The potential effects of whole grain-enriched diet on preventing osteoporosis

Abstract

Osteoporosis is a chronic systemic skeletal disease that mainly affects postmenopausal women and older men, and is characterized by the destruction of bone tissue microstructure, reduced bone content, and a tendency to fracture. Nutrients provided by food are necessary for human survival, and at the same time, the various components of food act back on the human body, affecting its health status. Recent studies have shown that whole grain nutrition is beneficial in relieving osteoporosis and improving bone health. This review focuses on the beneficial effects of dietary pattern including whole grains on bone mineral density and the classical mechanisms of whole grain-enriched diet in regulating bone resorption and bone formation. Whole grain nutritional interventions might offer new possibilities for the prevention and treatment of osteoporosis.

Introduction

Whole grains consist of the intact, ground, cracked, flaked or otherwise processed kernel after the removal of inedible parts such as the hull and husk. All anatomical components, including the endosperm, germ, and bran must be present in the same relative proportions as in the intact kernel (van der Kamp et al., 2021). Whole grains are relatively rich in nutrients and active ingredients including carbohydrates, proteins, fats, vitamins, minerals, non-starch polysaccharides and phytochemicals. Many studies have shown that regular consumption of whole grains contributes to maintaining a healthy weight, reducing the risk of cardiovascular disease (Barrett et al., 2019), modulating gut microbiota (Gong et al., 2018), and alleviating type 2 diabetes (Kyro et al., 2018), etc. Compare with healthy adults consumption with refined grains, whole grains diet for 6-wk has modest positive effect on gut microbiota, short-chain fatty acids (SCFAs), effector memory T cells, and the acute innate immune response (Vanegas et al., 2017). Those results suggest that consumption of common whole grains such as whole wheat, barley, oats, brown rice, buckwheat, sorghum, millet and quinoa exerts benefit on health promotion.

The whole grains usually provide more balanced nutrients (such as dietary fibre and micronutrients) and active ingredients, and exhibit stronger biological functions (Kyro et al., 2016). As shown in table 1, whole wheat has high levels of thiamin, riboflavin and niacin, and wheat bran contains a certain amount of dietary fibre and alkylresorcinol, which inhibit the absorption of cholesterol and regulate glucose metabolism (Horikawa et al., 2017; Liu et al., 2021). Oats are rich in vitamin E, β-glucan and a variety of phenolic compounds, and the total antioxidant and free radical scavenging abilities of oats are positively correlated with the polyphenol content (Yu et al., 2020; Yu et al., 2022). Studies also indicate that oats exert properties of anti-cancer, lowering blood sugar and preventing cardiovascular disease, which are usually related to the content of dietary fibre and phenolic compounds (Wehrli et al., 2021; Yu et al., 2022). Brown rice is composed of bran germ and endosperm, and rich in a range of nutritional and bioactive components such as protein, unsaturated lipids, dietary fibre, vitamins, minerals, anthocyanins, flavanoids and gamma-oryzanol (Lee et al., 2019; van der Kamp et al., 2021; Zhu et al., 2020). Compared with refined rice, the stronger antioxidant, antidiabetic, antiobesity, anticancer, anti-inflammatory, neuroprotective, cholesterol lowering activities of brown rice have been observed. Regarding bone health promoting of whole grain, Saleh et al. (2019). reported that a diet supplemented with phytate-reduced brown rice, inoculated with selected Lactobacillus sakei Wikim001, showed a bone-sparing effect on oophorectomy-induced trabecular bone loss and prevented deterioration of bone, since it has been known that phytate inhibits mineral absorption (Saleh et al., 2019; Yu et al., 2022). It has been suggested that the main anthocyanin substances in brown rice are cornetin and paeonin glucoside, both of which play a major role in antioxidant property (Gao et al., 2016; Tang et al., 2017). Buckwheat contains many bioactive compounds such as rutin, quercetin, phloroglucinol and other phenolic compounds (Xiong et al., 2019). The specific compound called buckwheat glycosyl alcohol is responsible for maintaining normal blood glucose level (Mir et al., 2016). The bioactive components in sorghum are mainly phenolic compounds including phenolic acids, flavonoids (3-deoxyanthocyanidins) and tannins which exert antioxidant property (Altaf et al., 2022). Millet is rich in essential amino acids, especially methionine and tryptophan, two amino acids which are usually deficiency in other grains. The content of calcium in millet is highest among whole grains, which suggests that millet has the potential to alleviate calcium deficiency and improve bone health (Puranik et al., 2017). Quinoa is naturally gluten free and a great source of complete protein, lipids, fibres, vitamins, and minerals such as calcium, magnesium, iron, copper and zinc (Filho et al., 2017). Taken together, increasing evidences indicate that whole grains exhibit higher nutritional and functional properties by providing a wider range of nutrients and active ingredients (Fig. 1).

