Öz
Amaç
β-talasemi, anemi ve sistemik etkilerle seyreden, yaşam boyu devam eden bir kan hastalığıdır. Özellikle yaş ilerledikçe, β-talasemide sık karşılaşılan komplikasyonlardan biri kemik zayıflığıdır. Osteoprotegerin (OPG) ve RANKL’nin yaşa bağlı osteoporozdaki ve β-talasemiye bağlı kemik hastalığındaki rolleri daha önce incelenmiştir. Bu çalışma, transfüzyona bağımlı β-talasemi (TDT) hastaları ile sağlıklı kontrollerde (SK) OPG ve nükleer faktör B ligandı için reseptör aktivatörü (RANKL) düzeylerini karşılaştırmayı amaçlamıştır.
Gereç ve Yöntem
Bu çalışmaya kan sayımları ve biyokimyasal profilleri değerlendirilen, ardından üretici talimatlarına göre OPG ve RANKL için ELISA yapılan 120 TDT hastası ve 60 SK dahil edilmiştir. Veriler Mann-Whitney U testi ve Spearman korelasyonu ile analiz edilmiş; p≤0,05 istatistiksel olarak anlamlı kabul edilmiştir.
Bulgular
Sağlıklı kontrollerin medyan yaşı biraz daha yüksek olup, genel olarak erkek oranı daha fazlaydı. Her iki grubun kan sayımları karşılaştırılabilir düzeydeydi, ancak beyaz kan hücresi sayısı SK’de biraz daha yüksekti. TDT grubunda demir yüklenmesini düşündüren yüksek serum ferritin düzeyleri saptandı. Bulgular, TDT hastalarında SK’lara kıyasla OPG ve RANKL düzeylerinin azaldığını göstermektedir. OPG düzeyi hem erkek hem kadın TDT hastalarında düşükken, RANKL düzeyi yalnızca erkek TDT hastalarında düşüktü. OPG ve RANKL’nin yaş ve serum ferritin ile çok zayıf ya da hiç korelasyon göstermediği belirlendi.
Sonuç
Sonuçlarımız, TDT hastalarında özellikle erkeklerde OPG ve RANKL düzeylerinin azaldığını ve bu parametrelerin yaş ile serum ferritinle çok zayıf bir ilişki gösterdiğini ortaya koymaktadır. Bununla birlikte, bu moleküllerin kemik metabolizmasındaki rollerini ve kemik yoğunluğu ile ilişkilerini araştırmak için ileri çalışmalara ihtiyaç vardır.
Anahtar Kelimeler:
Beta-talasemi, transfüzyona bağımlı β-talasemi, TDT, OPG, RANKL, kemik hastalığı
Kaynaklar
1Taher AT, Musallam KM, Cappellini MD. β-thalassemias. N Engl J Med. 2021;384:727-43.
2Borgna-Pignatti C, Gamberini MR. Complications of thalassemia major and their treatment. Expert Rev Hematol. 2011;4:353-66.
3Vichinsky E, Neumayr L, Trimble S, Giardina PJ, Cohen AR, Coates T, et al. Transfusion complications in thalassemia patients: a report from the centers for disease control and prevention (CME). Transfusion. 2014;54:972-81; quiz 971.
4Ahmed S, Jafri H, Rashid Y, Ehsan Y, Bashir S, Ahmed M. Cascade screening for beta-thalassemia in Pakistan: development, feasibility and acceptability of a decision support intervention for relatives. Eur J Hum Genet. 2022;30:73-80.
5Shah FT, Sayani F, Trompeter S, Drasar E, Piga A. Challenges of blood transfusions in β-thalassemia. Blood Rev. 2019;37:100588.
6Ali Z, Ismail M, Rehman IU, Rani GF, Ali M, Khan MTM. Long-term clinical efficacy and safety of thalidomide in patients with transfusion-dependent β-thalassemia: results from Thal-Thalido study. Sci Rep. 2023;13:13592.
7Li X, Hu S, Liu Y, Huang J, Hong W, Xu L, et al. Efficacy of thalidomide treatment in children with transfusion dependent β-thalassemia: a retrospective clinical study. Front Pharmacol. 2021;12:722502.
8Zhu W, He Y, Huang M, Fu S, Liu Z, Wang X, et al. Long-term follow-up of patients undergoing thalidomide therapy for transfusion-dependent β-thalassaemia: a single-center experience. Int J Gen Med. 2024;17:1729-38.
9Bordbar M, Omrani GR, Haghpanah S, Saki F, Karimi M, Zekavat O. Bone mineral density in transfusion-dependent thalassemia patients and its associated factors in Southern Iran. Arch Osteoporos. 2020;15:148.
10Naithani R, Seth T, Tandon N, Chandra J, Pati H, Saxena R, et al. Fractures and low bone mineral density in patients with beta thalassemia major. Indian J Hematol Blood Transfus. 2018;34:163-5.
11Meena MC, Hemal A, Satija M, Arora SK, Bano S. Comparison of bone mineral density in thalassemia major patients with healthy controls. Adv Hematol. 2015;2015:648349.
12Irani AD, Poorolajal J, Khalilian A, Esmailnasab N, Cheraghi Z. Prevalence of osteoporosis in Iran: a meta-analysis. J Res Med Sci. 2013;18:759-66.
13Hajimoradi M, Haseli S, Abadi A, Chalian M. Musculoskeletal imaging manifestations of beta-thalassemia. Skeletal Radiol. 2021;50:1749-62.
14Adamopoulos S, Petrocheilou GM. Skeletal radiological findings in thalassemia major. JRPMS. 2020;4:76-85.
