Department of Chemical Pathology/Metabolic Medicine, North Wing, St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, UK.
Osteoporosis Unit, Guy's Hospital, London, UK.
Calcif Tissue Int. 2024 Nov;115(5):562-569. doi: 10.1007/s00223-024-01284-3. Epub 2024 Sep 28.
Fibroblast Growth Factor (FGF) receptor signalling is important for skeletal development. The FGF19 subfamily which includes FGF19 and FGF21 are involved in bone metabolism, although their effects on bone mineral density (BMD) and bone strength remain unclear. To further characterise the influence of these two factors on the skeleton, we studied the association between circulating concentrations of FGF19 and 21 with BMD and parameters of hip geometry and strength in post-menopausal osteoporosis (PMO). The study cohort consisted of 374 women aged (mean [SD]) 68.7[12.3] years with PMO. FGF19 and FGF21 were measured in serum by ELISA. BMD was measured at the lumbar spine (LS), total hip (TH) and femoral neck (FN) (n = 277) by dual energy X-ray absorptiometry (DXA) and hip structural analysis (HSA) parameters (n = 263) at the narrow neck of the femur (NN), Intertrochanter (IT) and Femoral shaft (FS) were derived from DXA scans. FGF19 and 21 were not associated with prevalent fractures or BMD when corrected for covariates; age, BMI, smoking habits and alcohol intake. Log-transformed FGF 21 was negatively associated with HSA parameters including Outer Diameter (OD) (p = 0.019), Cross-sectional area (CSA) (p = 0.01), cross-sectional moment of inertia (CSMI) (p = 0.011), Section modulus (Z) (p = 0.002) and cortical thickness (Co Th) (p = 0.026) at the IT only. CSA, CSMI, Z and Co Th were significantly lower (p < 0.05) in women with FGF21 concentrations greater than the median (> 103.5 pg/ml). Our data suggest that FGF 21 may have potentially adverse effects on the skeleton. Further characterisation is needed, particularly as FGF 21 analogues or agonists may be used to treat obesity-related metabolic disorders.
成纤维细胞生长因子 (FGF) 受体信号在骨骼发育中很重要。FGF19 亚家族包括 FGF19 和 FGF21，它们参与骨代谢，但其对骨密度 (BMD) 和骨强度的影响尚不清楚。为了进一步研究这两种因子对骨骼的影响，我们研究了循环 FGF19 和 21 浓度与绝经后骨质疏松症 (PMO) 患者的 BMD 及髋部几何形状和强度参数之间的关系。研究队列包括 374 名年龄（平均[标准差]）为 68.7[12.3]岁的 PMO 女性。采用 ELISA 法检测血清中 FGF19 和 FGF21 的浓度。采用双能 X 线吸收法（DXA）测量腰椎（LS）、全髋（TH）和股骨颈（FN）的 BMD（n=277），采用髋结构分析（HSA）参数测量股骨颈狭窄处（NN）、转子间（IT）和股骨干（FS）的 BMD（n=263）。校正协变量（年龄、BMI、吸烟习惯和饮酒量）后，FGF19 和 21 与现患骨折或 BMD 无关。经对数转换的 FGF21 与 HSA 各参数呈负相关，包括外径（OD）（p=0.019）、横截面积（CSA）（p=0.01）、截面惯性矩（CSMI）（p=0.011）、截面模量（Z）（p=0.002）和皮质厚度（Co Th）（p=0.026）仅在 IT 处。CSA、CSMI、Z 和 Co Th 在 FGF21 浓度大于中位数（>103.5 pg/ml）的女性中明显较低（p<0.05）。我们的数据表明，FGF21 可能对骨骼有潜在的不良影响。需要进一步研究，特别是因为 FGF21 类似物或激动剂可能用于治疗肥胖相关的代谢紊乱。
