Glukokortikoid Osteoporozu ve Yönetimi
Synopsis
Glukokortikoidler otoimmun, inflamatuar birçok hastalıkta günümüzde sık kullanılan ilaçlardandır. Güçlü antiinflamatuar etkilerinin yanı sıra pek çok yan etkisi de bulunur. Glukokortikoid osteoporozu bu yan etkilerin önemlilerinden olup iyatrojenik osteoporozun en sık nedenidir. Glukokortikoidlerle tedavinin erken döneminde hızlı kemik kaybı ve artmış kırık riski geliştiğinden erken tanınması ve müdahale edilmesi gereklidir. Osteoporozun önlenmesi ve tedavisi konusunda antirezorptif ajanlar ilk seçenek olarak kullanılmakla birlikte anabolik ajanlar ve yeni geliştirilen moleküller ile devam eden çalışmalar mevcuttur. Hekimler ve hastalar arasında farkındalığın arttırılması, günlük yaşam biçiminin düzenlenmesi ve hasta eğitimi hastalığın önlenmesi ve tedavi başarısı için önem arz etmektedir.
References
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Stellato C. Post-transcriptional and nongenomic effects of glucocorticoids. Proceedings of the American Thoracic Society. 2004;1(3):255-63. doi: 10.1513/pats.200402-015MS. PMID: 16113443.
Oppong E, Cato AC. Effects of Glucocorticoids in the Immune System. Advances in Experimental Medicine and Biology. 2015;872:217-33. doi: 10.1007/978-1-4939-2895-8_9. PMID: 26215996.
Ronchetti S, Ricci E, Migliorati G. et al. How Glucocorticoids Affect the Neutrophil Life. International Journal of Molecular Sciences. 2018 Dec 17;19(12):4090. doi: 10.3390/ijms19124090. PMID: 30563002; PMCID: PMC6321245.
Walsh LJ, Wong CA, Pringle M. et al. Use of oral corticosteroids in the community and the prevention of secondary osteoporosis: a cross sectional study. British Medical Journal. 1996 Aug 10;313(7053):344-6. doi: 10.1136/bmj.313.7053.344. PMID: 8760745; PMCID: PMC2351752.
Overman RA, Yeh JY, Deal CL. Prevalence of oral glucocorticoid usage in the United States: a general population perspective. Arthritis Care Research (Hoboken). 2013 Feb;65(2):294-8. doi: 10.1002/acr.21796. PMID: 22807233.
Liu, D., Ahmet, A., Ward, L. et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy, Asthma & Clinical Immunology, 30 (2013). https://doi.org/10.1186/1710-1492-9-30
Angeli A, Guglielmi G, Dovio A. et al. High prevalence of asymptomatic vertebral fractures in post-menopausal women receiving chronic glucocorticoid therapy: a cross-sectional outpatient study. Bone. 2006 Aug;39(2):253-9. doi: 10.1016/j.bone.2006.02.005. Epub 2006 Mar 30. PMID: 16574519
Shaker JL, Lukert BP. Osteoporosis associated with excess glucocorticoids. Endocrinology & Metabolism Clinics of North America. 2005 Jun;34(2):341-56, viii-ix. doi: 10.1016/j.ecl.2005.01.014. PMID: 15850846.
Van Staa TP, Leufkens HG, Abenhaim L. et al. Use of oral corticosteroids and risk of fractures. Journal of Bone and Mineral Research. 2000 Jun;15(6):993-1000. doi: 10.1359/jbmr.2000.15.6.993. PMID: 10841167.
Steinbuch M, Youket TE, Cohen S. Oral glucocorticoid use is associated with an increased risk of fracture. Osteoporos International. 2004 Apr;15(4):323-8. doi: 10.1007/s00198-003-1548-3. Epub 2004 Feb 5. PMID: 14762652.
Komori T. Glucocorticoid Signaling and Bone Biology. Hormone and Metabolic Research. 2016 Nov;48(11):755-763. doi: 10.1055/s-0042-110571. Epub 2016 Nov 21. PMID: 27871116.
