ASSESSMENT OF SERUM SCLEROSTIN LEVEL AS A BIOMARKER ASSOCIATED WITH BONE DISORDERS IN Β-THALASSEMIA PATIENTS IN AL- NAJAF CITY, IRAQ

Aim of the study: To assess serum sclerostin in female patients with beta-thalassemia and compare with the healthy controls and to predict its complication associated with the bone pathophysiology, for designed improvement the lifestyle goodliness for these patients. Material and methods: Sixty-nine female beta-thalassemia (βT) patients (54 βT major and 15 βT Intermedia), aged 8-40 years who dependent on transfused blood, and 20 healthy controls were evaluated serum sclerostin, and was examined the relationship with hematological parameters RBC, Hb, PCV, WBC, PLT, BMI, splenic status, iron, and ferritin levels. The information of beta-thalassemia patients was collected and recorded by the questioner. Results: A significantly increased serum sclerostin level (mean 26.80±0.91) pg/ml was shown in βT patients compared with the healthy controls (10.03±0.68, p < 0.001) pg/ml. Furthermore, a significant decrease (p<0.05) of the sclerostin level was observed in β-thalassemia major compared to intermedia β-thalassemia patients. Serum sclerostin level revealed a significant increase in progress age; it is highest in the age group (30-40) year as compared with age group (8-18) and (19-29) year respectively. Sclerostin showed no associations with the RBC, Hb, PCV, and significantly positively correlated (p<0.05) with serum iron, ferritin levels, WBC, and PLT count. Significantly higher sclerostin levels in splenectomized and underweight groups were observed compared to unsplenectomized and normal-weight groups (p<0.05) of βT patients. Conclusion: Sclerostin plays an important role in beta-thalassemia patients and can serve as a biomarker associated with the bone pathophysiology and indicator to prevent the continuation of such serious diseases caused by iron overload in these patients.

Thalassemia, a human blood disorder

A group of inherited blood defects is known as Thalassemia is among the world’s most prevalent hemoglobinopathies. Thalassemias are of two types such as Alpha and Beta Thalassemia. The cause of these defects is gene mutations leading to low levels and/or malfunctioning α and β globin proteins, respectively. In some cases, one of these proteins may be completely absent. α and β globin chains form a globin fold or pocket for heme (Fe++) attachment to carry oxygen. Genes for alpha and beta-globin proteins are present in the form of a cluster on chromosome 16 and 11, respectively. Different globin genes are used at different stages in the life course. During embryonic and fetal developmental stages, γ globin proteins partner with α globin and are later replaced by β globin protein. Globin chain imbalances result in hemolysis and impede erythropoiesis. Individuals showing mild symptoms include carriers of alpha thalassemia or the people bearing alpha or beta-thalassemia trait. Alpha thalassemia causes conditions like hemolytic anemia or fatal hydrops fetalis depending upon the severity of the disease. Beta thalassemia major results in hemolytic anemia, growth retardation, and skeletal aberrations in early childhood. Children affected by this disorder need regular blood transfusions throughout their lives. Patients that depend on blood transfusion usually develop iron overload that causes other complications in the body systems like renal or hepatic impairment therefore, thalassemias are now categorized as a syndrome. The only cure for Thalassemias would be a bone marrow transplant, or gene therapy with currently no significant success rate. A thorough understanding of the molecular basis of this syndrome may provide novel insights and ideas for its treatment, as scientists have still been unable to find a permanent cure for this deadly disease after more than 87 years since it is first described in 1925.

Evaluation of relationship between biochemical parameters and osteoporosis in patients with β-thalassemia major

Background: Osteoporosis is one of the late complications of β-Thalassemia major. The pathogenesis of osteoporosis depends on different factors. Ineffectiveness of hematopoiesis is the major factor, and the other factors are defected by hormonal functions or biochemical parameters. Osteoclasts hyperactivity in thalassemia increases the serum receptor activator of nuclear factor Kappa B ligand (RANKL), which plays a crucial role in bone development. This study aimed to evaluate the biochemical and hormonal parameters in patients with β-thalassemia major and their association with osteoporosis. Materials and Methods: In this case-control study, 52 patients with β-thalassemia major and 23 with thalassemia minor as controls were enrolled. The patients’ Bone Mineral Density (BMD) was measured using the Dual Energy X-ray absorptiometry (DEXA) method, and 6 mL peripheral blood of the patients and controls was obtained to detect hormonal and biochemical parameters. Data were analyzed using ANOVA, Spearman correlation coefficient, and T-test. Results: The mean of BMD in patients was 0.59±0.01 and 0.69±0.11 in femur and vertebrae, respectively. The biochemical parameters in the (patients/ controls) including calcium and alkaline phosphatase (ALK) were 9.1/ 10.2 mg/dL and 171.1/310 IU, respectively indicating a significant decrease (P< 0.05) compared to the controls. On the contrary, the mean levels of Ferritin and Zinc were 1914.18 µg/L and 113.92 mg/mL, respectively which were significantly increased (P= 0.015 and P=0.045, respectively). There was a negative correlation between the femurs BMD of patients with the RANKL level (r= - 0.8, p = 0.034) and the vertebrae BMD of patients with a Parathormone (PTH) level (r= - 0.8, P = 0.028). Conclusion: The study results indicated that the hyperactivity of RANKL and PTH in thalassemia patients might cause osteoporosis; therefore, detecting biomarkers mentioned above could be useful to diagnose osteoporosis.

