Advances in the management of thalassemia have led to marked improvements in the life span and quality of life of children and young adults. This poses new challenges for the treating physicians. There is now increasing recognition that thalassemics have impaired bone health which is multifactorial in etiology. This paper aims to highlight the factors that predispose these patients to osteoporosis and suggests measures to minimise the impact on bone health.

1. Bone Health Issues in Thalassemia

2. Review Article
Till a few decades ago, thalassemic patients had severe
bone deformities due to marrow expansion, but did not
survive long enough to have problems of adolescence and
young adulthood. Now with optimal transfusions and
chelation, survival and quality of life have improved
dramatically. At the same time, regular blood transfusions
and the consequent iron deposition in various endocrine
glands can potentially cause several endocrinopathies with
increasing age. Issues like growth, hypogonadism and
compromised bone health, with increased fracture risk, are
therefore, becoming more important [1,2].
This is particularly crucial in the Indian context, where
deficiency of Vitamin D and calcium, low exercise levels,
rickets and osteomalacia, and osteoporosis are already
prevalent in the general population [3].
It is now well accepted that nearly half of the total bone
density accrual occurs during childhood and adolescence.
The peak bone density attained in adolescence largely
determines fracture risk. Hypogonadism, and consequent
cytokine abnormalities, are well known to cause low bone
density in any condition, and play a major role in causing
poor bone health in thalassemia [4]. Therefore
pediatricians must ensure that the impact of factors
affecting bone accrual is minimized [5]. The young
thalassemic today no longer has the deformed bones of
earlier generations, but continues to have several factors
which contribute to poor bone health (Table 1). These
factors need to be addressed aggressively from an early age
if bone density is to be improved. Furthermore, it has been
shown that regular screening and proper management of
possible endocrine complications can possibly secure
normal bone health in these patients [6].
This results in a variety of bone problems: bone pain
and/ or deformity, frank rickets or osteomalacia,
osteopenia, osteoporosis, pathological fractures, and
occasionally spinal deformities and nerve compression.
Fracture risk is of course related to bone strength, but also
to muscle size, function and activity levels. Attention
must be paid to improving bone and muscle health in
order to minimize fracture risk and other adverse
consequences. Thalassemics have been found to have low
levels of Vitamin D, which is linked not only to bone
health, but also decreased cardiac function, muscle
weakness, glucose insensitivity, and refractory congestive
heart failure [7].
Both for the families as well as the treating physicians,
understandably, the major focus is on achieving optimal
transfusion and chelation. As a consequence, other
important facets of care are often ignored. A number of
measures can go a long way in minimising the adverse
impact of this disease on bone health. By and large, they
are inexpensive and can be easily incorporated in their
care. What is required is increased awareness and
constant reinforcement to the families regarding these
measures. A conscious effort must be made to pay
attention to the following:
• To maintain optimal pre-transfusion haemoglobin.
• Ongoing encouragement to increase the intake of
low fat milk products.
• Annual monitoring of serum calcium and
phosphorus levels.
• Regular supplementation of Vitamin D, encourage-
ment to get sun exposure on the bare skin. Vitamin D
355 Apollo Medicine, Vol. 6, No. 4, December 2009
BONE HEALTH ISSUES IN THALASSEMIA
Anju Virmani and A Mahajan
Senior Consultant, Apollo Centre for Advanced Pediatrics, Indraprastha Apollo Hospitals,
Sarita Vihar, New Delhi 110 076, India.
Correspondence to: Dr Anju Virmani, Senior Consultant, Pediatric Endocrinology,
Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 076, India.
Advances in the management of thalassemia have led to marked improvements in the life span and quality of
life of children and young adults. This poses new challenges for the treating physicians. There is now
increasing recognition that thalassemics have impaired bone health which is multifactorial in etiology. This
paper aims to highlight the factors that predispose these patients to osteoporosis and suggests measures to
minimise the impact on bone health.
Key words: Thalassemia, Osteopenia, Osteoporosis.

