Effect of long-term glucocorticoid therapy on bone mineral density of the patients with congenital adrenal hyperplasia

Background and objectives. Congenital adrenal hyperplasia (CAH) is characterized by androgen excess which should be treated with life-long glucocorticoid therapy, thus can affect bone mineralization. We aimed to evaluate the bone mineral density (BMD) and determine the factors affecting bone mineralization in patients with CAH. Method. This prospective case-control study was conducted in children, adolescents and young adults with classical 21-hydroxylase CAH, and age-, sex-, and pubertal stage matched healthy controls. Lumbar1-4 BMD was determined by dual-energy X-ray absorptiometry. BMD z-score was calculated using national standards with respect to height age and was referred as “low BMD” if z-score < -1 SD. Univariate analyses were performed between low BMD and normal BMD groups, and multivariate logistic regression analysis was performed to assess the independent predictors of low BMD. Correlations of Body Mass Index (BMI)-z-score, average serum 17-hydroxyprogesterone level, duration of treatment, average and cumulative glucocorticoid doses with BMD z-score were evaluated with Spearman analyses. Results. Each group included 37 cases. BMD z-score of patients with CAH [0.47 (-0.04 – 1.56)] was higher than control group [-0.43 (-0.82 –0.05)]; p= < 0.001. Number of patients with low BMD was similar in both groups; [CAH: 6(16.2%), control: 5(13.5%); p= 0.744]. BMI- z-score was higher in patients with CAH when compared to control group; p= < 0.001. BMI z-score was lower in low BMD group as comparison to normal BMD group; p= 0.041. Each 1.0 decrease in BMI z-score, risk of having low BMD was found to increase by 1.79 (%95 CI: 1.03-3.12, p= 0.040). BMI-z-score, average serum 17-hydroxyprogesterone level, duration of treatment, average and cumulative glucocorticoid doses were not found to be correlated with BMD z-score. Conclusion. Long-term glucocorticoid therapy did not have negative effect on BMD of patients with CAH. Higher BMI z-score in patients with CAH may have a positive effect on preserving bone health. Precautions should be taken for increased risk of obesity.

___

1. Speiser PW, White PC. Congenital adrenal hyperplasia. N Engl J Med 2003; 349: 776-788.

2. Chakhtoura Z, Bachelot A, Samara-Boustani D, et al; Centre des Maladies Endocriniennes Rares de la Croissance and Association Surrénales. Impact of total cumulative glucocorticoid dose on bone mineral density in patients with 21-hydroxylase deficiency. Eur J Endocrinol 2008; 158: 879-887.

3. Arisaka O, Hoshi M, Kanazawa S, et al. Preliminary report: effect of adrenal androgen and estrogen on bone maturation and bone mineral density. Metabolism 2001; 50: 377-379.

4. Ceccato F, Barbot M, Albiger N, et al. Long-term glucocorticoid effect on bone mineral density in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Eur J Endocrinol 2016; 175: 101-106.

5. 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: 85-92.

6. Girgis R, Winter JS. The effects of glucocorticoid replacement therapy on growth, bone mineral density, and bone turnover markers in children with congenital adrenal hyperplasia. J Clin Endocrinol Metab 1997; 82: 3926-3929.

7. Gussinye M, Carrascosa A, Potau N, et al. Bone mineral density in prepubertal and in adolescent and young adult patients with the salt-wasting form of congenital adrenal hyperplasia. Pediatrics 1997; 100: 671-674.

8. Elnecave RH, Kopacek C, Rigatto M, Keller Brenner J, Sisson de Castro JA. Bone mineral density in girls with classical congenital adrenal hyperplasia due to CYP21 deficiency. J Pediatr Endocrinol Metab 2008; 21: 1155-1162.

9. Cetinkaya S, Kara C. The effect of glucocorticoid replacement therapy on bone mineral density in children with congenital adrenal hyperplasia. J Pediatr Endocrinol Metab 2011; 24: 265-269.

10. Okten A, Cakir M, Makuloglu M. Bone mineral status, bone turnover markers and vitamin D status in children with congenital adrenal hyperplasia. Minerva Endocrinol 2012; 37: 275-282.

11. Ganesh R, Suresh N, Janakiraman L. Bone mineral content and density in Indian children with congenital adrenal hyperplasia. Indian Pediatr 2018; 55: 880-882.

12. Paganini C, Radetti G, Livieri C, Braga V, Migliavacca D, Adami S. Height, bone mineral density and bone markers in congenital adrenal hyperplasia. Horm Res 2000; 54: 164-168.

13. de Almeida Freire PO, de Lemos-Marini SH, Maciel- Guerra AT, et al. Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a cross-sectional study of factors involved in bone mineral density. J Bone Miner Metab 2003; 21: 396- 401.

14. Demirel F, Kara O, Tepe D, Esen I. Bone mineral density and vitamin D status in children and adolescents with congenital adrenal hyperplasia. Turk J Med Sci 2014; 44: 109-114.

15. Ganesh R, Suresh N, Janakiraman L, Ravikumar K. Correlation of bone mineral parameters with anthropometric measurements and the effect of glucocorticoids on bone mineral parameters in congenital adrenal hyperplasia. Indian J Pediatr 2016; 83: 126-130.

16. Halper A, Sanchez B, Hodges JS, et al. Bone mineral density and body composition in children with congenital adrenal hyperplasia. Clin Endocrinol (Oxf) 2018; 88: 813-819.

17. Lin-Su K, New MI. Effects of adrenal steroids on the bone metabolism of children with congenital adrenal hyperplasia. Ann N Y Acad Sci 2007; 1117: 345-351.

