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\def\RunningAuthor{Safa A Faraj et al.}
\firstPage{676}
\articleType{Original Article}
\receivedDate{10 Dec 2020}
\acceptedDate{12 Jan 2021}
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\title{Bone mineral density in patients with thalassemia major, the experience of a single institute}
\author{Ahmed~I~Ansaf\textsuperscript{1},  
            Safa~A~Faraj\textsuperscript{*}\textsuperscript{1}, 
            Rahan~A~Mohammed\textsuperscript{2}~\\[5pt]{\textsuperscript{1}Department of Pediatrics, College of Medicine, Wasit University, Kut, Iraq}~\\{\textsuperscript{2}Department of Pediatrics, Shakhan general hospital, Mousel, Iraq}}

\begin{abstract}
Thalassemia is an inherited disorder causing an imbalance in the development of the globin chain with ineffective erythropoiesis and increased peripheral consumption. Expansion of bone marrow decreases bone mineral density. Bone disease in thalassemia is manifested as diffuse bone pain, scoliosis, spinal deformities, nerve compression, spontaneous fracture. Bone Mineral Density (BMD) is a useful indicator for bone monitoring and assessment and significant predictor of bone disease in thalassemia. The purpose of this study is to evaluate Bone Mineral Density in thalassemia patients and its correlation with other factors. The study was conducted in Hematology Center at Al-Karama Teaching Hospital, Wasit, Iraq, from the first of January to the thirty of April 2019. Fifty-eight thalassemia patients were enrolled in this study. Bone mineral density was assessed using Dual-Energy X-ray Absorptiometry technique (DEXA scan) for the lumber spine (L1-L4) at the Dexa unit in the rehabilitation Center in KUT. The patients were divided according to BMD by Z-Score \ensuremath{\leq } 15 years old patients, T score for adults ({\textgreater}15 years old) into three groups: a score \ensuremath{\geq } -1 defined as Normal BMD, Osteopenia (between \ensuremath{-}1 and \ensuremath{-}2.5 SD), and Osteoporosis (below \ensuremath{-}2.5 SD). The effect of Gender, Age, frequency of blood transfusion, Hb level, Serum Calcium, and Serum Ferritin on BMD was evaluated. Young patients (with age equal to or younger than 15 years) showed lower bone density than older patients. Also, Patients with Suboptimal blood transfusion had lower bone density than patients than good compliance blood transfusion program, P-value 0.001, 0.012, respectively. The results indicated a direct relationship between the age of the thalassemia patients and bone mass density, P-value = 0.0001, Pearson Correlation = 0.7. Low bone density was reported in young age and suboptimal blood transfusion.
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Thalassemia Major,\newline Bone Density,\newline Osteopenia,\newline Osteoporosis
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Safa~A~Faraj~\\ Phone:\ ~\\  Email:\ Safaafaraj@uowasit.edu.iq
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\section{Introduction}
Thalassemia is the most common inherited blood disorder caused by an imbalance in the development of globin chains. This disorder causes inefficient erythropoiesis and heightened peripheral hemolysis due to the increasing ineffective erythropoiesis. ``The cavity of the bone marrow is more extensive, and the cortical and tubular sections of the bone tissue decrease. \unskip~\citep{989855:21283812}

Treatment of thalassemia has significantly changed over the last two decades. Regular transfusion and proper chelation of iron have improved the life span and quality of life of patients''. Compliance to Desferal chelation therapy is going to be difficult for many patients. ``As the patients become grow older, they will need frequent transfusion that contributes to iron overload and end-organ damage, including endocrinopathies such as hypogonadotropic hypogonadism, hypothyroidism, diabetes mellitus, and hypoparathyroidism''. In addition to increased risk of Osteoporosis and cardiac insufficiency. \unskip~\citep{989855:21283811}

``Osteoporosis with accompanied suffer and morbidity increased in patients with transfusion-dependent \ensuremath{\beta }-thalassemia major''. \unskip~\citep{989855:21283810,989855:21283816}

