Bone health in Duchenne muscular dystrophy

Abstracts 2016 / Neuromuscular Disorders 26 (2016) S88–S212 contradistinction, utrophin-positive fibers were present in both our patient’s peripheral and esophageal skeletal muscle. Additional studies will be required to determine whether DMD-related gastric dysmotility is directly related to this loss of dystrophin in gastric smooth muscle, or if other neuromuscular elements involved in functional motility are alternatively compromised. http://dx.doi.org/10.1016/j.nmd.2016.06.128

P.108 Bone health in Duchenne muscular dystrophy H. Peay 1, A. Martin 2, P. Ruddle 1, J. Lavigne 2, K. Kinnett 2, A. Lucas 2 1 International Research Triangle Park, NC, USA; 2 Parent Project Muscular Dystrophy, NJ, USA Bone fragility in Duchenne (DMD) is well documented. The use of corticosteroids has been reported to increase the risk of vertebral and long bone fractures. Bisphosphonates have shown positive effects on bone mineral density, but questions remain about dose, preparation, therapy length, and when to initiate. In addition, more information is needed on the natural history of bone health and surveillance strategies. In the Duchenne connect self-report registry we collected data between October 2015 and March 2016 on steroid and bisphosphonate use, fracture, and physical function; 173 male participants with Duchenne are included in preliminary analyses. Participants had a median age of 9.3 (range 0.7 to 44). 28.9% (n = 50) reported fracture following minor or no trauma and 9.8% (n = 17) vertebral compression fracture. Bisphosphonate use was reported by 17.9% (n = 31) with a positive relationship between use and fracture (p < .0001). There was no relationship between current or previous steroid use (n = 142 for current/previous steroid users) and fracture history. Those using bisphosphonates who are also current/previous steroid users were more likely to have reported a fracture than individuals taking neither medication (p < .0001). Age was positively correlated with fracture (p < .0001), scoliosis (p < .0001) and bisphosphonate use (p = .016). Non-ambulatory patients were significantly more likely to report a fracture than ambulatory (p < .0001). Preliminary results show a relatively high rate of fracture, with no relationship to steroid use. We demonstrate the expected relationship between bisphosphonates and fracture. Our ability to obtain longitudinal data and a larger sample will allow us to further characterize this relationship in patients treated using a variety of regimens. Impact of BMI and time since loss of ambulation will also be evaluated. There is a potential for response bias that may be reduced as our response rate increases. http://dx.doi.org/10.1016/j.nmd.2016.06.129

P.109 Bone health monitoring clinical laboratory and image evaluation in Duchenne muscular dystrophy with steroid treatment R. Escobar 1, A. Ocon 1, S. Renan 1, E. Martinez 1, L. Lopéz 2, B. Goméz 1 1 Institución Nacional de Rehabilitación, México, Mexico; 2 Centro Medico 20 Noviembre, México, Mexico Steroid treatment in DMD delays the loss of muscle strength and preserves the ability to ambulate. However increases low bone mineral density (BMD) and risk of fractures. Hence the importance of monitoring bone health and provide interventions to improve it. Monitoring of bone health in DMD in the start and of steroids treatment with screening methods as quantitative computed tomography (QCT) and determination of 25 OH vitamin D at the end. Longitudinal study of a cohort of 31 patients, 25 (age 15.3 +/− 3.0) with steroids and 6 (age 15.1 +/− 2.4) without treatment. BMD was measured by QTC, evaluating T and Z score morphological findings in lumbar vertebrae (3 = normal, 2 = microfractures and 1 = microfractures sclerosis) and clinical scales of functionality (Brooke, Vignos); as well as covariates: age, weight, height, Serum 25 OH vitamin D, deflazacort dose, treatment time, consumption of vitamin D and when Z score > −2.5 with Alendronate. Statistical Analysis. Descriptive, Mann–Whitney U, Fisher Exact tests to compare the 2 groups,