Wong SC, Dobie R, Altowati MA. et al. Growth and the Growth Hormone-Insulin Like Growth Factor 1 Axis in Children With Chronic Inflammation: Current Evidence, Gaps in Knowledge, and Future Directions. Endocr Reviews. 2016 Feb;37(1):62-110. doi: 10.1210/er.2015-1026. Epub 2015 Dec 31. PMID: 26720129.
Suzuki Y, Ichikawa Y, Saito E. et al. Importance of increased urinary calcium excretion in the development of secondary hyperparathyroidism of patients under glucocorticoid therapy. Metabolism. 1983 Feb;32(2):151-6. doi: 10.1016/0026-0495(83)90221-4. PMID: 6298567.
Canalis E, Mazziotti G, Giustina A, et al. Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos International. 2007 Oct;18(10):1319-28. doi: 10.1007/s00198-007-0394-0. Epub 2007 Jun 14. PMID: 17566815.
Rebuffé-Scrive M, Krotkiewski M, Elfverson J. et al. Muscle and adipose tissue morphology and metabolism in Cushing's syndrome. The Journal of Clinical Endocrinology & Metabolism. 1988 Dec;67(6):1122-8. doi: 10.1210/jcem-67-6-1122. PMID: 3142910.
Askari A, Vignos PJ Jr, Moskowitz RW. Steroid myopathy in connective tissue disease. The American Journal of Medicine. 1976 Oct;61(4):485-92. doi: 10.1016/0002-9343(76)90327-2. PMID: 973643.
Cooper MS, Walker EA, Bland R. et al. Expression and functional consequences of 11beta-hydroxysteroid dehydrogenase activity in human bone. Bone. 2000 Sep;27(3):375-81. doi: 10.1016/s8756-3282(00)00344-6. PMID: 10962348.
Eastell R, Reid DM, Compston J. et al. A UK Consensus Group on management of glucocorticoid-induced osteoporosis: an update. Journal of Internal Medicine. 1998 Oct;244(4):271-92. doi: 10.1046/j.1365-2796.1998.00408.x. PMID: 9797491.
Ekenstam E, Stålenheim G, Hällgren R. The acute effect of high dose corticosteroid treatment on serum osteocalcin. Metabolism. 1988 Feb;37(2):141-4. doi: 10.1016/s0026-0495(98)90008-7. PMID: 3257542.
Adler RA, Hochberg MC. Suggested guidelines for evaluation and treatment of glucocorticoid-induced osteoporosis for the Department of Veterans Affairs. Archives of Internal Medicine. 2003 Nov 24;163(21):2619-24. doi: 10.1001/archinte.163.21.2619. PMID: 14638562.
Reeve J, Loftus J, Hesp R. et al. Biochemical prediction of changes in spinal bone mass in juvenile chronic (or rheumatoid) arthritis treated with glucocorticoids. The Journal of Rheumatology. 1993 Jul;20(7):1189–95.
Van Staa TP, Laan RF, Barton IP. et al. Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheumatology. 2003 Nov;48(11):3224-9. doi: 10.1002/art.11283. PMID: 14613287.
Kanis JA, Johansson H, Oden A, et al. Guidance for the adjustment of FRAX according to the dose of glucocorticoids. Osteoporos International. 2011 Mar;22(3):809-16. doi: 10.1007/s00198-010-1524-7. Epub 2011 Jan 13. PMID: 21229233.
Compston J, Cooper A, Cooper C. et al ; National Osteoporosis Guideline Group (NOGG). UK clinical guideline for the prevention and treatment of osteoporosis. Archives of Osteoporosis. 2017 Dec;12(1):43. doi: 10.1007/s11657-017-0324-5. Epub 2017 Apr 19. PMID: 28425085; PMCID: PMC5397452.
