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Evaluation of an association between RANKL and OPG with bone disease in people with cystic fibrosis
Shadaan Abid1, MinJae Lee2, Bailey Rodich3
1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
Insights
The RANKL/OPG ratio may serve as a biomarker for bone disease in Cystic Fibrosis (CF). Higher ratios indicate increased bone turnover, suggesting potential therapeutic targets for CF-related bone disease (CFBD).
Area of Science:
- Bone Biology
- Endocrinology
- Pulmonology
Background:
- Cystic Fibrosis (CF) survival is increasing, leading to a rise in extra-pulmonary complications like CF-related bone disease (CFBD).
- The exact causes of CFBD are not fully understood but are believed to be multifactorial.
- Bone remodeling involves the RANK/sRANKL/OPG pathway, crucial for osteoclastogenesis.
Purpose of the Study:
- To investigate the association between soluble RANKL (sRANKL) and OPG levels and CFBD.
- To assess the potential of sRANKL and OPG as biomarkers for bone turnover in individuals with CF.
- To explore the utility of the RANKL/OPG ratio in identifying CFBD.
Main Methods:
- Plasma samples from individuals with CF and healthy controls (HC) were analyzed for sRANKL and OPG levels.
- Levels were compared between groups and correlated with bone mineral density results in CF patients.
- Univariable and multivariable analyses were performed to control for confounding factors.
Main Results:
- Individuals with CF exhibited higher sRANKL and lower OPG levels compared to HC.
- The RANKL/OPG ratio was significantly higher in individuals with CF compared to HC.
- A higher RANKL/OPG ratio was observed in individuals with CFBD compared to those with CF but without bone disease, even after adjusting for other factors.
Conclusions:
- The RANKL/OPG ratio may be a valuable biomarker for bone turnover in CF, potentially surpassing current imaging recommendations.
- These findings suggest that therapies targeting the RANK/RANKL/OPG pathway could be beneficial for managing CFBD.
- Further investigation into the RANK/RANKL/OPG pathway is warranted for therapeutic development in CF.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
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