AUTHOR=Jiajue Ruizhi , Ni Xiaolin , Jin Chenxi , Yu Wei , Huo Li , Wu Huanwen , Liu Yong , Jin Jin , Lv Wei , Zhou Lian , Xia Yu , Chi Yue , Cui Lijia , Pang Qianqian , Li Xiang , Jiang Yan , Wang Ou , Li Mei , Xing Xiaoping , Meng Xunwu , Xia Weibo TITLE=Bone Volumetric Density, Microarchitecture, and Estimated Bone Strength in Tumor-Induced Rickets/Osteomalacia Versus X-linked Hypophosphatemia in Chinese Adolescents JOURNAL=Frontiers in Endocrinology VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.883981 DOI=10.3389/fendo.2022.883981 ISSN=1664-2392 ABSTRACT=Tumor-induced rickets/osteomalacia (TIR/O) severely impairs bone microarchitecture and bone strength. However, no study describes the microarchitectural quality of bone in adolescent patients with TIR/O. TIR/O affects bone quality more severely than inherited causes of hypophosphatemia, the most common form of which is X-linked hypophosphatemia (XLH). Nevertheless, differences of microarchitectural quality of bone between TIR/O and XLH have never been clarified. Therefore, in this study, we used high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess bone microarchitecture in five Chinese adolescent TIR/O patients, and were compared to fifteen age- and gender- matched XLH patients as well as to fifteen age- and gender- matched healthy controls. Compared to the healthy controls, the TIR/O patients presented with significantly lower volumetric bone mineral densities (vBMDs), severely affected bone microarchitecture, and profoundly weaker bone strength. The distal tibia was more severely affected than the distal radius. Compared to the XLH patients, the TIR/O patients showed deteriorated bone quality notably at the distal tibia and in the cancellous compartment, reflected by a 45.9% lower trabecular vBMD (p = 0.029), a 40.2% lower trabecular fraction (p = 0.020), a 40.6% weaker stiffness (p = 0.058), and a 42.7% weaker failure load (p = 0.039) at the distal tibia. Correlation analysis showed that a higher level of serum FGF23 and a lower level of serum phosphate were associated with a poorer bone microarchitecture and a weaker estimated bone strength in our studied hypophosphatemic patients. In conclusion, our study demonstrated significantly lower vBMDs, severely impaired bone microarchitecture, and profoundly weaker bone strength in Chinese adolescent patients with TIR/O, notably at the distal tibia, compared to the same parameters in age- and sex- matched healthy controls and XLH patients, which was possibly caused by the excessive FGF23 production and secretion, the chronic severe hypophosphatemia, and weak mechanical stimulus at the lower extremities. These findings further our understanding of the impact of different kinds of hypophosphatemic rickets/osteomalacia on bone quality.