Low bone mineral density is associated with altered systemic T cell subtypes in Hemophilia

Introduction One of the most prevalent consequences of hemophilia (HA) is the onset of osteoporosis at a young age. So, frequent monitoring of bone health is paramount for preventing fractures in HA patients. A DEXA scan is the gold standard test for assessing bone health and it uses low-level radiation to detect bone density. Due to the early manifestation of compromised bone health, HA subjects receive more DEXA scan measures and radiation exposure than non-HA subjects. Thus, having non-invasive markers to test bone mineral density (BMD) in HA would lower the risk of radiation-related adverse consequences in HA. Bone is the birthplace of immune cells, and there is constant communication between bone and immune cells. Immune factors serve as valuable diagnostic and prognostic markers in several disorders. Hence, the aim of this study was to assess immune cells as a marker of bone health in HA. Method For this study, we recruited HA subjects with normal and low T-scores (osteopenia and osteoporosis). We employed multi-parametric flow cytometry to enumerate the circulating immune cells and to analyze frequencies of pro-inflammatory cytokine-positive T cells. We used Pearson’s correlation analysis to describe the relationship between immune cells and various bone health indicators. Using receiver operating characteristic (ROC) analysis, we investigated whether immune markers could be used to discriminate between normal and low BMD in HA. Results HA subjects with a low bone T-score had lower levels of CD4 + and CD8 + naïve T cells compared to HA individuals with a normal T-score. However, the frequencies of CD4 + and CD8 + effector memory (EM) and terminally differentiated effector memory T cells (TEMRA) were significantly higher in subjects with low T-score than in their healthy T-score counterparts. In addition, immunomodulatory-Treg levels were reduced in low BMD subjects. CD8 + naïve T cells exhibited a positive correlation, whereas CD8 + TEMRA showed a negative correlation with various bone health indicators. Flow cytometry analysis demonstrated a significant increase in RANKL + CD4 + and CD8 + T cells in individuals with low BMD compared to normal BMD HA subjects. ROC curve analysis revealed that CD4 + and CD8 + naïve T cells, EM and TEMRA as well as Tregs were highly effective in discriminating between low and normal bone T-scores in HA with high sensitivity and specificity. Conclusion The impaired bone health in HA subjects is associated with diminished levels of naive T cell subsets and Tregs and augmented levels of EM and TEMRA compared to their healthy BMD counterparts. Our results suggest that T cell subsets could serve as a valuable non-invasive marker for diagnosing poor bone health in HA subjects. This cost-effective marker could limit radiation exposure in HA patients and be useful in community screening, as DEXA scans require special facilities and are rather expensive. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany