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Management of Medication-Related Osteonecrosis of the Jaws With Hyperbaric Oxygen Therapy: A Case Report.

Medication-related osteonecrosis of the jaw (MRONJ) refers to the condition where the maxillary or mandibular bone becomes exposed and necrotic as a result of bisphosphonate therapy. The number of patients on bisphosphonates is increasing and so are the MRONJ cases. Since the initial data were published in the early 2000s, research into MRONJ has expanded significantly to enhance the understanding of this emerging condition. Various treatment options are available, but none have been established as the definitive "gold standard" for managing this disease. Hyperbaric oxygen therapy (HOT) is one

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… Figure 3 Microscopic presentation showing necrotic bony trabeculae with empty osteocyte lacunae. Osteoclasts containing numerous intracytoplasmic vacuoles are seen at the periphery and in the intertrabecular spaces of the bony trabeculae. … These osteocytes, being terminal cells, eventually lose their functional capacity, leading to microfractures in the aging mineral matrix. …

CRLF1 and CLCF1 in Development, Health and Disease.

Cytokines and their receptors have a vital function in regulating various processes such as immune function, inflammation, haematopoiesis, cell growth and differentiation. The interaction between a cytokine and its specific receptor triggers intracellular signalling cascades that lead to altered gene expression in the target cell and consequent changes in its proliferation, differentiation, or activation. In this review, we highlight the role of the soluble type I cytokine receptor CRLF1 (cytokine receptor-like factor-1) and the Interleukin (IL)-6 cytokine CLCF1 (cardiotrophin-like cytokine fa

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… Bone formation relies on different cell types, osteoblasts, osteoclasts and osteocytes in bone and chondrocytes in cartilage. Osteoblasts, osteocytes, and chondrocytes arise from multipotent mesenchymal stem cells (MSCs) [ 90 , 91 ]. … Chondrocytes, osteoblasts, osteoclasts, and osteocytes rely on JAK1/STAT3/SOCS3 signalling during normal bone development. …

Gaucher Disease in Bone: From Pathophysiology to Practice.

Gaucher disease (GD) is a rare, genetic lysosomal disorder leading to lipid accumulation and dysfunction in multiple organs. Involvement of the skeleton is one of the most prevalent aspects of GD and a major cause of pain, disability, and reduced quality of life. Uniform recommendations for contemporary evaluation and management are needed. To develop practical clinical recommendations, an international group of experienced physicians conducted a comprehensive review of 20 years' of the literature, defining terms according to pathophysiological understanding and pointing out best practice and

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… Osteocytes, about 90% of adult skeleton cells, function as a mechanosensor and send signals to both osteoclasts and osteoblasts to remodel or maintain bone mass. … Osteocyte Wnt/beta‐catenin signaling is required for normal bone homeostasis . Mol Cell Biol . 2010 ; 30 ( 12 ): 3071 – 85 . 20404086 10.1128/MCB.01428-09 PMC2876685 87 Mistry PK , Liu J , Yang M , et al. …

Biologics for bone regeneration: advances in cell, protein, gene, and mRNA therapies.

Bone fractures represent a significant global healthcare burden. Although fractures typically heal on their own, some fail to regenerate properly, leading to nonunion, a condition that causes prolonged disability, morbidity, and mortality. The challenge of treating nonunion fractures is further complicated in patients with underlying bone disorders where systemic and local factors impair bone healing. Traditional treatment approaches, including autografts, allografts, xenografts, and synthetic biomaterials, face limitations such as donor site pain, immune rejection, and insufficient mechanical

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… For example, sclerostin, a glycoprotein secreted by osteocytes, is a negative regulator of bone formation by inhibiting the Wnt/β-catenin signaling pathway. … Human osteocyte expression of nerve growth factor: the effect of pentosan polysulphate sodium (PPS) and implications for pain associated with knee osteoarthritis. PLoS One 14 , e0222602 (2019). 82. Takano, S. et al. …

Sclerostin induced tumor growth, bone metastasis and osteolysis in breast cancer.

Breast cancer is the second leading cause of cancer-related deaths among women worldwide. Many patients suffer from bone metastasis. Sclerostin, a key regulator of normal bone remodeling, is critically involved in osteolytic bone diseases. However, its role in breast cancer bone metastasis remains unknown. Here, we found that sclerostin was overexpressed in breast cancer tumor tissues and cell lines. Inhibition of sclerostin by antibody (Scl-Ab) significantly reduced migration and invasion of MDA-MB-231 and MCF-7 cells in a time- and dose-dependent manner. In xenograft model, sclerostin inhibi

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… Regulation of Wnt/beta-catenin signaling within and from osteocytes. Bone. 2013;54:244–249. doi: 10.1016/j.bone.2013.02.022. 23. Galliera E, et al. Wnt signaling pathway inhibitors as promising diagnostic serum markers of osteolytic bone metastasis. … In vivo mechanical loading rapidly activates beta-catenin signaling in osteocytes through a prostaglandin mediated mechanism. Bone. 2015;76:58–66. doi: 10.1016/j.bone.2015.03.019. 31. Zahoor M, Cha PH, Min do S, Choi KY. …

The Interplay between Immune System and Microbiota in Osteoporosis.

