which would save 24,110 hospitalisations, 536,551 inpatient days and 206,605,754€ of direct medical costs (2014 costs in €: Austria, 23,890,554; Czech Republic, 5,779,856; Germany, 60,659,628; Greece, 15,941,728; Italy, 39,998,970; Spain, 17,249,548; and Switzerland, 43,085,469). Denosumab’s clinical superiority in the prevention of SREs over zoledronic acid could result in significant savings in the number and duration of hospitalisations, reducing direct medical costs associated with the management of SREs in Europe.

Cost-utility of adjuvant zoledronic acid in patients with breast cancer and low estrogen levels.

Adjuvant zoledronic acid (za) appears to improve disease-free survival (dfs) in women with early-stage breast cancer and low levels of estrogen (lle) because of induced or natural menopause. Characterizing the cost-utility (cu) of this therapy could help to determine its role in clinical practice. Using the perspective of the Canadian health care system, we examined the cu of adjuvant endocrine therapy with or without za in women with early-stage endocrine-sensitive breast cancer and lle. A Markov model was used to compute the cumulative costs in Canadian dollars and the quality-adjusted life-years (qalys) gained from each adjuvant strategy, discounted at a rate of 5% annually. The model incorporated the dfs and fracture benefits of adjuvant za. Probabilistic and one-way sensitivity analyses were conducted to examine key model parameters. Compared with a no-za strategy, adjuvant za in the induced and natural menopause groups was associated with, respectively, $7,825 and $7,789 in incremental costs and 0.46 and 0.34 in qaly gains for cu ratios of $17,007 and $23,093 per qaly gained. In one-way sensitivity analyses, the results were most sensitive to changes in the za dfs benefit. Probabilistic sensitivity analysis suggested a 100% probability of adjuvant za being a cost-effective strategy at a threshold of $100,000 per qaly gained. Based on available data, adjuvant za appears to be a cost-effective strategy in women with endocrine-sensitive breast cancer and lle, having cu ratios well below accepted thresholds.

Management of bone disease in myeloma patients: zoledronic acid or denosumab?

With improvement of survival owing to the recent implementation of new anti-myeloma (MM) agents, bone management will become more important for maintaining the quality of life (QoL) of patients. Bisphosphonates are currently the standard of care for MM-related bone disease. Zoledronic acid is recommended for newly diagnosed MM patients receiving front-line anti-MM treatment regardless of existing detectable bone lesions. Intriguingly, an overall survival benefit has been observed with zoledronic acid in patients on anti-MM treatment with documented bone disease at baseline. Denosumab, a human monoclonal antibody against RANKL, has been demonstrated to reduce bone-related events in patients with MM as effectively as zoledronic acid. Hypocalcemia is generally accepted as occurring more frequently and more severely with denosumab than with zoledronic acid, especially in patients with renal insufficiency. Bisphosphonates but not denosumab deposit in bone with a long half-life, which may make a difference in long-term efficacy as well as adverse effects. Clinical benefits of long-term anti-resorptive therapies after achieving a good response should be clarified, in order to avoid the emergence of severe complications. Impacts of new agents in combination with these anti-resorptive agents on bone metabolism have yet to be studied.

Denosumab versus zoledronic acid in patients previously treated with zoledronic acid.

Denosumab and zoledronic acid are potent antiresorptives. In this study in patients pre-treated with zoledronic acid, denosumab achieved similar increases with zoledronic acid in lumbar spine BMD despite the more prominent reduction of bone turnover markers. Denosumab reversibly reduced endogenous RANKL. We aimed to compare yearly changes in lumbar spine (LS) bone mineral density (BMD), bone turnover markers, free soluble receptor activator of nuclear factor kappaB ligand (sRANKL) and sclerostin levels between denosumab and zoledronic acid. Postmenopausal women with low bone mass previously treated with zoledronic acid for 1 year were assigned to denosumab injection (n = 32) or zoledronic acid infusion (n = 26). Procollagen type 1 N-terminal propeptide (P1NP), C-terminal cross-linking telopeptide of type 1 collagen (CTx), sRANKL, and sclerostin levels were measured in serum samples obtained at baseline and 3, 6, and 12 months after denosumab injection or zoledronic acid infusion. LS BMD was measured at baseline and 12 months. The mean LS increase was 4.5 and 4.4% with denosumab and zoledronic acid, respectively (p = 0.560). Denosumab caused a larger decrease in CTx at 3 months (p < 0.001) and P1NP at 3 (p < 0.001), 6 (p = 0.021), and 12 months (p = 0.042). Denosumab significantly decreased sRANKL by 87.4% at 3 months (p < 0.001). Sclerostin levels were not changed with either intervention (p = 0.162 and p = 0.214, respectively). In patients previously treated with zoledronic acid, denosumab reduces bone turnover more than zoledronic acid, but the increases in LS BMD are comparable. Furthermore, denosumab administration results in reversible inhibition of the metabolically significant endogenous free soluble RANKL levels. Serum sclerostin is not affected by either agent.

