Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jun 1;76(6):701-709.
doi: 10.1001/jamaneurol.2019.0242.

Fractures and Linear Growth in a Nationwide Cohort of Boys With Duchenne Muscular Dystrophy With and Without Glucocorticoid Treatment: Results From the UK NorthStar Database

Shuko Joseph  1   2 , Cunyi Wang  3 , Kate Bushby  4 , Michaela Guglieri  4 , Iain Horrocks  2 , Volker Straub  4 , S Faisal Ahmed  1 , Sze Choong Wong  1 ; UK NorthStar Clinical Network
Affiliations

Fractures and Linear Growth in a Nationwide Cohort of Boys With Duchenne Muscular Dystrophy With and Without Glucocorticoid Treatment: Results From the UK NorthStar Database

Shuko Joseph et al. JAMA Neurol. .

Erratum in

  • Incorrectly Categorized Group Author.
    [No authors listed] [No authors listed] JAMA Neurol. 2019 Jun 1;76(6):732. doi: 10.1001/jamaneurol.2019.0904. JAMA Neurol. 2019. PMID: 30985878 Free PMC article. No abstract available.
  • Error in Abstract.
    [No authors listed] [No authors listed] JAMA Neurol. 2019 Jun 1;76(6):732. doi: 10.1001/jamaneurol.2019.1455. JAMA Neurol. 2019. PMID: 31180456 Free PMC article. No abstract available.

Abstract

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 10 000 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 10 000 person-years (95% CI, 579-798). The highest fracture incidence rate was observed in those treated with daily deflazacort at 1367 per 10 000 person-years (95% CI, 796-2188). After adjusting for age at last visit, mean hydrocortisone equivalent dose, mobility status, and bisphosphonate use prior to first fracture, boys treated with daily deflazacort had a 16.0-fold increased risk for first fracture (95% CI, 1.4-180.8; P = .03). 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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Guglieri has research collaboration with ReveraGen, BioGen, and PTC Therapeutics and has been on advisory boards for PTC Therapeutics and Capricorn. Prof Straub has received speaker’s honoraria from Sanofi Genzyme and Bayer; has research collaborations with Ultragenyx and Sanofi; and has been on advisory boards for Audentes Therapeutics, Biogen, Bristol-Myer Squibb, Exonics Therapeutics, Italfarmaco SpA., Pfizer, Roche, Sanofi Genzyme, Sarepta Therapeutics, Summit Therapeutics, Tivorsan, and Wave Therapeutics. Prof Ahmed has unrestricted education support from Kyowa Kirin and Diurnal and has received consultancy fees from Acerus, Novo Nordisk, Pfizer, and Sandoz. Dr Wong has received speaker’s honoraria from Sandoz, consultancy fees from Novartis and has been on advisory board for UCB. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. CONSORT Diagram
Flow diagram of participant inclusion in fracture and growth analysis. Data from 832 participants were used to assess new fracture occurrence and growth according to age groups. A total of 564 participants had more than 1 visit and complete clinical data. These participants were used for analysis of fracture incidence and longitudinal growth. Numbers included in each analysis described in detail. Participants included in the longitudinal growth analysis had complete data for height and weight in addition to clinical data. GC indicates glucocorticoid.
Figure 2.
Figure 2.. Probability of First Fracture in Relation to Duration of Glucocorticoid (GC) Exposure
A, Probability of first fracture in all GC-treated boys (n = 520) in relation to duration of GC exposure using Kaplan-Meier analysis. Those who did not sustain fracture by last visit were included and marked as censored cases (vertical lines on Kaplan-Meier curve). B, Probability of first fracture in different GC regimen in relation to duration of GC exposure using Kaplan-Meier analysis. Those who did not sustain fracture were included and marked as censored cases (vertical lines on Kaplain-Meier curves).
Figure 3.
Figure 3.. Multivariate Cox Regression Analysis of Cumulative Hazard According to Glucocorticoid (GC) Regimen
Hazard ratio of sustaining the first fracture was analyzed using multivariate Cox regression adjusting for age at last assessment, average hydrocortisone equivalent (milligrams per meters squared per day), mobility status, and bisphosphonate use prior to the first fracture.
See this image and copyright information in PMC

References

    1. Matthews E, Brassington R, Kuntzer T, Jichi F, Manzur AY. Corticosteroids for the treatment of Duchenne muscular dystrophy. Cochrane Database Syst Rev. 2016;1(5):CD003725. - PMC - PubMed
    1. Moxley RT III, Pandya S, Ciafaloni E, Fox DJ, Campbell K. Change in natural history of Duchenne muscular dystrophy with long-term corticosteroid treatment: implications for management. J Child Neurol. 2010;25(9):1116-1129. doi:10.1177/0883073810371004 - DOI - PubMed
    1. Passamano L, Taglia A, Palladino A, et al. . Improvement of survival in Duchenne Muscular Dystrophy: retrospective analysis of 835 patients. Acta Myol. 2012;31(2):121-125. - PMC - PubMed
    1. Bushby K, Finkel R, Birnkrant DJ, et al. ; DMD Care Considerations Working Group . Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2010;9(1):77-93. doi:10.1016/S1474-4422(09)70271-6 - DOI - PubMed
    1. Parente L. Deflazacort: therapeutic index, relative potency and equivalent doses versus other corticosteroids. BMC Pharmacol Toxicol. 2017;18(1):1. doi:10.1186/s40360-016-0111-8 - DOI - PMC - PubMed

Publication types

MeSH terms