Highlights
- •Limited treatment options have been explored for CF related bone disease.
- •We demonstrated elevated RANKL, decreased OPG and elevated RANKL/OPG in people with CF relative to healthy controls.
- •We also show elevated RANKL/OPG in people with CF bone disease versus those without bone disease.
- •The RANKL/OPG difference persisted after adjusting for a number of variables known to impact bone health and may be a useful marker for low bone density in CF.
- •Further evaluation of the safety and efficacy of antiresorptive agents that target RANKL such as denosumab is warranted.
Abstract
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.
Keywords
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Article info
Publication history
Published online: August 27, 2022
Accepted:
August 16,
2022
Received in revised form:
August 15,
2022
Received:
February 14,
2022
Identification
Copyright
© 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
