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Talasemi majorlu hastalarda kemik mineral yoğunluğu ile hipogonadizm arasındaki ilişki

Yıl 2010, Cilt: 41 Sayı: 1, 13 - 22, 01.02.2010

Öz

Introduction ve Aim: The lifetime expectancy in patients with B-thalassemia major has significantly been extended after the introduction of hypertransfusion protocols. However these applications caused an increase of endocrine complications such as osteoporosis and hypogonadism. It's believed that the excessive iron load is responsible for osteoporosis and other complications as many other different factors. The aim of this research is to exemine the factors which may impact the bone turn over and compare bone mineral density of patients with B-thalassemia major either hypogonadism developed and undeveloped. Material and Methods: 43 thalassemia major patients who have the physical signs of puberty or in the ages of puberty have been examined. All patients' bone mineral density measurements have been made and they're classified as the patient group with hypogonadism and as the control group without hypogonadism. The results are analysed in accordance with the data used in pediatric endocrinology. Results: It'sfound that the incidence of hypogonadism is 48% (21 patients out of 43) and the incidence of bone disease is 30% (13 patients out of 43). There hasn't been any significant statistical difference between the types of chelation and the levels of ferritin. Conclusion: Although in literature it's been confrated in some research that there is a remarkable relationship between bone mineral density and hypogonadism existences, we haven't found any significant difference in bone mineral density between the patient group and the control group, evertheless, the level of vit D3 is higher in the control group than the patient group. Vit D3 levels can be impacted by many other factors. That s why vit D3 levels are lower in thalassemia major patients with hypogonadism and in order to determine as vit D3 supplement must be given those patients, more multicenter prospective studies are needed.

