Preview

Влияние заместительной терапии глюкокортикоидами на костный обмен при надпочечниковой недостаточности. Обзор литературы

https://doi.org/10.14341/omet12700

Полный текст:

Аннотация

Надпочечниковая недостаточность — синдром, обусловленный нарушением синтеза и секреции гормонов коры надпочечников, которые обеспечивают жизнедеятельность организма, энергетический и водно-солевой гомеостаз. Наиболее широкий гормональный дефицит отмечается при первичном гипокортицизме, когда наблюдается снижение не только уровней глюкокортикоидов (ГК) и надпочечниковых андрогенов, но и нарушение синтеза минералокортикоидов. Пожизненная заместительная терапия препаратами ГК при данной патологии может быть ассоциирована с риском потери костной массы и развитием остеопороза. Однако в настоящее время не разработаны четкие рекомендации по необходимости мониторинга минеральной плотности костной ткани на фоне лечения ГК у пациентов с надпочечниковой недостаточностью. В обзоре проводится анализ данных мировой литературы о ключевых патогенетических звеньях глюкокортикоид-индуцированного остеопороза, частоте снижения минеральной плотности кости и возникновения переломов у пациентов с гипокортицизмом, рассматриваются факторы, которые оказывают влияние на костный обмен у данной когорты больных: форма и доза назначаемого ГК, вариант (первичная, вторичная, надпочечниковая недостаточность при врожденной дисфункции коры надпочечников) и длительность гипокортицизма, возраст, пол, наличие сопутствующих эндокринных нарушений (гипогонадизм, недостаточность гормона роста). Обсуждаются результаты исследований, оценивающих состояние костного метаболизма при коррекции дефицита надпочечниковых андрогенов и терапии рекомбинантным гормоном роста при вторичной надпочечниковой недостаточности.

Об авторах

М. Ю. Юкина
Национальный медицинский исследовательский центр эндокринологии

Юкина Марина Юрьевна, кандидат медицинских наук

117036, Москва, ул. Дм. Ульянова, д. 11

eLibrary SPIN: 4963-8340



М. О. Чернова
Национальный медицинский исследовательский центр эндокринологии
Россия

Чернова Мария Олеговна, ординатор

Москва



Н. Ф. Нуралиева
Национальный медицинский исследовательский центр эндокринологии

Нуралиева Нурана Фейзуллаевна

Москва

eLibrary SPIN: 7373-2602



А. К. Еремкина
Национальный медицинский исследовательский центр эндокринологии

Еремкина Анна Константиновна, кандидат медицинских наук

Москва

eLibrary SPIN: 8848-2660



Е. А. Трошина
Национальный медицинский исследовательский центр эндокринологии

Трошина Екатерина Анатольевна, доктор медицинских наук, профессор

Москва

eLibrary SPIN: 8821-8990



Г. А. Мельниченко
Национальный медицинский исследовательский центр эндокринологии

Мельниченко Галина Афанасьевна, доктор медицинских наук, профессор

Москва

eLibrary SPIN: 8615-0038



Н. Г. Мокрышева
Национальный медицинский исследовательский центр эндокринологии

Мокрышева Наталья Георгиевна, доктор медицинских наук, профессор

Москва

eLibrary SPIN: 5624-3875



Список литературы

1. Юкина М.Ю., Трошина Е.А., Платонова Н.М., Бельцевич Д.Г. Надпочечниковая недостаточность / Сборник методических рекомендаций (в помощь практическому врачу). Под ред. Е.А. Трошиной. — Тверь; 2017. С. 149-192.

2. Martine KF, Simons A, Ramet J. Food Refusal, Loss of Appetite, Chronic Fatigue and Depression due to Central Adrenal Insufficiency Presenting as Anorexia Nervosa in an Adolescent Girl. J Clin Case Reports. 2013;03(10). doi: https://doi.org/10.4172/2165-7920.1000310

3. Chakera AJ, Vaidya B. Addison Disease in Adults: Diagnosis and Management. Am J Med. 2010;123(5):409-413. doi: https://doi.org/10.1016/j.amjmed.2009.12.017

4. Meyer G, Neumann K, Badenhoop K, Linder R. Increasing prevalence of Addison’s disease in German females: health insurance data 2008–2012. Eur J Endocrinol. 2014;170(3):367-373. doi: https://doi.org/10.1530/EJE-13-0756

5. Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and treatment of primary adrenal insufficiency: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(2):364-389. doi: https://doi.org/10.1210/jc.2015-1710

6. Bentivegna G, Osella G, Pia A, Terzolo M. Effects on bone health of glucocorticoid replacement therapy in primary and secondary adrenal insufficiency: A review. Curr Opin Endocr Metab Res. 2018;3(3):31-37. doi: https://doi.org/10.1016/j.coemr.2018.02.008

7. Johannsson G, Falorni A, Skrtic S, et al. Adrenal insufficiency: review of clinical outcomes with current glucocorticoid replacement therapy. Clin Endocrinol (Oxf ). 2015;82(1):2-11. doi: https://doi.org/10.1111/cen.12603

8. Crowley RK, Argese N, Tomlinson JW, Stewart PM. Central Hypoadrenalism. J Clin Endocrinol Metab. 2014;99(11):4027-4036. doi: https://doi.org/10.1210/jc.2014-2476

9. Мельниченко Г.А., Трошина Е.А., Юкина М.Ю., и др. Клинические рекомендации российской ассоциации эндокринологов по диагностике и лечению первичной надпочечниковой недостаточности у взрослых пациентов (проект) // Consilium Medicum. — 2017. — Т. 19. — №4. — С. 8-19.

10. Arlt W. Adrenal insufficiency. Clin Med (Northfield Il). 2008;8(2):211-215. doi: https://doi.org/10.7861/clinmedicine.8-2-211

11. Городецкий В.В., Тополянский А.В., Лаптев А.О. Глюкокортикоидная терапия сегодня: эффективность и безопасность // Лечащий врач. — 2002. — №3. — С. 10-14.

12. Falhammar H, Filipsson Nyström H, Wedell A, et al. Bone mineral density, bone markers, and fractures in adult males with congenital adrenal hyperplasia. Eur J Endocrinol. 2013;168(3):331-341. doi: https://doi.org/10.1530/EJE-12-0865

13. Giordano R, Marzotti S, Balbo M, et al. Metabolic and cardiovascular profile in patients with Addison’s disease under conventional glucocorticoid replacement. J Endocrinol Invest. 2009;32:917-923. doi: https://doi.org/10.3275/6437

14. Komerdus IV, Budul NА, Chekanova AV. Systemic effects of glucocorticoid drugs: a guide for the General practitioner (literature review). RMJ. 2017;1:45-48.

15. Moghadam-Kia S, Werth VP. Prevention and treatment of systemic glucocorticoid side effects. Int J Dermatol. 2010;49(3):239-248. doi: https://doi.org/10.1111/j.1365-4632.2009.04322.x

16. Teitelbaum, SL. Glucocorticoids and the osteoclast. Clin. Exp. Rheumatol. 2015;33;37–39

17. Chotiyarnwong P, McCloskey EV. Pathogenesis of glucocorticoid-induced osteoporosis and options for treatment. Nature Reviews Endocrinology. 2020;16:437-447. https://doi.org/10.1038/s41574-020-0341-0

18. Баранова И.А. Глюкокортикоидиндуцированный остеопороз: патогенез, профилактика, лечение // Современная ревматология. — 2008. — №1. — С. 31–39.

19. Mazziotti G, Formenti AM, Frara S, et al. Management of endocrine disease: Risk of overtreatment in patients with adrenal insufficiency: current and emerging aspects. Eur J Endocrinol. 2017;177(5):R231-R248. doi: https://doi.org/10.1530/EJE-17-0154

20. Pereira RMR, Carvalho JF de, Paula AP, et al. Diretrizes para prevenção e tratamento da osteoporose induzida por glicocorticoide. Rev Bras Reumatol. 2012;52(4):580-593. doi: https://doi.org/10.1590/S0482-50042012000400009

21. Briot K, Roux C. Glucocorticoid-induced osteoporosis. RMD Open. 2015;1(1):e000014-e000014. doi: https://doi.org/10.1136/rmdopen-2014-000014

22. Compston J. Glucocorticoid-induced osteoporosis: an update. Endocrine. 2018;61(1):7-16. doi: https://doi.org/10.1007/s12020-018-1588-2

23. Durmaz B. Steroid-Induced Osteoporosis; At a Glance. Am J Biomed Sci Res. 2019;4(3):147-149. doi: https://doi.org/10.34297/AJBSR.2019.04.000786

