High content omega-3 fish oil co-treatment maintains proper bone physiology in glucocorticoid treated autoimmune mice

Abstract

Despite the known side effects of glucocorticoid therapy, such as a higher risk of osteoporosis, fractures, and reduced bone density, it remains a frequently prescribed treatment for autoimmune disorders due to its strong anti-inflammatory and immunosuppressive properties. If strategies could be identified to reduce the side effects commonly associated with glucocorticoid use, it could lead to more frequent and safer use of this treatment option for autoimmune diseases. In this work, the combined effects of high content omega-3 fish oil (HCW3FO) and a synthetic glucocorticoid, methylprednisolone (MP) medication are investigated in relation to bone mineral density (BMD) reduction in arthritis prone female MRL-lpr/lpr mice. Two treatment groups were introduced to the mice when they were 4 months old: one group was given weekly injections of PBS, while the other group was given either 5 mg/kg MP or 20 mg/kg MP. Additionally, both groups were provided with the AIN93M diet, supplemented with either 4% corn oil or 4% HCW3FO daily, for a duration of 8 weeks. Prior to initiating the drug injections and dietary modifications, the mice underwent dual energy x-ray absorptiometry (DXA) scans to establish their baseline BMD values. To find out their ultimate BMD values, the mice underwent another DXA scan eight weeks later, right before being sacrificed. Over the course of eight weeks, the MP treatment did not lead to a significant reduction in BMD across various bone regions, except for the lumbar regions. Similarly, the HCW3FO treatment alone did not offer protection against BMD loss in MRL-lpr/lpr mice. However, when MP and HCW3FO were combined, it resulted in a remarkable preservation of BMD in different bone regions. This enhanced protection against BMD loss was associated with a reduced number of tartrate-resistant acid phosphatase (TRAP) positive areas and an increased number of alkaline phosphatase (ALP) positive areas in tibial sections as revealed by immunohistochemistry. Our findings provide compelling evidence that the combination of MP and HCW3FO maintains bone health in arthritis-prone MRL-lpr/lpr mice by promoting a balance between bone resorption and bone formation. Co-treatment with HCW3FO may hold promise as a potential strategy for preventing bone deterioration induced by long-term glucocorticoid therapy. Before moving on to clinical trials, more in vitro research into the mechanisms should be carried out alongside preclinical studies in mice with inflammatory diseases. QUCG-CAS-2122-2. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.