``Osteoporosis characterized by bone tissue loss and skeleton weakening, which results in reduced bone strength and increased rate of bone fracture. \unskip~\citep{989855:21283815} Bone mineral density (BMD) is a useful indicator for bone monitoring and assessment and is the most significant predictor of thalassemia in children. \unskip~\citep{989855:21283808}

The pathogenesis of thalassemia bone disease is multifactorial in which there is increased bone turnover with excessive bone remodelling and resorption. \unskip~\citep{989855:21283814} ``Expansion of the bone marrow, nutritional deficiency, and toxicity from chelating agents are additional essential factors''. Other risk factors include small body size, low baseline hemoglobin, stunted growth, high iron stores and shortage in calcium/vitamin. \unskip~\citep{989855:21283807}

``Bone mineral density (BMD) is a healthy bone status index and a primary predictor of fracture risk. \unskip~\citep{989855:21283808}

In Iraq, thalassemia is one major health medical problem. With unstable safety conditions and low health budget, most thalassemia patients have poor regular follow up. In this study, we measure the bone density of thalassemia patients and correlated with related factors.

\textbf{Patients and methods}

Fifty-eight thalassemia patients included in this cross-sectional study from the first period of January to the thirty of April 2019. All patients were followed by a hematologist at the Hematology Center at Al-Karama Teaching Hospital, Wasit, Iraq. Intermediate thalassemia patients were excluded from this study. Patients with a Hb level maintain program above 10 g/dl by blood transfusion of once every two to three weeks as average (10 ml of packed RBCs per transfusion) 

Patients with serum ferritin levels are higher than or equal to 1000 ng/dl treated with iron chelators: Deferoxamine (Desferal) 20-40 mg/dl five times per week by subcutaneous infusion pump or Deferasirox (X jade) 20 mg/kg orally once time per day at morning for seven days per week). All information about demographic data, blood indices, and a chemical biochemical investigation taken from patient files. The weight and height for age were calculated by measuring the weights and Hight of patients and comparing them within the global chart at the time of the study.

The scientific committee of the College of the Medicine / University of Wasit appointed the current study. Written consent was obtained from all patients participating in the study. About demographic data, the patients were divided according to gender, age, etc. and the patients were classified according to laboratory information into groups according to Hb level, serum calcium, and serum ferritin.

Bone mineral density was assessed using Dual-Energy X-ray Absorptiometry technique (DEXA scan) -(stratos 393 france device) for the lumber spine (L1-L4) at the Dexa unit in the rehabilitation Center in KUT. The results were divided according to DEXA scan report by Z-Score used for \ensuremath{\leq } 15 years old patients, T score used for adults ({\textgreater}15 years old) into three groups: a score \ensuremath{\geq } -1 defined as Normal BMD, Osteopenia (between \ensuremath{-}1 and \ensuremath{-}2.5 SD), and Osteoporosis (below \ensuremath{-}2.5 SD). \unskip~\citep{989855:21283819}

SPSS 20 (SPSS, Inc., Chicago, USA) was used for data analysis. Chi-square was used for analysis. Pearson's correlation was used to identify Correlations among the Z~or T score of bone density with other parameters.
    
\section{Results }
Overall, this study included 58 patients who met the inclusion criteria. The general characteristics of the study participants shown in Table~\ref{tw-f8289009385f}; about 59\% were male; the mean age was 15(7-37) years. Sixty percent of the patients were 15 years or less in age. More than 41\% of the patients were below normal weight for an age while 53\% have below normal (less than the 3 rd centile) Height for age. Splenectomy was done for six patients. Proper iron chelator compliance was recorded in 43 patients. About 60\% of the patients were received blood more than 25 times per year.

