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Impact of whole-body vibration exercise on physical performance and bone turnover in patients with monoclonal gammopathy of undetermined significance.

OBJECTIVE: Monoclonal Gammopathy of Undetermined Significance (MGUS) is a risk factor for reduced physical performance, osteoporosis, and fractures due to compromised musculoskeletal metabolism. In this condition it is unknown whether whole-body vibration (WBV) exercise favorably alters physical performance and bone metabolism. METHODS: To evaluate the effect of three-months WBV exercise (30 min; 2x/week) including an optional three-month extension on physical performance, bone metabolism and bone mineral density. Endpoints included functional assessments, bone turnover markers and bone miner

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… While only minor sclerostin expression is detected in primary MM cells from patients or MM cell lines, osteocytes seem to be the primary source for sclerostin in myeloma bone disease [11] , [13] . … While sclerostin is preferentially secreted by osteocytes, DKK-1 may preferentially stem from plasma cells in the bone marrow microenvironment [11] , [13] , [58] . …

Primary Osteoporosis Induced by Androgen and Estrogen Deficiency: The Molecular and Cellular Perspective on Pathophysiological Mechanisms and Treatments.

Primary osteoporosis is closely linked to hormone deficiency, which disrupts the balance of bone remodeling. It affects postmenopausal women but also significantly impacts older men. Estrogen can promote the production of osteoprotegerin, a decoy receptor for RANKL, thereby preventing RANKL from activating osteoclasts. Furthermore, estrogen promotes osteoblast survival and function via activation of the Wnt signaling pathway. Likewise, androgens play a critical role in bone metabolism, primarily through their conversion to estrogen in men. Estrogen deficiency accelerates bone resorption throug

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… Osteocyte (OS) Osteocytes are considered terminally differentiated bone cells arising from osteoblasts, which are distributed all over the entire skeleton. They have a long lifespan of up to 50 years, outnumbering osteoclasts by a thousandfold and osteoblasts by tenfold [ 54 ]. … For example, the distribution of ERα in osteocytes is more prevalent in cortical bone than that in trabecular bone [ 59 ], while ERβ in osteocytes shows higher expression in trabecular bone [ 59 ]. …

Mechanisms of bone pain: Progress in research from bench to bedside.

The field of research on pain originating from various bone diseases is expanding rapidly, with new mechanisms and targets asserting both peripheral and central sites of action. The scope of research is broadening from bone biology to neuroscience, neuroendocrinology, and immunology. In particular, the roles of primary sensory neurons and non-neuronal cells in the peripheral tissues as important targets for bone pain treatment are under extensive investigation in both pre-clinical and clinical settings. An understanding of the peripheral mechanisms underlying pain conditions associated with va

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… Osteocytes are the terminally differentiated osteoblasts and the dominant cell type embedded in the bone matrix. … Osteocytes are terminally differentiated osteoblasts. A recent study showed that osteocytes isolated from OA patients expressed a low level of NGF. The NGF production in osteocytes was further increased when the cells were incubated in tumor necrosis factor-alpha (TNF-α) 45 . …

Diffusion MRI for Assessment of Bone Quality; A Review of Findings in Healthy Aging and Osteoporosis.

Diffusion MRI (dMRI) is a growing imaging technique with the potential to provide biomarkers of tissue variation, such as cellular density, tissue anisotropy, and microvascular perfusion. However, the role of dMRI in characterizing different aspects of bone quality, especially in aging and osteoporosis, has not yet been fully established, particularly in clinical applications. The reason lies in the complications accompanied with implementation of dMRI in assessment of human bone structure, in terms of acquisition and quantification. Bone is a composite tissue comprising different elements, ea

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… Osteocytes located inside the lacunae (pores) of the lacunar‐canalicular porosity sense the mechanical loading and are activated by the drag induced by the fluid flow. 19 Abnormally high fluid flow informs the osteocytes to signal osteoblasts for bone formation, while abnormally low flow recruits the … However, bone blood flow changes could influence this process either through alteration of bone interstitial fluid to stimulate the osteocytes or by changing the milieu of the bone marrow. The latter stimulates bone‐lining cells near the marrow without activating the osteocytes. …

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

Заболеваемость ломками и ее связь со смертностью у нескольких пациентов, страдающих миеломой: общенациональное когортное исследование ( " Microma " )CAREMM-2105 - обучение).

