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Rocío López-Posadas, Cristina Mascaraque, Raquel González, María D Suárez, Antonio Zarzuelo, Olga Martínez-Augustin, Fermín Sánchez de Medina
BACKGROUND: Statins have antiinflammatory effects at the cardiovascular level because of inhibition of prenylation, which also probably underlies their therapeutic effects in preclinical models of inflammatory bowel disease. Another inhibitor of prenylation, namely alendronate, reduces colitis in rodents. In this study, we aim to explore the therapeutic potential of second-generation, nitrogen-containing bisphosphonates in 3 preclinical models of colitis. METHODS: The trinitrobenzenesulfonic acid and dextran sulfate sodium models of rat colitis and the adoptive lymphocyte transfer model of colitis in mice were used...
November 2016: Inflammatory Bowel Diseases
Jonathan Karnon, Ainul Shakirah Shafie, Nneka Orji, Sofoora Kawsar Usman
OBJECTIVE: Zoledronic acid and denosumab were funded by the Australian government for the management of osteoporosis at an equivalent price to alendronate. The price of alendronate has declined by around 65 %, but the price of the other two therapies has remained stable. Using data published since the listing, this paper reports current estimates of the value of denosumab compared to alendronate from an Australian health system perspective. METHODS: A cohort-based state transition model was developed that predicted changes in bone mineral density (BMD), and calibrated fracture probabilities as a function of BMD, age and previous fracture to estimate differences in costs and QALYs gained over a 10-year time horizon...
2016: Cost Effectiveness and Resource Allocation: C/E
Qing Chang, Rui Geng, Shanzheng Wang, Ding Qu, Xiangfei Kong
Treatment for multiple myeloma (MM) with a combined strategy of bone and tumor targeting remains a crucial technical challenge due to the incorporation of various functional components into one single system. Here, we developed dioleoyl phosphatidic acid (DOPA)-based paclitaxel (PTX)-loaded liposomes with modifications of alendronate and transferrin (Ald-/Tf-modified PTX-L), which were capable of bone affinity mediated by phosphate groups in DOPA and alendronate, and tumor targeting offered by transferrin. Ald-/Tf-modified PTX-L had clear and well-defined spherical shape with an intermediated size of 118...
October 17, 2016: Drug Delivery
Silvia Panzavolta, Paola Torricelli, Sonia Casolari, Annapaola Parrilli, Sofia Amadori, Milena Fini, Adriana Bigi
The systemic administration of bisphosphonates (BPs) for the treatment of metabolic diseases characterized by abnormal bone loss suffers from several adverse side effects, which can be reduced by implementation of alternative modes of administration. In this work, glutaraldehyde cross-linked gelatin scaffolds are proposed as delivery systems of calcium alendronate monohydrate (CaAL•H2 O). The 3D highly porous scaffolds display a relevant interconnected porosity (>94%), independently from CaAL•H2 O content (0, 3, and 6 wt%)...
October 17, 2016: Macromolecular Bioscience
Junwen Zhou, Tiansheng Wang, Xilan Zhao, Donald R Miller, Suodi Zhai
INTRODUCTION: Osteoporosis is an under-recognized problem threatening men. Bisphosphonates are the main treatment but their comparative efficacy is unclear for men with osteoporosis. Therefore, we performed this systematic review with network meta-analyses to summarize the evidence of comparative efficacy of bisphosphonates in men with osteoporosis. METHODS: We completed network meta-analyses with a frequentist model to compare the efficacy of different bisphosphonates...
June 2016: Rheumatol Ther
Dong Zheng, Koon Gee Neoh, En-Tang Kang
Immobilization of alendronate on orthopedic implants offers the possibility of enhancing osteogenesis without potentially adverse effects associated with systemic administration of this drug. In this work, alendronate was immobilized on titanium (Ti) via either its phosphate (Method 1) or amino (Method 2) groups, and responses of osteoblasts and human mesenchymal stem cells (hMSCs) on these surfaces were investigated. These modified substrates have similar surface roughness and are negatively charged. With similar amounts of immobilized alendronate, these two types of modified substrates showed comparable osteogenic stimulating effects in enhancing osteoblasts' alkaline phosphatase (ALP) activity and calcium deposition for the first 10days...
October 8, 2016: Journal of Colloid and Interface Science
M Yoshimura, K Moriwaki, S Noto, T Takiguchi
: Although an osteoporosis screening program has been implemented as a health promotion project in Japan, its cost-effectiveness has yet to be elucidated fully. We performed a cost-effectiveness analysis and found that osteoporosis screening and treatment would be cost-effective for Japanese women over 60 years. INTRODUCTION: The purpose of this study was to estimate the cost-effectiveness of osteoporosis screening and drug therapy in the Japanese healthcare system for postmenopausal women with no history of fracture...
