A Parent Project Muscular Dystrophy-sponsored International Workshop Report on Endocrine and Bone Issues in Patients with Duchenne Muscular Dystrophy: An Ever-changing Landscape.

In April 2023, over 30 experts and advocates from four countries met in Rome, Italy to discuss unmet needs in endocrine and bone health care for individuals with Duchenne muscular dystrophy (DMD). Despite recent advances in muscle-targeted therapy, long-term glucocorticoids (GC) remain the backbone of treatment for the foreseeable future. This affirms the need to intensify efforts that will mitigate serious complications of GC therapy, including unexpected mortality due to fat embolism syndrome following bone injury and also unrecognized adrenal suppression, early loss of ambulation linked to excess weight and/or fragility fracture, adverse cardiometabolic effects of GC, the psychosocial impact of profound growth and pubertal delay/hypogonadism, and the burden to families arising from monitoring and treating endocrine and skeletal complications of GC therapy.

Pharmacological and non-pharmacological therapies for prevention and treatment of osteoporosis in Duchenne Muscular Dystrophy: A systematic review.

Background: Long term glucocorticoid treatment in Duchenne Muscular Dystrophy (DMD) is associated with a high incidence of fragility fractures. This systematic review aims to assess the current evidence for pharmacological and non-pharmacological treatment for osteoporosis in children and adults with DMD.

Methods: Three online databases (Embase, Medline, Cochrane Library) were searched for studies that evaluated interventions for treatment or prevention of osteoporosis in DMD.

Incidence of Radiologically Confirmed Fractures in Adults With Duchenne Muscular Dystrophy.

Introduction/aims: An increased risk of low trauma fractures is well documented in children and adolescents with duchenne muscular dystrophy (DMD). There is limited evidence regarding the fracture incidence of adults with DMD. The aim of this study was to examine radiologically confirmed fractures in adults with DMD and review bone health monitoring.

The Outcome of Ongoing Adult Endocrine Engagement Following Transition From Paediatric Care.

Objective: Transition is important for continuity of care for patients with chronic health conditions. The aim of this service evaluation was to determine the effectiveness of a transition clinic at a tertiary hospital with long-term attendance in the adult endocrine service.

Design: Retrospective case notes review of patients seen by paediatric endocrinology at the Royal Hospital for Children, Glasgow, at the time of transition to adult services, between 2012 and 2022.

Sexual health and fertility in Duchenne muscular dystrophy-An exploratory study.

Introduction/aims: Recent clinical guidelines recommend that adolescents with Duchenne muscular dystrophy (DMD) who are on daily glucocorticoid treatment should be offered pubertal induction in order to ensure adult levels of sex hormones as they reach adulthood. However, it remains unclear how gonadal status, including androgen concentrations, impacts physical function and future fertility. The aim of this study was to give a voice to adults with DMD, exploring their perspectives around sexual health, hormone treatment, and fertility.

Frequency of Delayed Puberty in Boys with Contemporary Management of Duchenne Muscular Dystrophy.

Objective: Delayed puberty is thought to be common in boys with Duchenne muscular dystrophy (DMD) treated with long term oral glucocorticoid. The aim of this study was to report the frequency of delayed puberty in DMD from examination by a paediatric endocrinologist alongside detailed endocrine investigations.

Methods: All boys with DMD aged at least 14 years in January 2022 known to the paediatric neuromuscular service (2016-2022) were included.

Severity of acute phase reaction in children receiving the first dose of zoledronic acid and the impact of the underlying condition: a cross-sectional study.

Introduction: Zoledronic acid (ZA), used for treatment of children with osteoporosis, can cause acute phase reaction (APR) following the first infusion. Many institutions have a policy to admit and monitor all children for their first ZA infusion.

Objective: To determine if the APR with the first ZA dose warrants hospital-level care and evaluate if its severity correlates with the underlying condition.

Anti-RANKL Therapy Prevents Glucocorticoid-Induced Bone Loss and Promotes Muscle Function in a Mouse Model of Duchenne Muscular Dystrophy.

Bisphosphonates prevent bone loss in glucocorticoid (GC)-treated boys with Duchenne muscular dystrophy (DMD) and are recommended as standard of care. Targeting receptor activator of nuclear factor kappa-B ligand (RANKL) may have advantages in DMD by ameliorating dystrophic skeletal muscle function in addition to their bone anti-resorptive properties. However, the potential effects of anti-RANKL treatment upon discontinuation in GC-induced animal models of DMD are unknown and need further investigation prior to exploration in the clinical research setting.

Emergency and perioperative management of adrenal insufficiency in children and young people: British Society for Paediatric Endocrinology and Diabetes consensus guidance.

Adrenal insufficiency (AI) is characterised by lack of cortisol production from the adrenal glands. This can be a primary adrenal disorder or secondary to adrenocorticotropic hormone deficiency or suppression from exogenous glucocorticoids. Symptoms of AI in children may initially be non-specific and include growth faltering, lethargy, poor feeding, weight loss, abdominal pain, vomiting and lingering illnesses.

The Physiology and Mechanisms of Growth.

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The prevalence of hypertension in paediatric Turner syndrome: a systematic review and meta-analysis.

