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https://www.readbyqxmd.com/read/28107624/tocilizumab-alendronate-conjugate-for-treatment-of-rheumatoid-arthritis
#1
Hwiwon Lee, Suk Ho Bhang, Jeong Ho Lee, Hyemin Kim, Sei Kwang Hahn
An autoimmune disease of rheumatoid arthritis (RA) causes severe inflammation on the synovial membrane, which results in the destruction of articular cartilage and bone. Here, Tocilizumab (TCZ) - Alendronate (ALD) conjugate is synthesized for the early intervention of RA. A humanized monoclonal antibody of TCZ shows an immunosuppressive effect, targeting interleukin-6 (IL-6) receptor in the RA pathogenesis. ALD is an anti-inflammatory bisphosphonate drug which can bind to the exposed bone surface. ALD is conjugated selectively to N-glycan on Fc region of TCZ using a chemical linker of 3-(2-pyridyldithio) propionyl hydrazide (PDPH) - poly(ethylene glycol) - N-hydroxysuccinimide (PDPH-PEG-NHS)...
January 20, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28107028/interrelationship-of-clinical-radiographic-and-hematological-features-in-patients-under-bisphosphonate-therapy
#2
Valesca Sander Koth, Maria Antonia Figueiredo, Fernanda Gonçalves Salum, Karen Cherubini
OBJECTIVE: To analyze clinical, radiographic and hematological aspects of patients under bisphosphonate therapy. METHODS: A retrospective study was conducted where the records of patients taking bisphosphonates were analyzed considering the occurrence of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Evaluation included panoramic and periapical radiographies, hematological exams and clinical features. Radiographies were analyzed determining the presence or absence of bone sclerosis, osteolysis, persisting alveolar socket, narrowing of the mandibular canal, widening of the periodontal ligament space, periradicular radiolucency, sequestrum, and thickening of the lamina dura...
January 20, 2017: Dento Maxillo Facial Radiology
https://www.readbyqxmd.com/read/28105276/covalent-guanosine-mimetic-inhibitors-of-g12c-kras
#3
Yuan Xiong, Jia Lu, John Hunter, Lianbo Li, David Scott, Hwan Geun Choi, Sang Min Lim, Anuj Manandhar, Sudershan Gondi, Taebo Sim, Kenneth D Westover, Nathanael S Gray
Ras proteins are members of a large family of GTPase enzymes that are commonly mutated in cancer where they act as dominant oncogenes. We previously developed an irreversible guanosine-derived inhibitor, SML-8-73-1, of mutant G12C RAS that forms a covalent bond with cysteine 12. Here we report exploration of the structure-activity relationships (SAR) of hydrolytically stable analogues of SML-8-73-1 as covalent G12C KRAS inhibitors. We report the discovery of difluoromethylene bisphosphonate analogues such as compound 11, which, despite exhibiting reduced efficiency as covalent G12C KRAS inhibitors, remove the liability of the hydrolytic instability of the diphosphate moiety present in SML-8-73-1 and provide the foundation for development of prodrugs to facilitate cellular uptake...
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28105116/computer-assisted-quantitative-evaluation-of-bisphosphonate-treatment-for-paget-s-disease-of-bone-using-the-bone-scan-index
#4
Satoshi Nagano, Shunsuke Nakamura, Hirofumi Shimada, Masahiro Yokouchi, Takao Setoguchi, Yasuhiro Ishidou, Hiromi Sasaki, Setsuro Komiya
The purpose of the present study was to analyze the effect of treatment of Paget's disease of bone (PDB) with bone scintigraphy using a computer-assisted diagnosis system (BONENAVI) that quantitatively evaluates bone metabolism. Seven patients with PDB (three male, four female; average age, 60 years; age range, 33-80 years) underwent bone scintigraphy and measurement of serum alkaline phosphatase (ALP), bone-specific ALP (BAP), serum cross-linked N-telopeptide (NTx) of type I collagen, urinary NTx, and deoxypyridinoline (DPD) before and after bisphosphonate treatment...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28101496/medication-related-osteonecrosis-of-the-jaw-a-preliminary-retrospective-study-of-130-patients-with-multiple-myeloma
#5
Woo-Sung Choi, Jae-Il Lee, Hyun-Joong Yoon, Chang-Ki Min, Sang-Hwa Lee
BACKGROUND: Multiple myeloma (MM) is characterized by a neoplastic proliferation of plasma cells primarily in the bone marrow. Bisphosphonates (BP) are used as supportive therapy in the management of MM. This study aimed to analyze the incidence, risk factors, and clinical outcomes of medication-related necrosis of the jaw (MRONJ) in MM patients. METHODS: One hundred thirty MM patients who had previous dental evaluations were retrospectively reviewed. Based on several findings, we applied the staging and treatment strategies on MRONJ...
