1 Introduction

Over the past two decades, corticosteroids have become part of the standards of care in duchenne muscular dystrophy (DMD) as a disease-modifying therapy initiated in childhood, with ongoing use throughout affected individuals' lifespans. The use of corticosteroids has led to significant improvements in various clinical outcomes such as enhanced survival, delayed age at loss of ambulation, and positive effects on cardio-respiratory outcomes [1]. They are also used with the aim of preserving upper limb function even after loss of ambulation, and in reducing the need for spinal surgery for severe scoliosis [1, 2].

Whilst there is documented evidence of the benefits of corticosteroids in DMD, their use is associated with a range of significant side-effects including osteoporosis [3-5]. Osteoporosis leading to low trauma fractures in long bones and vertebrae is reported in up to 75% of children and adolescents with DMD treated with corticosteroids [6]. The incidence of clinical fractures (long bone fractures, and vertebral fractures presenting with significant back pain without spine screening) in children and adolescents with DMD is approximately four times higher than in healthy counterparts [5]. Information on fractures in adults with DMD is scarce and not well-studied. With the increased utilization of corticosteroids, and advancements in coordinated multi-disciplinary care, there is a growing population of adults with DMD [7, 8], warranting a focus on extra-skeletal health outcomes in addition to skeletal outcomes.

To complement the latest recommendations on bone health monitoring and management outlined in the International Care Considerations for DMD (2018) which is primarily targeted at pediatric management [9, 10], the United Kingdom Adult NorthStar Network released a consensus document providing clinical guidance in 2020 for the management of adults with DMD [11]. The document includes some general guidance on monitoring and management of osteoporosis for adults [11]. A comprehensive understanding of the scope of skeletal morbidity and its management in the adult population is essential for the development of more detailed guidance in this area. This analysis seeks to examine clinical fractures in adults with DMD in the West of Scotland, as well as to review bone health monitoring measures.

2 Methods

This retrospective 10 year review included all adults with DMD aged at least 16 years in 2022, and under the care of adult neurology and/or respiratory physicians in the West of Scotland between 1st January 2013 and 31st December 2022. The diagnosis of DMD was confirmed genetically. Clinical characteristics were sourced from online clinical records, incorporating both local and regional health databases. To be included in the study, individuals were required to have undergone at least two clinical follow-up visits in the adult clinic between 2013 and 2022. Radiologic images for all people in Scotland are stored in the digital national picture archiving and communication system (PACS). A review of PACS was conducted to ascertain if radiological examinations were performed, and radiology reports by consultant radiologists were used to ascertain if there were fractures. This process aimed to identify fractures throughout the follow-up period (2013–2022) for each individual, enabling the retrieval of all fractures imaged anywhere in Scotland. Electronic clinical records were screened to capture any fractures that were sustained outside of Scotland.

This study was conducted as an evaluation of clinical practice and clinical audit focused on the monitoring and management of bone fragility in adults with DMD. The study was registered as a clinical audit with our health board, NHS Greater Glasgow and Clyde (audit registration number INSCLIN2024-05). The investigation adhered to existing guidelines for clinical audit/service evaluation and was in accordance with the regulations set by the United Kingdom National Health Service Health Research Authority [12]. Formal ethical approval and written informed consent were deemed unnecessary. This study strictly followed the principles outlined in the Declaration of Helsinki.

3 Results

4 Discussion

This retrospective analysis of the fracture burden in adults with DMD revealed that approximately 14% experienced new low-trauma fractures, confirmed radiologically throughout the follow-up period.

The overall fracture incidence in men with DMD was more than double that of UK men aged 18–49 years (94.8 per 10,000 person-years) [13], while the fracture incidence among those with DMD treated with corticosteroids was over nine times higher than the national average. Fractures in healthy young men typically result from significant trauma, whereas nearly all fractures observed in our cohort of men with DMD were categorized as low-trauma fractures. Our data collection also encompassed the period of the coronavirus pandemic, during which the behavior and activity patterns of individuals, particularly those in higher-risk “shielding” groups like men with DMD, were notably altered. These changes may have influenced and potentially decreased the fracture burden in our report as reduced mobility and limited community interactions could have resulted in fewer instances of transferring and traveling outside their homes. In our study 14% of men developed new low trauma fracture during follow-up in the adult clinic. On the other hand, a recent retrospective review in a cohort of adult men with DMD reported that osteoporosis was observed in 54.7%, which is assumed to be cumulative impact from childhood [8]. That report did not clarify the definition of osteoporosis.

