LUMBOSACRAL BONE DENSITOMETRY IN CHILDREN WITH B-THLASSEMIA MAJOR

Qasim M H Almosawi 1 , Raid M R umran 2 , Alaa Jumaah Nasrawi 3 , Jasim Mohammed Hashim 4 and Aymen A. Al-bakaa 5 . 1. M,B,Ch,B.,CABP,MSc., Department of Pediatrics, College of Medicine, University of Kufa, AlZahraa teaching hospital, Najaf, Iraq. 2. Ass.Professor of pediatrics Department of Pediatrics, College of Medicine, University of Kufa, AlZahraa teaching hospital, Najaf, Iraq . 3. Professor of pediatrics Department of Pediatrics, College of Medicine, University of Kufa, AlZahraa teaching hospital, Najaf, Iraq. 4. Ass. Professor of pediatrics FICMS,CABP. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History

Thalassemia syndromes either include defect in production of alpha α globin chain where α thalassemia are usually caused deletion of one or more globin gene or the defect is in the β chain production. In β thalassemia the condition may also be due to gene deletion but more commonly is the consequence of abnormalities in the reading or processing of DNA. [2] Bone complications the bone pathological changes can be seen only in poorly controlled thalassemic patients because regular blood transfusion and well controlled hemoglobin levels may prevents these bony deformities. These deformities will be apparent after one year inform of trabecular changes and cystic formation in small bone and thickening of the cortex and increase of modularly space of long. Skull x-rays will show the characteristics picture of "hair-on-end" appearances. [3]. Thalassemia facies occur because of overgrowth of maxilla and absence of cavitation of nasal sinuses that lead to prominence of upper incisors and separation of orbits . [3 , 4] Osteoporosis Osteopenia Syndrome (OOS):-Osteoporosis is a disease of skeletal system that is characterized by low bone density and microarchitectural changes that lead to increase bone fragility and easy fracture . [5] With improvement in life expectancy of thalassemic patient , osteopenia osteoporosis syndrome (OOS) is an important cause of bone pain and factures in those patients. [6] Many researches proves a decreased in bone mass in thalassemic patients ( chatterjee , 2000 ;Morabito , 2004 ;Pignatti , 2006b ;Chan , 2002 ;Voskaridou , 2003 ). [7] The causes of OOS in thalassemia syndromes are multifactorial such as bone marrow expansion as a result of ineffective erythropoiesis , anemia , haemosiderosis, delayed puperty , use of chelating agents , multible endocrinopathies, low level of vitamin D and genetic factors . [8] Diagnosis and investigations:-Those patients are commonly presented by pain in the bone and it may be associated with past history of fractures . about 20 % of patient have no clinically apparent sign and symptoms. DEXA scan:-It is the best way to assess the bone mineral density (BMD).
1659 MRI:-Magnetic resonance imagaing (MRI) of the spine should be done to assess the extramedullary erythropoiesis , and also to check for other bone deformities.

Evaluation of iron load and chelating agent:-Management [9]
The goal of managements is to increase BMD score and decrease the risk of fracture.
Therapeutic options:-A lot of treatment modality are present for treating thalassemic patent with osteopenia-osteoporosis .The choice of treatment was determined by the patient age, the thalassemia type such as frequency of blood transfusion , severity of sign and symptom, previous fractures, treatment taken , other of risk factors of nephrocalcinosis and associated hypogonadism, hyperparathyroidism. [9] Fig.2:-Therapeutic options for OOS. [10] Diet and excersice . Vit.D and calcium supplementation . Sex hormones replacements in HRT.

