ABSTRACT
Bone disease in beta TM in the form of low bone mass remains a frequent, debilitating and poorly understood problem, even among well transfused and chelated patients. Receptor activator of nuclear factor kB ligand [RANKL] is a regulator of osteoclast formation and function, the activity of which appears to be a balance between interaction with its receptor and with antagonist binding protein osteoprotegerin [OPG]. L-carnitine enhanced osteoblasric activity as well. The objective is to define the role of RANKUOPG and L-carnitine systems-related bone loss in attempt for better management of osteopenialosteoporosis in beta TM children. The study included 69 I3TM children [45 males and 24 females, mean age 8.72 +/- 3. 70 ys and weight 22.84 +/- 7.04kg] attended the Children University Hospital [January-September 2008]. The patients were subdivided into 2 groups; one [n=34] received iron chelating [DFO] and the other group [n=35] did not receive any chelating drug. Fifteen healthy matched age, sex and BMI were included as controls. Serum OPG, sRANKL, L-carnitine, calcium, inorganic phosphorus and free fatty acids were measured by ELIZA and spectrophotometer. BMD, BMC and Z-score were measured by DEXA in 25 patients. There was a significantly lower serum level of OPG, L-carnitine and significantly higher sRANKL, sRANKL/OPG ratio, FFAs in patients than controls and in patients receiving DFO than those not receiving chelation. DEXA bone scanning detected osteopenia/osteoporosis in 12%and 88%of patients [mean Z score-3.38 +/- 1.19] with significantly higher osteoporosis in patients receiving DFO; more obvious in pelvis, L-spine, and femoral neck. L-carnitine correlated negatively with sRANKL, and positively with OPG. sRANKL correlated negatively with OPG. Z-score correlated negatively with age and positively with OPG. In conclusion, Reduced osteoblas tic activity and enhancing osteoclastic resorption are the basic mechanisms of bone loss in beta TM through decrease in L-carnitine and disturbed RANKL/OPG pathway. Recombinant OPG, L-carnitine and anti-RANKL supplement may be future agents that help in management of beta TM osteopenia/osteoporosis. Chelation with DFO seems to affect the bone density in such patients