Patients' information for laboratory data shown in Table~\ref{tw-0990ccec9b1d}, 34.5\% of the patients were with mean Calcium level below or equal to 8 mg/dl. In 69\% of the patients were Hb mean level of less than 10 g/dl.


\begin{table*}[!htbp]
\caption{\boldmath {Demographic data of the thalassemia patients} }
\label{tw-f8289009385f}
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\tbltoprule \rowcolor{kwdboxcolor}\textbf{Item} & \cAlignHack \textbf{No} & \cAlignHack \textbf{Frequency}\\
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 &
   &
  \\
Male &
  \cAlignHack 34 &
  \cAlignHack 58.6\\
Female &
  \cAlignHack 24 &
  \cAlignHack 41.4\\
\textbf{Age} &
   &
  \\
Less or equal to 15 years &
  \cAlignHack 35 &
  \cAlignHack 60.3\\
More than 15 years &
  \cAlignHack 23 &
  \cAlignHack 39.7\\
\textbf{Weight for age} &
   &
  \\
Normal &
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  \cAlignHack 58.6\\
Below normal (below 3rd centile) &
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  \cAlignHack 41.4\\
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   &
  \\
Normal &
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  \cAlignHack 46.6\\
Below normal (below 3rd centile) &
  \cAlignHack 31 &
  \cAlignHack 53.4\\
\textbf{Splenectomy} &
   &
  \\
Yes &
  \cAlignHack 6 &
  \cAlignHack 10.3\\
No &
  \cAlignHack 52 &
  \cAlignHack 89.7\\
\textbf{Iron chelator compliance} &
   &
  \\
Good &
  \cAlignHack 43 &
  \cAlignHack 74.1\\
Bad &
  \cAlignHack 15 &
  \cAlignHack 25.9\\
\textbf{Period of transfusion} &
   &
  \\
Less than 25 time &
  \cAlignHack 23 &
  \cAlignHack 39.7\\
More than 25 times &
  \cAlignHack 35 &
  \cAlignHack 60.3\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Laboratory data of thethalassemia patients} }
\label{tw-0990ccec9b1d}
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\tbltoprule \rowcolor{kwdboxcolor}\textbf{Item} & \cAlignHack \textbf{No} & \cAlignHack \textbf{Frequency}\\
\tblmidrule 
\textbf{Calcium level mg/dl} &
  \cAlignHack  &
  \cAlignHack \\
Less than or equal to 8 &
  \cAlignHack 20 &
  \cAlignHack 34.5\\
More than 8 mg &
  \cAlignHack 38 &
  \cAlignHack 65.5\\
\textbf{Hb level g/dl} &
  \cAlignHack  &
  \cAlignHack \\
Less than 10 &
  \cAlignHack 40 &
  \cAlignHack 69.0\\
Equal to or more than 10 &
  \cAlignHack 18 &
  \cAlignHack 31.0\\
\textbf{Serum ferritin mg/dl} &
  \cAlignHack  &
  \cAlignHack \\
Less or equal to 1500 &
  \cAlignHack 8 &
  \cAlignHack 13.8\\
More than 1500-3000 &
  \cAlignHack 10 &
  \cAlignHack 17.2\\
More than 3000 &
  \cAlignHack 40 &
  \cAlignHack 69.0\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Bone density of the thalassemia patients} }
\label{tw-a2796e2ac3d5}
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\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack \textbf{Bone density} & \cAlignHack \textbf{Frequency} & \cAlignHack \textbf{Percent}\\
\tblmidrule 
\cAlignHack Normal &
  \cAlignHack 8 &
  \cAlignHack 13.8\\
\cAlignHack Osteopenia &
  \cAlignHack 32 &
  \cAlignHack 55.2\\
\cAlignHack Osteoporosis &
  \cAlignHack 18 &
  \cAlignHack 31.0\\
\cAlignHack Total &
  \cAlignHack 58 &
  \cAlignHack 100.0\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Correlation between bone density and clinical variable} }
\label{tw-862b2e8bf008}