December 2017: Maxillofacial Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28099754/addressing-the-crisis-in-the-treatment-of-osteoporosis-a-path-forward
#6
Sundeep Khosla, Jane A Cauley, Juliet Compston, Douglas P Kiel, Clifford Rosen, Kenneth G Saag, Elizabeth Shane
Considerable data and media attention have highlighted a potential "crisis" in the treatment of osteoporosis. Specifically, despite the availability of several effective drugs to prevent fractures, many patients who need pharmacological therapy are either not being prescribed these medications or if prescribed a medication, are simply not taking it. Although there are many reasons for this "gap" in the treatment of osteoporosis, a major factor is physician and patient concerns over the risk of side effects, especially atypical femur fractures (AFFs) related to bisphosphonate (and perhaps other antiresorptive) drug therapy...
December 29, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28099343/efficacy-and-safety-of-bisphosphonates-in-management-of-low-bone-density-in-inflammatory-bowel-disease-a-meta-analysis
#7
Liwei Yao, Haiqing Wang, Wenwei Dong, Zhenxin Liu, Haijiao Mao
This study aims to determine whether bisphosphonates are safe, as well as effective against bone mineral loss in inflammatory bowel disease (IBD). A computerized search of electronic databases from 1966 to 2016 was performed. Randomized controlled trials (RCTs) were included in this review to evaluate the role of bisphosphonates in the management of osteoporosis in IBD patients. A revised 7-point Jadad scale was used to evaluate the quality of each study. Overall, 13 RCTs and 923 patients met the inclusion criteria of this meta-analysis...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28098117/denosumab-for-the-treatment-of-bisphosphonate-resistant-hypercalcemia-in-a-hemodialysis-patient
#8
Omar Dahmani, Christine Sophoclis, Malika Kebir, Djemai Bouguern, Aboubacry Sakho, Pascale Demarchi
The acronym of malignancy, iatrogenic, intoxication and immobilization, sarcoidosis, hyperparathyroidism and hyperthyroidism, milk-alkali syndrome, and paget is very helpful in diagnosing hypercalcemia. We report on a 94-year-old patient with history of end-stage renal failure secondary to benign nephroangiosclerosis, who was on maintenance hemodialysis during dialysis, his blood chemistry revealed mild hypercalcemia (2.66 mmol/L) with normal level of intact primary hyperparathyroidism (32.37 ng/mL) mandating the discontinuation of Vitamin D[3]...
January 2017: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/28097725/increased-cortical-porosity-in-women-with-hip-fracture
#9
D Sundh, A G Nilsson, M Nilsson, L Johansson, D Mellström, M Lorentzon
BACKGROUND: Hip fractures cause increased mortality and disability and consume enormous healthcare resources. Only 46% of hip fracture patients have osteoporosis at the total hip according to dual-energy X-ray absorptiometry (DXA) measurement. Cortical porosity increases with ageing and is believed to be important for bone strength. OBJECTIVE: To investigate whether older women with hip fracture have higher cortical porosity than controls, and if so whether this difference is independent of clinical risk factors and areal bone mineral density (aBMD)...
