Mohd Yusoff

Noor Aini

Roslee Rajikan

Suzana Shahar

Yeo Pei

Yeo Pei Sien

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International Journal of Public Health Research Vol 4 No 1 2014, pp (399-404)
399
Bone Health Status among Thalassemia Children
Yeo Pei Sien1*, Noor Aini Mohd Yusoff2, Suzana Shahar2 and Roslee Rajikan2
1 Institute for Public Health, Ministry of Health, Malaysia.
2 Dietetics Program, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Malaysia.
*For reprint and all correspondence: Yeo Pei Sien, Institute for Public Health, Jalan Bangsar, 50290 Kuala 
Lumpur, Malaysia.
Email: yeops@moh.gov.my
ABSTRACT
Received 21 July 2013
Accepted 4 November 2013
Introduction Low bone mineral density is a significant problem in children with 
Thalassemia which may lead to increased risk for fragility fractures and 
suboptimal peak bone mass. This cross-sectional study was conducted to 
determine the bone health status of Thalassemia children Universiti 
Kebangsaan Malaysia Medical Centre and Paediatrics Insititute Kuala 
Lumpur Hospital.
Methods A total of 81 respondents diagnosed with transfusion dependant beta 
Thalassemia (41 boys and 40 girls) aged between 7 to 19 years old completed 
the study. The data collected were demographic information, anthropometric 
measurements, dairy frequency questionnaires, dietary habits of the 
respondents and their parents, dietary intakes and bone densitometry using 
Ultrasound Bone Densitometer.
Results For Quantitative Ultrasound (QUS) parameters, T-score of 9.8% participants 
were lower than -1.0 and 30.9% of the participants had lower Speed of Sound 
(SOS) than healthy SOS. This study showed there was no difference in bone 
density by sex (p>0.05). The median bone density of boys was 1616.00 m/ 
sec (IQR= 39.00) and girls’ was 1579.00 m/ sec (IQR= 116.00). SOS was not 
increased with age, height and weight; but girls’ Body Mass Index (BMI). 
Malay children had significantly higher SOS than non-Malay children.
Conclusions This study highlights a need of proper intervention for the high risk group to 
achieve optimal bone health. 
Keywords Thalassemia children - Bone mineral density - Bone health status - QUS -
Malaysia.
PUBLIC HEALTH RESEARCH
Bone Health Status among Thalassemia 
400
INTRODUCTION
Low bone mineral density is a significant problem 
in patients with thalassemia which leads to 
decreased quality of life. Regular transfusions and 
increased compliance with iron chelation therapy 
are often accompanied by a series of serious 
complications including growth failure, osteopenia 
and osteoporosis in later life1.
Children with thalassemia major who 
were fully treated with transfusion and chelation 
therapy, were found to have reduced bone mineral 
density (BMD) at diagnosis and showed further 
reductions at follow-up2,3. These children may be at 
increased risk for fragility fractures and suboptimal 
peak bone mass1.
Thalassemias are particularly associated 
with people of Mediterranean origin, Arabs, and 
Asians. The estimated prevalence is 16% in people 
from Cyprus, 1% in Thailand, and 3-8% in 
populations from Bangladesh, China, India, 
Malaysia and Pakistan. In Malaysia, about 4.5% of 
the people are heterozygous carriers for beta 
thalassemia and these couples are at risk of 
producing a child with beta thalassemia major 
where affected births annually would be 2.1/ 10004.
A study in Iran found that the prevalence 
of lumbar osteoporosis and osteopenia in beta-
thalassemia major patients were 50.7% and 39.4%, 
while lumbar BMD abnormalities were associated 
with duration of chelation therapy. Femoral 
osteoporosis and osteopenia were present in 10.8% 
and 36.9% of the patients5.
As the combination of transfusion and 
chelation therapy has extended the life expectancy 
of thalassemia patients, improved survival of 
patients has allowed for adult complications that 
have a major impact on the quality of life. The 
objective of this study was to determine bone 
health status of thalassemic children using bone 
densitometry.
METHODS
This was a cross-sectional study conducted in 
paediatric thalassemic patients aged between 8-19 
years admitted as in-patient or out-patient at the 
Paediatrics Institute Kuala Lumpur Hospital 
(PIKLH) and Universiti Kebangsaan Malaysia 
Medical Centre (UKMMC), Kuala Lumpur. Data 
were collected from May 2009 until August 2009.
Ethical approval for this study was obtained from 
the Medical Research Secretariat, Universiti 
