X-linked hypophosphatemia (XLH) is characterized by excess
fibroblast growth factor 23 (FGF23) secretion, renal
phosphate wasting, and low 1,25(
OH)2 D3 . Adult patients present with
osteomalacia, hypomineralized periosteocytic lesions, bone fragility, and
pain.
Burosumab is a fully human monoclonal FGF23 antibody approved for XLH treatment. UX023-CL304 was an open-label, phase 3 study investigating the effects of
burosumab on
osteomalacia in adults with XLH, who remained untreated at least 2 years prior enrollment. Here, we present the effect of
burosumab on bone material properties. We analyzed transiliac bone biopsy samples from 11 individuals before and after 48 weeks of subcutaneous
burosumab treatment (1.0 mg/kg administered every 4 weeks). We used quantitative backscattered electron imaging (qBEI) and Fourier transform infrared imaging (FTIRI) to assess bone mineralization density distribution (BMDD), mineralized bone volume, properties of the organic matrix, and size of periosteocytic lesions. The outcomes were compared with reference values from healthy adults and with four XLH patients either untreated or treated by conventional
therapy. Prior to
burosumab, the average mineralization in cancellous bone was lower than in healthy reference. CaLow, the fraction of lowly mineralized matrix, and CaHigh, the fraction of highly mineralized matrix, were both elevated resulting in a broad heterogeneity in mineralization (CaWidth).
Burosumab resulted in a decrease of CaHigh toward normal range, whereas CaLow and CaWidth remained elevated. The mineralized bone volume was notably increased (+35.9%). The size of the periosteocytic lesions was variable but lower than in untreated XLH patients. FTIRI indicated decreased enzymatic
collagen crosslink ratio heterogeneity. In summary, matrix mineralization in XLH is very heterogeneous. Highly mineralized regions represent old bone packets, probably protected from osteoclastic resorption by osteoid seams. The concomitant decrease of highly mineralized matrix, persistence of lowly mineralized matrix, and increase in mineralized bone volume after
burosumab suggest a boost in mineralization of preexisting unmineralized or very lowly mineralized matrix, providing a potential explanation for previously observed improved
osteomalacia. © 2022 American Society for Bone and
Mineral Research (ASBMR).