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, Shuaifuyuan No.1, Wangfujing Street, Dongcheng District, Beijing, 100730, China.
Osteoporos Int. 2022 Oct;33(10):2193-2204. doi: 10.1007/s00198-022-06471-2. Epub 2022 Jun 29.
Gitelman syndrome (GS) is the disease model of the inactivation of thiazide-sensitive sodium chloride cotransporter (NCC), which is believed to benefit bone mass and reduce fracture risk. In this study, we found that GS patients have superior bone microarchitecture, which is associated with the disease status. Several decreased bone parameters with aging in healthy controls were reversed in GS patients to a certain extent.
To evaluate the impact of the inactivation of NCC on bone turnover and microarchitecture in Gitelman syndrome patients.
A cross-sectional study was conducted in 45 GS patients (25 males and 20 females). Serum procollagen type 1 N-terminal propeptide (P1NP), β-carboxy-terminal crosslinked telopeptide of type 1 collagen (β-CTX), and osteocalcin were measured. High-resolution peripheral quantitative computed tomography (HR-pQCT) was conducted to evaluate bone microarchitecture in GS patients and age- and sex-matched healthy controls. Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry (DXA) simultaneously.
GS patients had a relatively lower level of β-CTX. aBMD at several skeletal sites was improved in GS patients. HR-pQCT assessment revealed that GS patients had slightly thinner but significantly more compact trabecular bone (increased trabecular number and decreased thickness), notably decreased cortical porosity, and increased volume BMD (vBMD) at both the radius and tibia compared with controls. The disease severity, represented as the relationship with the minimum level of magnesium during the course and standard base excess, was associated with bone microarchitecture parameters after adjusting for age, sex, and BMI. The decreased vBMD and Tb.BV/TV, and increased Tb.Sp and Ct.Po with aging, were reversed in GS patients to a certain extent.
GS patients have superior bone microarchitecture, which suggests that the inactivation of NCC might be beneficial for avoiding osteoporosis.
评估 NCC 失活对 Gitelman 综合征患者骨转换和微结构的影响。
对 45 例 Gitelman 综合征患者（男 25 例，女 20 例）进行横断面研究。检测血清Ⅰ型前胶原 N 端前肽（P1NP）、β-胶原羧基端肽（β-CTX）和骨钙素。同时采用高分辨率外周定量 CT（HR-pQCT）评估 Gitelman 综合征患者和年龄、性别匹配的健康对照组的骨微结构。双能 X 线吸收法（DXA）同时测量面积骨密度（aBMD）。
Gitelman 综合征患者的 β-CTX 水平相对较低。Gitelman 综合征患者的多个骨骼部位的 aBMD 得到改善。HR-pQCT 评估显示，Gitelman 综合征患者的小梁骨稍薄但更致密（小梁数量增加，厚度减少），皮质骨孔隙度明显减少，桡骨和胫骨的体积 BMD（vBMD）增加。疾病严重程度，用病程中的最低镁水平与标准碱剩余的关系来表示，与调整年龄、性别和 BMI 后骨微结构参数相关。与年龄相关的 vBMD 和 Tb.BV/TV 降低，Tb.Sp 和 Ct.Po 增加在 Gitelman 综合征患者中得到了一定程度的逆转。
Gitelman 综合征患者的骨微结构较好，这表明 NCC 的失活可能有利于避免骨质疏松症。
