#apaperaday
Prof. Annemieke Aartsma-Rus is taking on a challenge by reading and commenting on a paper a day. She shares her insights, findings and thoughts via her @oligogirl Twitter account. See below the overview of January 2024.
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Prof. Aartsma-Rus reads and comments on the paper titled: Moving Beyond the 2018 Minimum International Care Considerations for Osteoporosis Management in Duchenne Muscular Dystrophy (DMD): Meeting Report from the 3rd International Muscle-Bone Interactions Meeting 7th and 14th November 2022
Today's pick is a meeting report on osteoporosis management in Duchenne by Phung et al and @drjarodwong . The report is published in @journal_nd DOI: 10.3233/JND-230176
Duchenne patients have a high risk for fractures, due to the myopathy (less weight bearing so osteoporosis), chronic steroid use (osteoporosis is a side affect) and frequent falls due to myopathy. Duchenne patients have 4 times more fractures than other young individuals
For vertebral fractures it is 535 times more! Within the first 8 years of steroid use, 75% of Duchenne patients experience at least 1 fracture. Consequences can be severe, e.g. loss of function & even death due to fat embolisms so there is a need for guidelines to monitor & manage . The report is from the 3rd meeting of muscle and bone experts working in the field of Duchenne, with 385 delegates from 55 different countries, who discusses the management, implementation of guidelines and future directives.
As usual with meeting reports there is a lot of information and I will outline highlights.
First, the FOR-DMD study assess functional effects and side effects from steroid use. This showed that daily deflazacort and prednisone had the largest impact on functional performance. The on/off regimen had an impact compared to no steroids, but less so than daily regimen. However, the on/off regimen had a lot lower incidence of fractures and osteoporosis than daily prednisone and (highest incidence) deflazacort.
In 2018 the standards of care for Duchenne were updated, to also include endocrine aspects, including bone management. They prescribed monitoring bone health and fractures with regular imaging, and when fractures were apparent, to treat with bisphosphonates intravenously Different participants presented how the guidelines were implemented in different regions, including @duchennecentrum and also the importance of standardized analysis of images and clear reporting, There were also patient representatives presenting on a sad case of a Duchenne patient dying after a fracture from fat embolism syndrome and a Duchenne patient on an on/off regimen with vertebral fractures causing a lot of pain and also loss of upper limb function. The @worldduchenne has been instrumental in organizing care conferences to discuss the care aspects (including bone management) for Duchenne to clinicians around the world. Furthermore, @MDAorg @ParentProjectMD @worldduchenne and @TREAT_NMD produced a family guide for care.
Another take home message is that bisphosphonates have very poor oral bioavailability, so they have to be infused. The experts recommend that everyone should follow the standards of care to monitor, diagnose and treat osteoporosis in Duchenne patients.
Authors outline that different therapeutic approaches to restore dystrophin or to improve muscle quality are now in late stage clinical development or are even approved. However, the long term impact of these on bone health remains to be seen.
The most notable one is of course vamorolone, the steroid analogue that does not seem to affect bone health after short term treatment. However, the long term impact is not yet clear as this drug was only recently approved.
Prof. Dr. Annemieke Aartsma-Rus is a professor of Translational Genetics at the Department of Human Genetics of the Leiden University Medical Center. Since 2013 she has a visiting professorship at the Institute of Genetic Medicine of Newcastle University (UK).
Her work currently focuses on developing antisense-mediated exon skipping as a therapy for Duchenne muscular dystrophy. In addition, in collaborative efforts she aims to bridge the gap between different stakeholders (patients, academics, regulators and industry) involved in drug development for rare diseases.
In 2013 she was elected a member of the junior section of the Dutch Royal Academy of Sciences (KNAW), which consists of what are considered the top 50 scientists in the Netherlands under 45. From 2015 to 2022, she was selected as the most influential scientist in Duchenne muscular dystrophy by Expertscape.