January 18, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28094562/effects-of-bisphosphonate-administration-on-cleft-bone-graft-in-a-rat-model
#10
Nicole Cheng, Juyoung Park, Jeffrey Olson, Taewoo Kwon, Deborah Lee, Rachel Lim, Sandy Ha, Reuben Kim, Xinli Zhang, Kang Ting, Sotirios Tetradis, Christine Hong
OBJECTIVE:   Bone grafts in patients with cleft lip and palate can undergo a significant amount of resorption. The aim of this study was to investigate the effects of bisphosphonates (BPs) on the success of bone grafts in rats. DESIGN:   Thirty-five female 15-week-old Fischer F344 Inbred rats were divided into the following experimental groups, each receiving bone grafts to repair an intraoral CSD: (1) Graft/saline: systemic administration of saline and (2) systemic administration of zoledronic acid immediately following surgery (graft/BP/T0), (3) 1 week postoperatively (graft/BP/T1), and (4) 3 weeks postoperatively (graft/BP/T2)...
January 17, 2017: Cleft Palate-craniofacial Journal
https://www.readbyqxmd.com/read/28093634/international-osteoporosis-foundation-and-european-calcified-tissue-society-working-group-recommendations-for-the-screening-of-adherence-to-oral-bisphosphonates
#11
A Diez-Perez, K E Naylor, B Abrahamsen, D Agnusdei, M L Brandi, C Cooper, E Dennison, E F Eriksen, D T Gold, N Guañabens, P Hadji, M Hiligsmann, R Horne, R Josse, J A Kanis, B Obermayer-Pietsch, D Prieto-Alhambra, J-Y Reginster, R Rizzoli, S Silverman, M C Zillikens, R Eastell
: Adherence to oral bisphosphonates is low. A screening strategy is proposed based on the response of biochemical markers of bone turnover after 3 months of therapy. If no change is observed, the clinician should reassess the adherence to the treatment and also other potential issues with the drug. INTRODUCTION: Low adherence to oral bisphosphonates is a common problem that jeopardizes the efficacy of treatment of osteoporosis. No clear screening strategy for the assessment of compliance is widely accepted in these patients...
January 16, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28092987/emerging-treatment-approaches-for-myeloma-related-bone-disease
#12
Maria Gavriatopoulou, Meletios A Dimopoulos, Efstathios Kastritis, Evangelos Terpos
Multiple myeloma is characterized by the presence of osteolytic lesions that leads to devastating skeletal-related events in the majority of patients. Myeloma bone disease is attributed to increased osteoclastic and suppressed osteoblastic activity. Areas covered: Bisphosphonates remain the main treatment option, however they have limitations on their own. Understanding the pathogenesis of myeloma bone disease may provide a roadmap for new therapeutic approaches. The pathway of RANKRANKLOPG pathway has revealed denosumab, a monoclonal antibody targeting RANKL as a novel emerging therapy for myeloma-related bone disease...
January 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28088977/-osteonecrosis-of-the-jaw-associated-with-long-time-withdrawal-of-bisphosphonates-in-multiple-myeloma-one-case-report
#13
W J Yu, X Y Qu, Q L Shi, Y H Yuan, J D Xu, J Y Li, L J Chen
No abstract text is available yet for this article.
December 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28087282/short-term-perioperative-teriparatide-therapy-for-the-prevention-of-medication-related-osteonecrosis-of-the-jaw-a-randomized-controlled-preclinical-study-in-rats
#14
Mohammad Zandi, Arash Dehghan, Amirhossein Mohammadi-Mofrad, Payam Amini, Farshid Vahdatinia
OBJECTIVE: Dentoalveolar procedures in patients receiving bisphosphonates and other antiresorptive agents are associated with an increased risk of medication-related osteonecrosis of the jaw (MRONJ). The aim of present study was to evaluate the effects of perioperative teriparatide (TPD) therapy in prevention of MRONJ. SUBJECTS AND METHODS: Two protocols of TPD therapy were studied. For protocol A, 25 TPD-treated (AT) and 25 control (AC) rats received 5 weekly injection of 0...
December 19, 2016: Journal of Cranio-maxillo-facial Surgery
https://www.readbyqxmd.com/read/28078478/hypercalcaemia-and-hypocalcaemia-finding-the-balance
#15
REVIEW
Jean-Jacques Body, Daniela Niepel, Giuseppe Tonini
CALCIUM METABOLISM IN CANCER AND HYPERCALCAEMIA OF MALIGNANCY: The balance between bone formation and resorption may be disrupted in patients with cancer, leading either to increased bone resorption, calcium release, and possibly hypercalcaemia, or to increased bone formation, sequestration of calcium, and possibly hypocalcaemia. In adults, hypercalcaemia of malignancy is most common in patients with tumours that produce factors that induce osteoclast activation and enhance bone resorption...
