Zoledronic acid improves bone mineral density in β-thalassemia patients with osteoporosis: a case control study

Yıl 2019, Cilt: 44 Sayı: 3, 882 - 890, 30.09.2019

Mehtap Evran Olgun Emel Gürkan Abdullah Tuli

https://doi.org/10.17826/cumj.432899

Öz

Purpose: This study addresses the efficacy of zoledronic acid treatment in osteoporotic patients with β-thalassemia.

Materials and Methods: Thirty-nine thalassemic patients were enrolled in this study. Bone mineral density was measured using Dual energy x-ray absorbtiometry (DEXA), and biochemical markers of osteoporosis in serum and urine were measured at 0, 6, and 12 months of treatment. Patients with thalassemia were randomly received either zoledronic acid 4 mg IV once every six months or calcitriol 0.25 mcg / day for 12 months. A subgroup analysis was also performed according to gonadal status. 

Results: There were 21 males and 18 females, mean age of 23.1 ± 1.3 and bone age of 16.3±0.35 years. At the end of 12 months, bone mineral densities of the lumbar vertebra and femoral neck significantly increased in the zoledronic acid group. In patients with hypogonadism who received hormone replacement therapy, t-scores significantly increased. Serum NTX levels indicated significant increase in both treatment groups compared with the control group at the end of the treatment. A significant increase was obtained in urinary NTX level in hypogonadal patients who received zoledronic acid, and in serum NTX and IGF-1 levels in normogonadal patients who received calcitriol. 

Conclusion: In our study, zoledronic acid resulted in significant improvement in bone mineral density and t-scores. This improvement was in correlation with IGF-1 levels.

Anahtar Kelimeler

β-thalassemia, osteoporosis, zoledronic acid, DEXA, serum and urinary NTX, IGF-I

Zoledronik asit osteoporozlu β-talasemi hastalarında kemik mineral yoğunluğunu arttırır: Bir vaka kontrol çalışması

Öz

Amaç: Bu çalışmada osteoporozu olan β-talasemi hastalarında zoledronik asit tedavisinin etkinliği incelenmiştir.

Gereç ve Yöntem: Çalışmaya 33 β-talasemili hasta ile kontrol grubu olarak yaş ve cinsiyetleri uyumlu 25 sağlıklı gönüllü alındı. Hastalarda 0. 6. ve 12.aylarda DEXA ve serum ve idrarda osteoporozun bazı biyokimyasal belirteçleri ölçüldü. Talasemili hastalar 12 ay süreyle her altı ayda bir 4 mg İV zoledronik asit ve 0.25 mcg/gün kalsitriol alanlar olmak üzere rastgele iki ayrı gruba ayrıldı. Gonadal fonksiyonlarına göre de iki alt gruba ayrılarak takip edildiler. 

Bulgular: Hastalar yaş ortalaması 23.1±1.3 ve kemik yaşı ortalaması 16.3±0.35 yıl olan 21 erkek, 18 kadından oluşmaktaydı. On iki ay sonunda zoledronik asit grubunda lumbar vertebra ve femur boynu kemik mineral yoğunluğu anlamlı artış gösterdi. Hipogonadik olup hormon replasmanı yapılan hastalarda lumbar vertebra ve femur boynu t-skoru anlamlı artış gösterdi. Serum NTX düzeyleri tedavinin sonunda her iki tedavi grubunda da kontrol grubuna göre belirgin olarak yükselme gösterdi. Hipogonadik hastalar içinde zolendronik asit alanlarda idrar NTXdüzeylerinde, normogonadik hastalar içinde kalsitriol alanlarda idrar NTX ve serum IGF-1 düzeylerinde anlamlı artış saptandı. 

Sonuç: Çalışmamızda zoledronik asit kemik mineral yoğunluğu ve t-skorlarında belirgin düzelmeler sağlamıştır. Bu düzelme IGF-1 düzeyi ile korelasyon göstermiştir. 