24. Park SY, Gong HS, Kim KM, et al. Korean Guideline for the Prevention and Treatment of Glucocorticoidinduced Osteoporosis. J Bone Metab. 2018;25(4):195. doi: https://doi.org/10.11005/jbm.2018.25.4.195

25. Jung C, Greco S, Nguyen HH, et al. Plasma, salivary and urinary cortisol levels following physiological and stress doses of hydrocortisone in normal volunteers. BMC Endocr Disord. 2014;14(1):91. doi: https://doi.org/10.1186/1472-6823-14-91

26. Falhammar H. Skeletal fragility induced by overtreatment of adrenal insufficiency. Endocrine. 2018;59(2):239-241. https://doi.org/10.1007/s12020-017-1501-4

27. Murray RD, Ekman B, Uddin S, et al. Management of glucocorticoid replacement in adrenal insufficiency shows notable heterogeneity - data from the EU-AIR. Clin Endocrinol (Oxf ). 2017;86(3):340-346. doi: https://doi.org/10.1111/cen.13267

28. Løvås K, Gjesdal CG, Christensen M, et al. Glucocorticoid replacement therapy and pharmacogenetics in Addison’s disease: effects on bone. Eur J Endocrinol. 2009;160(6):993-1002. doi: https://doi.org/10.1530/EJE-08-0880

29. Valero M-A, Leon M, Valdepeñas MPR, et al. Bone density and turnover in Addison’s disease: effect of glucocorticoid treatment. Bone Miner. 1994;26(1):9-17. doi: https://doi.org/10.1016/S0169-6009(08)80158-4

30. Wichers M, Springer W, Bidlingmaier F, Klingmüller D. The influence of hydrocortisone substitution on the quality of life and parameters of bone metabolism in patients with secondary hypocortisolism. Clin Endocrinol (Oxf ). 1999;50(6):759-765. doi: https://doi.org/10.1046/j.1365-2265.1999.00723.x

31. Панкратова Ю.В., Пигарова Е.А., Дзеранова Л.К. Витамин К-зависимые белки: остеокальцин, матриксный Gla-белок и их внекостные эффекты // Ожирение и метаболизм. — 2013. — Т. 10. — №2. — С. 11-18. doi: https://doi.org/10.14341/2071-8713-4818

32. Bone and Tooth Society of Great Britain, National Osteoporosis Society, Royal College of Physicians. Glucocorticoid-induced Osteoporosis: Guidelines for Prevention and Treatment; 2002.

33. Chikada N, Imaki T, Hotta M, et al. An Assessment of Bone Mineral Density in Patients with Addison’s Disease and Isolated ACTH Deficiency Treated with Glucocorticoid. Endocr J. 2004;51(3):355-360. doi: https://doi.org/10.1507/endocrj.51.355

34. Chandy DD, Bhatia E. Bone Mineral Density In Patients With Addison Disease On Replacement Therapy With Prednisolone. Endocr Pract. 2016;22(4):434-439. doi: https://doi.org/10.4158/EP151014.OR

35. Zelissen PMJ. Effect of Glucocorticoid Replacement Therapy on Bone Mineral Density in Patients with Addison Disease. Ann Intern Med. 1994;120(3):207. doi: https://doi.org/10.7326/0003-4819-120-3-199402010-00005

36. Ragnarsson O. Glucocorticoids — outcome in patients with glucocorticoid deficiency and Cushing’s syndrome. Göteborg; 2012.

37. Braatvedt GD, Joyce M, Evans M, et al. Bone Mineral Density in Patients with Treated Addison’s Disease. Osteoporos Int. 1999;10(6):435-440. doi: https://doi.org/10.1007/s001980050251

38. Schulz J, Frey KR, Cooper MS, et al. Reduction in daily hydrocortisone dose improves bone health in primary adrenal insufficiency. Eur J Endocrinol. 2016;174(4):531-538. doi: https://doi.org/10.1530/EJE-15-1096

39. Al Nofal A, Bancos I, Benkhadra K, et al. Glucocorticoid Replacement Regimens in Chronic Adrenal Insufficiency: A Systematic Review and Meta-Analysis. Endocr Pract. 2017;23(1):17-31. doi: https://doi.org/10.4158/EP161428.OR

40. Leelarathna L, Breen L, Powrie JK, et al. Co-morbidities, management and clinical outcome of auto-immune Addison’s disease. Endocrine. 2010;38(1):113-117. doi: https://doi.org/10.1007/s12020-010-9359-8

41. Björnsdottir S, Sääf M, Bensing S, et al. Risk of hip fracture in Addison’s disease: a populationbased cohort study. J Intern Med. 2011;270(2):187-195. doi: https://doi.org/10.1111/j.1365-2796.2011.02352.x.