The frequency of fragility fractures in growing children and adolescents with DMD has been better characterized. Published studies indicate that approximately 50% of children and adolescents with DMD, regardless of corticosteroid use, experience clinical low-trauma fractures of the long bones or vertebral fractures presenting with severe back pain [4]. Among those treated with daily corticosteroids, the frequency of fractures can be as high as 75% with long term follow-up [6]. A recent pediatric study analyzing 564 boys with DMD and complete corticosteroid records in the UK NorthStar database (2006–2015) identified a fracture incidence rate of 468 per 10,000 person-years [5], approximately four times higher than that of healthy boys. These findings suggest a potentially lower overall fracture incidence in adults with DMD (based on our results) compared to growing children and adolescents. This could be due to the fact that low-trauma long bone fractures may become less common following loss of ambulation. Yet, our report underscores that fractures in adults with DMD can still occur during day-to-day activities such as stretching and transfers without any trauma. While fracture incidence may appear lower in adults with DMD compared to younger individuals with DMD, fractures in people with complex health needs and physical disabilities often exert a substantial impact on quality of life and pose an increased burden on caregivers and families. Hence, fractures, even if categorized as “minor” in clinical terms within this population, should not be dismissed or trivialized.

Vertebral fractures are now recognized as a hallmark of glucocorticoid-associated osteoporosis and serve as a clinical indicator of osteoporosis in young individuals regardless of DXA bone density [14]. Recent International Care Considerations for bone health monitoring in DMD [10] advocate for regular lateral spine imaging to detect vertebral fractures, emphasizing that relying solely on symptoms may underestimate their frequency in this high-risk population. In a previous study, following an average of 4 years of daily corticosteroid exposure, 40% of young children with DMD were found to have vertebral fractures based on spine imaging [15]. In our present study, no new painful vertebral fractures were observed in adults with DMD.

The introduction of routine spine imaging in our pediatric neuromuscular services since 2016 aligns with International Care Considerations (2018) [10]. Clinical guidance from the UK Adult NorthStar network (2020), also recommends lateral spine imaging for vertebral fracture identification and DXA for bone density monitoring but the frequency of this should be individualized [11]. Practical challenges in implementation of bone monitoring include difficulties in image acquisition (such as the need for appropriate hoisting facilities and patient reluctance to be hoisted) and interpretation (due to severe scoliosis or metal instrumentation for severe scoliosis). Our audit revealed that only a small number of adult men with DMD underwent bone monitoring with lateral spine imaging and DXA bone density assessment, highlighting the need for enhanced national/international guidance and local pathways during periods of transition.

The current report is limited by several factors, notably the relatively small sample size and limitations in data collection. Clinical data were sourced from electronic health records (introduced in 2010), which have been in widespread use at our hospital since 2013. As a result, we encountered difficulties in tracking fracture occurrences from childhood through adulthood. Additionally, the restricted availability of routine lateral spine imaging in our adult cohort prevented a comprehensive study of vertebral fracture incidence in this cohort of adults. Despite these limitations, it is noteworthy that we did not observe any confirmed cases of new painful vertebral fracture. Nonetheless, this report documents the incidence of radiologically confirmed fractures in adults with DMD, providing valuable insights into this aspect of the condition.

5 Conclusion

In summary, our findings underscore the persistent occurrence of radiologically confirmed low-trauma long bone fractures in adults with DMD, which is particularly high among those on corticosteroid treatment. Considering the multifaceted health challenges faced by men with DMD, there is a clear need for enhanced and nuanced clinical guidance regarding the monitoring and management of bone health during transitions and throughout adulthood. Fractures in adults with complex health conditions and physical limitations can significantly impair quality of life and place additional strain on caregivers, highlighting the importance of not overlooking their impact.

Author Contributions

Gavin Langlands: data curation, formal analysis, writing – original draft. Jennifer McKechnie: data curation, writing – review and editing. Maria E. Farrugia: conceptualization, writing – review and editing. Sze Choong Wong: conceptualization, supervision, writing – review and editing.

Ethics Statement

We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Conflicts of Interest

The authors declare no conflicts of interest.