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\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.31879999999999995\linewidth-2\tabcolsep}p{\dimexpr.16940000000000005\linewidth-2\tabcolsep}p{\dimexpr.18199999999999996\linewidth-2\tabcolsep}p{\dimexpr.20720000000000002\linewidth-2\tabcolsep}p{\dimexpr.12259999999999998\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack  & \multicolumn{3}{p{\dimexpr(.5586\linewidth-2\tabcolsep)}}{\cAlignHack \textbf{Bone density}} & \cAlignHack \textbf{P value}\\
\rowcolor{kwdboxcolor}\textbf{Item} & \cAlignHack \textbf{Normal} & \cAlignHack \textbf{Osteopenia} & \cAlignHack \textbf{Osteoporosis} & \cAlignHack \\
\tblmidrule 
\textbf{Gender} &
   &
   &
   &
  \\
Male &
  \cAlignHack 7 (20.6) &
  \cAlignHack 17 (50) &
  \cAlignHack 10 (29.4) &
  \multicolumn{1}{p{\dimexpr(.12259999999999998\linewidth-2\tabcolsep)}}{\multirow{2}{\linewidth}{\cAlignHack 0.2}}\\
Female &
  \cAlignHack 1 (4.2) &
  \cAlignHack 15 (62.5) &
  \cAlignHack 8 (33.3) &
  \\
\textbf{Age} &
   &
   &
   &
  \\
Less or equal to 15 years &
  \cAlignHack 0 (0) &
  \cAlignHack 18 (51.4) &
  \cAlignHack 17 (48.6) &
  \multicolumn{1}{p{\dimexpr(.12259999999999998\linewidth-2\tabcolsep)}}{\multirow{2}{\linewidth}{\cAlignHack 0.001}}\\
More than 15 years &
  \cAlignHack 8 (34.8) &
  \cAlignHack 14 (60.9) &
  \cAlignHack 1 (4.3) &
  \\
\multicolumn{2}{p{\dimexpr(.4882\linewidth-2\tabcolsep)}}{\textbf{Frequency of blood transfusion}} &
   &
   &
  \\
Less than 25 time &
  \cAlignHack 1 (4.3) &
  \cAlignHack 10 (43.5) &
  \cAlignHack 12 (52.2) &
  \multicolumn{1}{p{\dimexpr(.12259999999999998\linewidth-2\tabcolsep)}}{\multirow{2}{\linewidth}{\cAlignHack 0.012}}\\
More than 25 times &
  \cAlignHack 7 (20.) &
  \cAlignHack 22 (62.9) &
  \cAlignHack 6 (17.1) &
  \\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Correlation between bone density and laboratory variable} }
\label{tw-7994d4623d55}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.3439\linewidth-2\tabcolsep}p{\dimexpr.15320000000000002\linewidth-2\tabcolsep}p{\dimexpr.17129999999999995\linewidth-2\tabcolsep}p{\dimexpr.1982\linewidth-2\tabcolsep}p{\dimexpr.1334\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor} & \textbf{Normal} & \textbf{Osteopenia} & \textbf{Osteoporosis} & \textbf{P value}\\
\tblmidrule 
\textbf{Hb level} &
   &
   &
   &
  \\
Less than 10 &
  5 (12.5) &
  21 (52.5) &
  14 (35) &
  \multicolumn{1}{p{\dimexpr(.1334\linewidth-2\tabcolsep)}}{\multirow{2}{\linewidth}{0.6}}\\
Equal or more than 10  &
  3 (16.7) &
  11(61.1) &
  4 (22.2) &
  \\
\textbf{Ferritin level mg/dl} &
   &
   &
   &
  \\
Less or equal to 1500 &
  1 (12.5) &
  3 (37.5) &
  4 (50) &
  \\
More than 1500-3000 &
  0 (0) &
  7 (70) &
  3 (30) &
  \multicolumn{1}{p{\dimexpr(.1334\linewidth-2\tabcolsep)}}{\multirow{2}{\linewidth}{0.4}}\\
More than 3000 &
  7 (17.5) &
  22 (55) &
  11(27.5) &
  \\
\textbf{Serum calcium mg/dl} &
   &
   &
   &
  \\
Less than or equal to 8 &
  4 (20) &
  12 (60) &
  4 (20) &
  \multicolumn{1}{p{\dimexpr(.1334\linewidth-2\tabcolsep)}}{\multirow{2}{\linewidth}{0.3}}\\
More than 8 mg &
  4 (10.5) &
  20 (52.6) &
  14 (36.8) &
  \\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
Only eight patients (13.8\%) were with serum ferritin lower than 1500 mg/dl and 40 (69\%) were s.ferritin more than 3000 mg/dl. All patients categorized according to bone density to three groups; eight patients were grouped as average bone density, thirty two (55.2\%) patients reported as osteopenia, and eight patients had osteoporosis results. As shown in Table~\ref{tw-a2796e2ac3d5}. Figure~\ref{f-04a49cc0e5ea} shows the DEXA scan expressed by the Z~score for young and T score for adult.


