Introduction:​ The societal factors in bone loss are numerous, ranging from old age to space flight. Although several treatment themes are available for bone loss, there continues to be a demand for new ideas as well as a better understanding of the topic. A novel treatment approach to attenuate bone loss has emerged in gap junction manipulation, specifically the knockout of bone specific connexin 43 proteins which make up gap junctions. Glycyrrhetinic acid (GA) has been shown as a non-specific gap junction inhibitor, and may also be an antiinflammatory. Thus, we hypothesized that GA may be an effective tool in attenuating bone loss during periods of bone unloading, as in bed ridden patients or spaceflight. We hypothesized that GA administration at 20mg/kg would block gap junction function, and attenuate bone loss induced by hind limb suspension (HLS) unloading.

Design:​ A randomized controlled trial was designed with twenty five male wild-type C57C1/BJ mice of skeletally mature age (6 months), and placed into 5 groups:​ ground control, ground control GA treatment, HLS no treatment, HLS vehicle, and HLS GA treatment. Experimental protocol utilized mechanical unloading based on a 3 week duration of HLS and GA intervention via subcutaneous injection;​ the ground control groups were not mechanically unloaded.

Assessments:​ Animals were evaluated primarily using MicroCT scan to evaluate physical characteristics of bone in the femur. Mechanical testing based on three point bending, and monitoring of basic body composition were also evaluated.

Conclusions:​ The original hypothesis predicted that GA treatment during HLS would result in an attenuation of bone loss. HLS alone does cause significant changes in several microarchitecture parameters, such as a 60% decrease in trabecular BV/TV, when compared to ground control 38%. However, our results did not show significant changes in MicroCT results between suspended control and suspended GA treatment groups;​ changes in bone characteristics were similar across all unloaded mice. GA ground control mice did not show significant differences from ground controls not receiving GA. Our hypothesis that GA would attenuate bone loss during unloading was not supported.