Evaluating RANKL and OPG levels in patients with Duchenne muscular dystrophy.
RANKL-OPG should be explored in DMD patients to potentially provide targeted therapy. We quantified RANKL and OPG levels in DMD patients compared with controls. RANKL, OPG, and RANKL:OPG significantly declined with age in DMD patients suggesting some bone turnover markers are difficult to assess or use as therapeutic indicators.


INTRODUCTION
Osteoporosis in Duchenne muscular dystrophy (DMD) is multi-factorial in nature with high prevalence of fractures. RANKL-OPG should be explored to potentially provide targeted therapy for these patients. We quantified RANKL, OPG, and RANKL:OPG levels in DMD patients compared with controls and analyzed the influence of age, glucocorticoid use, ambulatory status, bone density, and fracture history.


METHODS
DMD patients were enrolled at CHLA. Controls were recruited from general pediatric clinic and in collaboration with samples from a previously completed study. Free soluble RANKL and OPG levels were quantified using a sandwich ELISA.


RESULTS
Fifty DMD patients and 50 controls were enrolled. DMD patients had a significant decline in RANKL, OPG, and RANKL:OPG with age (p = < 0.0001, p = 0.026, and p = 0.002, respectively) while healthy controls showed no significant change. RANKL trended lower in patients on glucocorticoids (p = 0.05), attributed to the significantly older age in the treatment group. RANKL and RANKL:OPG levels were significantly lower in the non-ambulatory group compared with the ambulatory group (p = 0.010 and 0.036 respectively), again likely due to their older age. There was no correlation of RANKL, OPG, or RANKL:OPG with DXA Z-score or presence of vertebral fractures.


CONCLUSION
There was significant decline in RANKL, OPG, and RANKL:OPG with age in DMD patients compared with controls, potentially due to disease severity or worsening osteoblastic function. This suggests some bone turnover markers may be difficult to assess or use as therapeutic indicators in DMD patients. Larger studies are needed to evaluate the role of RANKL-OPG in DMD patients to provide better targeted therapy.
['Akhtar Ali|S|S|', 'Kang|H|H|', 'Olney|R|R|', 'Ramos-Platt|L|L|', 'Ryabets-Lienhard|A|A|', 'Cheung|C|C|', 'Georgia|S|S|', 'Pitukcheewanont|P|P|']
D015502:Absorptiometry, Photon D015415:Biomarkers D015519:Bone Density D016723:Bone Remodeling D016022:Case-Control Studies D002648:Child D003430:Cross-Sectional Studies D004797:Enzyme-Linked Immunosorbent Assay D005260:Female D005938:Glucocorticoids D006801:Humans D008297:Male D020388:Muscular Dystrophy, Duchenne D010024:Osteoporosis D053244:Osteoprotegerin D053245:RANK Ligand D016103:Spinal Fractures
RANKL OPG Muscular dystrophy Osteoporosis