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Bone Disease in Multiple Myeloma: Biologic and Clinical Implications.

Multiple Myeloma (MM) is a hematologic malignancy characterized by the proliferation of monoclonal plasma cells localized within the bone marrow. Bone disease with associated osteolytic lesions is a hallmark of MM and develops in the majority of MM patients. Approximately half of patients with bone disease will experience skeletal-related events (SREs), such as spinal cord compression and pathologic fractures, which increase the risk of mortality by 20-40%. At the cellular level, bone disease results from a tumor-cell-driven imbalance between osteoclast bone resorption and osteoblast bone form

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… The organic components include osteocytes, bone-lining cells, osteoclast cells (OCs), osteoblast cells (OBs), collagen fibers, proteoglycans, and glycoproteins [ 36 ]. The inorganic material consists of mostly calcium and phosphate and makes up 60% of bone mass [ 36 ]. … Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway PLoS ONE 2011 6 e25900 10.1371/journal.pone.0025900 21991382 PMC3186800 115. Yee A.J. Laubach J.P. Nooka A.K. O’Donnell E.K. Weller E.A. Couture N.R. Wallace E.E. Burke J.N. Harrington C.C. Puccio-Pick M. …

MicroRNA-21-5p profile in the alveolar bone following tooth extraction in medication-related osteonecrosis of the jaw rat model.

OBJECTIVE: This study aimed to compare microRNA-21-5p expressions at the extraction wound in the maxillary bones of rats with medication-related osteonecrosis of the jaw (MRONJ) and normal rats at different time points. MATERIALS AND METHODS: In total, 18 female, 8-week-old Sprague-Dawley rats were randomly assigned to the experimental group (n = 9) and the control group (n = 9). To establish MRONJ in the right maxillary first molar area in the experimental group, zoledronate (66 µg/kg) and dexamethasone (5 mg/kg) were administered intraperitoneally every other day for 2 weeks before tooth ex

Is Teriparatide Superior in Treating Osteoporotic Vertebral Compression Fractures in Comparison to Bisphosphonates Treatment Alone: A 2-Year Retrospective Analysis.

STUDY DESIGN: Retrospective cohort study. PURPOSE: This study aimed to compare the efficacy of bisphosphonates and teriparatide in the management of osteoporotic vertebral compression fractures with regard to pain management, prevention of nonunion, and radiological as well as clinical outcomes. OVERVIEW OF LITERATURE: Osteoporosis refers to a skeletal disorder characterized by decreased bone strength caused by poor bone density and quality causing fragility, resulting in long periods of pain-related immobilization. METHODS: In a 24-month follow-up retrospective study, 191 patients with ost

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… TTPD, an anabolic drug, acts on PTH type 1R receptors present in various cells such as osteoblasts, osteocytes, and renal tubular cells. PTH type 1R receptors are G-protein-coupled receptors that are important in the actions of PTH on calcium and phosphate homeostasis and bone metabolism. …

Кардиометаболическая многомерность увеличивает риск разлома гипса: продольное коотертное исследование на основе CHARLS.

В качестве сопутствующего явления Cardiometabolic Multimbidity (CMM) two или более заболеваний сердца, сахарного диабета, инсульта и гипертонии. Предыдущие исследования показали связь между кардиометаболическими заболеваниями и хрупкими трещинами; однако связь между ШМ и переломами бедра у китайского населения остается неясной. Таким образом, цель данного исследования заключается в изучении этой ассоциации в китайской когорте в целях информирования о стратегиях предотвращения переломов. 2011 в адрес 2020. Участники от 2011 Первоначально была включена группа базовых обследований. Впоследствии о

Circulating Levels of Soluble α-Klotho and FGF23 in Childhood Cancer Survivors: Lack of Association with Nephro- and Cardiotoxicity-A Preliminary Study.