Osteoporosis is a disease characterized by low bone mass and alterations of bone microarchitecture, with an increased risk of fractures. It is a multifactorial disorder that is more frequent in postmenopausal women but can be associated to other diseases (inflammatory and metabolic diseases). At present, several options are available to treat osteoporosis trying to block bone reabsorption and reduce the risk of fracture. Anyway, these drugs have safety and tolerance problems in long-term treatment. Recently, gut microbiota has been highlighted to have strong influence on bone metabolism, becom

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… In fact, RANKL is expressed not only by mesenchymal cells, osteoblasts and osteocytes, but also by activated T CD4+ lymphocytes, indicating that this is a molecule that bridges the skeletal and immune systems [ 34 ]. … Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nature Medicine. 2011;17(10):1231–1234. doi: 10.1038/nm.2452. 35. Lam J., Takeshita S., Barker J. E., Kanagawa O., Ross F. P., Teitelbaum S. L. …

Medication-Related Osteonecrosis: Why the Jawbone?

Medication-related osteonecrosis of the jaw (MRONJ) has emerged as a complication of anti-resorptive medications. Despite its low incidence rate, this problem has gained attention in recent years due to its devastating consequences and lack of preventive strategy. The fact that MRONJ incidence has been exclusive to the jawbones, despite the systemic effect of anti-resorptive medications, could be a starting point to unravel the multifactorial pathogenesis of this condition. This review aims to negotiate the question of why the jawbone is more susceptible to MRONJ than other skeletal sites. App

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… Figure 1 The standard method in quantifying MRONJ in experimental animals: ( a ) histology image of normal alveolar bone tissue, with the vast majority of osteocyte lacunae occupied with viable osteocytes (hence, the normal-looking nuclei); ( b ) alveolar bone in zoledronate-treated rat showing reduced … viability, evident by the large percentage of empty osteocyte lacunae. …

Medication-Related Osteonecrosis of the Jaw: Successful Medical Management of Complex Maxillary Alveolus with Sinus Involvement.

Medication-related osteonecrosis of the jaw (MRONJ) in cancer patients presents a considerable challenge in management. Current management is primarily based on interventions in a limited number of cases assessing a single approach. Medical management typically is reported to include antimicrobial therapy with or without surgery. Advances in the understanding of pathogenesis have led to the investigation of additional medical interventions for early-stage necrosis. We present 3 patients with advanced-stage MRONJ of the maxilla using combined medical modalities including antimicrobial therapy,

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… The pathobiology of MRONJ is thought to include medication-related cytotoxicity affecting osteocytes, osteoblasts, osteoblasts, fibroblasts, as well as bone marrow cells, resulting in microcirculatory dysfunction and connective tissue destruction [2, 4] . … Improving blood flow, regulation of TGF-β1/BP-signaling, and promotion of osteocyte and connective tissue cell function are potential actions of Pent-E with applicability in prevention and management of MRONJ [4] . …

Exosomes in the Repair of Bone Defects: Next-Generation Therapeutic Tools for the Treatment of Nonunion.

Nonunion with bone defects, a common complication after long bone fracture, is a major challenge for orthopaedic surgeons worldwide because of the high incidence rate and difficulties in achieving successful treatment. Bone defects are the main complications of nonunion. The conventional biological treatments for nonunion with bone defects involve the use of autologous bone grafts or bone graft substitutes and cell-based therapy. Traditional nonunion treatments have always been associated with safety issues and various other complications. Bone grafts have limited autologous cancellous bone an

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… Qin and colleagues found that muscle-secreting myostatin inhibits osteoblastic differentiation by blocking osteocyte-derived exosomal miR-218 , suggesting the presence of a potential communication mechanism between muscle and bone [ 111 ]. … Additionally, Solberg et al. showed that lysosomal membrane protein 1-positive exosomes contain RANK ligand, osteoprotegerin, and tartrate-resistant acid phosphatase isolated from rat osteoblasts and osteocytes [ 128 ]. …

Advances in the mechanism and therapies of achondroplasia.

