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Surgical management of bisphosphonate induced osteonecrosis of the jaws.

Recent literature contains numerous articles on osteonecrosis of the jaws (ONJ) associated with bisphosphonate treatment (BPT), with most advocating a conservative approach to management. A prospective study was designed to review the surgical management of cases of ONJ that did not respond to conservative management. Forty patients, referred with ONJ that did not respond to conservative management, were treated surgically and followed up for 6 months to 4 years. Four patients were taking i.v. BPT as part of their bone cancer management and 16 were taking oral BPT for osteoporosis. The surgica

Usefulness of bone formation markers in breast cancer.

The skeleton is the main site affected by metastases and breast cancer is the most frequent tumor to invade bone. The assessment of bone metastases is difficult and biochemical markers of bone formation (BFMs) could be a promising alternative. Although the essential role of osteoblasts in the metastatic process of bone destruction is now well established, little attention has been paid to BFMs. We conducted a Medline search for studies about BFMs in breast cancer. Our review allows us to conclude that BFMs have high specificity but low sensitivity for the diagnosis of bone metastases. The avai

Interventions for preventing bone disease in kidney transplant recipients: a systematic review of randomized controlled trials.

BACKGROUND: Before renal transplantation complex abnormalities of bone metabolism exist and lead to increased risk for fracture after transplantation. This study was conducted to assess the evidence available to guide targeted treatment to reduce bone disease in transplant recipients. METHODS: The Cochrane CENTRAL Registry, MEDLINE, and EMBASE were searched for randomized trials of interventions for bone disease after renal transplantation. Data were extracted on fracture, bone mineral density (BMD) by means of dual-energy X-ray absorptiometry, acute graft rejection, and adverse events. Analy

Physician practices of bone density testing and drug prescribing to prevent or treat osteoporosis during androgen deprivation therapy.

BACKGROUND: Androgen deprivation therapy (ADT) is a strong risk factor for osteoporosis. The current study identified physician practices in preventing or treating osteoporosis during ADT. The practices of interest are the uses of dual-energy X-ray absorptiometry (DXA) scans, bisphosphonates, calcium or vitamin D supplement, calcitonin, or estrogen. METHODS: A retrospective medical record review was conducted. Patients were included if they had received ADT with goserelin injection for >/= 1 year. Multivariable logistic regression analysis was performed to identify independent predictors of r

The bisphosphonate zoledronic acid induces cytotoxicity in human myeloma cell lines with enhancing effects of dexamethasone and thalidomide.

Bisphosphonates have recently been introduced in the therapeutic armamentarium for long-term treatment of patients with multiple myeloma. These pyrophosphate analogs not only reduce the occurrence of skeletal events but also provide clinical benefit to patients and improve the survival of some of them. The existence of these capabilities raises the possibility that these compounds may have a direct antiproliferative effect on tumor cells. To investigate whether these drugs exert a direct antitumor effect, we exposed human myeloma cell lines ARH-77 and RPMI-8226 to increasing concentrations of

Requirement of species-specific interactions for the activation of human gamma delta T cells by pamidronate.

Human gammadelta T cells bearing Vgamma2Vdelta2-TCR recognize various kinds of small nonpeptide Ags, and activation of them by a nitrogen-containing bisphosphonate Ag, pamidronate, requires Ag presentation by cells other than gammadelta T cells, including many human tumor cells. Present results demonstrated that tumor cell lines of nonhuman origins pulsed with pamidronate failed to activate human gammadelta T cells without exception, whereas most if not all human tumor cell lines could do so. Gammadelta T cells formed stable conjugates with pamidronate-pulsed human tumor cells and both conjuga

Effects of renal failure and metabolic diseases upon bone scanning in children.

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Hypophosphatemic Osteomalacia Induced by Low-Dose Adefovir-Related Fanconi Syndrome.