\bgroup
\fixFloatSize{images/0b290ba4-64b0-4617-9145-eb43c3ffeaa2-upicture1.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/0b290ba4-64b0-4617-9145-eb43c3ffeaa2-upicture1.png}{\includegraphics{images/0b290ba4-64b0-4617-9145-eb43c3ffeaa2-upicture1.png}}{}
\makeatother 
\caption{\boldmath {Z score according to bone density groups }}
\label{f-04a49cc0e5ea}
\end{figure}
\egroup
There was no correlation between bone density and gender of the patients, although most of the male and female patients were in osteopenia condition, 50\%, and 62.5\%, respectively. There was a significant correlation between bone density and the age of the patients; zero patients with age less than or equal to 15 years have average bone density, 18 (51.4\%) had osteopenia and 17 (48.6\%) had Osteoporosis, on the other hand, in older than 15 years old patients: 8 patients(34.8) had an average bone density, 14 (60.9\%) had osteopenia and one patient (4.3\%) had Osteoporosis, p-value 0.001.

 There was a significant correlation between the number of transfusion per year and BMD status: more than half the patients (52.2\%) with a history of blood transfusion less than 25 times have osteoporosis bone density, on the other hand, patients with a history of blood transfusion more than 25 times per year: 7 (20\%) had an average bone density, 22(62.9\%) of the have osteopenia and 6 (17.1) had Osteoporosis with p-value 0.012. Table~\ref{tw-862b2e8bf008}

There was no significant correlation between Hb level, serum ferritin, and serum calcium level with bone density status, p-value 0.6,0.4, and 0.3, respectively. About 52\% of patients with Hb level less than 10 g/dl had osteopenia, while 61.1\% of the patients who have Hb level more than 10 g/dl were osteopenia bone density. Osteopenia bone density also reported in thalassemia patients with serum ferritin level between 1500-3000 ng/dl, and serum ferritin more than 3000 ng/dl, 70\%, 55\% respectively. Sixty percent of the patients with serum calcium level equal or lass 8 mg/dl had osteopenia bone density status. As shown in Table~\ref{tw-7994d4623d55}.

The second Figure~\ref{f-75a0111e2745} shows the correlation between age and bone density, which shows the positive correlation between age and Z~and T score (r= 0.7, p value = 0.0001) while the Figure~\ref{f-624eb854d1b0} shows the correlation between ferritin and bone density and was a positive correlation despite the lack of statistical significance (r=0.23, p value= 0.7)


\bgroup
\fixFloatSize{images/85fade6c-6cfe-4c3a-a6e8-20c6ad711924-upicture2.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/85fade6c-6cfe-4c3a-a6e8-20c6ad711924-upicture2.png}{\includegraphics{images/85fade6c-6cfe-4c3a-a6e8-20c6ad711924-upicture2.png}}{}
\makeatother 
\caption{\boldmath {Correlation between age and lumber Z~scores bone scan}}
\label{f-75a0111e2745}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/e8297f44-e0db-406e-9233-d6eb6c351ee1-upicture3.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/e8297f44-e0db-406e-9233-d6eb6c351ee1-upicture3.png}{\includegraphics{images/e8297f44-e0db-406e-9233-d6eb6c351ee1-upicture3.png}}{}
\makeatother 
\caption{\boldmath {Correlation between serum ferritin and Lumber Z~scores bone scan}}
\label{f-624eb854d1b0}
\end{figure}
\egroup

    
\section{Discussion}
As bone density assessment is one of the investigations that were not easily, if ever available in Iraq, Iraq is a country that suffers from political and security instability, which negatively affected Thalassemia patients who suffer from many undiagnosed complications as a result of the lack of medicines and the necessary investigation for that.

