The lower risk of chronic noncommunicable diseases associated with the MedDiet is known. However, the study of the relationship between the MedDiet and bone health, more specifically bone mineral density (BMD), is recent ^[1][3]. So, current studies point to the potential benefits of the MedDiet for bone health (namely, bone mineral status, bone biomarkers and fracture incidence) ^[1][2][3][2,3,38]. In fact, several authors indicated that the low incidence of OP in Mediterranean countries could be explained by diet [2]. This diet, high in essential nutrients and other bioactive components (calcium and vitamin D, protein and magnesium (Mg), among others), is involved in maintaining healthy bones. Thus, an optimal and continuous nutrient supply is necessary to compensate for the constant remodeling of the skeleton and muscle wasting due to inflammation and oxidative stress ^[4][47]. In this regard, the anti-inflammatory properties of some of its components, such as fruits, vegetables, nuts, cereals, legumes, fish and, in particular, EVOO (as a main source of fat) seem to play a relevant role, decreasing the bone reabsorption process ^[5][6][7][8] (Figure 1) [7,48,49,50]. Contrarily, the Western or pro-inflammatory dietary pattern, rich in soft drinks, fried foods, meat, processed products, sweets and refined grains, is associated with OP and calcium nephrolitiasis ^[7][9][49,51].

However, the available data correlating the MedDiet with good bone health have been deemed controversial by a few studies. In fact, the association between the MedDiet and a lowered risk of fracture has been called into question ^[10][11][12][19,52,53].

The BMD was the common bone outcome measured in the majority of studies ^{[1][3][13][14]}[3,38,54,55]. In fact, several of them related adherence to the MedDiet to higher BMD as well as a reduced risk of fracture ^[1][14][3,55]. These works have been conducted in a postmenopausal and/or elderly population ^[2][15][16][2,56,57]. However, Pérez-Rey et al. analyzed a population of Spanish premenopausal women and detected a positive association between the degree of adherence to the MedDiet and bone density assessed by DXA, QUS and pQCT ^[3][38]. Likewise, in a Chinese middle-aged and elderly population, it was found that greater adherence to the MedDiet was related to higher BMD by DXA ^[15][56]. This association was also observed in an American population [2]. Nevertheless, Kotogianni et al. observed no significant effect of the Mediterranean dietary pattern on bone mass. However, a positive relationship was found between MedDiet adherence and bone mass ^[17][58]. Similarly, in the NU-AGE (New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe) multicenter randomized trial, participants aged 66–74 years who ingested a Mediterranean-like dietary pattern and a vitamin D3 supplement (400 IU/d) did not exhibit any effect on the BMD, but individuals with OP had a significantly reduced rate of bone loss of at the femoral neck ^[13][54].

The role of certain nutrients present in the MedDiet may have potential benefits for BMD (Table 1). Traditionally, studies have focused on the roles of calcium, vitamin D, protein and dairy, but there is growing evidence of a positive relationship between the components of fruits and vegetables and bone health. In fact, adequate intake of some of these components, such as phytochemicals (e.g., carotenoids, and genistein aglycone), vitamin C and selenium, could improve BMD. Specifically, the study of Marini et al. found that beta-carotene slowed bone reabsorption, and genistein aglycone administration decreased levels of bone reabsorption markers (pyrrolidonyl aminopeptidase (PYR), telopeptide of type I collagen (CTX) and receptor activator of nuclear factor B (RANKL) and increased new bone formation markers (IGF-I and osteoprotegerin (OPG)) ^[18][59]. Furthermore, vitamin C has been associated with BMD in the femoral neck and lumbar spine ^[8][19][50,60]. Regarding selenium, higher levels were positively related to site-specific BMD ^[20][61]. Similarly, other diets rich in fruits and vegetables, such as DASH (Dietary Approaches to Stop Hypertension), reduced serum osteocalcin by 8–11% and CTX by 16–18% ^[6][48].

Along the same lines, the dietary intake of OO has been positively associated with total, trabecular and cortical BMD ^[21][62]. Olive polyphenols have been shown to protect bone health via oxidative stress reduction and anti-inflammatory effects (Figure 1). A dose-dependent protective effect of oleuropein (a polyphenol from OO) has been discovered in a model of rats with bone loss ^[22][63]. Also, hydroxytyrosol, formed by the hydrolysis of oleuropein during the maturing of olives, could prevent osteopenia by increasing bone formation ^[23][64]. In this regard, olive polyphenols favor the growth and differentiation of pre-osteoblasts and decrease osteoclast formation ^{[24][25][26][27]}[65,66,67,68]. In addition, Fernandez-Real et al. showed that a MedDiet enriched with VOO, compared with a walnut-enriched MedDiet and a low-fat diet for two years, had a positive effect on serum markers of bone formation and caused a reduction in the circulating concentration of markers of bone reabsorption ^[28][69].

Another phenolic compound that belongs to the group of phytoestrogens and is present in vegetables and abundant in red grapes and red wine is resveratrol (RES). This compound promotes the maturation of osteoblasts and slows down the formation of osteoclasts in vitro. Hence, RES has been related to the preservation of bone mass, microarchitecture and strength in rats ^[29][70]. In fact, moderate alcohol intake, specifically red wine, a typical component of the MedDiet, might prevent bone loss in older men, and a moderate intake of wine might do so in women ^[30][31][71,72].