42. Camozzi V, Betterle C, Frigo AC, et al. Vertebral fractures assessed with dual-energy X-ray absorptiometry in patients with Addison’s disease on glucocorticoid and mineralocorticoid replacement therapy. Endocrine 2018;59:319-329. doi: https://doi.org/10.1007/s12020-017-1380-8

43. Koetz KR, Ventz M, Diederich S, Quinkler M. Bone Mineral Density Is Not Significantly Reduced in Adult Patients on Low-Dose Glucocorticoid Replacement Therapy. J Clin Endocrinol Metab. 2012;97(1):85-92. doi: https://doi.org/10.1210/jc.2011-2036

44. Frey KR, Kienitz T, Schulz J, et al. Prednisolone is associated with a worse bone mineral density in primary adrenal insufficiency. Endocr Connect. 2018;7(6):811-818. doi: https://doi.org/10.1530/EC-18-0160

45. Quinkler M, Ekman B, Marelli C, et al. Prednisolone is associated with a worse lipid profile than hydrocortisone in patients with adrenal insufficiency. Endocr Connect. 2017;6(1):1-8. doi: https://doi.org/10.1530/EC-16-0081

46. Riehl G, Reisch N, Roehle R, et al. Bone mineral density and fractures in congenital adrenal hyperplasia: Findings from the dsd‐LIFE study. Clin Endocrinol (Oxf ). 2020;92(4):284-294. doi: https://doi.org/10.1111/cen.14149

47. Chapman K, Holmes M, Seckl J. 11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action. Physiol Rev. 2013;93(3):1139-1206. doi: https://doi.org/10.1152/physrev.00020.2012

48. Miguel Novoa P de, Vela ET, García NP, et al. Guidelines for diagnosis and treatment of adrenal insufficiency in adults. Endocrinol y Nutr (English Ed. 2014;61:1-34. doi: https://doi.org/10.1016/S2173-5093(14)70069-8.

49. Johannsson G, Nilsson AG, Bergthorsdottir R, et al. Improved Cortisol Exposure-Time Profile and Outcome in Patients with Adrenal Insufficiency: A Prospective Randomized Trial of a Novel Hydrocortisone Dual-Release Formulation. J Clin Endocrinol Metab. 2012;97(2):473-481. doi: https://doi.org/10.1210/jc.2011-1926

50. Frara S, Chiloiro S, Porcelli T, et al. Bone safety of dual-release hydrocortisone in patients with hypopituitarism. Endocrine. 2018;60(3):528-531. doi: https://doi.org/10.1007/s12020-017-1512-1

51. ClinicalTrials.gov: Comparison of Chronocort® With Standard Glucocorticoid Therapy in Patients With Congenital Adrenal Hyperplasia. [Internet]. Available from: URL: https://clinicaltrials.gov/ct2/show/study/NCT02716818.

52. Falorni A, Minarelli V, Morelli S. Therapy of adrenal insufficiency: an update. Endocrine. 2013;43(3):514-528. doi: https://doi.org/10.1007/s12020-012-9835-4

53. Debono M, Ghobadi C, Rostami-Hodjegan A, et al. ModifiedRelease Hydrocortisone to Provide Circadian Cortisol Profiles. J Clin Endocrinol Metab. 2009;94(5):1548-1554. doi: https://doi.org/10.1210/jc.2008-2380

54. Mallappa A, Sinaii N, Kumar P, et al. A Phase 2 Study of Chronocort, a Modified-Release Formulation of Hydrocortisone, in the Treatment of Adults With Classic Congenital Adrenal Hyperplasia. J Clin Endocrinol Metab. 2015;100(3):1137-1145. doi: https://doi.org/10.1210/jc.2014-3809

