Genomes and Genes
Summary: Organic compounds which contain P-C-P bonds, where P stands for phosphonates or phosphonic acids. These compounds affect calcium metabolism. They inhibit ectopic calcification and slow down bone resorption and bone turnover. Technetium complexes of diphosphonates have been used successfully as bone scanning agents.
- Llombart A, Frassoldati A, Paija O, Sleeboom H, Jerusalem G, Mebis J, et al. Immediate Administration of Zoledronic Acid Reduces Aromatase Inhibitor-Associated Bone Loss in Postmenopausal Women With Early Breast Cancer: 12-month analysis of the E-ZO-FAST trial. Clin Breast Cancer. 2012;12:40-8 pubmed publisher..Immediate ZOL administration effectively prevented BMD loss and increased BMD in postmenopausal women with HR(+) EBC receiving adjuvant letrozole, regardless of BMD status at baseline. ..
- Miller P, Recker R, Reginster J, Riis B, Czerwinski E, Masanauskaite D, et al. Efficacy of monthly oral ibandronate is sustained over 5 years: the MOBILE long-term extension study. Osteoporos Int. 2012;23:1747-56 pubmed publisher..There were no tolerability concerns or new safety signals. Monthly treatment with ibandronate 100 and 150 mg is effective and well tolerated for up to 5 years in women with postmenopausal osteoporosis. ..
- Fleisher K, Jolly A, Venkata U, Norman R, Saxena D, Glickman R. Osteonecrosis of the jaw onset times are based on the route of bisphosphonate therapy. J Oral Maxillofac Surg. 2013;71:513-9 pubmed publisher..Research focusing on the clinical circumstances and physiologic events during early antiresorptive therapy may provide insight as to the critical risk factors. ..
- Morgan G, Child J, Gregory W, Szubert A, Cocks K, Bell S, et al. Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX): secondary outcomes from a randomised controlled trial. Lancet Oncol. 2011;12:743-52 pubmed publisher..Medical Research Council (London, UK), Novartis, Schering Health Care, Chugai, Pharmion, Celgene, and Ortho Biotech. ..
- Cornish J, Bava U, Callon K, Bai J, Naot D, Reid I. Bone-bound bisphosphonate inhibits growth of adjacent non-bone cells. Bone. 2011;49:710-6 pubmed publisher..It is concluded that bisphosphonates bound to a bone surface can act on adjacent non-bone cells and inhibit their growth. This greatly widens the range of potential target cells for these drugs. ..
- Santini D, Tampellini M, Vincenzi B, Ibrahim T, Ortega C, Virzi V, et al. Natural history of bone metastasis in colorectal cancer: final results of a large Italian bone metastases study. Ann Oncol. 2012;23:2072-7 pubmed publisher..00 month, respectively, P=0.009) and produced a trend toward improved overall survival versus no zoledronic acid. This study illustrates the burden of bone metastases from CRC and supports the use of zoledronic acid in this setting. ..
- Bianchi G, Czerwinski E, Kenwright A, Burdeska A, Recker R, Felsenberg D. Long-term administration of quarterly IV ibandronate is effective and well tolerated in postmenopausal osteoporosis: 5-year data from the DIVA study long-term extension. Osteoporos Int. 2012;23:1769-78 pubmed publisher..No tolerability concerns or new safety signals were observed. Treatment with IV ibandronate 2 mg bimonthly or 3 mg quarterly is effective and well tolerated for up to 5 years in women with postmenopausal osteoporosis. ..
- Puhaindran M, Farooki A, Steensma M, Hameed M, Healey J, Boland P. Atypical subtrochanteric femoral fractures in patients with skeletal malignant involvement treated with intravenous bisphosphonates. J Bone Joint Surg Am. 2011;93:1235-42 pubmed publisher..All patients in our study who had development of these fractures had prodromal symptoms of thigh pain. ..
- Yan T, Yin W, Zhou Q, Zhou L, Jiang Y, Du Y, et al. The efficacy of zoledronic acid in breast cancer adjuvant therapy: a meta-analysis of randomised controlled trials. Eur J Cancer. 2012;48:187-95 pubmed publisher..Additional studies are needed to evaluate the value of adjuvant treatment of zoledronic acid in premenopausal counterparts, differing disease stages and various pathological types of breast cancer. ..
