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Minimally effective concentration of zoledronic acid to suppress osteoclasts in vitro.

Zoledronic acid is regarded as the most potent bisphosphonate and is widely used in patients with osteoporosis; however, its side effects, including acute-phase reactions, gastrointestinal complaints, renal dysfunction and bisphosphonate-associated osteonecrosis impair the safety and quality of life of patients. The present study was designed to determine the minimal effective concentration of zoledronic acid through testing the dose-dependent effects of zoledronic acid on osteoclast suppression. A primary culture of bone marrow mononuclear cells obtained from C57 mice (age, 6 weeks) was estab

Bisphosphonate-Based Conjugates and Derivatives as Potential Therapeutic Agents in Osteoporosis, Bone Cancer and Metastatic Bone Cancer.

Metastatic bone cancer occurs in every type of cancer but is prevalent in lung, breast, and prostate cancers. These metastases can cause extensive morbidity, including a range of skeletal-related events, often painful and linked with substantial hospital resource usage. The treatment used is a combination of chemotherapy and surgery. However, anticancer drugs are still limited due to severe side effects, drug resistance, poor blood supply, and non-specific drug uptake, necessitating high toxic doses. Bisphosphonates are the main class of drugs utilized to inhibit metastatic bone cancer. It is

Targeted approaches in the treatment of osteoporosis: differential mechanism of action of denosumab and clinical utility.

Denosumab is a breakthrough biological drug approved by the Food and Drug Administration and European Medicines Agency for the treatment of osteoporosis in 2010. It is a fully human monoclonal antireceptor activator of nuclear factor kappa-B ligand antibody, which inhibits the activity of osteoclasts, resulting in an antiresorptive effect with a significant increase in bone mineral density. The FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis every 6 Months) trial, comparing denosumab with no treatment in 7868 women with postmenopausal osteoporosis, showed an important reduc

Bisphosphonate Use in Acute Spinal Cord Injury: A Focused Systematic Review on Zoledronic Acid.

Spinal cord injury (SCI) causes significant bone loss as a long-term complication, increasing fracture risk and healthcare costs. Bisphosphonates are widely studied for mitigating bone loss since they can prevent fractures and preserve rehabilitation potential in acute SCI patients. Zoledronic acid, in particular, stands out due to its high potency, dosing convenience, and better patient adherence. This review aims to evaluate the efficacy of bisphosphonates, particularly zoledronic acid, in mitigating bone loss in acute SCI. A systematic review was conducted following the Preferred Reporting

Screening, assessment, and treatment of osteoporosis for the nurse practitioner: key questions and answers for clinical practice--a Canadian perspective.

PurposeUsing a case-based approach, we review key clinical questions relevant to nurse practitioners (NPs) regarding the screening, assessment, and treatment of patients at risk for osteoporosis and fractures in a Canadian general practice setting.Data sourcesA case presentation with relevant questions and answers to guide management of a patient.ConclusionsOsteoporosis is a common condition in both the aging male and female populations. Screening, diagnosis, and treatment of osteoporosis is lagging behind relative to other chronic disease states. NPs have a unique opportunity to help reduce t

Bisphosphonates in the adjuvant treatment of cancer: experimental evidence and first clinical results. International Bone and Cancer Study Group (IBCG).

Several animal models, as well as a number of cell culture experiments, indicate a prophylactic effect of bisphosphonates in respect of subsequent bone metastasis. Moreover, in preliminary clinical trials involving patients with advanced breast cancer and local or remote metastases, biophosphonates produced a reduction in new skeletal metastases. This overview summarizes and discusses the results of the latest investigations. It opens with a section on the pathophysiology of bone metastasis, which is followed by a report on animal models and first studies of bisphosphonate treatment as a new a

A Narrative Review of Osteonecrosis of the Jaw: What a Clinician Should Know.

Medication-related osteonecrosis of the jaw (MRONJ) is an uncommon complication of antiresorptive therapy (ART) in patients receiving higher and more frequent doses of osteoclast inhibitors. The jaws are the most common site, as they have high bone turnover. The oral structures are exposed to various types of stresses, like mastication and dental diseases, which lead to microtrauma and increased bone remodeling. The hallmark feature of MRONJ is the area of exposed, necrotic, nonhealing, asymptomatic bone for more than eight weeks. Objective signs are pain in the jaw and oral cavity, loose teet

Oral Surgical Management of Bone and Soft Tissues in MRONJ Treatment: A Decisional Tree.