January 12, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28078129/osteonecrosis-of-the-jaw-associated-with-ziv-aflibercept
#16
Hani Mawardi, Peter Enzinger, Nadine McCleary, Reshma Manon, Alessandro Villa, Nathaniel Treister, Sook-Bin Woo
Medication-related osteonecrosis of the jaw (MRONJ) has been associated with medications that include bisphosphonates (BPs), denosumab, bevacizumab and sunitinib. Ziv-aflibercept is a recombinant human vascular endothelial growth factor (VEGF) receptor which has been used to treat patients with various advanced solid tumors. We report three patients without a history of the use of medications known to cause MRONJ presenting with jaw osteonecrosis typical for MRONJ following therapy with ziv-aflibercept. All patients had metastatic gastrointestinal cancer treated with ziv-aflibercept and were evaluated for MRONJ because of exposed bone in the oral cavity...
December 2016: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28074765/-osteoporosis-treatment-can-be-discontinued-based-on-an-individual-assessment
#17
Pia A Eiken, Bo Abrahamsen
In most patients, treatment of osteoporosis is a long-term challenge. Because alendronate and zoledronic acid accumulate in bone with some persistent antifracture efficacy after therapy, it is reasonable to consider a "drug holiday" for low-risk patients. It is recommended that the duration and length of drug holiday should be individualized for each patient. For all other bisphosphonates data are limited. For other antiresorptive and anabolic agents "drug holiday" is not recommended.
January 9, 2017: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/28071822/responses-to-treatment-with-teriparatide-in-patients-with-atypical-femur-fractures-previously-treated-with-bisphosphonates
#18
Nelson B Watts, Deborah Aggers, Edward F McCarthy, Tina Savage, Stephanie Martinez, Rachel Patterson, Erin Carrithers, Paul D Miller
If over-suppression of bone turnover explained the association between bisphosphonate use and atypical subtrochanteric femur fractures (AFF), this could be reversed with anabolic treatment such as teriparatide. We conducted a prospective, open label study in patients previously treated with bisphosphonates who sustained AFF, examining the response to 24 months treatment with teriparatide on bone mineral density (BMD), trabecular bone score (TBS), bone turnover markers (BTM) and fracture healing as well as quantitative histomorphometry...
January 10, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28070850/zolendronic-acid-conjugated-plga-ultrasmall-nanoparticle-loaded-with-methotrexate-as-a-supercarrier-for-bone-targeted-drug-delivery
#19
Vinay Raichur, Kusum Devi Vemula, Naini Bhadri, Rema Razdan
Drug delivery to deep-seated tissues such as bone has been a major complication till date. This preferential drug delivery is further important in targeting anti-tumour agents to bone metastasis owing to its complexity. The present study involves the formulation of PLGA nanoparticles and conjugation with zolendronic acid-a bisphosphonate which will anchor the nanosystem to bone due to its selective bone affinity. The conjugated nanosystem was characterized for particle size by TEM (average 36 nm) and morphology by AFM depicting surface irregularities due to ZOL conjugation on the surface of nanoparticles...
January 9, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28069877/bone-seeking-matrix-metalloproteinase-2-inhibitors-prevent-bone-metastatic-breast-cancer-growth
#20
Marilena Tauro, Gemma Shay, Samer S Sansil, Antonio Laghezza, Paolo Tortorella, Anthony M Neuger, Hatem Soliman, Conor C Lynch
Bone metastasis is common during breast cancer progression. Matrix metalloproteinase-2 (MMP-2) is significantly associated with aggressive breast cancer and poorer overall survival. In bone, tumor or host derived MMP-2 contributes to breast cancer growth and does so by processing substrates including type I collagen and transforming growth factorβ (TGFβ) latency proteins. These data provide strong rationale for the application of MMP-2 inhibitors to treat the disease. However, in vivo, MMP-2 is systemically expressed...
January 9, 2017: Molecular Cancer Therapeutics
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