{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:18:08Z","timestamp":1790615888238,"version":"4.1.0"},"reference-count":121,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Older adults experience a markedly increased risk of falls and fractures following hospital discharge, largely due to the rapid musculoskeletal deterioration associated with bed rest. Although age\u2010related muscle and bone loss typically develops gradually, acute physical inactivity accelerates key biological processes underlying sarcopenia and osteoporosis, including muscle atrophy, anabolic resistance, increased bone resorption and reduced mechanical loading. Emerging evidence indicates that muscle, bone and adipose tissue communicate through interconnected biochemical pathways; however, the shared biological mechanisms underlying this crosstalk during acute unloading remain poorly understood. To review the effects of disuse on the muscle\u2013bone\u2013adipose axis, emphasizing disruption of inter\u2010tissue signalling pathways and evaluating integrated countermeasures, a narrative review was conducted using PubMed, Scopus and Web of Science, focusing on human bed rest and disuse studies, musculoskeletal crosstalk and multimodal interventions involving exercise and nutrition in older adults. Disuse rapidly disrupts musculoskeletal homeostasis by uncoupling bone turnover and inducing muscle anabolic resistance. These changes are accompanied by alterations in myokine and osteokine signalling, including increased myostatin, reduced irisin, elevated RANKL, bone and muscle steatosis, and sclerostin upregulation, further compromising muscle\u2013bone interactions. Evidence supports multimodal interventions combining resistance exercise with optimized protein intake (1.2\u20131.5\u00a0g\/kg\/day) and nutritional supplements, including \u03b2\u2010hydroxy\u2010\u03b2\u2010methylbutyrate, vitamin D and creatine, to attenuate muscle and bone loss. Preventing disuse\u2010related musculoskeletal decline requires recognizing muscle and bone as an integrated functional unit. Tailored multimodal strategies may preserve musculoskeletal health and functional independence in hospitalized older adults, although implementation must consider frailty, comorbidities, safety and feasibility.<\/jats:p>","DOI":"10.1113\/ep093790","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:40:42Z","timestamp":1790613642000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Musculoskeletal decay and bone\u2013muscle crosstalk during physical disuse: Mechanisms and integrated countermeasures"],"prefix":"10.1113","author":[{"given":"Julia Margarita","family":"Reyes","sequence":"first","affiliation":[{"name":"Geriatrics Section Clinical Hospital University of Chile  Santiago Chile"},{"name":"Research Institute McGill University Health Centre  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8087-1030","authenticated-orcid":false,"given":"Guy","family":"Hajj\u2010Boutros","sequence":"additional","affiliation":[{"name":"Research Institute McGill University Health Centre  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Division of Geriatric Medicine, Department of Medicine McGill University  Montreal Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dounia","family":"Rouabhia","sequence":"additional","affiliation":[{"name":"Division of Geriatric Medicine, Department of Medicine McGill University  Montreal Qu\u00e9bec Canada"},{"name":"St Mary's Research Centre McGill University  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Morais","sequence":"additional","affiliation":[{"name":"Research Institute McGill University Health Centre  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Division of Geriatric Medicine, Department of Medicine McGill University  Montreal Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Salech","sequence":"additional","affiliation":[{"name":"Geriatrics Section Clinical Hospital University of Chile  Santiago Chile"},{"name":"Center for Advanced Clinical Research (CICA) Clinical Hospital University of Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8126-0637","authenticated-orcid":false,"given":"Gustavo","family":"Duque","sequence":"additional","affiliation":[{"name":"Research Institute McGill University Health Centre  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Division of Geriatric Medicine, Department of Medicine McGill University  Montreal Qu\u00e9bec Canada"},{"name":"Simone &amp; Edouard Schouela RUISSS McGill Centre of Excellence for Sustainable Health of Seniors (Schouela CEDurable) McGill University  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"issue":"4","key":"e_1_2_15_2_1","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.jamda.2020.12.006","article-title":"Longitudinal changes in muscle mass, muscle strength, and physical performance in acutely hospitalized older adults","volume":"22","author":"Aarden J. 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