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G.P.10 02 Bone health in Duchenne muscular dystrophy
718
Abstracts / Neuromuscular Disorders 16 (2006) 644–726
Neurology and Psychiatry, Pavia, Italy; 3 Orthopedic Clinic, Institute Citta` di Pavia, University of Pavia, Pavia, Italy Osteoporosis is characterized by loss of both bone mass and microarchitectural integrity, resulting in an increased risk of fractures with associated morbidity and mortality. Bone mass in the elderly is related to the rate of involutional bone loss and mainly to the peak bone mass reached in childhood and adolescence. The peak bone mass appears as being the key issue problem in prophylactic strategy of osteoporotic therapy. Reduced bone density is now well recognized in children and adolescents affected by Duchenne Muscular Dystrophy (DMD) even before motor impairment is clinically relevant; only one study has been performed so far about Spinal Muscular Atrophy (SMA) patients as far as we know, surprisingly a normal bone density nevertheless an even more severe motor impairment. The aim of this study was to determine quantitative ultrasound velocity, which is related to bone mass, in patients with DMD and SMA. The work is in progress and more patients will be included by next summer. Each patient is included accordingly with his follow-up time table. The sample so far consists of 14 patients, 12 males and 2 females; 4 non-ambulant; 10 affected by Duchenne (DMD), 2 by Becker Muscular dystrophy (BMD) and 2 by Spinal Muscular Atrophy (SMA). The rage range was from 3 yrs 8 mths to 18 yrs. Quantitative ultrasound velocity was measured by Sunlight Omnisense, a device designed to measure SOS (Speed of Sound) at multiple skeletal sites, by axial transmission method. The purpose of the study is to investigate whether osteopenia/osteoporosis is always associated with neuromuscular pathology and if that is related to motor impairment. In order to critically interpret the sonographic results of the children included in our study, we have drawn a diagram of reference with the data obtained by the same device in the control group. Speed of sound values, indicative of bone density, obtained in children affected by DMD and SMA were compared with those obtained by means of the same device in a control group of 700 Italian healthy children and adolescents aged 6–19 years. Correlation between degree of disability and SOS has been analysed. 5 subjects had normal SOS values, 6 were classified as osteopenic and 3 as osteoporotic. Only 1 child in the ‘‘osteopenic’’ group had a possible pathologic bone fracture in the cuboid some years ago. Six DMD patients are on steroids. Due to the small sample we cannot perform any statistical analysis so far. As described in the literature the most of our DMD patients had reduced SOS, but we also found some DMD in the ‘‘Normal’’ group, apparently with no correlation with steroid therapy, age, or motor impairment. Both of the younger DMD patients (3 years 8 months/3 yrs 11 mths) are in the ‘‘not normal’’ group. doi:10.1016/j.nmd.2006.05.235
G.P.10 02 Bone health in Duchenne muscular dystrophy B.L. Wong 1,*, M.Y. Shao 1, M. Hurtubise 2, A. El-Bohy 1, M. Knue 1, P. Morehart 1, J.E. Heubi 1 1 Cincinnati Children’s Hospital Medical Center, Cincinnati, USA; 2 University of Cincinnati, Cincinnati, USA Patients with Duchenne muscular dystrophy (DMD) are at risk for osteoporosis and fractures secondary to muscle weakness, loss of mobility and chronic corticosteroid therapy. To assess the prevalence of reduced bone mineral density (BMD) and fractures in patients with DMD, a cross-sectional study of 45 patients with DMD was conducted between June and August 2005. The primary outcome variable was BMD of distal femur [DF]] (R1 – cancellous bone, R3 – cortical bone,
R2 – between R1 and R3) and lumbar spine (LS) as measured by DEXA z scores. The secondary outcome variables were fractures (per history and radiographs of spine and lone bones), DEXA lean body mass adjusted for weight, cumulative corticosteroid dose, calcium intake, serum 25 OH vitamin D levels and functional mobility level. Patients: n = 45 (ages 3.3–26, mean age 12.3 years), 24 on chronic steroids, 22 wheel chair dependent and 23 independent ambulators. For all DMD patients, DEXA z score (±SEM) for LS was 1.05 (±0.20); DF R1: 2.9 (±0.32), R2: 2.56 (±0.43), R3: 2.60 (±0.48) and whole body (WB): 1.78 (±0.25). DEXA z scores for LS were 1.08 (±0.34) vs 1.03 (±0.25); DF R1: 4.36 (±0.45) vs 1.63 (±0.23) [p < 0.0001]; R2: 4.33 (±0.63) vs 1.02 (±0.37) [p < 0.0001]; R3: 4.71 (±0.69) vs 0.76 (±0.38) [p < 0.0001] for non-steroid treated vs. treated subjects, respectively. LS, all 3 DF and WB DEXA z scores did not correlate with 25 OH Vitamin D levels and dietary calcium intake. DF R1, R2 and R3 z scores correlated with weight adjusted lean body mass (p < .0001) and with functional mobility levels (p < .0001). Analysis of covariance for comparing the steroid group and the non-steroid group adjusted for one of the four covariates (BMI, height, calcium intake and functional mobility level) found height and