Bone Abstracts

Objectives: Low bone mineral density (BMD) and increased frequency of peripheral and vertebral fractures have been reported in boys with Duchenne muscular dystrophy (DMD), but studies on the determinants of low BMD are still very few. We are currently carrying out a multicenter, prospective study aimed to identify the characteristics of DMD boys with a higher risk of bone loss and fractures.

Methods: Forty-two DMD boys (mean age 9.9±3.3 years) underwent BMD evaluation (by dual energy X-ray absorptiometry (DXA), with calculation of bone mineral apparent density (BMAD)), evaluation of bone turnover markers (plasma osteocalcin (OC); serum bone-specific alkaline phosphatase (BSAP) and C-terminal telopeptide (CTx)), serum osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), interleukin 6 (IL-6), and (for the first time in DMD) serum Dickkopf related protein 1 (Dkk1). All subjects were on long-term glucocorticoid (GC) treatment.

Results: At baseline DXA evaluation, 32/42 (76.2%) patients had Z-score spine BMAD ≤2.0; 9/42 (21.4%) patients had sustained at least one vertebral fracture (all at thoracic spine; eight of nine patients with fractures were aged ≥11 years); and 10/42 patients (23.8%) had serum 25OH-vitamin D levels <20 ng/ml. Bone formation markers (OC, BSAP) were within normal range for age, while bone resorption markers (CTx) were increased (P<0.05). The RANKL/OPG ratio was significantly higher than normal (78.2±37.4 vs 28±11 in normal controls; P<0.001), while Dkk1 was lower than normal (25.3±19 pg/ml vs 37±18.3 pg/ml in normal controls; P<0.02). BMAD Z-scores were significantly correlated (inversely) with age (P<0.01) and duration of GC treatment (P=0.02), and also (directly) with 25OH-vitamin D levels (P<0.01). Significant inverse correlations were found between BMAD Z-scores and Dkk1 levels (P<0.01) and between BMAD Z-scores and IL-6 (P<0.05).

Conclusion: In our study, spine BMD in DMD children was influenced by age and steroids (i.e. higher age or prolonged GC treatment corresponded to lower BMD). Other relevant determinants were 25OH-vitamin D status, IL-6 levels, imbalance between RANKL and OPG with insufficient compensation due to Dkk1 reduction.

Funding: The study was supported by a grant from Parent Project Italy.

Disclosure: The authors declared no competing interests.