The role of delayed bone age in the evaluation of stature and bone health in glucocorticoid treated patients with Duchenne muscular dystrophy

E J Annexstad,I Holm,K Godang,A G Myhre,J Westvik,M Rasmussen,J Bollerslev

doi:10.1186/s13633-019-0070-0

Abstract

BackgroundLow bone mineral density and an increased risk of appendicular and vertebral fractures are well-established consequences of Duchenne muscular dystrophy (DMD) and the risk of fractures is exacerbated by long-term glucocorticoid treatment. Monitoring of endocrine and skeletal health and timely intervention in at-risk patients is important in the management of children with DMD.MethodsAs part of the Norwegian Duchenne muscular dystrophy cohort study, we examined the skeletal maturation of 62 boys less than 18 years old, both currently glucocorticoid treated (n = 44), previously treated (n = 6) and naïve (n = 12). The relationship between bone age, height and bone mineral density (BMD) Z-scores was explored.ResultsThe participants in the glucocorticoid treated group were short in stature and puberty was delayed. Bone age was significantly delayed, and the delay increased with age and duration of treatment. The difference in height between glucocorticoid treated and naïve boys was no longer significant when height was corrected for delayed skeletal maturation. Mean BMD Z-scores fell below − 2 before 12 years of age in the glucocorticoid treated group, with scores significantly correlated with age, duration of treatment and pubertal development. When BMD Z-scores were corrected for by retarded bone age, the increase in BMD Z-scores was significant for all age groups.ConclusionOur results suggest that skeletal maturation should be assessed in the evaluation of short stature and bone health in GC treated boys with DMD, as failing to consider delayed bone age leads to underestimation of BMD Z-scores and potentially overestimation of fracture risk.

Highlights

Low bone mineral density and an increased risk of appendicular and vertebral fractures are wellestablished consequences of Duchenne muscular dystrophy (DMD) and the risk of fractures is exacerbated by long-term glucocorticoid treatment
Several studies have described a higher incidence of low-trauma long-bone fractures in steroid-naïve boys with DMD compared to the normal population [5, 6], and a significantly increased risk of appendicular and vertebral fractures in glucocorticoid (GC) treated DMD [7]
We examined the extent of delay in skeletal maturation and the relationship between bone age delay, growth and Dual-energy X-ray absorptiometry (DXA) measured Bone Mineral Density (BMD) Z-scores in GC treated boys with DMD

Summary

Introduction

Low bone mineral density and an increased risk of appendicular and vertebral fractures are wellestablished consequences of Duchenne muscular dystrophy (DMD) and the risk of fractures is exacerbated by long-term glucocorticoid treatment. The physiological process of bone modelling and remodelling in childhood involves complex and sensitive endocrine and immunological signalling systems, which may be affected by factors such as physical conditioning, poor linear growth, obesity, pubertal delay, vitamin D deficiency, and alterations in calcium homeostasis [1, 2]. Low Bone Mineral Density (BMD) and an increased risk of fractures is a well-established consequence of many chronic diseases in childhood, including Duchenne muscular dystrophy (DMD) [3, 4]. Steroid induced obesity, poor linear growth [13], hypogonadism and pubertal delay [14] add to the complexity of bone health evaluation in GC treated DMD [15]

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