1. High prevalence of fractures in glycogen storage disease type I (GSD-I) R.M. van der Ende, D.H. Martens, G.P.A. Smit, T.G.J. Derks, E. van der Veer
Rixt van der Ende
Section of Metabolic Diseases, Beatrix Children’s Hospital and Laboratory of Metabolic Diseases, Department of Laboratory Medicine
UMC Groningen, The Netherlands
June 4th 2015
Rixt van der Ende, June 4th 2015

2. INTRODUCTION Glycogen storage disease 1 (GSD-1)1
Inherited inborn error of metabolism
Deficiency of glucose-6-phosphatase
Inadequate conversion of glucose-6-phosphate into glucose (glycogenolysis and gluconeogenesis)
Fasting intolerance (hypoglycemia), failure to thrive and hepatomegaly
Rixt van der Ende, June 4th Bali DS et al. Glycogen Storage Disease Type I Apr 19 [Updated 2013 Sep 19]. GeneReviews® [Internet].

3. INTRODUCTION Osteopenia is a well-recognized complication in GSD-I2,3
Multifactorial pathophysiology
Previous cohort studies did not include bone fractures
Rixt van der Ende, June 4th Minarich LA et al. (2012). Bone mineral density in glycogen storage disease type Ia and Ib. Genet Med. 3 Rake JP et al. (2003). Bone mineral density in children, adolescents and adults with glycogen storage disease type Ia: a cross-sectional and longitudinal study. J Inherit Metab Dis .

4. RESEARCH QUESTION
What is the prevalence of bone fractures, related to bone mass density (BMD) and bone turnover markers (BTM)?
Hypothesis: GSD-I patients with fractures have lower BMD and BTM values
Rixt van der Ende, June 4th 2015

5. MATERIALS AND METHODS Single center retrospective cohort study
59 GSD-I patients, mean age 28.8 years
Questionnaire about life-time fractures
BMD assessment of radius, femur and lumbar spine
BTM (osteocalcin, PINP, sCTX) measurement
Z-scores
Rixt van der Ende, June 4th 2015

6. RESULTS Response rate: 36 (61%) patients returned the questionnaire
Fourteen (39%) had had one or more fractures
Rixt van der Ende, June 4th 2015

7. RESULTS Mean Z-scores BMD Radius = -1.60 (±0.32) Femur = -1.20 (±0.18)
Lumbar spine = (±0.24)
Mean Z-scores BTM
Osteocalcin = (±0.21)
PINP = ( )
sCTX = (±0.16)
BTM Z-scores did not differ significantly between patients with and patients with no life-time fractures
Rixt van der Ende, June 4th 2015

8. RESULTS: Z-score radius
No fractures = (±0.34)
Fractures = -1.95
( ,00)
P = 0.013
Rixt van der Ende, June 4th 2015

9. RESULTS: Z-score femur
No fractures = (±0.22)
Fractures = (±0.31)
P = 0.061
Rixt van der Ende, June 4th 2015

10. RESULTS: Z-score lumbar spine
No fractures = -0.65
( )
Fractures = (±0.36)
P = 0.059
Rixt van der Ende, June 4th 2015

11. CONCLUSION High prevalence of life-time fractures in GSD-I patients
GSD-I patients with life time fractures:
Significantly lower radius BMD Z-score
Suggestion of lower femur and lumbar spine BMD Z-score
Close monitoring of BMD during follow up!
Rixt van der Ende, June 4th 2015

12. DISCUSSION Sample size BMD influences Age (puberty) Gender
Physical activity
Intoxications (smoking and alcohol)
Vitamin D status
Rixt van der Ende, June 4th 2015

13. FUTURE PROSPECTIVES
Association between bone fractures and metabolic control?
Supplementary vitamin D or treatment bisphosphonates in GSD-I patients
International registry
Patients from different GSD expertise centra
Rixt van der Ende, June 4th 2015

14. QUESTIONS?
Rixt van der Ende, June 4th 2015