Monitoring of treatment:-
The management should be followed by biochemical parameters and DEXA scan should be done to the spine and neck of femoral to calculate the T-scores. An increase of 1 -2 % each year is suggested in the neck of femur. After 3 years of pamidronate , usually the BMD effect remain the same. Also long -time treatment for more than 5 years is not recommended as it may cause osteosclerosis.
Management of hypogonadism must be monitored from assessment of serum sex steroid levels. Vitamin D therapy may carry the risk of nephrocalcinosis and bisphpsphonate so it should be given with caution. Thalassemic patients who is on thyroxine and steroid treatment should be monitored because excess replacement can augment osteoporosis . [40] Bone densitometry is used to prove osteoporosis and to determine the risk of future fracture. It measures the bone density the hip, vertebra, forearm, and femur.
Bone densitometry may be conducted by using x-rays, dual-energy x-ray absorptiometry (DEXA or DXA) or by quantitative CT scanning using special software. Ordinary x-rays may show weak bones. However, at the time where bone weakness is clear on x-rays, the treatment is to late be successful. Bone densitometry testing can detect reduced bone density at earlier grade so the treatment may be helpful. [11] First, BMD result is compared with the BMD results from a young healthy (25-35 years old) of similar gender and race. The standard deviation (SD) is the difference between BMD and that of the young healthy adults. This result is called T-score. When the T-scores positive it is mean that the bone is healthy and strong; when the T-scores is negative it is mean that the bone is weak.
The WHO define the osteoporosis according to the following figure [12] : 1660  A T-score within 1 SD (+1 or -1) of the young adult mean indicates normal bone density.  A T-score of 1 to 2.5 SD below the young adult mean (-1 to -2.5 SD) indicates low bone mass.  A T-score of ≥ 2.5 SD below the young adult mean (> -2.5 SD) indicates the presence of osteoporosis.
The Methods:-A total number of fifty (50) beta thalassemia major , regularly transfused patients at Al-zahraa' teaching hospital in thalassemia centre containing ( 685 registered patients ) were randomly selected from visitors of that centre selecting one patients every five of them in a cross sectional study from 1 st . of October 2011 to 30 th of November 2012 . With ages between ( 2 -15 ) years age.Permission had been taken from patients for legal and ethical purposes . Bone mineral densit ( BMD) of lumbar region ( L2 -L 4) using deual X-ray absorbiometry scan (DEXA scan ) , ( Dexxuim3 osteosys) was done by a radiologist at Al-Sader teaching hospital / Alnajaf city .Patient sent in a regular schedule , as two patients / week separately in a total period of ( 12 months ) .Results collected and interpretated depending on WHO diagnosis criteria of BMD when T-score < ( -2.5) considered as osteoporosis and between ( -1 to -2.5 ) as osteopenia. Blood collected , analyzed for : S.Ca. , S.Ph. , S.ALP , PTH , S.ferritin for each patient. Data interpretated using SPSS version 18 .Results considered stastically significant with ( p value < 0.05 ) .
The Results:-Fifty ( 50 ) patients , 37 ( 74 % ) were males and 13 ( 26 % ) were females ,age ranged( 2 years -15 years), patients divided into mainly 3 age groups as shown in (fig. :4).    Hemoglobin level for all patients was above ( 8 mg./dl.) ( mean = 9.0187 ) , related to readings of DEXA scan for normal and abnormal readings , there was no significant difference between two groups ( p value = 0.4 ) . ; s.ca , s.ph. and s.ALP show no significant effect of them on DEXA scan readings in their normal or abnormal values . Parathyroid hormone levels ranges ( 60.4 +/-19.9 to 61.3+/-30.2 ) in normal and abnormal DEXA readings respectively also show no significance.All 50 patients in all groups showed high levels of their s.ferritin (mean = 3767.1000 ) with significant changes in DEXA readings (Z-score > -2.5 or more ) with those of elevated s.ferritin (>1000 ng./ml.)
The pathogenesis of osteoporosis could be a consequence of anemia on bone metabolism, or secondary to hemosiderosis of various endocrine glands, hepatic dysfunction, chronic illness and chelation therapy. [15] Karimi et al. [16] , studied BMD by DEXA in Iranian patients with beta thalassemia major and intermediate and found significant correlation between low bone mass and low Hb level.In current study , Hb.level show no any significant effect on BMD in all age groups included ( p = 0.4) that may be explained by including those patients with controlled Hb.level that were 9g./dl. and above .
Studies by Benigno et al. [17] , showed relationship between BMD Z-scores and chronological age but without significance. In currnt study, there was a statistical significance (p=0.048 ) between chronological age and BMD scores explained by that increasing in age making patient more susceptible to skeletal changes such as widening in trabecular bone and so decrease in BMD (table :3).
As all our patients had serum ferritin levels above 1500 ng/ml. , it is possible to hypothesize negative effect of iron overload on degree of bone mineralization , so there was statistical significance between level of serum ferritin in high levels and BMD in an inverse way . [18] No available studies present relating high serum ferritin and low BMD.
We noted a high incidence of hyperphosphatemia both in patient and control with abnormal DEXA and there was no statistical significance between phosphorus levels and Z scores (p=0.887).
The present study (38%) had hyperparathyroidism which could be explained probably by low vitaminD levels that show no significane effect on BMD ( p = 0.892) .