Adefovir dipivoxil (ADV), an antiviral agent for chronic hepatitis B virus infection, has been associated with nephrotoxicity, particularly Fanconi syndrome, even at low doses (10 mg/day). Fanconi syndrome is a generalized proximal tubular dysfunction leading to phosphate wasting and hypophosphatemic osteomalacia. Here, the author reports a case of a 58-year-old man with a 2-year history of bone pain involving the left foot, upper back, and left scapula, later extending to the right foot and chest wall, without antecedent trauma. Magnetic resonance imaging revealed insufficiency fractures in b

Review of imaging techniques for evaluating morphological and functional responses to the treatment of bone metastases in prostate and breast cancer.

Bone metastases are very common complications associated with certain types of cancers that frequently negatively impact the quality of life and functional status of patients; thus, early detection is necessary for the implementation of immediate therapeutic measures to reduce the risk of skeletal complications and improve survival and quality of life. There is no consensus or universal standard approach for the detection of bone metastases in cancer patients based on imaging. Endorsed by the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and the

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… Bone scintigraphy Bone scintigraphy (BS) with technetium-labeled diphosphonates ( 99m Tc-HDP) continues to be the technique of choice and the most widely used in the evaluation of osteoblastic or mixed metastatic bone disease [ 27 , 49 ]. … Once deposited in the bone, diphosphonates are absorbed by hydroxyapatite crystals on bone mineralization surfaces [ 50 ]. A change of only 5–10% in the lesion/healthy bone ratio is sufficient to induce pathological deposition of the radiopharmaceutical [ 23 ]. …

Drug-induced ocular inflammation.

AIM: Drug-induced ocular inflammation is rare and may be overlooked as a cause of uveitis. The main objective was to describe the causes of drug-induced ocular inflammation. Secondary objectives included uveitis complications and drug rechallenge reactions. METHODS: A retrospective chart review at Auckland District Health Board's tertiary uveitis clinic (Auckland, New Zealand) was performed. Participants were identified using the uveitis database, which consists of 2,750 subjects. Fifty eyes of 35 subjects had drug-induced inflammation. RESULTS: Drug-induced inflammation occurred in 1.3% of

Zoledronic acid induces apoptosis and S-phase arrest in mesothelioma through inhibiting Rab family proteins and topoisomerase II actions.

Zoledronic acid (ZOL), a nitrogen-containing bisphosphonate, produced anti-tumor effects through apoptosis induction or S-phase arrest depending on human mesothelioma cells tested. An addition of isoprenoid, geranylgeraniol but not farnesol, negated these ZOL-induced effects, indicating that the ZOL-mediated effects were attributable to depletion of geranylgeranyl pyrophosphates which were substrates for prenylation processes of small guanine-nucleotide-binding regulatory proteins (small G proteins). ZOL-treated cells decreased a ratio of membrane to cytoplasmic fractions in RhoA, Cdc42 and Ra

Effects of locally administered tiludronic acid on experimental periodontitis in rats.

BACKGROUND: It appears there are no studies evaluating the influence of the bisphosphonate tiludronic acid (TIL) on periodontitis. The purpose of this study is to evaluate via microtomographic, histopathologic, histometric, and immunohistochemical analyses the effects of local administration of TIL on ligature-induced periodontitis in rats. METHODS: Forty-eight rats were divided into six groups: C (control), EP (experimental periodontitis), EP-Saline, EP-TIL0.1, EP-TIL0.3, and EP-TIL1. In EP, a ligature was placed around maxillary second molars. In EP-TIL0.1, EP-TIL0.3, and EP-TIL1, TIL solut

Bisphosphonate-related osteonecrosis of the jaws: a potential alternative to drug holidays.

In 2011, the American Dental Association Council on Scientific Affairs released an update by their expert panel on managing the care of patients receiving antiresorptive therapy for the prevention and treatment of osteoporosis. In this report, the panel found no study results that confirmed the effectiveness of drug holidays to prevent antiresorptive agent-induced osteonecrosis of the jaws without increasing the risks of low bone mass. The purpose of this article is to provide suggestions for a pattern of patient care for individuals who desire or require an invasive surgical procedure of the

Bisphophonates in CKD patients with low bone mineral density.

