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Introduction Osteopenia, defined as a bone mineral density (BMD) T-score between −1.0 and −2.5, is a precursor to osteoporosis and fragility fracture which results in substantial morbidity. Patients with gastrointestinal (GI) cancer are particularly vulnerable due to disease-specific mechanisms of bone loss and treatment-related toxicities, which compound the risk of osteoporotic fractures and adverse oncological outcomes. Despite this, the global prevalence of osteopenia and incidence of osteoporotic fracture in GI cancer populations remains poorly quantified, limiting opportunities for targeted surveillance, preventive strategies and policy development. Objective This systematic review and meta-analysis will estimate the global prevalence of osteopenia and global incidence of osteoporotic fracture in cohorts of adults with non-metastatic GI cancer and explore variation across treatment type, cancer site, geographical region and diagnostic modality. Methods and analysis This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) guidance. We will conduct a comprehensive search of MEDLINE, Embase, CINAHL, PubMed, Web of Science, Cochrane Central and ClinicalTrials.gov from 1994 to 2026. Eligible studies will include observational or interventional cohorts reporting prevalence of osteopenia, assessed using dual-energy X-ray absorptiometry (DXA) or CT scan, or incidence of fragility fracture, as determined by imaging findings, administrative codes or clinical history in cohorts of adult non-metastatic cancer populations. Five reviewers will independently and in pairs screen citations and full-text articles, extract data, and assess study quality using the Joanna Briggs Institute checklist for prevalence studies for each outcome. The primary outcome is the global pooled prevalence of osteopenia (diagnosed using DXA), calculated using a random-effect generalised linear mixed model. Secondary outcomes are the global pooled incidence rate of fragility fracture, and the pooled fragility fracture incidence rate ratio (IRR) comparing patients with GI cancer with the general population. All estimates will be presented with 95% confidence intervals. Heterogeneity will be assessed with I 2 , τ 2 and prediction intervals for each outcome. Sources of heterogeneity in osteopenia prevalence will be explored through subgroup analyses by primary cancer location, treatment exposure, and geographical region. Sensitivity analyses, including an analysis of the pooled prevalence of osteopenia diagnosed using CT, and limited to studies deemed low risk of bias, will be performed. Publication bias will be evaluated using Doi plots supplemented with Luis Furuya-Kanamori indices. We will assess certainty in the evidence-base in duplicate by using the Grading of Recommendations Assessment, Development and Evaluation methodology for systematic reviews involving prognosis. Ethics and dissemination This study is a secondary analysis of aggregate, de-identified data extracted from previously published studies. As such, no new data were collected from human participants, and formal ethics board approval is not required. All aggregated data and analytical code used to complete this study will be made available on request to the corresponding author. The findings from this study will be disseminated through publication in a peer-reviewed scientific journal and presentation at national and international conferences. PROSPERO registration number CRD420261286673.
Bocchinfuso et al. (Wed,) studied this question.