Osteoporosis and Dietary Inflammatory Index

*Olga Cvijanović Peloza, Sandra Pavičić Žeželj, Gordana Kenđel Jovanović, Ivana Pavičić, Ana Terezija Jerbić Radetić, Sanja Zoričić Cvek, Jasna Lulić Drenjak, Gordana Starčević Klasan, Ariana Fužinac Smojver and Juraj Arbanas*

#### **Abstract**

Healthy bones are constantly being renewed and proper nutrition is an important factor in this process. Anti-inflammatory diet is designed to improve health and prevent the occurrence and development of chronic diseases associated with inadequate diet. Proper nutrition is based on the anti-inflammatory pyramid and changes in poor eating habits are the long-term strategy for preventing inflammation and chronic diseases. Inflammatory factors from food may play a role in the development of osteoporosis and an anti-inflammatory diet may be a way to control and reduce long-term inflammation and prevent bone loss. Pro-inflammatory cytokines from the fat tissue, through activation of the RANKL/RANK/OPG system could intervene with bone metabolism in a way of increased bone loss. Therefore the special attention need to be given to obese patients due to twofold risk, one related to proinflammatory cytokines release and the other related to the deprivation of the vitamin D in the fat tissue.

**Keywords:** chronic diseases, cytokines, dietary inflammatory index, obesity, osteoporosis

#### **1. Introduction**

Along with water and oxygen, food is the basis of life. The food contains essential compounds, and their lack leads to imbalance, affects the metabolism and functioning of organic systems, creating a prerequisite for diseases [1]. Adequate nutrition is one of the crucial factors in maintaining good health in adulthood. It also forms the basis of proper growth and development of children and adolescents [2].

The main guidelines for improving nutrition are listed in the National Food Policies. Similarly to existing policies, the Croatian Food Policy, states that proper nutrition is one that:


According to data available from the World Health Organization, it is important to recognize the dangers arising from excessive food consumption and the danger of insufficient energy intake of some nutrients. Hundreds of millions of people suffer from diseases that are the result of an unbalanced diet or consuming excessive amounts of food. There is increasing data that diet rich in lipids, rather saturated fatty acids than unsaturated, high intake of sugar and sodium, but lower intake of micronutrients and complex carbohydrates leads to an increase in cardiovascular diseases, obesity, diabetes, osteoporosis, and cancer [4].

Available data that refers to the science of nutrition, suggest two major directions in history. Firstly, energy intake and nutritional needs were investigated, while nowadays, research is focused on nutrients that have a positive impact on human health and the impact of diet on gene expression [5].

Many nutrients have been linked to bone health, including some like dairy, fish, vegetables and soy which can improve it, while unbalanced and salty diet can influence it negatively. Calcium is the most abundant mineral in the body, 1.5-2% of total body weight is mostly found in bones and teeth, about 99% and 1% is found in extracellular fluid and soft tissues. Calcium plays a role in regulating normal muscle and nerve irritability, regulates cell membrane permeability to sodium and participates in blood coagulation. Calcium ingested with food is absorbed by 10-30%. There is an increased need for calcium in pregnancy and lactation [6]. Milk and dairy products are the best sources of calcium, but it can also be found in some types of green leafy vegetables, fish, meat, and grains [7]. The recommended daily intake of calcium in Croatia is 800 mg [8].

Phosphorus is also linked to bone health. Phosphorous and calcium are major constituents of the hydroxyapatite [9]. Recommended daily intake of phosphorus is 700 mg/day [9]. Foods rich in phosphorus are fish, meat, cereals and carbonated beverages [10].

Vitamin D plays a leading role in bone health. It is a fat-soluble vitamin and needs bile salts for its absorption [6]. The metabolism of phosphorus and calcium affects the physiological role of vitamin D, as it conditions their resorption and deposition in bone tissue. Vitamin D deficiency in the body causes rickets in children, and osteomyelitis in adults [6]. Vitamin D is found in eggs, liver, fish oil and butter. Food is poor in vitamin D, so it is necessary to expose the skin to UV radiation.

