Effects of zoledronic acid on osteoblasts in three-dimensional culture
Conclusion ZA sensitivity of osteoblasts depends on concentration and experimental models. The dual dose-dependent effects of ZA on osteoblasts cultured as spheroids, thereby promoting or inhibiting cell proliferation, may provide opportunities in tissue engineering. At last, the hFOB spheroid culture system represents a valuable model for the exploration of the molecular basis of BPs action on osteoblasts and for the development and evaluation of implantable biomaterials in bone sites. (Source: Journal of Dental Sciences)
Source: Journal of Dental Sciences - October 12, 2014 Category: Dentistry Source Type: research

Epidemiology, pharmacology and clinical characterization of bisphosphonate-related osteonecrosis of the jaw. A retrospective study of 70 cases.
CONCLUSIONS: 25% of the BRONJ cases were related to the administration of oral bisphosphonates, especially alendronate. Zoledronic acid was the bisphosphonate that required the fewest milligrams to induce osteonecrosis. Single bone exposure was the most common clinical finding, especially in the molar mandibular region in patients with metastatic disease. PMID: 25308796 [PubMed - as supplied by publisher] (Source: Acta Otorrinolaringologica Espanola)
Source: Acta Otorrinolaringologica Espanola - October 9, 2014 Category: ENT & OMF Authors: Pelaz A, Junquera L, Gallego L, García-Consuegra L, García-Martínez L, Cutilli T, Olay S Tags: Acta Otorrinolaringol Esp Source Type: research

Pathologic fracture in patients with metastatic prostate cancer
Purpose of review: This review will describe the management of patients with prostate cancer and bone metastases with a particular emphasis on recent advances in this area. Recent findings: Two osteoclast-targeted agents have been shown to decrease the incidence of skeletal-related events in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases. These agents are the bisphosphonate zoledronic acid and the monoclonal antibody denosumab. Recent advances in the field include the approval of several agents shown to extend survival in mCRPC. Among these agents, the androgen-pathway inhibitors,...
Source: Current Opinion in Urology - October 2, 2014 Category: Urology & Nephrology Tags: BONE HEALTH IN UROLOGIC PATIENTS: Edited by Benjamin K. Canales Source Type: research

Severe visual loss secondary to retinal toxicity after intravenous use of bisphosphonate in an eye with known chloroquine maculopathy
Conclusion:Exposure to zoledronic acid seems to have precipitated acute visual loss in an eye with known chloroquine toxicity after 15 years of quiescence. Retinal toxicity may represent a rare adverse reaction to zoledronic acid, but this case suggests that caution should be used when administering this medication to patients with compromised retinal integrity. (Source: Retinal Cases and Brief Reports)
Source: Retinal Cases and Brief Reports - October 1, 2014 Category: Opthalmology Tags: Case Report Source Type: research

Abstract 725: Combination therapy of telomerase-specific oncolytic adenovirus and zoledronic acid in human osteosarcoma cells
In this study, we investigated the in vitro and in vivo antitumor effects of combination therapy with ZOL and OBP-301 in human osteosarcoma cells. Four human osteosarcoma cell lines, HOS, SaOS-2, U2OS and MNNG/HOS were used. We used XTT assay to examine the antitumor effect of ZOL and OBP-301 individually and combinatory on days 2,3,5. ZOL was treated at concentration of 0 to 10µM, and OBP-301 was infected at multiplicity of infections (MOI) of 0 to 100 plaque forming units (PFU)/cell. Combination index was calculated with the CalcuSyn software (BioSoft) and combined antitumor effect between ZOL and OBP-301 was analy...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Yamakawa, Y., Hasei, J., Tazawa, H., Omori, T., Osaki, S., Sasaki, T., Yoshida, A., Kunisada, T., Urata, Y., Ozaki, T., Fujiwara, T. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 1628: Direct anti-cancer effects of zoledronic acid on human cancer cell
Zoledronic Acid (ZA) is a potent nitrogen-containing bisphosphonates (NBP) has been extensively used to limit bone turnover in a various diseases including tumors. Recently, clinical trails of Zoledronic Acid demonstrated direct anti-cancer effects as well as the known skeletal-related events. We investigated the effect of 4 NBPs on human tumor cells proliferation and found ZA is most potent for GBM cell, breast cell and GBM patients' stem-cell-like cells. ZA also effectively inhibited GBM tumor growth in mouse model. ZA stimulated strong autophagy but not apoptotic signals in all tested cells. One intermediate product of ...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Jiang, P., Mukthavavam, R., Nomura, N., Pingle, S. C., Kesari, S. Tags: Cancer Chemistry Source Type: research

Abstract 2982: Macrophages modulate adaptive resistance to anti-angiogenic therapy
Targeted anti-angiogenic therapies were a highly anticipated addition to cancer treatment, but their clinical use has been tempered by the development of resistance. To understand the role of immune cells in potentially mediating such resistance, we carried out systematic immune cell profiling in a syngeneic ovarian cancer mouse model following treatment with the B20 anti-VEGF antibody. Following injection of luciferase-labeled cancer cells and initiation of treatment, mice (n=8/group) were divided into B20-sensitive and resistant groups based on longitudinal bioluminescence imaging of tumor burden. Immune cell profiling c...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Dalton, H. J., Pradeep, S., Armaiz-Pena, G. N., Previs, R., Davis, A., Rupaimoole, R., Zand, B., Hailemichael, Y., Overwijk, W. W., Lopez-Berestein, G., Sood, A. K. Tags: Tumor Biology Source Type: research