55. Hagenfeldt K, Martin Ritzen E, Ringertz H, et al. Bone mass and body composition of adult women with congenital virilizing 21-hydroxylase deficiency after glucocorticoid treatment since infancy. Eur J Endocrinol. 2000:667-671. doi: https://doi.org/10.1530/eje.0.1430667

56. King JA, Wisniewski AB, Bankowski BJ, et al. Long-Term Corticosteroid Replacement and Bone Mineral Density in Adult Women with Classical Congenital Adrenal Hyperplasia. J Clin Endocrinol Metab. 2006;91(3):865-869. doi: https://doi.org/10.1210/jc.2005-0745

57. Sciannamblo M, Russo G, Cuccato D, et al. Reduced Bone Mineral Density and Increased Bone Metabolism Rate in Young Adult Patients with 21-Hydroxylase Deficiency. J Clin Endocrinol Metab. 2006;91(11):4453-4458. doi: https://doi.org/10.1210/jc.2005-2823

58. Bachelot A, Plu-Bureau G, Thibaud E, et al. Long-Term Outcome of Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency. Horm Res Paediatr. 2007;67(6):268-276. doi: https://doi.org/10.1159/000098017

59. Falhammar H, Filipsson H, Holmdahl G, et al. Fractures and Bone Mineral Density in Adult Women with 21-Hydroxylase Deficiency. J Clin Endocrinol Metab. 2007;92(12):4643-4649. doi: https://doi.org/10.1210/jc.2007-0744

60. Stikkelbroeck NMML, Oyen WJG, van der Wilt G-J, et al. Normal Bone Mineral Density and Lean Body Mass, but Increased Fat Mass, in Young Adult Patients with Congenital Adrenal Hyperplasia. J Clin Endocrinol Metab. 2003;88(3):1036-1042. doi: https://doi.org/10.1210/jc.2002-021074

61. Jääskeläinen J, Voutilainen R. Bone mineral density in relation to glucocorticoid substitution therapy in adult patients with 21-hydroxylase deficiency. Clin Endocrinol (Oxf ). 1996;45(6):707-713. doi: https://doi.org/10.1046/j.1365-2265.1996.8620871.x

62. New M, Yau M, Lekarev O, et al. Congenital Adrenal Hyperplasia. Endotext [Internet]. Ed. by Feingold KR, Anawalt B, Boyce A, et al. South Dartmouth (MA): MDText.com, Inc.; 2000.

63. El-Maouche D, Collier S, Prasad M, et al. Cortical bone mineral density in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Clin Endocrinol (Oxf ). 2015;82(3):330-337. doi: https://doi.org/10.1111/cen.12507

64. Whittle E, Falhammar H. Glucocorticoid Regimens in the Treatment of Congenital Adrenal Hyperplasia: A Systematic Review and Meta-Analysis. J Endocr Soc. 2019;3(6):1227-1245. doi: https://doi.org/10.1210/js.2019-00136

65. Dabas A, Vats P, Sharma R, et al. Management of Infants with Congenital Adrenal Hyperplasia. Indian Pediatrics. 2020;57:159-165.

66. Goldstein I, Clayton AH, Goldstein AT, et al. Textbook of Female Sexual Function and Dysfunction. Chichester, UK: John Wiley & Sons, Ltd; 2018. doi: https://doi.org/10.1002/9781119266136

67. Qiu X, Gui Y, Xu Y, et al. DHEA promotes osteoblast differentiation by regulating the expression of osteoblast-related genes and Foxp3+ regulatory T cells. Goldstein I, Clayton AH, Goldstein AT, Kim NN, Kingsberg SA, eds. Biosci Trends. 2015;9(5):307-314. doi: https://doi.org/10.5582/bst.2015.01073

68. Miller KK, Biller BMK, Beauregard C, et al. Effects of Testosterone Replacement in Androgen-Deficient Women with Hypopituitarism: A Randomized, Double-Blind, PlaceboControlled Study. J Clin Endocrinol Metab. 2006;91(5):1683-1690. doi: https://doi.org/10.1210/jc.2005-2596

69. Gurnell EM, Hunt PJ, Curran SE, et al. Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial. J Clin Endocrinol Metab. 2008;93(2):400-409. doi: https://doi.org/10.1210/jc.2007-1134

70. Hunt PJ. Improvement in Mood and Fatigue after Dehydroepiandrosterone Replacement in Addison’s Disease in a Randomized, Double Blind Trial. J Clin Endocrinol Metab. 2000;85(12):4650-4656. doi: https://doi.org/10.1210/jc.85.12.4650

