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The remodelling cycle occurs within the basic multicellular unit and comprises five co-ordinated steps; activation, resorption, reversal, formation and termination. These steps occur simultaneously but asynchronously at multiple different locations within the skeleton. Study of rare human bone disease and animal models have helped to elucidate the cellular and molecular mechanisms that regulate the bone remodelling cycle. The key signalling pathways controlling osteoclastic bone resorption and osteoblastic bone formation are receptor activator of nuclear factor-\u03baB (RANK)\/RANK ligand\/osteoprotegerin and canonical Wnt signalling. Cytokines, growth factors and prostaglandins act as paracrine regulators of the cycle, whereas endocrine regulators include parathyroid hormone, vitamin D, calcitonin, growth hormone, glucocorticoids, sex hormones, and thyroid hormone. Disruption of the bone remodelling cycle and any resulting imbalance between bone resorption and formation leads to metabolic bone disease, most commonly osteoporosis. The advances in understanding the cellular and molecular mechanisms underlying bone remodelling have also provided targets for pharmacological interventions which include antiresorptive and anabolic therapies. This review will describe the remodelling process and its regulation, discuss osteoporosis and summarize the commonest pharmacological interventions used in its management.<\/jats:p>","DOI":"10.1177\/0004563218759371","type":"journal-article","created":{"date-parts":[[2018,4,26]],"date-time":"2018-04-26T12:42:48Z","timestamp":1524746568000},"page":"308-327","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":636,"title":["The bone remodelling cycle"],"prefix":"10.1177","volume":"55","author":[{"given":"JS","family":"Kenkre","sequence":"first","affiliation":[{"name":"Section of Investigative Medicine, Imperial College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0817-0082","authenticated-orcid":false,"given":"JHD","family":"Bassett","sequence":"additional","affiliation":[{"name":"Molecular Endocrinology Laboratory, Department of Medicine, Imperial College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,3,4]]},"reference":[{"key":"bibr1-0004563218759371","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.04151206"},{"key":"bibr2-0004563218759371","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-14-0584"},{"key":"bibr3-0004563218759371","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.157"},{"key":"bibr4-0004563218759371","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.12.003"},{"key":"bibr5-0004563218759371","doi-asserted-by":"publisher","DOI":"10.1038\/nature21697"},{"key":"bibr6-0004563218759371","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra053077"},{"key":"bibr7-0004563218759371","first-page":"115","volume":"21","author":"Manolagas SC.","year":"2000","journal-title":"Endocr Rev"},{"key":"bibr8-0004563218759371","volume-title":"Wheater's functional histology: a text and colour atlas","author":"Young B.","year":"2006","edition":"5"},{"key":"bibr9-0004563218759371","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-11-0048"},{"key":"bibr10-0004563218759371","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2014.111"},{"key":"bibr11-0004563218759371","doi-asserted-by":"publisher","DOI":"10.1038\/nature01657"},{"key":"bibr12-0004563218759371","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2448"},{"key":"bibr13-0004563218759371","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2474"},{"key":"bibr14-0004563218759371","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1997.3501"},{"key":"bibr15-0004563218759371","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1276205"},{"key":"bibr16-0004563218759371","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3254"},{"key":"bibr17-0004563218759371","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80257-3"},{"key":"bibr18-0004563218759371","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00622-5"},{"key":"bibr19-0004563218759371","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2011.01.006"},{"key":"bibr20-0004563218759371","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2008.02.030"},{"key":"bibr21-0004563218759371","first-page":"103","volume":"32","author":"Caetano-Lopes J","year":"2007","journal-title":"Acta Reumatol Port"},{"key":"bibr22-0004563218759371","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2006.01.001"},{"key":"bibr23-0004563218759371","doi-asserted-by":"publisher","DOI":"10.1038\/nature01658"},{"key":"bibr24-0004563218759371","doi-asserted-by":"crossref","unstructured":"Ross FP. 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