In the current study, thirty-two patients (55\%) were diagnosed with osteopenia. This percent is higher than what reported Fouzia's study, where (49\%) of the patients have osteopenia. \unskip~\citep{989855:21283821} In this study, eighteen patients (31\%) had Osteoporosis, which is less than what recorded in the same Previous study (47.33\%). Le and colleagues conducted a study of thalassemia patients, and the percentage of patients who had Osteoporosis was 62\%, which is similar to what reported in this study. \unskip~\citep{989855:21283819}

Many complications cause morbidity in thalassemia patients, Osteoporosis is one of the most important of these complications, especially in patients who live longer because of improved treatment methods. In our daily clinic at the thalassemia center, many patients especially young age had a complain of severe diffuse bone pain in the back at the lower vertebral bodies with or without severe pain at lower or upper limbs. Also, fractures recorded in three patients, they are not included in this study sample.

So this nescessitate looking for bone mineral status for our patients, including calcium level, vit D3 level which is not easily available in routine outpatients thalassemia clinic and doing DEXA scan for these patients suffered from diffuse bone pain was of great value to diagnose abnormal bone density and to try to give them appropriate management like calcium and vitamin D with aldronate tab in a weekly dose to heal the damaged bone, which greatly affects on quality of life to our patient including the better tolerance to physical activity, disappearance the signs o~accompanied mood changes like decreased physical activities, depression and anxiety.

There are several reasons that may lead to the occurrence of Osteoporosis in our patients with thalassemia, such as an increase in bone marrow activity which leads to bone expansion, iron chelators (availability and compliance), an increase in serum ferritin level and a disorder in the work of hormones responsible for regulating the action of calcium and vitamin D with a sexual hormones deficiency as a result of gonadal function impairment. \unskip~\citep{989855:21283813,989855:21283820}

There was no relationship between bone density and gender. The same results were mentioned in several studies, including a Kerimi study. \unskip~\citep{989855:21283820} In this study, low bone density was more of a young age, and this corresponds to what was recorded in Khadijeh study and Voskaridou study. This can due to that children have low bone volume and increased bone expansion. \unskip~\citep{989855:21283817,989855:21283818}

The incidence of Osteoporosis was the high percentage in patients who were transferring blood less than others with optimum transfusion with a clear statistical significance. This is not consistent with Mahmoudi's stud. \unskip~\citep{989855:21283809} Chronic hypoxia, more bone expansion, and impaired puberty can result from a suboptimal blood transfusion. \unskip~\citep{989855:21283817}

 In our study, there was no clear statistical difference between Hb level and Osteoporosis, and this corresponds to what was mentioned in the Shamshirsaz study and Khadijah study \unskip~\citep{989855:21283822,989855:21283817}. Increased blood transfusion can lead to increased iron overload and a decrease in calcium, which leads to Osteoporosis. \unskip~\citep{989855:21283805}

There was no significant statistical difference for other factors, such as calcium level and serum ferritin, and this is what was mentioned in the Shamshirsaz study, even though calcium can be essential in bone formation and Preventing Osteoporosis. \unskip~\citep{989855:21283822} The small size of the sample and some patients already taking calcium supplements may be a reason for obtaining these results. 

Age and Osteoporosis had an inverse relationship, and this is what was mentioned in Khadijah study, which can explain the effectiveness of bone expansion according to age in addition to the use of iron chelators that may affect the bone expansion. \unskip~\citep{989855:21283817,989855:21283822}

Through the mentioned results, several factors may lead to the occurrence of Osteoporosis in patients with thalassemia and even the genetic factor can play an important role in this aspect \unskip~\citep{989855:21283806}. There is a need to studied more about the relation between abnormal bone density in thalassmic patients with vitamin D level and supplementation, growth and gonadal hormones relationship.
    
\section{Conclusions}
The present study reported a high percentage of thalassemia patients who had abnormal bone density within the studied sample. Osteoporosis and osteopenia are severe complications that can be prevented through early diagnosis and treatment of factors that cause it, some of which have been mentioned in this research. Follow-up of patients by monitoring the level of hormones and the level of serum ferritin, as well as conducting a DEXA bone scan for patients is important in determining low bone density in its early stages.

\textbf{Funding Support}

The authors declare that they have no funding support for this study.

\textbf{Conflict of Interest}

The authors declare that they have no conflict of interest for this study.
    

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