Background/Objectives: The survival rate among pediatric cancer patients has reached 80%; however, these childhood cancer survivors (CCSs) are at a heightened risk of developing chronic conditions in adulthood, particularly kidney and cardiovascular diseases. The aims of this study were to assess the serum α-Klotho and FGF23 levels in CCSs and to determine their association with nephro- and cardiotoxicity. Methods: This study evaluated a cohort of 66 CCSs who remained in continuous remission, with a mean follow-up of 8.41 ± 3.76 years. Results: The results of this study revealed that CCSs exhi

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… Fibroblast growth factor-23 is a phosphaturic hormone secreted primarily by bone osteocytes and osteoblasts and regulates the renal reabsorption of phosphate, sodium, and calcium, as well as the expression of α-Klotho [ 12 ]. …

Sclerotic bone: a sign of bone reaction in patients with medication related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction associated with antiresorptive drugs such as bisphosphonates and denosumab. When dealing with advanced and/or multiple MRONJ lesions undergoing surgical therapy, the extent of surgery is often a topic of discussion. The aim of this study was to identify the differences in bone density in and around the MRONJ lesion before and after surgical treatment to evaluate the needed surgical extend of the modelling osteotomy. In this retrospective study 26 patients with MRONJ lesions that were surgically treated in our dep

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… This observation can be explained by the principles of bone metabolism: in damaged bone, apoptotic osteocytes signal the location and size of damage to lining cells leading to the formation of the bone remodelling compartment (BRC). …

The role of the bone microenvironment in regulating myeloma residual disease and treatment.

Multiple myeloma is an incurable haematological cancer. The increase in targeted therapies has improved the number of myeloma patients achieving a complete response and improved progression-free survival following therapy. However, a low level of disease or minimal residual disease (MRD) still persists which contributes to the inevitable relapse in myeloma patients. MRD has been attributed to the presence of dormant myeloma cells and their subsequent reactivation, which is controlled by the microenvironment and specialised niches within the bone marrow. This contributes to the evasion of the i

Silencing of SPARC represses heterotopic ossification via inhibition of the MAPK signaling pathway.

Heterotopic ossification (HO), the pathologic formation of extraskeletal bone, can be disabling and lethal. However, the underlying molecular mechanisms were largely unknown. The present study aimed to clarify the involvement of secreted protein acidic and rich in cysteine (SPARC) and the underlying mechanism in rat model of HO. The mechanistic investigation on roles of SPARC in HO was examined through gain- and loss-of-function approaches of SPARC, with alkaline-phosphatase (ALP) activity, mineralized nodules, and osteocalcin (OCN) content measured. To further confirm the regulatory role of S

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… Additionally, SPARC is highly expressed in osteoblasts in both normal bone and HO tissues in comparison with preosteoclasts and young osteocytes [ 19 ]. …

Direct phenotypic conversion of human fibroblasts into functional osteoblasts triggered by a blockade of the transforming growth factor-β signal.

A procedure to generate functional osteoblasts from human somatic cells may pave the way to a novel and effective transplantation therapy in bone disorders. Here, we report that human fibroblasts were induced to show osteoblast phenotypes by culturing with ALK5 i II, which is a specific inhibitor for activin-like kinase 5 (ALK5) (tumor growth factor-β receptor 1 (TGF-β R1)). Cells cultured with ALK5 i II expressed osteoblast-specific genes and massively produced calcified bone matrix, similar to the osteoblasts induced from mesenchymal stem cells (MSC-OBs). Treatment with vitamin D3 in additio

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… TGF-β is produced by osteoblasts and osteocytes, while its roles in osteogenesis are very much complicated. It was reported that TGF-β induced migration of MSCs and enhanced bone fracture healing 36 . …

Bone-targeted agents in multiple myeloma.

Osteolytic bone disease, characterized by bone pain, increased risk of pathologic fractures, tumor-induced hypercalcemia known as skeletal-related events (SREs), is a frequent complication of patients with multiple myeloma (MM) and persists even in the absence of active disease, resulting in a major cause of morbidity and mortality. The interaction between myeloma cells and their surrounding cells in the bone marrow (BM) microenvironment promotes both myeloma cell growth and bone destruction and forms the vicious cycle of MM bone disease. Therefore, therapeutic strategies targeting the interac

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… BM microenvironment is composed of various kinds of cells including BM stromal cells (BMSCs), osteocytes, OCs, osteoblasts (OBs), vascular endothelial cells and immune cells. …

The interrelationship between prostate cancer and osteoporosis: new perspectives on shared molecular pathways and treatment strategies.