- Dore R. Data from extension trials: denosumab and zoledronic acid. Curr Osteoporos Rep. 2012;10:16-21 pubmed publisher..As treatment of osteoporosis may extend for many years, the collection of long-term efficacy and safety data is warranted. This paper discusses data from the extension trials of denosumab and zoledronic acid. ..
- Peterson J, Bedrossian E. Bisphosphonate-associated orbital inflammation--a case report and review. Orbit. 2012;31:119-23 pubmed publisher..Despite a paucity of rechallenge data, available reports suggest that development of orbital inflammation does not necessarily exclude patients from future bisphosphonate use. ..
- Hamilton E, Clay T, Blackwell K. New perspectives on zoledronic acid in breast cancer: potential augmentation of anticancer immune response. Cancer Invest. 2011;29:533-41 pubmed publisher..These new data provide growing insight into a potential mechanism of action for some of the anticancer activity demonstrated by zoledronic acid in breast cancer clinical trials. ..
- Wehrhan F, Hyckel P, Guentsch A, Nkenke E, Stockmann P, Schlegel K, et al. Bisphosphonate-associated osteonecrosis of the jaw is linked to suppressed TGF?1-signaling and increased Galectin-3 expression: a histological study on biopsies. J Transl Med. 2011;9:102 pubmed publisher..To discriminate between BRONJ-specific impairments in TGF?1 signaling and secondary inflammatory changes, the results were compared to the expression of TGF?1 and Galectin-3 in mucosal tissues with osteoradionecrosis...
- Yu Y, Lieu S, Hu D, Miclau T, Colnot C. Site specific effects of zoledronic acid during tibial and mandibular fracture repair. PLoS ONE. 2012;7:e31771 pubmed publisher..This may predispose mandible bone to adverse effects of ZA in disease conditions. These results also imply that therapeutic effects of ZA may need to be optimized using time and dose-specific treatments in cranial versus long bones...
- Safra T, Bernstein Molho R, Greenberg J, Pelles Avraham S, Stephansky I, Sarid D, et al. The protective effect of zoledronic acid on bone loss in postmenopausal women with early breast cancer treated with sequential tamoxifen and letrozole: a prospective, randomized, phase II trial. Oncology. 2011;81:298-305 pubmed publisher..The addition of ZOL to letrozole was safe and efficacious in maintaining LS BMD in postmenopausal patients with hormone receptor-positive breast cancer and who were receiving letrozole following 2.5-3 years of tamoxifen. ..
- Qi M, Hu J, Li J, Li J, Dong W, Feng X, et al. Effect of zoledronate acid treatment on osseointegration and fixation of implants in autologous iliac bone grafts in ovariectomized rabbits. Bone. 2012;50:119-27 pubmed publisher..Combined systemic and local use of ZOL exerts best effects when compared to their single use...
- Ho Y, Lin J, Wu C. Oral bisphosphonates and risk of esophageal cancer: a dose-intensity analysis in a nationwide population. Cancer Epidemiol Biomarkers Prev. 2012;21:993-5 pubmed publisher..Our data suggest that bisphosphonates are not likely risk factors for esophageal cancer in Taiwan. The study shows no evidence of an association between bisphosphonate use and esophageal cancer risk from Asian perspective. ..
- Compston J. Pathophysiology of atypical femoral fractures and osteonecrosis of the jaw. Osteoporos Int. 2011;22:2951-61 pubmed publisher..Other possible pathogenetic factors include suppression of bone turnover, altered immune status and adverse effects of bisphosphonates on the oral mucosa...
- Zhao X, Xu X, Zhang Q, Jia Z, Sun S, Zhang J, et al. Prognostic and predictive value of clinical and biochemical factors in breast cancer patients with bone metastases receiving "metronomic" zoledronic acid. BMC Cancer. 2011;11:403 pubmed publisher..Patients with baseline serum NTx of more than 18 nM BCE might benefit more from weekly low-dose of zoledronic acid. ClinicalTrials.gov unique identifier: ClinicalTrials.gov: NCT00524849. ..
