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However, there is a growing body of literature on the neuronal regulation of bone and skeletal muscle structure and function, which may provide insights into the pathogenesis of osteosarcopenia. This review aims to integrate these neuronal regulatory mechanisms to form a comprehensive understanding and inspire future research that could uncover novel strategies for preventing and treating osteosarcopenia. Specifically, the review explores the functional adaptation of weight\u2010bearing bone to mechanical loading throughout evolutionary development, from Wolff's law and Frost's mechanostat theory to the mosaic hypothesis, which emphasizes neuronal regulation. The recently introduced bone osteoregulation reflex points to the importance of the osteocytic mechanoreceptive network as a receptor in this neuronal regulation mechanism. Finally, the review focuses on the bone myoregulation reflex, which is known as a mechanism by which bone loading regulates muscle functions neuronally. Considering the ageing\u2010related regressive changes in the nerve fibres that provide both structural and functional regulation in bone and skeletal muscle tissue and the bone and muscle tissues they innervate, it is suggested that neuronal mechanisms might play a central role in explaining osteosarcopenia in older adults.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16244-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1113\/jp285666","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T06:56:47Z","timestamp":1723186607000},"page":"672-688","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Exploring neuronal mechanisms of osteosarcopenia in older adults"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7462-1358","authenticated-orcid":false,"given":"Ilhan","family":"Karacan","sequence":"first","affiliation":[{"name":"Physical Medicine and Rehabilitation Department Hamidiye Medical School Health Science University Istanbul  Istanbul Turkey"},{"name":"Istanbul Physical Therapy Rehabilitation Training and Research Hospital  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9962-075X","authenticated-orcid":false,"given":"Kemal S\u0131tk\u0131","family":"T\u00fcrker","sequence":"additional","affiliation":[{"name":"Physiology, Faculty of Dentistry Istanbul Gelisim University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,9]]},"reference":[{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0838.2009.01084.x"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medengphy.2009.02.006"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2021.111465"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00167-005-0673-2"},{"key":"e_1_2_2_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650070903"},{"key":"e_1_2_2_7_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1402.018"},{"key":"e_1_2_2_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11657-020-0706-y"},{"key":"e_1_2_2_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105427"},{"key":"e_1_2_2_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2015.02.016"},{"key":"e_1_2_2_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2021.111613"},{"key":"e_1_2_2_12_1","doi-asserted-by":"publisher","DOI":"10.1589\/jpts.27.2279"},{"key":"e_1_2_2_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2012.09.010"},{"issue":"2","key":"e_1_2_2_14_1","first-page":"132","article-title":"Role of innervation in the control of bone remodelling","volume":"4","author":"Chenu C.","year":"2004","journal-title":"Journal of Musculoskeletal & Neuronal Interactions"},{"key":"e_1_2_2_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.770143"},{"issue":"4","key":"e_1_2_2_16_1","first-page":"521","article-title":"Adaptive bone modelling in the middle ear is substance\u2010P dependent","volume":"19","author":"Chole R. 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