{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:41:30Z","timestamp":1789170090260,"version":"build-2803163510"},"reference-count":97,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2018,6,8]],"date-time":"2018-06-08T00:00:00Z","timestamp":1528416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bone is the preferential site of metastasis for breast and prostate tumor. Cancer cells establish a tight relationship with the host tissue, secreting factors that stimulate or inhibit bone cells, receiving signals generated from the bone remodeling activity, and displaying some features of bone cells. This interplay between tumor and bone cells alters the physiological bone remodeling, leading to the generation of a vicious cycle that promotes bone metastasis growth. To prevent the skeletal-related events (SRE) associated with bone metastasis, approaches to inhibit osteoclast bone resorption are reported. The bisphosphonates and Denosumab are currently used in the treatment of patients affected by bone lesions. They act to prevent or counteract the SRE, including pathologic fractures, spinal cord compression, and pain associated with bone metastasis. However, their primary effects on tumor cells still remain controversial. In this review, a description of the mechanisms leading to the onset of bone metastasis and clinical approaches to treat them are described.<\/jats:p>","DOI":"10.3390\/ijms19061709","type":"journal-article","created":{"date-parts":[[2018,6,8]],"date-time":"2018-06-08T11:19:31Z","timestamp":1528456771000},"page":"1709","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Cellular and Molecular Mediators of Bone Metastatic Lesions"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9297-5184","authenticated-orcid":false,"given":"Giulia","family":"Battafarano","sequence":"first","affiliation":[{"name":"Bone Physiopathology Group, Multifactorial Disease and Complex Phenotype Research Area, Bambino Ges\u00f9 Children\u2019s Hospital, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Rossi","sequence":"additional","affiliation":[{"name":"Bone Physiopathology Group, Multifactorial Disease and Complex Phenotype Research Area, Bambino Ges\u00f9 Children\u2019s Hospital, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Marampon","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Policlinico Umberto I, Sapienza University of Rome, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3848-412X","authenticated-orcid":false,"given":"Andrea","family":"Del Fattore","sequence":"additional","affiliation":[{"name":"Bone Physiopathology Group, Multifactorial Disease and Complex Phenotype Research Area, Bambino Ges\u00f9 Children\u2019s Hospital, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1053\/ctrv.2000.0210","article-title":"Metastatic bone disease: Clinical features, pathophysiology and treatment strategies","volume":"27","author":"Coleman","year":"2001","journal-title":"Cancer Treat. 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