Patients with chronic kidney disease-mineral and bone disorder (CKD-MBD) have a high risk of bone fracture because of low bone mineral density and poor bone quality. Osteoporosis also features low bone mass, disarranged microarchitecture, and skeletal fragility, and differentiating between osteoporosis and CKD-MBD in low bone mineral density is a challenge and usually achieved by bone biopsy. Bisphosphonates can be safe and beneficial for patients with a glomerular filtration rate of 30 mL/min or higher, but prescribing bisphosphonates in advanced CKD requires caution because of the increased

The activity of γδ T cells against paediatric liver tumour cells and spheroids in cell culture.

BACKGROUND: Chemoresistance and advanced tumour stage at time of diagnosis are the major reasons for poor treatment results in hepatoblastoma (HB) and paediatric hepatocellular carcinoma (HCC). Positive results with transplantation of liver and bone marrow revealed the impact of the immune system on the treatment of liver malignancies. AIM: Cytotoxic-immune-cells-like natural killer (NK) and T cells are major player in the defence against developing tumours. This study aimed to specifically analyse the ability of ex-vivo expanded γδ T cells to recognise and lyse HB and HCC cell lines in cocul

A comparative study of clinical characteristics, work-up, treatment, and association to malignancy in dermatomyositis between two tertiary skin centers in the USA and Singapore.

BACKGROUND: To date, no study has compared the clinical characteristics, malignancy associations, and treatment of dermatomyositis in predominantly Caucasian vs. Asian populations. MATERIALS AND METHODS: This prospective study was conducted to compare clinical characteristics of dermatomyositis, its relationship to malignancy, and treatment between two tertiary medical centers in the USA and Singapore. A total of 19 newly-diagnosed patients in the USA and 15 patients in Singapore were enrolled. Dermatomyositis or amyopathic dermatomyositis were diagnosed based on clinical assessment, skin and

Antagonism of inhibitor of apoptosis proteins increases bone metastasis via unexpected osteoclast activation.

UNLABELLED: Inhibitor of apoptosis (IAP) proteins play a central role in many types of cancer, and IAP antagonists are in development as anticancer agents. IAP antagonists cause apoptosis in many cells, but they also activate alternative NF-κB signaling through NF-κB-inducing kinase (NIK), which regulates osteoclasts. In bone metastasis, a positive feedback loop between tumors and osteoclasts promotes tumor growth and osteolysis. We therefore tested the effect of IAP antagonists on the bone microenvironment for metastasis. In both drug-sensitive and drug-resistant tumors, growth in bone was fa

Influence of dentures in the initial occurrence site on the prognosis of bisphosphonate-related osteonecrosis of the jaws: a retrospective study.

OBJECTIVE: This retrospective cohort study was conducted to investigate the influence of wearing dentures in the initial occurrence site of bisphosphonate-related osteonecrosis of the jaws (BRONJ). STUDY DESIGN: A questionnaire regarding the prevalence, therapy, and outcome of jawbone lesions during 2006-08 was mailed to 248 medical institutions with an oral and maxillofacial surgery department in Japan. RESULTS: Ninety-nine patients wearing dentures had significantly shorter duration until occurrence than 151 patients not wearing dentures. In addition, remission of BRONJ affecting the mandi

Prognostic factors for skeletal complications from metastatic bone disease in breast cancer.

Skeletal morbidity is common in patients with bone metastases from breast cancer (BC) and can undermine patients' functional independence and quality of life. Previously defined prognostic factors may not reflect current treatment standards and the use of antiresorptive therapies. We report a comprehensive multivariate analysis of potential prognostic factors for skeletal-related events (SREs) using data from a phase III, randomized study of zoledronic acid in patients with bone metastases from BC. The trial evaluated the number and timing of SREs (pathologic fracture, palliative radiotherapy

Bone metastases: molecular mechanisms and novel therapeutic interventions.

It has been long recognized that skeleton represents one of the most favored metastatic sites for common cancers like breast and prostate. During the last decade the molecular mechanisms that are responsible for the development of bone metastasis have been gradually illuminated. It appears that the bone microenvironment has a pivotal role in this process. Metastatic tumor cells interact with bone triggering a cascade of molecular events that produce osteolytic and/or osteoblastic phenomena. In this review, we summarize and discuss the most significant factors and signaling pathways implicated