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).

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).

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.

The authors have declared no competing interest.

The authors thank Weston Park Cancer Charity (RCN 509803-2) for funding REAs clinical research fellowship, and for providing the financial support for the initial pilot study (Grant no. R2L).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was conducted according to the guidelines of the Declaration of Helsinki, and was given ethical approval by the Health Research Authority and Health and Care Research Wales (HCRW), and the Yorkshire and The Humber - Bradford Leeds Research Ethics Committee, United Kingdom (REC 18/YH/0275).

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No original data is included in this manuscript.

No new data were created or analysed in this study. Data sharing is not applicable to this article.