Cardiovascular related deaths account for over 40% of the excess mortality in Turner syndrome (TS). Hypertension, a modifiable risk factor for both aortic dilatation and dissection, is more commonly encountered in TS during childhood and adolescence. Treatment of hypertension is currently recommended beyond the age of 16 years in TS to help reduce the risk of aortic dissection.

The effect of COVID-19 on the presentation of thyroid disease in children.

Introduction: Although studies suggest a potential link between COVID-19 and thyroid dysfunction in adults, there are insufficient data to confirm that association in children, and whether there is any effect on presentation to healthcare services.

Aims: To identify whether presentations of thyroid dysfunction in children to a tertiary paediatric hospital changed as a result of the COVID-19 pandemic.

Methods: A retrospective case note review was conducted of all children with abnormal thyroid function tests between 1 January 2016 and 31 December 2021 at a tertiary paediatric endocrine centre in the United Kingdom.

Objective and subjective measures of sleep in men with Muscular Dystrophy.

Purpose: Despite poor sleep quality being recognised in Duchenne Muscular Dystrophy, reports from milder forms of Muscular Dystrophy (MD), and accompanied associations with quality of life (QoL), pain and fatigue, remain limited however.

Methods: Adult males (n = 15 Beckers MD (BMD), n = 12 Limb-Girdle MD (LGMD), n = 12 Fascioscapulohumeral (FSHD), n = 14 non-MD (CTRL)) completed assessments of body composition (Bio-electrical impedance), sleep (7-day 24-hour tri-axial accelerometer, Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index, QoL (SF36-v2), pain (Visual analogue scale), fatigue (Modified Fatigue Index Scale) and functional assessments (Brookes and Vignos).

Results: FSHD and BMD reported worse sleep than CTRL on the PSQI.

3T-MRI-based age, sex and site-specific markers of musculoskeletal health in healthy children and young adults.

Objective: The aim of this study is to investigate the role of 3T-MRI in assessing musculoskeletal health in children and young people.

Design: Bone, muscle and bone marrow imaging was performed in 161 healthy participants with a median age of 15.0 years (range, 8.

Pathogenesis of Musculoskeletal Deficits in Children and Adults with Inflammatory Bowel Disease.

Musculoskeletal deficits are among the most commonly reported extra-intestinal manifestations and complications of inflammatory bowel disease (IBD), especially in those with Crohn's disease. The adverse effects of IBD on bone and muscle are multifactorial, including the direct effects of underlying inflammatory disease processes, nutritional deficits, and therapeutic effects. These factors also indirectly impact bone and muscle by interfering with regulatory pathways.

Observer Agreement of Vertebral Fracture Grading Using Dual Energy Absorptiometry Vertebral Fracture Assessment in Duchenne Muscular Dystrophy.

Routine screening of the spine for vertebral fracture is recommended in the recent international standards of care for boys with Duchenne muscular dystrophy (DMD). Recent international consensus endorses the use of dual energy absorptiometry vertebral fracture assessment for identification of vertebral fractures in children, which could be used instead of spine radiographs. This study aims to evaluate the inter-observer agreement for vertebral fracture classification in boys with DMD, and the impact on clinical management.

Skeletal disproportion in girls with Turner syndrome and longitudinal change with growth-promoting therapy.

Objective: Short stature in Turner syndrome (TS) may be accompanied by skeletal disproportion. This retrospective study investigates growth and disproportion from early childhood to adult height.

Study Design: Data were collected from 59 girls prior to growth hormone (rhGH) treatment and in 30 girls followed up longitudinally.

Clinical utility of urinary gonadotrophins in hypergonadotrophic states as Turner syndrome.

Background Girls with Turner syndrome (TS) are at an increased risk of primary ovarian insufficiency (POI). Good correlation between serum and urinary gonadotrophins exists in children assessed for disorders of puberty, but there is little evidence of their reliability in hypergonadotropic states. Objectives To determine whether there was a correlation between serum and urinary Luteinising Hormone (uLH) and Follicle-Stimulating Hormone (uFSH) in hypergonadotrophic states, and whether uFSH could suggest an ovarian failure in TS as Anti-Mullerian Hormone (AMH).

Muscle deficits with normal bone microarchitecture and geometry in young adults with well-controlled childhood-onset Crohn's disease.

Background: Muscle-bone deficits are common in pediatric Crohn's disease; however, few studies have assessed long-term musculoskeletal outcomes in adults with childhood-onset Crohn's disease. This study assessed the prevalence of musculoskeletal deficits in young adults with childhood-onset Crohn's disease compared with healthy controls.

Methods: High-resolution MRI and MR spectroscopy were used to assess bone microarchitecture, cortical geometry and muscle area, and adiposity at distal femur and bone marrow adiposity (BMA) at lumbar spine.

A comparison of the bone and growth phenotype of , and murine models with the C57BL/10 wild-type mouse.

The muscular dystrophy X-linked () mouse is commonly used as a mouse model of Duchenne muscular dystrophy (DMD). Its phenotype is, however, mild, and other mouse models have been explored. The mouse carries a human-like mutation in the gene and has a severe muscle phenotype, but its growth and bone development are unknown.