Risk Factors Associated with Incident Vertebral Fractures in Steroid-treated Males with Duchenne Muscular Dystrophy
Kim Phung, Laura McAdam, Jinhui Ma, Hugh J McMillan, Stefan Jackowski, Maya Scharke, Mary-Ann Matzinger, Nazih Shenouda, Khaldoun Koujok, Jacob L Jaremko, Nagwa Wilson, Scott Walker, Colleen Hartigan, Nasrin Khan, Marika Page, Marie-Eve Robinson, David S Saleh, Kevin Smit, Frank Rauch, Kerry Siminoski, Leanne M Ward- Biochemistry (medical)
- Clinical Biochemistry
- Endocrinology
- Biochemistry
- Endocrinology, Diabetes and Metabolism
Abstract
Purpose
Prevention of fractures is an unmet need in glucocorticoid (GC)-treated Duchenne muscular dystrophy. This study explored factors associated with incident vertebral fractures (VFs) to inform future fracture prevention efforts.
Methods
VFs were evaluated prospectively at study baseline and 12 months on lateral spine radiographs in participants aged 4 to 25 years with Duchenne muscular dystrophy. Clinical factors were analyzed for their association with the change in Spinal Deformity Index (sum of the Genant-defined VF grades from T4 to L4) between baseline and 12 months.
Results
Thirty-eight males were evaluated (mean ± SD age at baseline 11.0 ± 3.6 years; mean ± SD GC duration at baseline 4.1 ± 3.1 years; 74% ambulatory). Nine of 38 participants (24%) had 17 incident VFs, of which 3/17 VFs (18%) were moderate/severe. Participants with 12-month incident VF had lower mean ± SD baseline lumbar spine areal bone mineral density Z-scores (−2.9 ± 1.0 vs −1.9 ± 1.1; P = .049) and lower total body less head areal bone mineral density Z-scores (−3.1 ± 1.2 vs −1.6 ± 1.7; P = .036). Multivariable linear regression showed that at least 1 VF at baseline (P < .001), a higher number of antecedent non-VF (P < .001), and greater bone age delay at baseline (P = .027) were significant predictors of an increase in the Spinal Deformity Index from baseline to 12 months.
Conclusion
The observation that ≥ 1 prevalent VF and/or non-VF were the strongest predictors of incident VFs at 12 months supports the need for prevention of first fractures in this high-risk setting. Bone age delay, a marker of GC exposure, may assist in the prioritization of patients in efforts to prevent first fractures.