Zeynep Anıl ŞAHİN, İsmail Gökhan ŞAHİN, Leyla BOZATLI, Işık GÖRKER

Dikkat Eksikliği ve Hiperaktivite Bozukluğu Tanısı Alan Çocuk ve Ergenlerde Uzun Süreli Metilfenidat Kullanımının Büyüme ve Kemik Yoğunluğu Üzerine Etkilerinin Araştırılması

Bu çalışmamızdaki amacımız, Dikkat Eksikliği ve Hiperaktivite Bozukluğu (DEHB) tanılı olgularda en sık kullandığımız farmakolojik tedavi ajanı olan metilfenidatın büyüme ve kemik yapısı üzerine etkilerini araştırmaktır. Trakya Üniversitesi Tıp Fakültesi, Çocuk ve Ergen Ruh Sağlığı ve Hastalıkları Anabilim Dalı tarafından DEHB tanısı ile takip edilen; 30 erkek vaka, olgu grubu olarak çalışmaya dahil edildi ve benzer yaş grubundaki kontrol grubu ile karşılaştırıldı. Gruplar; yaş (yıl), boy uzunluğu (cm), vücut ağırlığı (kg) ve vücut kitle indeksi (kg/m2), 25-hidroksikolekalsiferol (Vitamin D), serum kalsiyum değerleri (mg/dl) ve DEXA (Dual enerjili x-ray absorpsiyometrisi) sonuçları ile karşılaştırılarak değerlendirildi. Çalışmamızda büyüme parametreleri [boy(cm), vücut ağırlığı (kg), vücut kitle indeksi (kg/m2)], Vitamin D düzeyleri, lomber ve kalça kemik mineral yoğunluğu açısından gruplar arasında istatistiksel olarak anlamlı fark saptanmadı. Serum kalsiyum düzeyleri, proksimal femur ve lomber vertebra Z skorlarının olgu grubunda istatistiksel olarak anlamlı düzeyde düşük olduğu tespit edildi (p=0.001; p=0.013; p=0.015). Metilfenidat tedavisi, DEHB olgularında altın standart farmakolojik tedavidir. Literatürde hiçbir çalışmada DEHB olgularında metilfenidat kullanımına bağlı olarak kontrol grubuna kıyasla daha iyi büyüme parametreleri ve kemik yoğunluğu saptanmamıştır. Literatürle uyumlu olarak çalışmamızda büyüme parametreleri açısından gruplar arası fark saptanmadı. Kemik parametrelerinde ise, kalça ve lomber vertebra Z skorları ve serum kalsiyum düzeylerinin olgu grubunda istatistiksel olarak anlamlı düzeyde düşük olduğu tespit edildi. Vitamin D düzeyleri açısından gruplar arası istatistiksel olarak anlamlı fark tespit etmemiş olmamıza rağmen ortalama değerler açısından olgu grubumuzun Vitamin D eksikliği, kontrol grubumuzun ise Vitamin D yetersizliği tanımına uymasının önemli olduğunu düşünüyoruz.

Anahtar Kelimeler:

Kemik Büyümesi, Absorptiometri, DEHB, Metilfenidat

Investigation of the Effects of Long-Term Methylphenidate Use on Growth and Bone Density in Children and Adoles with Diagnosis of Attention Deficit Hyperactivity Disorder