18. Kandemir N, Yordam N. Congenital adrenal hyperplasia in Turkey: a review of 273 patients. Acta Paediatr 1997; 86: 22-25.

19. Volkl TM, Simm D, Beier C, Dorr HG. Obesity among children and adolescents with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Pediatrics 2006; 117: e98-e105.

20. Neyzi O, Bundak R, Gokcay G, et al. Reference values for weight, height, head circumference, and body mass index in Turkish children. J Clin Res Pediatr Endocrinol 2015; 7: 280-293.

21. Zimmermann A, Sido PG, Schulze E, et al. Bone mineral density and bone turnover in Romanian children and young adults with classical 21-hydroxylase deficiency are influenced by glucocorticoid replacement therapy. Clin Endocrinol (Oxf) 2009; 71: 477-484.

22. Goksen D, Darcan S, Coker M, Kose T. Bone mineral density of healthy Turkish children and adolescents. J Clin Densitom 2006; 9: 84-90.

23. Bianchi ML. Osteoporosis in children and adolescents. Bone 2007; 41: 486-495.

24. Carter DR, Bouxsein ML, Marcus R. New approaches for interpreting projected bone densitometry data. J Bone Miner Res 1992; 7: 137-145.

25. Bachrach LK, Gordon CM; Section on Endocrinology. Bone densitometry in children and adolescents. Pediatrics 2016; 138: e20162398.

26. Christiansen P, Molgaard C, Muller J. Normal bone mineral content in young adults with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Horm Res 2004; 61: 133-136.

27. Sahakitrungruang T, Wacharasindhu S, Supornsilchai V, Srivuthana S, Kingpetch K. Bone mineral density and body composition in prepubertal and adolescent patients with the classical form of 21-hydroxylase deficiency. J Med Assoc Thai 2008; 91: 705-710.

28. Vandewalle S, Taes Y, Van Helvoirt M, et al. Bone size and bone strength are increased in obese male adolescents. J Clin Endocrinol Metab 2013; 98: 3019- 3028.

29. Delvecchio M, Soldano L, Lonero A, et al. Evaluation of impact of steroid replacement treatment on bone health in children with 21-hydroxylase deficiency. Endocrine 2015; 48: 995-1000.

30. Yilmaz D, Ersoy B, Bilgin E, Gumuser G, Onur E, Pinar ED. Bone mineral density in girls and boys at different pubertal stages: relation with gonadal steroids, bone formation markers, and growth parameters. J Bone Miner Metab 2005; 23: 476-482.

31. Martin S, Munoz L, Perez A, et al. Clinical and molecular studies related to bone metabolism in patients with congenital adrenal hyperplasia. J Pediatr Endocrinol Metab 2014; 27: 1161-1166.
Turkish Journal of Pediatrics-Cover
  • ISSN: 0041-4301
  • Yayın Aralığı: 6
  • Başlangıç: 1958
  • Yayıncı: Hacettepe Üniversitesi Çocuk Sağlığı Enstitüsü Müdürlüğü
Sayıdaki Diğer Makaleler

Zinc deficiency and febrile seizure: a systematic review and meta-analysis

Farhad HEYDARIAN, Alireza Ataei NAKHAEI, Hasan Mehrad MAJD, Elham BAKHTIARI

Effect of gestational diabetes on the vitamin D levels in the neonates: a case control study

Arathy VIJAY, Smriti SINHA, Seema Pavaman SINDGIKAR, Vijaya D. SHENOY

Congenital myotonia: a review of twenty cases and a new splice-site mutation in the CLCN1 gene

Nezir ÖZGÜN, Hasan TAŞLIDERE

Role of kallistatin in pediatric patients with pulmonary arterial hypertension

Özge PAMUKÇU, Derya AY, Kazım ÜZÜM, Didem BARLAK KETİ, Mehmet KÖSE, Ali BAYKAN, Süleyman SUNKAK, Nazmi NARİN

The remarkable response to ponatinib therapy in a child with blastic phase of chronic myeloid leukemia

Tekin AKSU, Şule ÜNAL, Fatma GÜMRÜK

Eczema herpeticum emerging during atopic dermatitis in infancy

Ayşegül ERTUĞRUL, Zeynep Şengül EMEKSİZ, Ezgi ULUSOY SEVERCAN, Serap ÖZMEN, İlknur BOSTANCI

Effect of long-term glucocorticoid therapy on bone mineral density of the patients with congenital adrenal hyperplasia

Sezin ÜNAL, Ayfer ALİKAŞİFOĞLU, Alev OZON, Nazlı GÖNÇ, Nurgun KANDEMİR

Predictive value of an early amplitude-integrated electroencephalogram for short-term neurologic outcomes in preterm infants

Kyung Hee PARK, Young Mi KIM, Yun-Jin LEE, Mi Hye BAE, Na Rae LEE, Young Mi HAN, Hye-Young KIM, Su Young KIM, Shin Yun BYUN

Management of pediatric cardiac transplantation candidates with pulmonary hypertension and high pulmonary vascular resistance

Kahraman YAKUT, Birgül VARAN, İlkay ERDOĞAN, Nimet CİNDİK, Mahmut GÖKDEMİR, Ayten GÜMÜŞ, Kürşad TOKEL, Atilla SEZGİN

Two cases of Vici syndrome presenting with corpus callosum agenesis, albinism, and severe developmental delay

Mina HIZAL, Batuhan YEKE, Yılmaz YILDIZ, Ali ÖZTÜRK, Berrak BİLGİNER GÜRBÜZ, Turgay COŞKUN