{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:21:30Z","timestamp":1792736490670,"version":"4.5.0"},"reference-count":73,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,9,23]],"date-time":"2012-09-23T00:00:00Z","timestamp":1348358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>Eur J Clin Invest 2012; 42 (12): 1332\u20131341<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      <jats:bold>Background\u2002<\/jats:bold>\n                      Bone remodelling maintains skeletal integrity by osteoclasts removing foci of damaged bone and osteoblasts replacing them with new bone. Diseases associated with increased bone resorption have increased remodelling often with inadequate bone formation and increased risk of fracture. New therapies are needed for these diseases to reduce resorption and increase formation.\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:bold>Design\u2002<\/jats:bold>\n                      The molecular mechanisms regulating osteoclast and osteoblast functions have become better understood in the past 20\u2003years and have led to questioning of the long\u2010held notion that osteoblastic cells have the dominant regulatory role over osteoclastic cells in bone remodelling. Here, we review current knowledge of how osteoclast formation and functions are regulated and describe how enhanced understanding of these has led to development of new drugs for the management of common bone diseases characterized by increased bone resorption.\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:bold>Results\u2002<\/jats:bold>\n                      Osteoclast formation and functions are regulated by cytokines, especially receptor activator of NF\u2010\u03baB ligand (RANKL) and macrophage\u2010colony\u2010stimulating factor (M\u2010CSF). The differentiation, activity and lifecycle of osteoclasts are regulated in part by other cells that reside within the bone. These include osteoblasts, osteocytes and immune cells, which express these cytokines in response to most factors that promote bone resorption. RANKL and M\u2010CSF activate numerous signalling pathways, which are potential targets for therapeutic intervention. Importantly, osteoclastic cells also function as positive and negative regulators of osteoblastic bone formation.\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:bold>Conclusions\u2002<\/jats:bold>\n                      There are multiple targets within osteoclasts for pharmacologic intervention to prevent bone loss in osteoporosis and other resorptive bone diseases. However, novel therapies could also affect osteoblastic cell functions.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/j.1365-2362.2012.02717.x","type":"journal-article","created":{"date-parts":[[2012,8,14]],"date-time":"2012-08-14T11:41:00Z","timestamp":1344944460000},"page":"1332-1341","source":"Crossref","is-referenced-by-count":165,"title":["The osteoclast, bone remodelling and treatment of metabolic bone disease"],"prefix":"10.1111","volume":"42","author":[{"given":"Brendan F.","family":"Boyce","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Rosenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne E.","family":"de Papp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le 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