Buckley L, Guyatt G, Fink HA. et al. 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Rheumatology. 2017 Aug;69(8):1521-1537. doi: 10.1002/art.40137. Epub 2017 Jun 6. Erratum in: Arthritis Rheumatology. 2017 Nov;69(11):2246. PMID: 28585373.
Lekamwasam S, Adachi JD, Agnusdei D, et al ; Joint IOF-ECTS GIO Guidelines Working Group. A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis. Osteoporos International. 2012 Sep;23(9):2257-76. doi: 10.1007/s00198-012-1958-1. Epub 2012 Mar 21. PMID: 22434203
Buckley LM, Leib ES, Cartularo KS. et al. Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial. Annals of Internal Medicine. 1996 Dec 15;125(12):961-8. doi: 10.7326/0003-4819-125-12-199612150-00004. PMID: 8967706.
Adachi JD, Bensen WG, Bianchi F. et al. Vitamin D and calcium in the prevention of corticosteroid induced osteoporosis: a 3 year followup. The Journal of Rheumatology. 1996 Jun;23(6):995-1000. PMID: 8782129.
Adachi JD, Saag KG, Delmas PD. et al. Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial. Arthritis Rheumatology. 2001 Jan;44(1):202-11. doi: 10.1002/1529-0131(200101)44:1<202::AID-ANR27>3.0.CO;2-W. PMID: 11212161.
de Nijs RN, Jacobs JW, Lems WF et al. Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis. The New England Journal of Medicine. 2006 Aug 17;355(7):675-84. doi: 10.1056/NEJMoa053569. PMID: 16914703.
Allen CS, Yeung JH, Vandermeer B. et al. Bisphosphonates for steroid-induced osteoporosis. Cochrane Database of Systematic Reviews. 2016 Oct 5;10(10):CD001347. doi: 10.1002/14651858.CD001347.pub2. PMID: 27706804; PMCID: PMC6461188.
Barasch A, Cunha-Cruz J, Curro FA. et al. Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR dental PBRN. Journal of Dental Research. 2011 Apr;90(4):439-44. doi: 10.1177/0022034510397196. Epub 2011 Feb 11. PMID: 21317246; PMCID: PMC3144129.
Schilcher J, Koeppen V, Aspenberg P. et al. Risk of atypical femoral fracture during and after bisphosphonate use. Acta Orthopaedica. 2015;86(1):100-107. doi:10.3109/17453674.2015.1004149.
Akashi K, Nishimura K, Kageyama G, et al. FRI0553 The efficacy of 2-years denosumab treatment for glucocorticoid-induced osteoporosis (GIOP). Annals of the Rheumatic Diseases. 2017;76 Suppl 2:699.
Yamaguchi Y, Morita T, Kumanogoh A. The therapeutic efficacy of denosumab for the loss of bone mineral density in glucocorticoid-induced osteoporosis: a meta-analysis. Rheumatology Advances in Practice. 2020 Mar 13;4(1):rkaa008. doi: 10.1093/rap/rkaa008. PMID: 32373775; PMCID: PMC7197806.
Lane NE, Sanchez S, Modin GW. et al. Bone mass continues to increase at the hip after parathyroid hormone treatment is discontinued in glucocorticoid-induced osteoporosis: results of a randomized controlled clinical trial. Journal of Bone and Mineral Research. 2000 May;15(5):944-51. doi: 10.1359/jbmr.2000.15.5.944. PMID: 10804025.
Devogelaer JP, Adler RA, Recknor C. et al. Baseline glucocorticoid dose and bone mineral density response with teriparatide or alendronate therapy in patients with glucocorticoid-induced osteoporosis. The Journal of Rheumatology. 2010 Jan;37(1):141-8. doi: 10.3899/jrheum.090411. Epub 2009 Nov 16. PMID: 19918047.
Rittmaster RS, Bolognese M, Ettinger MP. et al. Enhancement of bone mass in osteoporotic women with parathyroid hormone followed by alendronate. The Journal of Clinical Endocrinology & Metabolism. 2000 Jun;85(6):2129-34. doi: 10.1210/jcem.85.6.6614. PMID: 10852440.