In addition, moderate fish intake is a feature of the MedDiet. Fish contains numerous nutrients that have a beneficial effect on bones. Specifically, it is a source of high-quality protein, omega-3 fatty acids, vitamins A and D, and minerals such as selenium, calcium, iodine and zinc ^[12][53]. In fact, the recent review by Perna et al. indicates that fish has a positive impact on BMD mainly due to the anti-inflammatory effect of omega-3 fatty acids. In particular, DHA are positively related with bone mineral accumulation and with peak BMD in young men. DHA seems to be a vital constituent of healthy modeling bone because it accumulates in the osteoblast-rich periosteum of the femur in growing rats ^[32][33][10,73]. Moreover, omega-3 fatty acids favor duodenal calcium absorption and lead to decreased calcium excretion ^[32][34][10,74].

Also, the intake of legumes and cereals (grains) is high in the Mediterranean dietary pattern. These foods are rich in vitamin B, calcium and phytochemicals. Their adequate consumption has been related to higher BDM and decreased bone loss with aging. Therefore, the data suggest that legumes and grains may protect bone metabolism in humans ^[35][36][75,76].

In contrast to the Mediterranean dietary pattern, a higher adherence to pro-inflammatory dietary patterns, distinguished by its content in processed food, fats and red meat, has been linked to lower BMD and increased peripheral inflammation ^[7][49].

Different strategies to decrease the increase in fragility fractures have been sought. Among them, adherence to a healthy diet such as the MedDiet was linked to a lower rate of hip fractures ^[2][37][2,44]. This reduction in the number of hip fractures was also observed in Mediterranean population or Americans who follow the Mediterranean dietary pattern compared to the rate of fractures in the population of Northern Europe ^[2][38][2,77]. According to Haring et al., a lower risk of hip fractures was reported with higher adherence to the MedDiet in women aged 50–79 years in a post hoc analysis of longitudinal data from the United States Women’s Health Initiative (median follow-up of 15.9 years) [2]. Similarly, the EPIC (European Prospective Investigation into Cancer and Nutrition) study in men and women (N = 188,795 participants, 802 incident hip fractures) observed that a higher adherence to the MedDiet reduced the incidence of hip fractures by 7%, particularly in men ^[11][52]. Also, the meta-analysis of Malmir specified that higher adherence to the MedDiet was associated with a 21% decreased hip fracture risk ^[1][3].

To explain the inverse association between MedDiet adherence and hip fractures, whether or not type 2 diabetes mellitus (T2DM) and body mass index (BMI) mediated this relationship was analyzed. The state of systemic inflammation that encourages the development of chronic noncommunicable diseases such as OP, obesity and T2DM ^[39][40][78,79], could play a role. In fact, Cauley et al. observed that baseline markers of inflammation were higher among subjects who subsequently experienced an incident fracture ^[41][80]. However, Mitchell et al. reported a direct effect on hip fracture risk via pathways other than T2DM and BMI, yet they could not rule out the mediating effects of BMI and T2DM, even if their effects canceled each other out ^[42][81].

On the other hand, better MedDiet adherence in middle-aged women (45–65 years), with or without OP, was associated with a lower bone risk fracture ^[43][82]. However, the evidence of a protective effect of the MedDiet on total fracture risk has been contradictory. In fact, a small older French population study found that higher MedDiet adherence was associated with a nonsignificant reduced risk of fractures to the hip, spine and wrist ^[10][19].

Nevertheless, it is necessary to emphasize that causality has not been established by these studies, as they are not randomized trials; most are cross-sectional and observational. In addition, the effect of the MedDiet is possibly due to particular dietary components whose intake should be increased. For example, in the PREDIMED (Prevention with Mediterranean diet) trial, greater consumption of EVOO was associated with a lower risk of OP-related fractures in an older Mediterranean population at high cardiovascular risk ^[5][7]. Specifically, individuals in the highest tertile of EVOO consumption had a 51% lower risk of fractures than those in the lowest tertile. Total and standard OO intake has not been associated with fracture risk ^[5][7]. Therefore, EVOO is the best quality oil compared to other OOs. Indeed, EVOO has the highest amounts of bioactive and antioxidant components, such as polyphenols, with probable beneficial effects on bone metabolism ^[44](Figure 1) [83]. In contrast, regular OO is more than 80% refined, with fewer antioxidant and anti-inflammatory compounds ^[5][7]. Also, fish, a source of omega-3 PUFA, has been inversely associated with hip fracture risk ^[45][84]. Other typical Mediterranean foods have been demonstrated to reduce the risk of fracture, such as legumes, cereals ^[36][76] and wine ^[43][82]. Also, high fruit and vegetable intake can give antioxidant power due to vitamins such as vitamin C. Specifically, this is required for collagen synthesis and osteoblast generation. In this regard, a higher vitamin C intake has been related to higher BMD at the femoral neck and lumbar spine and a lower fracture risk ^[46][47][9,85]. In addition, a dose–response relationship between fruit and vegetable intake and hip fracture has been described. Hence, consumption of fewer than five servings of fruit and vegetables per day was associated with higher rates of hip fracture ^[48][86]. Also, the combination of fruit and vegetables with fermented milk (yogurt or sour milk) was shown to decrease the rate of hip fracture ^[49][87].

In contrast, supplementing the diet with sugar does not promote bone health. In fact, a substudy of PREDIMED, PREDIMED-Reus detected that a higher dietary glycemic index and higher dietary glycemic load values could increase the risk of osteoporotic fracture ^[50][88].

On the other hand, Jennings et al. reported that the additive effects of individual components within the Mediterranean diet in a non-Mediterranean region have a greater effect on fracture incidence than the individual components of this diet ^[13][54].

In summary, different factors have to be considered. However, adherence to a Mediterranean dietary pattern with an adequate consumption of OO, preferably EVOO, fish, fruit and vegetables, avoiding high-glycemic-index sugars, could decrease the risk of fractures related to OP (Table 1).