الفهرس 
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Abstract
Summary
Thalassemia is an autosomal recessively inherited early onset blood disorder that results in the underproduction of hemoglobin (used by red blood cells to transport oxygen), causing severe anemia and a lifetime reliance on blood transfusions. People with thalassemia typically also require regular chelation therapy to remove excess iron from their bodies. Different types of thalassemia exist, depending on the hemoglobin gene affected (alpha/beta) and severity, with beta-thalassemia major being the most common, but also one of the most severe types.
Osteopenia and osteoporosis are among the most common causes of morbidity in adult patients with Beta Thalassemia .The pathogenesis of bone abnormality in patients with Thalassemia is complex and multifactorial. It may be altered by complications of iron overload, nutritional status, lifestyle and reduced physical activity ,type of iron chelators, increased osteoclast maturation, decreased osteoblast activity, and genetic factors and imbalanced receptor–activator of nuclear factor-kappa B ligand (RANKL)/ RANK, and osteoprotegerin
In this study we estimate level of Osteoprotegrin in Beta thalassemic patient and its role in Thalassemia associated osteoporosis.
This study was conducted on 40Egyptian patients with beta thalassemia (20 Beta Thalassemia major and 20 Beta Thalassemia intemedia ) and 40 healthy controls of matched age and sex.
All patients and controls were be subjected to the following:
1-History taking.
2-Clinical Examination.
3-Investigations includes:
Laboratory investigations (For all cases (thalassemic patients and healthy controls):
General laboratoty investigations
Complete blood count ( red blood cell indices from peripheral blood samples).
Serum iron concentration, serum ferritin and TIBC.
TSH, Serum calcium level and PTH.
Specific laboratoty investigations
Measurement of serum human osteoprotgrin by ELISA kit.
For patients only:
Hemoglobin type and quantification will be performed by (HPLC) High-performance liquid chromatography to determine type of Beta Thalassemia.
Radiological investigationsfor patients
DEXA scan(dual-energy x-ray absorptiometry).
This study demonstrated the following :
• There was no statistical significant difference as regards sex distribution among cases, however Female Sex was predominant in both types of thalassemia average was 55% and 75% resepectively in BTM (Beta Thalasemia Major) and BTI ((Beta Thalasemia Intermedia).
(Cases were divided into 20 BTM & 20 BTI .There was a statistical significant younger age of thalassemia major cases and mean was (24.6±3.4) versus intemedia type and mean was ( 28.3±4.3 ).
• There was no statistical significant difference in presence of spelenctomy between two thalassemia types. However the number of patients with splenectomy inThalassemia major BTM (11) average (55 %) was higher than the number of patients with splenectomy in Thalassemia intermedia BTI (7) average (35 %) .
• There was a statistical significant high mean of (Platelats and ferritin) levels and lower mean of Hb and lower mean of (TSH, PTH and calcium levels) in cases in comparison to healthy controls.
• There was a statistical significant lower mean of (TIBC, TSH, and PTH level ) in thalassemia major cases versus thalassemia intermedia cases ,but they are all still in normal reference ranges in both types of Beta Thalassemia (BTM &BTI) ,in addition to significant a higher mean of (Platelats and TFS% level) in thalassemia major cases. On the other hand, there was no statistical significant difference as regards other investigations (HB , TLC, Iron, ferritin and Calcium). However ( hemoglobin ,iron and calcium ) levels were lower in beta thalassemia major patients in comparison to beta thalassemia intermedia patients and ferritin was relatively higher in beta thalassemia major patients than beta thalassemia intermedia patients .
• There was a statistical significant lower mean of all DEXA (T and Z scores measures) among thalassemia major cases versus intermedia type.That mean that osteoporosis and bone affection more severe in beta thalassemia major.
• As regards DEXA results (T-score) there was a statistical significant higher percentage of radius osteoporosis (90%) and osteopenia in spine (65%) among thalassemia major cases in comparison to thalasemia intermedia , with no difference in femur T-score. In addition there was a statistical significant higher percentage of osteoporosis (90%) among thalassemia major cases in final DEXA diagnosis.
• As regards DEXA results (Z-score) there was a statistical significant higher percentage of radius osteoporosis (90%) and osteopenia in spine (70%) and femur (35%) among major thalassemia cases in comparison to thalasemia intermedia. As regards total DEXA diagnosis there was a statistical significant higher percentage of osteoporosis (85%) among thalassemia major cases.