15Ansari-Moghadam AR, Adineh H, Zareban I, Almasy Z, Maghsudlu M. Bone mineral density (BMD) and chemical biomarkers among patients with thalassemia major and intermedia in Iran. Health Scope. 2018;7.
16Kyriakou A, Savva SC, Savvides I, Pangalou E, Ioannou YS, Christou S, et al. Gender differences in the prevalence and severity of bone disease in thalassaemia. Pediatr Endocrinol Rev. 2008;6(Suppl 1):116-22.
17Nakhakes C, Jaruluxananan S, Saengsuda Y, Saengsuda S. Risk factors for osteoporosis and the relationship between osteoporosis and hemoglobin level in adult patients with thalassemia in Rajavithi hospital. Asian Biomedicine. 2015;9:169-74.
18Mahmoodi Nesheli H, Farahanian E. Relation between bone mineral density and serum ferritin levels in patients with thalassemia major. CJP. 2016;2:158-63.
19Liang B, Burley G, Lin S, Shi YC. Osteoporosis pathogenesis and treatment: existing and emerging avenues. Cell Mol Biol Lett. 2022;27:72.
20Chi G, Qiu L, Ma J, Wu W, Zhang Y. The association of osteoprotegerin and RANKL with osteoporosis: a systematic review with meta-analysis. J Orthop Surg Res. 2023;18:839.
21Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys. 2008;473:139-46.
22Kohli SS, Kohli VS. Role of RANKL-RANK/osteoprotegerin molecular complex in bone remodeling and its immunopathologic implications. Indian J Endocrinol Metab. 2011;15:175-81.
23Ismail N, Galal A, Hamed H, Adolf S, Ragab S, Mawgoud SAE, et al. The roles of osteoprotegerin and rankl in pathogenesis of osteoporosis in Egyptian beta thalassemia major patients. Journal of Applied Sciences Research. 2010;6:937-42.
24Youssry I, Saad N, Madboly M, Samy RM, Hamed ST, Tawfik H, et al. Bone health in pediatric transfusion-dependent beta-thalassemia: circulating osteoprotegerin and RANKL system. Pediatr Blood Cancer. 2022;69:e29377.
25Salah H, Atfy M, Fathy A, Atfy M, Mansor H, Saeed J. The clinical significance of OPG/sRANKL ratio in thalassemia patients suffering from osteopenia or osteoporosis in Egyptian patients. Immunol Invest. 2010;39:820-32.
26Yavropoulou MP, Anastasilakis AD, Tzoulis P, Tournis S, Rigatou E, Kassi E, et al. Approach to the management of β thalassemia major associated osteoporosis - a long-standing relationship revisited. Acta Biomed. 2022;93:e2022305.
27Mahachoklertwattana P, Sirikulchayanonta V, Chuansumrit A, Karnsombat P, Choubtum L, Sriphrapradang A, et al. Bone histomorphometry in children and adolescents with beta-thalassemia disease: iron-associated focal osteomalacia. J Clin Endocrinol Metab. 2003;88:3966-72.
28Ekbote V, Khadilkar A, Chauthmal S, Padidela R, Khadilkar S, Mughal Z, et al. Assessment of bone density by DXA in poorly controlled children with β-thalassemia: correction for hepatic iron overload by manual analysis. J Clin Densitom. 2021;24:383-7.
29Fung EB. The importance of nutrition for health in patients with transfusion-dependent thalassemia. Ann N Y Acad Sci. 2016;1368:40-8.
30Soliman AT, Yassin M, Alyafei F, Alaaraj N, Hamed N, Osman S, et al. Nutritional studies in patients with β-thalassemia major: a short review. Acta Biomed. 2023;94:e2023187.
31Zoga J, Kallco M, Refatllari E. Correlation of OPG/RANKL in patients with thalassemia major in the center of haemoglobinopathy Lushnje, Albania. ESI Preprints. 2024;28:600.
32Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis. 2010;5:11.
33Pietrapertosa AC, Minenna G, Colella SM, Santeramo TM, Renni R, D’Amore M. Osteoprotegerin and RANKL in the pathogenesis of osteoporosis in patients with thalassaemia major. Panminerva Med. 2009;51:17-23.
34Baldini M, Marcon A, Ulivieri FM, Seghezzi S, Cassin R, Messina C, et al. Bone quality in beta-thalassemia intermedia: relationships with bone quantity and endocrine and hematologic variables. Ann Hematol. 2017;96:995-1003.
35Shuto T, Wachi T, Shinohara Y, Nikawa H, Makihira S. Increase in receptor activator of nuclear factor κB ligand/osteoprotegerin ratio in peri-implant gingiva exposed to Porphyromonas gingivalis lipopolysaccharide. J Dent Sci. 2016;11:8-16.
36López Roldán A, García Giménez JL, Alpiste Illueca F. Impact of periodontal treatment on the RANKL/OPG ratio in crevicular fluid. PLoS One. 2020;15:e0227757.
37De Leon-Oliva D, Barrena-Blázquez S, Jiménez-Álvarez L, Fraile-Martinez O, García-Montero C, López-González L, et al. The RANK-RANKL-OPG system: a multifaceted regulator of homeostasis, immunity, and cancer. Medicina (Kaunas). 2023;59:1752.
38Sayed SZ, Abd El-Hafez AH, Abu El-Ela MA, Mourad MA, Mousa SO. OPG/RANK/RANKL axis relation to cardiac iron-overload in children with transfusion-dependent thalassemia. Sci Rep. 2023;13:12568.
