Serum C-C Motif Ligand 11/eotaxin-1 May Serve as a Candidate Biomarker for Postmenopausal Osteoporosis

J Med Biochem. 2019 May 11;38(3):353-360. doi: 10.2478/jomb-2018-0042. eCollection 2019 Jul.

Abstract

Background: The chemokine C-C motif ligand 11, also known as eotaxin-1, has been identified as a novel mediator of inflammatory bone resorption. However, little is known regarding a potential role for CCL11/Eotaxin-1 in postmenopausal osteoporosis.

Objective: The scope of this study was to explore the relationship between serum CCL11/Eotaxin-1 concentrations and disease progression of postmenopausal females with osteoporosis.

Methods: A total of 83 postmenopausal women diagnosed with osteoporosis were enrolled. Meanwhile, 82 postmenopausal women with normal bone mineral density (BMD) and 85 healthy controls inner child-bearing age were enrolled as control. The Dual-energy X-ray absorptiometry was used to examine the BMDs at the femoral neck, lumbar spine 1-4 and total hip of all participants. Serum CCL11/Eotaxin-1 levels were examined by enzyme-linked immunosorbent assay. We also included inflammation marker interleukin-6 (IL-6) as well as a serum marker of bone resorption C-telopeptide cross-linked collagen type 1 (CTX-1). The Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) were recorded to evaluate the clinical severity in POMP females.

Results: Serum CCL11/Eotaxin-1 levels were significantly elevated in postmenopausal osteoporotic patients PMOP patients compared with PMNOP and healthy controls. We observed a significant negative correlation of serum CCL11/Eotaxin-1 levels with lumbar spine, femoral neck and total hip BMD. Furthermore, serum CCL11/ Eotaxin-1 concentrations were also positively related to the VAS and ODI scores. Last, serum CCL11/ Eotaxin-1 concentrations were positively associated with IL-6 and CTX-1 levels. These correlations remain significant after adjusting for age and BMI. Multivariate linear regression analysis demonstrated that CCL11/Eotaxin-1 could serve as an independent marker.

Conclusions: Serum CCL 11/Eotaxin-1 may serve as a candidate biomarker for postmenopausal osteoporosis. Therapeutics targeting CCL11/Eotaxin-1 and its related signalling way to prevent and slow progression of PMOP deserve further study.

Uvod: Hemokin (C-C motiv) ligand 11, poznat i pod nazivom eotaksin-1, identifikovan je kao novi posrednik zapaljenske resorpcije kostiju. Međutim, malo se zna o potencijalnoj ulozi CCL11/Eotaksin-1 u postmenopauzalnoj osteoporozi.Cilj Cilj ove studije bio je istraživanje odnosa između serumskih koncentracija CCL11/Eotaksin-1 i progresije bolesti osteoporoze kod žena u postmenopauzi.

Metode: U istraživanju su ukupno učestvovale 83 žene sa dijagnozom osteoporoze u postmenopauzi. U međuvremenu su u studiju uključene 82 žene u postmenopauzi sa normalnom mineralnom gustinom kostiju (BMD) i 85 zdravih žena sposobnih za rađanje kao kontrolna grupa. Za ispitivanje BMD-a na vratu femura, lumbalne kičme 1–4 i celog kuka svih učesnica korišćena je dvoenergentska rentgenska apsorpciometrija. Serumske koncentracije CCL11/Eotakisn-1 su ispitane pomoću enzimski vezanih imunosorbentnih testova. Takođe smo uključili i inflamatorni marker interleukin-6 (IL-6), kao i serumski marker koštane resorpcije C-telopeptidnog ukrštenog kolagena tipa 1 (CTKS-1). Zabeleženi su rezultati na Vizuelnoanalognoj skali (VAS) kao i Oswestry indeks invalidnosti (ODI) za procenu ozbiljnosti kliničke slike kod žena sa postmenopauzalnom osteoporozom.

Rezultati: Serumski CCL11/Eotaksin-1 nivoi su bili značajno povišeni kod pacijenata sa postmenopauzalnom osteoporozom (PMOP) u poređenju sa PMNOP i zdravom kontrolnom grupom. Posmatrali smo značajnu negativnu korelaciju serumskih nivoa CCL11/Eotaksin-1 sa BMD-omlumbalne kičme, vratom femura i celog kuka. Pored toga, serumska koncentracija CCL11/Eotaksin-1 takođe je pozitivno povezana sa rezultatima VAS i ODI. Poslednje, serumska koncentracija CCL11/ Eotaksin-1 je bila pozitivno povezana sa nivoima IL-6 i CTKS-1. Ove korelacije i dalje ostaju značajne nakon usklađivanja sa godinama i BMI. Multivarijantna linearna regresiona analiza pokazala je da CCL11/Eotaksin-1 može poslužiti kao nezavisni marker.

Zaključak: Serumski CCL 11/Eotaksin-1 može poslužiti kao kandidat za biomarker za postmenopauzalna osteoporozu. Terapija koja targetira CCL11/Eotaksin-1 i njegov signalni put u cilju sprečavanja i usporavanja progresije PMOP-a zaslužuje dalja istraživanja.

Keywords: chemokine C-C motif chemokine 11; disease severity; eotaxin-1; postmenopausal osteoporosis.