Ni Xiaolin, Feng Yiming, Guan Wenmin, Chi Yue, Li Xiang, Gong Yiyi, Zhao Nan, Pang Qianqian, Yu Wei, Wu Huanwen, Huo Li, Liu Yong, Jin Jin, Zhou Xi, Lv Wei, Zhou Lian, Xia Yu, Liu Wei, Jiajue Ruizhi, Wang Ou, Li Mei, Xing Xiaoping, Fukumoto Seiji, Jiang Yan, Xia Weibo
Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Department of Pulmonary and Critical Care Medicine, Center for Respiratory Diseases, China-Japan Friendship Hospital, Institute of Respiratory Medicine Chinese Academy of Medical Science, National Clinical Research Center of Respiratory Diseases, Beijing, China.
J Bone Miner Res. 2022 Mar;37(3):454-464. doi: 10.1002/jbmr.4476. Epub 2022 Jan 3.
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. Previous studies have revealed generalized mineralization defects and low areal bone mineral density (aBMD) in TIO. However, data on the bone microarchitecture in TIO are limited. In this study, we evaluated the microarchitecture in the peripheral (distal radius and tibia) and axial (lumbar spine) skeleton using high-resolution peripheral quantitative computed tomography (HR-pQCT) and trabecular bone score (TBS) and investigated related factors in a large cohort of Chinese patients with TIO. A total of 186 patients with TIO who had undergone dual-energy X-ray absorptiometry (DXA) or HR-pQCT scans were enrolled. Compared with age-, sex-, and body mass index (BMI)-matched healthy controls, TIO patients (n = 113) had lower volumetric BMD, damaged microstructure, and reduced bone strength in the peripheral skeleton, especially at the tibia. The average TBS obtained from 173 patients was 1.15 ± 0.16. The proportion of patients with abnormal TBS (<1.35) was higher than that with low L to L aBMD Z-score (Z ≤ -2) (43.9% versus 89.6%, p < 0.001). Higher intact fibroblast growth factor 23 (iFGF23), intact parathyroid hormone (iPTH), alkaline phosphatase, and β-isomerized C-terminal telopeptide of type I collagen (β-CTx) levels, more severe mobility impairment, and a history of fracture were associated with poorer HR-pQCT parameters but not with lower TBS. However, greater height loss and longer disease duration were correlated with worse HR-pQCT parameters and TBS. Moreover, TBS was correlated with both trabecular and cortical HR-pQCT parameters in TIO. In conclusion, we revealed impaired bone microarchitecture in the axial and peripheral skeleton in a large cohort of Chinese TIO patients. HR-pQCT parameters and TBS showed promising advantages over aBMD for assessing bone impairment in patients with TIO. A longer follow-up period is needed to observe changes in bone microarchitecture after tumor resection. © 2021 American Society for Bone and Mineral Research (ASBMR).
肿瘤诱导的骨软化症（TIO）是一种罕见的副肿瘤综合征，由肿瘤过度产生成纤维细胞生长因子23（FGF23）引起。既往研究已揭示TIO患者存在全身矿化缺陷和低面积骨密度（aBMD）。然而，关于TIO患者骨微结构的数据有限。在本研究中，我们使用高分辨率外周定量计算机断层扫描（HR-pQCT）和小梁骨评分（TBS）评估了中国一大群TIO患者外周（桡骨远端和胫骨）和中轴（腰椎）骨骼的微结构，并研究了相关因素。共纳入186例接受双能X线吸收测定（DXA）或HR-pQCT扫描的TIO患者。与年龄、性别和体重指数（BMI）匹配的健康对照相比，TIO患者（n = 113）外周骨骼，尤其是胫骨的骨体积密度较低、微结构受损且骨强度降低。173例患者的平均TBS为1.15±0.16。TBS异常（<1.35）的患者比例高于腰椎至腰椎aBMD Z评分低（Z≤-2）的患者比例（43.9%对89.6%，p<0.001）。较高的完整成纤维细胞生长因子23（iFGF23）、完整甲状旁腺激素（iPTH）、碱性磷酸酶和I型胶原β-异构化C末端肽（β-CTx）水平、更严重的活动障碍和骨折史与较差 的HR-pQCT参数相关，但与较低的TBS无关。然而，更大的身高降低和更长的病程与更差的HR-pQCT参数和TBS相关。此外，TBS与TIO患者的小梁和皮质HR-pQCT参数均相关。总之，我们揭示了一大群中国TIO患者中轴和外周骨骼的骨微结构受损。HR-pQCT参数和TBS在评估TIO患者的骨损伤方面显示出优于aBMD的优势。需要更长的随访期来观察肿瘤切除后骨微结构的变化。©2021美国骨与矿物质研究学会（ASBMR）