BACKGROUND: The aim of the present work was to analyze a 10-year retrospective series of surgically treated medication-related osteonecrosis of the jaws (MRONJ) cases, reporting the clinical outcome and success rate for each adopted procedure in order to draw a treatment algorithm that is able to standardize clinical decision making and maximize the success of oral surgical treatment of MRONJ. METHODS: Different surgical approaches were categorized taking into consideration two variables a) hard tissue management (defined as debridement, saucerization or marginal resective surgery of maxillar

Osteoimmunopathology in HIV/AIDS: A Translational Evidence-Based Perspective.

Infection with the human immunodeficiency virus-1 (HIV) and the resulting acquired immune deficiency syndrome (AIDS) alter not only cellular immune regulation but also the bone metabolism. Since cellular immunity and bone metabolism are intimately intertwined in the osteoimmune network, it is to be expected that bone metabolism is also affected in patients with HIV/AIDS. The concerted evidence points convincingly toward impaired activity of osteoblasts and increased activity of osteoclasts in patients with HIV/AIDS, leading to a significant increase in the prevalence of osteoporosis. Research

'Bone Health-Across a Woman's Lifespan'.

Despite a high burden of osteoporosis and minimal trauma fractures worldwide, there is still a treatment gap in timely diagnosis and optimal treatment. There is also a lack of international consensus and guidelines on the management of bone fragility in premenopausal women. This review article provides an overview of the current understanding of factors impacting women's bone health across the adult lifespan, as well as dilemmas in the diagnosis, assessment and management of osteoporosis in premenopausal and postmenopausal women, premature ovarian insufficiency and bone health following breast

Investigation of the Effectiveness of Surgical Treatment on Maxillary Medication-Related Osteonecrosis of the Jaw: A Literature Review.

AIM: Medication-related osteonecrosis of the jaw (MRONJ) occurs after exposure to medication (antiresorptive or antiangiogenic agents) for bone-related complications. It is more common in the mandible than in the maxilla. The present study investigated maxillary MRONJ in elderly patients through a meta-analysis. METHODS: Keywords, including "MRONJ", "maxilla", and "surgery", were entered into databases, including Embase, PubMed/MEDLINE, Cochrane Library, and ProQuest, which were searched systematically. RESULTS: Investigating 77 studies, we found that 18 (2 case reports and 16 case series) p

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… Regarding medication, 79.1% of patients were taking bisphosphonates during the treatment period, with the most frequently administered being zoledronate (35.6%), followed by alendronate (10.2%), ibandronate (6.1%), risedronic acid (3.2%), and pamidronate (2.9%). …

Zoledronic Acid Modulation of TRPV1 Channel Currents in Osteoblast Cell Line and Native Rat and Mouse Bone Marrow-Derived Osteoblasts: Cell Proliferation and Mineralization Effect.

Bisphosphonates (BPs) reduce bone pain and fractures by balancing the osteoblast/osteoclast ratio. The behavior of ion channels in the presence of BPs is not known. To investigate this, the effect of zoledronic acid BP (ZOL) (3 × 10-8 to 5 × 10-4 M) treatment, on ion channels, cell proliferation, and mineralization, has been investigated on preosteoclast-like cells, RAW264.7, preosteoblast-like cells MC3T3-E1, and rat/mouse native bone marrow-derived osteoblasts. In whole-cell patch clamp on cell line- and bone marrow-derived osteoblasts, ZOL potentiated outward currents. On RAW264.7, ZOL (10-

Molecular-Based Treatment Strategies for Osteoporosis: A Literature Review.

Osteoporosis is an unavoidable public health problem in an aging or aged society. Anti-resorptive agents (calcitonin, estrogen, and selective estrogen-receptor modulators, bisphosphonates, anti-receptor activator of nuclear factor κB ligand antibody along with calcium and vitamin D supplementations) and anabolic agents (parathyroid hormone and related peptide analogs, sclerostin inhibitors) have major roles in current treatment regimens and are used alone or in combination based on the pathological condition. Recent advancements in the molecular understanding of bone metabolism and in bioengin

Thai Osteoporosis Foundation (TOPF) position statements on management of osteoporosis.