Abstract 2992: Zoledronic acid inhibits angiogenesis through Rac1 inactivation in ovarian cancer
Conclusion ZA inhibits ovarian cancer angiogenesis through the inactivation of Rac1, suggesting that ZA combined with paclitaxel could be a novel therapeutic approach to ovarian cancer angiogenesis. Citation Format: Viany Gonzalez-Villasana, Cristian Rodriguez-Aguayo, Enrique Fuentes-Mattei, Sunila Pradeep, Cristina Ivan, Anil K. Sood, Gabriel Lopez-Berestein. Zoledronic acid inhibits angiogenesis through Rac1 inactivation in ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Sup...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Gonzalez-Villasana, V., Rodriguez-Aguayo, C., Fuentes-Mattei, E., Pradeep, S., Ivan, C., Sood, A. K., Lopez-Berestein, G. Tags: Tumor Biology Source Type: research

Abstract 3130: Zoledronic acid inhibits proliferation and metastasis of human pancreatic cancer in the patient-derived orthotopic xenograft (PDOX) model by targeting tumor-educated macrophages
In this study, EMφ and NMφ were compared for their ability to enhance tumor progression. We initially demonstrated that the cancer cells exposed to the conditioned medium harvested from EMφ culture significantly increased proliferation (p = 0.016) and had more migration stimulation capability (p
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Hiroshima, Y., Hassenein, M. K., Menen, R., Katz, M. H. g., Fleming, J. B., Sato, S., Murakami, T., Yamamoto, M., Uehara, F., Miwa, S., Yano, S., Momiyama, M., Maawy, A., Chishima, T., Tanaka, K., Bouvet, M., Endo, I., Hoffman, R. M. Tags: Tumor Biology Source Type: research

Abstract 4807: Zoledronic acid overcomes the resistance to the anti-angiogenic therapy and normalizes tumor vessels by switching from a M2- to a M1-like macrophages phenotype in a mouse model of spontaneous cervical cancer
Recent studies described a resistance to the anti-angiogenic therapy both in pre-clinical and clinical settings. Several mechanisms that contribute to this resistance has been so far proposed and, among these, the recruitment of bone marrow-derived cells to the tumors, seems to be critical. We have previously showed that an amino-bisphosphonate, Zoledronic acid (ZA), in a mouse model of spontaneous cervical carcinogenesis (HPV16/E2) by targeting MMP-9+ tumor-associated macrophages (TAM), strongly inhibited cancer progression and angiogenesis. Stemming from these data we sought to investigate whether ZA by acting on TAM, wa...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Capano, S., Maione, F., Casanovas, O., Bussolino, F., Giraudo, E. Tags: Tumor Biology Source Type: research

Abstract 5311: Proteomic characterization of zoledronic acid-resistant prostate cancer cells identified key proteins in cytoskeleton organization and cancer stem cell markers associated with a very aggressive phenotype
The aminobiphosphonate Zoledronic acid (ZOL) inhibit osteoclast-mediated bone resorption and it is used to prevent skeletal complications from bone metastases. Accumulating evidences in both preclinical and clinical studies indicated that ZOL might also have anticancer activity. We have recently selected for the first time the ZOL-resistant DU145R80 prostate cancer (PCa) cell line that demonstrated an antiapoptotic and proangiogenic phenotype with increased invasive capability and epithelial to mesenchymal transition (EMT), compared to parental DU145 cells. Interestingly, we also demonstrated that both the acquired resista...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Milone, M. R., Pucci, B., Iannelli, F., Lombardi, R., Bifulco, K., Bruzzese, F., Gennaro, E. D., Avallone, A., Carriero, M. V., Budillon, A. Tags: Molecular and Cellular Biology Source Type: research

Hypernociceptive responses following the intratibial inoculation of RM1 prostate cancer cells in mice
CONCLUSIONThe intratibial inoculation of RM1 cells in immunocompetent mice induces hypernociceptive responses and can be useful to perform studies of bone cancer induced pain related to androgen‐independent prostate cancer. The antinociceptive role derived from the blockade of the CCR2 chemokine receptors is further envisaged. Prostate © 2014 Wiley Periodicals, Inc. (Source: The Prostate)
Source: The Prostate - September 28, 2014 Category: Urology & Nephrology Authors: María Llorián‐Salvador, Marta Pevida, María Teresa Fernández‐García, Ana Lastra, Álvaro Obaya, Santiago Cal, Agustín Hidalgo, Luis Menéndez, Ana Baamonde Tags: Original Article Source Type: research

