Review
Flavonoids in Bone Erosive Diseases: Perspectives in Osteoporosis Treatment

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Highlights

  • Flavonoids act to promote bone deposition and inhibit bone resorption.

  • Flavonoids, through reduction of oxidative stress, favor bone deposition and inhibit bone resorption, regulating bone homeostasis.

  • Flavonoids act through several mechanisms, such as epigenetic regulation (acetylation/deacetylation, miRNA expression).

  • Flavonoids are demonstrated to act on osteoblast differentiation and activity.

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. Phytochemicals with therapeutic and preventive effects against bone resorption have recently received increasing attention since they are potentially more suitable for long-term use than traditional therapeutic chemical compounds. In this systematic review of the literature of the past 5 years, comprehensive information is provided on flavonoids with potential antiresorption and pro-osteogenic effects. It aims to highlight the molecular mechanisms of these molecules, often epigenetic, and their possible pharmacological use, which is of great importance for the prevention and treatment of osteoporosis (OP).

Section snippets

Flavonoids: Bone Homeostasis and Osteoporosis Treatment

Osteoporosis (OP) is a worldwide chronic progressive bone disease characterized by increased bone resorption leading to bone loss and reduced mineral content, which lead to increased risk of bone fractures (≥8.9 million fractures/year) [1]. OP is often associated with a reduced quality of life, due to disability, pain, and depression, often related to fractures (i.e., hip, vertebra, wrist). Primary OP occurs mainly with aging or during postmenopause, while secondary OP is related to various

Search Strategies and Results of Collected References

The following literature search was conducted in four different databases: MEDLINE, ScienceDirect, EMBASE, and Web of Science. The strings used in the bibliographic search were: (Osteoporosis AND Flavonoid). In the MEDLINE database (PubMed search engine) 377 articles were retrieved by considering publications written in English (AND "English" [language]) and published after 1 January 2015 (AND ("2015/01/01"[Date - Entrez]: "2020/04/30"[Date - Entrez])). Reviews (NOT Review [Publication Type])

Polyphenols: Flavonoid Classes in Bone Homeostasis

Polyphenols are secondary metabolites produced by plants as a defense against pathogens or UV radiation. Flavonoids are the most studied polyphenols for OP treatment, and numerous molecules have been isolated, identified, and characterized.

The term flavonoid is used to describe a broad collection of plant compounds characterized by a flavone ring that constitutes the backbone of the structure. They are ubiquitous molecules playing an integral role in the growth and development of plants. They

The Roles of Flavonoids in Bone Tissue Homeostasis

Numerous flavonoids regulate bone homeostasis by interacting with the different signal transduction pathways of bone tissue cells. Effects favoring osteoblastogenesis and an increase of OB activity with improved bone deposition are mainly exerted by flavonoids; some of these compounds also act by inhibiting osteoclastogenesis and OC activity.

During OB differentiation, some isoflavones, flavonols, and anthocyanins cause the upregulation of BMP-2 expression, some flavones, isoflavones, flavonols,

Perspectives on the Use of Flavonoids in OP

Flavonoids have beneficial and protective effects on pathological bone loss and OP development. Despite the continuing increase in knowledge on their mechanisms of action, mostly derived from in vitro and in vivo preclinical studies, to our knowledge there are still no purified phytochemical compounds marketed as supplements or drugs for OP treatment.

Among the possible treatment strategies with the use of purified compounds, it might be useful to administer compounds that simultaneously have an

Concluding Remarks

The flavonoids reported in this review have been shown to have predominantly protective actions aimed at hindering pathological bone loss, highlighting specific effects primarily on OBs, but also on OC differentiation and activity through the same interactors (Figure 3); however, few clinical trials have been conducted. Several preclinical studies have demonstrated the protective effects of flavonoids. Although the epigenetic roles of these compounds are certain [55], few studies have

Author Contributions

D.B. and E.D. conceived and designed the search strategy for articles, selected the bibliography, and wrote the manuscript. Vi.C., Va.C., A.D.L., and L.R. revised the section ‘Polyphenols: Flavonoid Classes in Bone Homeostasis’. C.G. provided pharmacological feedback. F.C. provided feedback in the epigenetics field. M.F. and G.G. provided critical feedback on the entire manuscript. D.B., E.D., Vi.C., A.D.L., Va.C., L.R., C.G., M.F., F.C., and G.G. approved the submitted version of the

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