G.P.9.08 Duchenne muscular dystrophy – decreased bone turnover and bone mineral density

Abstracts / Neuromuscular Disorders 17 (2007) 764–900 decrease in contrast uptake in some muscles post-exercise. The calf muscles and gluteus maximus showed a greater tendency to increased uptake of contrast than the thigh muscles post-exercise. Quantification of signal intensity can be used to investigate fat infiltration and muscle water content in a comparative analysis. DMD boys’ inter-individual variation in signal intensities prevented some results from reaching significance. This technique will be employed in future scans of the same children to quantify the change in fat infiltration and muscle water content over time. doi:10.1016/j.nmd.2007.06.187

G.P.9.08 Duchenne muscular dystrophy – decreased bone turnover and bone mineral density Ahlander, A. 1,*; So¨derpalm, A. 2; Magnusson, P. 3; Karlsson, J. 2; Kroksmark, A. 4; Tulinius, M. 4; Swolin-Eide, D. 4 1 Institution of Clinical Sciences, Paediatrics, Go¨teborg, Sweden; 2 Institute of Clinical Sciences, Go¨teborg University, Ortopaedics, Go¨teborg, Sweden; 3 Faculty of Health Sciences, Clinical Chemistry, Linko¨ping, Sweden; 4 Institute of Clinical Sciences, Go¨teborg University, Paediatrics, Go¨teborg, Sweden Background: Duchenne muscular dystrophy (DMD), the most common muscular dystrophy in childhood, implies an increased risk of osteoporosis. Objectives. Examination of bone mineral density, bone turnover, body composition, calciotropic hormones and muscle strength in 24 boys with DMD (2.3–19.7 years), most of whom were being treated with prednisolone, and 24 age-matched healthy boys (2.7–19.6 years). Methods: Bone mineral density was measured by DXA (GE Lunar Prodigy) and DXL (Demetech). Motor function was classified according to the Vignos scale. Isometric muscle strength was measured using an electronic handheld myometer. Results: Our study demonstrated lower bone mineral density in the DMD group for total body, spine, hip, heel and forearm measurements and the differences between patients and controls increased with increasing age. Biochemical markers of both bone formation and resorption revealed reduced bone turnover in DMD patients. The fracture rate was not higher in DMD patients. The DMD patients had low vitamin D levels but high leptine levels compared to the control group. Correlations were found between heel bone mineral density and motor function and isometric muscular strength. Conclusions: Patients with DMD demonstrate a lower mineral bone density and a decreased bone turnover compared to controls. Interventions that increase bone formation should be considered. doi:10.1016/j.nmd.2007.06.188

G.P.9.09 Immediate release oral pentoxifylline is poorly tolerated in Duchenne muscular dystrophy boys Escolar, D. 1,*; Tesi-Rocha, C. 2; Clemens, P. 3; Iannaccone, S. 4; Pestronk, A. 5; Kuntz, N. 6; Zimmerman, A. 2; Henricson, E. 7; Arrieta, A. 2; Nei, L. 8; Markle, B. 9; Connolly, A. 5 1 Chidren’s National Medical Center, Department of Neurology, Washington, United States; 2 Children’s National Medical Center, Center for Genetic Medicine, Washington, United States; 3 University of Pittsburgh, Department of Neurology, Pittsburgh, United States; 4 Southwestern Medical Center, Department of Pediatric Neurology, Dallas, United States; 5 Washington University, St. Louis, Department of Neurology, St. Louis, United States; 6 Mayo Clinic, Department of Neurology, Rochester, United States; 7 University of California at Davis, Physical Medicine and Rehabilitation, Sacramento, United States; 8 Georgetown University, Department of Biostatistics, Washington, United States; 9 Children’s National Medical Center, Department of Radiology, Washington, United States

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Objectives: The objective of this open label pilot study of oral, immediate release pentoxyfylline was to assess the tolerability, safety and efficacy on muscle strength and function in Duchenne muscular dystrophy (DMD). Methods: This was an open label prospective study with a 3 month lead-in period followed by 12 months of treatment with a 20 mg/ kg/day dose of pentoxifylline (maximal administered dose was 598 mg/ day). Study subjects were 4–9 year-old steroid-naive DMD boys. The primary efficacy measure was a total quantitative muscle testing (QMT) score. The secondary and exploratory endpoint measures were manual muscle strength, arm and leg QMT, timed function tests, muscle MRI, serum TNF-alpha and TGF-beta levels and adverse event profiles. Results: Twenty patients were screened, 17 enrolled and nine completed the study protocol. The study population was 4.3–8.5 years of age, with a mean of 6.0 years (1.3) and median of 5.8 years. QMT and MMT measures did not show a significant change during the 3 month lead-in or 12 months treatment periods. However, five of the eight patient withdrawals were due to intolerable adverse events. Eleven of the 17 patients experienced nausea and vomiting and two of these patients experienced moderate (grade 3) to severe (grade 4) leucopenia. Conclusions: The immediate release oral formulation of pentoxifylline, while allowing for accurate dosing, is not well tolerated in children with DMD. The 12% incidence of leucopenia in this study was higher than expected since as the reported incidence rate in adults is less than 1%. Leucopenia rapidly improved with withdrawal of the drug. The 65% incidence of vomiting was also higher than expected compared to a 4.5% reported incidence in adults. The lack of deterioration in strength and function over 12 months in steroid naı¨ve DMD children with mean age close to 6 suggests a possible beneficial effect on disease progression and warrants further study with a different formulation of pentoxifylline. ‘‘Stabilization’’ of strength in DMD boys this age, however, must be viewed with caution in the light of prior studies which confirm a true ‘‘honeymoon period’’ in strength and function in DMD. doi:10.1016/j.nmd.2007.06.189

G.P.9.10 Clinical development of the French UMD–DMD database Humbertclaude, V. 1,*; Tuffery-Giraud, S. 1; Ben Yaou, R. 2; Hamroun, D. 1; Khau Van Kien, P. 1; Leturcq, F. 3; Chelly, J. 3; Claustres, M. 1; Be´roud, C. 1 1 CHU Montpellier, INSERM U827, Laboratoire de Ge´ne´tique Mole´culaire, Montpellier, France; 2 INSERM U582, Institut de Myologie, Paris, France; 3 CHU Cochin, Laboratoire de Biochimie et Ge´ne´tique Mole´culaire, Paris, France A French UMD–DMD database was created to collect the molecular and clinical data from patients with a mutation in the dystrophin gene. We present the clinical side of the French UMD–DMD database, in particular the development of new tools for clinical data analysis, prerequisite for the study of phenotype–genotype correlations. Molecular data are completed by a clinical synthesis of the patient. Clinical items were selected after an extensive study of the literature and validated with physicians from the 9 ‘‘French Reference Centers for Neuromuscular Diseases’’. Four curators collect anonymous data from all diagnostic laboratories and physicians. New algorithms were thus developed to analyze this phenotypic information using the 4D language (4DÒ). Three levels of information represent each clinical data: symptom, severity, age of onset. Each affected organ system is described with a limited range of qualitative and quantitative items, including diagnosis, motor function, clinical examination, intellectual and psychological problems, orthopaedic complications, heart, respiratory, digestive and urologic problems, growth, age at last examination, death. This list includes 175 items. Using new tools from UMD–DMD, the user can create various analysis matrices that allow to choose clinical items of interest and statistical functions. The functions ‘‘Graph per symptom’’ or ‘‘Graph per age’’ show the distribution of the various severities for a selected symptom or their age of occurrence either for all records or for a subset of records. The ‘‘LVEF and FVC evolution’’ function