Association of Body mass index and serum ferritin level in pediatrics with Beta-thalassemia major disease

Background: Beta-thalassemia major is a type of inherited blood disease that results in variable outcomes such as severe anemia due to haemoglobin chains. Recurrent and lifelong blood transfusions as a treatment in beta-thalassemia major disease lead to iron deposition in various organs and cause the failure of multiple organs. Failure of affected organs leads to Body mass index (BMI) abnormality. This study aimed to evaluate the association between BMI and serum ferritin level as a marker for iron overload. Materials and Methods: A cross-sectional study designed and conducted with total number of 740 paediatrics, with mean age about 14.2±8.7 years old and with beta-thalassemia major requiring recurrent blood transfusion. Patient information, including demographics, serum ferritin level and percentage of BMI, was recorded and analysed by SPSS 25.0 and the statistical significant level, considered as 0.05. Results: A total number of 740 paediatrics with beta-thalassemia major disease (mean age about 14.2±8.7 years) were included to study to examine the association between serum ferritin level and their BMI. The total mean serum level of ferritin calculated about 3326 ± 3859 Nanogram/mililitter (ng/ml). Totally, 447 (60.4%) case of them had BMI percentile less than 5%, 274 (37.02%), 16 (2.16%) and 3 (0.4%) had BMI percentile 5%-85%, 85%-95% and more than 95%. There was no relation between gender and serum ferritin levels. The relationship between age and BMI has been positive (P=0.002). Finally, it resulted that there was a negative relationship between the BMI percentile and mean serum ferritin levels in paediatrics with beta-thalassemia major (P=0.031). Conclusion: Frequent Blood transfusion is associated with elevated serum ferritin level in paediatrics with beta-thalassemia major disease and experiencing lower percentiles of BMI in these patients.

Thalassemia Major and Associated Psychosocial Problems: A Narrative Review

Thalassemia is an inherited disease that causes the production of damaged hemoglobin chains. Patients are diagnosed with thalassemia major due to major clinical signs and deep anemia. This study aimed to examine the major thalassemia and psychosocial aspect of it, which is such an important issue, to serve as a roadmap for better handling these patients and to contribute to the literature. The method used in this study was narrative review. A literature review was conducted by searching the materials published in databases including Web of Science, PubMed, Scopus, and Google Scholar search engine from 2001 to 2020. Besides WHO website was searched. Thalassemia major damages the heart, liver, lungs and endocrine organs due to anemia and iron accumulation. In addition, the patient may experience mental and social problems due to the congenital nature of the disease and its lifelong duration. The psychosocial problems and treatment burdens of thalassemia patients are very high. There are many studies about the prevalence and physical consequences of thalassemia. However, there are not enough articles and researches describing the psychosocial effects of thalassemia on patients and what can be done about these effects. For this reason, this paper focuses on the process of thalassemia and the psychosocial problems it creates to contribute to the literature and to be a roadmap for better handling these patients.

The Impact of Vitamin K2 (Menaquionones) in Children’s Health and Diseases: A Review of the Literature

Vitamin K2 activates vitamin K-dependent proteins that support many biological functions, such as bone mineralization, the inhibition of vascular stiffness, the improvement of endothelial function, the maintenance of strong teeth, brain development, joint health, and optimal body weight. Due to the transformation of food habits in developed countries over the last five decades, vitamin K and, specifically, vitamin K2 intakes among parents and their offspring have decreased significantly, resulting in serious health implications. The therapeutics used in pediatric practice (antibiotics and glucocorticoids) are also to blame for this situation. Low vitamin K status is much more frequent in newborns, due to both endogenous and exogenous insufficiencies. Just after birth vitamin K stores are low, and since human milk is relatively poor in this nutrient, breast-fed infants are at particular risk of a bleeding disorder called vitamin K deficiency bleeding. A pilot study showed that better vitamin K status is associated with lower rate of low-energy fracture incidence. An ongoing clinical trial is intended to address whether vitamin K2 and D3 supplementation might positively impact the biological process of bone healing. Vitamin K2 as menaquinone-7 (MK-7) has a documented history of safe and effective use. The lack of adverse effects of MK-7 makes it the ideal choice for supplementation by pregnant and nursing women and children, both healthy and suffering from various malabsorptions and health disorders, such as dyslipidemia, diabetes, thalassemia major (TM), cystic fibrosis (CF), inflammatory bowel diseases (IBD), and chronic liver diseases. Additionally, worthy of consideration is the use of vitamin K2 in obesity-related health outcomes.