Comparing Hospital-Based Resource Utilization and Costs for Prostate Cancer Patients With and Without Bone Metastases
Abstract Background Since 2010, several new treatments for prostate cancer (PCa), which have entered the US market, are poised to have an impact on treatment approaches; however, there is a paucity of evidence with respect to treatment patterns and costs. As new treatment patterns emerge, it will be imperative to understand treatment patterns and costs of care prior to the advent of novel treatments. Objective As the PCa treatment landscape is evolving, this study sought to compare the hospital-based utilization and costs in two cohorts of patient...
Source: Applied Health Economics and Health Policy - September 26, 2014 Category: Health Management Source Type: research

Low-level laser therapy for osteonecrotic lesions: effects on osteoblasts treated with zoledronic acid
Conclusion LLLT showed limited effects on bisphosphonate-treated osteoblasts. (Source: Supportive Care in Cancer)
Source: Supportive Care in Cancer - September 25, 2014 Category: Cancer & Oncology Source Type: research

304p * assessment of bisphosphonates use as adjuvant therapy in breast cancer
Aim: Breast cancer is the most frequently diagnosed cancer in females. It is the leading cause of cancer deaths in females ranking as the first malignancy affecting females in Egypt and accounts for 30% of female cancers, 39.5% are postmenopausal. Adjuvant aromatase inhibitors (AI) alone or sequentially after tamoxifen increases disease free survival in postmenopausal women compared with tamoxifen alone, but at the expense of increased bone loss. Bisphosphonates including zoledronic acid have been shown to reduce cancer treatment-induced bone loss.Methods: This is a prospective randomized phase III study where 120 postmeno...
Source: Annals of Oncology - September 24, 2014 Category: Cancer & Oncology Authors: Abu-Taleb, F. M., El-Zawahry, H. M., Zekri, Z. K., Gaafar, R. M. M., Al Lahloubi, N. M. A., Zakhari, N., Elfarargy, O., Alnagar, A. A. R. Tags: breast cancer, early stage Source Type: research

799p * prognostic value of computer-aided diagnosis system for bone scans in hormone-naive prostate cancer patients with bone metastases
The objective of this study was to evaluate the CA-BSI for prognostic factor in hormone-naive prostate cancer with bone metastases.Methods: The study included 75 hormone-naive prostate cancer patients with bone metastases initially treated with combined androgen blockade therapy between 2005 and 2013 at our institution. BONENAVI® system was used for calculation program of CA-BSI. We evaluated the correlation between prognosis and clinicopathological characteristics, value of PSA, extent of disease (EOD) grade, pretreatment bone scan index (BSI) and the number of hot spots. Statistical analyses were assessed using cox p...
Source: Annals of Oncology - September 24, 2014 Category: Cancer & Oncology Authors: Yoneyama, S., Miyoshi, Y., Takebayashi, S., Noguchi, K. Tags: genitourinary tumours, prostate Source Type: research

Background: Non-Small Cell Lung Cancer (NSCLC) is a heterogeneous disease for which patients (pts) may benefit from targeted therapies. RANK ligand (RANKL) and its receptor RANK are expressed in a subset of NSCLC tumors (Branstetter, 2013). Results from preclinical models show that RANKL acts directly on RANK-expressing tumor cells to promote tumor progression and metastases (Gonzalez-Suarez, 2010; Tan, 2011). Denosumab is a fully human monoclonal antibody that binds RANKL, approved for the prevention of skeletal-related events in pts with solid tumors and bone metastases. In a study of pts with solid tumors receiving stan...
Source: Annals of Oncology - September 24, 2014 Category: Cancer & Oncology Authors: Spigel, D. R., Hirsch, F. R., De Boer, R. H., Natale, R., Crawford, J., Weiss, G. J., Glaspy, J., Feng, A., Braun, A., Jain, R. Tags: NSCLC, metastatic Source Type: research

1513p * risk factors for hypocalcemia in patients with cancer receiving denosumab
Conclusions: The risk of hypoCa after Dmab for MBD is associated with the # of bone mets and elevated bone turnover markers, especially high BSAP with>2 mets. BSAP may indicate the potential for deposition of Ca in undermineralized matrix. Pts with high bone turnover may be more susceptible to hypoCa when osteoclasts are rapidly inhibited, particularly when Ca and vitamin D intake is insufficient.Disclosure: J. Body: Consultant for and received research funding from Amgen; received honoraria from Amgen and Novartis; H.G. Bone: Consultant for and received honoraria from Amgen and Novartis; C. van Poznak: Received researc...
Source: Annals of Oncology - September 24, 2014 Category: Cancer & Oncology Authors: Body, J., Bone, H. G., van Poznak, C., De Boer, R. H., Stopeck, A., Damiao, R., Fizazi, K., Henry, D. H., Ibrahim, T., Lipton, A., Saad, F., Shore, N. D., Takano, T., Wang, H., Bracco, O. L., Balakumaran, A., Kostenuik, P. J. Tags: supportive care Source Type: research

