Vitamin D in Patients With Duchenne Muscular Dystrophy

Abstract

Objectives: Duchenne Muscular Dystrophy (DMD) is one of the neuromuscular junction dystrophies, characterized by deficiency of dystrophin and inherited as an X-linked recessive trait. It has a progressive nature, and results in loss of ambulation and death. Poor bone-marrow health is an important issue in terms of morbidity in DMD. Vitamin D is an important pre-prohormone related to bone health. Although steroids used in treatment of DMD are effective on progression of the disease they have adverse effects on bone heatlh and 25(OH)-vitamin D (vitamin D) levels. We aimed in the present study to investigate levels of vitamin D and its relationship with steroid use and ambulation in the patients with DMD.

Material and Metods: The present study is a case-control study including 96 male patients aged between 2 to 18 years with diagnosis of DMD and 48 healthy volunteers with matching gender and age distribution.

Results: Deficiency or insufficiency of vitamin D level was found in 95.83% of the patients with DMD. The patients with DMD were compared to the healthy volunteers and significantly lower level of vitamin D was found in the group of patients (p = 0.003). No significant difference was found in levels of vitamin D between the patients with DMD who were using steroids and those not using steroids and between the patient who were ambulated or not ambulated (p = 0.741 and p=0.785).

Conclusion: Majority of the patients with DMD had deficient or insufficient level of vitamin D. Thus, in the terms of protecting bone health it is important to assess level of vitamin D regularly from the early stages of the disease and during the routine controls, to implement additional treatments in the case of deficiency or insufficiency.

Keywords

• Duchenne Muscular Dystrophy,Vitamin D,Steroid

Duchenne Muskuler Distrofili Hastalarda Vitamin D Düzeyi

Abstract

Amaç: Duchenne Musküler Distrofi (DMD), kavşak tipi distrofilerden olup X’e bağlı resesif geçen, distrofin eksikliği karakterize kas hastalığıdır. İlerleyicidir, ambulasyon kaybı ve erken dönemde ölümlere yol açar. Zayıf kemik sağlığı DMD’de morbidite açısından önemli bir sorundur. Vitamin D, kemik sağlığı açısından önemli bir preprohormondur. DMD tedavisinde kullanılan steroidlerin hastalığın progresyonu üzerinde etkin tedavisi olmasına rağmen kemik sağlığı ve vitamin D üzerinde olumsuz etkileri bulunmaktadır. DMD’li hastalarda serum 25(OH)vitamin D (vitamin D) düzeylerini, vitamin D’nin steroid kullanımı ve ambulasyonla ilişkisini değerlendirmeyi amaçlandık.

Materyal-Metot: Vaka kontrol olan çalışmaya doksan altı kesin DMD tanısı almış, 2-18 yaş, erkek hasta ve kırk sekiz benzer yaş ortalaması ve cinsiyette sağlıklı gönüllüler alındı.

Bulgular: DMD’li hastalarda %95,83 oranında vitamin D düzeylerinde eksiklik – yetersizlik saptandı. DMD ‘li hastalar ile sağlıklı gönüllüler karşılaştırıldı, vitamin D düzeylerinde hasta grubunda anlamlı düşüklük saptandı (p=0.003). DMD’li steroid alan ve almayanlar ile ambulasyonu olan ve olmayan hastalar arasında vitamin D düzeyleri açısından fark saptanmadı (p=0.741 ve p=0.785).

Sonuç: DMD’li hastalarda, yüksek oranda vitamin D düzeylerinde eksiklik-yetersizlik mevcuttu. Bu nedenle D vitamin düzeylerinin erken dönemden itibaren ve rutin kontrollerde düzenli değerlendirilmesi ve eksiklik-yetersizliğinde ilave tedavilerinin yapılması kemik sağlığını korumak açısından oldukça önemlidir.

