Bone Abstracts (2016) 5 OC5.6 | DOI: 10.1530/boneabs.5.OC5.6

The metabolic alterations behind bone fragility in Duchenne muscular dystrophy

Francesca Broggi1, Silvia Vai1, Lorenzo Maggi2, Ksenija Gorni3, Grazia D’Angelo4, Marika Pane5 & Maria Luisa Bianchi1


1Experimental Laboratory for Children’s Bone Metabolism Research, Bone Metabolism Unit Istituto Auxologico Italiano IRCCS, Milano, Italy; 2Unità Operativa Malattie Neuromuscolari Istituto Nazionale Neurologico C. Besta IRCCS, Milano, Italy; 3Centro Clinico Nemo Ospedale Niguarda, Milano, Italy; 4Istituto Medea IRCCS La Nostra Famiglia, Bosisio Parini, Italy; 5Dipartimento Neurologia Pediatrica Policlinico Universitario Gemelli Università Cattolica, Roma, Italy.


Low bone mineral density (BMD) and an increased rate of both peripheral and vertebral fractures have been observed in patients with Duchenne muscular dystrophy (DMD), but studies on bone metabolic alterations in this disease are still very few.

We are now presenting the preliminary findings of an ongoing multicenter, prospective study aimed to identify the characteristics of DMD boys carrying a higher risk of bone loss and fractures, through the evaluation of BMD, bone turnover parameters, and genetic configuration.

On 37 DMD boys (mean age 10.6±3.2 years), we evaluated BMD (by DXA), bone mineral apparent density (BMAD), bone turnover markers (plasma osteocalcin (OC); serum bone-specific alkaline phosphatase (BSAP) and C-terminal telopeptide (CTx); urinary N-terminal telopeptide (NTx)), serum osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL) and (for the first time in DMD boys) serum Dickkopf related protein 1 (Dkk1).

At baseline evaluation, 28/37 patients (75.7%) had a significantly reduced lumbar spine BMAD (Z-score ≤−2). OC was 50.42±22.28 ng/ml; BSAP 23.13±8.58 pg/ml; CTx 738.20±349.26 ng/ml; NTx 333.92±251.82 nMBCE/mMCR. While bone formation markers (OC, BSAP) were within normal range for age, bone resorption markers (CTx, NTx) were increased (P<0.05). The RANKL/OPG ratio was significantly higher than normal (112.3±107.2; normal controls 28±11; P<0.001), while Dkk1 was lower than normal (17.44±17.1 pg/ml; normal controls 37±18.3 pg/ml; P<0.02). Significant correlations were observed between RANKL/OPG ratios and BMAD Z-scores (P=0.03) and between Dkk1 levels and BMAD Z-scores (P<0.005).

These data confirm that the BMD reduction observed in DMD seems due to increased bone resorption. Moreover, the imbalance between RANKL and OPG, and the insufficient compensation due to Dkk1 reduction could also concur in determining the low BMD and increased fragility fracture risk in boys affected by DMD, although further studies are needed to confirm this hypothesis.

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