1516p * hypomagnesaemia in cancer patients: underestimated problem? when supportive care is detrimental: the example of protonic pump inhibitors
Aim: Magnesium ( Mg) is an important cofactor for many enzymes and metabolic reactions. Serum Mg levels
Source: Annals of Oncology - September 24, 2014 Category: Cancer & Oncology Authors: Traverso, E. S., Varese, P., Angelini, I., Cosentino, C., Simoni, C., Bennicelli, E., Prasso, F., Paolieri, F., Pizzo, L., Petronio, M., Zucchi, M., Altmura, P. Tags: supportive care Source Type: research

Background: Denosumab is a monoclonal antibody against RANK-Ligand with a higher activity in preventing skeletal related events (SREs) than zoledronic acid but without impact on disease progression or death. SREs are pathologic bone fractures, surgery or radiation to the bone or spinal cord compression. The relative effects on SREs in patients with bone metastases from castration resistant prostate cancer and breast cancer are similar (hazard ratio 0.82). Denosumab is usually well tolerated but a dose-dependent increase in risk of osteonecrosis of the jaw in up to 8% of patients and cases of fatal hypocalcaemia have been o...
Source: Annals of Oncology - September 24, 2014 Category: Cancer & Oncology Authors: Templeton, A. J., Stalder, L., Albiges Sauvin, L., Bernhard, J., Brauchli, P., Gillessen, S., Hayoz, S., Klingbiel, D., Matter-Walstra, K., Thurlimann, B., von Moos, R. Tags: supportive care Source Type: research

Background: A characteristic feature of multiple myeloma (MM) is bone destruction mediated by osteoclasts. This breakdown of bone releases factors that mediate myeloma cell growth, creating a cycle of skeletal damage and tumor cell growth. Patients with MM and bone lesions can experience debilitating pain and skeletal complications including pathologic fractures, need for radiotherapy or surgery to bone, and spinal cord compression, collectively termed skeletal-related events (SREs). RANKL is the key mediator of osteoclast activity. Denosumab, a fully human monoclonal antibody specific to RANKL, inhibits the formation, fun...
Source: Annals of Oncology - September 24, 2014 Category: Cancer & Oncology Authors: Terpos, E., Raje, N., Durie, B. G., Garcia-Sanz, R., Shimizu, K., Willenbacher, W., Zhu, L., Braun, A., Jain, R., Palumbo, A. Tags: supportive care Source Type: research

Influence of early zoledronic acid administration on bone marrow fat in ovariectomized rats.
Abstract Although the primary target cell of bisphosphonates is the osteoclast, increasing attention is being given to other effector cells influenced by bisphosphonates, such as osteoblasts and marrow adipocytes. Early zoledronic acid (ZA) treatment to ovariectomized (OVX) rats has been found to fully preserve bone microarchitecture over time. However, little is known regarding the influence of ZA on marrow adipogenesis. The purpose of this study was to monitor the ability of early administration of ZA in restoring marrow adiposity in an estrogen-deficient rat model. Thirty female Sprague-Dawley rats were randoml...
Source: Endocrinology - September 22, 2014 Category: Endocrinology Authors: Li GW, Xu Z, Chang SX, Zhou L, Wang XY, Nian H, Shi X Tags: Endocrinology Source Type: research

Zoledronic acid at the time of castration prevented castration-induced bone metastasis in mice
Androgen deprivation therapy (ADT) is known to cause bone loss in a majority of patients with castration-resistant prostate cancer (CRPC). A study published in this issue of Endocrine-Related Cancer by Ottewell and colleagues shows that ADT increased bone resorption and triggered growth of disseminated prostate cancer (CaP) cells to form bone metastasis using an in vivo model. However, prevention of bone decay by weekly administration of zoledronic acid (ZOL) at the time of castration prevented ADT-induced tumor growth in bone. Recently, two publications from Japan have demonstrated that ZOL combined with ADT improved outc...
Source: Endocrine-Related Cancer - September 22, 2014 Category: Endocrinology Authors: Ghosh, P. M., Gao, A. C. Tags: Commentary Source Type: research

Zoledronic acid exerts antitumor effects in NB4 acute promyelocytic leukemia cells by inducing apoptosis and S phase arrest.
Abstract The aim of this study was to investigate the antitumor effect of zoledronic acid (ZOL) in the NB4 human acute promyelocytic leukemia (APL) cell line and explore the potential mechanism of action of this compound. NB4 cells were exposed to various concentrations (0-200μM) of ZOL. Cell viability was measured by MTS assay. The extent of cell apoptosis and distribution of cells in the different phases of the cell cycle were analyzed with flow cytometry. The expression of apoptosis- and cell cycle-related proteins was assayed by Western blot. The combined effect of ZOL and arsenic trioxide (ATO) on the prol...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - September 19, 2014 Category: Drugs & Pharmacology Authors: Liu SS, Wang XP, Li XB, Liang JY, Liu LL, Lu Y, Zhong XY, Chen YX Tags: Biomed Pharmacother Source Type: research

