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Ion Channels in Multiple Myeloma: Pathogenic Role and Therapeutic Perspectives.

Ion channels are pore-forming proteins that allow ions to flow across plasma membranes and intracellular organelles in both excitable and non-excitable cells. They are involved in the regulation of several biological processes (i.e., proliferation, cell volume and shape, differentiation, migration, and apoptosis). Recently, the aberrant expression of ion channels has emerged as an important step of malignant transformation, tumor progression, and drug resistance, leading to the idea of "onco-channelopathy". Here, we review the contribution of ion channels and transporters in multiple myeloma (

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… These findings are in line with other literature data showing the expression of P2X7 in osteoblasts, osteoclasts, and osteocytes, and its involvement in the regulation of cell proliferation, differentiation, and bone biology [ 56 ]. …

Targeting Bone Metastases in Metastatic Castration-Resistant Prostate Cancer.

Skeletal involvement in metastatic castrate-resistant prostate cancer (mCRPC) is common and results in significant morbidity and mortality. The interaction of prostate cancer with the bone microenvironment contributes to progression of cancer in the bone leading to skeletal-related events (SREs). Studies aimed at targeting the bone have been carried out over the recent years. Bisphosphonates are synthetic pyrophosphate analogs first investigated for their role in SRE prevention with zoledronic acid as the main bisphosphonate that is approved by the US Food and Drug Administration for retardati

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… increased bone formation and bone resorption, which opens the door to multiple mechanisms of action to target the bone microenvironment (see Fig. 1 for selected bone-targeted agents and their proposed mechanisms of action). 13 , 14 In addition, the complex interplay of osteoblasts, bone lining cells, osteocytes …

Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium.

X-linked hypophosphatemia (XLH) is the most common genetic form of hypophosphatemic rickets and osteomalacia. In this disease, mutations in the PHEX gene lead to elevated levels of the hormone fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting and impaired skeletal and dental mineralization. Recently, international guidelines for the diagnosis and treatment of this condition have been published. However, more specific recommendations are needed to provide guidance at the national level, considering resource availability and health economic aspects. A national multidiscip

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… DMP1 as well as PHEX are highly expressed in osteocytes, although it remains unknown how they alter the phosphate-FGF23 set point ( 55 ). ENPP1 is a critical enzyme in the generation of the mineralization inhibitor pyrophosphate. … Clinical, biochemical and radiographic features of Raine syndrome may be very similar to sporadic XLH, but distinctive facial features, cerebral calcifications and osteomalacia surrounding the osteocyte lacunae on bone biopsy are a typical hallmark of this condition ( 69 ). …

Update on the role of bone turnover markers in the diagnosis and management of osteoporosis: a consensus paper from The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), International Osteoporosis Foundation (IOF), and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).

PurposeThe International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) have proposed procollagen type I N propeptide (PINP) and β isomerized C-terminal telopeptide of type I collagen (β-CTX-I) as reference bone turnover markers (BTMs) for osteoporosis. This report examines the published literature since the 2011 IOF-IFCC position paper in order to determine the clinical potential of the reference BTMs and newer markers for the prediction of fracture risk and monitoring the treatment of osteoporosis.MethodsEvidence for the re

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… Regulators involved in bone formation Sclerostin is an osteocytic protein inhibiting bone formation. High concentrations were found to be strongly predictive of incident fracture in a Saudi cohort of postmenopausal women [ 265 ], a finding also noted in the Study of Osteoporotic Fractures [ 266 ]. … A bone-produced hormone with various targets: FGF23 FGF23 is a hormone produced by osteocytes regulating phosphate metabolism, including renal phosphate excretion, PTH secretion and 1,25-dihydroxyvitamin D production and/or catabolism. …

Множественные модели миэломы и витро человека для моделирования заболеваний и скрининга на лечение.

Множественная миелома (ММ) — гематологическая порча, характеризующаяся неконтролируемым расширением злокачественных плазменных клеток в микроокружающей среде костного мозга. В то время как культуры подвески клеточных линий MM и мусриновых моделей были краеугольным камнем исследований MM патогенез, эти традиционные системы не могут воспроизвести критические аспекты микроопухоли человека. В частности, нынешние модели неадекватно учитывают ключевые биологические вопросы, включая механизмы приобретения лекарственного сопротивления, стратегии уклонения от иммунитета и роль клеточного перекрестка в

Down-regulation of EHMT2 through irisin-mediated epigenetic modification promotes osteogenesis via promoting DLX3 transcription.

BACKGROUND: Irisin, a cleavage peptide by fibronectin type III domain-containing protein 5 (FNDC5), has been recognized as a promotor of osteogenesis to alleviate osteoporosis (OP). However, the detailed regulatory mechanism of osteogenesis remains unclear. This study uncovered the mechanisms underlying bone formation. METHODS: Osteogenic activity was evaluated by ALP and ARS staining. Expression of target molecules and osteogenic-related factors was assessed by RT-qPCR, Western blotting, and immunohistochemical staining. The binding of euchromatic histone lysine methyltransferase 2 (EHMT2) to

Dissecting the effects of 223Radium on the bone microenvironment.

