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Pathogenesis of bone disease in multiple myeloma: from bench to bedside.

Osteolytic bone disease is the hallmark of multiple myeloma, which deteriorates the quality of life of myeloma patients, and it affects dramatically their morbidity and mortality. The basis of the pathogenesis of myeloma-related bone disease is the uncoupling of the bone-remodeling process. The interaction between myeloma cells and the bone microenvironment ultimately leads to the activation of osteoclasts and suppression of osteoblasts, resulting in bone loss. Several intracellular and intercellular signaling cascades, including RANK/RANKL/OPG, Notch, Wnt, and numerous chemokines and interleu

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… It is expressed in the periosteum as a response to mechanical load and it is implicated in cell migration of bone-remodeling cells. …

Clinical considerations for medication-related osteonecrosis of the jaw: a comprehensive literature review.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ), which was first reported as bisphosphonate-related osteonecrosis of the jaw (BRONJ) in bisphosphonate users, is a rare but severe soft and hard tissue disease induced by several types of medications. There has been a deluge of information about MRONJ, such as epidemiology, risk factors, clinical recommendations for dental treatment to prevent it, and treatment strategies in medication-prescribed users. The aim of this study was to comprehensively review recent articles and provide the current scientific information about MRONJ, e

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… Moreover, it has been recommended that smoothing the remaining sharp edges of alveolar bone and wound closure with mucoperiosteal flaps lined by periosteum should be performed [ 30 ]. …

Chinese expert consensus on the diagnosis and treatment of bone metastasis in lung cancer (2022 edition).

Lung cancer is the leading cause of cancer-related deaths worldwide. Bone is a common metastatic site of lung cancer, about 50% of bone metastatic patients will experience skeletal related events (SREs). SREs not only seriously impact the quality of life of patients, but also shorten their survival time. The treatment of bone metastasis requires multi-disciplinary therapy (MDT) and development of individualized treatment plan. In order to standardize the diagnosis and treatment of bone metastasis in lung cancer, the expert group of the MDT Committee of the Chinese Medical Doctor Association ha

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… Meanwhile, severe pain is not only caused by the pain factos produced by tumor cells, such as prostaglandin, interleukin-1 (IL-1), and the tumor necrosis factor (TNF), but also caused by the tumor involvement in the periosteum, nerve, and soft tissue. …

Current options for the treatment of Paget's disease of the bone.

Paget's disease of bone (PDB) is a chronic bone remodelling disorder characterized by increased osteoclast-mediated bone resorption, with subsequent compensatory increases in new bone formation, resulting in a disorganized mosaic of woven and lamellar bone at affected skeletal sites. This disease is most often asymptomatic but can be associated with bone pain or deformity, fractures, secondary arthritis, neurological complications, deafness, contributing to substantial morbidity and reduced quality of life. Neoplastic degeneration of pagetic bone is a relatively rare event, occurring with an i

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… It may arise from increased vascularity, from distortion of the periosteum due to disorganized remodeling, or from a focus of mechanical stress. Alternatively, another source of pain may be from irritation of nerves supplying affected bones. …

Recent advances in CAR-MSCs: the new engine of cellular immunotherapy evolution.

In recent years, the development of chimeric antigen receptor (CAR) technology has greatly promoted the progress of cellular immunotherapy. Among them, CAR-T cell therapy has shown remarkable clinical effects in the treatment of hematological malignancies. However, this therapy still faces a series of challenges, including immunogenicity, toxic side effects, and insufficient maintenance of long-term efficacy. The latest research progress has extended CAR technology to mesenchymal stem cells (MSCs), and the resulting CAR-MSCs combine the precise targeting ability of CAR molecules with the inher

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… For example, MSCs derived from the BM, synovium, and periosteum present the highest alizarin red positivity rate for osteogenesis; amniotic MSCs demonstrate superior chondrogenic potential [ 63 ]; the number of BM-MSCs decreases sharply with age. …

Adiponectin signalling in bone homeostasis, with age and in disease.