Множественная миелома (ММ), как известно, подрывает целостность костей, что ведет к повышению риска переломов, что подрывает качество жизни и увеличивает смертность. В ходе этого исследования были исследованы случаи переломов у пациентов, страдающих ММ, и была изучена связь между переломами после диагностирования ММ и смертностью с использованием базы данных Корейской национальной службы медицинского страхования. Повреждения были сопоставлены между пациентами MM (n = 9365) и 1::1 Сопоставимая контрольная группа с общим населением. Пациенты MM продемонстрировали значительно более высокую кумуля

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… Nakashima T Evidence for osteocyte regulation of bone homeostasis through RANKL expression Nat. Med. 2011 17 1231 1234 10.1038/nm.2452 21909105 Nakashima, T. et al. Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat. … Poole KE Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation Faseb J 2005 19 1842 1844 10.1096/fj.05-4221fje 16123173 Poole, K. E. et al. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. …

Molecular events in the jaw vascular unit: A traditional review of the mechanisms involved in inflammatory jaw bone diseases.

Inflammatory jaw bone diseases are common in stomatology, including periodontitis, peri-implantitis, medication-related osteonecrosis of the jaw, radiation osteomyelitis of the jaw, age-related osteoporosis, and other specific infections. These diseases may lead to tooth loss and maxillofacial deformities, severely affecting patients' quality of life. Over the years, the reconstruction of jaw bone deficiency caused by inflammatory diseases has emerged as a medical and socioeconomic challenge. Therefore, exploring the pathogenesis of inflammatory diseases associated with jaw bones is crucial fo

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… Osteocytes Osteocytes are dendritic-shaped cells embedded in the bone matrix and regulate bone formation and resorption. One study has found that osteocytes play an important role in the bone defect reparation and periodontitis. … Nevertheless, the accumulation of oxidative stress biomarkers, such as reactive oxygen species, leads to osteocyte apoptosis and bone loss [ 25 – 26 ] . …

Drug delivery for age-related bone diseases: From therapeutic targets to common and emerging therapeutic strategies.

With the accumulation of knowledge on aging, people have gradually realized that among the many factors that cause individual aging, the accumulation of aging cells is an essential cause of organ degeneration and, ultimately, age-related diseases. Most cells present in the bone microenvironment gradually age over time, leading to an imbalance of osteogenesis, osteoclastogenesis, adipogenesis, and chondrogenesis. This imbalance contributes to age-related bone loss and the development of age-related bone diseases, such as osteoporosis. Bone aging can prolong the lifespan and delay the developmen

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… An increasing number of studies have shown that osteocytes play an indispensable role in bone aging and loss caused by aging. … Osteoblasts either undergo apoptosis or form new osteocytes ( Raggatt and Partridge, 2010 ). Bone mineralization begins and is completed at this stage ( Bala, 2010 ). Osteoclasts, osteoblasts, and osteocytes are three important bone tissue cells directly involved in bone remodeling. …

Novel Developments in the Treatment of Multiple Myeloma-Associated Bone Disease.