October 14, 2016: Osteoporosis International
R Y van der Velde, C E Wyers, E Teesselink, P P M M Geusens, J P W van den Bergh, F de Vries, C Cooper, N C Harvey, T P van Staa
INTRODUCTION: Given the expected increase in the number of patients with osteoporosis and fragility fractures it is important to have concise information on trends in prescription rates of anti-osteoporosis drugs (AOD). METHODS: We undertook a retrospective observational study using the UK Clinical Practice Research Datalink (CPRD) in the UK between 1990 and 2012 in subjects 50years or older, stratified by age, sex, geographic region and ethnicity. Yearly prescription incidence rates of any AOD and of each specific AOD were calculated as the number of patients first prescribed these AODs per 10,000person-years (py)...
October 11, 2016: Bone
Diego H Díaz, Julieta A Rodas, Clarisa E Bozzini, Patricia M Mandalunis, Natalia D Escudero
Bisphosphonates are the first choice therapy for the pharmaco logical treatment of osteoporosis. Following reports of cases of bisphosphonaterelated osteonecrosis of the jaw and atypical femur fracture, the safety of longterm use of bisphosphonates has been evaluated, resulting in the proposal of strontium as an alternative drug. No experimental study using a sequential administration design has been reported to date. Hence, the aim of this study was to evaluate the effect on bone tissue of ovariectomized rats of administration of alendronate followed by strontium ranelate...
September 2016: Acta Odontológica Latinoamericana: AOL
Zohaib Akram, Tariq Abduljabbar, Sergio Varela Kellesarian, Mohamed Ibrahim Abu Hassan, Fawad Javed, Fahim Vohra
AIMS: The aim of this systematic review was to assess the efficacy of bisphosphonate therapy as an adjunct to scaling and root planing (SRP) in the management of periodontitis. METHODS: Databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Cochrane Oral Health Group Trials Register databases) were searched up to and including July 2016. The primary outcome was probing depth (PD), and the secondary outcomes were changes in clinical attachment level (CAL) and bone defect (BD) fill...
October 8, 2016: British Journal of Clinical Pharmacology
Christian Schem, Robert J Tower, Philipp Kneissl, Anna-Christina Rambow, Graeme M Campbell, Christine Desel, Timo Damm, Thorsten Heilmann, Sabine Fuchs, Maaz Zuharya, Anna Trauzold, Claus C Glüer, Sarah Schott, Sanjay Tiwari
Bisphosphonates have effects which are anti-resorptive, anti-tumor and anti-apoptotic to osteoblasts and osteocytes, but an effective means of eliciting these multiple activities in the treatment of bone metastases has not been identified. Antimetabolite-bisphosphonate conjugates have potential for improved performance as a class of bone specific anti-neoplastic drugs. The primary objective of the study was to determine whether an antimetabolite-bisphosphonate conjugate will preserve bone formation concomitant with anti-resorptive and anti-tumor activity...
October 7, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Dr Dharmendra Kanoriya, Dr A R Pradeep, Dr Vibhuti Garg, Dr Sandeep Singhal
BACKGROUND: Different materials have been instigated for renewal of lost supporting periodontal structures and tested for furcation defects treatment. Platelet-rich fibrin (PRF) is a pool of growth promoting factors and cytokines which promotes bone regeneration and maturation of soft tissue. Alendronate (ALN), an influential member of bisphosphonate group is known to enhance osteoblastogenesis and inhibits osteoclastic bone resorption, thus promoting tissue regeneration. This randomized trial was done to assess the effectiveness of PRF and 1% ALN gel combination in mandibular degree II furcation defects treatment in comparison to PRF and access therapy alone...
October 7, 2016: Journal of Periodontology
Silvina R Mastaglia, Gabriel Aguilar, Beatriz Oliveri
Bisphosphonates (BPs) are the most widely used drugs to treat osteoporosis. However, recent reports associated to long-term BPs use with atypical low-impact fractures and prodromal pain. It is estimated that 26% of the cases of atypical fractures associated with the long-term use of BPs show delayed healing or nonunion. Teriparatide [PTH1-34] (TPTD) is an anabolic drug shown to be effective in stimulating bone formation. The aim was to describe the course of a right diaphyseal femoral fracture sustained by a patient on long-term BPs treatment...
June 2016: Eur J Rheumatol
Pablo H Cutini, María B Rauschemberger, Marisa J Sandoval, Virginia L Massheimer
In this work we investigate whether, despite the procalcific action of alendronate on bone, the drug would be able to regulate in vitro the main cellular events that take part in atherosclerotic lesion generation. Using endothelial cell cultures we showed that Alendronate (1-50μM) acutely enhances nitric oxide production (10-30min). This stimulatory action of the bisphosphonate involves the participation of MAPK signaling transduction pathway. Under inflammatory stress, the drug reduces monocytes and platelets interactions with endothelial cells induced by lipopolysaccharide...