Table 1. The nutrient characteristics and health benefits of common whole grains

Type	Nutrient characteristic	Health benefit	Reference
Whole wheat	High level of thiamin, riboflavin, niacin, and alkylresorcinol	Reducing the absorption of cholesterol and regulating glucose metabolism	(Horikawa et al., 2017; Liu et al., 2021)
Oats	Rich in vitamin E, β-glucan and a variety of phenolic compounds such as avenanthramides	Exerting properties of free radical scavenging ability, anti-cancer, lowering blood sugar and preventing cardiovascular disease	(Yu et al., 2020; Yu, Zhou, et al., 2022)
Brown rice	Containing high quality protein, unsaturated lipids, dietary fiber, vitamins, minerals, anthocyanins, flavanoids, gamma-oryzanol, and anthocyanin substances	With stronger antioxidant, antidiabetic, antiobesity, anticancer, anti-inflammatory, neuroprotective, cholesterol lowering, and bone health promoting activities than refined rice	(Mir et al., 2016; Saleh et al., 2019; Yu, Gaine, et al., 2022)
Buckwheat	Specific ingredients of rutin, quercetin, phloroglucinol, and buckwheat glycosyl alcohol	Modulating the structure and diversity of the microbiota and maintaining normal blood glucose level	(Gao et al., 2016; Peng et al., 2020)
Sorghum	Phenolic compounds including phenolic acids, flavonoids (3-deoxyanthocyanidins) and tannins	Exerting antioxidant property	(Xiong et al., 2019)
Millet	With high level of essential amino acids, especially methionine and tryptophan and calcium	Alleviating calcium deficiency and improving bone health	(Puranik et al., 2017)
Quinoa	Gluten free, hydrophilic (e.g. phenolics, betacyanins) and lipophilic (e.g. fatty acids, tocopherols, and carotenoids) nutrients	Suppressing inflammatory response and lowering the risk of the oxidative stress related diseases	(Filho et al., 2017; Tang et al., 2017)

Fig. 1

Whole grains derived phytochemicals and their potential functions.

The classical structures of phytochemicals derived from whole grains such as alkylresorcinol, β-glucan, avenanthramides, anthocyanins, oryzanol, flavonoids, quercetin, phloroglucinol, tannins, and rutin were listed. And the potential functions of these phytochemicals on regulating cholesterol metabolism, gut microbiota abundance, bone health, mitochondrial maintenance, preventing cardiovascular diseases, cancer, nervous system diseases, anti-obesity and antioxidant effects were also exhibited.