Osteolytic bone disease is present in about 80% of patients with multiple myeloma at the time of diagnosis. Managing bone disease in patients with multiple myeloma is a challenge and requires a multi-faceted treatment approach with medication, surgery, and radiation. The established treatments with intravenous or subcutaneous antiresorptives can cause debilitating adverse events for patients, mainly osteonecrosis of the jaw, which, traditionally, has been difficult to manage. Now, oral surgery is recommended and proven successful in 60-85% of patients. Patients with spinal involvement may bene

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… Osteocyte CIITA aggravates osteolytic bone lesions in myeloma Nat. Commun. 2022 13 3684 10.1038/s41467-022-31356-7 35760800 PMC9237076 102. Delgado-Calle J. Bellido T. Roodman G.D. Role of osteocytes in multiple myeloma bone disease Curr. Opin. Support. Palliat. … Direct Cell-To-Cell Interactions Between Osteocytes and Multiple Myeloma (MM) Cells Upregulate Sost and Downregulate OPG Expression In Osteocytes: Evidence For Osteocytic Contributions To MM-Induced Bone Disease Blood 2013 122 3140 10.1182/blood.V122.21.3140.3140 104. Panaroni C. Fulzele K. …

Switching Homes: How Cancer Moves to Bone.

Bone metastases (BM) are a very common complication of the most prevalent human cancers. BM are extremely painful and may be life-threatening when associated with hypercalcaemia. BM can lead to kidney failure and cardiac arrhythmias and arrest, but why and how do cancer cells decide to "switch homes" and move to bone? In this review, we will present what answers science has provided so far, with focus on the molecular mechanisms and cellular aspects of well-established findings, such as the concept of "vicious cycle" and "osteolytic" vs. "osteosclerotic" bone metastases; as well as on novel co

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… Osteocytes. In: Rosen C.J., editor. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Wiley; Washington, DC, USA: 2008. pp. 22–27. 18. Temiyasathit S., Jacobs C.R. The osteocyte primary cilium and its role in bone mechanotransduction. Ann. N. Y. Acad. … Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. 2007;5:464–475. doi: 10.1016/j.cmet.2007.05.001. 22. Bonewald L.F. The amazing osteocyte. J. Bone Miner. Res. 2011;26:229–238. doi: 10.1002/jbmr.320. 23. Noble B.S. The osteocyte lineage. Arch. …

Organoids as Innovative Models for Bone and Joint Diseases.

Bone is one of the key components of the musculoskeletal system. Bone and joint disease are the fourth most widespread disease, in addition to cardiovascular disease, cancer, and diabetes, which seriously affect people's quality of life. Bone organoids seem to be a great model by which to promote the research method, which further could improve the treatment of bone and joint disease in the future. Here, we introduce the various bone and joint diseases and their biology, and the conditions of organoid culture, comparing the in vitro models among 2D, 3D, and organoids. We summarize the differin

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… Osteocytes, which derive from osteoblasts and account for 90% of all bone cells, can detect mechanical loading. … After undergoing daily fluid shear stress, the stimulated osteocytes promoted osteoclast differentiation. …

Calcium Phosphate Bone Substitutes in the Prevention of Bisphosphonate-Related Osteonecrosis of the Jaw: A Review.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is characterized by exposed necrotic bone that often progresses with increasing pain and impaired quality of life. Zoledronate, the most potent and widely used bisphosphonate, has been strongly associated with BRONJ development following invasive dental procedures. Given the rising incidence of BRONJ, understanding and implementing effective preventive strategies have become imperative. Biomaterials based on synthetic hydroxyapatite and beta-tricalcium phosphate have been investigated as potential preventive agents. Their therapeutic rati

The Role of Extracellular Vesicles in Bone Metastasis.

Multiple types of cancer have the specific ability to home to the bone microenvironment and cause metastatic lesions. Despite being the focus of intense investigation, the molecular and cellular mechanisms that regulate the metastasis of disseminated tumor cells still remain largely unknown. Bone metastases severely impact quality of life since they are associated with pain, fractures, and bone marrow aplasia. In this review, we will summarize the recent discoveries on the role of extracellular vesicles (EV) in the regulation of bone remodeling activity and bone metastasis occurrence. Indeed,

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… Moreover, it was shown that osteocytes secrete vesicles regulating bone remodeling; indeed, osteocyte exosomes containing miR-218 can mediate the downregulation of sclerostin, thus stimulating osteoblast differentiation. … Sato et al. suggested that exosomes derived from osteocytes could act in the bone microenvironment, or could be released into circulation [ 62 ]. 2.1.2. …

Pathogenesis and Treatment of Myeloma-Related Bone Disease.