Locally Aggressive Fibrous Dysplasia Mimicking Malignancy: A Report of Four Cases and Review of the Literature.
We report four unusual cases of fibrous dysplasia with an aggressive radiographic appearance. They occurred in the rib (1), ilium (2), and distal femur (1). Two patients had pain and two had swelling. Radiologically, all were associated with cortical destruction and an associated soft tissue mass, and initially they were interpreted as potentially malignant. Three patients underwent biopsy and one patient did not have a biopsy. Histopathologic analysis by an experienced bone pathologist confirmed fibrous dysplasia in all patients. Two patients were treated surgically; one patient with zoledronic acid and one patient curren...
Source: Pain Physician - September 12, 2014 Category: Anesthesiology Authors: Muthusamy S, Subhawong T, Conway SA, Temple HT Tags: Clin Orthop Relat Res Source Type: research

Reassessment of Fracture Risk in women after 3 years of treatment with Zoledronic Acid: when is it reasonable to discontinue treatment?
Abstract Context: Data are needed to guide therapeutic decisions about stopping bisphosphonates after an initial treatment period. Objective: To define significant predictors of fracture and quantify fracture incidence in risk factor-defined subgroups of women who discontinue zoledronic acid (ZOL) after 3 years of treatment. To determine if continuing ZOL reduces fracture risk in subgroups. Design: 3 year extension of HORIZON. Setting: Multicenter trial. Participants: 1233 women who previously received 3 ZOL treatments during Core trial. Intervention: Randomization to 3 additional annual ZOL (Z6, n=616) or placebo...
Source: The Journal of Clinical Endocrinology and Metabolism - September 12, 2014 Category: Endocrinology Authors: Cosman F, Cauley JA, Eastell R, Boonen S, Palermo L, Reid IR, Cummings SR, Black DM Tags: J Clin Endocrinol Metab Source Type: research

Rare association between penile squamous cell carcinoma and parathyroid related peptide (PTH-rP) secretion
We report on a rare case of an adult with severe hypercalcemia secondary to the ectopic secretion of parathyroid-related peptide (PTH-rP) from a penile squamous cell cancer (PC). A patient of 47 years old was admitted with warty lesions and areas of ulceration covered by purulent material in a large area of the groin, scrotum and penis. Laboratory tests revealed severe hypercalcemia and elevation of PTH-rP; the biopsy reported PC. Hypercalcemia was successfully treated with zoledronic acid, however, the tumor displayed aggressive behavior, which resulted in a poor prognosis for the patient.Relatamos um caso raro em um adul...
Source: Arquivos Brasileiros de Endocrinologia e Metabologia - September 10, 2014 Category: Endocrinology Source Type: research

Effect of intravenous hydration in patients receiving bisphosphonate therapy
Conclusion Hydration plays an important role in the treatment of hypercalcaemia by pamidronate and zoledronic acid: it enhances kidney protection (i.e., creatinine clearance). (Source: International Journal of Clinical Pharmacy)
Source: International Journal of Clinical Pharmacy - September 10, 2014 Category: Drugs & Pharmacology Source Type: research

Prostate cancer: Androgen suppression duration and zoledronic acid: under the RADAR.
PMID: 25200412 [PubMed - as supplied by publisher] (Source: Clinical Prostate Cancer)
Source: Clinical Prostate Cancer - September 9, 2014 Category: Cancer & Oncology Authors: Hutchinson L Tags: Nat Rev Clin Oncol Source Type: research

Breast cancer: Zoledronic acid-more than just a bone drug.
PMID: 25200411 [PubMed - as supplied by publisher] (Source: Clinical Breast Cancer)
Source: Clinical Breast Cancer - September 9, 2014 Category: Cancer & Oncology Authors: Mathew A, Brufsky A Tags: Nat Rev Clin Oncol Source Type: research

Prostate cancer: Androgen suppression duration and zoledronic acid: under the RADAR
Nature Reviews Clinical Oncology 11, 559 (2014). doi:10.1038/nrclinonc.2014.150 Author: Lisa Hutchinson Each year, more than 5,000 men in Australia and New Zealand are diagnosed with locally advanced prostate cancer. Unfortunately, in at least 25% of cases, the cancer has metastasized to the bone and lymph glands that is undetectable by current imaging methods. As a result, (Source: Nature Clinical Practice Oncology)
Source: Nature Clinical Practice Oncology - September 9, 2014 Category: Cancer & Oncology Authors: Lisa Hutchinson Tags: Research Highlight Source Type: research

Breast cancer: Zoledronic acid—more than just a bone drug
Nature Reviews Clinical Oncology 11, 564 (2014). doi:10.1038/nrclinonc.2014.152 Authors: Aju Mathew & Adam Brufsky Several clinical trials have investigated the antitumour effect of bisphosphonates when used as adjuvant treatment for early stage breast cancer. Among these, the results of the AZURE trial, although negative, highlight the potential benefit of treatment with zoledronic acid in postmenopausal women with high-risk early stage breast cancer. (Source: Nature Clinical Practice Oncology)
Source: Nature Clinical Practice Oncology - September 9, 2014 Category: Cancer & Oncology Authors: Aju MathewAdam Brufsky Tags: News and Views Source Type: research

