3D-DXA reveals significant effects of burosumab on trabecular and cortical skeletal envelopes in symptomatic adults with X-linked Hypophosphatemia.

Fractures and pseudofractures cause considerable morbidity in adults with X-linked Hypophosphatemia (XLH). They frequently occur in cortically-enriched bones of the lower extremities. Burosumab, a neutralizing antibody to FGF23, heals fractures in adults with XLH, presumably by healing osteomalacia. Histomorphometry has documented healing of osteomalacia in trabecular bone. The effects of burosumab on cortical bone have not been reported. Therefore, 3D-DXA measurements of the proximal femur were used to examine the impact of 1 yr of burosumab therapy on cortical and trabecular bone in symptomatic adults with XLH. Twenty volunteers from the registration trial for burosumab were separately consented for this study. DXA scans of the hip were obtained before and 6, 12 and 18-24 mo (mo.) after drug therapy (1 mg/kg every 4 wk). 3D-DXA analyses were performed using 3D-Shaper software (3D-Shaper Medical). Changes in femoral neck (FN) areal BMD (aBMD), total hip (TH) aBMD, TH trabecular volumetric BMD (vBMD), FN trabecular vBMD, TH cortical surface BMD (sBMD), FN cortical sBMD, and FN cross-sectional moment of inertia (CSMI) were analyzed. Both TH and FN trabecular vBMD showed significant increases over the course of therapy (13.6% and 14.1% respectively at the end of treatment compared to baseline; p < .0001 for each). Fractures and pseudofractures often occur in the cortically-enriched FN in XLH. Burosumab induced a significant increase in FN cortical sBMD between 6 and 12 mo. (p < .05) and between 6 and 18-24 mo. of drug treatment (p < .05). The FN CSMI, an indicator of FN strength, also significantly increased at 12 and 18-24 mo. when compared to baseline; p < .05 and p < .01 respectively. These data demonstrate that burosumab increases both cortical and trabecular bone in the hip a site of frequent fracture in XLH.