Multiple myeloma is a hematologic malignancy of plasma cells that causes bone-destructive lesions and associated skeletal-related events (SREs). The pathogenesis of myeloma-related bone disease (MBD) is the imbalance of the bone-remodeling process, which results from osteoclast activation, osteoblast suppression, and the immunosuppressed bone marrow microenvironment. Many important signaling cascades, including the RANKL/RANK/OPG axis, Notch signaling, the Wnt/β-Catenin signaling pathways, and signaling molecules, such as DKK-1, sclerostin, osteopontin, activin A, chemokines, and interleukins

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… Sclerostin is a glycoprotein inhibitor of osteoblast Wnt signaling produced by osteocytes, which causes a decrease in bone formation [ 156 ]. … Increased osteocyte death in multiple myeloma patients: Role in myeloma-induced osteoclast formation. Leukemia. 2012;26:1391–1401. doi: 10.1038/leu.2011.381. 11. …

Pathophysiology and treatment of osteoporosis: challenges for clinical practice in older people.

Osteoporosis, a common chronic metabolic bone disease is associated with considerable morbidity and mortality. As the prevalence of osteoporosis increases with age, a paralleled elevation in the rate of incident fragility fractures will be observed. This narrative review explores the origins of bone and considers physiological mechanisms involved in bone homeostasis relevant to management and treatment. Secondary causes of osteoporosis, as well as osteosarcopenia are discussed followed by an overview of the commonly used pharmacological treatments for osteoporosis in older people.

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… The cellular component of bone is chiefly composed of three cells: osteocytes, osteoblasts, and osteoclasts. Osteocytes are found in the lacunae of the matrix and have a mechano-sensory function in bone formation. Osteoblasts synthesize osteoid whilst osteoclasts enzymatically resorb bone [ 5 ]. … By the end of bone formation, approximately 10 to 15% of mature osteoblasts are entombed by the new bone matrix and differentiate into osteocytes. At rest osteocytes express sclerostin, which prevents WNT signalling (an inducer of bone formation) in osteoblasts [ 21 ]. …

Biological and Clinical Aspects of Metastatic Spinal Tumors.

Spine metastases are a common life-threatening complication of advanced-stage malignancies and often result in poor prognosis. Symptomatic spine metastases develop in the course of about 10% of malignant neoplasms. Therefore, it is essential for contemporary medicine to understand metastatic processes in order to find appropriate, targeted therapeutic options. Thanks to continuous research, there appears more and more detailed knowledge about cancer and metastasis, but these transformations are extremely complicated, e.g., due to the complexity of reactions, the variety of places where they oc

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… Osteocyte Physiology and Pathology Osteocytes have an impressive lifespan of up to 25 years, during which they undertake several important physiological functions. … They differentiate from osteoblasts with four stages of formation, type I preosteocytes (osteoblastic osteocytes), type II preosteocytes (osteoid osteocytes), and type III preosteocytes (young and old osteocytes) [ 90 ]. …

Printing the Pathway Forward in Bone Metastatic Cancer Research: Applications of 3D Engineered Models and Bioprinted Scaffolds to Recapitulate the Bone-Tumor Niche.

Breast cancer commonly metastasizes to bone, resulting in osteolytic lesions and poor patient quality of life. The bone extracellular matrix (ECM) plays a critical role in cancer cell metastasis by means of the physical and biochemical cues it provides to support cellular crosstalk. Current two-dimensional in-vitro models lack the spatial and biochemical complexities of the native ECM and do not fully recapitulate crosstalk that occurs between the tumor and endogenous stromal cells. Engineered models such as bone-on-a-chip, extramedullary bone, and bioreactors are presently used to model cellu