Our aim in this study is to investigate the effects of methylphenidate, which is the most commonly used pharmacological treatment agent, on growth and bone structure in patients with Attention Deficit Hyperactivity Disorder (ADHD). Patients with the diagnosis of ADHD was followed; 30 male cases were included in the study as a case group and compared with the control group in the similar age group. Groups; age (years), height (cm), body weight (kg) and body mass index (kg/m2), 25-hydroxycholecalciferol (Vitamin D), serum calcium values (mg/dl) and DEXA (Dual energy x-ray absorptiometry) compared with the results. In our study, no statistically significant difference was found between the groups in terms of growth parameters, Vitamin D levels, lumbar and hip bone mineral density. Serum calcium levels, proximal femur and lumbar vertebra Z scores were found to be statistically significantly lower in the case group (p=0.001; p=0.013; p=0.015). Methylphenidate treatment is the gold standard pharmacological treatment in ADHD cases. In no study in the literature, better growth parameters and bone density were found in ADHD cases compared to the control group due to the use of methylphenidate. Consistent with the literature, no difference was found between the groups in terms of growth parameters in our study. In bone parameters, hip and lumbar vertebra Z scores and serum calcium levels were found to be statistically significantly lower in the case group. Although we did not find a statistically significant difference between the groups in terms of vitamin D levels, we think that it is important that our case group conforms to the definition of Vitamin D deficiency and that our control group complies with the definition of Vitamin D deficiency in terms of mean values.

Keywords:

Bone Development, Absorptiometry, ADDH, Methylphenidate, Absorptiometri, Absorptiometri, Absorptiometri, DEHB DEHB, Kemik Büyümesi, Metilfenidat, Metilfenidat,

