Bone Health in Adults With Duchenne Muscular Dystrophy: A Survey on Osteoporosis, Fractures and Treatment.

Background and Rationale Duchenne muscular dystrophy (DMD) is a genetic disorder caused by mutations in the dystrophin gene, resulting in progressive muscle weakness and multiple complications, including respiratory and cardiac impairment, osteoporosis (OP), and fragility fractures (FF). Bone fragility is a major concern, as lower-limb fractures may accelerate the loss of independent ambulation and complicate daily care. Despite increased life expectancy, bone health in adults with DMD remains insufficiently investigated. This study aims to address this knowledge gap and improve the understanding and management of skeletal complications in this population.

Objectives

The study aims to: (1) determine the prevalence of fragility fractures in adults with DMD; (2) identify childhood and adolescent risk or protective factors affecting adult bone health; (3) collect data on fracture treatment; (4) measure serum analytes involved in bone metabolism and bone-muscle crosstalk; and (5) identify genetic modifiers associated with increased fracture risk.

Study Population

Approximately 200 patients with DMD aged over 18 years will be recruited from 15 Italian tertiary referral centers specializing in neuromuscular diseases. A control group of healthy males aged over 18 years will be recruited exclusively at the coordinating center. Controls will undergo only a blood collection of approximately 3 mL for serum analysis.

Study Design and Procedures Patients will undergo respiratory assessment, including peak expiratory flow (PEF), forced vital capacity (FVC), and respiratory support requirements; orthopedic assessment of scoliosis, contractures, deformities, and previous spinal fusion surgery; motor function assessment using the North Star Ambulatory Assessment (NSAA); upper-limb function assessment using the Performance of the Upper Limb (PUL) scale; and the Six-Minute Walk Test (6MWT). Imaging procedures will include a lateral thoracolumbar spine radiograph (T4-L4) and dual-energy X-ray absorptiometry (DXA) of the lumbar spine (L1-L4) and total body less head (TBLH). Clinical and medical history data will be recorded using a dedicated case report form (CRF).

Biological Samples and Analyses One blood sample of approximately 3 mL will be collected for serum extraction and analysis of metabolites involved in bone metabolism and bone-muscle crosstalk. Samples will be centralized at the coordinating center and then sent to the University of Campania "Luigi Vanvitelli" for analysis. Healthy control samples will be used for comparison.

Two additional blood tubes, totaling approximately 6 mL, will be collected for DNA extraction and genome-wide association studies (GWAS), aimed at identifying genetic modifiers associated with increased fracture risk. These samples will be centralized and subsequently sent to the University of Padua for genetic analysis.

Data Management and Ethics Study data will be anonymized and managed in accordance with the General Data Protection Regulation (GDPR, EU 2016/679) and the Declaration of Helsinki. Patients and/or their legally authorized representatives will receive the study information and provide written informed consent before participation. Investigators will declare any potential conflicts of interest.

Expected Outcomes The study will characterize bone health and fragility fracture prevalence in adults with DMD, describe fracture management, and investigate clinical, developmental, biochemical, and genetic factors associated with fracture risk. The findings may help improve fracture prevention, bone health monitoring, and clinical management in this population.