- Martin M, Bell R, Bourgeois H, Brufsky A, Diel I, Eniu A, et al. Bone-related complications and quality of life in advanced breast cancer: results from a randomized phase III trial of denosumab versus zoledronic acid. Clin Cancer Res. 2012;18:4841-9 pubmed..We evaluated further results from this study related to skeletal complications and health-related quality of life (HRQoL)...
- Thurnher M, Nussbaumer O, Gruenbacher G. Novel aspects of mevalonate pathway inhibitors as antitumor agents. Clin Cancer Res. 2012;18:3524-31 pubmed publisher..This review focuses on these novel capabilities of mevalonate pathway inhibitors to beneficially affect tumor biology and contribute to tumor immune surveillance. ..
- Takiguchi S, Nishino Y, Inoue K, Ikeda M, Kataoka Y, Matsusue K, et al. The bisphosphonate incadronate inhibits intraperitoneal dissemination in an in vivo pancreatic cancer model. Oncol Rep. 2012;28:111-6 pubmed publisher..The potent effects of incadronate in reducing tumor burden and ascites suggest that it will be of value in regimens for the treatment of pancreatic cancer. ..
- Silverman S, Christiansen C. Individualizing osteoporosis therapy. Osteoporos Int. 2012;23:797-809 pubmed publisher..It will be important to incorporate newer agents (e.g., bazedoxifene, tissue selective estrogen complex) into this individualized treatment paradigm to optimize clinical outcomes in patients with osteoporosis. ..
- Aapro M, Coleman R. Bone health management in patients with breast cancer: current standards and emerging strategies. Breast. 2012;21:8-19 pubmed publisher..This review summarizes the available data for bisphosphonate benefits in both the adjuvant and metastatic settings in the context of evolving clinical practice. ..
- Koeppen V, Schilcher J, Aspenberg P. Atypical fractures do not have a thicker cortex. Osteoporos Int. 2012;23:2893-6 pubmed publisher..The concept of a generally increased cortical thickness in patients with atypical fractures should be reconsidered. ..
- Abtahi J, Tengvall P, Aspenberg P. A bisphosphonate-coating improves the fixation of metal implants in human bone. A randomized trial of dental implants. Bone. 2012;50:1148-51 pubmed publisher..012). In conclusion, a thin, bisphosphonate-eluting fibrinogen coating might improve the fixation of metal implants in human bone. This might lead to new possibilities for orthopedic surgery in osteoporotic bone and for dental implants. ..
- Thaler R, Spitzer S, Karlic H, Berger C, Klaushofer K, Varga F. Ibandronate increases the expression of the pro-apoptotic gene FAS by epigenetic mechanisms in tumor cells. Biochem Pharmacol. 2013;85:173-85 pubmed publisher..In conclusion the shown epigenetic mechanism underlying the anti-neoplastic activity of farnesyl-transferase-inhibition, also explains the clinical success of other drugs, which target this pathway. ..
- Koto K, Murata H, Kimura S, Sawai Y, Horie N, Matsui T, et al. Zoledronic acid significantly enhances radiation?induced apoptosis against human fibrosarcoma cells by inhibiting radioadaptive signaling. Int J Oncol. 2013;42:525-34 pubmed publisher..This sequential treatment also increased the generation of reactive oxygen species (ROS). These results suggest that the combination of ZOL with IR may be beneficial in treating patients with soft tissue sarcoma...
- Huang C, Zheng C, Wu C, Lo L, Lu K, Chu P. Effects of pamidronate and calcitriol on the set point of the parathyroid gland in postmenopausal hemodialysis patients with secondary hyperparathyroidism. Nephron Clin Pract. 2012;122:93-101 pubmed publisher..These findings suggest that in considering pamidronate treatment in postmenopausal patients with osteoporosis receiving HD, it might be safer to add calcitriol to prevent the increased PTH secretion. ..
