Researchers have recently discovered that a new drug called locamidazole effectively mimics the effects of exercise by preventing bone and muscle density reduction during periods of inactivity.
By Dr. Mehmood Asghar (B.D.S, M.Phil., Ph.D.)
We all look forward to enjoying our weekends and holidays. Perhaps not just to enjoy busy life activities, but also to relax and rest. I don't doubt that some of us secretly dream of spending our time off doing absolutely nothing. But, unfortunately, as alluring as it may seem, a sedentary lifestyle – either due to laziness or a mobility-hampering illness – comes with its drawbacks, particularly the loss of muscle mass and bone density due to prolonged inactivity.
Defying Nature
What if we could defy nature and still enjoy the benefits of exercise while resting and relaxing? As impossible as it may seem, scientists at Tokyo Medical and Dental University (TMDU), Japan, have made an exciting find. The researchers at the Department of Cell Signaling, Graduate School of Medical and Dental Sciences, TMDU, have discovered a drug called Locamidazole (LAMZ) that has the same effect on the body as exercise.
Promoting the production or stimulation of the body's inherent molecules to increase bone formation and muscle generation is not new (Cary et al., 2013; Liu et al., 2021; Sapkota et al., 2020). However, this Japanese research group took an innovative approach. They studied more than 300 single molecules that offered three main effects: osteoblast and muscle cell proliferation and the inhibition of osteoclasts, the desired outcome being bone and muscle formation while preventing bone resorption.
The Research Findings
After successfully demonstrating the efficacy of LAMZ in-vitro, Ono et al. (2022) performed in-vivo tests on mice and published their findings in Bone Research. When mice were fed LAMZ orally, it was observed that they had increased muscle width, which resulted in fewer fatigue episodes during 15-minute episodes of treadmill activity and could run 70% longer than non-treated mice. Furthermore, micro-CT imaging showed that the LAMZ-treated mice had increased bone volume, indicated by improved trabecular bone thickness and enhanced bone mineral content.
Additionally, a tail-suspension disuse model was used to assess the exercise-mimicking effect of LAMZ during periods of inactivity. The results showed that LAMZ-treated mice had a 20% bone mineral loss than 35% for the control mice. Furthermore, LAMZ-treated mice retained higher muscle width than the non-treated ones. This shows that while LAMZ may not wholly offset the adverse effects of inactivity, it could effectively blunt the effects of osteoporosis and sarcopenia.
The research suggests that the drug is effective, but how does it work? It turns out that LAMZ-treated cells have a significantly increased expression of a long-named protein called peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α). But let's not get confused by the protein's tongue-twisting name. Simply put, PGC-1α enhances the formation of mitochondria – the powerhouses of the body's cells – resulting in increased metabolism, the same effect achieved after exercising. Furthermore, LAMZ increases the intracellular calcium concentration in myocytes and osteoblasts – having the same effect as physical activity – and explains its exercise-mimicking potential.
What's the Catch?
The initial findings of this study are fascinating and may have far-reaching effects. But certain aspects need further consideration. For example, although LAMZ increases muscle mass in treated mice, it does not affect their overall weight. Furthermore, this drug was tested on 7-week-old mice, the equivalent of a young adult – having high levels of sex hormones. Will LAMZ have the same effect on older mice with lower sex hormone concentrations? It is yet to be discovered.
The Bottom Line
LAMZ is highly effective for non-mobile, hospitalized individuals to resist inactivity-induced muscle mass and bone loss. But it is not a complete cure for inactivity or the loss of muscle and bone loss that comes with inactivity. However, it may not be too far-fetched to speculate that in the future, scientists may be able to discover a drug that could substitute for exercise.
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Author: Dr. Mehmood Asghar is a dentist and Assistant Professor of Dental Biomaterials at the National University of Medical Sciences, Pakistan. Dr. Asghar received his undergraduate and postgraduate dental qualifications from the National University of Science and Technology (NUST) and obtained a Ph.D. in Restorative Dentistry from Malaysia. Apart from his hectic clinical and research activities, Dr. Asghar likes to write evidence-based, informative articles for dental professionals and patients. Dr. Asghar has published several articles in International journals.
References
- Cary, R. L., Waddell, S., Racioppi, L., Long, F., Novack, D. V., Voor, M. J., & Sankar, U. (2013). Inhibition of Ca2+/calmodulin–dependent protein kinase kinase 2 stimulates osteoblast formation and inhibits osteoclast differentiation. Journal of Bone and Mineral Research, 28(7), 1599-1610.
- Liu, Y., Wang, Q., Zhang, Z., Fu, R., Zhou, T., Long, C., He, T., Yang, D., Li, Z., & Peng, S. (2021). Magnesium supplementation enhances mTOR signaling, facilitating myogenic differentiation and improving aged muscle performance. Bone, 146, 115886.
- Ono, T., Denda, R., Tsukahara, Y., Nakamura, T., Okamoto, K., Takayanagi, H., & Nakashima, T. (2022). Simultaneous augmentation of muscle and bone by locomomimetism through calcium-PGC-1α signaling. Bone Research, 10(1), 52. https://doi.org/10.1038/s41413-022-00225-w
- Sapkota, M., Gao, M., Li, L., Yang, M., Shrestha, S. K., Choi, H., & Soh, Y. (2020). Macrolactin A protects against LPS-induced bone loss by regulation of bone remodeling. European Journal of Pharmacology, 883, 173305.