Gifre L, Ruiz-Gaspà S, Monegal A. et al. Effect of glucocorticoid treatment on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover. Bone. 2013 Nov;57(1):272-6. doi: 10.1016/j.bone.2013.08.016. Epub 2013 Aug 24. PMID: 23981659.
Stellato C. Post-transcriptional and nongenomic effects of glucocorticoids. Proceedings of the American Thoracic Society. 2004;1(3):255-63. doi: 10.1513/pats.200402-015MS. PMID: 16113443.
Oppong E, Cato AC. Effects of Glucocorticoids in the Immune System. Advances in Experimental Medicine and Biology. 2015;872:217-33. doi: 10.1007/978-1-4939-2895-8_9. PMID: 26215996.
Ronchetti S, Ricci E, Migliorati G. et al. How Glucocorticoids Affect the Neutrophil Life. International Journal of Molecular Sciences. 2018 Dec 17;19(12):4090. doi: 10.3390/ijms19124090. PMID: 30563002; PMCID: PMC6321245.
Walsh LJ, Wong CA, Pringle M. et al. Use of oral corticosteroids in the community and the prevention of secondary osteoporosis: a cross sectional study. British Medical Journal. 1996 Aug 10;313(7053):344-6. doi: 10.1136/bmj.313.7053.344. PMID: 8760745; PMCID: PMC2351752.
Overman RA, Yeh JY, Deal CL. Prevalence of oral glucocorticoid usage in the United States: a general population perspective. Arthritis Care Research (Hoboken). 2013 Feb;65(2):294-8. doi: 10.1002/acr.21796. PMID: 22807233.
Liu, D., Ahmet, A., Ward, L. et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy, Asthma & Clinical Immunology, 30 (2013). https://doi.org/10.1186/1710-1492-9-30
Angeli A, Guglielmi G, Dovio A. et al. High prevalence of asymptomatic vertebral fractures in post-menopausal women receiving chronic glucocorticoid therapy: a cross-sectional outpatient study. Bone. 2006 Aug;39(2):253-9. doi: 10.1016/j.bone.2006.02.005. Epub 2006 Mar 30. PMID: 16574519
Shaker JL, Lukert BP. Osteoporosis associated with excess glucocorticoids. Endocrinology & Metabolism Clinics of North America. 2005 Jun;34(2):341-56, viii-ix. doi: 10.1016/j.ecl.2005.01.014. PMID: 15850846.
Van Staa TP, Leufkens HG, Abenhaim L. et al. Use of oral corticosteroids and risk of fractures. Journal of Bone and Mineral Research. 2000 Jun;15(6):993-1000. doi: 10.1359/jbmr.2000.15.6.993. PMID: 10841167.
Steinbuch M, Youket TE, Cohen S. Oral glucocorticoid use is associated with an increased risk of fracture. Osteoporos International. 2004 Apr;15(4):323-8. doi: 10.1007/s00198-003-1548-3. Epub 2004 Feb 5. PMID: 14762652.
Komori T. Glucocorticoid Signaling and Bone Biology. Hormone and Metabolic Research. 2016 Nov;48(11):755-763. doi: 10.1055/s-0042-110571. Epub 2016 Nov 21. PMID: 27871116.
Wong SC, Dobie R, Altowati MA. et al. Growth and the Growth Hormone-Insulin Like Growth Factor 1 Axis in Children With Chronic Inflammation: Current Evidence, Gaps in Knowledge, and Future Directions. Endocr Reviews. 2016 Feb;37(1):62-110. doi: 10.1210/er.2015-1026. Epub 2015 Dec 31. PMID: 26720129.
Suzuki Y, Ichikawa Y, Saito E. et al. Importance of increased urinary calcium excretion in the development of secondary hyperparathyroidism of patients under glucocorticoid therapy. Metabolism. 1983 Feb;32(2):151-6. doi: 10.1016/0026-0495(83)90221-4. PMID: 6298567.
