A recent study, initially published in Nature Communications, shows that anti-oxidation specific epitope (OSE) antibodies protect against osteoporosis, illuminating the potential for a novel approach to treatment.
The data presented in the report by Elena Ambrogini (Division of Endocrinology, Department of Internal Medicine, University of Arkansas for Medical Sciences College of Medicine; Central Arkansas Veterans Healthcare System, Little Rock, USA) and colleagues are the first to suggest that anti-OSE antibodies protect against the adverse effect of OSEs on the skeleton, and that the titre of endogenous anti-OSE antibodies is insufficient to maintain maximal cancellous bone mass under normal conditions.
In humans, B-1 lymphocyte cells decline with age, leading to a corresponding decline in the levels of the natural antibodies that they produce. As this means there are fewer antibodies acting against the OSEs, the authors postulate that declining antibody levels contribute to the pathogenesis of age-related diseases, such as osteoporosis, writing, “The decline of anti-PC IgM levels in older mice may indicate that such decline contributes to the pathogenesis of involutional osteoporosis.” A high fat diet can also induce B-1 lymphocyte decline. However, further work is required to establish a cause-effect association between lower levels of anti-OSE antibodies and osteoporosis.
Nevertheless, the investigators hypothesise that increasing the titre of antibodies to OSEs may attenuate and perhaps reverse age-dependent bone loss. Describing the mechanism for such a treatment, Ambrogini et al explain, “This could be achieved by immunisation strategies to increase endogenous titres of OSE antibodies, or by passive immunisation with exogenously generated antibodies. Such novel therapeutic approaches could be used for the treatment of osteoporosis and atherosclerosis simultaneously.”
In the study, Ambrogini and colleagues used a genetically modified mouse developed at the University of California San Diego (UCSD), where researchers conducted a related study that showed this same protein also has a beneficial effect on cardiovascular disease, specifically atherosclerosis. This research was published in Nature.
“Together, the two studies provide proof of principle for a new therapy for two very common diseases, osteoporosis and atherosclerosis, simultaneously,” Ambrogini explains. “In the case of osteoporosis, this would be a new anabolic therapy, meaning that it can build new bone as opposed to only preventing the loss of old bone.”
Robert L Jilka (University of Arkansas for Medical Sciences College of Medicine, Little Rock, USA), a co-author on the study, has been studying the relationship between atherosclerosis and osteoporosis for about 10 years.
“We have known for quite some time that there was some sort of connection between osteoporosis, atherosclerosis and the high-fat diet,” Jilka says. “Investigators all over the world have been studying this for a while without much success as to the reason for this connection.”
Ambrogini’s research career has been funded by the Osteoporosis Center’s National Institutes of Health program project; Central Arkansas Veterans Healthcare System; the Arkansas Biosciences Institute; the University of Arkansas for Medical Sciences Translational Research Institute; and the College of Medicine’s Barton Endowment and Initiative for Bone and Joint Research.
The University of Arkansas for Medical Sciences Center for Musculoskeletal Disease Research also provided support. The centre is funded by US$11.3 million in federal funds over five years from an NIH Centers of Biomedical Research Excellence (COBRE) grant. The grant supports junior researchers like Ambrogini as they work to secure their own independent funding and establish their careers.
“It would not have been possible for Dr Ambrogini to do this work in a vacuum,” says vice chancellor for research Lawrence Cornett. “The work of Dr Manolagas, Dr O’Brien and Dr Jilka, along with the vast assembly of knowledge and talent found among the scientists and support staff in the two bone research centres, was essential. This is yet another illustration of the importance of team science and long-term, consistent support for research.”
“I am excited and look forward to the translation of this science into a treatment for these conditions, which affect so many of my patients,” Ambrogini comments.