Kebangsaan Malaysia Medical Centre, Clinical 
Research Centre (CRC) and the Ministry of Health 
Research& Ethics Committee (MREC), Malaysia 
(Reference Ethical Approval No.: FF-290-2008). 
Sampling 
Convenience sampling of 158 thalassemic patients 
diagnosed with transfusion dependant beta 
thalassemia (major, intermediate) who met the 
inclusion criteria been chosen. The lists of 
thalassemia patients were obtained from the 
Daycare Centre in the two hospitals. This study 
was done over a period of 4 months. Eighty four 
(84) participants agreed to participate. Inclusion 
criteria: (a) Patients with thalassemia syndrome 
(including transfusion dependent beta-thalassemia, 
E/beta-thalassemia major and intermediate); and 
(b) age 7-19 years old. Exclusion criteria: (a) 
Thalassemic patients with malabsorption diseases, 
other gastrointestinal problems, asthma, or on any 
other medications; (b) patients currently taking a 
bisphosphonate medication for osteopenia. (c) 
patients who have had a bone marrow transplant. 
(d) chronic use of systemic corticosteroids; and (f) 
patients currently use calcium supplement.
After the written consent was obtained 
from the parent, each participant was interviewed 
for demographic information, dairy frequency 
questionnaires, dietary habits of subjects and their 
parents, and dietary intakes. Body weight and 
height of participants were measured.
Ultra Sound Bone Densitometry
Bone densitometry test was performed by using 
Ultrasound Bone Densitometer CM-200 (Furuno 
Electric Co., Ltd., Japan) to measure participants’ 
bone mineral density (BMD). QUS parameters that 
had been assessed were Speed of Sound (SOS) and 
T-score. SOS is a measurement which the sound 
velocity in cancellous bone is calculated from Time 
of Flight (TOF) measurement by transmission 
ultrasound methods6. The TOF method measures 
the sound travel time through coupled medium 
(gel), soft tissue and bone sample, between fixed 
ultrasound transducer separations. The calcaneal 
QUS values in mainland Chinese children and 
adolescents were used as reference SOS7. T-score 
is a comparison of a patient's BMD to that of a 
healthy thirty-year-old of the same sex and 
ethnicity8.
Statistical analyses
All statistical analyses were done with SPSS 
software, version 16.0. Mann-Whitney U test was 
used to determine difference between QUS 
parameters and age groups. Spearman Correlation 
was used to determine the relationship between 
SOS and anthropometry data.
RESULTS
A total of 84 subjects participated in the study 
(response rate 53.2%). However, data from 3 
participants had to be excluded in this report due to 
missing data and withdrawal. Forty one (50.6%) 
participants were boys and 40 participants (49.4%) 
were girls. Median age of participants was 13 
(IQR=5) years old. The proportion of ethnicity was 
69.1% Malays, 25.9%  Chinese, 1.2% Indian and 
3.7% others. 
International Journal of Public Health Research Vol 4 No 1 2014, pp (399-404)
401
Bone health status of participants was 
measured using QUS parameters, i.e. Speed of 
Sound (SOS) dan T-score. Median SOS dan T-
score for boys were 1616.00 m/second (IQR= 
39.00) and 2.23 (IQR= 1.12) respectively. Where 
else, the median SOS and T-score of girls were 
1579.00 m/second (IQR= 116.00) and 1.24 (IQR= 
3.52) respectively. QUS paremeters of participants 
by age groups and sex was shown in Table 1. For 
the purpose of comparison with the age groups as 
the Recommended Nutrient Intakes for Malaysia9, 
the ages were grouped as such. Result showed that 
there was no difference in bone density by sex. 
Table 2 shows the relationship between 
SOS with participants’ age, height, weight and 
BMI. Age, weight and height were not associated 
with QUS parameters among boys and girls.
Malay participants had higher SOS 
compared to other ethnic groups. The association 
by participants’ ethnicity, family income, 
frequency of transfusion, chelation and 
anthropometry data with SOS was shown in Table 
3. There was no association found between SOS 
and those variables.
Table 1 QUS parameter by sex and age group
Age Group
(years)
n SOS (m/sec) T-score
Median (IQR)      x2              p Median (IQR)      x2               p
Boys
      7-9
      10-12
      13-15
      16-18
      19-20*
      Total
12
7
13
5
2
39
1606.50 (36.25)
1612.00 (73.00)
1621.00 (40.00)
1598.00(162.00)
1629.50 (0)
3.079 (4)   0.545 1.96 (1.03)
2.11 (2.08)
2.37 (1.15)
1.71 (4.63)
2.62 (0)
   
