0. ScOT-DMD study: What have we learnt and what have we achieved?
Jarod Wong
On behalf of Shuko Joseph
Scottish Muscle Network Annual Conference
Edinburgh Training & Conference Venue
1st September 2017

1. ScOT-DMD
SeCondary Osteoporosis & its Therapy in Duchenne Muscular Dystrophy (ScOT–DMD) Funded by CSO, Action Duchenne and Muscular Dystrophy UK

2. Overview
Study 1: Scottish Bone Health Study Study 2: North Star UK Bone Health Study Study 3: Prospective Longitudinal study Study 4: MRI Study Study 5: Feasibility questionnaire study

3. Study 1
Retrospective study of bone health & its management in Scotland
1/3 fracture femur
1/2 of limb fracture due to minor falls
1/4 due to fall from wheel chair
44/91 (48%) at least one fracture episode
By 10.3 years, there is a 50% probability of sustaining a fracture
8% painful VF and 40% non-VF

4. Study 1

5. Study 2 Retrospective study of Fracture & Growth in UK DMD population
North star data base from 23 centres in UK
Total number of patients 832 (3925 assessment records)

6. Study 2

7. Study 2

8. Vertebral fractures in chronic disease may often be asymptomatic
Study 3
Vertebral fractures in chronic disease may often be asymptomatic
(Steroid-Associated Osteoporosis In The Paediatric Population)
Halton J et al JBMR 2009, Huber AM et al Arthritis Care Res 2010, Rodd C et al Arthritis Care Res 2011, feber J et al Osteoporos Int 2012, Alos N et al, J Clin Oncol 2012, Phan V et al, Osteoporos Int 2014, Le Blanc et al, JBMR 2015, Cummings EA et al JCEM 2015
Newer generation DXA may allow identification of VF similar to spine x-ray

9. 2 year longitudinal study of bone health (5-18 years DMD boys)

10. Study 3 Preliminary findings FRACTURES
Vertebral fracture identified in almost 50% of the cohort (including those with previous vertebral fracture)
About 10% developed new vertebral fracture over 12 months follow-up
TESTES AND PUBERTY
Bilateral impalpable testes in about 15% on clinical examination and confirmed on ultrasound
- Absent puberty in about 66% of boys older than 14 years
Low testosterone levels as adults after 3 years of testosterone therapy
Testes remain small, implications for fertility
Recruitment closed in Scotland
Further funding MD-UK to extend study to Leeds (to recruit 30 boys)

11. Bisphosphonate & Fracture Cohort
TBLH BMC SDS
LS BMAD SDS * **
***
****
* p=0.57
*** p=0.24
**p=0.73
****p=0.78

12. Study 4
MRI assessment of trabecular bone microarchitecture

13. Study 4 MRI assessment of cortical geometry
MRS assessment of bone marrow adiposity as a marker of bone formation

14. Further funding to allow longitudinal study (MD-UK)
24 consented, aiming for 36
Further funding to allow longitudinal study (MD-UK)

15. Feasibility study of future bone targeted therapy trials
Questionnaire survey of opinions of boys and families affected by DMD and professionals involved in their care
To assess feasibility of future clinical trials involving bone protective therapy

16. Other collaborations- Research
Claire Wood
MRC Academic Fellowship and MD-UK
“Characterisation of skeletal development and the use of anabolic agents in murine models of DMD”
Kieren Hollingsworth/ MRI team
MRI muscle bone studies in Glasgow and Newcastle
Newcastle
Lars Savendahl
DMD bone research meetings (London 2016, Prague 2017, Stockholm 2018)
Proposed translational research on glucocorticoid and gonadal function in DMD
Stockholm
Leanne Ward and Volker Straub/ Ros Quinlivan
ENMC workshop
Clinical trials of bone protective therapy in DMD
Ottawa

17. Other collaborations- Clinical
1- SMN guidance on bone monitoring
2- SMN guidance on secondary adrenal insufficiency in DMD
3- Vertebral fracture information sheet
4- Secondary adrenal insufficiency information sheet
5- Instructional video on how to perform emergency IM hydrocortisone injection
6- Puberty and hypogonadism information sheet

21. 7T MRI for research in muscle-bone research
Hooijmans et al PlosOne 2017

22. Acknowledgements Scottish Muscle Network North Star Clinical Network
Chief Scientist Office
Muscular Dystrophy UK
Action Duchenne
Developmental Endocrinology
Research Group
Glasgow Neuromuscular Team