Margaret Zacharin1,2,3, Angelina Lim1,3,4, James Gryllakis1, Aris Siafarikas5,6,7,8, Craig Jefferies9, Julie Briody10, Natasha Heather9, Janne Pitkin1,3, Jaiman Emmanuel11, Katherine J Lee1, Xiaofang Wang1, Peter J Simm1,2,3, Craig F Munns12,13. 1. Murdoch Children's Research Institute, Royal Children's Hospital, Parkville 3052, Victoria, Australia. 2. Department of Pediatrics, University of Melbourne, Parkville 3052, Victoria, Australia. 3. Department of Endocrinology, Royal Children's Hospital, Victoria, Australia. 4. Centre for Medicine Use and Safety, Monash University, Parkville 3052, Australia. 5. Department of Endocrinology and Diabetes, Perth Children's Hospital, Perth, Western Australia, Australia. 6. Faculty of Health and Medical Sciences, Paediatrics, The University of Western Australia, Nedlands, Western Australia, Australia. 7. Institute for Health Research, University of Notre Dame, Fremantle, Western Australia, Australia. 8. Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia. 9. Starship Children's health, Auckland NZ, and Liggins institute, University of Auckland, New Zealand. 10. Department of Nuclear Medicine, Children's Hospital at Westmead, Sydney, Australia. 11. Department of Radiology, Royal Children's Hospital , Parkville 3052, Victoria, Australia. 12. Department of Endocrinology, Children's Hospital at Westmead, Sydney, Australia. 13. Discipline of Paediatrics & Child Health, University of Sydney, Sydney, 2006, Australia.
Abstract
CONTEXT: Patients with glucocorticoid-dependent Duchenne muscular dystrophy (DMD) have increased fracture risk and reduced bone mineral density (BMD), often precipitating mobility loss. OBJECTIVE: To investigate use of zoledronic acid (ZA) in DMD in improving BMD. METHODS: Two arm, parallel, randomized controlled trial, set in pediatric hospitals across Australia and New Zealand. Sixty-two (31 per arm) boys with glucocorticoid-dependent DMD between 6 and 16 years were included. Five ZA infusions (0.025 mg/kg at months 0, and 3, and 0.05 mg/kg at months 6, 12, and 18), plus calcium and vitamin D, were compared with calcium and vitamin D alone. The main outcome measures were change in lumbar spine (LS) BMD raw and Z-score by dual energy absorptiometry x-ray (DXA) at 12 and 24 months, secondary outcomes assessing mobility, fracture incidence, bone turnover, peripheral quantitative computerized (pQCT) and pain scores. RESULTS: At 12 and 24 months, mean difference in changes of LS BMD Z-score from baseline was 1.2 SD (95% CI 0.9-1.5), higher by 19.3% (14.6-24.0) and 1.4 SD (0.9-1.9), higher by 26.0% (17.4-34.5) in ZA than control arms respectively (both P < .001). Five controls developed Genant 3 vertebral fractures, 0 in the ZA arm. Mobility, pain, and bone turnover markers were similar between arms at 12 and 24 months. Trabecular BMC and vBMD pQCT at radius and tibia were greater at 12 months in the ZA cohort than control; the evidence for this difference remained at 24 months for radius but not tibia. CONCLUSION: ZA improved BMD in glucocorticoid-dependent DMD boys. Although the small cohort precluded demonstrable fracture benefit, improved BMD might reduce incident vertebral fracture.
RCT Entities:
CONTEXT: Patients with glucocorticoid-dependent Duchenne muscular dystrophy (DMD) have increased fracture risk and reduced bone mineral density (BMD), often precipitating mobility loss. OBJECTIVE: To investigate use of zoledronic acid (ZA) in DMD in improving BMD. METHODS: Two arm, parallel, randomized controlled trial, set in pediatric hospitals across Australia and New Zealand. Sixty-two (31 per arm) boys with glucocorticoid-dependent DMD between 6 and 16 years were included. Five ZA infusions (0.025 mg/kg at months 0, and 3, and 0.05 mg/kg at months 6, 12, and 18), plus calcium and vitamin D, were compared with calcium and vitamin D alone. The main outcome measures were change in lumbar spine (LS) BMD raw and Z-score by dual energy absorptiometry x-ray (DXA) at 12 and 24 months, secondary outcomes assessing mobility, fracture incidence, bone turnover, peripheral quantitative computerized (pQCT) and pain scores. RESULTS: At 12 and 24 months, mean difference in changes of LS BMD Z-score from baseline was 1.2 SD (95% CI 0.9-1.5), higher by 19.3% (14.6-24.0) and 1.4 SD (0.9-1.9), higher by 26.0% (17.4-34.5) in ZA than control arms respectively (both P < .001). Five controls developed Genant 3 vertebral fractures, 0 in the ZA arm. Mobility, pain, and bone turnover markers were similar between arms at 12 and 24 months. Trabecular BMC and vBMD pQCT at radius and tibia were greater at 12 months in the ZA cohort than control; the evidence for this difference remained at 24 months for radius but not tibia. CONCLUSION:ZA improved BMD in glucocorticoid-dependent DMDboys. Although the small cohort precluded demonstrable fracture benefit, improved BMD might reduce incident vertebral fracture.
Authors: Julia Dunn; Jaclyn Tamaroff; Anna DeDio; Sara Nguyen; Kristin Wade; Nicolette Cilenti; David R Weber; David R Lynch; Shana E McCormack Journal: Front Neurosci Date: 2022-03-14 Impact factor: 5.152