Achondroplasia (ACH), is the prevailing type of genetic dwarfism in humans, caused by mutations in fibroblast growth factor receptor 3 (FGFR3) that are inherited in an autosomal dominant manner. FGFR3 is mainly expressed in condensed mesenchyme, chondrocytes, and mature osteoblasts and osteoclasts, in which it regulates the formation, development, growth, and remodeling of the skeletal system. Mutations in FGFR3 causing ACH result in enhanced FGFR3 signaling through combined mechanisms including enhancing FGF dimerization and tyrosine kinase activity and stabilizing FGF receptors. In ACH, supp

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… Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation. Proc Natl Acad Sci USA. 2014;111(33):12097–12102. doi: 10.1073/pnas.1302703111. 21. Yang G., Zhu L., Hou N., et al. Osteogenic fate of hypertrophic chondrocytes. … Excessive osteocytic Fgf23 secretion contributes to pyrophosphate accumulation and mineralization defect in Hyp mice. PLoS Biol. 2016;14(4) doi: 10.1371/journal.pbio.1002427. 133. van Gastel N., Carmeliet G. Metabolic regulation of skeletal cell fate and function in physiology and disease. …

Pathogenesis and treatment of multiple myeloma bone disease.

Multiple myeloma (Plasma cell myeloma), a malignancy of the plasma cells, exhibits tumor expansion preferentially in the bone marrow and the development of bone-destructive lesions. Multiple myeloma is still an incurable disease with changes in the bone marrow microenvironment in favor of the survival and proliferation of multiple myeloma cells and bone destruction. In this review, we described the recent findings on the regulators involved in the development of myeloma bone diseases, and succinctly summarize currently available therapeutic options and the development of novel bone modifying a

New Generation of Meso and Antiprogestins (SPRMs) into the Osteoporosis Approach.

Receptor activator of nuclear factor κB (RANK) and its ligand (RANKL) play key roles in bone metabolism and the immune system. The RANK/RANKL complex has also been shown to be critical in the formation of mammary epithelia cells. The female hormones estradiol and progesterone closely control the action of RANKL with RANK. Blood concentration of these sex hormones in the postmenopausal period leads to an increase in RANK/RANKL signaling and are a major cause of women's osteoporosis, characterized by altered bone mineralization. Knowledge of the biochemical relationships between hormones and RAN

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… Moreover, estrogen blocks osteoblast apoptosis and increases their viability by Sema3A secretion induction in osteocytes [ 42 , 43 ]. Sema3A is a membrane-associated secreted protein involved either in bone resorption and its formation. … Fluorescent risedronate analogues reveal bisphosphonate uptake by bone marrow monocytes and localization around osteocytes in vivo. J. Bone Miner. Res. 2010;25:606–616. doi: 10.1359/jbmr.091009. 76. Russell R.G.G., Watts N.B., Ebetino F.H., Rogers M. …

The role of biomarkers in the management of bone-homing malignancies.

Bone represents a common site of metastasis from several solid tumours, including breast, prostate and lung malignancies. The onset of bone metastases (BM) is associated not only with serious skeletal complications, but also shortened overall survival, owing to the lack of curative treatment options for late-stage cancer. Despite the diagnostic advances, BM detection often occurs in the symptomatic stage, underlining the need for novel strategies aimed at the early identification of high-risk patients. To this purpose, both bone turnover and tumour-derived markers are being investigated for th

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… Some osteoblasts become osteocytes, namely dendritic cells acting as mechano-transducers. Bone turnover is regulated by the RANK-L/RANK/OPG axis. … Some osteoblasts become osteocytes, namely dendritic cells acting as mechano-transducers. Bone turnover is regulated by the RANK-L/RANK/OPG axis. …

Osteoprotective Roles of Green Tea Catechins.

Osteoporosis is the second most common disease only secondary to cardiovascular disease, with the risk of fracture increasing with age. Osteoporosis is caused by an imbalance between osteoblastogenesis and osteoclastogenesis processes. Osteoclastogenesis may be enhanced, osteoblastogenesis may be reduced, or both may be evident. Inflammation and high reactive oxygen enhance osteoclastogenesis while reducing osteoblastogenesis by inducing osteoblast apoptosis and suppressing osteoblastic proliferation and differentiation. Catechins, the main polyphenols found in green tea with potent anti-oxida

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… Bone has dynamic turnover through a remodeling process controlled by osteoclasts, osteoblasts, and osteocytes. … Age-dependent bone loss is associated with reduced osteoblast numbers, enhanced apoptosis of osteoblasts and osteocytes, and decreased rate of bone formation [ 32 , 33 , 34 ]. …

Bone Research Society 2021 Abstracts

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… Advances in our understanding of the bone remodeling cycle have demonstrated that the osteocyte is central to its control, by regulating the differentiation and activity of the major bone cells involved, the osteoclasts and the osteoblasts. … At present, in vitro bone models lack osteocytes, due to the challenging and demanding conditions required for maintaining them in long‐term culture. …

Antiresorptive medication-related osteonecrosis of the jaw: Incidence and preventive measures utilization in cancer patients.