3. Apollo Medicine, Vol. 6, No. 4, December 2009 356
Review Article
ethnicity, etc. In a child whose growth is
compromised, interpretation becomes even more
difficult. Serial scans annually or every two years are
the best way to monitor these patients.
• Bisphosphonate therapy is useful in a subgroup of
patients because thalassemia is associated with high
bone turnover, with increased resorption and
remodelling. Generally, it is reserved for those who
have deteriorating bone density in spite of other
measures. Over-treatment can actually result in
increased brittleness of bone, and increased fracture
risk [8,9].
Growth charting, Vitamin D supplementation,
encouragement of adequate calcium intake and active
exercise, and gonadal hormone replacement at the right
age are simple, inexpensive measures which would go a
long way in reducing the morbidity and mortality due to
poor bone health in thalassemics.
REFERENCES
1. Vogiatzi MG, Autio KA, Schneider R, Giardina PJ. Low
bone mass in prepubertal children with thalassemia
major: insights into the pathogenesis of low bone mass in
thalassemia. J Pediatr Endocrinol Metab 2004; 17: 1415-
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2. Karimi M, Ghiam AH, Hashiemia A, et al. Bone mineral
density in beta-thalassemia major and intermedia. Indian
Pediatr 2007; 44(1): 29-32.
3. Marwaha RK, Tandon N, Reddy D, et al. Vitamin D and
bone mineral density status of healthy school children in
northern India. Am J Clin Nutr 2005; 82 (2): 477-482.
4. Morabito N, Gaudio A, Lasco A, et al. Osteoprotegerin
and RANKL in the pathogenesis of thalassemia-induced
osteoporosis: new pieces of the puzzle. J Bone Mineral
Res 2004; 19:722-727.
5. Voskaridou E, Terpos E. Pathogenesis and management
of osteoporosis in thalassemia. Pediatric endocrinology
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6. Christoforidis A, Kazantzidou E, Tsatra I, et al. Normal
lumbar bone mineral density in optimally treated children
and young adolescents with -thalassaemia major.
Hormones 2007; 6(4):334-340.
7. Wood JC, Claster S, Carson S, et al. Vitamin D
deficiency, cardiac iron and cardiac function in
thalassemia major. Br J Hematol 2008; 141(6):891-894.
8. Gaudio A, Morabito N, Xourafa A, et al. Bisphosphonates
in the treatment of thalassemia-associated osteoporosis.
J Endocrinol Invest.2008; 31(2):181-184.
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sachets given every 1-3 months are a safe, inexpensive
way of maintaining adequate Vitamin D levels.
• Once hypoparathyroidism is suspected, calcitriol
should be started in place of cholecalciferol.
• Monitoring of serum T4 andTSH levels annually after
10 years of age.
• Ongoing encouragement to undertake physical
activity, especially weight bearing games like running
and jumping.
• Regular measurement of height, at least every 6
months, with charting on a growth chart on which the
target height (i.e. mid-parental height, which gives the
genetic potential) is marked.
• Regular monitoring of the pubertal status from 12
years. Delayed or absent puberty is a major
contributor to poor bone accrual and/or increased
bone loss, and should be addressed. Secondary
gonadal failure can also occur later in life, even after a
normal puberty, and may not be detected unless
looked for.
• In case of primary gonadal failure, gonadal
replacement therapy should be initiated no later than
14 years; starting with very low doses, and building up
gradually. If gonadal failure occurs later in life, HRT
in adult doses should be begun promptly.
• If growth falters and the child is euthyroid, growth
hormone assessment and replacement may be
required.
• Monitoring of bone mineral density (BMD) using
DXA is useful to give an idea of fracture risk. Several
factors affect the reading: age, growth status,
Table 1. Factors adversely affecting bone mass
accrual in thalassemics
(i) Chronic anemia, ill health, poor weight bearing
(ii) Marrow expansion in those poorly transfused
(iii) Poor calcium intake
(iv) Reduced Vitamin D levels, worsened by low sun
exposure, skin pigmentation and hepatic
involvement
(v) Low levels of exercise
(vi) Hypoparathyroidism
(vii) Hypothyroidism
(viii) Hypogonadotrophic hypogonadism
(ix) Insufficiency of GH, IGF-1, IGF-BP3, other growth
factors
(x) Direct toxicity of iron, chelators, on the bone