Abstract
Background
Beta thalassemia major (β-TM) is a common cause of skeletal morbidity and is associated with increased bone fracture risk, particularly in inadequately transfused children. The aim of this study was to investigate some potential biochemical markers as possible early predictors of BMD variations in children with β-TM.
Methods
The study included 38 children with β-TM and 40 sex-age matched controls. All patients were subjected to BMD assessment by dual-energy X-ray absorptiometry (DEXA). Serum beta-crosslaps (beta-CTx), osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B ligand (RANKL), urinary deoxypyridinoline (DPD) and ferritin levels were compared between the groups.
Results
Serum OPG levels were significantly lower in thalassemic children than in controls. The mean ratio of RANKL/OPG was significantly higher in the thalassemic patients than in the control group. Osteoporosis was detected in 10 (3 female and 7 male) of 38 patients (26.3%) according to the femur Z score and in 6 of them (4 male and 2 female) (15.8%) according to the spine Z score.
Conclusions
Serum OPG concentrations can be used as a biochemical marker in screening patients with beta-thalassemia major for the development of osteoporosis.
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What is already known about this topic?
It is well known that beta-thalassemia major is associated with a number of comorbidities, including osteoporosis. Screening children with beta-thalassemia major for osteoporosis with dual-energy X-ray absorptiometry (DEXA) is necessary for detecting osteoporosis and improving bone health. However, DEXA is a radiological tool with X-ray exposure that is not available in every centre. Therefore, there is a need for biochemical markers.
What does this study add?
This study shows that serum osteoprotegerin concentrations can be used as a biochemical marker in screening patients with beta-thalassemia major for the development of osteoporosis.
Background
Beta thalassemia major (β-TM) is a common cause of skeletal morbidity and increased bone fracture risk in thalassemic patients [1]. Its pathogenesis is multifactorial and mainly includes bone marrow expansion, endocrine dysfunction and iron overload [20, 21]. In a study conducted on patients with sickle cell anaemia, the mean lumbar spine Z score was significantly lower in prepubertal girls than in boys. However, there was no significant difference in the pubertal group [22]. When the prepubertal thalassemic patients in this study were evaluated according to sex, the mean spine DEXA Z score results were higher in females than males. In contrast, the mean femur Z score was higher in males than females.
Iron accumulation has a negative effect on bone mineralisation. BMD was significantly influenced by noneffective chelation in children with beta-thalassemia major [23]. According to the results of this study, it was confirmed that DEXA Z scores similarly decreased with increasing levels of ferritin.
Limitations
One of the most important limitations of the study is that the participants were not homogeneous in terms of the duration of thalassemia disease. This may affect the degree of osteoporosis in these patients, and thus the correlation between osteoporosis and the potential markers studied. The inability to perform DEXA examination in healthy controls is another important limitation. The possibility of osteoporosis among these patients may confound the comparisons between patients with β-TM and healthy controls. Therefore, there is a need for larger-scale studies comparing the results of a more homogeneous study group in terms of disease duration and a control group that is proven to be free of osteoporosis.
Conclusion
Osteoporosis is a multifactorial disease and may occur early, especially in chronic diseases such as thalassemia. Because of the difficulties in diagnosis and follow-up, screening with DEXA and measuring ferritin level and RANKL/OPG ratios on a regular basis is essential. It should be kept in mind that osteoporosis may develop with advancing age in both sexes.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- β-CTX:
-
Beta-crosslaps
- β-TM:
-
Beta Thalassemia Major
- DPD:
-
Deoxypyridinoline
- DEXA:
-
Dual-Energy X-ray
- RANKL:
-
Activator of nuclear factor-kappa B ligand
- OPG:
-
Osteoprotegerin
- TURKAK:
-
Turkish Accreditation Agency
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Acknowledgements
We are grateful to children and their families who gave consent to participate to the study.
Funding
This study was funded by the Department of Scientific Research Projects (no: 1106 M 0107) in Mustafa Kemal University.
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TC and OS conceived the study; TC, SU and AB wrote manuscript draft; TC and SM performed data curation; TC, OS and SU performed patient enrollment; TC, SU and AB revised the manuscript. All the authors read and approved the final version of the manuscript.
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The protocol was approved by the ethical committee of the University of Mustafa Kemal (Protocol number 2011/12).
All methods were carried out in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
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Çelik, T., Sangün, Ö., Ünal, Ş. et al. Assessment of biochemical bone markers of osteoporosis in children with thalassemia major. Ital J Pediatr 48, 105 (2022). https://doi.org/10.1186/s13052-022-01290-x
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DOI: https://doi.org/10.1186/s13052-022-01290-x