Keywords

• Duchenne Muskuler Distrofi,vitamin D,Steroid

References

1. Emery AE. Population frequencies of inherited neuromuscular diseases – a world survey. Neuromuscul Disord 1991;1:19-29.
2. Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol 2010;9:177-89.
3. Dubowitz V. Steroids in Duchenne muscular dystrophy. Neuromuscul Disord 2013;23:527-8.
4. Bell JM, Shields MD, Watters J, Hamilton A, Beringer T, Elliott M, et al. Interventions to prevent and treat corticosteroid-induced osteoporosis and prevent osteoporotic fractures in Duchenne muscular dystrophy. Cochrane Database Syst Rev 2017;1:CD010899.
5. Joyce NC, Hache LP, Clemens PR. Bone health and associated metabolic complications in neuromuscular diseases. Phys Med Rehabil Clin N Am 2012;23:773-99.
6. Goltzman D. Functions of vitamin D in bone. Histochem Cell Biol 2018;149:305-12.
7. Morgenroth VH, Hache LP, Clemens PR. Insights in to bone health in Duchenne muscular dystrophy. Bonekey Rep 2012;1:9.
8. Lips P. Vitamin D physiology. Prog Biopshys Biol 2006;92:1-8.

9. Massafra UM, Migliaccio S, Bancheri C, Chiacchiararelli F, Fantini F, Leoni F, et al. Approach in glucocorticoid induced osteoporosis prevention: Results from the Italian multicenter observational study. J Endocrinol Invest 2013;36:92-6.
10. Biggar WD, Bachrach LK, Henderson RC, Kalkwarf H, Plotkin H, Wong BL. Bone health in Duchenne muscular dystrophy: a workshop report from the meeting in Cincinnati, Ohio, July 8, 2004. Neuromuscul Disord 2005;15:80-5.
11. Kim HJ. New understanding of glucocorticoid action in bone cells. BMB Rep 2010;43:524-529. DOI:10.5483/BMBRep.2010.43.8.524
12. James KA, Cunniff C, Apkon SD, Mathews K, Lu Z, Holtzer C. Risk factors for first fractures among males with Duchenne or Becker muscular dystrophy. J Pediatr Orthop 2015;35:640-4.
13. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266-81.
14. Holick MF, Binkley NC, Bischoff-Ferrari HA et al. Evaluation, treatment, and prevention of vitamin d deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2011;96:1911-30.
15. Perera N, Sampaio H, Woodhead H, Farrar M. Fracture in Duchenne muscular dystrophy: natural history and vitamin D deficiency. J Child Neurol 2016;31:1181-7.
16. Dogan N, Colak A, Guden N, Ustuner F. Vitamin D deficiency in children in Aegean Region in Turkey. Cumhuriyet Med J 2015;37:17-22. DOI: 10.7197/cmj.v37i1.5000013903
17. Munot P, Krishnakumar D, Robb S, Davies T, Muntoni F, Manzur A. Prevalence of vitamin D deficiency in 157 boys with Duchenne muscular dystrophy. Arch Dis Child 2010;95:957-61.
18. Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, pharmacological and psychosocial management. Lancet Neurol 2010;9:77-93.
19. Bianchi ML, Mazzanti A, Galbiati E, Saraifoger S, Dubini A, Cornelio F, et al. Bone mineral density and bone metabolism in Duchenne muscular dystrophy. Osteoporos Int 2003;14:761-7.
20. Alshaikh N, Brunklaus A, Davis T, Robb SA, Quinlivan R, Munot P, et al. Vitamin D in corticosteroid-naïve and corticosteroid-treated Duchenne muscular dystrophy: what dose achieves optimal 25(OH) vitamin D levels? Arch Dis Child 2016;101:957-.
21. McDonald DG, Kinali M, Gallagher AC, Mercuri E, Muntoni F, Roper H, et al. Fracture prevalence in Duchenne muscular dystrophy. Dev Med Child Neurol 2002;44:695-8.
22. Larson CM, Henderson RC. Bone mineral density and fractures in boys with Duchenne muscular dystrophy. J Pediatr Orthop 2000;20:71-4.
23. Buckner JL, Bowden SA, Mahan JD. Optimizing bone health in Duchenne muscular dystrophy. Int J Endocrinol 2015;928385.
24. Looker AC, Mussolino ME. Serum 25-hydroxyvitamin D and hip fracture risk in older U.S. white adults. J Bone Miner Res 2008;23:143-50.
25. Bianchi ML, Morandi L, Andreucci E, Vai S, Frasunkiewicz J, Cottafava R. Low bone density and bone metabolism alterations in Duchenne muscular dystrophy: response to calcium and vitamin D treatment. Osteoporos Int 2011;22:529-39.
26. Fidan F, Berat MA, Tosun A. Pandemic era: vitamin D deficiency and insufficiency. Turk Osteoporoz Derg 2014;20:71-4.