The Role of Macronutrients, Micronutrients and Flavonoid Polyphenols in the Prevention and Treatment of Osteoporosis

Abstract

Osteoporosis is considered an age-related disorder of the skeletal system, characterized primarily by decreased bone mineral density (BMD), microstructural quality and an elevated risk of fragility fractures. This silent disease is increasingly becoming a global epidemic due to an aging population and longer life expectancy. It is known that nutrition and physical activity play an important role in skeletal health, both in achieving the highest BMD and in maintaining bone health. In this review, the role of macronutrients (proteins, lipids, carbohydrates), micronutrients (minerals-calcium, phosphorus, magnesium, as well as vitamins-D, C, K) and flavonoid polyphenols (quercetin, rutin, luteolin, kaempferol, naringin) which appear to be essential for the prevention and treatment of osteoporosis, are characterized. Moreover, the importance of various naturally available nutrients, whether in the diet or in food supplements, is emphasized. In addition to pharmacotherapy, the basis of osteoporosis prevention is a healthy diet rich mainly in fruits, vegetables, seafood and fish oil supplements, specific dairy products, containing a sufficient amount of all aforementioned nutritional substances along with regular physical activity. The effect of diet alone in this context may depend on an individual's genotype, gene-diet interactions or the composition and function of the gut microbiota.

Keywords: flavonoid polyphenols; macronutrients; micronutrients; nutrition; osteoporosis; prevention; treatment.

Figure 1

Schematic representation of osteoblast (left) and osteoclast (right) differentiation with the involvement of selected important signaling pathways and regulators. Positive effects are depicted by green arrowheads. The blue arrows and font show the production of selected molecules important in the signaling pathway and also for the processes of bone formation and resorption. Osteoblastogenesis is regulated by different signaling pathways (including TGF-β/BMP, WNT), resulting in activation of downstream transcription factors such as Runx2 and leading to the expression of osteoblastogenic markers by osteoblasts, e.g., type I collagen, ALP, OPN, BSP and OCN. The canonical WNT pathway activates downstream signaling cascades, resulting in β-catenin translocation into the nucleus which enhances osteoblastogenic target gene expression. TGF-β and BMPs are secreted growth factors belonging to the TGF-β superfamily, which play an essential role in development, tissue homeostasis and regeneration. Canonical TGF-β signaling mobilizes transcription factors Smad2 and Smad3 to interact with other transcription factors and induces Runx2-mediated gene expression. Similar to TGF-β, canonical BMP signaling also transmits signals through Smad transcription factors. Moreover, BMPs and TGF-β can induce Runx2 through the MAPK signaling pathway. Osteocytes represent a differentiated stage of the osteoblast lineage and they have key regulatory roles in bone and mineral homeostasis. Osteoclasts differentiate from cells of the monocyte/macrophage lineage in response to the osteoclastogenic cytokines M-CSF, RANKL and ITAM. As a result, mononuclear osteoclast precursors finally fuse into mature polykaryons which produce protons and proteolytic enzymes (especially cathepsin K) to dissolve bone minerals and degrade bone matrix proteins. MSC, mesenchymal stem cell; TGF-β, transforming growth factor beta; BMP, bone morphogenetic protein; MAPK, mitogen-activated protein kinase; Runx2, runt-related transcription factor 2; WNT, Wnt glycoproteins; PTH, parathyroid hormone; OPN, osteopontin; BSP, bone sialoprotein; ALP, alkaline phosphatase; OCN, osteocalcin; HSC, hematopoietic stem cell; M-CSF, macrophage-colony stimulating factor; ITAM, immunoreceptor tyrosine-based activation motif; RANK, receptor activator of nuclear factor κΒ; RANKL, receptor activator of nuclear factor κΒ ligand; CATK, cathepsin K.

Figure 2

Chemical structures of described flavonoid polyphenols.

Figure 3

Effects of described flavonoid polyphenols on bone microstructural and biochemical parameters in vivo (left) and on bone cell parameters in vitro (right). The increase and decrease in a given parameter is indicated by red arrows pointing up and down, respectively. Q, quercetin; R, rutin; L, luteolin; K, kaempferol; N, naringin.