3.079 (4)   0.545
Girls
      7-9
      10-12
      13-15
      16-18
      19-20**
      Total
5
12
13
7
1
39
1612.00(100.50)
1551.00(121.25)
1607.00(100.50)
1527.50(139.75)
5.131 (4)   0.274 2.24 (3.05)
0.40 (3.68)
2.09 (3.09)
-0.32 (4.23)
5.058(4)   0.281
  * IQR could not be obtained since n=2
  **Analysis was omitted since n=1
Table 2 Relationship of age, height, weight and BMI with SOS among boys and girls
SOS
Boys (n=39) Girls (n=39)
R p r P
Age 0.003 0.985 -0.271 0.095
Height 0.096 0.559 -0.207 0.207
Weight 0.110 0.506 -0.299 0.065
BMI 0.124 0.453 -0.320 0.047*
     * p< 0.05
Table 3 Relationship with SOS by participants’  ethnicity, family income, frequency of transfusion, chelation 
therapy and anthroppometry data 
SOS
Low (n/ %) High (n/ %) χ2 p
Ethnicity
  Malay
  Non Malay
12/ 15.6
14/ 18.2
40/ 51.9
11/ 14.3
8.183 0.004**
Bone Health Status among Thalassemia 
402
Family income
  <RM1500
  ≥RM1500
7/ 10.1
15/ 21.8
7/ 10.1
40/ 58.0
2.654 0.120
Frequency of transfusion
   1/ bulan
  > 1/ bulan
25/ 32.5
1/ 1.3
44/ 57.1
7/ 9.1
1.805 0.254
Chelation
  Yes
  No
0/ 0
25/ 33.3
10/ 13.3
40/ 53.4
- -
Height-for-age
  Stunted
  Normal
10/ 13.0
16/ 20.8
25/ 32.5
26/ 33.7
0.774 0.379
Weight-for-age
  Malnutrition
  Normal
10/ 13.0
16/ 20.8
28/ 36.3
23/ 29.9
1.862 0.172
BMI-for-age
  Underweight
  Normal
6/ 7.8
20/ 26.0
16/ 20.8
35/ 45.4
0.581 0.446
   ** p< 0.05
DISCUSSION
In this study, we found no difference between 
BMD of boys and girls. This was in contrast to the 
findings of Jensen et. al. who reported that the bone 
lesions in thalassemic patients were more frequent 
and more prominent in males5, but in agreement 
with the some previous reports10-12. A study in 
Southeast Asian Thalassemia children also found 
broadband ultrasound attenuation and SOS were 
independent on sex13. Our finding might be 
influenced by the small number of participants in 
this study.
SOS of participants was compared with 
the calcaneal QUS values in mainland Chinese 
children and adolescents7. There was 30.9% of 
participants’ SOS lower than the reference SOS 
while 80% of them were girls. Low SOS was found 
in the age group of 7 to 9 years old. The 
participants whose T-Score less than -1.0 were 
among those aged between 12 until 19 years old 
(9.8%) and 87.5% of them were girls.
However, T-score is not appopriate to 
make the comparison because it is the bone mineral 
density at the site when compared to the young 
normal reference mean. Hence, T-score might over 
predict the osteopenia among children. The Z-score 
would be a better value to be used as it is the 
number of standard deviations a patient's BMD 
differs from the average BMD of their age, sex, and 
ethnicity14.
There were no relationships found 
between SOS and the anthropometry data of 
participants in our study, except for girls’ BMI. 
However, Zhu (2007) found the age, height and 
body weight of participants were related with SOS, 
except for the boys’ weight& BMI and girls’ height 
were not correlated with SOS in China7. Wünche 
(2000) in Germany also found SOS was correlated 
with increasing of age, height and weight15.
This study found that there was a 
significant difference between ethnicity and the 
bone health status, but could find no significant the 
relation among family income, frequency of 
transfusion, chelation, height-for-age, weight-for-
age and BMI-for-age. Previous studies found bone 
density is lower in Chinese and Japanese, and 
higher in black subjects when compared with white 
subjects16-17. The body proportions are different for 
different ethnic groups. Further more, the complex
interactions between genetic, geographical 
differences and environmental factors also 
determine the formation of bone18-20. 
Ultrasound Bone Densitometer was used 
in the study though DEXA (Dual Energy X-ray 
Absorptiometry) is considered as a reference 
standard to measure bone density. Ultrasound Bone 
Densitometer is safe for children due to not using 
any radioactive X-ray for detecting BMD, and has 
high correlativity with DEXA21. Ultrasound
method also has other advantages such as simpler 
to use, more cost-effective, and reproducibility22-23. 
Besides that, QUS technology is also able to assess 
bone changes in the growing bone24.
There are some limitations should be 
considered in this study. Firstly, the dimension of 
the subjects’ feet was not examined which may 
affect the result of QUS because its location 
between the transducer was not guaranteed. 
Additionally, the pubertal status of subjects was not 
assessed using Tanner’s Method. As children with 
chronic disease have delayed growth or delayed 
maturity in bone, QUS at calcaneus is influenced 
by the growth process and may cause the incorrect 
interpretation. Further studies are warranted to 
International Journal of Public Health Research Vol 4 No 1 2014, pp (399-404)
403
investigate the confounding factors that may 
influence QUS result.
CONCLUSIONS
There was no difference between BMD of boys and 
girls. This study found that there was significant 
difference between ethnicity and the bone health 
status. QUS can be an useful screening or 
assessment tool to improve the care for thalassemia 
children. 
ACKNOWLEDGEMENTS
I would like to extend thanks to the Director 
General of Health, Malaysia for permission to 
publish this paper. The support given by the 
participating UKM undergraduate students and all 
Daycare staff at IPKLH and UKMMC who 
contributed to this study are gratefully 
acknowledged. 
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