\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[greek,ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Bone Mineral Density and Dickkopf-1 in Adolescents with Non-deletional
Hemoglobin H Disease}



\author[1]{Pattara Wiromrat}%
\author[1]{Aree Rattanathongkom}%
\author[1]{Napat Laoaroon}%
\author[1]{Kunanya  Suwannaying}%
\author[1]{Patcharee Komwilaisak}%
\author[1]{Ouyporn Panamonta}%
\author[1]{Nantaporn Wongsurawat}%
\author[2]{Nat Nasomyont}%
\affil[1]{Khon Kaen University Faculty of Medicine}%
\affil[2]{Cincinnati Children's Hospital Medical Center}%


\vspace{-1em}



  
  \date{June 18, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
\textbf{Background:} Low bone mineral density (BMD) is prevalent in
individuals with \selectlanguage{greek}β-\selectlanguage{english}thalassemia which might be related to increased
circulating dickkopf-1 (Dkk-1). These data are limited in \selectlanguage{greek}α-\selectlanguage{english}thalassemia.
\textbf{Objectives:} To evaluate the prevalence of low BMD in
adolescents with non-deletional hemoglobin (Hb) H disease. Additionally,
we aimed to examine the association between serum Dkk-1 concentration
and BMD. \textbf{Methods:} Participant medical records were reviewed.
The lumbar spine (LS) and total body (TB) BMD were measured and
converted into height-adjusted z-scores. Serum Dkk-1, osteocalcin and
C-telopeptide of type-I collagen (CTX) concentrations were also
analyzed. \textbf{Results:} Thirty-seven participants (59\% female, 86\%
Tanner stage [?]2, 95\% regularly transfused) had mean age 14.6 \selectlanguage{ngerman}± 3.2
years, and average pretransfusion Hb and ferritin concentrations of 8.8
± 1.0 g/dL and 958 ± 513 ng/mL, respectively. No participants had
experienced fracture. The prevalence of low LSBMD and TBBMD was 42\% and
17\%, respectively. LSBMD z-score was lower in males vs. females
(p-value = 0.029). LSBMD and TBBMD z-scores were correlated positively
with BA, Tanner stage, and BMI, and negatively with Dkk-1 (p-values
\textless{}0.05). Dkk-1 was correlated positively with history of
delayed puberty, and negatively with transfusion interval (p-values =
0.038). Osteocalcin and CTX did not correlate with BMD or Dkk-1.
Multiple regression analysis showed Dkk-1 inversely associated with
TBBMD z-score adjusting for confounders (p-value = 0.009).
\textbf{Conclusions:} We demonstrated a high prevalence of low BMD in
adolescents with non-deletional Hb H disease. Moreover, Dkk-1 inversely
associated with TBBMD suggesting it may serve as bone biomarker in
thalassemia.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Bone Mineral Density and Dickkopf-1 in Adolescents with
Non-deletional Hemoglobin H Disease}

*Pattara Wiromrat\textsuperscript{1}, M.D., *Aree
Rattanathongkom\textsuperscript{1}, M.D.; Napat
Laoaroon\textsuperscript{2}, M.D.; Kunanya
Suwannaying\textsuperscript{2}, M.D.; Patcharee
Komwilaisak\textsuperscript{2}, M.D.; Ouyporn
Panamonta\textsuperscript{1}, M.D.; Nantaporn
Wongsurawat\textsuperscript{3}, M.D., Ph.D.; Nat
Nasomyont\textsuperscript{4}, M.D., M.S

\emph{*Pattara Wiromrat and Aree Rattanathongkom are co-first authors
and equally contributed.}\textbf{Affiliations:}

\textsuperscript{1}Section of Endocrinology, Department of Pediatrics,
Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

\textsuperscript{2}Section of Hematology-Oncology, Department of
Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen,
Thailand

\textsuperscript{3}Section of Nuclear Medicine, Department of Radiology,
Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

\textsuperscript{4}Division of Endocrinology, Cincinnati Children's
Hospital Medical Center and Department of Pediatrics, University of
Cincinnati College of Medicine, Cincinnati, Ohio, USA.

\textbf{Address all correspondence to:}

Pattara Wiromrat, M.D., 123 Section of Endocrinology, Department of
Pediatrics, Khon Kaen University, Mitraparp Highway, Khon Kaen, Thailand
40002

Email: patwiro@kku.ac.th; Phone: +66 86 716 8485; Fax\textbf{:} +66 43
363 012

\textbf{Running title:} Bone mass and dickkopf-1 in \selectlanguage{greek}α-\selectlanguage{english}thalassemia

\textbf{Keywords:} \selectlanguage{greek}α-\selectlanguage{english}thalassemia, Adolescents, Bone mineral density,
Dickkopf-1, Non-deletional hemoglobin H disease

\textbf{Note:} Part of this study was presented as a poster presentation
at the European Society for Pediatric Endocrinology 2022 meeting in
Rome, Italy, 15-17 September 2022 (published in Horm Res Paediatr
2022;95(suppl 2):1-616. doi: 10.1159/000525606)\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
\textbf{Abbreviations} & \textbf{Full terms}\tabularnewline
\midrule
\endhead
25OHD & 25-hydroxy vitamin D\tabularnewline
\selectlanguage{greek}β-\selectlanguage{english}TI & \selectlanguage{greek}β-\selectlanguage{english}thalassemia intermedia\tabularnewline
\selectlanguage{greek}β-\selectlanguage{english}TM & \selectlanguage{greek}β-\selectlanguage{english}thalassemia major\tabularnewline
BA & Bone age\tabularnewline
BMD & Bone mineral density\tabularnewline
BMI & Body mass index\tabularnewline
CS & Constant Spring\tabularnewline
CTX & C-terminal telopeptide of type-I collagen\tabularnewline
Dkk-1 & Dickkopf-1\tabularnewline
Hb & Hemoglobin\tabularnewline
IGF-1 & Insulin-like growth factor-1\tabularnewline
LIC & Liver iron concentration\tabularnewline
LS & Lumbar spine\tabularnewline
OC & Osteocalcin\tabularnewline
RANK & Receptor activator of NF-kB\tabularnewline
TAO & Thalassemia-associated osteoporosis\tabularnewline
TB & Total body\tabularnewline
TSH & Thyroid-stimulating hormone\tabularnewline
USTCRN & United States Thalassemia Clinical Research
Network\tabularnewline
\bottomrule
\end{longtable}



\textbf{}

\selectlanguage{english}
\FloatBarrier
\end{document}

