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Biomarker-Driven Approaches to Bone Metastases: From Molecular Mechanisms to Clinical Applications.

Bone metastases represent a critical complication in oncology, frequently indicating advanced malignancy and substantially reducing patient quality of life. This review provides a comprehensive analysis of the complex interactions between tumor cells and the bone microenvironment, emphasizing the relevance of the "seed and soil" hypothesis, the RANK/RANKL/OPG signaling axis, and Wnt signaling pathways that collectively drive metastatic progression. The molecular and cellular mechanisms underlying the formation of osteolytic and osteoblastic lesions are examined in detail, with a particular foc

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

Impact of bisphosphonate drugs on dental implant healing and peri-implant hard and soft tissues: a systematic review.

OBJECTIVE: Implantology represents the gold standard for oral rehabilitation, unfortunately, often, despite there are no local contraindications to this type of rehabilitation, there are uncertainties regarding the general health of our patients. Many patients nowadays take bisphosphonate drugs, often without first seeking advice from an oral surgeon or a dentist. The purpose of this review is precisely to highlight any contraindications to this type of treatment reported in the literature, in patients who take or have taken bisphosphonate drugs. METHODS: For this study the scientific informa

Complementarity of surgical therapy, photobiomodulation, A-PRF and L-PRF for management of medication-related osteonecrosis of the jaw (MRONJ): an animal study.

BACKGROUND: This study aimed to evaluate the complementarity of surgical therapy, photobiomodulation (PBM), advanced platelet-rich fibrin (A-PRF), and Leukocyte and platelet-rich fibrin (L-PRF) for the management of medication-related osteonecrosis of the jaw (MRONJ). METHODS: Sixty rats underwent injection of zoledronate followed by left mandibular first and second molar extractions to induce MRONJ lesions. All rats were examined for the signs of MRONJ 8 weeks post-dental extraction. Forty-nine rats with positive signs of MRONJ were appointed to seven different groups as follows: control (Ct

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… Park J-H Kim J-W Kim S-J Does the addition of bone morphogenetic protein 2 to platelet-rich fibrin improve healing after treatment for medication-related osteonecrosis of the jaw? J Oral Maxillofac Surg 2017 75 6 1176 1184 10.1016/j.joms.2016.12.005 28042979 38. …

Pharmacological inhibition of myostatin effectively ameliorates osteolytic lesions in syngeneic and xenograft breast cancer mouse models.

Breast cancer (BC)-derived bone metastases colonize bone and drive severe bone degradation through complex interactions with bone-resorbing osteoclasts (OCs). Subsequent bone resorption liberates matrix-stored factors, such as TGF-β and calcium, which further stimulate tumor proliferation and exacerbate bone destruction. Myostatin (Mstn), a member of the TGF-β superfamily, is known to enhance OC differentiation and bone resorption in models of musculoskeletal disease; however, its role in BC-associated bone lesions and metastases remains unknown. Here, we demonstrate that bone metastases from

RANKL Drives Bone Metastasis in Mammary Cancer: Protective Effects of Anti-Resorptive Treatments.

Receptor activator of nuclear factor-κB ligand (RANKL) is essential for osteoclast formation and bone resorption, in osteolytic conditions such as osteoporosis and bone metastases. However, its role in metastasis progression remains incompletely understood. Herein, we examined whether the overexpression of human RANKL in transgenic mice (TgRANKL) affects their susceptibility to breast cancer bone metastasis compared to their wild-type (WT) littermates. Bone metastasis was induced by injecting EO771 mouse mammary adenocarcinoma cells into the caudal artery of syngeneic WT and TgRANKL mice. RANK

Epigenetic modification in diabetic kidney disease.