Efecto del ácido zoledrónico en pacientes pediátricos con diagnóstico clínico de osteogénesis imperfecta: un estudio de cohorte

Introducción: la osteogénesis imperfecta es un trastorno congénito caracterizado por la fragilidad del hueso, causado por mutaciones en los genes del procolágeno tipo I. La incidencia es variable, encontrando un caso por cada 5.000 a 70.000 nacidos vivos. Debido a las limitaciones en el tratamiento se ha planteado el uso de bifosfonatos como el ácido zoledrónico. Objetivo: describir el efecto del tratamiento con ácido zoledrónico endovenoso en pacientes pediátricos con osteogénesis imperfecta atendidos en el Hospital Universitario San José (Popayán, Colombia) durante 2013 y 2014. Materiales y métodos: se realizó un estudio observacional tipo cohorte de carácter cerrado y sin grupo de comparación. El tratamiento con ácido zoledrónico se realizó trimestralmente durante un año, tiempo en el que se determinaron los efectos positivos y adversos del tratamiento. Resultados: seis pacientes presentaron diagnóstico de osteogénesis imperfecta; uno fue excluido porque inició tratamiento quirúrgico, los demás iniciaron tratamiento con ácido zoledrónico. Un paciente se retiró voluntariamente y cuatro completaron el estudio, dos sin fracturas y dos con una fractura durante este período. La densidad mineral ósea de la columna lumbar y femoral presentó mejoría, documentándose en dos pacientes valores normales a los tres meses de finalizado el tratamiento. La intensidad del dolor óseo, según la escala visual análoga al inicio del estudio, fue entre 5 y 8, y al final entre 0 y 2. No se encontraron cambios en la limitación funcional ni efectos adversos. Conclusiones: la terapia con ácido zoledrónico endovenoso en pacientes con osteogénesis imperfecta mejora el curso de la enfermedad independientemente de la severidad.

Safety and effectiveness of zoledronic acid therapy used in osteogenesis imperfecta patients

Introduction: Osteogenesis imperfecta is an inheritable disease characterized by deficiency of collagen type 1 due to mutation in CO1A1 and CO1A2 genes which leads to an increase in bone fragility and fractures rate. Most medical centres use pamidronate for standard treatment of osteogenesis imperfecta. However, zoledronic acid is used for the standard treatment of osteoporosis, and it has higher potency than pamidronate and faster intravenous infusion. Few studies have demonstrated the safety and effectiveness of zoledronic acid in patients with osteogenesis imperfecta. Objectives: The aim of our retrospective chart review study was to estimate the safety and effectiveness of zoledronic acid in patients with osteogenesis imperfecta. Methods: The study included 16 patients diagnosed with osteogenesis imperfecta at King Abdulaziz Medical City, Jeddah, within the last 10 years (10 males and 6 females) with a mean age of 8.9±5.2, all patients received zoledronic acid therapy and they were monitored before and after treatment. Results: It was found that the average number of fractures in patients before using zoledronic acid was 3.8±1.8, which dropped after zoledronic acid dropped to 0.93±1.2. The difference in fractures was significant, with a mean of 2.8±1.2 (P≤ 0.05). After zoledronic acid therapy the mean functional measures were as follows: calcium level 2.4mmol/l, phosphate level 1.5mmol/l, alkaline phosphatase level 223IU/l and vitamin D level 50nmol/l. Conclusion: The study showed that using zoledronic acid therapy in osteogenesis imperfecta patients was effective as it significantly decreased the number of fractures. Since calcium and vitamin D profiles were within normal range this indicates zoledronic acid therapy is safe. Infusion of zoledronic acid is convenient for the patient since it requires a one-day admission as opposed to a three-day admission for pamidronate infusion. Further studies are required to standardize the optimal dosing and improve the efficacy of the treatment.

Cost-Effectiveness of denosumab vs. Brand or generic zoledronic acid in patients with prostate cancer in kazakhstan.

Cost-Effectiveness of denosumab vs. Brand or generic zoledronic acid in patients with prostate cancer in kazakhstan.

Cost-Effectiveness of Denosumab vs. Brand or Generic zoledronic Acid in Patients with Breast Cancer in Kazakhstan.

Denosumab is recomended for preventing skeletal-related events (SREs) in adults with bone metastases from breast cancer (BC). Since recently generic zoledronic acid (ZA) became available, the aim of present study was to access the cost-effectiveness of denosumab vs. brand or generic ZA in the prevention of SREs in Kazakhstani patients with BC. An excel-based Markov model was constructed with 4-week model cycles to analyse the cost-effectiveness of the treatments from the perspective of Ministry of Health with a 10-year time horison for BC cohort. Direct costs (in 2014 tenge) included costs of drug, adverse event and SRE(pathologic fracture, surgery to bone, radiation to bone, spinal cord compression) treatment. A discount rate of 3% per year was applied for all costs. Effectiveness was appraised based on the number of SREs. The health states were defined according to SRE occurance,SRE history and death. The model assumed that a maximum of 1 SRE could occur in each cycle. Transition probabilities were derived from the relevant phase III trials. Results were present in the incremental total cost per SRE avoided. One-way sensitivity analyses were performed to examine the robustness of the model. Over 10-year period, denosumab incurred 1044 tenge lower costs than brand ZA, 568558 tenge higher costs than generic ZA, 1.28 fewer SREs per BC patient. The estimated incremental total direct costs per SRE avoided with the use of denosumab were -816 tenge (instead of brand ZA) and 444186 tenge (instead of generic ZA). Results were robust to one-way sensitivity analyses. With assumption that brand and generic ZAs are equally effective in the prevention of SREs in BC patients, denosumab seems to be cost-effective alternative for brand ZA, and costly alternative for generic ZA from a perspective of Ministry of Health of Republic of Kazakhstan.