Endocrine treatment in Duchenne muscular dystrophy – current practices and future directions

In this issue of JPEM, two articles are devoted to the endocrinological treatment of boys with Duchenne muscular dystrophy (DMD) [1], 2]. DMD is a severe X-linked genetic disorder that causes progressive muscle degeneration, leading to disability and shortened life expectancy. To date, there is no curative treatment for the disease. The chronic use of glucocorticoids is a standard treatment delaying the progression of muscle weakness [3]. Glucocorticoid treatment is usually initiated from the age of 4–5 years. But its use leads to significant endocrine complications, in particular growth retardation, delayed puberty and osteoporosis implying a high disease but also psychosocial burden on boys with DMD. In light of these challenges, the use of testosterone to induce puberty and bisphosphonates to treat osteoporosis has become an integral part of the care of young people with DMD.

The scoping review by Sodero et al. highlights the importance of testosterone therapy in boys with DMD who experience delayed puberty [1]. The review pooled data from six trials involving 58 paediatric patients and showed that testosterone therapy was effective in inducing puberty, leading to the appearance of secondary sexual characteristics and improvements in bone health. The trials did not report any major side effects, and three of them found improvements in patients’ quality of life. The results of this review highlight the potential benefits of testosterone therapy, not only in ensuring normal pubertal development but also in improving the overall wellbeing of these patients. However, the authors also acknowledged the limitations of the available evidence, particularly the small sample sizes and lack of standardised treatment protocols, which point to the need for larger, more comprehensive trials to confirm the long-term efficacy and safety of these interventions.

On the other hand, the international survey conducted by McCarrison et al. sheds light on current clinical practice in the management of delayed puberty and osteoporosis in DMD patients [2]. The survey found significant variability among clinicians in the use of both bisphosphonates for osteoporosis and testosterone for pubertal induction. While more than 80 % of clinicians initiate bisphosphonate therapy after a vertebral or long bone fracture, a significant percentage would consider initiating therapy in the absence of a fracture, particularly if there were signs of declining bone health. For testosterone therapy, the majority of clinicians reported starting testosterone treatment between the ages of 12 and 14 years, with intramuscular injections being the most common method. However, the duration of testosterone therapy varied, with some clinicians using short courses and others extending treatment into adulthood. The variation in practice highlights the lack of clear guidelines and consensus on the optimal timing, duration and methods of both testosterone and bisphosphonate therapy in DMD.

The differences in clinical practice identified by McCarrison et al. highlight the need for further clarification and standardisation in the management of these endocrine complications in DMD. The revised 2018 DMD Care Considerations provide general recommendations but lack detailed guidance on long-term management, particularly in relation to the transition to adult care [3], 4]. In addition, while the guidelines suggest starting testosterone therapy at the onset of pubertal delay (≥14 years of age), there is no consensus on when to start osteoporosis treatment or whether it should be administered proactively before fractures occur [4]. For the latter in particular, there is still insufficient evidence to start intravenous therapy in children, which can be burdensome and stressful for families and children. Furthermore, there is a paucity of clearly defined outcome measures and biomarkers to monitor the effects of treatment and to define stopping criteria.

Together, these two studies highlight the need for a more structured approach to the management of endocrinological issues in DMD. Although promising, the evidence is still at an early stage and more robust clinical trials are needed to determine the most effective treatment protocols. Given the rarity of DMD, it is challenging to conduct large-scale trials, but it is essential to gather data from smaller clinical trials or registries that can help formulate more precise treatment guidelines.

The psychosocial impact of these treatments also deserves attention. In particular, delayed puberty is not just a physical challenge for people with DMD – it affects their self-esteem, body image and overall quality of life. Addressing these issues through timely and effective treatment can significantly improve patients’ psychological well-being, as shown in the studies reviewed by Sodero et al. [1]. Therefore, endocrinologists and other healthcare providers should take a holistic approach, considering both physical and psychological outcomes when planning and monitoring treatment.

In conclusion, while current practices in the management of DMD-associated endocrine disorders offer hope, significant gaps remain in our understanding of how best to manage these patients in the long term. It is essential that treatment protocols continue to be refined and that more data from clinical trials or registries are collected to establish treatment recommendations and thus to guide clinicians in providing the best possible care for children and adolescents with DMD. Attention must also be paid to the psychosocial aspects of these treatments to ensure that patients achieve not only physical health but also a better quality of life. With ongoing research and international collaboration, the future of DMD treatment holds the promise of more effective and personalised care.