Kaynakça

  • 1- Canatan D. Aydınok Y (Editörler): Talasemi hakkında herşey. A. Eleftheriou: About Thalassemia. Antalya 2005; 117-118
  • 2- Fosburg MT and Nathan DG: Treatment of Cooley's anemia. Blood, 1990; 76;435-444
  • 3- Borgna-Pignatti C.Cristofori G: Transfusion therapy of thalassemia.In(Eds:Bayık M, Canatan D, Politis C, Rossi U) Transfusion treatment of thalassemia and other chronic anemias. Proceedings of the ESTM/ITSS residential course. Antalya,20-25 April 2004; 129-131
  • 4 - Gibbons R, Higgs DR, Olivieri NF, Wood WG. The _ thalassaemias. In The Thalassaemia Syndromes 4th edition. Weather all D J and Clegg JB (eds) Blackwell Sciense Ltd, 2001Oxford, pp- 287-356
  • 5- Taner J. M. Growth at Adolescence, 2nded. Oxford, England, Blackwell Scientific Publications, 1962
  • 6- Firdevs B, Günöz H. Pediatrik endokrinolojide kullanılan kaynak veriler. Kurtoğlu S. Pediatrik Endokrinoloji. 1. Basım. Akyseri. Pediatrik Endokrinoloji ve Oksoloji Derneği Yayınları; 2003; 747-807
  • 7- Baytan B, Sağlam H, Erdöl Ş, Beyazıt AN, Özgür T, Güneş AM, Günay Ü. Evaluation of Endocrine Complications in Patients With Thalassemia Major. Güncel Pediatri 2008;6:58-65
  • 8- Karimi M, Ghiam AF, Hashemi A, Alinejad S, Soweid M, Kashef S. "Bone mineral density in beta-thalassemia major and intermedia. " Indian Pediatr. 2007;44:29-32
  • 9- Bielinski BK, Darbyshire P, Mathers L, Boivin CM, Shaw NJ. Bone density in the Asian thalassaemic population: a cross-sectional review. Acta Paediatr. 2001;90:1262-1266
  • 10- Kyriakou A, Savva SC, Savvides I, Pangalou E, Ioannou YS, Christou S, Skordis N. Gender differences in the prevalence and severity of bone disease in thalassaemia. Pediatr Endocrinol Rev. 2008;1:116-122
  • 11- Bisbocci D, Livorno P, Modina P, Gambino M, Damiano P, Cantoni R, Villata E, Chiandussi L. Osteodystrophy in thalassemia major] Ann Ital Med Int. 1993;8:224-226
  • 12- Gamberini MR, De Sanctis V, Gilli G. Hypogonadism, diabetes mellitus, hypothyroidism, hypoparathyroidism: incidence and prevalence related to iron overload and chelation therapy in patients with thalassaemia major followed from 1980 to 2007 in the Ferrara Centre. Pediatr Endocrinol Rev. 2008;1:158-169
  • 13- Borgna-Pignatti C, De Stefano P, Zonta L, Vullo C, De Sanctis V, Melevendi C, Naselli A, Masera G, Terzoli S, Gabutti V, et al. Growth and sexual maturation in thalassemia major. J Pediatr 1985;106:150-155
  • 14- Ghosh S, Bandyopadhyay SK, Bandyopadhyay R, Roy D, Maisnam I, Ghosh MK. A study on endocrine dysfunction in thalassaemia. J Indian Med Assoc. 2008;106:655-656, 658-9
  • 15- Hala Saleh Al-Rimawi, M.D., F.R.C.P, Mohammad Fayez Jallad, M.D., M.R.C.O.G., Zouhair Odeh Amarin, M.D., F.R.C.O.G., andRula Al Sakaan, M.D. "Pubertal evaluation of adolescent boys with beta-thalassemia major and delayed puberty" Fertility and Sterility. 2006, 86, No. 4, October 2006
  • 16- H.S. Al-Rimawia, M.F. Jalladb, Z.O. Amarinb, B.R. Obeidatb Hypothalamic-pituitary-gonadal function in adolescent females with beta-thalassemia major. International Journal of Gynecology and Obstetrics. 2005;90:44-47
  • 17- Alireza Abdollah Shamshirsaz, Mir Reza Bekheirnia, Mohammad Kam gar, Nima Pourzahedgilani, Navid Bouzari, Mohammadreza Habibzadeh, Reza Hashemi, Amirhooshang Abdollah Shamshirsaz, Shahriar Aghakhanil, Hooman Homayoun and Bagher Larijani"Metabolic and endocrinologic complications in beta- thalassemia major: a multicenter study in Tehran " BMC Endocrine Disorders 2003, 3:4
  • 18- John Papadimas, Dimitrios G. Goulis, Eudokia Mandala, George Georgiadis, Vassiliki Zournatzi, Basil C. Tarlatzis, John N. Bontis "?-Thalassemia And Gonadal Axis: A Cross-Sectional, Clinical Study İn A Greek Population " Hormones 2002, 1:179-187
  • 19- Multicentre study on prevalence of endocrine complications in thalassaemia major. Italian Working Group on Endocrine Complications in Non-endocrine Diseases. Clin Endocrinol (Oxf). 1995;42:581-6