INTRODUCTION: Antiresorptive drugs are commonly used to treat cancer and bone metastases. These drugs can impose the risk of osteonecrosis of the jaw (ONJ). ONJ is a serious complication that can lead to significant morbidity and mortality. This study aimed to investigate the incidence and preventive measures utilization of ONJ among cancer patients treated with antiresorptive agent. MATERIALS AND METHODS: This retrospective cohort study investigated 210 adult patients with cancer on either zoledronic acid (ZA) or denosumab at a tertiary cancer center. The primary endpoint was to determine th

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… Bisphosphonates affect osteocytes, increasing the expression of RANKL and Sclerostin, which in turn inhibit bone formation through the WNT (Wingless-related integration site) signaling pathway. … Zoledronate enhances osteocyte-mediated osteoclast differentiation by IL-6/RANKL axis. Int. J. Mol. Sci. 2019;20:1467. doi: 10.3390/ijms20061467. Kim S.H., Lee Y.-K., Kim T.-Y., Ha Y.-C., Jang S., Kim H.Y. …

Cancer Cells Exploit Notch Signaling to Redefine a Supportive Cytokine Milieu.

Notch signaling is a well-known key player in the communication between adjacent cells during organ development, when it controls several processes involved in cell differentiation. Notch-mediated communication may occur through the interaction of Notch receptors with ligands on adjacent cells or by a paracrine/endocrine fashion, through soluble molecules that can mediate the communication between cells at distant sites. Dysregulation of Notch pathway causes a number of disorders, including cancer. Notch hyperactivation may be caused by mutations of Notch-related genes, dysregulated upstream p

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… As a consequence, Notch activity hampers osteocytes viability and promotes RANKL and sclerostin secretion that, in turn, supports the recruitment of OCL precursors ( 95 ). … The authors showed that co-cultured multiple myeloma cells and osteocytes reciprocally activated Notch signaling. Notch activation in osteocytes induced apoptosis that in a second phase was amplified by high levels of TNFα secreted by MM cells. …

ACY‑1215, a HDAC6 inhibitor, decreases the dexamethasone‑induced suppression of osteogenesis in MC3T3‑E1 cells.

Glucocorticoid‑induced osteoporosis is the commonest form of drug‑induced osteoporosis. Histone deacetylase 6 (HDAC6) is involved in the differentiation from mesenchymal stem cells to osteoblasts. However, the role of ricolinostat (ACY‑1215, HDAC6 inhibitor) in the dexamethasone (Dex)‑induced proliferation and differentiation of preosteoblasts remains to be elucidated. The protein expression and mRNA expression levels of HDAC6, osteopontin (OPN), runt‑related transcription factor 2 (Runx2), osterix (Osx), collagen I (COL1A1) and glucocorticoid receptor (GR) in MC3T3‑E1 cells were analyzed by w

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… GR has multiple effects on osteocytes in osteoporosis; however, these have been only rarely investigated ( 28 ). Plotkin et al ( 29 ) demonstrated that GCs mediate the apoptosis of bone cells via GR. … osteoarthritic osteoblasts Biomed Pharmacother 118 109357 2019 10.1016/j.biopha.2019.109357 31548177 28 Komori T Regulation of skeletal development by the Runx family transcription factors J Cell Biochem 95 445 453 2005 10.1002/jcb.20420 15786491 29 Plotkin L Manolagas S Bellido T Glucocorticoids induce osteocyte …

The Neuro-Bone Axis in Metastatic Progression: Innervation, Neuro-Immune-Osteoclast Crosstalk, and Therapeutic Opportunities.

Bone metastases represent a major cause of morbidity in advanced cancers, yet the neural regulation of metastatic growth within bone remains largely unexplored. The skeletal system is richly innervated by sensory and sympathetic nerve fibers that influence bone remodeling, hematopoiesis, and immune surveillance. Emerging evidence suggests that disseminated tumor cells exploit these neural circuits to create a growth-permissive microenvironment. Tumor-secreted neurotrophic factors can induce nerve sprouting, while sympathetic activation via β-adrenergic receptors promotes osteoclastogenesis, im

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… Activation of osteocytic β2-adrenergic receptors (clenbuterol, isoproterenol) elevates RANKL levels and the RANKL/OPG ratio, promoting osteoclastogenesis in cocultures [ 81 , 82 ]. … This stimulation also upregulates RANKL in osteoblasts/osteocytes, enhancing osteoclastogenesis and releasing growth factors from bone matrix that fuel metastatic growth [ 80 , 85 , 126 ]. …

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

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… Osteocytes, osteoblasts and osteoclasts are the main cells within bone (Fig. 1 ). Osteocytes found in the lacunae of the matrix have a mechano-sensory function, and osteoblasts synthesize osteoid whilst osteoclasts enzymatically resorb bone [ 18 ]. … A subpopulation of mature osteoblasts further differentiate into osteocytes within the mineralized bone. …