Osteoporosis is frequently regarded as a complication associated with androgen deprivation therapy (ADT) in patients with prostate cancer. Nevertheless, a notably higher incidence of osteoporosis has been observed in prostate cancer patients even in the absence of ADT, when compared to age-matched healthy individuals. This phenomenon is likely attributable to the synergistic effects of aging, chronic inflammation, and tumor-related factors, which collectively contribute to accelerated bone loss in this population. Accumulating evidence has demonstrated that signaling pathways such as RANKL/RAN

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… Sclerostin is a secreted factor produced by osteocytes [ 75 ] . Similar to DKK1, it blocks Wnt signaling by binding to LRP5 and LRP6 [ 140 ] . … Osteocytes Produces RANKL Via Wnt-TGFβ Signaling Axis for Osteoclastogenesis . Int J Bio Sci . 2025 ; 21 : 5821–41 . 41079923 10.7150/ijbs.117481 PMC12509901 [25] Park J Yan G Kwon KC . …

EZH2 serves as a viable therapeutic target for myeloma-induced osteolytic bone destruction.

Myelomatous bone disease is a complication characterized by lytic bone lesions, reduced bone formation, bone pain, and increased fracture risk. Understanding these underlying mechanisms is crucial for developing effective therapeutic approaches. Here we show the role of enhancer of zeste homolog 2 (EZH2) in bone lesions induced by myeloma cells. Our research reveals that cytokines produced by myeloma-associated adipocytes activate the expression of EZH2 in myeloma cells. Furthermore, we find that EZH2 forms a transcriptional repression complex with transcription factor AP2α. This complex promo

Osteoporosis and the Potential of Cell-Based Therapeutic Strategies.

Osteoporosis, the most common chronic metabolic bone disease, is characterized by low bone mass and increased bone fragility. Nowadays more than 200 million individuals are suffering from osteoporosis and still the number of affected people is dramatically increasing due to an aging population and longer life, representing a major public health problem. Current osteoporosis treatments are mainly designed to decrease bone resorption, presenting serious adverse effects that limit their safety for long-term use. Numerous studies with mesenchymal stem cells (MSCs) have helped to increase the knowl

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… BSP is produced by many different cell types during bone morphogenesis such us osteoblasts, osteoclasts, osteocytes and hypertrophic chondrocytes [ 55 , 56 ]. … Sclerostin, expressed by osteocytes and articular chondrocytes, is the product of SOST gene. It is an endogenous inhibitor of the Wingless-type mouse mammary virus integration site (Wnt) signaling pathway. …

Stem cell therapy as a potential treatment option for psoriasis.

Psoriasis is a chronic inflammatory dermatological disorder characterized by white scales and clearly demarcated erythematous plaques. The prevalence of psoriasis varies from country to country and can occur at any age, implying that ethnicity, environmental factors, and genetic background all play a role in its onset. According to the World Psoriasis Day Consortium, 125 million people globally and 2%-3% of the overall community have psoriasis. The introduction of biological treatments has revolutionized the treatment of moderate to severe psoriasis. These novel drugs, particularly those targe

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… MSCs are distinguished by specific surface indicators and their ability to adhere to plastic substrates and develop into adipocytes, osteocytes, and chondrocytes in vitro. MSCs consist of various types of cells, and the most well-known are bone marrow-derived stromal stem cells. …

Bone targeted nano-drug and nano-delivery.

There are currently no targeted delivery systems to satisfactorily treat bone-related disorders. Many clinical drugs consisting of small organic molecules have a short circulation half-life and do not effectively reach the diseased tissue site. This coupled with repeatedly high dose usage that leads to severe side effects. With the advance in nanotechnology, drugs contained within a nano-delivery device or drugs aggregated into nanoparticles (nano-drugs) have shown promises in targeted drug delivery. The ability to design nanoparticles to target bone has attracted many researchers to develop n

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… The basic calcium component of common cements, ceramics and Ca-BGs ensures these materials with appropriate mechanical characteristics in bone substitution application and bioactive interfaces to interact with osteocytes. … Bone-derived exosomes are naturally existing nano-sized extracellular vesicles secreted by various bone cells, such as bone marrow stromal cells, osteoclasts, osteoblasts and osteocytes, containing multifarious proteins, lipids and nucleic acids. …

Molecular Mechanisms Leading from Periodontal Disease to Cancer.

