{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:52:43Z","timestamp":1790952763778,"version":"4.1.0"},"reference-count":205,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T00:00:00Z","timestamp":1709164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alfaisal University College of Medicine Office of Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The treatment of patients with advanced cancer poses clinical problems due to the complications that arise as the disease progresses. Bone metastases are a common problem that cancer patients may face, and currently, there are no effective drugs to treat these individuals. Prostate, breast, and lung cancers often spread to the bone, causing significant and disabling health conditions. The bone is a highly active and dynamic tissue and is considered a favorable environment for the growth of cancer. The role of osteoblasts and osteoclasts in the process of bone remodeling and the way in which their interactions change during the progression of metastasis is critical to understanding the pathophysiology of this disease. These interactions create a self-perpetuating loop that stimulates the growth of metastatic cells in the bone. The metabolic reprogramming of both cancer cells and cells in the bone microenvironment has serious implications for the development and progression of metastasis. Insight into the process of bone remodeling and the systemic elements that regulate this process, as well as the cellular changes that occur during the progression of bone metastases, is critical to the discovery of a cure for this disease. It is crucial to explore different therapeutic options that focus specifically on malignancy in the bone microenvironment in order to effectively treat this disease. This review will focus on the bone remodeling process and the effects of metabolic disorders as well as systemic factors like hormones and cytokines on the development of bone metastases. We will also examine the various therapeutic alternatives available today and the upcoming advances in novel treatments.<\/jats:p>","DOI":"10.3390\/ijms25052846","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T06:07:53Z","timestamp":1709273273000},"page":"2846","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Bridging the Gap in Understanding Bone Metastasis: A Multifaceted Perspective"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6954-7790","authenticated-orcid":false,"given":"Basant","family":"Elaasser","sequence":"first","affiliation":[{"name":"Department of Anatomy, College of Medicine, Alfaisal University, Riyadh 1153, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour","family":"Arakil","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Medicine, Alfaisal University, Riyadh 1153, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9708-2111","authenticated-orcid":false,"given":"Khalid S.","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Medicine, Alfaisal University, Riyadh 1153, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1002\/mc.23666","article-title":"GRP78 Promotes Bone Metastasis of Prostate Cancer by Regulating Bone Microenvironment through Sonic Hedgehog Signaling","volume":"63","author":"Yang","year":"2023","journal-title":"Mol. 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