Bone is the hard and highly mineralized tissue that functions to support and protect various organs in our body (Arai et al., 2019). It is a dynamic tissue that constantly undergoes remodeling with a life-long coupled process of bone formation by osteoblasts and resorption by osteoclasts (Peng et al., 2020). The process of bone formation, growth, modeling and remodeling involves the dynamic coordination of multiple progenitor cells and mature bone cells. Osteoporosis, a major public health problem worldwide, is a systemic disease characterized by reduced bone mass and bone quality, increased bone fragility and fractures, which in turn lead to reduced quality of life and increased disability and mortality (He et al., 2019; Li et al., 2021). The pathogenesis of osteoporosis is usually considered to be related to the imbalance in skeletal turnover that bone resorption by osteoclasts exceeds bone formation by osteoblasts (Puranik et al., 2017). Osteoporosis is clinically classified as primary osteoporosis (type I), secondary osteoporosis (type II) and idiopathic osteoporosis (type III). Primary osteoporosis is mainly manifested as post-menopausal osteoporosis and age-related osteoporosis; Secondary osteoporosis is triggered by certain metabolic diseases or long-term use of certain medications; Idiopathic osteoporosis occurs mainly in adolescents and the cause is still unknown (Yu et al., 2023; Zhang et al., 2022). According to the latest epidemiological results, the prevalence of osteoporosis in China among adults aged 40 years and older was 5 % in men and 20.6 % in women (Wang et al., 2021). The data from 40 studies with a total sample size of 79 127 elders in Asia, European, and America indicated that the worldwide prevalence of osteoporosis was 21.7 % (Salari et al., 2021). Osteoporotic fractures become increasingly common in women older than 55 years and men older than 65 years (Compston et al., 2019). And the annual cost of osteoporosis-related fracture is approximately $ 17.9 and £ 4 billion in United States of America and United Kingdom, respectively (Clynes et al., 2020). Hence, osteoporosis has brought a great health threat to global older people and a huge stress on economic burden.

The risk factors of osteoporosis include genetic factors, disease factors, drug factors, environmental factor, etc. Genetic factors mainly include race, gender, and age. Generally, the percentage of osteoporosis is lower in people of the black race than those of East Asia and white races (Morin et al., 2022). Gender and age are also important factors related to the occurrence of osteoporosis. Women especially postmenopausal women are easier to develop osteoporosis than men, and the risk is increasing with age (Pietschmann et al., 2009). Chronic kidney disease, celiac disease, rheumatoid arthritis, thyroid hormone diseases, etc. are also inductors of osteoporosis (Delitala et al., 2020; Kovacev-Zavisic et al., 2015; Sharma et al., 2022; Wysham et al., 2021). For drug factors, long-term use of glucocorticoid may reduce the lifespan and activity of osteoblast and acts as a dangerous trigger for osteoporosis occurrence (Compston, 2018; Lane, 2019). In addition, therapy with aromatase inhibitor (Tenti et al., 2020), proton pump inhibitor (Lespessailles et al., 2022), thiazolidinediones (Lecka-Czernik, 2010), or antiepileptic drugs (Miziak et al., 2014) also trends to result in bone loss and induce osteoporosis. In recent years, the environmental factors including deficiency of physical activity and sunlight exposure (Kopiczko, 2020), low body weight (Mundy, 2000), insufficient intake of calcium and vitamin D (Liu et al., 2020), and unhealthy living habits (such as preferred coffee and carbonated drinks, smoking, and alcohol intake) (Bijelic et al., 2017; Zeng et al., 2022) causing osteoporosis are attracted more attention. To prevent osteoporosis, the strategy of nutritional support is widely reported. Besides calcium and/or vitamin D supplementation, dietary intake of complete protein (Yu et al., 2023; Zhang et al., 2022), polyunsaturated fatty acids (Choi et al., 2022), dietary fibre (Lucas et al., 2018), and phytochemicals (such as polyphenol and flavonoids) (Wong et al., 2020) also contributes to increase bone mass. Therefore, dietary intervention has been highly expected to prevent osteoporosis and enhance bone health (Fig. 2).

Fig. 2

The relationship between dietary factors and osteoporosis.

The dietary factors involved in regulating osteoporosis are listed. The risk factors for osteoporosis occurrence include low vitamin D, calcium or high phosphorus intake, excessive alcohol or coffee consumption, and high caloric diet; And the potential beneficial factors for osteoporosis prevention consist of milk and dairy products consumption, fruits and vegetables enriched diet, and optimal protein supplementation.

In this review, the relationship between whole grains diet and osteoporosis has been introduced, and the potential mechanisms in promoting osteoblast differentiation, inhibiting osteoclast production, enhancing calcium absorption, and regulating muscle-bone axis are explored.