  • 20- Flynn DM, Fairney A, Jackson D, Clayton BE. Hormonal changes in thalassaemia major. Arch Dis Child 1976; 51: 828-836
  • 21- Napoli N, Carmina E, Bucchieri S, Sferrazza C, Rini GB, Di Fede G. Low serum levels of 25- hydroxy vitamin D in adults affected by thalassemia majör or intermedia.Bone. 2006;38:888-892
  • 22- Moulas A, ChallaA, Chaliasos N, Lapatsanis PD. Vitamin D metabolites (25-hydroxyvitamin D, 24,2 5-dihydroxy vitamin D and 1,25- dihydroxyvitamin D) and osteocalcin in beta- thalassaemia. Acta Paediatr. 1997;86:594-599
  • 23- Molyvda-Athanasopoulou E, Sioundas A, Karatzas N, Aggellaki M, Pazaitou K, Vainas I. Bone mineral density of patients with thalassemia major: four-year follow-up. Calcif Tissue Int. 1999;64:481-484. 24- Soliman AT, El Banna N, Abdel Fattah M, ElZalabani MM, Ansari BM. Bone mineral density in prepubertal children with beta-thalassemia: correlation with growth and hormonal data. Metabolism. 1998;47:541-548
  • 25- Duran Canatan, Yeşim Aydınok. Talasemi Ve Hemoglobinopatilerde Endokrin Komplikasyonlar Ve Tedavisi. Talasemi ve Hemoglobinopatiler tanı ve tedavi 2007;193-200
  • 26- Morabito N, LascoA, GaudioA, CrisafulliA, Di Pietro C, Meo A, Frisina N. Bisphosphonates in the treatment of thalassemia-induced osteoporosis. Osteoporos Int. 2002;13:644-649
  • 27- Soliman AT, Elzalabany M, Armer M, Ansari BM. Growth and pubertal development in transfusion dependent children and adolescents with thalassemia major and sickle cell disease: a comparative study. J Trop Pediatr. 1999; 45: 23-30
  • 28- Valenti S, Giusti M, McGuinness D, Guido R, Mori PG, Giordano G, Dahi KD. Delayed puberty in males with beta-thalassemia major: pulsatile gonadotropin-releasing hormone administration induces changes in gonadotropin isoform profiles and an increase in sex steroids. Eur J Endocrinol. 995,-133:48-56
  • 29- Bronspiegel-Weintrob N, OlivieriNF, Tyler B, Andrews DF, Freedman MH, Holland FJ. Effect of age at the start of iron chelation therapy on gonadal function in betathalassemia major. N Engl J Med 1990; 323:713-719
  • 30- Ümit Dündar, Alphan Kupesiz, Sebahat Özdem, Erdal Gilgil, Tiraj e Tuncer, Akifyeşilipek, Meral Gültekin "Bone metabolism and mineral density in patients with beta thalassemia major" Saudi Med J 2007;28:1425-1429
  • 31- Skordis N, Michaelidou M, Sawa SC, loannou Y, Rousounides A, Kleanthous M, Skordos G, Christou S. The impact of genotype on endocrine complications in thalassaemia major. Eur J Haematol. 2006; 77:150-156
  • 32- Jensen CE, Tuck SM, Agnew JE, Koneru S, Morris RW, Yardumian A, Prescott E, Hoffbrand AV, Wonke B. High prevalence of low bone mass in thalassaemia major. Br J Haematol. 1998;103:911-915
  • 33- Vullo C, De Sanctis V, Katz M, Wonke B, Hoffbrand AV, Bagni B, Torresani T, Tolis G, Masiero M, Di Palma A, Borgatti L: Endocrine abnormalities in thalassemia. Ann NY Acad Sci 1990, 612:293-310
  • 34- De Sanctis V, Vullo C, Katz M, Wonke B, Hoffbrand VA, Di Palma A, Bagni B: Endocrine complications in thalassemia major. In In Advances and Controversies in Thalassemia Therapy Edited by: Buckner CD, Gale RP, Lucarelli G. New York: AlanLiss; 1989:77-83
  • 35- Gabriele OF. Hypoparathyroidism associate with thalassemia. South Med J. 1971;64:115-116
  • 36- Chern JP, Lin KH. Hypoparathyroidism in transfusion-dependent patients with betathalassemia. J Pediatr Hematol Oncol. 2002;24:291-293
  • 37- Benigno V, BertelloniS, Baroncelli GI, Bertacca L, Di Peri S, Cuccia L, Borsellino Z, Maggio MC. Effects of thalassemia major on bone mineral density in late adolescence. J Pediatr Endocrinol Metab. 2003;16:337-342
  • 38- Marıa G. Vogıatzı, Karen A. Autio, Jeffrey E. Mait, Robert Schneider, Martin Lesser, And Patricia J. Gıardına "Low Bone Mineral Density in Adolescents with beta Thalassemia " Ann. N. Y. Acad. Sci. 2005;1054: 462-466.

