DMD is the most common subtype of MD with severe clinical symptoms. Patients with DMD show progressive muscle and respiratory weakness, loss of ambulation at the age of 10 years, and have a median life expectancy with ventilatory support ranging from 21.0 to 39.6 years . Most clinicians are aware of the benefits of glucocorticoid therapy to improve life expectancy and preserve respiratory function [8,12]. To the best of our knowledge, this is the first database study to investigate the current status of clinical practice directly related to disease progression in patients with DMD in South Korea. According to the database, the number of patients aged >20 years and the mean age at death increased yearly.
Long-term steroid use in patients with DMD has prolonged life expectancy and changed the overall natural history , although their prescription has still not been standardized, and there are mixed opinions about the time of initiation and whether to continue the use of steroids after the loss of ambulation [11,14,15]. According to the results of the present study, steroid prescription is mostly not initiated at the time of DMD diagnosis owing to gait abnormalities; this is inconsistent with the findings of recent studies placing emphasis on the benefits of early initiation of steroid therapy before the onset of physical decline [14,15]. Deflazacort tended to be increasingly prescribed to younger patients compared with prednisolone; however, the age of initiation did not decrease over the years. The long-term outcomes of the many different regimens (up to 29 identified) are not clear. Although the benefits of glucocorticoid therapy are well-established, considering the benefit-to-risk ratio of the drugs, uncertainty remains regarding the appropriate regimen and the use of steroid therapy after the loss of ambulation [16-18]. Although it has been reported that glucocorticoid therapy is effective in terms of maintaining upper limb function and cardiorespiratory function , the long-term use of steroids can cause various side effects, such as bone health problems, obesity, and behavioral changes , and consensus has not been reached regarding maintaining the prescription of steroids during the non-ambulant period. On examining the drug prescription regimen data collected in this study, it was confirmed that the percentage of non-ambulant patients taking steroids increased by year. Previous studies have compared the superiority between prednisolone and deflazacort; however, it is difficult to draw a definite conclusion from these results. Based on the data of this study, the percentage of deflazacort prescriptions was similar to that for prednisolone in recent years. Although deflazacort prescription dose in the ambulant group increased by age and year, the dose prescription for both deflazacort and prednisolone did not reach the recommendation of the current DMD care consideration (prednisolone: 0.75 mg/kg per day; deflazacort: 0.9 mg/kg per day). Considering the fact that the recent clinical trials for DMD treatment are excluding the patients not receiving corticosteroid therapy as the recommended regimen, discussion among clinicians is required to confirm the findings of this study
Bone health management
With regard to glucocorticoid-treated DMD cases, there is a high incidence of glucocorticoid-induced osteoporosis, and the resulting bone fragility may lead to secondary vertebral and long-bone fractures . In the current care considerations, serial spine radiography is recommended over DXA scan to determine asymptomatic bone fragility . In a recent expert study, 60% of the patients underwent routine bone health assessment, and DXA was the most common method, followed by spine X-rays and biochemical marker assessment . In the present study, among the patients assessed for bone health monitoring, less than 30% underwent spine radiography, DXA, scan and Vitamin D level examination. DXA was confirmed to be the most commonly used method among all tests. The tests were conducted with longer time intervals than the recommendation. Approximately 40% of patients were prescribed vitamin D and bisphosphonate; however, considering the additional needs for DXA scan based on our results, the percentage of patients requiring the prescription may also increase.
Orthopedic management of DMD is necessary to minimize joint contractures and prolong ambulatory function as much as possible. A custom-molded night-time ankle-foot orthosis prescription can be used from the ambulatory stage to delay the progression of the equinovarus contracture of the ankle and extend the ambulatory stage; even if the patient becomes wheelchair-bound, it is possible to assume a proper sitting posture by maintaining the ankle joint. In this study, approximately 5% of the patients were given prescriptions, and as the study data only included 3 years of available benefits payment table records, the actual prescription rate is presumed to be higher. With the onset of the non-ambulatory stage, scoliosis progresses rapidly, causing discomfort in the sitting posture; this can also lead to compromised respiratory function . Monitoring of radiography assessment annually or every 6 months after the confirmatory diagnosis of scoliosis is recommended . The assessment frequency in the applicable age group was judged to be longer than expected in this study.
There is a low-level evidence that spinal orthoses can delay the progression of scoliosis. However, there were cases in which spinal orthosis was prescribed, assuming that the initial mobile curve could be corrected and maintained with the aid of an orthosis . Although we confirmed that it was prescribed to some patients, our result was analyzed during the 3 years for which data were available. Surgery is recommended for functional improvement, sitting balance, and improvement of pain and the quality of life at a young age when a spinal curve of ≥20° has been measured [24,25]. Even with the consideration that corticosteroid therapy slows mild spinal curvature and reduces the necessity of spine surgery , the results of our study confirmed that a low percentage of our patients underwent spinal surgery , and the age of undergoing surgery was found to be higher than in the early 10s, which is the aged at which patients become wheelchair-bound . As posterior spinal instrumentation and fusion are recommended in non-ambulatory individuals, the percentage of posterior approach was three time higher than anterior approach in our data.
This study describes the current status of corticosteroid use and bone health management related to DMD, and it is the first study in a South Korean population in this regard.
There are some limitations to our study. First, we could not extract a complete list of patients with DMD from those with MD solely based on the diagnosis codes owing to the limitations of big data. In this study, we identified patients with MD who were prescribed corticosteroids and had the typical clinical course of DMD for analysis. Furthermore, as many patients with DMD are diagnosed based on non-covered genetic testing instead of a muscle biopsy or EMG as a result of advances in diagnostic techniques, we could not perform an epidemiological analysis encompassing incidence and time of diagnosis. A 2007 Korean study examined the prevalence and current status of MD; however, it was only able to investigate the prevalence by disease type for the same reason . Thus, it is important to establish a nationwide DMD registry in Korea to examine the clinical course and management status of DMD and reach a consensus. Second, with regard to orthosis prescription, information could only be obtained from 2016 onward, when payment based on the benefits payment table was possible. Therefore, data before 2016 could not be analyzed. A further study that can analyze long-term data will be useful to understand the current status of DMD management in greater detail.