Lovastatin, a drug used to lower cholesterol and help prevent cardiovascular disease, has been shown to improve bone healing in an animal model of neurofibromatosis type 1 (NF1). The research, reported today in the open access journal BMC Medicine, will be of great interest to NF1 patients and their physicians.
Many NF1 patients suffer from bowing, spontaneous fractures and pseudarthrosis (incomplete healing) of the tibias (shinbones). Mateusz Kolanczyk from Stefan Mundlos' laboratory in the Max Planck Institute for Molecular Genetics, Berlin, led a team that investigated lovastatin's ability to prevent pseudarthrosis in a new animal model of human NF1 disease.
Current therapies are often futile when applied to pseudarthrosis of the tibia; in some cases, amputation is the only option. To better understand this problem, Kolanczyk and his colleagues developed this mouse model. He said, "In our model, the mice showed tibial bowing similar to that observed in NF1 patients, however since mouse legs are not subjected to the same excessive mechanical forces as humans, we also applied a bone injury model". The authors drilled a 0.5mm hole in the tibia of anaesthetised mice. As they describe, "This enables analysis of the complex process of bone repair while at the same time causing the least possible distress to the animals".
The process of bone repair was examined 7, 14 and 28 days post-injury. The authors found that the mice given the statin treatment had marked improvements in bone healing compared to the control animals. As they report, "Lovastatin appears to accelerate cortical bone repair primarily by enhancing new bone formation within the bone marrow cavity and by replacing fibro-cartilaginous tissue in the injury site with mineralised bone matrix".
Kolanczyk concludes, "Our results suggest the usefulness of lovastatin, a drug approved in 1987 for the treatment of high cholesterol, in the treatment of neurofibromatosis-related fracture healing abnormalities". The experimental model presented here constitutes a valuable tool for the preclinical testing of other candidate drugs that target similar bone problems.
Notes to Editors
1. Modelling NF1 tibial dysplasia and its treatment with lovastatin
Mateusz Kolanczyk, Jirko Kuehnisch, Nadine Kossler, Monika Osswald, Sabine Stumpp, Boris Thurisch, Uwe Kornak and Stefan Mundlos
BMC Medicine (in press)
During embargo, article available here: http://www.biomedcentral.com/imedia/1667189777189248_article.pdf?random=956593
After the embargo, article available at journal website: http://www.biomedcentral.com/bmcmed/
Please name the journal in any story you write. If you are writing for the web, please link to the article. All articles are available free of charge, according to BioMed Central's open access policy. Article citation and URL available on request at email@example.com on the day of publication
2. Dr Bruce R Korf of the Department of Genetics, University of Alabama at Birmingham, has provided an accompanying commentary.
Statins, bone, and neurofibromatosis type 1
Bruce R Korf
BMC Medicine (in press)
3. BMC Medicine publishes original research articles, technical advances and study protocols in any area of medical science or clinical practice. To be appropriate for BMC Medicine, articles need to be of special importance and broad interest. BMC Medicine (ISSN 1741-7015) is indexed/tracked/covered by PubMed, MEDLINE, BIOSIS, CAS, Scopus, EMBASE, Thomson Scientific (ISI) and Google Scholar.
4. BioMed Central (http://www.biomedcentral.com/) is an independent online publishing house committed to providing immediate access without charge to the peer-reviewed biological and medical research it publishes. This commitment is based on the view that open access to research is essential to the rapid and efficient communication of science.
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.