Talasemi majorlu hastalarda kemik mineral yoğunluğu ile hipogonadizm arasındaki ilişki

Yıl 2010, Cilt: 41 Sayı: 1, 13 - 22, 01.02.2010

Öz

Giriş ve Amaç: Beta-Talasemi majörlü hastalarda yaşam süresi hipertransfüzyon protokollerinin uygulanmasından sonra belirgin olarak uzamıştır. Bununla birlikte, bu osteoporoz, hipogonadizm gibi endokrin komplikasyonların artmasına yol açmıştır. Komplikasyonların gelişiminde olduğu gibi osteoporozda da aşırı demir birikimi sorumlu tutulmakla birlikte aynı zamanda çok çeşitli faktörlerinde bu konuda etkili olabileceğine inanılmaktadır. Bu çalışmanın amacı beta-talasemi majörlü hastalardan, hipogonadizm gelişen ve gelişmeyen olguların, kemik mineral yoğunluklarını karşılaştırmak ve kemik yapım yıkımını etkileyebilecek faktörleri araştırmaktır. Materyal ve Metod: Talasemi majör tanısı ile izlenen hastalardanpuberteyaş sınırını dolduran veyapuberte muayenesi ile puberteye girdikleri belirlenen, 43 hasta değerlendirmeye alındı. Tüm hastaların kemik mineral yoğunluğu ölçümleri yapıldı. Hormonal değerlerine göre hipogonad olanlar (hasta grubu) ve hipogonad olmayanlar (kontrol grubu) olarak ikiye ayrıldı. Hastaların sonuçları pediatrik endokrinolojide kullanılan kaynak veriler ile değerlendirildi. Bulgular: Hipogonadizm sıklığı % 48 (43 hastanın 21 'i), kemik hastalığı ise % 30 (43 hastanın 13 u) olarak bulundu. Şelasyon tipleri ile ferritin düzeyleri arasında istatistiksel olarak anlamlı bir fark bulunmadı. Sonuç: Bu çalışmada literatürleri incelediğimizde bazı çalışmalarda hipogonadizm ile kemik mineral yoğunluğu arasında anlamlı bir ilişki bulunmuş olmasına rağmen bizim yaptığımız bu çalışmada hipogonadizm gelişmiş olan ile hipogonadizm gelişmemiş olan hasta grupları arasında kemik mineral yoğunluğu açısından anlamlı bir fark olmadığı görülmüştür. Fakat çalışmamızda vit D3 düzeyleri kontrol grubunda hasta grubuna göre daha yüksek bulunmuştur. Bilindiği gibi vit D3 düzeyini etkileyen çok fazla faktör bulunmaktadır. Bu nedenledir ki hipogonadizm gelişmiş olan talasemi majorlu hastalarda vit D3 düzeyi daha düşüktür ve bu hastalara vit D3 desteği yapılmalıdır diyebilmek için diğer-faktörlerin elimine edildiği, çok merkezli prospektif çalışmalara ihtiyaç vardır.