Anahtar Kelimeler

β-talasemi, zoledronik asit, osteoporoz, DEXA

Kaynakça

• 1. Perisano C, Marzetti E, Spinelli MS, Calla CAM, Graci C, Maccauro G. Physiopathology of Bone Modifications in β-Thalassemia. Anemia 2012; 2012: 320737, 5 pages.2. Terpos E, Voskaridou E. Treatment options for thalassemia patients with osteoporosis. Ann N Y Acad Sci 2010;1202:237-43. 3). Mahachoklertwattana P, Chuansumrit A, Sirisrirot R, Chouptum L. Bone mineral density, biochemical and hormonal profiles in suboptimally treated children and adolescents with β-thalassemia disease. Clinical Endocrinology 2003;58:273-79.4. Doggrell SA. Zoledronic Acid Once-yearly: What Role in the Prevention of Non-vertebral Osteoporotic Fractures? Therapeutics 2010;2:539–47.5. Morabito N, Catalano A, Gaudio A, Morini E, Bruno LM, Basile G, et al. Effects of strontium ranelate on bone mass and bone turnover in women with thalassemia major-related osteoporosis. J Bone Miner Metab 2016;34(5):540-46. 6.Marshall WA, Tanner JM. Variations in the pattern of pubertal changes inboys. Arch.Dis.Child 1970;4(239):23. 7. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser, 1994;843:1-129. Review. PubMed PMID: 7941614.8. Saki N, Abroun S, Salari F, Rahim F, Shahjahani M, Mohammadi-Asl J. Molecular Aspects of Bone Resorption in β-Thalassemia Major. CELL JOURNAL (Yakhteh) 2015;17 (2):193.9. Lasco A, Morabito N, Gaudio A, Buemi M, Wasniewska M, Frisina N. Effects of hormonal replacement therapy on bone metabolism in young adults with beta-thalassemia major. Osteoporosis Int 2001;12:570-75.10. Guisti A. Bisphosphonates in the management of thalassemia-associated osteoporosis: a systematic review of randomised controlled trials. J Bone Miner Metab 2014;32:606–15. 11. Pietra P, Pizzarelli G, Spina M, Riccobene S, Fiore CE. Quantitative ultrasound of bone and clodronate effects in thalassemia-induced osteoporosis. J Bone Miner Metab 2003;21:402-8.12. Voskaridou E, Anagnostopoulos A, Konstantopoulos K, Stoupa E, Spyropoulou E,Kiamouris C, ET AL. Zoledronic acid for the treatment of osteoporosis in patients with beta-thalassemia: results from a single-center, randomized,placebo-controlled trial. Haematologica 2006 Sep;91(9): 1193-202. 13. Gilfillan CP, Strauss BJ, Rodda CP, Bowden DK, Kean AM, Obaid M. A randomized, double-blind, placebo-controlled trial of intravenous zoledronic acid in the treatment of thalassemia-associated osteopenia. Calcif Tissue Int 2006;79(3:138-44.14. Perifanis V, Vyzantiadis T, Vakalopoulou S, Tziomalos K, Garypidou V, Athanassiou-Metaxa M. Treatment of beta-thalassaemia-associated osteoporosis with zoledronic acid. Br J Haematol 2004 Apr;125(1):91-2.15. Mamtani M, Kulkarni H. Bone recovery after zoledronate therapy in thalassemia-induced osteoporosis: a meta-analysis and systematic review. Osteoporos Int 2010;21:183-87. 16. Yigitoglu PH, Guzel R, Evran M, Gurkan E. Use of Zoledronic Acid in Thalassemia-Induced Osteoporosis:Two Case Reports and Review of the Literature. Turk J Phys Med Rehab 2012;58:154-58. 17. Khan AA, Sándor GK, Dore E, Morrison AD, Alsahli M, Amin F,et al. Canadian Taskforce on Osteonecrosis of the Jaw. Bisphosphonate associated osteonecrosis of the jaw. J Rheumatol 2009 Mar;36(3):478-90. 18. Withold W. Monitoring of bone turnover; biological, preanalytical and technical criteria in the assesment of biochemical markers [abstract]. European Journal of Clinical Chemistry and Clinical Biochemistry 1996; 34: 785-99 19. Lasco A, Morabito N, Gaudio A, Crisafulli A, Meo A, Denuzzo G. Osteoporosis and β-thalassemia major: Role of the IGF-I/IGFBP-III axis. J Endocrinol İnvest 2002;25:338-44.20. Voskaridou, E, Christoulas D, Konstantinidou M, Tsiftsakis E, Alexakos P, Terpos E. Continuous improvement of bone mineral density two years post zoledronic acid discontinuation in patients with thalassemia-induced osteoporosis: long term follow up a randomized, placebo-controlled trial. Haematologica 2008;93:1588–90. 21. Rosen HN, Moses AC, Garber J, Ross DS, Lee SL, Greenspan SL. Utility of biochemical markers of bone turnover in the follow-up of patients treated with bisphosphonates. Calcif Tissue Int 1998;63(5):363-68.22. Rosen HN, Moses AC, Garber J, Iloputaife ID, Ross DS, Lee SL, et al.Serum CTX: a new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of variability and large changes with bisphosphonate therapy. Calcif Tissue Int 2000 Feb;66(2):100-3.