Radium-223 (223Ra) is a bone-seeking, alpha-particle-emitting radionuclide that is approved for the treatment of patients with metastatic prostate cancer and is currently being tested in clinical trials for primary and metastatic cancers to the bone. 223Ra accumulates in mineralized bone areas with high bone turnover, where its effects are confined within 100 μm of the bone-marrow interface due to the short tissue penetrance of the alpha particles. A recent clinical study has shown a significantly increased fracture rate associated with the administration of 223Ra, mostly in tumor-free bones.

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… Osx, also called Sp7, is a cell-specific transcription factor expressed by mature osteoblasts and osteocytes that regulates their differentiation 28 . Sp7-mCherry mice were treated with 223 Ra (300 kBq/kg) or vehicle and euthanized at different timepoints up to 60 days. …

Remineralization Rate of Lytic Lesions of the Spine in Multiple Myeloma Patients Undergoing Radiation Therapy.

Study DesignRetrospective cohort study.ObjectiveIn general, Multiple Myeloma (MM) patients are treated with systemic therapy including chemotherapy. Radiation therapy can have an important supportive role in the palliative management of MM-related osteolytic lesions. Our study aims to investigate the degree of radiation-induced remineralization in MM patients to gain a better understanding of its potential impact on bone mineral density and, consequently, fracture prevention. Our primary outcome measure was percent change in bone mineral density measured in Hounsfield Units (Δ% HU) between pre

Identified Medications Causing Medication-Related Osteonecrosis of the Jaw: A Literature Review.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse event that occurs in patients treated with certain medications, leading to a major side effect that can result in substantial morbidity. MRONJ is known to be associated with antiresorptive (AR) and antiangiogenic (AA) medicines, but recent evidence suggests that other medications may also be involved. Recognizing a broad range of drug-induced risk factors is important, notably in light of the increasing number of drugs associated with MRONJ. The primary objective of this review is to update and synthesize findings from th

Macrophage miR-149-5p induction is a key driver and therapeutic target for BRONJ.

Bisphosphonate-related (BP-related) osteonecrosis of the jaw (BRONJ) is one of the severe side effects of administration of BPs, such as zoledronic acid (ZA), which can disrupt the patient's quality of life. Although the direct target of skeletal vasculature and bone resorption activity by BPs has been phenomenally observed, the underlying mechanism in BRONJ remains largely elusive. Thus, it is urgently necessary to discover effective therapeutic targets based on the multifaceted underlying mechanisms in the development of BRONJ. Here, we determined the inhibitory role of ZA-treated macrophage

Current progress and mechanisms of bone metastasis in lung cancer: a narrative review.

Lung cancer is a kind of malignant tumor with rapid progression and poor prognosis. Distant metastasis has been the main cause of mortality among lung cancer patients. Bone is one of the most common sites. Among all lung cancer patients with bone metastasis, most of them are osteolytic metastasis. Some serious clinical consequences like bone pain, pathological fractures, spinal instability, spinal cord compression and hypercalcemia occur as well. Since the severity of bone metastasis in lung cancer, it is undoubtedly necessary to know how lung cancer spread to bone, how can we diagnose it and

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… Paracrine and endocrine actions of bone-the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts. Bone Res 2018;6:16. 10.1038/s41413-018-0019-6 31. Rahim F, Hajizamani S, Mortaz E, et al. Molecular regulation of bone marrow metastasis in prostate and breast cancer. …

Sphingosine kinase 2 inhibition synergises with bortezomib to target myeloma by enhancing endoplasmic reticulum stress.

The proteasome inhibitor bortezomib has proven to be invaluable in the treatment of myeloma. By exploiting the inherent high immunoglobulin protein production of malignant plasma cells, bortezomib induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), resulting in myeloma cell death. In most cases, however, the disease remains incurable highlighting the need for new therapeutic targets. Sphingosine kinase 2 (SK2) has been proposed as one such therapeutic target for myeloma. Our observations that bortezomib and SK2 inhibitors independently elicited induction of ER st

Obesity is associated with suppressed bone turnover: a systematic review and meta-analysis.

BackgroundObesity is an increasingly serious public health issue on a global scale. Although there is increasing research on the relationship between obesity and biochemical markers of bone turnover, this relationship is complex and unclear. We conducted a systematic review and meta-analysis aimed at comparing the concentrations of biochemical markers of bone turnover between individuals with obesity and those with normal-weight.MethodA systematic search was conducted using the PubMed, EMBASE, Web of Science, Cochrane Library, and EBSCO databases from database inception to December 15, 2025. T

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… Discussion In the regulation of bone homeostasis, osteoblasts are responsible for extracellular matrix synthesis, osteoclasts continuously remove old bone, while osteocytes play a key role in modulating skeletal responses to hormonal and mechanical stimuli. …

Efficacy, safety and economy of denosumab and zoledronic acid in the treatment of bone metastases of solid tumors and multiple myeloma: a systematic review and meta-analysis.