Kaynakça

  • 1- Canatan D. Aydınok Y (Editörler): Talasemi hakkında herşey. A. Eleftheriou: About Thalassemia. Antalya 2005; 117-118
  • 2- Fosburg MT and Nathan DG: Treatment of Cooley's anemia. Blood, 1990; 76;435-444
  • 3- Borgna-Pignatti C.Cristofori G: Transfusion therapy of thalassemia.In(Eds:Bayık M, Canatan D, Politis C, Rossi U) Transfusion treatment of thalassemia and other chronic anemias. Proceedings of the ESTM/ITSS residential course. Antalya,20-25 April 2004; 129-131
  • 4 - Gibbons R, Higgs DR, Olivieri NF, Wood WG. The _ thalassaemias. In The Thalassaemia Syndromes 4th edition. Weather all D J and Clegg JB (eds) Blackwell Sciense Ltd, 2001Oxford, pp- 287-356
  • 5- Taner J. M. Growth at Adolescence, 2nded. Oxford, England, Blackwell Scientific Publications, 1962
  • 6- Firdevs B, Günöz H. Pediatrik endokrinolojide kullanılan kaynak veriler. Kurtoğlu S. Pediatrik Endokrinoloji. 1. Basım. Akyseri. Pediatrik Endokrinoloji ve Oksoloji Derneği Yayınları; 2003; 747-807
  • 7- Baytan B, Sağlam H, Erdöl Ş, Beyazıt AN, Özgür T, Güneş AM, Günay Ü. Evaluation of Endocrine Complications in Patients With Thalassemia Major. Güncel Pediatri 2008;6:58-65
  • 8- Karimi M, Ghiam AF, Hashemi A, Alinejad S, Soweid M, Kashef S. "Bone mineral density in beta-thalassemia major and intermedia. " Indian Pediatr. 2007;44:29-32
  • 9- Bielinski BK, Darbyshire P, Mathers L, Boivin CM, Shaw NJ. Bone density in the Asian thalassaemic population: a cross-sectional review. Acta Paediatr. 2001;90:1262-1266
  • 10- Kyriakou A, Savva SC, Savvides I, Pangalou E, Ioannou YS, Christou S, Skordis N. Gender differences in the prevalence and severity of bone disease in thalassaemia. Pediatr Endocrinol Rev. 2008;1:116-122
  • 11- Bisbocci D, Livorno P, Modina P, Gambino M, Damiano P, Cantoni R, Villata E, Chiandussi L. Osteodystrophy in thalassemia major] Ann Ital Med Int. 1993;8:224-226
  • 12- Gamberini MR, De Sanctis V, Gilli G. Hypogonadism, diabetes mellitus, hypothyroidism, hypoparathyroidism: incidence and prevalence related to iron overload and chelation therapy in patients with thalassaemia major followed from 1980 to 2007 in the Ferrara Centre. Pediatr Endocrinol Rev. 2008;1:158-169
  • 13- Borgna-Pignatti C, De Stefano P, Zonta L, Vullo C, De Sanctis V, Melevendi C, Naselli A, Masera G, Terzoli S, Gabutti V, et al. Growth and sexual maturation in thalassemia major. J Pediatr 1985;106:150-155
  • 14- Ghosh S, Bandyopadhyay SK, Bandyopadhyay R, Roy D, Maisnam I, Ghosh MK. A study on endocrine dysfunction in thalassaemia. J Indian Med Assoc. 2008;106:655-656, 658-9
  • 15- Hala Saleh Al-Rimawi, M.D., F.R.C.P, Mohammad Fayez Jallad, M.D., M.R.C.O.G., Zouhair Odeh Amarin, M.D., F.R.C.O.G., andRula Al Sakaan, M.D. "Pubertal evaluation of adolescent boys with beta-thalassemia major and delayed puberty" Fertility and Sterility. 2006, 86, No. 4, October 2006
  • 16- H.S. Al-Rimawia, M.F. Jalladb, Z.O. Amarinb, B.R. Obeidatb Hypothalamic-pituitary-gonadal function in adolescent females with beta-thalassemia major. International Journal of Gynecology and Obstetrics. 2005;90:44-47
  • 17- Alireza Abdollah Shamshirsaz, Mir Reza Bekheirnia, Mohammad Kam gar, Nima Pourzahedgilani, Navid Bouzari, Mohammadreza Habibzadeh, Reza Hashemi, Amirhooshang Abdollah Shamshirsaz, Shahriar Aghakhanil, Hooman Homayoun and Bagher Larijani"Metabolic and endocrinologic complications in beta- thalassemia major: a multicenter study in Tehran " BMC Endocrine Disorders 2003, 3:4
  • 18- John Papadimas, Dimitrios G. Goulis, Eudokia Mandala, George Georgiadis, Vassiliki Zournatzi, Basil C. Tarlatzis, John N. Bontis "?-Thalassemia And Gonadal Axis: A Cross-Sectional, Clinical Study İn A Greek Population " Hormones 2002, 1:179-187
  • 19- Multicentre study on prevalence of endocrine complications in thalassaemia major. Italian Working Group on Endocrine Complications in Non-endocrine Diseases. Clin Endocrinol (Oxf). 1995;42:581-6