Prostate cancer: Androgen suppression duration and zoledronic acid: under the RADAR
Nature Reviews Urology 11, 599 (2014). doi:10.1038/nrurol.2014.252 Author: Lisa Hutchinson Each year, more than 5,000 men in Australia and New Zealand are diagnosed with locally advanced prostate cancer. Unfortunately, in at least 25% of cases, the cancer has metastasized to the bone and lymph glands, and is undetectable by current imaging methods. As a result, (Source: Nature Reviews Urology)
Source: Nature Reviews Urology - September 9, 2014 Category: Urology & Nephrology Authors: Lisa Hutchinson Tags: Research Highlight Source Type: research

Characterisation of gamma delta (γδ) T cell populations in patients with sepsis.
Characterisation of gamma delta (γδ) T cell populations in patients with sepsis. Cell Biol Int. 2014 Sep 5; Authors: Galley HF, Lowes DA, Thompson K, Wilson ND, Wallace CA, Webster NR Abstract Gamma delta (γδ) T cells contribute to both innate and acquired immune responses during infection. In this pilot study, we measured the in vitro responses of γδT cell populations from patients with sepsis compared to cells from healthy subjects. We also measured production of interferon (IFN)γ. Mononuclear cells were isolated from 10 healthy control subjects and 20 patie...
Source: Cell Biology International - September 5, 2014 Category: Cytology Authors: Galley HF, Lowes DA, Thompson K, Wilson ND, Wallace CA, Webster NR Tags: Cell Biol Int Source Type: research

Acute effect of zoledronic acid on the risk of cardiac dysrhythmias
Abstract There have been recent concerns regarding the risk of serious adverse events, such as cardiac dysrhythmia and atrial fibrillation (AF), associated with bisphosphonate use in osteoporosis. This open-label, non-randomized, crossover pilot study evaluated short-term effects of zoledronic acid and placebo on the occurrence of cardiac dysrhythmias and prodysrhythmic profile in postmenopausal women with osteoporosis and low risk of cardiac dysrhythmias. Fifteen postmenopausal women (mean age 70.7 ± 6.9 years) with osteoporosis received placebo infusion on day 1 and zoledronic acid 5 mg on ...
Source: Internal and Emergency Medicine - September 5, 2014 Category: Emergency Medicine Source Type: research

Implications of High-Dosage Bisphosphonate Treatment on Bone Tissue in the Jaw and Knee Joint
Abstract Bisphosphonates are bone antiresorptive agents traditionally used on a relatively large scale for treatment of bone metabolic diseases and on a smaller scale for bone metastasis treatment. A study on the effects of bisphosphonate treatment on healthy instead of diseased animals will give more insight into the basic mechanisms of bisphosphonates and their effects on different bone sites. We aimed to assess the effect of BP on the mouse knee and jaw joint. Three-month old female C57BL/6 mice were used (twenty-four and eighteen control and experimental group, respectively). At baseline and after treatment wi...
Source: Calcified Tissue International - September 3, 2014 Category: Orthopaedics Source Type: research

[Comment] Role of bisphosphonates in non-metastatic prostate cancer
Bone is the most common site for distant metastases in prostate cancer and accounts for most morbidity attributable to end-stage prostate cancer. Treatments targeted at bone—eg, zoledronic acid and denosumab—reduce the risk of complications in the setting of metastatic castration-resistant prostate cancer. report oncological endpoints of the Randomised Androgen Deprivation and Radiotherapy (RADAR) study, which aimed to address two important issues in the management of locally advanced prostate cancer: first, what duration of androgen suppression is best for patients treated with external-beam radiotherapy (EBRT...
Source: The Lancet Oncology - September 1, 2014 Category: Cancer & Oncology Authors: Fred Saad Tags: Comment Source Type: research

[Corrections] Correction to Lancet Oncol 2012; 13: 1261, 1263
Denham JW, Wilcox C, Joseph D, et al. Quality of life in men with locally advanced prostate cancer treated with leuprorelin and radiotherapy with or without zoledronic acid (TROG 03.04 RADAR): secondary endpoints from a randomised phase 3 factorial trial. Lancet Oncol 2012; 13: 1260–70—In this Article, the PSA strata for randomisation should read “(20 μg/L)”. Data for initial PSA groupings and radiation dose in were incorrect; the corrected table is shown below. These corrections have been made to the online version as of Sept 1 2014. (Source: The Lancet Oncology)
Source: The Lancet Oncology - September 1, 2014 Category: Cancer & Oncology Authors: The Lancet Oncology Tags: Corrections Source Type: research

[Articles] Short-term androgen suppression and radiotherapy versus intermediate-term androgen suppression and radiotherapy, with or without zoledronic acid, in men with locally advanced prostate cancer (TROG 03.04 RADAR): an open-label, randomised, phase 3 factorial trial
Compared with STAS, ITAS plus zoledronic acid was more effective for treatment of prostate cancers with a Gleason score of 8–10, and ITAS alone was effective for tumours with a Gleason score of 7 or lower. Nevertheless, these findings are based on secondary endpoint data and post-hoc analyses and must be regarded cautiously. Long- term follow-up is necessary, as is external validation of the interaction between zoledronic acid and Gleason score. STAS plus zoledronic acid can be ruled out as a potential therapeutic option. (Source: The Lancet Oncology)
Source: The Lancet Oncology - September 1, 2014 Category: Cancer & Oncology Authors: James W Denham, David Joseph, David S Lamb, Nigel A Spry, Gillian Duchesne, John Matthews, Chris Atkinson, Keen-Hun Tai, David Christie, Lizbeth Kenny, Sandra Turner, Nirdosh Kumar Gogna, Terry Diamond, Brett Delahunt, Christopher Oldmeadow, John Attia, A Tags: Articles Source Type: research

