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Hypercalcemia of Malignancy and Medication-Related Osteonecrosis of the Jaw Following Denosumab Discontinuation in Metastatic Breast Cancer: A Case Report.

Hypercalcemia of malignancy (HCM) is a common and serious complication in patients with advanced cancer and is associated with significant morbidity and mortality. Standard long-term management of HCM relies on anti-resorptive therapies such as bisphosphonates and denosumab, both of which act by inhibiting osteoclast-mediated bone resorption but carry the risk of medication-related osteonecrosis of the jaw (MRONJ). This case illustrates a patient with metastatic breast cancer (MBC) who developed recurrent, severe hypercalcemia after discontinuing denosumab due to MRONJ, followed by profound hy

Role of Actinomyces spp. and related organisms in the development of medication-related osteonecrosis of the jaw (MRONJ): Clinical evidence based on a case series.

Medication-related osteonecrosis of the jaw (MRONJ) is an increasingly common consequence of antiresorptive treatment, which often leads to the development of necrotic exposed bone surfaces with inflammatory processes affecting the jawbone. Although the development of MRONJ is often associated with the inflammatory response or infections caused by the colonizing members of the oral microbiota, the exact pathogenesis of MRONJ is still not fully understood. In the present paper, we aimed to provide additional, microbiological culture-supported evidence, supporting the "infection hypothesis" that

Interleukin-17 plays a role in dental pulp inflammation mediated by zoledronic acid: a mechanism unrelated to the Th17 immune response?

ObjectiveTo evaluate the influence of RORγT inhibition by digoxin on inflammatory changes related to interleukin-17 (IL-17) in the pulp of rats treated with zoledronate (ZOL).MethodologyForty male Wistar rats were divided into a negative control group (NCG) treated with saline solution, a positive control group (PCG) treated with ZOL (0.20 mg/kg), and three groups treated with ZOL and co-treated with digoxin 1, 2, or 4 mg/kg (DG1, 2, and 4). After four intravenous administrations of ZOL or saline solution in a 70-day protocol, the right molars were evaluated by histomorphometry (number of bloo

Clinical values of serum Semaphorin 4D (Sema4D) in medication‑related osteonecrosis of the jaw.

BACKGROUND: Bisphosphonates (BPs) are widely used in clinical practice to prevent and treat bone metabolism-related diseases. Medication-related osteonecrosis of the jaw (MRONJ) is one of the major sequelae of BPs use. Early prediction and intervention of MRONJ are of great significance. METHODS: Ninety-seven patients currently on treatment with BPs or with a history of BPs usage and 45 healthy volunteers undergoing dentoalveolar surgery were included in this study. Participants' serum Semaphorin 4D (Sema4D) levels were measured and analyzed before participants underwent surgery (T0) and afte

Navigating Stomatologic Complications Secondary to Antineoplastic Agents-A Comprehensive Review.

This review systematically examines the oral complications associated with conventional and novel anti-cancer therapies. It highlights that while molecularly targeted agents including monoclonal antibodies targeting the vascular endothelial growth factor and its receptor, the epidermal growth factor receptor, tyrosine kinase inhibitors, and immune checkpoint inhibitors tend to exhibit a lower overall toxicity profile compared to traditional cytotoxic chemotherapeutics, they are nonetheless linked to significant oral adverse events. These complications encompass inflammatory mucosal reactions k

Medication-related osteonecrosis of the jaw: an evidence-based 2025 position statement from a Korean multidisciplinary task force.

With a rapidly aging population and increasing use of antiresorptive agents, medication-related osteonecrosis of the jaw (MRONJ) represents a growing clinical challenge worldwide. To address the need for tailored clinical guidance, a multidisciplinary task force was convened. Five Korean academic societies-the Korean Society for Bone and Mineral Research, the Korean Association of Oral and Maxillofacial Surgeons, the Korean Association of Maxillofacial Plastic and Reconstructive Surgeons, the Korean Society of Osteoporosis, and the Korean Endocrine Society-collaborated to develop this position

Oral complications and management strategies for patients undergoing cancer therapy.

With cancer survival rate climbing up over the past three decades, quality of life for cancer patients has become an issue of major concern. Oral health plays an important part in one's overall quality of life. However, oral health status can be severely hampered by side effects of cancer therapies including surgery, chemotherapy, radiotherapy, and hematopoietic stem cell transplantation. Moreover, prevention and treatment of these complications are often overlooked in clinical practice. The present paper aims at drawing health care professionals' attention to oral complications associated wit

Awareness of the risk of developing medication-related osteonecrosis of the jaw among bisphosphonate users.