Proteins of animal or vegetable origin are important part of the diet of children and adults. The recommended daily protein intake is 0.8 g/kg per day and is not sufficient for the elderly [11, 12]. Proteins are needed for the collagen synthesis in bone and have a positive effect on bone health especially in the elderly when protein-energy malnutrition leads to an increased risk of fractures [11].

In addition to macronutrient proteins, fats additionally affect bone. Fats area unit outlined as organic compounds found in foods of animal and plant origin. The role of fats within the body is multiple: additionally to carbohydrates, they are the most supply of energy, change the perform of nerve impulses, regulate temperature, and area unit carriers of fat-soluble vitamins. The counseled daily fat intake ought to be a minimum of 15% of the overall daily energy intake (WHO) [6]. Diet wealthy in saturated fatty acids and lack of physical activity will result in blubber. Fat tissue produces adipokines, which are pleiotropic molecules that not solely

**31**

*Osteoporosis and Dietary Inflammatory Index DOI: http://dx.doi.org/10.5772/intechopen.96772*

could negatively influence bone health [15].

consumes less energy.

onions, shallots, garlic, leeks.

they can all fall into two categories:

coconut [16].

regulate food intake and energy metabolism however are concerned within the complicated interactions between fat tissue and bone [13, 14]. Some investigations imply that cytokines of fat tissue intervene with bone metabolism. General inflammation, a key element within the pathological process of metabolic syndrome,

The anti-inflammatory diet is similar to the Mediterranean diet, designed to improve health and to prevent the occurrence and development of chronic diseases associated with an inadequate diet. Excessive consumption of certain foods, especially industrially processed, stress, insufficient physical activity and too much adipose tissue cause low-grade chronic inflammation, which can precipitate cardiovascular disease, insulin resistance, type II diabetes, arthritis, neurological diseases, thyroid disease, carcinomas and some mental diseases. An anti-inflammatory diet does not necessarily mean a major change to the usual diet, it may contain local, common foods, but it is of utmost importance to avoid food with a high risk for diseases. On the other hand, an anti-inflammatory diet provides a certain ratio of nutrients that regulate energy consumption in a better way, acts on satiety and

It is important to note that this diet is rich in many nutrients that balance health

In addition to the usual foods that make up the Mediterranean diet, the basis of the anti-inflammatory diet is vegetables that grow above ground - cabbage, broccoli, cauliflower, kale, Brussels sprouts, spinach, chicory, chard, kale, eggplant, olives, beans, artichokes, asparagus, zucchini, lettuce, endive, dill, chicory, rocket, cucumbers, tomatoes, peppers, fennel, celery, pumpkin, onions, spring

Of the fruits, these are avocado, lemon, and spices such as ginger, turmeric with pure herbs that have a special role - parsley leaf, thyme, oregano, basil, rosemary, sage, cinnamon, cumin, clove, mint, lavender, anise, and fennel. Of the oils, coldpressed oils are recommended - olive, pumpkin, flaxseed, and less often hemp and

Postmenopausal osteoporosis is characterized by rapid bone loss, especially in during the first 5 years of the menopause. Clinical symptoms of osteoporosis are usually not present, which is why it is called silent disease. Decrease in estrogen levels trigger numerous changes in bone metabolism which result in bone mass loss and bone quality disorders. They firstly alter trabecular bone and subsequently cortical frame, all together leading to fracture of single bones. Fractures can occur

In clinical practice, there are several approaches in diagnosing osteoporosis, and

The technique most commonly used by physicians to make a quantitative diagnosis of osteoporosis is to measure bone mineral density by dual-energy X-ray absorptiometry - DEXA. The advantage of this technique is simple and quick application, which enables BMD values to be available to the physician in a short period of time. Usually, BMD is measured in the places that are most susceptible

in any bone, but mostly affect hip, vertebrae of the spine, and wrist [17].

and prevent the onset and development of various chronic diseases.

