S Akhtar Ali1, H Kang2, R Olney3, L Ramos-Platt4, A Ryabets-Lienhard5, C Cheung5, S Georgia6,7, P Pitukcheewanont5. 1. Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles (CHLA), 4650 Sunset Blvd, # 61, Los Angeles, CA, 90027, USA. saramakhtar@gmail.com. 2. University of Southern California, Los Angeles, CA, USA. 3. Division of Endocrinology, Nemour Children's Hospital, Jacksonville, FL, USA. 4. Center for Neurology, CHLA, Los Angeles, CA, USA. 5. Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles (CHLA), 4650 Sunset Blvd, # 61, Los Angeles, CA, 90027, USA. 6. Saban Research Institute, CHLA, Los Angeles, CA, USA. 7. Diabetes & Obesity Program, Center for Endocrinology, Diabetes and Metabolism, CHLA and Keck School of Medicine of USC, Los Angeles, CA, USA.
Abstract
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.
RANKL-OPG should be explored in DMDpatients to potentially provide targeted therapy. We quantified RANKL and OPG levels in DMDpatients compared with controls. RANKL, OPG, and RANKL:OPG significantly declined with age in DMDpatients 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 DMDpatients compared with controls and analyzed the influence of age, glucocorticoid use, ambulatory status, bone density, and fracture history. METHODS:DMDpatients 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 DMDpatients and 50 controls were enrolled. DMDpatients 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 DMDpatients 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 DMDpatients. Larger studies are needed to evaluate the role of RANKL-OPG in DMDpatients to provide better targeted therapy.