Dietary pattern and osteoporosis protection Dietary pattern enriched in whole grains prevents osteoporosis

Dietary patterns mainly include Western diet, Eastern diet, Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH) diet, and planetary health diet, which are important factors on modifying the onset and progression of chronic metabolic diseases such as osteoporosis (Fabiani et al., 2019; Munoz-Garach et al., 2020; van den Brink et al., 2019; Willett et al., 2019). In terms of the differences in dietary composition, Western diet is rich in highly processed foods such as red meat, fried foods, dessert and sweets, high-fat dairy products, refined grains, etc. In contrast to Western diet, Mediterranean diet contains more vegetables, fruits, whole grains, nuts, and legumes (Zielinska et al., 2022). Similar to Mediterranean diet, intake of the plant foods such as vegetables, fruits, and whole grains is more recommended in Eastern diet and DASH diet (Song et al., 2021). The concept of planetary health diet, coordinating with healthy diet and sustainable foods system, has been put forward in 2019 (Willett et al., 2019). This dietary pattern also largely consists of vegetables, fruits, whole grains, legumes, and includes no or a low quantity red and processed meat, and refined grains (Willett et al., 2019). In comparison with people receiving other dietary patterns, the occurrence ratio of osteoporosis in people consuming Western diet is much higher. Clinical trial indicated that receiving Mediterranean-like dietary pattern with vitamin D supplement (10 µg/d) contributed to reducing bone loss in older Europeans with osteoporosis (Jennings et al., 2018). The healthy patterns emphasized the consumption of fruit, vegetables, and whole grains contribute to improving bone mineral density (BMD), while the Western pattern consuming much more red and processed meat, fried foods, and refined grains is reversely associated with bone health (Fabiani et al., 2019). Study also showed that higher intake of total vegetables, whole grains, and fruits is helpful to reduce the percentage of osteoporosis in elderly people (Fan et al., 2022). Dietary pattern with “fruit, milk and whole grain” or “dairy and whole grain” was associated with increased BMD (Shin et al., 2017; Shin et al., 2015; van den Hooven et al., 2015). In general, healthy dietary pattern enriched in whole grains was expected to prevent osteoporosis and reduce the risk of fragility fracture.

Dietary patterns and postmenopausal osteoporosis prevention

Postmenopausal women are susceptible to post-menopausal osteoporosis due to estrogen deficiency which results in increasing osteoclast activity, reducing bone density, and suffering from fractures when exposed to minor external forces (Ma et al., 2019; Prince et al., 1991). Several studies indicated that dietary pattern was correlated with post-menopausal osteoporosis. As shown in Table 2, dietary patterns with sweets, high-fat diets, or low vegetable and fruit diets might increase the risk of reduced BMD (de Franca et al., 2016; Shin et al., 2013). Conversely, diet pattern containing whole grains and high vegetable and fruit intake was beneficial for improving BMD and reducing the risk of low-trauma fracture (Langsetmo et al., 2011; Rivas et al., 2013). However, the reverse effect of cereal grains-fruits pattern on BMD of spine and hip was also reported (Chen et al., 2015). Therefore, more studies are still needed to focus on and verify the effect of whole grains diet on bone health.

Table 2. The relationship between dietary patterns and bone health

Country	Dietary patterns	Research Method	Participant Information	Conclusion	Reference
China	1) healthy; 2) low quality dietary	Case–control study	726 patients with hip fractures aged 55–80 years	Avoiding a low-quality diet is associated with a lower risk of hip fractures	(Zeng et al., 2014)
Australia	1) traditional (high intake of rice, pork, fish, poultry, dry tofu, beef, fresh vegetables and offal); 2) modern (high intake of fruits, milk, cake, fast foods, eggs, soy milk and deep fried products)	Follow-Up Study	15 572 adults aged ≥18 years	Modern dietary and/or animal-sourced nutrient patterns are prospectively associated with fracture risk	(Melaku et al., 2017)
Frence	Mediterranean diet	Questionnaire	1 482 individuals aged 67 years or older	The Mediterranean dietary pattern is not associated with a reduced risk of fracture in elderly French people	(Feart et al., 2013)
USA	1) meat, dairy, and bread; 2) meat, dairy, and bread; 3) sweet baked products; 4) alcohol; 5) candy; 6) fruit, vegetables, and cereal	cluster analysis	907 individual aged 69–93 years	BMD was significantly higher in men with diets higher in fruit, vegetables and grains than in men with other dietary patterns, but the results were not significant in women	(Tucker et al., 2002)
Danish	1) grain and cereal products; 2) red and processed meats; 3) fruits; 4) vegetables; 5) fish and seafoods; 6) confectionery; 7) dairy products; 8) legums and nuts	Controlled trial	184 individuals aged 65 years or older	Red and processed meats and confectionery were the only food groups found to be negatively associated with BMD	(Schacht et al., 2019)

