Mesenchymal stromal cell infusions of umbilical cord-derived mesenchymal stromal cells in children with Recessive Dystrophic Epidermolysis Bullosa (MissionEB): a qualitative sub study of a randomised,

Driven predominantly by population aging, the global prevalence of type 2 diabetes mellitus (T2DM) and osteoporosis has risen to concerning levels. According to the recent International Diabetes Federation Atlas, the global diabetes burden has reached a staggering 537 million adults, with T2DM accounting for the overwhelming majority []. In parallel, approximately 200 million people suffer from osteoporosis, which contributes to as many as 9 million fragility fractures annually []. China mirrors this trend, with an adult diabetes prevalence of 12.8% [] and age-standardized osteoporosis rates of 6.46% in men and 29.13% in women aged 50 years and older []. An analysis of the Chinese basic medical insurance database (2013–2017) reveals that 68.5% of vertebral fracture cases occurred in elderly women, with a mean age of 70.26 years []. This dual epidemic of metabolic and skeletal disorders poses a significant public health challenge in aging societies. The fracture risk assessment tool (FRAX) has limitations in evaluating fracture risk in postmenopausal women with T2DM, as it does not adequately capture the roles of immunoinflammatory activity and malnutrition—key pathophysiological contributors to bone fragility in this population []. Previously, we explored the prognostic value of multiple indicators for predicting fragility fractures in postmenopausal women with T2DM, including the Geriatric Nutritional Risk Index (GNRI) [], the systemic immune-inflammation index (SII) [], and the systemic immune-inflammation index-to-albumin ratio (SAR) []. The present study aims to determine whether the hemoglobin, albumin, lymphocyte, and platelet (HALP) score serves as an effective prognostic marker for fragility fractures and whether it enhances the predictive performance of the FRAX-estimated 10-year probability of fragility fractures in this population. The HALP score, derived from the formula (hemoglobin × albumin × lymphocytes) / platelets, is a recently proposed biomarker that can be readily calculated from routine blood test results []. Initially validated as a prognostic indicator in cancer research [], its components reflect several critical pathophysiological pathways: hemoglobin depletion due to chronic inflammation [], hypoalbuminemia linked to malnutrition-associated musculoskeletal loss [], lymphopenia that impairs immunosurveillance mediated by the receptor activator of nuclear factor kappa B ligand (RANKL) [], and thrombocytosis that promotes the release of inflammatory mediators []. In addition, platelet-derived growth factors enhance the chemotaxis of osteoclast precursors, thereby initiating bone loss []. Recent evidence confirms the HALP score’s predictive value for mortality among elderly patients with femoral fractures [], supporting its potential application to diabetic bone disease. The HALP score objectively quantifies the inflammatory burden using lymphocyte and platelet counts and hemoglobin levels, and assesses nutritional status using hemoglobin and albumin levels. This makes it an ideal candidate metric (as a FRAXplus tool) for enhancing the FRAX assessment. Unlike the existing factor-adjusted FRAXplus developed by the FRAX team (), this study proposes, for the first time, a novel fracture risk stratification that integrates the HALP score into FRAX.