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1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Arlington, VA, American Psychiatric Publishing; 2013.
2. Polanczyk G, Rohde LA. Epidemiology of attention-deficit/hyperactivity disorder across the lifespan. Curr Opin Psychiatry. 2007;20(4):386-92.
3. Faraone SV, Sergeant J, Gillberg C et al. The worldwide prevalence of ADHD: is it an American condition? World Psychiatry. 2003;2:104–13.
4. Skounti M, Philalithis A, Galanakis E. Variations in prevalence of attention deficit hyperactivity disorder worldwide. Eur J Pediatr. 2007;166:117–23.
5. Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child Adolesc Psychiatr Clin N Am. 2000;9:541–55.
6. Aktepe E. Dikkat eksikliği hiperaktivite bozukluğu tanısı konan çocuk ve ergenlerde eş tanılar ve sosyodemografik özellikler. Yeni Symposium. 2011;4:9.
7. Davies W. Sex differences in attention deficit hyperactivity disorder: candidate genetic and endocrine mechanisms. Front Neuroendocrinol. 2014;35:331-46.
8. Skounti M, Philalithis A, Galanakis E. Variations in prevalence of attention deficit hyperactivity disorder worldwide. Eur J Pediatr. 2007;166:117-23.
9. Faraone SV, Perlis RH, Doyle AE et al. Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatr. 2005;57:1313-23.
10. Akgün GM, Tufan AE, Yurteri N et al. Genetic Basis of Attention Deficit Hyperactivity Disorder. Curr App Psychiatr. 2011;3(1):15-48.
11. Asherson P. IMAGE Consortium. Attention-deficit hyperactivity disorder in the post-genomic era. Eur Child Adolesc Psychiatr. 2004;13(1):50-70.
12. Thapar A, Cooper M. Attention deficit hyperactivity disorder. Lancet. 2016;387:1240–50.
13. Akay AP, Ercan ES. Çocuk ve Ergen Ruh Sağlığı ve Hastalıkları. In: Ercan ES, Mukaddes NM, Yazgan Y ve ark. Dikkat Eksikliği ve Hiperaktivite Bozukluğu, 2016;33-55. 1st ed. Ankara: HYB Basım Yayın. 14. Chung J, Tchaconas A, Meryash D et al. Treatment of attention-deficit/hyperactivity disorder in preschool-age children: child and adolescent psychiatrists’ adherence to clinical practice guidelines. J Child Adolesc Psychopharmacol. 2016;26(4):335–43.
15. Austerman J. ADHD and behavioral disorders: Assessment, management and an update from DSM-5. Cleve Clin J Med. 2015;11(1):2-7.
16. Erselcan T, Özen A, Yüksel D et al. Prodecure guideline for bone density measurement. Turk J Nucl Med. 2009;18(1):31-40.
17. Njeh CF, Fuerst T, Hans D et al. Radiation exposure in bone mineral assessment. Appl Rad Isotope. 1999;50:215-36.
18. Hart NH, Nimphius S, Rantalainen T et al. Mechanical basis of bone strength: influence of bone material, bone structure and muscle action. J Musculoskelet Neuronal Interact. 2017;17(3):114–39.
19. Poulton A, Bui Q, Melzer E et al. Stimulant medication effects on growth and bone age in children with attention-deficit/hyperactivity disorder: a prospective cohort study. Int Clin Psychopharmacol. 2016;31(2):93-9.
20. Swanson JM, Elliott GR, Greenhill LL. Effects of stimulant medication on growth rates across 3 years in the MTA follow-up. J Am Acad Child Adolesc Psychiatr. 2007;46(8):1015-27.
21. Howard JT, Walick KS, Rivera JC. Preliminary Evidence of an Association Between ADHD Medications and Diminished Bone Health in Children and Adolescents. J Pediatr Orthop. 2017;37(5):348-54.
22. Komatsu DE, Thanos PK, Mary MN et al. Chronic exposure to methylphenidate impairs appendicular bone quality in young rats. Bone. 2012;50(6):1214-22.
23. Schermann H, Ankory R, Shlaifer A et al. Lower risk of stress fractures in young adults with ADHD under chronic treatment with methylphenidate. Bone. 2019;120:20-4.
24. Chen VC, Yang YH, Liao YT et al. The association between methylphenidate treatment and the risk for fracture among young ADHD patients: A nationwide population-based study in Taiwan PLoS One. 2017;12(3): e0173762.
25. Uddin SMZ, Robison LS, Fricke D et al. Methylphenidate regulation of osteoclasts in a dose- and sex-dependent manner adversely affects skeletal mechanical integrity. Sci Rep. 2018;8(1):1515.
26. Robison LS, Michaelos M, Gandhi J et al. Sex differences in the physiological and behavioral effects of chronic oral methylphenidate treatment in rats. Front Behav Neurosci. 2017;11:53.
27. Biederman J, Spencer TJ, Monuteaux MC et al. A naturalistic 10-year prospective study of height and weight in children with attention-deficit hyperactivity disorder grown up: sex and treatment effects. J Pediatr. 2010;157(4):635-40.
28. Peyre H, Hoertel N, Cortese S et al. Long-term effects of ADHD medication on adult height: results from the NESARC. J Clin Psychiatr. 2013;74(11):1123-4.
29. Vitamin D Eksikliği, 2018 [internet]. Türk Endokrinoloji ve Metabolizma Derneği Osteoporoz ve Diğer Metabolik Kemik Hastalıkları Çalışma Grubu (Erişim tarihi 01.10.2019) http://temd.org.tr/hastalar-icin/10-osteoporoz.
30. Holick MF. The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord. 2017;18:153-65.
31. Mohammadpour N, Jazayeri S, Tehrani-Doost M et al. Effect of vitamin D supplementation as adjunctive therapy to methylphenidate on ADHD symptoms: A randomized, double blind, placebo-controlled trial. Nutr Neurosci. 2018;21(3):202-9.
32. Poulton A, Briody J, McCorquodale T et al. Weight loss on stimulant medication: how does it affect body composition and bone metabolism? - A prospective longitudinal study. Int J Pediatr Endocrinol. 2012:2012(1):30.
33. Lahat E, Weiss M, Shlomo AB et al. Bone mineral density and turnover in children with attention-deficit hyperactivity disorder receiving methylphenidate. J Child Neurol. 2000;15:436-9.
34. Granato MF, Ferraro AA, Lellis DM et al. Associations between attention-deficit hyperactivity disorder (ADHD) treatment and patient nutritional status and height. Behav Neurol. 2018.;2018:7341529.
35. Poulton A. Growth on stimulant medication; clarifying the confusion: a review Arch Dis Child. 2005;90:801–6.
36. Feuer AJ, Thai A, Demmer RT et al. Association of stimulant medication use with bone mass in children and adolescents with attention-deficit/hyperactivity disorder. JAMA Pediatr. 2016;170(12):e162804.