Bone Mineral Density and Trabecular Bone Score in Adults With X-Linked Hypophosphatemia and Tumor-Induced Osteomalacia

Abstract Purpose X-linked hypophosphatemia (XLH) and tumor-induced osteomalacia (TIO) are both driven by elevated fibroblast growth factor 23 (FGF23) and share overlapping clinical and biochemical features, making them difficult to distinguish. We aimed to compare bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA), trabecular bone score (TBS), and biochemical parameters between adults with XLH and TIO, and to identify DXA-based thresholds for their differential diagnosis. Methods Retrospective, multicenter observational study including 70 adults (46 XLH, 24 TIO) from three academic referral centers in Argentina, Brazil, and Chile. Biochemical parameters, DXA Z-scores at the lumbar spine, femoral neck, total hip, and forearm, and TBS Z-scores were compared between groups. Receiver operating characteristic (ROC) analyses with bootstrap confidence intervals assessed the discriminatory accuracy of DXA and TBS parameters. Results Patients with XLH presented significantly higher lumbar spine (median 1.95 vs. −2.40), femoral neck (− 0.50 vs. −2.05), and total hip BMD Z-scores (0.30 vs. −2.25), as well as higher TBS Z-scores (1.80 vs. 0.00), than TIO patients (all p < 0.001). Forearm Z-scores did not differ significantly. ROC analyses showed excellent discrimination for lumbar spine (area under the curve [AUC] 0.914), total hip (AUC 0.914), and femoral neck Z-scores (AUC 0.893), and good discrimination for TBS (AUC 0.813). TIO patients showed more profound hypophosphatemia and markedly elevated alkaline phosphatase. Conclusion In adults with FGF23-mediated hypophosphatemia, lumbar spine and hip BMD Z-scores and TBS discriminate XLH from TIO with excellent accuracy. DXA-based phenotyping may support the diagnostic workup of FGF23-mediated bone diseases.