**2. Osteoporosis and dietary inflammatory index**

• Clinical assessment of risk factors for osteoporosis

• Determination of bone mineral density (BMD)

#### *Osteoporosis and Dietary Inflammatory Index DOI: http://dx.doi.org/10.5772/intechopen.96772*

*Osteoporosis - Recent Advances, New Perspectives and Applications*

diseases, obesity, diabetes, osteoporosis, and cancer [4].

health and the impact of diet on gene expression [5].

intake of calcium in Croatia is 800 mg [8].

beverages [10].

radiation.

According to data available from the World Health Organization, it is important to recognize the dangers arising from excessive food consumption and the danger of insufficient energy intake of some nutrients. Hundreds of millions of people suffer from diseases that are the result of an unbalanced diet or consuming excessive amounts of food. There is increasing data that diet rich in lipids, rather saturated fatty acids than unsaturated, high intake of sugar and sodium, but lower intake of micronutrients and complex carbohydrates leads to an increase in cardiovascular

Available data that refers to the science of nutrition, suggest two major directions in history. Firstly, energy intake and nutritional needs were investigated, while nowadays, research is focused on nutrients that have a positive impact on human

Many nutrients have been linked to bone health, including some like dairy, fish, vegetables and soy which can improve it, while unbalanced and salty diet can influence it negatively. Calcium is the most abundant mineral in the body, 1.5-2% of total body weight is mostly found in bones and teeth, about 99% and 1% is found in extracellular fluid and soft tissues. Calcium plays a role in regulating normal muscle and nerve irritability, regulates cell membrane permeability to sodium and participates in blood coagulation. Calcium ingested with food is absorbed by 10-30%. There is an increased need for calcium in pregnancy and lactation [6]. Milk and dairy products are the best sources of calcium, but it can also be found in some types of green leafy vegetables, fish, meat, and grains [7]. The recommended daily

Phosphorus is also linked to bone health. Phosphorous and calcium are major constituents of the hydroxyapatite [9]. Recommended daily intake of phosphorus is 700 mg/day [9]. Foods rich in phosphorus are fish, meat, cereals and carbonated

Vitamin D plays a leading role in bone health. It is a fat-soluble vitamin and needs bile salts for its absorption [6]. The metabolism of phosphorus and calcium affects the physiological role of vitamin D, as it conditions their resorption and deposition in bone tissue. Vitamin D deficiency in the body causes rickets in children, and osteomyelitis in adults [6]. Vitamin D is found in eggs, liver, fish oil and butter. Food is poor in vitamin D, so it is necessary to expose the skin to UV

Proteins of animal or vegetable origin are important part of the diet of children and adults. The recommended daily protein intake is 0.8 g/kg per day and is not sufficient for the elderly [11, 12]. Proteins are needed for the collagen synthesis in bone and have a positive effect on bone health especially in the elderly when

In addition to macronutrient proteins, fats additionally affect bone. Fats area unit outlined as organic compounds found in foods of animal and plant origin. The role of fats within the body is multiple: additionally to carbohydrates, they are the most supply of energy, change the perform of nerve impulses, regulate temperature, and area unit carriers of fat-soluble vitamins. The counseled daily fat intake ought to be a minimum of 15% of the overall daily energy intake (WHO) [6]. Diet wealthy in saturated fatty acids and lack of physical activity will result in blubber. Fat tissue produces adipokines, which are pleiotropic molecules that not solely

protein-energy malnutrition leads to an increased risk of fractures [11].

• ensures a sufficient amount of minerals;

• ensures sufficient intake of vitamins;

• provides the body's needs for water [3].

**30**

regulate food intake and energy metabolism however are concerned within the complicated interactions between fat tissue and bone [13, 14]. Some investigations imply that cytokines of fat tissue intervene with bone metabolism. General inflammation, a key element within the pathological process of metabolic syndrome, could negatively influence bone health [15].

The anti-inflammatory diet is similar to the Mediterranean diet, designed to improve health and to prevent the occurrence and development of chronic diseases associated with an inadequate diet. Excessive consumption of certain foods, especially industrially processed, stress, insufficient physical activity and too much adipose tissue cause low-grade chronic inflammation, which can precipitate cardiovascular disease, insulin resistance, type II diabetes, arthritis, neurological diseases, thyroid disease, carcinomas and some mental diseases. An anti-inflammatory diet does not necessarily mean a major change to the usual diet, it may contain local, common foods, but it is of utmost importance to avoid food with a high risk for diseases. On the other hand, an anti-inflammatory diet provides a certain ratio of nutrients that regulate energy consumption in a better way, acts on satiety and consumes less energy.