• Among thalassemia cases there was no significant difference in (T-score ) DEXA results in different gender , but there was a statistical significant higher percentage of Osteoporosis diagnosed by (Z-DEXA score) among females.
• Among thalassemia cases there was no significant difference in T-score DEXA results in different spelenctomy groups, but there was a significant statistical higher percentage of Osteoporosis diagnosis by Z- score DEXA among cases did spelenctomy.
• There was a significant statistical lower mean of all BMD measures among thalassemia major cases versus thalassemia intermedia ,that mean that BMD was lower in thalassemia major cases.
• There was a significantstatistical high mean of Osteoprotegrin level among thalassemia cases versus controls. Also significant lower mean in control group in comparison to both thalassemia subtypes, with no difference between the two thalassemia types (intermedia and major) , but it is higher in thalassemia major than thalassemia intermedia .
• There was a statistical significant high mean of Osteoprotegrin level among males in Thalassemia cases .
• There was no significant correlation between Osteoprotegrin level and both age and all laboratory investigations among Thalassemia cases.
• There was significantstatistical correlation between Osteoprotegrin level and number of affected joints among Thalassemia cases.
• There was no significant difference as regards Osteoprotegrin level in different DEXA final results (T and Z scores) among Thalassemia cases, but the mean of OPG was higher in osteoprotic patients 0.64than osteopenic and normal DEXA results respectively 0.59 and 0.50,so level of OPG is related to the degree of bone affection ,osteoprotic patients had the highest OPG level.
• There was no significant correlation between Osteoprotegrin level and DEXA results (T and Z scores) and also with BMD levels among Thalassemia cases.
• Among Thalassemia cases there was a statistical positive correlation with between each of age and hemoglobin level with Dexa (T and Z –scores) in radius, and a statistical significant negative correlation between Platelats and both spine and femur (T and Z-DEXA scores). In addition ferritin level was negatively correlated with spine( T-DEXA score) and both spine and femur T and Z -DEXA scores. There was a statistical significant negative correlation between transferin saturation and both spine and femur (T and Z ) DEXA scores
• Among thalassemia cases there was a statistical positive correlation between each of age and hemoglobin level with BMD Forearm Radius. Also there was a negative correlation between each of Platelats and Transfertin saturation levels with both AP spine and LT Femur BMD measures. Finally there was a statistical negative correlation between Ferritin level and AP spine BMD measures.
Conclusion:
Osteoporosis represents a major problem among β-thalassemia patients. OPG played important role in the development of osteoporosis in β thalassemia as it stimulate osteoblast which responsible for bone formation so it is reduction leads to osteoporosis .OPG was elevated in β-thalassemia patients in our study and other studies, and this elevation may be acompensatory mechanism to osteoporosis and bone abnormalities in beta thalassemia patients and that elevation may be due to increased osteoblast activity ,on the other hand it is reduced in other researches and this reduction may be decreased osteoblast action. OPG may be used as a marker for osteoporosis and osteopenia in Beta Thalassemia patients( revealed by DEXA scan) however there was no significant difference as regards Osteoprotegrin level in different DEXA final results (T and Z scores) among Thalassemia cases,but the mean of OPG was higher in osteoprotic patients 0.64 than osteopenic and normal DEXA results respectively (0.59 and 0.50) ,so level of OPG may be related to the degree of bone affection ,osteoprotic patients had the highest OPG level , and many researches are needed to cofirm that, , also we found correlation between Osteoprotegrin level and number of affected joints among Thalassemia cases.
Uptill now DEXA scan is the gold standard in early detection of osteopenia and osteoporosis which is also found in our study and we found that osteoporosis and bone affection were more severe in BTM (Beta Thalassemia Major) than BTI (Beta Thalassemia Intermedia)
Our data showed that the OPG (Osteoprotegrin ) represents an important mediator in osteoporosis of Beta Thalassemic patients and OPG (Osteoprotegrin) could be good indicator of the presence of osteoporosis and could be considered as a potential target for novel therapeutic agents.
Although this study is to some extent limited in statistical power because of the small sample size and further studies with a greater number of patients are needed assessing OPG (Osteoprotegrin) production in bone or bone marrow stromal cells, either in vivo or ex vivo to further validate our findings.