Adiponectin is the most abundant circulating adipokine and is primarily involved in glucose metabolism and insulin resistance. Within the bone, osteoblasts and osteoclasts express the adiponectin receptors, however, there are conflicting reports on the effects of adiponectin on bone formation and turnover. Many studies have shown a pro-osteogenic role for adiponectin in in vivo murine models and in vitro: with increased osteoblast differentiation and activity, alongside lower levels of osteoclastogenesis. However, human studies often demonstrate an inverse relationship between adiponectin conc

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… Skeletal cell fate decisions within periosteum and bone marrow during bone regeneration. J. Bone Miner. Res. 2009;24:274–282. doi: 10.1359/jbmr.081003. 44. Michaud J, Im D-S, Hla T. Inhibitory role of sphingosine 1-phosphate receptor 2 in macrophage recruitment during Inflammation. J. …

Nuances in the treatment of malignant tumors of the clival and petroclival region.

Introduction Malignancies of the clivus and petroclival region are mainly chordomas and chondrosarcomas. Although a spectrum of malignancies may present in this area, a finite group of commonly encountered malignant pathologies will be the focus of this review, as they are recognized to be formidable pathologies due to adjacent critical neurovascular structures and challenging surgical approaches. Objectives The objective is to review the literature regarding medical and surgical management of malignant tumors of the clival and petroclival region with a focus on clinical presentation, diagnost

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… Cranial nerve VI travels through the subarachnoid space and pierces the meningeal layer of dura immediately behind the petroclival synchondrosis and then travels in the intradural space, then between the meningeal layer and the petroclival periosteum, in a superolateral orientation toward Dorello's canal …

Balancing the Scales: The Dual Role of Interleukins in Bone Metastatic Microenvironments.

Bone metastases, a common and debilitating consequence of advanced cancers, involve a complex interplay between malignant cells and the bone microenvironment. Central to this interaction are interleukins (ILs), a group of cytokines with critical roles in immune modulation and inflammation. This review explores the dualistic nature of pro-inflammatory and anti-inflammatory interleukins in bone metastases, emphasizing their molecular mechanisms, pathological impacts, and therapeutic potential. Pro-inflammatory interleukins, such as IL-1, IL-6, and IL-8, have been identified as key drivers in pro

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… Using a human periosteum-derived cell model, it was found that both IL-17A and IL-17F promote osteogenic differentiation and bone formation. Blocking these cytokines with Bimekizumab, effectively inhibited this process. … 17A and IL-17F, improves bone health | Infections, nasopharyngitis, oral candidiasis | Effective in hidradenitis suppurativa and spondyloarthritis; improves key outcomes such as disease activity, functional status, and quality of life | Inhibits osteogenic differentiation and bone formation in human periosteum-derived …

Infectious Diseases

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… Imaging of choice for specific body sites (vertebrae, diabetic foot) ULTRASOUND —fluid collection adjacent to the bone without intervening soft tissue, elevation of the periosteum by >2 mm, and thickening of the periosteum. …

Disruption of the microenvironmental ecosystem in subchondral bone marrow lesions: Roles in osteoarthritis pathophysiology, pain and progression.

This narrative review explores the role of subchondral bone in the pathophysiology of osteoarthritis (OA), emphasizing the biomechanical and biochemical contributions that it makes to disease progression. A fresh perspective is presented by the authors in the form of a novel hypothesis that implicates mechano-inflammatory disruption of the bone marrow (BM) microenvironmental ecosystem (BM niche), unresolved inflammation, and fibrosis as key drivers of OA pathogenesis and pain. BMLs, detectable via magnetic resonance imaging (MRI), serve as dynamic imaging biomarkers that correlate with pain se

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… Biomechanical stress, pro-inflammatory cytokines (e.g., IL-1 β), plus growth factors belonging to the family of growth differentiation factors (GDFs) (e.g., TGF-β, BMPs) [ 66 , 67 ], and altered joint biomechanics stimulate mesenchymal progenitor cells in the periosteum to undergo chondrogenesis, followed …

Diagnosis and Treatment of Bone Metastases in Breast Cancer: Radiotherapy, Local Approach and Systemic Therapy in a Guide for Clinicians.

