AUTHOR=Loid Petra , Hauta-alus Helena , Mäkitie Outi , Magnusson Per , Mäkitie Riikka E. 

TITLE=Lipocalin-2 is associated with FGF23 in WNT1 and PLS3 osteoporosis

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.954730

DOI=10.3389/fendo.2022.954730

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p>The pathogenic mechanisms of early-onset osteoporosis caused by <italic>WNT1</italic> and <italic>PLS3</italic> mutations are incompletely understood and diagnostic biomarkers of these disorders are limited. Recently, lipocalin-2 has been recognized as an osteokine involved in bone development and homeostasis. However, the role of lipocalin-2 in WNT1 and PLS3 osteoporosis is unknown.</p></sec><sec><title>Objective</title><p>We aimed to investigate if plasma lipocalin-2 could be utilized as a biomarker for WNT1 and PLS3 osteoporosis and to evaluate the association between lipocalin-2 and other parameters of bone metabolism.</p></sec><sec><title>Methods</title><p>We measured plasma lipocalin-2 in 17 <italic>WNT1</italic> and 14 <italic>PLS3</italic> mutation-positive patients and compared them to those of 34 mutation-negative (MN) healthy subjects. We investigated possible associations between lipocalin-2 and several bone biomarkers including collagen type I cross-linked C-telopeptide (CTX), alkaline phosphatase (ALP), type I procollagen intact N-terminal propeptide (PINP), intact and C-terminal fibroblast growth factor 23 (FGF23), dickkopf-1 (DKK1) and sclerostin as well as parameters of iron metabolism (iron, transferrin, transferrin saturation, soluble transferrin receptor and ferritin).</p></sec><sec><title>Results</title><p>We found no differences in plasma lipocalin-2 levels in WNT1 or PLS3 patients compared with MN subjects. However, lipocalin-2 was associated with C-terminal FGF23 in WNT1 patients (<italic>r</italic>=0.62; <italic>p=</italic>0.008) and PLS3 patients (r=0.63, p=0.017), and with intact FGF23 in PLS3 patients (<italic>r</italic>=0.80; <italic>p</italic>&lt;0.001). In addition, lipocalin-2 correlated with serum transferrin in WNT1 patients (<italic>r</italic>=0.72; <italic>p</italic>=0.001).</p></sec><sec><title>Conclusion</title><p>We conclude that plasma lipocalin-2 is not altered in <italic>WNT1</italic> or <italic>PLS3</italic> mutation-positive subjects but is associated with FGF23 in abnormal WNT1 or PLS3 signaling and with iron status in abnormal WNT1 signaling.</p></sec>