Effective treatments are needed that provide the efficacy of traditional corticosteroids while potentially reducing select side effects.
Due to their anti-inflammatory effects, traditional corticosteroids are the foundational treatment in Duchenne muscular dystrophy (DMD).1
Corticosteroids are proven effective at delaying declines in muscle strength, delaying the time to loss of ambulation, lowering the rate of new‑onset cardiomyopathy, and potentially prolonging life. In addition, corticosteroids may help to slow cardiac function decline in individuals with DMD.2-4
Despite their benefits, corticosteroids carry many potential side effects for patients with DMD.
Side effects and safety concerns commonly associated with traditional corticosteroids include5-7:
Weight gain
Osteotoxicity & poor
bone health
Growth failure
or delay
Behavioural changes
Cushingoid
appearance
HCPs should stay vigilant when managing patients’ disease with corticosteroids. For patients experiencing weight gain and Cushingoid appearance, diet management is recommended. Monitoring a patient’s height as often as every 6 months can help identify growth delay. Establishing a baseline assessment of a patient’s mood and temperament prior to therapy is important to help identify any treatment-related changes.8
Unwanted side effects and safety concerns are a common reason for treatment discontinuation.9
Monitoring for side effects is essential for all patients on corticosteroid therapy. To manage side effects, dose reductions are frequently used, leading to a below‑average dose of corticosteroids.
Patients and their care team
should work together to weigh the benefits and risks of
traditional
corticosteroids use.9
Traditional corticosteroids increase risks of bone fragility and fractures.
In a study of 408 patients (ages 3-19 years) with DMD treated with glucocorticoids10:
Most treated individuals experienced at least one fracture by age 18
Compression fractures of the spine occurred in nearly 60% of patients by age 18
Monitoring bone health with imaging and biomarkers is essential
for all patients with
DMD using traditional corticosteroids.11
Several biomarkers that indicate bone health include11:
- Serum levels of calcium, phosphorus, alkaline phosphatase (ALP), and vitamin D should be monitored against the normal range
- Urine calcium, sodium, and creatinine should also be examined
Additional biomarkers have been investigated in patients with DMD.10
- Osteocalcin is a marker of bone formation
- Type 1 procollagen intact amino-terminal propeptide (PINP) is a marker of healthy bone turnover
Imaging is an important tool for monitoring bone health.11
- DEXA scans: Perform baseline scans at age 3 or at the beginning of glucocorticoid treatment; continue routine scans for patients on maintenance glucocorticoid therapy
- Spine radiograph: Perform radiograph if spinal deformity or vertebral fractures are suspected
- Bone age radiograph: Assess the extent of growth failure in patients with DMD using a left wrist radiograph
Bone health biomarkers and regular imaging should be part of all DMD care plans. Ensure your care team is including bone health in their annual assessments8,11
Best practices for bone health management in patients with DMD have not yet been established but several interventions have been recommended.8
Vitamin D
Vitamin D supplementation should be given to those with proven deficiencies. This should also be considered for others whose healthy levels cannot be maintained8
Calcium
Consult a dietitian to address
dietary calcium intake and
the need for possible
supplementation8
Bisphosphonates
Intravenous
bisphosphonates should be
given for those experiencing
vertebral fracture11
Vitamin D
Vitamin D supplementation should be given to those with proven deficiencies. This should also be considered for others whose healthy levels cannot be maintained8
Calcium
Consult a dietitian to address
dietary calcium intake and
the need for possible
supplementation8
Bisphosphonates
Intravenous
bisphosphonates should be
given for those experiencing
vertebral fracture11
References: 1. Nitahara-Kasahara Y, Takeda S, Okada T. Inflammatory predisposition predicts disease phenotypes in muscular dystrophy. Inflamm Regen. 2016;36:14. 2.McDonald CM, Henricson EK, Abresch RT, et al. Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study. Lancet. 2018;391(10119):451-461. 3.Matthews E, Brassington R, Kuntzer T, Jichi F, Manzur AY. Corticosteroids for the treatment of Duchenne muscular dystrophy. Cochrane Database Syst Rev. 2016;2016(5):CD003725. 4.Mah JK. Current and emerging treatment strategies for Duchenne muscular dystrophy. Neuropsychiatr Dis Treat. 2016;12:1795-1807. 5.Bello L, Gordish-Dressman H, Morgenroth LP, et al. Prednisone/prednisolone and deflazacort regimens in the CINRG Duchenne Natural History Study. Neurology. 2015;85(12):1048-1055. 6.Ward LM, Hadjiyannakis S, McMillan HJ, et al. Bone Health and Osteoporosis Management of the Patient With Duchenne Muscular Dystrophy. Pediatrics. 2018; 142(Suppl 2): S34-S42. 7.Ward LM. Glucocorticoid-Induced Osteoporosis: Why Kids Are Different. Front. Endocrinol. 2020; 11:576. 8. Birnkrant DJ, Bushby K, Bann CM, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol. 2018; 17(3): 251-267. 9. Cowen L, Mancini M, Martin A, Lucas A, Donovan JM. Variability and trends in corticosteroid use by male United States participants with Duchenne muscular dystrophy in the Duchenne Registry. BMC Neurol. 2019;19(1):84. 10. Buckner JL, Bowden SA, Mahan JD. Optimizing bone health in Duchenne muscular dystrophy. Int J Endocrinol. 2015;2015:928385. 11. Birnkrant DJ, Bushby K, Bann CM, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol. 2018;17(4):347-361.