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… Osteocytes help to regulate the activities of osteoblasts and osteoclasts via mechanotransduction, and represent ~90–95% of cells in the bone [ 48 , 49 ]. Osteocytes are formed when osteoblasts become terminally differentiated and embedded in the bone matrix. … Osteoblast and osteocyte: Games without frontiers Arch. Biochem. Biophys. 2014 561 3 12 10.1016/j.abb.2014.05.003 24832390 40. Mullender M.M. Van Der Meer D. Huiskes H.R. Lips P. Osteocyte density changes in aging and osteoporosis Bone 1996 18 109 113 10.1016/8756-3282(95)00444-0 8833204 41. …

The Crosstalk Between B Cells and the Skeletal System During Development, Aging, and in Pathological Conditions.

Purpose of reviewIn this review, we describe the interaction between B cells and bone during development, aging, and disease. RECENT FINDINGS: There is an increased interest in identifying the mechanisms of interaction between immune cells and the skeletal system. This knowledge is critical for understanding the pathology of autoimmune diseases and developing therapeutic interventions. Humoral immunity depends on B cells and their secreted immunoglobulin (antibodies). Earlier studies described B cell influence on the skeletal system, with a major focus on the role of plasma cells and secreted

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… Thus, aging induces decreased activity of osteoprogenitors, osteoblasts, and osteocytes [ 60 ] and increased osteoclastogenesis [ 61 ] and adipocyte formation, culminating in bone fragility [ 53 ]. … Senescent and apoptotic osteocytes and aging: exercise to the rescue? Bone. 2019;121:255–8. 61. Kim H-N, Xiong J, MacLeod RS, Iyer S, Fujiwara Y, Cawley KM, et al. Osteocyte RANKL is required for cortical bone loss with age and is induced by senescence. …

The Impact of a 6-Week Nordic Walking Training Cycle and a 14-Hour Intermittent Fasting on Disease Activity Markers and Serum Levels of Wnt Pathway-Associated Proteins in Patients with Multiple Myeloma.

Background: Multiple myeloma (MM) accounts for about 10-15% of all diagnosed hematologic malignancies and about 1-2% of all cancer cases. Approximately 80-90% of MM patients develop bone disease and the changes rarely regress. It is only possible to stop or slow their progression. A major role in bone destruction in MM is attributed to the Wnt signaling pathway, and its action can be modified by various types of interventions including training and diet. Therefore, the aim of this project was to evaluate the effects of a Nordic Walking (NW) training cycle and intermittent fasting (IF) on the l

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… The modulation of SOST levels is the mechanism by which osteocytes coordinate osteogenesis in response to increased mechanical stimulation. This is likely through the release of local inhibition of Wnt signaling [ 14 ]. … In bone, as a result of shear stress on bone tubular fluid during exercise, integrin synthesis is stimulated, which induces the Wnt pathway in osteocytes and osteoblasts [ 4 , 17 ]. …

Dynamics of Bone Disease Biomarkers Dickkopf-1 and Sclerostin in Patients with Multiple Myeloma.

Dickkopf-1 (DKK-1) and sclerostin are essential Wnt/β-catenin pathway inhibitors, playing an important role in multiple myeloma bone disease (MBD). We aimed to examine the serum DKK-1 and sclerostin variations in newly diagnosed multiple myeloma (NDMM) patients at diagnosis and in the course of therapy, including autologous stem cell transplantation (ASCT). This study included 41 NDMM-patients and 33 controls. MBD was assessed by whole-body low-dose computed tomography. DKK-1 and sclerostin were assayed by commercial ELISA kits. At diagnosis, NDMM-patients revealed significantly higher DKK-1 a

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… Another antagonist of Wnt/β-catenin signaling is the small monomeric glycoprotein sclerostin, encoded by the Sost gene, secreted from osteocytes and articular chondrocytes [ 14 ]. … In a key paper of McDonald et al., it was shown that in MM, DKK-1 is expressed by MPCs, in contrast to sclerostin, which main source are osteocytes, but not MPCs [ 15 ]. …