Age-related osteoporosis is degenerative disease. Dietary patterns are also related to maintaining BMD and muscle function in elderly. Study proved that the consumption of more animal-source foods was associated with a greater susceptibility to fracture in older people, while a diet rich in fruit, milk and whole grains contributed to higher bone density (Melaku et al., 2017). According to Schacht et al. (2019)., adherence to a dietary index characterized by high intakes of whole grains, dairy products, fish, legumes, nuts, fruit, and vegetables was not found to be associated with BMD in a group of community-dwelling older Danes. However, based on their narrative review, the food groups commonly associated with improved BMD and muscle function are similar (Schacht et al., 2019). Idiopathic adolescent osteoporosis is a relatively rare condition, and its etiology and pathogenesis still remains unclear. Since adolescence is a critical time for bone development, in current theories, idiopathic adolescent osteoporosis may be due to the imbalance of bone formation and bone resorption during adolescent bone building and bone rebuilding, resulting in decreased bone matrix formation and increased bone resorption, and the presence of risk factors that affect bone tissue growth have a lifelong impact on bone health. Monjardino T (Monjardino et al., 2015) found no consistent association between adolescents’ dietary patterns and forearm BMD, while Shin S (Shin et al., 2013) found that the intake of milk and cereal is important for the bone health of Korean adolescents, whose diets are composed mainly of grains and vegetables. Therefore, a dietary pattern that includes milk and cereals may be at least partially beneficial for bone development in adolescents. Clinical trial also uncovered the potential relationship among dietary patterns, bone mass, and muscle strength in a group of middle-aged Australian women suggesting that maintaining a healthy diet, i.e. a high consumption of a plant-based diet-vegetables, legumes, fruit, tomatoes, nuts, snacks, garlic, whole grains- and a low intake of high-fat dairy products helps adults to achieve bone and muscle strength (Wu et al., 2017).

Generally, dietary patterns adherence to a Mediterranean (Palomeras-Vilches et al., 2019; Savanelli et al., 2017; Zupo et al., 2020) or Asian diet (Hirata et al., 2016; Messina, 2014) contribute to prevent osteoporosis, while a Western diet (Fairweather-Tait et al., 2011; Movassagh et al., 2017) might reduce bone density. It can be attributed to the different composition of various foods in each dietary pattern. Considered as the core of the Mediterranean diet or the Asian diet, olive oil or the supplementation of soy isoflavones with omega-3 fatty acids has been reported to be beneficial for bone status (Palomeras-Vilches et al., 2019). Furthermore, the intake of whole grains is also important for promoting bone health (Langsetmo et al., 2011; Melaku et al., 2017; Rivas et al., 2013).

Potential mechanisms of whole grains in osteoporosis prevention Ingredients from whole grains regulate bone metabolism by promoting osteoblast differentiation

Osteoblasts are responsible for bone formation and ingredients from whole grains can alleviate osteoporosis via regulating osteoblasts differentiation-related signaling pathways. Alkaline phosphatase (ALP) is a marker of osteoblast differentiation, and runt related transcription factor 2 (Runx2) and osterix act as key regulators during osteoblast differentiation and promote the transformation of preosteoblasts into osteoblasts. In addition, osteoblast-related factors including osteocalcin, type I collagen and osteopontin also regulate multiple processes of bone formation via combining with osteoblast-specific activating elements (Zhang et al., 2022).