OBJECTIVE: In this retrospective observational study, we evaluated awareness among patients using bisphosphonates (BPs) regarding the risk of developing medication-related osteonecrosis of the jaw (MRONJ) and whether they received appropriate dental screening and treatment prior to commencing medication. METHODS: Patients using BPs who attended the endodontics clinic at Jordan University Hospital in 2019 were interviewed using a pre-designed questionnaire. Data were analysed using descriptive statistics and chi-squared tests. RESULTS: In total, 110 patients were interviewed (84 women, 26 men

Hypophosphatasia.

Hypophosphatasia (HPP) is an inherited metabolic disease caused by loss-of-function mutations in the tissue non-specific alkaline phosphatase (TNAP) gene. Reduced activity of TNAP leads to the accumulation of its substrates, mainly inorganic pyrophosphate and pyridoxal-5'-phosphate, metabolic aberrations that largely explain the musculoskeletal and systemic features of the disease. More than 400 ALPL mutations, mostly missense, are reported to date, transmitted by either autosomal dominant or recessive mode. Severe disease is rare, with incidence ranging from 1:100,000 to 1:300,000 live births

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… They almost invariably report early tooth loss, and their radiographic skeletal changes are very subtle, e.g., low bone mass. On the other hand, severe childhood HPP can be challenging and heterogeneous. … Primary dentition is more sensitive to low ALP function, and this is important, as premature tooth loss can affect nutrition and speech. The poorly mineralized cementum leads to decreased tooth root anchorage to the periodontal ligament. …

From Osteoclast Differentiation to Osteonecrosis of the Jaw: Molecular and Clinical Insights.

Bone physiology relies on the delicate balance between resorption and formation of its tissue. Bone resorption depends on a process called osteoclastogenesis in which bone-resorbing cells, i.e., osteoclasts, are produced by the differentiation of more undifferentiated progenitors and precursors. This process is governed by two main factors, monocyte colony-stimulating factor (M-CSF) and receptor activator of NFκB ligand (RANKL). While the former exerts a proliferating effect on progenitors/precursors, the latter triggers a differentiation effect on more mature cells of the same lineage. Bone h

ITF6475, a New Histone Deacetylase 6 Inhibitor, Prevents Painful Neuropathy Induced by Paclitaxel.

Chemotherapy-induced peripheral neuropathy remains a significant side effect of cancer treatment, often requiring dose reductions or even discontinuation of therapy. Paclitaxel (PTX), a widely used chemotherapeutic agent for solid tumors, is particularly neurotoxic, and no effective treatment exists for paclitaxel-induced peripheral neuropathy (PIPN). Histone deacetylases (HDACs) are enzymes that remove acetyl groups from histone and non-histone proteins, including transcription factors and cytoskeletal components. This study evaluates the HDAC6 inhibitor ITF6475 for its potential to prevent P

Implications of Systemic Inflammation and Periodontitis for Major Depression.

Increasing evidence suggests that infection and persistent low-grade inflammation in peripheral tissues are important pathogenic factors in major depression. Major depression is frequently comorbid with systemic inflammatory diseases/conditions such as rheumatoid arthritis, allergies of different types, multiple sclerosis, cardiovascular disease, inflammatory bowel disease, chronic liver disease, diabetes, and cancer, in which pro-inflammatory cytokines are overexpressed. A number of animal studies demonstrate that systemic inflammation induced by peripheral administration of lipopolysaccharid

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… Periodontitis can be classified as gingivitis, when the inflammation is localized in the gingival tissues, or it may assume a more severe destructive form, with the inflammatory process reaching deeper connective and bone tissue, causing bone and attachment loss, that may ultimately lead to tooth loss … Impact of tooth loss on the quality of life. Gerodontology 29 e632 – e636 . 10.1111/j.1741-2358.2011.00535.x 21883422 Shelton R. C. ( 2007 ). The molecular neurobiology of depression. Psychiatr. Clin. North Am. 30 1 – 11 . 10.1016/j.psc.2006.12.005 17362799 PMC2136411 Socransky S. S. Haffajee A. …

A REVIEW OF SALIVARY BIOMARKERS OF PERIODONTAL DISEASE.

BackgroundPeriodontal disease is a complex multifactorial disease resulting from the interplay amongst microbiota, host immune response (influenced by genetic make-up) and lifestyle factors. The chronic inflammatory nature of the disease results in the destruction of the component of the periodontium. The process of the disease is associated with inflammation, collagen degradation and, bone loss which correlate with clinical features of periodontal disease. The clinical diagnosis of periodontal disease entails clinical examination involving the evaluation of probing depth, bleeding on probing,

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… On account of the slow and innocuous progression of periodontal disease, its harmful effect on the periodontal ligament, cementum, alveolar bone, and gingiva can result in tooth loss and its associated effects on the quality of life of the patient. … IL-1 polymorphisms connote the risk of tooth loss and advancing periodontal diseases as they have been found to be associated with IL1β gene (3953/4C>T) polymorphisms 42 . …

Survival Rates and Clinical Outcomes of Implant Overdentures in Old and Medically Compromised Patients.