Diabetic kidney disease (DKD) is a common microangiopathy in diabetic patients and the main cause of death in diabetic patients. The main manifestations of DKD are proteinuria and decreased renal filtration capacity. The glomerular filtration rate and urinary albumin level are two of the most important hallmarks of the progression of DKD. The classical treatment of DKD is controlling blood glucose and blood pressure. However, the commonly used clinical therapeutic strategies and the existing biomarkers only partially slow the progression of DKD and roughly predict disease progression. Therefor

Non-Interventional Prospective Observational Study of Platelet Rich Fibrin as a Therapy Adjunctive in Patients with Medication-Related Osteonecrosis of the Jaw.

BACKGROUND: Medication-related osteonecrosis (MRONJ) of the jaw is a severe and feared side effect of antiresorptive therapy in the oncological setting. With growing evidence that impaired angiogenesis may represent a key factor in pathogenesis, the aim of this study was to evaluate an autologous platelet concentrate as a possible additive in surgical therapy to optimize vascularization and, subsequently, resolution rates. MATERIAL AND METHODS: A non-interventional, prospective, multicenter study was conducted, and all patients with stage I-III MRONJ, undergoing antiresorptive therapy for an

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… Does the Addition of Bone Morphogenetic Protein 2 to Platelet-Rich Fibrin Improve Healing After Treatment for Medication-Related Osteonecrosis of the Jaw? J. Oral Maxillofac. Surg. 2017;75:1176–1184. doi: 10.1016/j.joms.2016.12.005. 23. …

Mechanism of Action of Bortezomib and the New Proteasome Inhibitors on Myeloma Cells and the Bone Microenvironment: Impact on Myeloma-Induced Alterations of Bone Remodeling.

Multiple myeloma (MM) is characterized by a high capacity to induce alterations in the bone remodeling process. The increase in osteoclastogenesis and the suppression of osteoblast formation are both involved in the pathophysiology of the bone lesions in MM. The proteasome inhibitor (PI) bortezomib is the first drug designed and approved for the treatment of MM patients by targeting the proteasome. However, recently novel PIs have been developed to overcome bortezomib resistance. Interestingly, several preclinical data indicate that the proteasome complex is involved in both osteoclast and ost

YKL-40-A Protein in the Field of Translational Medicine: A Role as a Biomarker in Cancer Patients?

YKL-40 is a 40 kDa glycoprotein produced by cancer cells, inflammatory cells and stem cells. It probably has a role in cell proliferation and differentiation, inflammation, protection against apoptosis, stimulation of angiogenesis, and regulation of extracellular tissue remodelling. Plasma levels of YKL-40 are often elevated in patients with localized or advanced cancer compared to age-matched healthy subjects. Several studies have demonstrated that high plasma YKL-40 is an independent prognostic biomarker of short survival in patients with different types of cancer. However, there is not yet

From Osteoclast Differentiation to Osteonecrosis of the Jaw: Molecular and Clinical Insights.

Bone physiology relies on the delicate balance between resorption and formation of its tissue. Bone resorption depends on a process called osteoclastogenesis in which bone-resorbing cells, i.e., osteoclasts, are produced by the differentiation of more undifferentiated progenitors and precursors. This process is governed by two main factors, monocyte colony-stimulating factor (M-CSF) and receptor activator of NFκB ligand (RANKL). While the former exerts a proliferating effect on progenitors/precursors, the latter triggers a differentiation effect on more mature cells of the same lineage. Bone h

Модулирование ренального фиброза: новая роль фактора роста гепатоцитов.

Введение и обоснование фактора роста Hepatocyte (HGF) является многофункциональным белком, связанным с ростом и расширением клеток. Известно, что HGF в значительной степени проявляется в почечной ткани и в ее роли в залечивании ран и распространении тканей. Эта обзорная статья была направлена на изучение патогенеза HGF в почечной фиброзе в дополнение к его связи с взаимосвязанными подстрекательскими заболеваниями, такими, как гипертония и диабет. 2025 - выявление и сопоставление исследований, посвященных взаимосвязи между почечным фиброзом и ГФУ в доклинических и клинических условиях. Полученн

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

Hypercalcemia in Cancer: Causes, Effects, and Treatment Strategies.

