Lookup NU author(s): Emerita Professor Katherine Bushby,
Dr Michela Guglieri,
Professor Volker Straub
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
© 2019 American Medical Association. All rights reserved. Importance: Based on studies with relatively small sample size, fragility fractures are commonly reported in glucocorticoid (GC)-treated boys with Duchenne muscular dystrophy (DMD). Objective: To determine the fracture burden and growth impairment in a large contemporary cohort of boys with DMD in the United Kingdom and in relation to GC regimen. Design, Setting, and Participants: A retrospective review of fracture morbidity and growth from 832 boys with DMD in the UK NorthStar database (2006-2015), which systematically captures information from 23 participating centers. A total of 564 boys had more than 1 visit. No numbers of boys who refused were collected, but informal data from 2 centers in London and from Scotland show that refusal is very low. Data were analyzed between October 2006 and October 2015. Main Outcomes and Measures: Fracture incidence rate per 10000 person-years was determined. Cox regression analysis was used to identify factors associated with first fracture. Results: Median age at baseline was 6.9 years (interquartile range, 4.9-7.2 years). At baseline, new fractures were reported in 7 of 564 participants (1.2%). During a median follow-up of 4 years (interquartile range, 2.0-6.0 years), incident fractures were reported in 156 of 564 participants (27.7%), corresponding to an overall fracture incidence rate of 682 per 10000 person-years (95% CI, 579-798). The highest fracture incidence rate was observed in those treated with daily deflazacort at 1367 per 10000 person-years (95% CI, 796-2188). After adjusting for age at last visit, mean hydrocortisone equivalent exposure, mobility status, and bisphosphonate use prior to first fracture, boys treated with daily deflazacort had a 18.6-fold increase risk for first fracture (95% CI, 1.7-208.6; P =.02). Using adjusted regression models, change in height standard deviation scores was -1.6 SD lower (95% CI, -3.0 to -0.1; P =.03) in those treated with daily deflazacort compared with GC-naive boys, whereas there were no statistical differences in the other GC regimen. Conclusions and Relevance: In this large group of boys with DMD with longitudinal data, we document a high fracture burden. Boys treated with daily deflazacort had the highest fracture incidence rate and the greatest degree of linear growth failure. Clinical trials of primary bone protective therapies and strategies to improve growth in boys with DMD are urgently needed, but stratification based on GC regimen may be necessary..
Author(s): Joseph S, Wang C, Bushby K, Guglieri M, Horrocks I, Straub V, Ahmed SF, Wong SC
Publication type: Article
Publication status: Published
Journal: JAMA Neurology
Pages: Epub ahead of print
Online publication date: 11/03/2019
Acceptance date: 26/10/2018
ISSN (print): 2168-6149
ISSN (electronic): 2168-6157
Publisher: American Medical Association
Altmetrics provided by Altmetric