71. Christiansen JJ, Bruun JM, Christiansen JS, et al. Long-term DHEA substitution in female adrenocortical failure, body composition, muscle function, and bone metabolism: a randomized trial. Eur J Endocrinol. 2011;165(2):293-300. doi: https://doi.org/10.1530/EJE-11-0289

72. Johannsson G, Burman P, Wirén L, et al. Low Dose Dehydroepiandrosterone Affects Behavior in Hypopituitary Androgen-Deficient Women: A Placebo-Controlled Trial. J Clin Endocrinol Metab. 2002;87(5):2046-2052. doi: https://doi.org/10.1210/jcem.87.5.8494

73. Locatelli V, Bianchi VE. Effect of GH/IGF-1 on Bone Metabolism and Osteoporsosis. Int J Endocrinol. 2014;2014(5):1-25. doi: https://doi.org/10.1155/2014/235060

74. Sigurjonsdottir HA, Andrew R, Stimson RH, et al. Lack of regulation of 11β-hydroxysteroid dehydrogenase type 1 during short-term manipulation of GH in patients with hypopituitarism. Eur J Endocrinol. 2009;161(3):375-380. doi: https://doi.org/10.1530/EJE-09-0315

75. Fleseriu M. Recombinant growth hormone treatment, osteoporosis and fractures, more complicated than it seems! Endocrine. 2018;59(3):463-465. doi: https://doi.org/10.1007/s12020-017-1519-7

76. Mazziotti G, Bianchi A, Bonadonna S, et al. Increased Prevalence of Radiological Spinal Deformities in Adult Patients With GH Deficiency: Influence of GH Replacement Therapy. J Bone Miner Res. 2006;21(4):520-528. doi: https://doi.org/10.1359/jbmr.060112

77. Barake M, Klibanski A, Tritos NA. Effects of Recombinant Human Growth Hormone Therapy on Bone Mineral Density in Adults With Growth Hormone Deficiency: A Meta-Analysis. J Clin Endocrinol Metab. 2014;99(3):852-860. doi: https://doi.org/10.1210/jc.2013-3921

78. Ragnar Agnarsson H, Johannsson G, Ragnarsson O. The Impact of Glucocorticoid Replacement on Bone Mineral Density in Patients With Hypopituitarism Before and After 2 Years of Growth Hormone Replacement Therapy. J Clin Endocrinol Metab. 2014;99(4):1479-1485. doi: https://doi.org/10.1210/jc.2013-3851

79. Mazziotti G, Porcelli T, Bianchi A, et al. Glucocorticoid replacement therapy and vertebral fractures in hypopituitary adult males with GH deficiency. Eur J Endocrinol. 2010;163(1):15-20. doi: https://doi.org/10.1530/EJE-10-0125

80. Lukert BP. Glucocorticoid Replacement—How Much Is Enough? J Clin Endocrinol Metab. 2006;91(3):793-794. doi: https://doi.org/10.1210/jc.2005-2737

81. Husebye ES, Allolio B, Arlt W, et al. Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J Intern Med. 2014;275(2):104-115. doi: https://doi.org/10.1111/joim.12162

82. Buckley L, Guyatt G, Fink HA, et al. 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Rheumatol. 2017;69(8):1521-1537. doi: https://doi.org/10.1002/art.40137


Дополнительные файлы

Для цитирования:


Юкина М.Ю., Чернова М.О., Нуралиева Н.Ф., Еремкина А.К., Трошина Е.А., Мельниченко Г.А., Мокрышева Н.Г. Влияние заместительной терапии глюкокортикоидами на костный обмен при надпочечниковой недостаточности. Обзор литературы. Ожирение и метаболизм. 2020;17(4):357-368. https://doi.org/10.14341/omet12700

For citation:


Yukina M.Yu., Chernova M.O., Nuralieva N.F., Eremkina A.K., Troshina E.A., Melnichenko G.A., Mokrysheva N.G. Effect of glucocorticoids on bone metabolism in replacement therapy of adrenal insufficiency. Literature review. Obesity and metabolism. 2020;17(4):357-368. (In Russ.) https://doi.org/10.14341/omet12700

Просмотров: 58


Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.


ISSN 2071-8713 (Print)
ISSN 2306-5524 (Online)