It is important to note that this diet is rich in many nutrients that balance health and prevent the onset and development of various chronic diseases.

In addition to the usual foods that make up the Mediterranean diet, the basis of the anti-inflammatory diet is vegetables that grow above ground - cabbage, broccoli, cauliflower, kale, Brussels sprouts, spinach, chicory, chard, kale, eggplant, olives, beans, artichokes, asparagus, zucchini, lettuce, endive, dill, chicory, rocket, cucumbers, tomatoes, peppers, fennel, celery, pumpkin, onions, spring onions, shallots, garlic, leeks.

Of the fruits, these are avocado, lemon, and spices such as ginger, turmeric with pure herbs that have a special role - parsley leaf, thyme, oregano, basil, rosemary, sage, cinnamon, cumin, clove, mint, lavender, anise, and fennel. Of the oils, coldpressed oils are recommended - olive, pumpkin, flaxseed, and less often hemp and coconut [16].

#### **2. Osteoporosis and dietary inflammatory index**

Postmenopausal osteoporosis is characterized by rapid bone loss, especially in during the first 5 years of the menopause. Clinical symptoms of osteoporosis are usually not present, which is why it is called silent disease. Decrease in estrogen levels trigger numerous changes in bone metabolism which result in bone mass loss and bone quality disorders. They firstly alter trabecular bone and subsequently cortical frame, all together leading to fracture of single bones. Fractures can occur in any bone, but mostly affect hip, vertebrae of the spine, and wrist [17].

In clinical practice, there are several approaches in diagnosing osteoporosis, and they can all fall into two categories:


The technique most commonly used by physicians to make a quantitative diagnosis of osteoporosis is to measure bone mineral density by dual-energy X-ray absorptiometry - DEXA. The advantage of this technique is simple and quick application, which enables BMD values to be available to the physician in a short period of time. Usually, BMD is measured in the places that are most susceptible

to fractures (hip, spine and forearm). Based on bone mineral density values, the World Health Organization has defined indicators for the diagnosis of osteoporosis in menopausal women. Thus, osteoporosis can be diagnosed in women whose BMD values are 2.5 and more standard deviations (SD) lower than the average peak bone mass values that apply to young, healthy, white women (standard). By comparing the measured values of BMD and standards (peak bone mass), the T coefficient is obtained. The Z coefficient represents the deviation of the measured value of BMD from the average bone mass of persons of the same age, expressed in standard deviations. Values of T coefficient of -2.5 and less, and Z coefficient of -1 and less, speak in favor of osteoporosis. Values of T > 1 indicate increased bone mass; values of T coefficient between -1 and -2 indicate osteopenia and those values of T coefficient between -1 and -2.5 indicate normal bone mass [17]. Numerous prospective studies have given bone mineral density results that have shown a good association with the occurrence of fractures in subjects (R2 = 0.4 - 0.9). In a study conducted by Marshall et al. on 90,000 women, more than 2,000 of whom had fractures, it was shown, that decrease in BMD of 1 SD for a given age, is associated with the risk of one to one and a half bone fractures [17]. Referring to the results of Marshall et al., BMD values have increasingly been used in clinical practice to assess the risk of bone fractures. However, there are a number of limiting circumstances that do not allow the notion of BMD as a surrogate in the assessment of bone strength and bone biomechanical abilities. Interpretation of BMD values is sometimes illogical and cannot be used in fracture risk assessment. This is supported by the finding of 50% of women who had a fracture, and whose BMD values measured on the spine and hip were above the -2.5 SD threshold to be able to diagnose osteoporosis at all. Another limitation relates to faults that occur during scanning, so that poor patient position or changes in patient orientation in serial images give inaccurate BMD values or values that are often difficult to interpret [18]. Risk factors for bone fractures include excessive alcohol consumption, female gender, positive fracture in medical history, female hip fracture, oral glucocorticoid use, lack of physical activity and nutritional factors [18, 19]. Lifestyle factors which are the most investigated in relation to bone health are nutrition and physical activity. Recent Meta-Analyses showed that exercises can significantly improve trabecular volumetric BMD values measured on tibia and can increase lumbar spine and femoral neck BMD, in postmenopausal women [19]. Mechanical strain activates osteocytes, which initiate bone remodeling resulting in repair of bone tissue damaged by microcracks. On the opposite, bone damage or long-term immobilization results in osteocyte apoptosis and increased osteoclastogenesis.

