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Novel Compound for Bone Regeneration

A new study looks at using formononetin as a potential therapy to improve bone regeneration and found that this compound is as effective as parathyroid hormone, an approved fracture-healing drug, at healing fractures in an animal model.

Many elderly individuals can easily suffer accidental fractures as a result of osteoporosis, a disease that causes bone weakening. Furthermore, osteoporosis is linked to systemic inflammation and slower fracture healing, which exacerbates the situation. Other conditions that are also associated with inflammation, such as diabetes and rheumatoid arthritis can likewise adversely impact fracture healing. With these widespread diseases that can complicate bone regeneration, scientists have been interested in administering treatments that can accelerate bone healing. INFUSE® Bone Graft and parathyroid hormone (PTH) are currently available as such, but these treatments remain very expensive and have multiple undesirable side effects. Thus, new therapies that are more effective, less dangerous, and cheaper need to be discovered to approach this common worldwide problem. One study, recently published in the British Journal of Nutrition, tests formononetin as an agent to enhance bone regeneration in a mouse model.

The authors of this paper removed ovaries from some of the mice to mimic postmenopausal osteoporosis. Mice also underwent a drill-hole injury under anaesthetic conditions to generate a fracture in the femur. Lastly, they were then administered formononetin (orally) or PTH (injected under the skin) as therapies that would help improve bone recovery.PTH is known to improve bone regeneration, whereas formononetin has not been validated as a therapy. Ten days of treatment following the fracture, it appeared that bone quality decreased in mice that had ovaries removed. However, when the mice were treated with either formononetin or PTH, the mice had enhanced bone quality based on multiple parameters. In experiments that extend the treatment period to 21 days, results demonstrate that both treatments once again have benefits in bone regeneration, but for some parameters of bone quality, the treatments increase the quality of bone to a level even higher than that of normal mice.

Specifically, the authors want to determine whether formononetin caused more minerals to be deposited at the site of injury. By obtaining the femurs of mice after 10 or 21 days of treatment to improve bone healing, slices of the femur were then stained and observed under a microscope. This allowed the authors to observe that formononetin not only promoted more tissue formation but also increased mineral deposition at the fracture. These effects were seen at both 10 or 21 days and also observed with PTH. Finally, the study addressed the molecular pathways of bone regeneration that were involved at the injury site and noted the increase in the presence of the pathways when mice were treated with formononetin.

This study demonstrates the potential of formononetin as a fracture-healing drug, as it has effects that are comparable to PTH, which is an established treatment for bone regeneration. Granted, this was performed in an animal study and further clinical studies will have to validate whether formononetin can boost bone regeneration to a similar amount in humans. Since this compound can be administered orally, patients can easily receive treatment, as compared to an injection of PTH. Of note, formononetin has no observable side effects in mice, which will be conducive to testing in humans. This fact, in addition to the results of this study, shows the high potential of this compound as a future bone regeneration drug.

Written by Branson Chen, BHSc

Reference: Singh KB, Dixit M, Dev K, Maurya R, Singh D. Formononetin, a methoxy isoflavone, enhances bone regeneration in a mouse model of cortical bone defect. British Journal of Nutrition. 2017 Jul:1-2.

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