functional mobility level separately had significant effects as a covariate for the 3 DF z scores (p < 0.0001). When all above parameters were placed in the regression model as covariates with steroids, functional mobility level had significant effects for all 3 DF scores (p < 0.005), and height was significant for DF R3 scores (p = 0.04). Calcium intake was 1404.1 (±387.7) mg/day. Vitamin D intake was 498 (±62) IU/day and 25 OH vitamin D level was 26.78 (±1.67) ng/ ml. Twenty of 45 (44%) patients had a history of fractures; 9/20 (45%) were on steroids; 5 patients had spine compression fractures (all on steroids). WB DEXA z scores correlated with fracture history (p = 0.0003). BMD is reduced in patients with DMD despite adequate calcium and vitamin D intake. Osteoporosis in the lower extremities is more profound in non-steroid treated DMD patients compared to steroid treated patients and is correlated with worsening functional mobility and decreased muscle mass. Further larger studies are needed to define the risk factors for osteoporosis and fractures in DMD patients to enable effective treatment interventions. doi:10.1016/j.nmd.2006.05.236
G.P.10 03 Functional ability monitoring in Duchenne muscular dystrophy using posture and walking time recording in a home environment C. Bloetzer 1,*, B. Najafi 2, K. Aminian 2, P.Y. Jeannet 1 1 Neuropediatric Unit, Department of Pediatrics, CHUV, Lausanne, Switzerland; 2 Laboratory of Movement Analysis and Measurement, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland Developing new tools to better assess disease progression in neuromuscular disorders is important, particularly in the light of new therapeutic possibilities. In this pilot study, the daily functional ability of Duchenne (DMD) patients and healthy controls was measured using a small and light, wireless ambulatory system (ASUR) attached to the child’s t-shirt. ASUR is composed of three accelerometers and one gyroscope which identify body postures and periods of walking. Seven DMD patients (age 4–10 years) and 2 healthy controls (age 5 and 7 years) were studied in their home environment for one day while parents kept a diary of their activities. A validated motor function measure scale (MFM) was performed in patients 6 years or older (n = 5) before the recordings. There was good correlation of recorded data with parent’s diary. For patients 8 years or younger (n = 5), mean time spend sitting (Si) was 31% ± 6.5; standing (St) 41% ± 6.4; lying (Ly) 3% ± 1.7; walking (Wa) 25% ± 4.5; mean number of walking episodes (WE) was 371 ± 165; and mean number of continuous walking
Abstracts / Neuromuscular Disorders 16 (2006) 644–726
Neurology and Psychiatry, Pavia, Italy; 3 Orthopedic Clinic, Institute Citta` di Pavia, University of Pavia, Pavia, Italy Osteoporosis is characterized by loss of both bone mass and microarchitectural integrity, resulting in an increased risk of fractures with associated morbidity and mortality. Bone mass in the elderly is related to the rate of involutional bone loss and mainly to the peak bone mass reached in childhood and adolescence. The peak bone mass appears as being the key issue problem in prophylactic strategy of osteoporotic therapy. Reduced bone density is now well recognized in children and adolescents affected by Duchenne Muscular Dystrophy (DMD) even before motor impairment is clinically relevant; only one study has been performed so far about Spinal Muscular Atrophy (SMA) patients as far as we know, surprisingly a normal bone density nevertheless an even more severe motor impairment. The aim of this study was to determine quantitative ultrasound velocity, which is related to bone mass, in patients with DMD and SMA. The work is in progress and more patients will be included by next summer. Each patient is included accordingly with his follow-up time table. The sample so far consists of 14 patients, 12 males and 2 females; 4 non-ambulant; 10 affected by Duchenne (DMD), 2 by Becker Muscular dystrophy (BMD) and 2 by Spinal Muscular Atrophy (SMA). The rage range was from 3 yrs 8 mths to 18 yrs. Quantitative ultrasound velocity was measured by Sunlight Omnisense, a device designed to measure SOS (Speed of Sound) at multiple skeletal sites, by axial transmission method. The purpose of the study is to investigate whether osteopenia/osteoporosis is always associated with neuromuscular pathology and if that is related to motor impairment. In order to critically interpret the sonographic results of the children included in our study, we have drawn a diagram of reference with the data obtained by the same device in the control group. Speed of sound values, indicative of bone density, obtained in children affected by DMD and SMA were compared with those obtained by means of the same device in a control group of 700 Italian healthy children and adolescents aged 6–19 years. Correlation between degree of disability and SOS has been analysed. 5 subjects had normal SOS values, 6 were classified as osteopenic and 3 as osteoporotic. Only 1 child in the ‘‘osteopenic’’ group had a possible pathologic bone fracture in the cuboid some years ago. Six DMD patients are on steroids. Due to the small sample we cannot perform any statistical analysis so far. As described in the literature the most of our DMD patients had reduced SOS, but we also found some DMD in the ‘‘Normal’’ group, apparently with no correlation with steroid therapy, age, or motor impairment. Both of the younger DMD patients (3 years 8 months/3 yrs 11 mths) are in the ‘‘not normal’’ group. doi:10.1016/j.nmd.2006.05.235