As one of whole grains, black rice was reported to be beneficial for promoting bone health. The results from models of murine C3H10T1/2 multipotent cells and 3T3-L1 cells indicated that black rice (Oryza sativa L.) alcohol extract elevated the activity of ALP and Osterix mRNA level, which promoted osteoblast differentiation by activating Wnt signaling pathway (Jang et al., 2015). Meta-analysis also demonstrated that red yeast rice and its extracts, fermented by mycelium of Aspergillus oryzae, contributed to promoting osteoblast proliferation, increasing ALP expression, improving BMD and bone matrix mineralization (Wu et al., 2020). In addition, animal study showed that the anthocyaninrich extract of black rice (Oryza sativa L. japonica) reduced blood glucose, increased BMD and decreased serum bone turnover index in dose-dependent manner, and finally alleviated diabetes-induced bone loss (Qi et al., 2019). In addition, dark purple rice (Oryza sativa L. Cv. Superjami) bran extract (including cyanidin-3-glucoside, γ-oryzanol, and ferulic acid, etc.) exerted therapeutic effects on postmenopausal bone loss in ovariectomized rats via reducing oxidative stress and upregulating ALP and osteocalcin expression (Chung et al., 2021). Wheat (T. aestivum) aqueous extract treatment contributed to alleviating glucocorticoid-induced osteoporosis by increasing ALP level, altering bone integrity, extending osteoblast lifespan and promoting osteoblast formation (Banji et al., 2014). Alkylresorciols (ARs), a well-known biomarker of whole wheat, is usually found in wheat and rye. Reports showed that ARs exerted antioxidant capacity via upregulating SIRT3-FoxO3a signal pathway (Liu et al., 2020). Study also indicated that activation of SIRT3-FoxO3a signal pathway contributed to promoting osteoblast differentiation (Yoon et al., 2023). It indirectly suggested that ARs might play important roles in improving bone health via regulating osteoblast differentiation. In general, ingredients from whole grains contributed to combating osteoporosis partially via promoting osteoblasts differentiation and proliferation and enhancing osteoblasts activity.

Whole grains derived phytochemicals inhibit osteoclast production

In the skeleton, bone marrow stromal cells can differentiate into bone resorption-dominant osteoclasts, osteogenesis-dominant osteoblasts and other immune cells depending on the microenvironment (Yarilina et al., 2011). Upon macrophage colony-stimulating factor stimulation, the expression of receptor activator of NF-κB ligand (RANK) increases in osteoclast precursor cells, which subsequently binds with RANK ligand (RANKL) and initiates osteoclast differentiation and formation (Yang et al., 1998). Osteoprotegerin (OPG), acts as a receptor for soluble RANKL, can compete with RANK in binding to RANKL, thereby inhibiting osteoclast production (Yu et al., 2023). The RANKL/RANK/OPG signaling pathway plays critical roles in regulating differentiation and resorption activity of osteoclasts and is involved in physiological and pathological bone reconstruction processes.

Phytic acid is a naturally occurring phosphorus compound in whole grains. As one of phytic acids, inositol hexakisphosphate (IP6) inhibited RANKL-induced osteoclastogenesis and reduced the expression levels of the osteoclast markers TRAP, calcitonin receptor, and histone K in RAW 264.7 cells (Bosco et al., 2021). In addition, IP6 (1 µM) also inhibited the osteoclastogenesis of human peripheral blood mononuclear cells and resorption activity (Arriero Mdel et al., 2012). However, as one of phytic acids, IP6 has strong chelating capacity and potentially hinders mineral absorption. The in vivo study focusing its impact on mineral absorption is deficient. More animal studies should be done to further explore the relationship of IP-6 administration and mineral absorption. Avenanthramides (Avns) are the polyphenols only identified in oats. Report indicated that Avns exhibited the ability to suppress RANKL expression in MLO-Y4 osteocytic cells and promote osteoclasts apoptosis (Pellegrini et al., 2016). Collectively, whole grains-derived phytochemicals might play essential roles in mitigating osteoporosis process via inactivating osteoclasts differentiation and activity.

