New Steroid May Spare Bone Markers Suppressed by Prednisone

TOPLINEBoys with Duchenne muscular dystrophy (DMD) who were treated with prednisone showed reductions in multiple blood markers of bone and cartilage, whereas those treated with vamorolone did not show these changes and the markers returned toward baseline after switching from prednisone to vamorolone.METHODOLOGYResearchers analyzed data from a randomized double-blind trial (2018-2021) to identify blood biomarkers associated with prednisone-related changes in bone and cartilage and to compare prednisone with vamorolone.They included 121 steroid-naive boys with DMD, aged 4 to less than 7 years, who could perform time to stand from supine in less than 10 seconds.Participants were randomly assigned to 24 weeks of placebo, prednisone (0.75 mg/kg/d), or vamorolone (6 mg/kg/d) in the first period. After a 4-week taper/washout, the placebo and prednisone groups switched to vamorolone for a second 24-week period.The team measured clinical markers of bone turnover (alkaline phosphatase [ALP], osteocalcin, procollagen type I N propeptide [P1NP], and type 1 collagen cross-linked C-telopeptide [CTX1]) and tracked growth (height z score) using blood samples at baseline and weeks 12, 24, 28, 40, and 48.Proteomics was performed on serum at baseline and weeks 12, 24, and 48, and roughly 7000 proteins were assayed to identify prednisone-specific changes in bone- and cartilage-related proteins.TAKEAWAYPrednisone was associated with reductions in traditional bone turnover markers compared with placebo: alkaline phosphatase (ALP) by 39%, osteocalcin by 24%, P1NP by 37%, and CTX1 by 35% (P < .001 for all), while vamorolone did not significantly alter these markers.Proteomics analysis identified 10 serum proteins reduced in prednisone group but not in vamorolone group, each corresponding to genes causing genetic disorders of bone or cartilage.Change in height z-score over 24 weeks correlated most strongly with change in ALP.All 10 novel biomarkers returned to baseline levels after participants crossed over from prednisone to vamorolone.IN PRACTICE"Vamorolone did not result in significant changes of these growth-related biomarkers, and cross-over from prednisone to vamorolone restored all biomarkers to pre-treatment (placebo) levels. They may be useful to monitor hypertrophic chondrocyte function (cellular activity) in DMD and other disorders," the authors of the study wrote.SOURCEThe study was led by Rebecca A. Tobin, Carleton University, Ottawa, Canada. It was published online on August 3 in Scientific Reports.LIMITATIONSResearchers included only young males with X-linked recessive DMD. Only a high-dose vamorolone group was analyzed for proteomics. Researchers could not determine whether improvements in biomarkers translated into better long-term bone strength or lower risk for fractures.DISCLOSURESThe study was supported by the Foundation to Eradicate Duchenne, the National Institutes of Health, and the European Commission. Several authors reported being employed by and owning stock in ReveraGen BioPharma. Two authors reported being employees of Santhera Pharmaceuticals. One author reported receiving support from a university and hospital in Canada.This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.