Bone Fragility and Fracture Characteristics in Patients With Spinal and Bulbar Muscular Atrophy

Abstract

Background: Spinal and bulbar muscular atrophy (SBMA) is a hereditary neuromuscular disorder linked to androgen receptor gene mutations, often associated with metabolic abnormalities. We aimed to investigate the incidence of fragility fractures and the underlying mechanisms in SBMA.

Methods: Consecutive genetically confirmed SBMA patients and healthy controls (HC) were enrolled. We surveyed fracture history and assessed motor function, bone metabolism markers, and bone mineral density (BMD) using dual-energy X-ray absorptiometry. Longitudinal BMD changes were also analyzed between SBMA patients and HC.

Results: A total of 109 SBMA patients and 21 HC were included. Fragility fractures in SBMA patients were mainly observed in cortical bone-dominant regions. Their lower limb BMD was significantly reduced (SBMA 1.10 g/cm, HC 1.19 g/cm; p < 0.05) and further decreased overtime. Despite low bone resorption markers, bone formation markers showed no difference between the groups, suggesting that SBMA patients exhibit characteristics of low turnover osteoporosis. Serum 25-hydroxyvitamin D levels were lower in SBMA patients than in HC (15.4 ng/mL vs. 19.4 ng/mL; p < 0.01). Longitudinal analysis revealed that SBMA patients had a higher incidence of fragility fractures than HC (log-rank test, p < 0.05), with the first fragility fracture occurring 10 years after the onset of muscle weakness. Low baseline BMD was a predictor of fragility fractures (adjusted OR = 0.32; 95% CI: 0.17-0.60; p < 0.05).

Conclusions: SBMA patients have a high fragility fracture incidence, particularly in cortical bone, with a progressive BMD decrease. Low bone turnover and vitamin D deficiency are associated with these fractures.

Keywords: Bone; Bone Density; Bulbo‐Spinal Atrophy; Fractures; Osteoporosis; Vitamin D; X‐Linked.