Studies on the survival rate of implant overdentures in medically compromised patients are limited because most studies exclude patients with systemic diseases affecting implant prognosis. This retrospective study aimed to evaluate the survival rate and clinical outcomes of dental implants used for overdentures in medically compromised patients. A total of 20 patients (9 men, 11 women; mean age: 67.55 ± 6.84 years, range: 53-81 years) were included. Fourteen patients had more than two systemic diseases, and nine patients had more than three systemic diseases. The mean follow-up period was 39.0

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… Effects of tooth loss on brain structure: A voxel-based morphometry study. J. Prosthodont. Res. 2018;62:337–341. doi: 10.1016/j.jpor.2017.12.007. 32. Oh B., Han D.H., Han K.T., Liu X., Ukken J., Chang C., Dounis K., Yoo J.W. …

Routine scale and polish for periodontal health in adults.

BACKGROUND: Many dentists or hygienists provide scaling and polishing for patients at regular intervals, even for those at low risk of devel … hs and the other at 36 months. Neither study measured adverse effects, changes in attachment level, tooth loss or halitosis.Comparison 1: routine scaling and polishing versus no scheduled scaling and polishingTwo studies compared planned, regular interval (six- and 12-monthly) scale and polish treatments versus no scheduled treatment. We found little or no d …

Medication-Related Osteonecrosis of the Jaw: An Evidence-Based 2025 Position Statement from a Korean Multidisciplinary Task Force.

With a rapidly aging population and increasing use of antiresorptive agents, medication-related osteonecrosis of the jaw (MRONJ) represents a growing clinical challenge worldwide. To address the need for tailored clinical guidance, a multidisciplinary task force was convened. Five Korean academic societies-the Korean Society for Bone and Mineral Research, the Korean Association of Oral and Maxillofacial Surgeons, the Korean Society of Maxillofacial Plastic and Reconstructive Surgeons, the Korean Osteoporosis Society, and the Korean Endocrine Society-collaborated to develop this position statem

Dental Implant Placement in Patients on Bisphosphonate Therapy: a Systematic Review.

OBJECTIVES: The review aims to study dental implant placement purposefulness for patients who have been treated or are on treatment with bisphosphonate medication. MATERIAL AND METHODS: Structured search strategy was applied on electronic databases: MEDLINE, PubMed, PubMed Central and ResearchGate. Scientific publications in English between 2006 and 2017 were identified in accordance with inclusion, exclusion criteria. Publication screening, data extraction, and quality assessment were performed. Outcome measures included implant failure or implant-related osteonecrosis of the jaw. RESULTS:

A pathologic mandibular fracture revealing a bifocal location of Langerhans cell histiocytosis.

IntroductionLangerhans cell histiocytosis is a rare disease. When it occurs in the cranium/facial bones, the mandibular location is the most frequent.Presentation of caseA 31 years-old man was referred to our department for a mandibular chronic discomfort during an acute exacerbation, spontaneous teeth mobility and an alteration of the dental occlusion revealing a pathologic mandibular fracture.The diagnosis was confirmed by a subsequent CT scan.The surgical procedure was performed under general anesthesia by a maxillo-facial senior surgeon. The therapeutic plan combined teeth extractions, enu

The role of LGR4 in bone metabolism and tumor bone metastasis.

The Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) is a member of the G protein-coupled receptor family and plays an important role in bone metabolism and tumor bone metastasis. LGR4 affects bone metabolism by regulating the differentiation and activity of osteoblasts and osteoclasts, and is involved in the balance between bone resorption and bone formation. Deficiency of LGR4 leads to osteoporosis, whereas the up-regulation of LGR4 may help to alleviate the development of traumatic osteoarthritis. Furthermore, in breast cancer and multiple myeloma, LGR4 promotes tumor cell

Bisphosphonate-related osteonecrosis of the jaw mimicking bone metastasis.

Osteonecrosis of the jaw is usually a potential complication of bisphosphonate therapy. In a cancer patient, this disease entity can be misdiagnosed as a metastatic lesion. Our aim is to make clinicians aware of bisphosphonate associated osteonecrosis of the jaw to prevent misdiagnosis and initiate proper treatment at the earliest. We present the case of a breast cancer patient with multiple bony metastases and a jaw lesion presumed to be metastases. After no response to palliative radiation, repeat radiological imaging studies revealed osteonecrosis of the jaw. Correlating a patient's clinica