Periodontitis is prevalent in half of the adult population and raises critical health concerns as it has been recently associated with an increased risk of cancer. While information about the topic remains somewhat scarce, a deeper understanding of the underlying mechanistic pathways promoting neoplasia in periodontitis patients is of fundamental importance. This manuscript presents the literature as well as a panel of tables and figures on the molecular mechanisms of Porphyromonas gingivalis and Fusobacterium nucleatum, two main oral pathogens in periodontitis pathology, involved in instigati

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… RANKL Isoforms and Function The majority of RANKL is present in the form of membrane-bound protein presented on the surface of numerous cells such as T and B lymphocytes, mesenchymal cells, chondrocytes, osteoblasts, osteocytes and megakaryocytes [ 96 ]. … The roles of osteocytes in alveolar bone destruction in periodontitis J. Transl. Med. 2020 18 1 15 10.1186/s12967-020-02664-7 33308247 PMC7733264 74. Yasuda H. Shima N. Nakagawa N. Mochizuki S.I. Yano K. Fujise N. Sato Y. Goto M. Yamaguchi K. Kuriyama M. …

Systemic Ozone Therapy Improves Oral Hard and Soft Tissue Healing in Medication-Related Osteonecrosis of the Jaw (MRONJ): A Study in Senescent Female Rats.

Background/Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a challenging condition often associated with bisphosphonate use, leading to impaired bone healing and difficult clinical management. Given the lack of predictable therapeutic options, this study investigated the effects of systemic ozone therapy on MRONJ healing. This study aimed to analyze the effects of systemic ozone therapy on oral hard and soft tissue healing in senescent rats with medication-related osteonecrosis of the jaw (MRONJ) induced by antiresorptive therapy. Methods: Twenty-eight senescent Wistar rats,

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… Even with some gaps in the bone matrix, the number of cells of the osteoblastic lineage was noticeable, with osteocytes embedded in the mineralized bone matrix and osteoblasts in the adjacent region of the bone tissue (bt), juxtaposed to the connective tissue (ct) loaded with cells. …

Osteolytic Breast Cancer Causes Skeletal Muscle Weakness in an Immunocompetent Syngeneic Mouse Model.

Muscle weakness and cachexia are significant paraneoplastic syndromes of many advanced cancers. Osteolytic bone metastases are common in advanced breast cancer and are a major contributor to decreased survival, performance, and quality of life for patients. Pathologic fracture caused by osteolytic cancer in bone (OCIB) leads to a significant (32%) increased risk of death compared to patients without fracture. Since muscle weakness is linked to risk of falls which are a major cause of fracture, we have investigated skeletal muscle response to OCIB. Here, we show that a syngeneic mouse model of

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… Healthy bone has endocrine functions that are achieved both by active signaling from bone cells such as osteoblasts and osteocytes as well as passive release of cytokines and minerals stored in the bone matrix. …

The Effect of Bisphosphonates on Fracture Healing Time and Changes in Bone Mass Density: A Meta-Analysis.

BackgroundOsteoporosis is a common complication of acute fracture, which can lead to fracture delayed union or other complications and resulting in poor fracture healing. Bisphosphate is a common anti-osteoporosis drug, but its application in fracture patients is still controversial because of its inhibitory effect on bone resorption.MethodStudies were acquired from literature databases in accordance with established inclusion criteria. Standard mean difference (SMD) and 95% confidence intervals (Cls) were calculated to evaluate the effectiveness of the bisphosphonates treatment in fracture pa

Altered Long Noncoding RNA Expression Profile in Multiple Myeloma Patients with Bisphosphonate-Induced Osteonecrosis of the Jaw.

Bisphosphonates (BPs) are inhibitors of osteoclast-mediated bone resorption used for the treatment of multiple myeloma (MM) patients with osteolytic lesions. Bisphosphonate-induced osteonecrosis of the jaw (BONJ) is an infrequent drug-caused adverse event of these agents. Long noncoding RNAs (lncRNAs) are a set of more than 200 base pairs, noncoding RNA molecules, which are critical posttranscriptional regulators of gene expression. Our study was aimed at evaluating 17 lncRNAs, whose targets were previously validated as key elements in MM, bone metabolism, and angiogenesis in MM subjects witho