#2635 association between plasma lyso-gb3 levels and bone mineral density in patients with fabry disease

Abstract Background and Aims Fabry disease is a rare X-linked genetic disorder that contributes to various clinical manifestations including cardiac hypertrophy, renal dysfunction, cerebrovascular disease, angiokeratoma, and anhidrosis. Several previous reports showed that male patients with Fabry disease had decreased bone mineral density (BMD). However, the association of BMD with clinical characteristics and biomarkers of organ damage in patients with Fabry disease has not been sufficiently studied. Therefore, we aimed to investigate their associations in patients with Fabry disease. Method Patients with Fabry disease who attended our hospital from January 2008 to June 2021 were included in this study. Patients without enough clinical and laboratory data were excluded from the present study. The remaining fifteen patients were assessed in this study. We examined clinical characteristics, biomarkers including blood globotriaosylsphingosine (lyso-Gb3) levels, and BMD, and compared them between male and female patients. We measured the lumbar spine and femoral BMD by dual-energy bone X-ray absorptiometry and calculated the Z-score. Furthermore, we also examined ΔBMD, defined as the two-year change in the Z-score, for ten patients who underwent BMD measurement before and after starting ERT. Because two patients already had received ERT, two did not undergo BMD measurement, and one took an anti-osteoporotic agent, they were excluded from the analysis. Results Both lumbar spine BMD and femoral BMD decreased in male patients, while they were preserved in female patients (lumbar spine Z-score: -1.9 ± 2.0 versus 0.8 ± 0.8, p < 0.05; femoral Z-score: -1.0 ± 1.4 versus 0.6 ± 0.6, p < 0.05) among all the study patients. Lumbar spine and femoral BMD showed a significantly negative correlation with blood lyso-Gb3 levels. Moreover, blood lyso-Gb3 levels were significantly correlated with the lumbar spine BMD (r = -0.92; p < 0.01) and femoral BMD (r = -0.91; p < 0.01) in male patients. On the other hand, there was no significant correlation of blood lyso-Gb3 levels with the lumbar spine BMD (r = 0.66, p = 0.18) and femoral BMD (r = 0.11; p = 0.99) in female patients. After starting ERT, blood lyso-Gb3 levels were significantly reduced in both male and female patients. The lumbar spine ΔBMD in male patients improved whereas that in female patients remained unchanged despite no changes in kidney function and serum calcium and phosphate levels. Conclusion Our findings suggested that lumbar spine BMD and femoral BMD decreased in male patients with Fabry disease possibly due to the deposition of lyso-Gb3 in bone tissue and ERT could improve BMD in these patients.