10.1 Introduction

Duchenne muscular dystrophy (DMD) is a recessive X-linked disorder resulting from mutations in the gene encoding for dystrophin. Dystrophin is an intracytoplasmic protein that functions as a component of a large glycoprotein complex whose function is to stabilize the sarcolemma. When dystrophin is nonfunctional, the glycoprotein complex is compromised and the resulting membrane instability and increased mechanical stress results in myofiber necrosis, which triggers a state of muscle inflammation. A chronic state of mononuclear cell infiltration precedes the onset of weakness in the DMD muscle, ¹ and this inflammatory state affects state affects the skeleton and spine.

DMD is the most prevalent form of muscular dystrophy in children, affecting approximately 1 in 4,700 males. ² While there is variability in the phenotype of boys with DMD, the clinical manifestations in untreated children follow a predictable course. This progressive disorder is characterized by muscle fiber degeneration causing gradual worsening of muscle weakness. The onset of weakness usually occurs between 2 and 3 years of age, and is subtle at first. Weakness begins in the proximal musculature, and the Gower’s sign, in which children use their arms to “climb up their body” when standing from the floor, can be used to suggest this diagnosis in young children. The weakness is progressive, and walking ability slowly declines. This decline in ambulatory capability is associated with hypertrophy of the musculature and the development of contractures. An infiltration of fatty-fibrous tissue into the muscles causes hypertrophy and contributes to contracture development. By the teen years, patients become full-time wheelchair users. The progressive muscle weakness affects respiratory function and eventually cardiac function. There is a roughly 2% per year decline in predicted pulmonary function tests. Ultimately, patients succumb to the disease in their third decade of life from respiratory decline and/or cardiomyopathy.

10.2 Natural History of Scoliosis

Almost all untreated boys with this disorder develop progressive scoliosis. While muscle weakness is the principle cause, some authors believe there may be other contributing factors. ³ For instance, kyphosis associated with full-time wheelchair use may unlock the facet joints allowing for more lateral motion ⁴ ; others have suggested that the chronic inflammatory state causes contracture of the paraspinal musculature that in turn could act as a tether. ^{3 ,​ 5} Spinal deformity starts after boys become full-time wheelchair users. ^{6 ,​ 7} The one exception is boys with a hyperextended spine. However, this is a rare occurrence, and since studies evaluating the natural history were undertaken before genetic testing was in widespread use, it is not clear if these boys did indeed have a mutation in the DMD gene. There is relentless progression once a scoliotic curve reaches 20 degrees in a nonambulatory child, although the pace of progression varies from patient to patient. ⁸ A subpopulation of boys develop very large curves that make seating difficult, resulting in pain and a rather poor overall quality of life. ⁷ There is also a progressive decline in pulmonary function, although it is not clear if the scoliosis progression is directly related to the pulmonary decline. ^{9 ,​ 10}

10.3 Glucocorticoid Treatment in Duchenne Muscular Dystrophy

Over the past decade, glucocorticoids, such as prednisone and deflazacort, have come into widespread use in DMD. These agents were initially utilized for short time periods in boys transitioning to full-time wheelchair use. They were found to slow the decline in strength, but concerns about side effects and the finding that once the agents were stopped strength returned to the same level as in boys who did not use the drugs limited their use. However, starting in the late 1990s, long-term glucocorticoid treatment was attempted in patients to determine if the benefits would outweigh possible side effects. The initial cohort of boys treated with long-term deflazacort now has been followed for 20 years. Treatment with deflazacort results in a significant slowing of the progressive decline in muscle strength and function, pulmonary function, and cardiac function. This results in continuation of mobility, a decreased incidence of skeletal deformity, and improved survival. ^{11 ,​ 12 ,​ 13} Side effects of therapy, however, do exist, such as cataracts and osteoporosis, resulting in long bone and vertebral compression fractures. ^{11 ,​ 12 ,​ 13} These side effects can be managed with appropriate ophthalmologic and medical management. Interestingly, however, a recent population study ¹⁴ found that steroid use did not increase fracture incidence, raising the possibility that long-term suppression of the inflammation associated with the disease by glucocorticoids may also improve bone health. While there have been discussions about the relative efficacy of different glucocorticoids, there is no comparative data showing the superiority of one drug over another.

10.4 Nonoperative Management of Scoliosis

Although there have been attempts to control scoliosis progression with bracing in DMD, spinal orthosis use has not been shown to alter the natural history of curve progression. ⁴ Extremity surgery and bracing to keep boys standing longer was at one time thought to slow scoliosis progression, by keeping the lumbar spine lordotic and “locking” the facets, but this too has not been shown to alter the natural history of relentless curve progression. ¹⁵

Long-term use of glucocorticoids results in a substantial attenuation in the natural history of scoliosis development. Early analysis of a cohort of boys treated with glucocorticoids showed an 80% decline in the chance of developing scoliosis by age 20 years. ¹⁶ Long-term follow-up of this cohort showed that this reduced rate of developing scoliosis persists into adulthood (Fig. 10‑1). ¹⁷ In addition, data from acquired paralysis suggest that if the spine remains relatively straight after skeletal maturity, it is unlikely to progress in later life. ^{18 ,​ 19} Data from more recent studies confirm a substantially reduced rate of development of scoliosis in other cohorts of boys treated with glucocorticoids. ^{12 ,​ 20 ,​ 21} Not all these studies found as dramatic a reduction in the development of scoliosis as in the early reported cohort. However, taken together, these studies suggest a dose response effect in the prevention of scoliosis and slowing its progression rate from over 90% to less than 30%. There is still much to be learned about the impact of this treatment on scoliosis, including the duration of treatment needed and long-term risks. Compliance is likely also an issue, and boys using the drug intermittently are less likely to show an effect.