Low values of body mass index are also associated with the risk of bone fractures as well as low values of bone mineral density [18]. When for some reason it is not possible to determine bone mineral density values, then the body mass index provides useful data to assess fracture risk. It can be said that the above risk factors are not in themselves sufficient in the assessment of fracture risk or in the assessment of bone mineral density values. However, risk factors are useful as a complement to the densitometry finding in the clinical interpretation of fracture risk. The intensity of bone remodeling can be assessed by determining the values of biochemical markers in serum and urine [20].

Under physiological conditions, bone remodeling maintains the bone mass that the body needs not only for metabolic needs, but also to perform important biomechanical functions.

Higher intensity of bone resorption leads to a negative balance of bone remodeling which affects the change of structural and material properties of bone.

**33**

*\**

**Table 1.**

*Osteoporosis and Dietary Inflammatory Index DOI: http://dx.doi.org/10.5772/intechopen.96772*

not misinterpreted [21, 22] .

N-terminal telopeptide (NTx), and deoxypyridinoline. Bone-forming markers include bone-specific alkaline phosphatase (bALP), osteocalcin and residuals that are released by the action of lysine on the procollagen molecule [20]. A large number of investigations which have taken inflammatory etiology of osteoporosis into consideration, have measured experimentally and also in patients the levels of the receptor activator of nuclear factor κB (RANK), its functional ligand (sRANKL) and decoy receptor to RANKL, osteoprotegerin (OPG). sRANKL is a member of the TNF-α family of the cytokines and induces maturation, differentiation and activity of osteoclasts in direct manner or indirectly, as result of macrophage-colony stimulating factor stimulation. Estrogen related bone loss, which is pronounced in the first 5 years of the menopause can be also related to RANKL activation. Care should be taken in determining the value of bone markers so that the results obtained are

To relate research with dietary inflammatory potential and its effect on human health, scientists have developed and validated the "Dietary Inflammatory Index - DII" [23]. DII has been shown to be statistically significantly associated with inflammatory biomarkers, particularly IL-6, TNF-α, hs-CRP, and with the combined score of inflammatory biomarkers [24]. DII is an index for assessment of an individual's dietary inflammatory ability, designed on 1943 scientific papers, and is composed of 45 nutritional parameters, which are rated according to pro-inflammatory or antiinflammatory effect [23] (**Table 1**). It is based on results published in the scientific literature and then standardized with global intake values for all dietary parameters included in the DII index. (Parameter that has a pro-inflammatory effect is scored with +1, while parameter with anti-inflammatory effect with -1 and with 0 parameters without effect. The DII index is increasingly used to assess the association of the inflammatory potential of the diet with various inflammatory chronic diseases [25], cardiovascular disease [25], carcinomas [26–33], premature death as a result of chronic non-communicable diseases [25], asthma [34] and depression and anxiety [35, 36] (**Table 2**). The biggest potential of the DII index is in the selection of anti-

inflammatory food, and control over inflammatory diseases.