The adjusted incidence rate of hip fracture in Thailand has increased more than 31% from 1997 to 2006. Mortality and morbidity after hip fracture are also high. One year mortality after a hip fracture has increased from 18% in 1999 to 21% in 2007. The Thai Osteoporosis Foundation (TOPF) developed the first Clinical Practice Guideline (CPG) in 2002 and keeps updating the CPG since then. This latest version of the CPG is our attempt to provide comprehensive positional statement on the diagnosis, prevention and treatment of osteoporosis in Thailand. The study group who revised this position state

Bisphosphonate induced osteonecrosis of jaw in breast cancer patients: A systematic review.

BackgroundBisphosphonate therapy is widely used for the treatment of bone metastasis in breast cancer patients.AimThe aim of this study is to estimate the overall prevalence of bisphosphonate induced osteonecrosis of jaw (BONJ) in breast cancer patients with bone metastasis.Materials and methodsA literature review was conducted to search and evaluate all the articles that contained original data on the prevalence of BONJ in breast cancer patients from the year 2003-2009. Pubmed search terms used were bisphosphonate, osteonecrosis, breast cancer and jaw. Eleven publications that fulfilled the i

Treatment Considerations for Severe Osteoporosis in Older Adults.

Osteoporosis, a chronic metabolic bone disease, increases the predisposition to fragility fractures and is associated with considerable morbidity, high health care cost as well as mortality. An elevation in the rate of incident fragility fractures will be observed proportional with the increase in the number of older people worldwide. Severe osteoporosis is currently defined as having a bone density determined by dual-energy X-ray absorptiometry that is more than 2.5 standard deviations (SD) below the young adult mean with one or more past fractures due to osteoporosis. Nutrition, physical act

Potential role of the comprehensive tooth extraction procedure in preventing medication related osteonecrosis of the jaw (MRONJ): a prospective cohort study.

BACKGROUND: This article aims to elucidate the potential role of a comprehensive tooth extraction procedure in preventing mdication-related osteonecrosis of the jaw (MRONJ) through a prospective cohort study. By systematically assessing clinical outcomes following this procedure, the study seeks to provide evidence regarding its effectiveness in MRONJ prevention, thereby contributing to improved clinical guidelines and patient care related to dental extractions in at-risk populations. METHODS: Patients using anti-resorptive agents (ARAs) who required extraction of at least one tooth were incl

The Rationale for Using Neridronate in Musculoskeletal Disorders: From Metabolic Bone Diseases to Musculoskeletal Pain.

Neridronate or ((6-amino-1-hydroxy-1-phosphonohexyl) phosphonic acid) is an amino-bisphosphonate (BP) synthetized in Italy in 1986. Bisphosphonates are molecules with a P-C-P bond in their structure that allows strong and selectively binding to hydroxyapatite (HAP) as well as osteoclasts inhibition through different mechanisms of action. Neridronate was initially used to treat Paget disease of the bone, demonstrating effectiveness in reducing bone turnover markers as well as pain. The interesting molecular properties of neridronate foster its wide use in several other conditions, such as osteo

Protection of bone in premenopausal women with breast cancer: focus on zoledronic acid.

Maintaining bone health is important for patients with breast cancer (BC), the most commonly diagnosed cancer in American women. Indeed, bone loss is common throughout the BC disease continuum. In the metastatic BC setting, patients are likely to develop bone metastases, a painful complication that can lead to potentially debilitating skeletal-related events. Bone health is equally important for patients with early BC. During adjuvant therapy for early BC, the largest challenge to bone health is from accelerated bone mineral density (BMD) loss. Although decreased BMD is well recognized in olde

Drug assumption and awareness about adverse drug reactions. The right to know. The case of the bone-modyfing agents: a systematic review.

INTRODUCTION: Medication-related osteonecrosis of the Jaw (MRONJ) is an adverse drug reaction that affects the mandible and maxilla of patients exposed to BMA and AA therapies, causing the progressive destruction and death of bone. To date, oral health preventive measures remain the most effective strategy to reduce MRONJ incidence, and, in this sense, the major goal is to diagnose, treat, and eradicate any oral diseases that could compromise oral health. The present systematic review aims to investigate the awareness of MRONJ among patients assuming BMAs. METHODS: A systematic literature sea