- Basi D, Hughes P, Thumbigere Math V, Sabino M, Mariash A, Lunos S, et al. Matrix metalloproteinase-9 expression in alveolar extraction sockets of Zoledronic acid-treated rats. J Oral Maxillofac Surg. 2011;69:2698-707 pubmed publisher..RANKL is increased in ZA-treated rats, which suggests that increased MMP-9 expression is due, in part, to augmented RANKL expression. ..
- Cardwell C, Abnet C, Veal P, Hughes C, Cantwell M, Murray L. Exposure to oral bisphosphonates and risk of cancer. Int J Cancer. 2012;131:E717-25 pubmed publisher..Although reductions in breast and colorectal cancer incidence were observed in bisphosphonate users it is unclear, particularly for breast cancer, to what extent confounding by low bone density may explain the association. ..
- Doi Y, Miyazaki M, Yoshiiwa T, Hara K, Kataoka M, Tsumura H. Manipulation of the anabolic and catabolic responses with BMP-2 and zoledronic acid in a rat femoral fracture model. Bone. 2011;49:777-82 pubmed publisher..Our results suggest that this combination facilitates bone healing and has potential clinical application. ..
- Coleman R, Marshall H, Cameron D, Dodwell D, Burkinshaw R, Keane M, et al. Breast-cancer adjuvant therapy with zoledronic acid. N Engl J Med. 2011;365:1396-405 pubmed publisher..Funded by Novartis Pharmaceuticals and the National Cancer Research Network; AZURE Current Controlled Trials number, ISRCTN79831382.). ..
- Nicol A, Tokuyama H, Mattarollo S, Hagi T, Suzuki K, Yokokawa K, et al. Clinical evaluation of autologous gamma delta T cell-based immunotherapy for metastatic solid tumours. Br J Cancer. 2011;105:778-86 pubmed publisher..Therapy with aminobisphosphonate-activated V?9V?2 T cells is feasible and well tolerated, but therapeutic benefits appear only likely when used in combination with other therapies. ..
- Dominguez L, Di Bella G, Belvedere M, Barbagallo M. Physiology of the aging bone and mechanisms of action of bisphosphonates. Biogerontology. 2011;12:397-408 pubmed publisher..g., risedronate) may allow better access to osteocyte network. Effects of BPs on bone senescence, cancer cells apoptosis and prevention of cardiovascular calcifications may open new avenues for biogerontological research. ..
- Tsubaki M, Itoh T, Satou T, Imano M, Komai M, Ogawa N, et al. Nitrogen-containing bisphosphonates induce apoptosis of hematopoietic tumor cells via inhibition of Ras signaling pathways and Bim-mediated activation of the intrinsic apoptotic pathway. Biochem Pharmacol. 2013;85:163-72 pubmed publisher..This is the first study to show that the specific molecular pathways of N-BP-induced apoptosis. ..
- Solomayer E, Gebauer G, Hirnle P, Janni W, Luck H, Becker S, et al. Influence of zoledronic acid on disseminated tumor cells in primary breast cancer patients. Ann Oncol. 2012;23:2271-7 pubmed publisher..9 ± 0.8 DTCs in the control group. In addition, ZOL was generally well tolerated. Treatment with ZOL improves elimination of DTCs. Further studies are needed to determine whether the reduction in DTCs by ZOL provides clinical benefit. ..
- Okazaki R, Hagino H, Ito M, Sone T, Nakamura T, Mizunuma H, et al. Efficacy and safety of monthly oral minodronate in patients with involutional osteoporosis. Osteoporos Int. 2012;23:1737-45 pubmed publisher..Safety profiles were also comparable. Minodronate at monthly doses of 30 or 50 mg has similar efficacy to the daily 1 mg dose in terms of BMD and bone turnover markers with similar tolerability. ..
- Serpa Neto A, Tobias Machado M, Esteves M, Senra M, Wroclawski M, Fonseca F, et al. Bisphosphonate therapy in patients under androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2012;15:36-44 pubmed publisher..16%, respectively. This benefit of bone loss prevention could be reached without major side effects (cardiovascular or gastrointestinal events). Bisphosphonates are effective in preventing bone loss in patients with PC who are under ADT. ..