October 2, 2016: Journal of Molecular and Cellular Cardiology
Ming-Song Lee, Chao-Ming Su, Jih-Chao Yeh, Pei-Ru Wu, Tien-Yao Tsai, Shyh-Liang Lou
Osteoporosis is a result of imbalance between bone formation by osteoblasts and resorption by osteoclasts (OCs). In the present study, we investigated the potential of limiting the aggravation of osteoporosis by reducing the activity of OCs through thermolysis. The proposed method is to synthesize bisphosphonate (Bis)-conjugated iron (II, III) oxide (Fe3O4) nanoparticles and incorporate them into OCs. The cells should be subsequently exposed to radiofrequency (RF) to induce thermolysis. In this study, particles of Fe3O4 were first synthesized by chemical co-precipitation and then coated with dextran (Dex)...
2016: International Journal of Nanomedicine
Gad Rennert, Mila Pinchev, Naomi Gronich, Walid Saliba, Anath Flugelman, Idit Lavi, Hadassah Goldberg, Georgeta Fried, Mariana Steiner, Arie Bitterman, Keren Landsman, Hedy Rennert
PURPOSE: Bisphosphonates are used for treatment or prevention of osteoporosis and of bone metastases. The use of oral bisphosphonates was suggested to be associated with reduced risk of developing breast cancer and their positive influence on breast cancer survival was only demonstrated with third generation bisphosphonates. We studied the association of use of oral bisphosphonates after breast cancer diagnosis on overall and breast cancer survival. EXPERIMENTAL DESIGN: A nested case-control analysis was performed using data from the population-based Breast Cancer in Northern Israel Study (BCINIS)...
September 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Pingju Ge, Fugeng Sheng, Yiguang Jin, Li Tong, Lina Du, Lei Zhang, Ning Tian, Gongjie Li
Magnetic resonance (MR) is currently used for diagnosis of osteosarcoma but not well even though contrast agents are administered. Here, we report a novel bone-targeted MR imaging contrast agent, Gd2-diethylenetriaminepentaacetate-bis(alendronate) (Gd2-DTPA-BA) for the diagnosis of osteosarcoma. It is the conjugate of a bone cell-seeking molecule (i.e., alendronate) and an MR imaging contrast agent (i.e., Gd-DTPA). Its physicochemical parameters were measured, including pKa, complex constant, and T1 relaxivity...
September 25, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Sung Eun Kim, Young-Pil Yun, Kyu-Sik Shim, Hak-Jun Kim, Kyeongsoon Park, Hae-Ryong Song
The aim of this study was to evaluate the in vitro osteogenic effects and in vivo new bone formation of three-dimensional (3D) printed alendronate (Aln)-releasing poly(caprolactone) (PCL) (Aln/PCL) scaffolds in rat tibial defect models. 3D printed Aln/PCL scaffolds were fabricated via layer-by-layer deposition. The fabricated Aln/PCL scaffolds had high porosity and an interconnected pore structure and showed sustained Aln release. In vitro studies showed that MG-63 cells seeded on the Aln/PCL scaffolds displayed increased alkaline phosphatase (ALP) activity and calcium content in a dose-dependent manner when compared with cell cultures in PCL scaffolds...
2016: Biomedical Materials
Naomi O Hodgins, Wafa' T Al-Jamal, Julie T-W Wang, Ana C Parente-Pereira, Mao Liu, John Maher, Khuloud T Al-Jamal
Nitrogen-containing bisphosphonates (N-BP), including zoledronic acid (ZOL) and alendronate (ALD), have been proposed as sensitisers in γδ T cell immunotherapy in pre-clinical and clinical studies. Therapeutic efficacy of N-BPs is hampered by their rapid renal excretion and high affinity for bone. Liposomal formulations of N-BP have been proposed to improve accumulation in solid tumours. Liposomal ALD (L-ALD) has been suggested as a suitable alternative to liposomal ZOL (L-ZOL), due to unexpected mice death experienced in pre-clinical studies with the latter...
November 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Liping Wang, Tian-Zhi Guo, Tzuping Wei, Wen-Wu Li, Xiaoyou Shi, J David Clark, Wade S Kingery
BACKGROUND: Bisphosphonates are used to prevent the bone loss and fractures associated with osteoporosis, bone metastases, multiple myeloma, and osteogenesis deformans. Distal limb fractures cause regional bone loss with cutaneous inflammation and pain in the injured limb that can develop into complex regional pain syndrome (CRPS). Clinical trials have reported that antiresorptive bisphosphonates can prevent fracture-induced bone loss, inhibit serum inflammatory cytokine levels, and alleviate CRPS pain...
October 2016: Anesthesia and Analgesia
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