Baricitinib for the treatment of age-related osteoporosis

Osteoporosis is a common age-related disease that affects millions of people worldwide and is associated with an enormous economic burden. As still only a small number of osteoporotic patients is adequately treated, there is an urgent need to develop new treatment strategies. Proinflammatory cytokines are special proteins produced by various cells in the body in response to the presence of bacteria, viruses, fungi, parasites or tissue damage. They are also involved in immune and inflammatory responses and play an important role in the pathogenesis of osteoporosis. Baricitinib belongs to the group of Janus kinase (JAK) inhibitors, is an anti-inflammatory agent that mediates cytokine signaling and is approved for the treatment of rheumatoid arthritis. From previous preclinical studies it is evident, that in young animals treatment with baricitinib has a positive effect on bone formation; nevertheless, data in a model of age-related osteoporosis are lacking. Based on this gap in research, in our study 60 eight-month-old female SAMP8 mice will be randomly assigned to receive baricitinib or control vehicle. The SAMP8 mouse was selected for this study because it is an established model of age- related osteoporosis. After a treatment period of six weeks, the bones will be examined by micro-CT and histomorphometry. Furthermore, flow cytometry, ELISA analyses, RNA sequencing and integrative data analysis with a systems biology approach will be performed. The main objective of this study is to test the effect of baricitinib on bone microarchitecture by micro-CT. Since it is known from previous studies that baricitinib has a positive effect on new formation of bone in young mice and that bone formation is reduced in age-related osteoporosis, we hypothesize that baricitinib will improve bone properties in our mouse model of age-related osteoporosis (SAMP8). Additional objectives of this study include investigations of bone remodeling and cytokine production by immune cells and transcriptomic analyses. The generated results of this study will demonstrate the role of baricitinib as a bone active compound and provide a clear rationale for the clinical development of baricitinib for osteoporosis treatment in advanced age.