Canalis E, Mazziotti G, Giustina A, et al. Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos International. 2007 Oct;18(10):1319-28. doi: 10.1007/s00198-007-0394-0. Epub 2007 Jun 14. PMID: 17566815.
Rebuffé-Scrive M, Krotkiewski M, Elfverson J. et al. Muscle and adipose tissue morphology and metabolism in Cushing's syndrome. The Journal of Clinical Endocrinology & Metabolism. 1988 Dec;67(6):1122-8. doi: 10.1210/jcem-67-6-1122. PMID: 3142910.
Askari A, Vignos PJ Jr, Moskowitz RW. Steroid myopathy in connective tissue disease. The American Journal of Medicine. 1976 Oct;61(4):485-92. doi: 10.1016/0002-9343(76)90327-2. PMID: 973643.
Cooper MS, Walker EA, Bland R. et al. Expression and functional consequences of 11beta-hydroxysteroid dehydrogenase activity in human bone. Bone. 2000 Sep;27(3):375-81. doi: 10.1016/s8756-3282(00)00344-6. PMID: 10962348.
Eastell R, Reid DM, Compston J. et al. A UK Consensus Group on management of glucocorticoid-induced osteoporosis: an update. Journal of Internal Medicine. 1998 Oct;244(4):271-92. doi: 10.1046/j.1365-2796.1998.00408.x. PMID: 9797491.
Ekenstam E, Stålenheim G, Hällgren R. The acute effect of high dose corticosteroid treatment on serum osteocalcin. Metabolism. 1988 Feb;37(2):141-4. doi: 10.1016/s0026-0495(98)90008-7. PMID: 3257542.
Adler RA, Hochberg MC. Suggested guidelines for evaluation and treatment of glucocorticoid-induced osteoporosis for the Department of Veterans Affairs. Archives of Internal Medicine. 2003 Nov 24;163(21):2619-24. doi: 10.1001/archinte.163.21.2619. PMID: 14638562.
Reeve J, Loftus J, Hesp R. et al. Biochemical prediction of changes in spinal bone mass in juvenile chronic (or rheumatoid) arthritis treated with glucocorticoids. The Journal of Rheumatology. 1993 Jul;20(7):1189–95.
Van Staa TP, Laan RF, Barton IP. et al. Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheumatology. 2003 Nov;48(11):3224-9. doi: 10.1002/art.11283. PMID: 14613287.
Kanis JA, Johansson H, Oden A, et al. Guidance for the adjustment of FRAX according to the dose of glucocorticoids. Osteoporos International. 2011 Mar;22(3):809-16. doi: 10.1007/s00198-010-1524-7. Epub 2011 Jan 13. PMID: 21229233.
Compston J, Cooper A, Cooper C. et al ; National Osteoporosis Guideline Group (NOGG). UK clinical guideline for the prevention and treatment of osteoporosis. Archives of Osteoporosis. 2017 Dec;12(1):43. doi: 10.1007/s11657-017-0324-5. Epub 2017 Apr 19. PMID: 28425085; PMCID: PMC5397452.
Buckley L, Guyatt G, Fink HA. et al. 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Rheumatology. 2017 Aug;69(8):1521-1537. doi: 10.1002/art.40137. Epub 2017 Jun 6. Erratum in: Arthritis Rheumatology. 2017 Nov;69(11):2246. PMID: 28585373.
Lekamwasam S, Adachi JD, Agnusdei D, et al ; Joint IOF-ECTS GIO Guidelines Working Group. A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis. Osteoporos International. 2012 Sep;23(9):2257-76. doi: 10.1007/s00198-012-1958-1. Epub 2012 Mar 21. PMID: 22434203
Buckley LM, Leib ES, Cartularo KS. et al. Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial. Annals of Internal Medicine. 1996 Dec 15;125(12):961-8. doi: 10.7326/0003-4819-125-12-199612150-00004. PMID: 8967706.