Curcuma -0,785 533 mg Saturated

**World average daily intake**

Isoflavonoids -0,593 1,20 mg Total fats 0,298 71,4 g Beta carotene -0,584 3718 mcg Trans fats 0,229 3,15 g Green/black tea -0,536 1,69 g Energy 0,180 2056 kcal Mg -0,484 310 mg Cholesterol 0,110 279 mg

*Positive inflammation effective score = proinflammatory; negative inflammation effective score = antiinflammatory.*

*10 most effective antiinflammatory nutrients based on their activity level (inflammation effective score).*

**Nutrient Inflammation** 

fats

**effective score\***

0,373 28,6 g

**World average daily intake**

**effective score\***

Ginger -0,453 59 g Vitamin D -0,446 6,26 mcg Omega-3 FA -0,436 1,06 g Vitamin C -0,424 118 mg Garlic -0,412 4,35 g

**Nutrient Inflammation** 

Bone resorption markers include tartrate-resistant acid phosphatase (TRAP) and type I collagen cleavage products such as C-terminal telopeptide (CTx),

#### *Osteoporosis and Dietary Inflammatory Index DOI: http://dx.doi.org/10.5772/intechopen.96772*

*Osteoporosis - Recent Advances, New Perspectives and Applications*

to fractures (hip, spine and forearm). Based on bone mineral density values, the World Health Organization has defined indicators for the diagnosis of osteoporosis in menopausal women. Thus, osteoporosis can be diagnosed in women whose BMD values are 2.5 and more standard deviations (SD) lower than the average peak bone mass values that apply to young, healthy, white women (standard). By comparing the measured values of BMD and standards (peak bone mass), the T coefficient is obtained. The Z coefficient represents the deviation of the measured value of BMD from the average bone mass of persons of the same age, expressed in standard deviations. Values of T coefficient of -2.5 and less, and Z coefficient of -1 and less, speak in favor of osteoporosis. Values of T > 1 indicate increased bone mass; values of T coefficient between -1 and -2 indicate osteopenia and those values of T coefficient between -1 and -2.5 indicate normal bone mass [17]. Numerous prospective studies have given bone mineral density results that have shown a good association with the occurrence of fractures in subjects (R2 = 0.4 - 0.9). In a study conducted by Marshall et al. on 90,000 women, more than 2,000 of whom had fractures, it was shown, that decrease in BMD of 1 SD for a given age, is associated with the risk of one to one and a half bone fractures [17]. Referring to the results of Marshall et al., BMD values have increasingly been used in clinical practice to assess the risk of bone fractures. However, there are a number of limiting circumstances that do not allow the notion of BMD as a surrogate in the assessment of bone strength and bone biomechanical abilities. Interpretation of BMD values is sometimes illogical and cannot be used in fracture risk assessment. This is supported by the finding of 50% of women who had a fracture, and whose BMD values measured on the spine and hip were above the -2.5 SD threshold to be able to diagnose osteoporosis at all. Another limitation relates to faults that occur during scanning, so that poor patient position or changes in patient orientation in serial images give inaccurate BMD values or values that are often difficult to interpret [18]. Risk factors for bone fractures include excessive alcohol consumption, female gender, positive fracture in medical history, female hip fracture, oral glucocorticoid use, lack of physical activity and nutritional factors [18, 19]. Lifestyle factors which are the most investigated in relation to bone health are nutrition and physical activity. Recent Meta-Analyses showed that exercises can significantly improve trabecular volumetric BMD values measured on tibia and can increase lumbar spine and femoral neck BMD, in postmenopausal women [19]. Mechanical strain activates osteocytes, which initiate bone remodeling resulting in repair of bone tissue damaged by microcracks. On the opposite, bone damage or long-term immobilization results in osteocyte apoptosis

Low values of body mass index are also associated with the risk of bone fractures as well as low values of bone mineral density [18]. When for some reason it is not possible to determine bone mineral density values, then the body mass index provides useful data to assess fracture risk. It can be said that the above risk factors are not in themselves sufficient in the assessment of fracture risk or in the assessment of bone mineral density values. However, risk factors are useful as a complement to the densitometry finding in the clinical interpretation of fracture risk. The intensity of bone remodeling can be assessed by determining the values of

Under physiological conditions, bone remodeling maintains the bone mass that the body needs not only for metabolic needs, but also to perform important biome-

Higher intensity of bone resorption leads to a negative balance of bone remodel-

Bone resorption markers include tartrate-resistant acid phosphatase (TRAP) and type I collagen cleavage products such as C-terminal telopeptide (CTx),

ing which affects the change of structural and material properties of bone.