- Kuiper J, Forster C, Sun C, Peel S, Glogauer M. Zoledronate and pamidronate depress neutrophil functions and survival in mice. Br J Pharmacol. 2012;165:532-9 pubmed publisher..This work suggests that bisphosphonates have the potential to depress the innate immune system for a prolonged time, possibly contributing to the pathogenesis of BRONJ. ..
- Bergner R. Bisphosphonate therapy in renal osteodystrophy--a review. J Nephrol. 2013;26:450-5 pubmed publisher..However, large randomized placebo-controlled trials are required before the use of bisphosphonates in renal osteopathy can be generally recommended. ..
- Khalili H, Huang E, Ogino S, Fuchs C, Chan A. A prospective study of bisphosphonate use and risk of colorectal cancer. J Clin Oncol. 2012;30:3229-33 pubmed publisher..In a large prospective cohort, we did not observe an association between long-term use of bisphosphonates and risk of colorectal cancer. ..
- Coleman R, de Boer R, Eidtmann H, Llombart A, Davidson N, Neven P, et al. Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results. Ann Oncol. 2013;24:398-405 pubmed publisher..46; P = 0.0334). Immediate zoledronate in postmenopausal women receiving letrozole preserved BMD and is associated with improved DFS compared with letrozole alone. Clinical Trials Registration No NCT00171340. ..
- Welton J, Morgan M, Marti S, Stone M, Moser B, Sewell A, et al. Monocytes and ?? T cells control the acute-phase response to intravenous zoledronate: insights from a phase IV safety trial. J Bone Miner Res. 2013;28:464-71 pubmed publisher..These findings have diagnostic and prognostic implications for patients with and without malignancy and are relevant for V?9/V?2 T-cell-based immunotherapy approaches. ..
- Schindeler A, Birke O, Yu N, Morse A, Ruys A, Baldock P, et al. Distal tibial fracture repair in a neurofibromatosis type 1-deficient mouse treated with recombinant bone morphogenetic protein and a bisphosphonate. J Bone Joint Surg Br. 2011;93:1134-9 pubmed publisher..5% (p < 0.07). These data support the concept that preventing bone loss in combination with anabolic stimulation may improve the outcome following surgical treatment for children with congenital pseudarthosis of the tibia and NF1. ..
- Lipton A, Cook R, Brown J, Body J, Smith M, Coleman R. Skeletal-related events and clinical outcomes in patients with bone metastases and normal levels of osteolysis: exploratory analyses. Clin Oncol (R Coll Radiol). 2013;25:217-26 pubmed publisher..However, the disease course has not been well characterised in patients with bone metastases but normal NTX levels. Therefore, the aim of this study was to evaluate the patterns of skeletal morbidity in patients with normal NTX levels...
- Norton J, Hayashi T, Crain B, Corr M, Carson D. Role of IL-1 receptor-associated kinase-M (IRAK-M) in priming of immune and inflammatory responses by nitrogen bisphosphonates. Proc Natl Acad Sci U S A. 2011;108:11163-8 pubmed publisher..In vivo, this property renders the NBPs as effective adjuvants that enhance both cellular and antibody responses to antigens. ..
- Shane E, Burr D, Abrahamsen B, Adler R, Brown T, Cheung A, et al. Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2014;29:1-23 pubmed publisher..When BPs are stopped, risk of an AFF may decline. Lower limb geometry and Asian ethnicity may contribute to the risk of AFFs. There is inconsistent evidence that teriparatide may advance healing of AFFs...
- Ott S. Bisphosphonate safety and efficacy in chronic kidney disease. Kidney Int. 2012;82:833-5 pubmed publisher..The effects on vascular calcifications need further study, because low bone turnover might exacerbate vascular calcifications in patients with CKD. Even if bisphosphonates prove safe, their efficacy in this population is uncertain. ..
- Marra M, Salzano G, Leonetti C, Porru M, Franco R, Zappavigna S, et al. New self-assembly nanoparticles and stealth liposomes for the delivery of zoledronic acid: a comparative study. Biotechnol Adv. 2012;30:302-9 pubmed publisher..The effects of the NPs were also higher in terms of neo-angiogenesis inhibition. These results suggest the future preclinical development of ZOL-encapsulating NPs in the treatment of human cancer. ..