Reasonable diet rich in fermentable whole grains improves BMD and calcium absorption

Calcium and phosphorus are the main mineral components of bone tissue and BMD is an important indicator of bone strength. Dietary composition is significantly associated with bone density and consumption of fermented foods is beneficial for bone health (Kelaiditi et al., 2016). After treatment with fermented wheat, the indicators of bone metabolism such as hydroxyproline (HOP), tartrated resistant acid phosphatase (TRACP) and ALP were measured. The results revealed a dose-dependent intestinal calcium absorption and BMD improvement in retinoic acid-induced osteoporosis rats (Altaf et al., 2022). Calcium deficiency is leading factor for osteoporosis in children. Publication indicated that certain processing could double the bioavailability of calcium in finger millet and a finger millet-based diet, and therefore enhanced calcium absorption and improved children’s bone growth (Liu et al., 2006). Indigestible carbohydrates contained in cereals, such as soluble corn fibre (SCF), could be fermented by bacteria in the lower intestine and produce SCFA. Animal experiment demonstrated that SCF supplementation improved calcium absorption, mineral retention and bone content (Wu et al., 2017). Clinical trial also confirmed that the bone mass in adolescents was significantly increased after supplementation with SCF for 1 year (Palacios et al., 2020). And SCF consumption also increased bone calcium retention in a dose-dependent manner in postmenopausal women (Zhao et al., 2022). It means that fermentable whole grains enriched diet contributes to improve bone healthy. However, excessive intake of whole grains may result in reducing nutrients absorption via forming a barrier in the small intestinal cavity.

Potential combined effects of whole grains diet on modulating muscle-bone axis

Skeletal muscle usually attached to the surface of bone tissue and form the musculoskeletal apparatus, which play an irreplaceable role in maintaining posture, coordinating movement, and balancing internal environment (Bosco et al., 2021). Recent reports demonstrated that skeletal-bone axis exerted critical roles in maintaining bone health (Kaji, 2014; Karava et al., 2021). The relationship between muscle and bone can be briefly described in these two ways: (1) Biomechanical relationship: the gradually increasing volume of muscle is usually accompanied with the enhancing mass, size and strength of bone (Cooper et al., 2012). (2) Altering the level of endocrine hormones: both myocytes and osteocytes have endocrine functions that are regulated by many similar factors and are inextricably linked. Both oestrogen and testosterone are involved in the regulation of skeletal and muscular growth and development. Regardless of gender, testosterone plays an important role in the development and maintenance of muscle and bone integration, with testosterone levels positively correlating with bone density and muscle strength, while oestrogen levels positively correlate with body mass, muscle mass and muscle strength (Taaffe et al., 2005; van Geel et al., 2009; Vlachopoulos et al., 2017). Whole grains diet also affects muscle mass and has an impact on bones. Supplementation of oat β-glucan led to upregulating skeletal muscle cell differentiation-related genes expression, downregulating muscle atrophy related genes expression, and promoted muscle health (Ceylan et al., 2021). Study also indicated that adherence to a Mediterranean diet characterized by a high intake of whole grains could improve the quality and function of skeletal muscle and alleviate osteoporosis caused by reduced bone density (Kelaiditi et al., 2016). However, the direct correlation of whole grains diet and muscle-bone axis is still weak, more studies and evidences are needed for further clarifying their relationship.

Conclusion

Osteoporosis is a bone disease mostly associated with aging and hormone level alteration. Whole grains contain various functional ingredients beneficial to human health, which is one of the research hotspots in recent years. In addition to macronutrients and micronutrients, whole grains are also rich in non-nutrient bioactive components such as phenolic compounds, saponin, lignans and phytosterols. These substances play an important role in chronic disease prevention. For osteoporosis caused by aging and other reasons, ingredients from whole grains contribute to promoting osteoblast differentiation, suppressing osteoclast production, and modulating muscle-bone axis. Especially, fermentable whole grains improve calcium absorption and BMD, and may prevent osteoporosis. It is foreseeable that whole grain foods may be an important dietary strategy for osteoporosis prevention.

Acknowledgements　This work was supported by the National Key R&D Program of China (grant number 2022YFF1100204); Beijing Nova Program (grant number Z181100006218043); Beijing Natural Science Foundation (grant number 7172210); and Cultivation Project of Double First-Class Disciplines of Food Science and Engineering, Beijing Technology & Business University (BTBU) (grant number BTBUYXTD202201).

Author contributions　Conceptualization, YYH, WJ; writing-original draft, ZJJ, ZMJ; writing-review and editing, YYH, WJ, SBG.

Conflict of interest　There are no conflicts of interest to declare.

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