  • 20- Flynn DM, Fairney A, Jackson D, Clayton BE. Hormonal changes in thalassaemia major. Arch Dis Child 1976; 51: 828-836
  • 21- Napoli N, Carmina E, Bucchieri S, Sferrazza C, Rini GB, Di Fede G. Low serum levels of 25- hydroxy vitamin D in adults affected by thalassemia majör or intermedia.Bone. 2006;38:888-892
  • 22- Moulas A, ChallaA, Chaliasos N, Lapatsanis PD. Vitamin D metabolites (25-hydroxyvitamin D, 24,2 5-dihydroxy vitamin D and 1,25- dihydroxyvitamin D) and osteocalcin in beta- thalassaemia. Acta Paediatr. 1997;86:594-599
  • 23- Molyvda-Athanasopoulou E, Sioundas A, Karatzas N, Aggellaki M, Pazaitou K, Vainas I. Bone mineral density of patients with thalassemia major: four-year follow-up. Calcif Tissue Int. 1999;64:481-484. 24- Soliman AT, El Banna N, Abdel Fattah M, ElZalabani MM, Ansari BM. Bone mineral density in prepubertal children with beta-thalassemia: correlation with growth and hormonal data. Metabolism. 1998;47:541-548
  • 25- Duran Canatan, Yeşim Aydınok. Talasemi Ve Hemoglobinopatilerde Endokrin Komplikasyonlar Ve Tedavisi. Talasemi ve Hemoglobinopatiler tanı ve tedavi 2007;193-200
  • 26- Morabito N, LascoA, GaudioA, CrisafulliA, Di Pietro C, Meo A, Frisina N. Bisphosphonates in the treatment of thalassemia-induced osteoporosis. Osteoporos Int. 2002;13:644-649
  • 27- Soliman AT, Elzalabany M, Armer M, Ansari BM. Growth and pubertal development in transfusion dependent children and adolescents with thalassemia major and sickle cell disease: a comparative study. J Trop Pediatr. 1999; 45: 23-30
  • 28- Valenti S, Giusti M, McGuinness D, Guido R, Mori PG, Giordano G, Dahi KD. Delayed puberty in males with beta-thalassemia major: pulsatile gonadotropin-releasing hormone administration induces changes in gonadotropin isoform profiles and an increase in sex steroids. Eur J Endocrinol. 995,-133:48-56
  • 29- Bronspiegel-Weintrob N, OlivieriNF, Tyler B, Andrews DF, Freedman MH, Holland FJ. Effect of age at the start of iron chelation therapy on gonadal function in betathalassemia major. N Engl J Med 1990; 323:713-719
  • 30- Ümit Dündar, Alphan Kupesiz, Sebahat Özdem, Erdal Gilgil, Tiraj e Tuncer, Akifyeşilipek, Meral Gültekin "Bone metabolism and mineral density in patients with beta thalassemia major" Saudi Med J 2007;28:1425-1429
  • 31- Skordis N, Michaelidou M, Sawa SC, loannou Y, Rousounides A, Kleanthous M, Skordos G, Christou S. The impact of genotype on endocrine complications in thalassaemia major. Eur J Haematol. 2006; 77:150-156
  • 32- Jensen CE, Tuck SM, Agnew JE, Koneru S, Morris RW, Yardumian A, Prescott E, Hoffbrand AV, Wonke B. High prevalence of low bone mass in thalassaemia major. Br J Haematol. 1998;103:911-915
  • 33- Vullo C, De Sanctis V, Katz M, Wonke B, Hoffbrand AV, Bagni B, Torresani T, Tolis G, Masiero M, Di Palma A, Borgatti L: Endocrine abnormalities in thalassemia. Ann NY Acad Sci 1990, 612:293-310
  • 34- De Sanctis V, Vullo C, Katz M, Wonke B, Hoffbrand VA, Di Palma A, Bagni B: Endocrine complications in thalassemia major. In In Advances and Controversies in Thalassemia Therapy Edited by: Buckner CD, Gale RP, Lucarelli G. New York: AlanLiss; 1989:77-83
  • 35- Gabriele OF. Hypoparathyroidism associate with thalassemia. South Med J. 1971;64:115-116
  • 36- Chern JP, Lin KH. Hypoparathyroidism in transfusion-dependent patients with betathalassemia. J Pediatr Hematol Oncol. 2002;24:291-293
  • 37- Benigno V, BertelloniS, Baroncelli GI, Bertacca L, Di Peri S, Cuccia L, Borsellino Z, Maggio MC. Effects of thalassemia major on bone mineral density in late adolescence. J Pediatr Endocrinol Metab. 2003;16:337-342
  • 38- Marıa G. Vogıatzı, Karen A. Autio, Jeffrey E. Mait, Robert Schneider, Martin Lesser, And Patricia J. Gıardına "Low Bone Mineral Density in Adolescents with beta Thalassemia " Ann. N. Y. Acad. Sci. 2005;1054: 462-466.
Toplam 37 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Makaleler
Yazarlar