ObjectiveTo conduct a comprehensive comparison of the efficacy, safety, and cost-effectiveness of denosumab versus zoledronic acid in patients with bone metastases from solid tumors and multiple myeloma.MethodsA systematic search of PubMed, Web of Science, Embase, and major Chinese databases was performed for studies published up to 30 September 2025. Eligible evidence included randomized controlled trials, cohort studies, and pharmacoeconomic analyses. Random-effects models were applied for quantitative synthesis. The certainty of evidence for key outcomes was assessed using the GRADE framewo

Lenalidomide use in multiple myeloma (Review).

Lenalidomide is a second-generation new immunomodulatory medication used to treat multiple myeloma (MM). Its mechanism of action involves affecting the expression of vascular endothelial growth factor, interleukin-6, cytochrome c, caspase-8, as well as other factors including immunological modulation and the direct killing of cells, among others, rendering it a fundamental medication, useful for the treatment of MM. Combining lenalidomide with other medications such dexamethasone, bortezomib, ixazomib, carfilzomib and daratumumab can markedly alleviate MM. When autologous-hematopoietic stem ce

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… PMC3357942 24 Bou Zerdan M Nasr L Kassab J Saba L Ghossein M Yaghi M Dominguez B Chaulagain CP Adhesion molecules in multiple myeloma oncogenesis and targeted therapy Int J Hematol Oncol 11 IJH39 2022 10.2217/ijh-2021-0017 35663420 PMC9136637 25 Qu X Mei J Yu Z Zhai Z Qiao H Dai K Lenalidomide regulates osteocytes …

Alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions - an in vivo experiment.

PURPOSE: Medication-related osteonecrosis occurs exclusively in the jaw bones. However, the exact pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) and the unique predisposition of the jaw bones have not been elucidated, making its treatment a challenge. Recent evidence indicates that macrophages might play a pivotal role in MRONJ pathogenesis. The aim of the present study was to compare the macrophage populations between the craniofacial and extracranial skeleton and to investigate the changes induced by zoledronate (Zol) application and surgical interventions. MATERIALS AN

Emerging Roles of Osteoclasts in the Modulation of Bone Microenvironment and Immune Suppression in Multiple Myeloma.

Multiple myeloma (MM) is one of the most common forms of hematologic malignancy resulting from cancerous proliferation of mature malignant plasma cells (MPCs). But despite the real improvement in therapeutics in the past years, it remains largely incurable. MM is the most frequent cancer to involve bone due to the stimulation of osteoclast (OCL) differentiation and activity. OCLs have a unique capacity to resorb bone. However, recent studies reveal that they are not restrained to this sole function. They participate in the control of angiogenesis, medullary niches, and immune responses, includ

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… Interaction between RANK expressed on pre-OCLs and RANKL expressed on MSCs, OBLs, and osteocytes plays a key role in the differentiation, fusion, survival, and activity of OCLs, whereas osteoprotegerin (OPG), a decoy receptor for RANK ligand secreted mainly by stromal cells, inhibits RANK-RANKL signaling …

The emerging role of exosomes in innate immunity, diagnosis and therapy.

Exosomes, which are nano-sized transport bio-vehicles, play a pivotal role in maintaining homeostasis by exchanging genetic or metabolic information between different cells. Exosomes can also play a vital role in transferring virulent factors between the host and parasite, thereby regulating host gene expression and the immune interphase. The association of inflammation with disease development and the potential of exosomes to enhance or mitigate inflammatory pathways support the notion that exosomes have the potential to alter the course of a disease. Clinical trials exploring the role of exo

Bone and joint quality remains impaired in long-term controlled acromegaly: an HR-pQCT study.

CONTEXT: Joint and bone disorders are frequent, disabling complications of acromegaly that progress despite biochemical remission. HR-pQCT provides a precise assessment of bone and joint quality. OBJECTIVE: To evaluate joint and bone quality in patients with long-term controlled acromegaly. DESIGN: Cross-sectional study. PARTICIPANTS: 17 acromegaly patients and 17 age- and sex-matched controls. MEASURES: HR-pQCT of hand joints, tibia, and radius; bone microindentation; vertebral fracture assessment; dual X-ray absorptiometry; circulating bone biomarkers; questionnaires. RESULTS: Patients

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… Bone turnover markers have been found to be increased in active acromegaly [ 27 ], whereas sclerostin—an inhibitor of bone formation secreted by osteocytes—has shown a more divergent pattern as relates to acromegaly activity, with both significantly higher and lower values being reported [ 33 , 39 , …

Management of Bone Health Considerations in Patients with Cancer.

Background: Older adults with cancer are surviving longer due to earlier detection and more effective treatments for advanced stages. This population is at an elevated risk of osteoporosis due to age-related changes in bone density as well as the impact of cancer and cancer treatments on the skeletal system. Main Body: Cancer treatments are associated with increased bone loss and fracture risk via a variety of mechanisms. International guidelines recommend screening for cancer treatment-induced bone loss and provide treatment algorithms for pharmacological agents for those on hormonal therapy.