Abid Shadaan, Lee MinJae, Rodich Bailey, Hook Jessica S, Moreland Jessica G, Towler Dwight, Maalouf Naim M, Keller Ashley, Ratti Gregory, Jain Raksha
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
Department of Population & Data Sciences, Division of Biostatistics, University of Texas Southwestern Medical Center, Dallas, TX.
J Cyst Fibros. 2023 Jan;22(1):140-145. doi: 10.1016/j.jcf.2022.08.011. Epub 2022 Aug 28.
As people with Cystic Fibrosis (CF) live longer, extra-pulmonary complications such as CF-related bone disease (CFBD) are becoming increasingly important. The etiology of CFBD is poorly understood but is likely multifactorial. Bones undergo continuous remodeling via pathways including RANK (receptor activator of NF-κB)/sRANKL (soluble ligand)/OPG (osteoprotegerin). We sought to examine the association between sRANKL (stimulant of osteoclastogenesis) and OPG levels (inhibitor of osteoclast formation) and CFBD to investigate their potential utility as biomarkers of bone turnover in people with CF.
We evaluated sRANKL and OPG in plasma from people with CF and healthy controls (HC) and compared levels in those with CF to bone mineral density results. We used univariable and multivariable analysis to account for factors that may impact sRANKL and OPG.
We found a higher median [IQR] sRANKL 10,896pg/mL [5,781-24,243] CF; 2,406pg.mL [659.50-5,042] HC; p= 0.0009), lower OPG 56.68pg/mL [36.28-124.70] CF; 583.20pg/mL [421.30-675.10] HC; p < 0.0001), and higher RANKL/OPG in people with CF no BD than in HC (p < 0.0001). Furthermore, we found a higher RANKL/OPG ratio 407.50pg/mL [214.40-602.60] CFBD; 177.70pg/mL [131.50-239.70] CF no BD; p = 0.007) in people with CFBD versus CF without bone disease. This difference persisted after adjusting for variables thought to impact bone health.
The current screening recommendations of imaging for CFBD may miss important markers of bone turnover such as the RANKL/OPG ratio. These findings support the investigation of therapies that modulate the RANK/RANKL/OPG pathway as potential therapeutic targets for bone disease in CF.
随着囊性纤维化（CF）患者寿命延长，诸如CF相关骨病（CFBD）等肺外并发症变得愈发重要。CFBD的病因尚不清楚，但可能是多因素的。骨骼通过包括RANK（核因子κB受体激活剂）/sRANKL（可溶性配体）/OPG（骨保护素）在内的途径进行持续重塑。我们试图研究sRANKL（破骨细胞生成刺激剂）和OPG水平（破骨细胞形成抑制剂）与CFBD之间的关联，以探讨它们作为CF患者骨转换生物标志物的潜在效用。
我们评估了CF患者和健康对照（HC）血浆中的sRANKL和OPG，并将CF患者的水平与骨密度结果进行比较。我们使用单变量和多变量分析来考虑可能影响sRANKL和OPG的因素。
我们发现CF患者的sRANKL中位数[四分位间距]更高（10,896pg/mL [5,781 - 24,243]；HC为2,406pg/mL [659.50 - 5,042]；p = 0.0009），OPG更低（CF为56.68pg/mL [36.28 - 124.70]；HC为583.20pg/mL [421.30 - 675.10]；p < 0.0001），且无BD的CF患者的RANKL/OPG高于HC（p < 0.0001）。此外，我们发现与无骨病的CF患者相比，CFBD患者的RANKL/OPG比值更高（CFBD为407.50pg/mL [214.40 - 602.60]；无BD的CF为177.