İbrahim Şilfeler Bu kişi benim

Salih Güler Bu kişi benim

Bayram Ali Dorum Bu kişi benim

Yekta Canbak Bu kişi benim

Hilal Kurnaz Bu kişi benim

Fügen Pekün Bu kişi benim

Yayımlanma Tarihi 1 Şubat 2010
Yayımlandığı Sayı Yıl 2010 Cilt: 41 Sayı: 1

Kaynak Göster

APA Şilfeler, İ., Güler, S., Dorum, B. A., Canbak, Y., vd. (2010). Talasemi majorlu hastalarda kemik mineral yoğunluğu ile hipogonadizm arasındaki ilişki. Zeynep Kamil Tıp Bülteni, 41(1), 13-22. https://doi.org/10.16948/zktb.75355
AMA Şilfeler İ, Güler S, Dorum BA, Canbak Y, Kurnaz H, Pekün F. Talasemi majorlu hastalarda kemik mineral yoğunluğu ile hipogonadizm arasındaki ilişki. Zeynep Kamil Tıp Bülteni. Şubat 2010;41(1):13-22. doi:10.16948/zktb.75355
Chicago Şilfeler, İbrahim, Salih Güler, Bayram Ali Dorum, Yekta Canbak, Hilal Kurnaz, ve Fügen Pekün. “Talasemi Majorlu Hastalarda Kemik Mineral yoğunluğu Ile Hipogonadizm arasındaki ilişki”. Zeynep Kamil Tıp Bülteni 41, sy. 1 (Şubat 2010): 13-22. https://doi.org/10.16948/zktb.75355.
EndNote Şilfeler İ, Güler S, Dorum BA, Canbak Y, Kurnaz H, Pekün F (01 Şubat 2010) Talasemi majorlu hastalarda kemik mineral yoğunluğu ile hipogonadizm arasındaki ilişki. Zeynep Kamil Tıp Bülteni 41 1 13–22.
IEEE İ. Şilfeler, S. Güler, B. A. Dorum, Y. Canbak, H. Kurnaz, ve F. Pekün, “Talasemi majorlu hastalarda kemik mineral yoğunluğu ile hipogonadizm arasındaki ilişki”, Zeynep Kamil Tıp Bülteni, c. 41, sy. 1, ss. 13–22, 2010, doi: 10.16948/zktb.75355.
ISNAD Şilfeler, İbrahim vd. “Talasemi Majorlu Hastalarda Kemik Mineral yoğunluğu Ile Hipogonadizm arasındaki ilişki”. Zeynep Kamil Tıp Bülteni 41/1 (Şubat 2010), 13-22. https://doi.org/10.16948/zktb.75355.
JAMA Şilfeler İ, Güler S, Dorum BA, Canbak Y, Kurnaz H, Pekün F. Talasemi majorlu hastalarda kemik mineral yoğunluğu ile hipogonadizm arasındaki ilişki. Zeynep Kamil Tıp Bülteni. 2010;41:13–22.
MLA Şilfeler, İbrahim vd. “Talasemi Majorlu Hastalarda Kemik Mineral yoğunluğu Ile Hipogonadizm arasındaki ilişki”. Zeynep Kamil Tıp Bülteni, c. 41, sy. 1, 2010, ss. 13-22, doi:10.16948/zktb.75355.
Vancouver Şilfeler İ, Güler S, Dorum BA, Canbak Y, Kurnaz H, Pekün F. Talasemi majorlu hastalarda kemik mineral yoğunluğu ile hipogonadizm arasındaki ilişki. Zeynep Kamil Tıp Bülteni. 2010;41(1):13-22.