Flavonoids in bone erosive diseases


Flavonoids promote bone deposition and inhibit bone resorption, according to a review of flavonoids in bone erosive diseases.

The review in the journal Trends in Endocrinology & Metabolism concluded that these functions are accomplished through reduction of oxidative stress, thus regulating bone homeostasis.1

“Imbalance of bone homeostasis, with excessive bone resorption compared with bone formation, leads to the development of progressive osteopenia leading to lower bone resistance to load, with consequent pain and functional limitations,” wrote the Italian authors, who conducted a systematic review of the literature from the last 5 years using four databases: Medline, ScienceDirect, Embase and Web of Science.

Flavonoids also act on osteoblast differentiation and activity.

Of the 35 studies selected on flavonoids isolated from plants that showed protective effects against osteoporosis through their effects on the survival, proliferation, and differentiation of cells implicated in bone homeostasis, 17 were in vitro studies, 18 were in vivo studies, and two of the in vivo studies were clinical studies.

One of the goals of the review is to highlight the molecular mechanisms of action of these flavonoids, including epigenetic regulation like acetylation/deacetylation and microRNA (miRNA) expression. Another goal is their potential pharmacological use for the prevention and treatment of osteoporosis.

Phytochemicals with therapeutic and preventive effects against bone resorption are being given increasing attention, due to being potentially more suitable for long-term use than traditional therapeutic chemical compounds.

However, the authors are unaware of any purified phytochemical compounds marketed as supplements or drugs for osteoporosis therapy. But they said it might be useful to administer purified compounds that simultaneously affect both bone deposition and remodeling.

Some flavonoids, such as the isoflavones (daidzein, genistein, puerarin, cladrin, calycosin), flavonols (icariin), flavanols (EAF) and anthocyanins (cyanidin, petunidin) both stimulate cell type osteoblasts (OBs) and inhibit cell type osteoclasts (OCs).

Concerning flavonoid compounds, “we have noted that these molecules are tested primarily in OB differentiation, rather than OC differentiation,” wrote the authors. “Therefore, further preclinical studies are needed to compensate for the deficiencies in knowledge on the mechanisms of action of these compounds on both OBs and OCs, before a clinical trial on one of these compounds could be considered.”

The included studies demonstrate that flavonoids mostly provide protective actions to hinder pathological bone loss, with specific effects primarily on OBs, but also on OC differentiation and activity through the same interactors.

Although numerous in vivo studies show a reduction of bone loss in several osteoporotic models by treating with flavonoids, only a few of them highlight the cellular and molecular mechanisms underlying this effect.

The two major limitations of clinical use of flavonoids for bone health is the lack of detailed mechanisms responsible for bone protection and the absence of clinical trials on these molecules with large cohorts of osteoporotic patients.

Among the unanswered questions are whether flavonoids can be used as a supplement or therapy to prevent or heal bone fractures by regulating bone homeostasis, whether these molecules can be employed to recover bone loss and heal osteoporotic fractures, and whether combined therapy with phytochemicals and other drugs will improve the effects on osteoporosis.



  1. Bellavia D, Dimarco E, Costa V, et al. Flavonoids in bone erosive diseases: perspectives in osteoporosis treatment. Trends Endrocrinol Metab. Published online December 4, 2020. doi:org/10.1016/j.tem.2020.11.007
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