{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T14:56:31Z","timestamp":1793890591273,"version":"4.8.0"},"posted":{"date-parts":[[2026,1,22]]},"group-title":"Hematology","reference-count":22,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Cancer-induced bone disease is a huge burden on patient lives and costs the NHS millions of pounds every year. Breast, prostate and lung cancer can all lead to poor skeletal outcomes, but patients particularly at risk are those with a diagnosis of multiple myeloma (1). Despite response to tumour targeting treatments, patients experience debilitating bone pain and fractures, affecting quality of life (2, 3). Currently, myeloma patients who are eligible, are offered treatment with induction chemotherapy followed by autologous stem cell transplant (ASCT). Most eligible patients also receive bisphosphonates, to reduce skeletal morbidity, but this treatment is not optimal, or even conducive for bone recovery. Therefore, we wanted to assess whether current induction chemotherapy regimens have the capacity to reset the bone marrow microenvironment (BMME).<\/jats:p>\n                <jats:p>This prospective observational cohort study will recruit newly diagnosed myeloma patients from Sheffield Teaching Hospitals NHS Foundation Trust. Ethical approval has been granted to undergo two recruitment periods; cohort 1 (20 participants, forming a pilot study) and cohort 2 (up to 100 participants with a streamlined follow-up design).<\/jats:p>\n                <jats:p>Macro-architectural skeletal bone disease will be assessed by whole-body low-dose CT (WBLDCT) scans, in which osteolytic lesions will be monitored longitudinally. Micro-architecture will be assessed by micro-CT scanning bone marrow trephine samples, and analysing changes in trabecular bone. Bone integrity will be assessed using computational models of both whole body skeletal and micro trephine images. Fasting serum samples will be collected to assess changes in bone turnover markers. This will be supported by histomorphometry and immunohistochemistry analysis of trephine sections. All samples \/ imaging will be performed at baseline and follow-up. Monitoring of quality of life (validated questionnaires) and occurrence of skeletal related events (SREs) will also take place. The observational period will end one year post ASCT. Data collected from this study, will provide an invaluable opportunity to comprehensively assess myeloma-induced bone disease and broaden our understanding of the disease course. It may also prove a valuable resource to guide the design of interventional clinical studies exploring novel bone-targeted therapies, including bone anabolic therapeutics, moving forward.<\/jats:p>","DOI":"10.64898\/2026.01.20.26344424","type":"posted-content","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T19:45:12Z","timestamp":1769111112000},"source":"Crossref","is-referenced-by-count":2,"title":["Bone Recovery After Treatment Study (BRATS) - A Protocol for a Prospective, Observational Study in Multiple Myeloma"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0911-4250","authenticated-orcid":false,"given":"R.E.","family":"Andrews","sequence":"first","affiliation":[{"name":"School of Medicine and Population Health, and Mellanby Centre for Musculoskeletal Research, Medical School, Beech Hill Road, Sheffield, S10 2RX, UK"},{"name":"Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield S10 2JF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Jolly","sequence":"additional","affiliation":[{"name":"Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield S10 2JF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.E.","family":"Brown","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, and Mellanby Centre for Musculoskeletal Research, Medical School, Beech Hill Road, Sheffield, S10 2RX, UK"},{"name":"Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield S10 2JF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5446-923X","authenticated-orcid":false,"given":"M.A.","family":"Lawson","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, and Mellanby Centre for Musculoskeletal Research, Medical School, Beech Hill Road, Sheffield, S10 2RX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.D.","family":"Chantry","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, and Mellanby Centre for Musculoskeletal Research, Medical School, Beech Hill Road, Sheffield, S10 2RX, UK"},{"name":"Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield S10 2JF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026012415400550000_2026.01.20.26344424v1.1","doi-asserted-by":"publisher","DOI":"10.1053\/ctrv.2000.0210"},{"key":"2026012415400550000_2026.01.20.26344424v1.2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.08574.x"},{"key":"2026012415400550000_2026.01.20.26344424v1.3","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1186\/s12885-016-2410-2","article-title":"The impact of disease-related symptoms and palliative care concerns on health-related quality of life in multiple myeloma: a multi-centre study","volume":"16","year":"2016","journal-title":"BMC Cancer"},{"key":"2026012415400550000_2026.01.20.26344424v1.4","doi-asserted-by":"crossref","unstructured":"Andrews RE , Brown JE , Lawson MA , Chantry AD . Myeloma Bone Disease: The Osteoblast in the Spotlight. 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