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McNemar test to compare qualitative changes. Pearson r correlation and multivariate analysis of covariance analysis with p < 0.05. Results. Steroid: T score of −2.0 to −3.3 (p = 0.0001) Z score −2.5 to −3.6 (p = 0.0001). Microfractures with sclerosis 16% to 12%, normal morphologies 52% to 36%, microfractures 32% to 52% (p = 0.37). Improved Brooke upper (p = 0.02), Brooke lower (p = 0.0001) Vignos (p = 0.0001 ); changes in Z score −1.02, −2.13, −0.73 and −0.68 (ANOVA, p = 0.016 ). No steroid: T score at −0.31 and −1.31 (p = 0.04); 56 % steroid improved in Vignos while 100 % Non steroid ≥5 (p = 0.017 ) remain. The results support that the use of steroids in DMD improves clinical scales, but had lower T and Z score correlated with morphological changes than those not treated. http://dx.doi.org/10.1016/j.nmd.2016.06.130

P.110 ECG abnormalities correlate with myocardial fibrosis by cardiac magnetic resonance imaging in DMD K. Hor 1, S. Raman 2, S. Subramanian 2, T. Moran 2, T. Gnyawali 2, K. Lao 1, W. Benson 3, L. Cripe 1 1 Nationwide Children’s Hospital, Columbus, USA; 2 The Ohio State University, Columbus, USA; 3 Milwaukee Children’s Hospital, Milwaukee, USA Duchenne muscular dystrophy (DMD) is characterized by progressive cardiomyopathy. Electrocardiographic (ECG) abnormalities are prevalent but nonspecific. The noninvasive cardiac imaging technique of late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) identifies myocardial fibrosis in a typical pattern in DMD cardiomyopathy. We hypothesized that ECG abnormalities could predict the presence of myocardial fibrosis by LGECMR. 164 DMD patients (age 10.9 + 3.4 years) underwent simultaneous LGECMR and ECG between 2005 and 2011. ECGs were analyzed for abnormalities prevalent in DMD: short PR interval (<120 msec), R/S wave ratio > 1 in lead V1, abnormal Q waves and sinus tachycardia (HR > 100/min). ECG and CMR analysis were conducted by blinded investigators. 15 (9%) had myocardial fibrosis by LGE-CMR and 4 (2%) had reduced LVEF (<50%) by CMR. 157 (96%) demonstrated one or more ECG abnormalities, 124 (76%) had 2 or more abnormalities, 68 (41%) 3 or more abnormalities. Abnormalities included a short PR interval (84), R/S wave ratio > 1 in lead V1 (86), abnormal Q waves (111) and sinus tachycardia (80). Short PR and R/S > 1 in V1 demonstrated increased risk for LGE with an odds ratio of 3.47 (95% CI 1.17–10.33l, p value = 0.02). Additionally, the presence of short PR, R/S > 1 in V1, abnormal Q wave and sinus tachycardia was also associated with increased risk for presence of LGE with slightly higher odds ratio of 3.84 (95% CI 1.06–13.67, p value = 0.03). Conversely, the absence of short PR and R/S > 1 in V1 had a high negative predictive value for LGE (119/127 patients, 94%). DMD patients with specific ECG abnormalities are more likely to have fibrosis by LGE-CMR, and patients without such abnormalities are less likely to demonstrate fibrosis. ECG may serve as a clinical biomarker to guide the timing of CMR evaluation. This could have implications for treatment as well as future clinical trials. http://dx.doi.org/10.1016/j.nmd.2016.06.131

P.111 Cardiac evaluation in Duchenne muscular dystrophy patients presenting with acute severe chest pain K. Hor 1, S. Raman 2, M. Mah 1, L. Cripe 1 1 Nationwide Children’s Hospital, Columbus, USA; 2 The Ohio State University, Columbus, USA Cardiovascular complications are a leading cause of morbidity and mortality in patients with Duchenne muscular dystrophy (DMD). Chest pain in the DMD patient is often overlooked as it is frequently attributed to the musculoskeletal system. Rarely does it prompt a complete cardiac evaluation. We report a case series of 7 DMD patients (2010–2016) who presented with