Castration-induced bone loss triggers growth of disseminated prostate cancer cells in bone
The objective of this study was to use an in vivo model mimicking androgen ablation to establish the effects of this intervention on disseminated prostate cancer cells in bone. We mimicked the effects of androgen deprivation on bone metastasis by castrating 12-week-old BALB/c nude mice that had disseminated, hormone-insensitive PC3 prostate cancer cells present in the long bones. Castration caused increased bone resorption and loss of bone volume, compared with sham operation. In addition, castration triggered growth of disseminated PC3 cells to form bone metastasis in 70% of animals. In contrast, only 10% of sham-operated...
Source: Endocrine-Related Cancer - September 1, 2014 Category: Endocrinology Authors: Ottewell, P. D., Wang, N., Meek, J., Fowles, C. A., Croucher, P. I., Eaton, C. L., Holen, I. Tags: Research Source Type: research

Osteoporosis medication dispensing for older Australian women from 2002 to 2010: influences of publications, guidelines, marketing activities and policy
ConclusionsOverall dispense of AOM from 2002 reached a peak in 2007 and thereafter declined despite increases in therapeutic options and improved subsidised access. The recent decline in overall AOM dispensing seems to be explained largely by negative publicity rather than specific changes in guidelines and policy. Copyright © 2014 John Wiley & Sons, Ltd. (Source: Pharmacoepidemiology and Drug Safety)
Source: Pharmacoepidemiology and Drug Safety - August 30, 2014 Category: Drugs & Pharmacology Authors: Geeske Peeters, Susan E. Tett, Emma L. Duncan, Gita D. Mishra, Annette J. Dobson Tags: Original Report Source Type: research

The effects of bisphosphonate zoledronic acid in hepatocellular carcinoma, depending on mevalonate pathway
ConclusionsOur results indicated that ZOL prevented cell growth and metastasis based on direct antitumor effects in hepatoma cells. The use of ZOL could not only suppress the progression to bone metastatic lesions but also prevented growth of primary HCC. (Source: Journal of Gastroenterology and Hepatology)
Source: Journal of Gastroenterology and Hepatology - August 29, 2014 Category: Gastroenterology Authors: Yohji Honda, Shoichi Takahashi, Yizhou Zhang, Atsushi Ono, Eisuke Murakami, Niu Shi, Tomokazu Kawaoka, Daiki Miki, Masataka Tsuge, Nobuhiko Hiraga, Hiromi Abe, Hidenori Ochi, Michio Imamura, Hiroshi Aikata, Kazuaki Chayama Tags: Experimental Hepatology Source Type: research

New agents for prostate cancer
The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has been revolutionized by the arrival of multiple novel agents in the past 2 years. Immunotherapy in the form of sipuleucel-T, androgen axis inhibitors, including abiraterone acetate and enzalutamide, a chemotherapeutic agent, cabazitaxel, and a radiopharmaceutical, radium-223, have all yielded incremental extensions of survival and have been recently approved. A number of other agents appear promising in early studies, suggesting that the armamentarium against castrate-resistant prostate cancer is likely to continue to expand. Emerging a...
Source: Annals of Oncology - August 25, 2014 Category: Cancer & Oncology Authors: Agarwal, N., Di Lorenzo, G., Sonpavde, G., Bellmunt, J. Tags: reviews Source Type: research

Normocalcemic primary hyperparathyroidism: long-term follow-up associated with multiple adenomas
In conclusion, this is an unusual presentation of NPHPT and highlights the long-term complications.Hiperparatiroidismo primário normocalcêmico (NPHPT) caracteriza-se pela elevação do hormônio da paratiroide (PTH), na ausência da elevação dos níveis séricos de cálcio e exclusão de causas secundárias. O caso descrito ilustra o seguimento de uma mulher na pós-menopausa com NPHPT que evoluiu com múltiplos adenomas. Este caso relata uma paciente de 77 anos de idade que tem dor generalizada crônica e osteoporose. O PTH ini...
Source: Arquivos Brasileiros de Endocrinologia e Metabologia - August 23, 2014 Category: Endocrinology Source Type: research

Randomized phase 2 study of bone‐targeted therapy containing strontium‐89 in advanced castrate‐sensitive prostate cancer
CONCLUSIONSThe data showed that bone‐targeted therapy using 1 dose of Sr‐89 combined with chemohormonal ablation therapy did not favorably affect the PFS of patients with castrate‐sensitive prostate cancer. The combined therapy was feasible and safe. Whether such bone‐targeted therapy provides a favorable outcome for those patients with a greater tumor burden in the bone warrants further investigation. Cancer 2014. © 2014 American Cancer Society. (Source: Cancer)
Source: Cancer - August 22, 2014 Category: Cancer & Oncology Authors: Mehmet Asim Bilen, Marcella M. Johnson, Paul Mathew, Lance C. Pagliaro, John C. Araujo, Ana Aparicio, Paul G. Corn, Nizar M. Tannir, Franklin C. Wong, Michael J. Fisch, Christopher J. Logothetis, Shi‐Ming Tu Tags: Original Article Source Type: research