Adachi JD, Bensen WG, Bianchi F. et al. Vitamin D and calcium in the prevention of corticosteroid induced osteoporosis: a 3 year followup. The Journal of Rheumatology. 1996 Jun;23(6):995-1000. PMID: 8782129.
Adachi JD, Saag KG, Delmas PD. et al. Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial. Arthritis Rheumatology. 2001 Jan;44(1):202-11. doi: 10.1002/1529-0131(200101)44:1<202::AID-ANR27>3.0.CO;2-W. PMID: 11212161.
de Nijs RN, Jacobs JW, Lems WF et al. Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis. The New England Journal of Medicine. 2006 Aug 17;355(7):675-84. doi: 10.1056/NEJMoa053569. PMID: 16914703.
Allen CS, Yeung JH, Vandermeer B. et al. Bisphosphonates for steroid-induced osteoporosis. Cochrane Database of Systematic Reviews. 2016 Oct 5;10(10):CD001347. doi: 10.1002/14651858.CD001347.pub2. PMID: 27706804; PMCID: PMC6461188.
Barasch A, Cunha-Cruz J, Curro FA. et al. Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR dental PBRN. Journal of Dental Research. 2011 Apr;90(4):439-44. doi: 10.1177/0022034510397196. Epub 2011 Feb 11. PMID: 21317246; PMCID: PMC3144129.
Schilcher J, Koeppen V, Aspenberg P. et al. Risk of atypical femoral fracture during and after bisphosphonate use. Acta Orthopaedica. 2015;86(1):100-107. doi:10.3109/17453674.2015.1004149.
Akashi K, Nishimura K, Kageyama G, et al. FRI0553 The efficacy of 2-years denosumab treatment for glucocorticoid-induced osteoporosis (GIOP). Annals of the Rheumatic Diseases. 2017;76 Suppl 2:699.
Yamaguchi Y, Morita T, Kumanogoh A. The therapeutic efficacy of denosumab for the loss of bone mineral density in glucocorticoid-induced osteoporosis: a meta-analysis. Rheumatology Advances in Practice. 2020 Mar 13;4(1):rkaa008. doi: 10.1093/rap/rkaa008. PMID: 32373775; PMCID: PMC7197806.
Lane NE, Sanchez S, Modin GW. et al. Bone mass continues to increase at the hip after parathyroid hormone treatment is discontinued in glucocorticoid-induced osteoporosis: results of a randomized controlled clinical trial. Journal of Bone and Mineral Research. 2000 May;15(5):944-51. doi: 10.1359/jbmr.2000.15.5.944. PMID: 10804025.
Devogelaer JP, Adler RA, Recknor C. et al. Baseline glucocorticoid dose and bone mineral density response with teriparatide or alendronate therapy in patients with glucocorticoid-induced osteoporosis. The Journal of Rheumatology. 2010 Jan;37(1):141-8. doi: 10.3899/jrheum.090411. Epub 2009 Nov 16. PMID: 19918047.
Rittmaster RS, Bolognese M, Ettinger MP. et al. Enhancement of bone mass in osteoporotic women with parathyroid hormone followed by alendronate. The Journal of Clinical Endocrinology & Metabolism. 2000 Jun;85(6):2129-34. doi: 10.1210/jcem.85.6.6614. PMID: 10852440.
Gifre L, Ruiz-Gaspà S, Monegal A. et al. Effect of glucocorticoid treatment on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover. Bone. 2013 Nov;57(1):272-6. doi: 10.1016/j.bone.2013.08.016. Epub 2013 Aug 24. PMID: 23981659.
Pages
119-130
Published
April 3, 2023
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1.
Varman B. Glukokortikoid Osteoporozu ve Yönetimi. In: Kelle B, editor. Fizik Tedavi ve Rehabilitasyonda Güncel Konular [Internet]. Türkiye: Academician Publishing Book DOI Portal; 2023 [cited 2026 Jul. 16]. pp. 119-30. Available from: https://omp35.books.akademisyen.net/index.php/akya/catalog/book/2533/chapter/13796