The standard care for metastatic breast cancer (MBC) is systemic therapies with imbrication of focal treatment for symptoms. Recently, thanks to implementation of radiological and metabolic exams and development of new target therapies, oligometastatic and oligoprogressive settings are even more common-paving the way to a paradigm change of focal treatments role. In fact, according to immunophenotype, radiotherapy can be considered with radical intent in these settings of patients. The aim of this literature review is to analyze available clinical data on prognosis of bone metastases from brea

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… Due to the release of chemical mediators, bone metastases are a common cause of cancer pain, with increasing of pressure in the bone, microfractures, stretching of the periosteum, reactive muscle spasm, nerve root infiltration, compression of the nerve due to collapse of the bone [ 12 ]. …

Understanding the Progression of Bone Metastases to Identify Novel Therapeutic Targets.

Bone is one of the most preferential target site for cancer metastases, particularly for prostate, breast, kidney, lung and thyroid primary tumours. Indeed, numerous chemical signals and growth factors produced by the bone microenvironment constitute factors promoting cancer cell invasion and aggression. After reviewing the different theories proposed to provide mechanism for metastatic progression, we report on the gene expression profile of bone-seeking cancer cells. We also discuss the cross-talk between the bone microenvironment and invading cells, which impacts on the tumour actions on su

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… Indeed, bone tissue is densely innervated by primary afferent neurons and sympathetic neurons located in the intramedullary bone and the periosteum. Bone resorption inhibitors decrease substantially the pain caused by expanding bone metastases. …

Loss of EGFR activity in skeletal stem/progenitor cells is associated with impaired fracture healing in aged mice.

The cellular and molecular events responsible for fracture healing becoming delayed with aging remain unclear. Epidermal growth factor receptor (EGFR) signaling has been reported to play a critical role in bone regeneration. However, knowledge of its specific function in skeletal stem cells during aging-induced fracture delayed union remains scant. In the present study, we first demonstrated that EGFR activity in skeletal stem/progenitor cells decreased as mice aged and thus resulted in delayed fracture healing. To further investigate whether the EGFR signaling can be targeted as a potential t

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… Periosteum contains skeletal stem cells with high bone regenerative potential controlled by Periostin Nat. Commun. 9 2018 773 10.1038/s41467-018-03124-z 29472541 PMC5823889 29 Buch T. Heppner F.L. Tertilt C. …

The osteoblast in regulation of tumor cell dormancy and bone metastasis.

Breast and prostate cancer are among the most common malignancies worldwide. After treatment of the primary tumor, distant metastases often occur after a long disease-free interval. Bone is a major site for breast and prostate cancer metastasis and approximately 70% of patients with advanced disese suffer from osteolytic or osteoblastic bone metastases, a stage at which the disease is incurable. In bone, the disseminated tumor cells (DTCs) can become quiescent or "dormant", a state where they are alive but not actively dividing. Alternatively, the cancer cells can proliferate, disturb the bone

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… A subset of MSCs termed “skeletal stem cells (SSCs)” represent cells that reside in the bone marrow, periosteum and growth plate and have the capacity to differentiate into osteoblasts, chondrocytes and adipocytes. …

GBA1 as a risk gene for osteoporosis in the specific populations and its role in the development of Gaucher disease.