G.P.10 02 Bone health in Duchenne muscular dystrophy B.L. Wong 1,*, M.Y. Shao 1, M. Hurtubise 2, A. El-Bohy 1, M. Knue 1, P. Morehart 1, J.E. Heubi 1 1 Cincinnati Children’s Hospital Medical Center, Cincinnati, USA; 2 University of Cincinnati, Cincinnati, USA Patients with Duchenne muscular dystrophy (DMD) are at risk for osteoporosis and fractures secondary to muscle weakness, loss of mobility and chronic corticosteroid therapy. To assess the prevalence of reduced bone mineral density (BMD) and fractures in patients with DMD, a cross-sectional study of 45 patients with DMD was conducted between June and August 2005. The primary outcome variable was BMD of distal femur [DF]] (R1 – cancellous bone, R3 – cortical bone,
R2 – between R1 and R3) and lumbar spine (LS) as measured by DEXA z scores. The secondary outcome variables were fractures (per history and radiographs of spine and lone bones), DEXA lean body mass adjusted for weight, cumulative corticosteroid dose, calcium intake, serum 25 OH vitamin D levels and functional mobility level. Patients: n = 45 (ages 3.3–26, mean age 12.3 years), 24 on chronic steroids, 22 wheel chair dependent and 23 independent ambulators. For all DMD patients, DEXA z score (±SEM) for LS was 1.05 (±0.20); DF R1: 2.9 (±0.32), R2: 2.56 (±0.43), R3: 2.60 (±0.48) and whole body (WB): 1.78 (±0.25). DEXA z scores for LS were 1.08 (±0.34) vs 1.03 (±0.25); DF R1: 4.36 (±0.45) vs 1.63 (±0.23) [p < 0.0001]; R2: 4.33 (±0.63) vs 1.02 (±0.37) [p < 0.0001]; R3: 4.71 (±0.69) vs 0.76 (±0.38) [p < 0.0001] for non-steroid treated vs. treated subjects, respectively. LS, all 3 DF and WB DEXA z scores did not correlate with 25 OH Vitamin D levels and dietary calcium intake. DF R1, R2 and R3 z scores correlated with weight adjusted lean body mass (p < .0001) and with functional mobility levels (p < .0001). Analysis of covariance for comparing the steroid group and the non-steroid group adjusted for one of the four covariates (BMI, height, calcium intake and functional mobility level) found height and functional mobility level separately had significant effects as a covariate for the 3 DF z scores (p < 0.0001). When all above parameters were placed in the regression model as covariates with steroids, functional mobility level had significant effects for all 3 DF scores (p < 0.005), and height was significant for DF R3 scores (p = 0.04). Calcium intake was 1404.1 (±387.7) mg/day. Vitamin D intake was 498 (±62) IU/day and 25 OH vitamin D level was 26.78 (±1.67) ng/ ml. Twenty of 45 (44%) patients had a history of fractures; 9/20 (45%) were on steroids; 5 patients had spine compression fractures (all on steroids). WB DEXA z scores correlated with fracture history (p = 0.0003). BMD is reduced in patients with DMD despite adequate calcium and vitamin D intake. Osteoporosis in the lower extremities is more profound in non-steroid treated DMD patients compared to steroid treated patients and is correlated with worsening functional mobility and decreased muscle mass. Further larger studies are needed to define the risk factors for osteoporosis and fractures in DMD patients to enable effective treatment interventions. doi:10.1016/j.nmd.2006.05.236
G.P.10 03 Functional ability monitoring in Duchenne muscular dystrophy using posture and walking time recording in a home environment C. Bloetzer 1,*, B. Najafi 2, K. Aminian 2, P.Y. Jeannet 1 1 Neuropediatric Unit, Department of Pediatrics, CHUV, Lausanne, Switzerland; 2 Laboratory of Movement Analysis and Measurement, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland Developing new tools to better assess disease progression in neuromuscular disorders is important, particularly in the light of new therapeutic possibilities. In this pilot study, the daily functional ability of Duchenne (DMD) patients and healthy controls was measured using a small and light, wireless ambulatory system (ASUR) attached to the child’s t-shirt. ASUR is composed of three accelerometers and one gyroscope which identify body postures and periods of walking. Seven DMD patients (age 4–10 years) and 2 healthy controls (age 5 and 7 years) were studied in their home environment for one day while parents kept a diary of their activities. A validated motor function measure scale (MFM) was performed in patients 6 years or older (n = 5) before the recordings. There was good correlation of recorded data with parent’s diary. For patients 8 years or younger (n = 5), mean time spend sitting (Si) was 31% ± 6.5; standing (St) 41% ± 6.4; lying (Ly) 3% ± 1.7; walking (Wa) 25% ± 4.5; mean number of walking episodes (WE) was 371 ± 165; and mean number of continuous walking