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However, clinical and radiological features alone have been shown to fail to predict skeletal related events of a bone metastasis (SREs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study focuses on key molecular players including Matrix Metalloproteinases (MMPs), Integrins, Bone Morphogenetic Proteins (BMPs), Parathormone\u2010related Protein (PTHrP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The RANK\/RANKL\/Osteoprotegerin (OPG) pathway, and N\u2010terminal peptide (NTx), involved in the metastatic process and bone integrity disruption. Elevated levels of these molecules have been pointed out as potential biomarkers for predicting SREs, but they have been poorly investigated. Moreover, batimastat, marimastat, tanomastat, andecaliximab, and HIV protease targeting MMPs; Volociximab\/M200, cilengitide, abituzumab, and FAK inhibitors targeting integrins; LDN193189, DMH1, and ISLR modulators targeting BMPs; and PTH (7\u201333)\u2010CBD targeting PTHrP have shown promising results antagonizing these molecules, but no effect on preventing and managing metastatic fractures has been assessed yet.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This paper underscores the importance of advanced molecular biology and transcriptomics in identifying novel therapeutic targets. The integration of these biomarkers with clinical and radiological assessments using artificial intelligence tools could revolutionize the diagnostics and treatment strategies for patients with bone metastases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.70901","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T05:10:52Z","timestamp":1745989852000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Inside a Metastatic Fracture: Molecular Bases and New Potential Therapeutic Targets"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5603-4002","authenticated-orcid":false,"given":"Alessandro","family":"Bruschi","sequence":"first","affiliation":[{"name":"Orthopedic and Traumatology Unit IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"},{"name":"Department of Biomedical and Neuromotor Sciences University of Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Sambri","sequence":"additional","affiliation":[{"name":"Orthopedic and Traumatology Unit IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0546-670X","authenticated-orcid":false,"given":"Michele","family":"Fiore","sequence":"additional","affiliation":[{"name":"Orthopedic and Traumatology Unit IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"},{"name":"Department of Medical and Surgical Sciences Alma Mater Studiorum University of Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Bubbico","sequence":"additional","affiliation":[{"name":"Orthopedic and Traumatology Unit IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Scollo","sequence":"additional","affiliation":[{"name":"Orthopedic and Traumatology Unit IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Pace","sequence":"additional","affiliation":[{"name":"Orthopedic and Traumatology Unit IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renato","family":"Zunarelli","sequence":"additional","affiliation":[{"name":"Orthopedic and Traumatology Unit IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Montanari","sequence":"additional","affiliation":[{"name":"Orthopedic and Traumatology Unit IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberta","family":"Cappelli","sequence":"additional","affiliation":[{"name":"Department of Radiology IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Di Prinzio","sequence":"additional","affiliation":[{"name":"Orthopedic and Traumatology Unit IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimiliano","family":"De Paolis","sequence":"additional","affiliation":[{"name":"Orthopedic and Traumatology Unit IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.otsr.2016.11.001"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.blo.0000093842.72468.73"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.adc9985"},{"key":"e_1_2_8_5_1","first-page":"1","article-title":"Skeletal Metastases in Pancreatic Cancer: A Retrospective Study and Review of the Literature","volume":"82","author":"Borad M. 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