BACKGROUND: Osteoporosis and its primary complication, fragility fractures, contribute to substantial global morbidity and mortality. Gaucher disease (GD) is caused by glucocerebrosidase (GBA1) deficiency, leading to skeletal complications. This study aimed to investigate the impact of the GBA1 gene on osteoporosis progression in GD patients and the specific populations. METHODS: We selected 8115 patients with osteoporosis (T-score ≤ - 2.5) and 55,942 healthy individuals (T-score > - 1) from a clinical database (N = 95,223). Monocytes from GD patients were evaluated in relation to endoplasmic

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… Lan K-C Wei K-T Lin P-W Lin C-C Won P-L Liu Y-F Chen Y-J Cheng B-H Chu T-MG Chen J-F Huang K-E Chang C Kang H-Y Targeted activation of androgen receptor signaling in the periosteum improves bone fracture repair Cell Death Dis 2022 13 2 123 10.1038/s41419-022-04595-1 35136023 PMC8826926 …

Pain Management in Patients with Multiple Myeloma: An Update.

Most patients with multiple myeloma (MM) suffer from chronic pain at every stage of the natural disease process. This review focuses on the most common causes of chronic pain in MM patients: (1) pain from myeloma bone disease (MBD); (2) chemotherapy-induced peripheral neuropathy as a possible consequence of proteasome inhibitor therapy (i.e., bortezomib-induced); (3) post-herpetic neuralgia as a possible complication of varicella zoster virus reactivation because of post-transplantation immunodepression; and (4) pain in cancer survivors, with increasing numbers due to the success of antiblasti

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… Acute and sharp pain after bone fracture is related to the sensory innervation of the periosteum, in which, conversely to the cortical bone, the density of A-delta and C-fibers is 1000 times greater [ 11 ]. …

Anterior Approach Total Ankle Arthroplasty with Patient-Specific Cut Guides.

BACKGROUND: Over the last 30 years, total ankle arthroplasty (TAA) has become a viable surgical option for end-stage ankle arthritis1,2. The … ension on the skin. The anterior distal tibia and the dorsal talus are cleaned of all soft tissues, periosteum, and possible residual cartilage in order to obtain a good cortical read. The patient-specific cut guides (INFINITY PROPHECY, Total Ankle System; Wright Medical Technology) are placed first at the distal tibia and are fixed with temporary pins. Ante …

Исцеление литических повреждений и восстановление костного здоровья в множестве миеломы посредством ингибиции склеростинов.

Множественная миелома (ММ) связана с изнурительным заболеванием костей, которое создает серьезные терапевтические проблемы. Болезнь костей MM характеризуется повышенной ресорбцией костей и подавлением остеобластов, что препятствует ремонту поврежденных костей. Склеростин, антагонист Wnt сигнализатора, выше у пациентов MM, и его ингибиция с нейтрализующим антителом (Scl-ab) была продемонстрирована для восстановления остеобластной функции в мышиных моделях MM. Однако остается неясным, может ли Scl-ab способствовать ремонту скелета, обеспечивать эффективный контроль над опухолью в сочетании с ант

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… After 2 weeks of treatment, a time point at which MM-induced bone loss and Scl-ab-induced bone anabolic effects are both evident, the muscle, periosteum, and epiphyses were removed from the tibias and femurs. The final dose of Scl-ab was administered 10 h before tissue collection. …

Exosomes: A new option for osteoporosis treatment.

Osteoporosis is a systemic bone disease characterized by reduced bone mass and destruction of bone microarchitecture, leading to increased bone fragility and susceptibility to fracture. However, the pathogenesis and molecular mechanisms of this disease remain unclear. Extracellular vesicles, structures originating from the plasma membrane and ranging from 30 nm to 5 µm in diameter, play an important role in intercellular communication in the bone microenvironment. Exosomes are extracellular vesicles that deliver cargo molecules, including endogenous proteins, lipids and nucleic acids. These ca

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… Exosomes and osteoblasts Osteoblasts are mainly derived from differentiation of MSCs in the periosteum and bone marrow, [ 78 , 79 ] as they play a key role in the synthesis, secretion and mineralization of the bone matrix. …

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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… Located in the periosteum and endosteum, OBs produce the components of the extracellular matrix, such as structural macromolecules, including type-I collagen, proteoglycans, and cell-attachment proteins; OBs lay the foundation for bone mineralization [ 36 ]. …