Calcium plays central roles in numerous biological processes, thereby, its levels in the blood are under strict control to maintain homeostatic balance and enable the proper functioning of living organisms. The regulatory mechanisms ensuring this balance can be affected by pathologies such as cancer, and as a result, hyper- or hypocalcemia can occur. These states, characterized by elevated or decreased calcium blood levels, respectively, have a significant effect on general homeostasis. This article focuses on a particular form of calcium metabolism disorder, which is hypercalcemia in neoplasm

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

Emergence of Cancer-Associated Fibroblasts as an Indispensable Cellular Player in Bone Metastasis Process.

Bone metastasis is frequently complicated in patients with advanced solid cancers such as breast, prostate and lung cancers, and impairs patients' quality of life and prognosis. At the first step of bone metastasis, cancer cells adhere to the endothelium in bone marrow and survive in a dormant state by utilizing hematopoietic niches present therein. Once a dormant stage is disturbed, cancer cells grow through the interaction with various bone marrow resident cells, particularly osteoclasts and osteoblasts. Consequently, osteoclast activation is a hallmark of bone metastasis. As a consequence,

Anemia in Chronic obstructive pulmonary disease: Prevalence, pathogenesis, and potential impact.

Chronic obstructive pulmonary disease (COPD) is a common preventable and treatable lifestyle-related disease with high global prevalence. COPD is associated with significant morbidity and mortality worldwide. Comorbidities are important events in the natural history of the disease and have a negative effect on the morbidity and mortality of COPD patients. Cardiac diseases, lung cancer, osteoporosis, and depression are common comorbidities reported for COPD. Recently, anemia has been recognized as a frequent comorbidity in COPD patients. The prevalence of anemia in patients with COPD varies fro

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… Inanemia of multiplemyeloma, hepcidinisinduced by increased bone morphogenetic protein 2. Blood. 2010;116:3635–44. doi: 10.1182/blood-2010-03-274571. 46. Besson-Fournier C, Latour C, Kautz L, Bertrand J, Ganz T, Roth MP, et al. …

Osteocytes and Bone Metastasis.

Bone is the most frequent site of breast cancer and prostate cancer metastasis, and one of the most common sites of metastasis for many solid tumors. Once cancer cells colonize in the bone, it imposes a major clinical challenge for the treatment of the disease, and fatality rates increase drastically. Bone, the largest organ in the body, provides a fertile microenvironment enriched with nutrients, growth factors and hormones, a generous reward for cancer cells. Dependent on cancer type, cancer cells can cause osteoblastic (bone forming) or osteolytic lesions to promote the net resorption and/o

The Mode-of-Action of Targeted Alpha Therapy Radium-223 as an Enabler for Novel Combinations to Treat Patients with Bone Metastasis.

Bone metastasis is a common clinical complication in several cancer types, and it causes a severe reduction in quality of life as well as lowering survival time. Bone metastases proceed through a vicious self-reinforcing cycle that can be osteolytic or osteoblastic in nature. The vicious cycle is characterized by cancer cells residing in bone releasing signal molecules that promote the differentiation of osteoclasts and osteoblasts either directly or indirectly. The increased activity of osteoclasts and osteoblasts then increases bone turnover, which releases growth factors that benefit metast

Complete Blood Count Parameters and Bone Health: Clinical and Experimental Evidence.

Osteoporotic fractures pose a significant burden in aging populations, yet current assessment strategies may overlook systemic factors influencing bone health. Emerging evidence suggests that complete blood count (CBC) parameters, including red blood cell indices, white blood cell (WBC) counts and subtypes, and platelet counts, are associated with skeletal fragility and fracture risk. Anemia has been consistently linked to reduced bone mineral density and increased fracture susceptibility, potentially due to impaired oxygen delivery and osteoblast dysfunction. Elevated red cell distribution wi