A Phase IB multicentre dose‐determination study of BHQ880 in combination with anti‐myeloma therapy and zoledronic acid in patients with relapsed or refractory multiple myeloma and prior skeletal‐related events
Summary Dickkopf‐1 (DKK1), expressed by myeloma cells, suppresses osteoblast function and plays a key role in bone disease in multiple myeloma. BHQ880, a human neutralizing IgG1 anti‐DKK1 monoclonal antibody, is being investigated for its impact on multiple myeloma‐related bone disease and as an agent with potential anti‐myeloma activity. The primary objectives of this Phase IB study were to determine the maximum tolerated dose (MTD) of BHQ880 and to characterize the dose‐limiting toxicity (DLT) of escalating doses in combination with anti‐myeloma therapy and zoledronic acid. Twenty‐eight patients were enroll...
Source: British Journal of Haematology - August 19, 2014 Category: Hematology Authors: Swaminathan P. Iyer, Joseph Taddeus Beck, A. Keith Stewart, Jatin Shah, Kevin R. Kelly, Randi Isaacs, Sanela Bilic, Suman Sen, Nikhil C. Munshi Tags: Research Paper Source Type: research

Osteoclast inhibition impairs chondrosarcoma growth and bone destruction
Abstract Because Chondrosarcoma is resistant to available chemotherapy and radiation regimens, wide resection is the mainstay in treatment, which frequently results in high morbidity and which may not prevent local recurrence. There is a clear need for improved adjuvant treatment of this malignancy. We have observed the presence of osteoclasts in the microenvironment of chondrosarcoma in human pathological specimens. We utilized the Swarm rat chondrosarcoma (SRC) model to test the hypothesis that osteoclasts affect chondrosarcoma pathogenesis. We implanted SRC tumors in tibia of Sprague‐Dawley rats and analyzed bone hist...
Source: Journal of Orthopaedic Research - August 15, 2014 Category: Orthopaedics Authors: Jesse E. Otero, Jeff W. Stevens, Allison E. Malandra, Douglas C. Fredericks, Paul R. Odgren, Joseph A. Buckwalter, Jose Morcuende Tags: Research Article Source Type: research

Chondroprotective effect of high‐dose zoledronic acid: An experimental study in a rabbit model of osteoarthritis
ABSTRACT To address the need to impact the subchondral bone‐articular cartilage interaction for the treatment of degenerative osteoarthritis (OA), bisphosphonates may be used as a means to inhibit the subchondral bone resorption. The purpose of the present study is to evaluate the chondroprotective effect of zoledronic acid (ZOL) in a model of OA. Eighteen adult male rabbits underwent an anterior cruciate ligament transection and were separated into two groups: ZOL group (n = 10) received 0.6 mg/kg intravenous injection of ZOL on day 1, 15, and 29 and placebo group (n = 8) received sali...
Source: Journal of Orthopaedic Research - August 13, 2014 Category: Orthopaedics Authors: Kalliopi Lampropoulou‐Adamidou, Ismene Dontas, Ioannis P. Stathopoulos, Lubna Khaldi, Pavlos Lelovas, John Vlamis, Ioannis K. Triantafillopoulos, Nikolaos A. Papaioannou Tags: Research Article Source Type: research

Everolimus and zoledronic acid-a potential synergistic treatment for lung adenocarcinoma bone metastasis.
Abstract Non-small-cell lung cancer (NSCLC) frequently metastasizes to bone. It is known that zoledronic acid is cytostatic to tumors, and everolimus, the inhibitor for mammalian target of the rapamycin, could inhibit many types of cancer. Herein, we evaluated the effect of zoledronic acid alone and in combination with everolimus on treating lung adenocarcinoma bone metastasis in vitro and in vivo. Mice treated with zoledronic acid in combination with everolimus had more apoptotic lung cancer cells and more cells were arrested in the G1/G0 phase. The phosphorylation of p70S6K was inhibited in the combination treat...
Source: Acta Biochimica et Biophysica Sinica - August 6, 2014 Category: Biochemistry Authors: Yu Y, Song Z, Yang S, Yang X, Zhang J, Lu S Tags: Acta Biochim Biophys Sin (Shanghai) Source Type: research

[Bone and Calcium Abnormalities in Malignancy. The treatment for cancer with bone metastases -Whether to use Zoledoronate or Denosumab for bone metastases-].
This article will focus on medical treatment for bone metastases especialy from breast cancer. PMID: 25065876 [PubMed - in process] (Source: Clinical Genitourinary Cancer)
Source: Clinical Genitourinary Cancer - August 1, 2014 Category: Cancer & Oncology Authors: Kohno N Tags: Clin Calcium Source Type: research