Unraveling the Puzzle of Bone Health in Klinefelter Syndrome: Association Between DXA‐Derived Lumbar Bone Strain Index and Body Composition Parameters in a Single Center Cohort

Objective: Klinefelter syndrome (KS) is frequently characterized by skeletal fragility with increased risk of fractures, independently of testosterone levels and bone mineral density (BMD). Unfavorable body composition might negatively influence bone health in KS patients. Recently, a new dual-energy X-ray absorptiometry (DXA)-derived index of bone strength, the bone strain index (BSI), has emerged as a promising tool for assessing fracture risk and bone quality derangement, particularly in secondary osteoporosis. The aim of this study was to investigate the associations between lumbar BSI (l-BSI), trabecular bone score (TBS) and body composition parameters in a cohort of adult patients with KS. Design: Cross-sectional study. Patients: Forty four patients with 47, XXY KS (median age 39.5 years, range 18-61) followed at an Italian referral center. Measurements: BMD, BSI, TBS, and body composition parameters were evaluated by total body DXA. Correlations between body composition and bone parameters were analyzed. Results: l-BSI was significantly associated with fat mass index (FMI) (rho = 0.64, p < 0.001), fat-to-lean mass index ratio (rho = 0.66, p < 0.001), and visceral fat mass (rho = 0.56, p < 0.001). A strong negative correlation between l-BSI and TBS (rho: -0.73, p < 0.001) was also observed. Patients with impaired TBS and those with later age at KS diagnosis showed significantly higher l-BSI values (p < 0.001). Later age at KS diagnosis also correlated with higher body fat indexes. Conclusions: Increased adiposity may have detrimental effects on lumbar bone quality and strength as assessed by l-BSI in adult patients with KS. Later diagnosis of KS may contribute to unfavorable body composition and impaired skeletal health.