{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T04:08:15Z","timestamp":1792382895861,"version":"4.4.0"},"reference-count":111,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T00:00:00Z","timestamp":1570147200000},"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 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 NF\u03baB 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 homeostasis requires a perfect space\u2013time coordination of the involved signals. When osteoclastogenesis is poorly balanced with the differentiation of the bone forming counterparts, i.e., osteoblasts, physiological bone remodelling can turn into a pathological state, causing the systematic disruption of bone tissue which results in osteopenia or osteolysis. Examples of these conditions are represented by osteoporosis, Paget\u2019s disease, bone metastasis, and multiple myeloma. Therefore, drugs targeting osteoclastogenesis, such as bisphosphonates and an anti-RANKL monoclonal antibody, have been developed and are currently used in the treatment of such diseases. Despite their demonstrated therapeutic efficacy, these agents are unfortunately not devoid of side effects. In this regard, a condition called osteonecrosis of the jaw (ONJ) has been recently correlated with anti-resorptive therapy. In this review we will address the involvement of osteoclasts and osteoclast-related factors in the pathogenesis of ONJ. It is to be hoped that a better understanding of the biological mechanisms underlying bone remodelling will help in the design a medical therapeutic approach for ONJ as an alternative to surgical procedures.<\/jats:p>","DOI":"10.3390\/ijms20194925","type":"journal-article","created":{"date-parts":[[2019,10,7]],"date-time":"2019-10-07T03:34:01Z","timestamp":1570419241000},"page":"4925","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["From Osteoclast Differentiation to Osteonecrosis of the Jaw: Molecular and Clinical Insights"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5281-6840","authenticated-orcid":false,"given":"Alexandre","family":"Anesi","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences for Children &amp; Adults, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3764-7046","authenticated-orcid":false,"given":"Luigi","family":"Generali","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medicine, Dentistry and Morphological Sciences with Transplant Surgery, Oncology and Regenerative Medicine Relevance, University of Modena and Reggio Emilia, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Sandoni","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giuseppe Campi 287, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Pozzi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences for Children &amp; Adults, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Grande","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giuseppe Campi 287, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and activation","volume":"423","author":"Boyle","year":"2003","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nrrheum.2011.23","article-title":"Advances in osteoclast biology: Old findings and new insights from mouse models","volume":"7","author":"Edwards","year":"2011","journal-title":"Nat. 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