**32**

chanical functions.

and increased osteoclastogenesis.

biochemical markers in serum and urine [20].

N-terminal telopeptide (NTx), and deoxypyridinoline. Bone-forming markers include bone-specific alkaline phosphatase (bALP), osteocalcin and residuals that are released by the action of lysine on the procollagen molecule [20]. A large number of investigations which have taken inflammatory etiology of osteoporosis into consideration, have measured experimentally and also in patients the levels of the receptor activator of nuclear factor κB (RANK), its functional ligand (sRANKL) and decoy receptor to RANKL, osteoprotegerin (OPG). sRANKL is a member of the TNF-α family of the cytokines and induces maturation, differentiation and activity of osteoclasts in direct manner or indirectly, as result of macrophage-colony stimulating factor stimulation. Estrogen related bone loss, which is pronounced in the first 5 years of the menopause can be also related to RANKL activation. Care should be taken in determining the value of bone markers so that the results obtained are not misinterpreted [21, 22] .

To relate research with dietary inflammatory potential and its effect on human health, scientists have developed and validated the "Dietary Inflammatory Index - DII" [23]. DII has been shown to be statistically significantly associated with inflammatory biomarkers, particularly IL-6, TNF-α, hs-CRP, and with the combined score of inflammatory biomarkers [24]. DII is an index for assessment of an individual's dietary inflammatory ability, designed on 1943 scientific papers, and is composed of 45 nutritional parameters, which are rated according to pro-inflammatory or antiinflammatory effect [23] (**Table 1**). It is based on results published in the scientific literature and then standardized with global intake values for all dietary parameters included in the DII index. (Parameter that has a pro-inflammatory effect is scored with +1, while parameter with anti-inflammatory effect with -1 and with 0 parameters without effect. The DII index is increasingly used to assess the association of the inflammatory potential of the diet with various inflammatory chronic diseases [25], cardiovascular disease [25], carcinomas [26–33], premature death as a result of chronic non-communicable diseases [25], asthma [34] and depression and anxiety [35, 36] (**Table 2**). The biggest potential of the DII index is in the selection of antiinflammatory food, and control over inflammatory diseases.


#### **Table 1.**

*10 most effective antiinflammatory nutrients based on their activity level (inflammation effective score).*


**35**

**Table 3.**

*Osteoporosis and Dietary Inflammatory Index DOI: http://dx.doi.org/10.5772/intechopen.96772*

> **Ethnicity/ participants**

Iran/3363 adult participants (age span 35-45 years)

Spain/7447 PREDIMED participants (men aged 55-80; women aged 60-80)

*DII and its correlation with carcinomas and other diseases.*

**DII Objectives Main results**

To examine the association between DII score and psychological disorders

To examine the relationship between DII and indices of general and abdominal obesity

> To investigate whether the DII scores are associated with increased risks of fractures

To examine DII in relation to risk of fracture and BMD

To investigate association between DII with bone health and obesity in young adults

To examine the relationship between the DII and BMD in lumbar spine and femoral neck

Higher DII score was associated with anxiety and psychological distress

Proinflammatory diet is associated with central and abdominal obesity

Higher DII scores are associated with higher incidence of fractures in women

Lower risk of fractures in women with highest DII

No significant association between DII and femoral neck BMD

DII is associated with obesity parameters but not to osteoporosis in adulthood

DII based on 45 nutrient parameters

DII food parameterspecific for an individual

*IWHS - Iowa Women's Health Study; CRC – colorectal carcinoma; WHI - Women's Health Initiative; MASHAD - Mashhad Stroke and Heart Atherosclerotic Disorder; PREDIMED - Prevención con Dieta Mediterránea.*

**Ethnicity/participants DII Objectives Main results**

DII based on 24 nutrient parameters

DII based on 32 nutrient parameters

DII based on 25 nutrient parameters

DII based on 25 nutrient parameters

*Association between dietary inflammatory indeks with chronic diseases and cancers.*

North America/3648 participants (mean age

United States/160191 postmenopausal women

Spain/599 participants (age span 18-25)

*Association between dietary inflammatory index (DII) with bone mineral density and fracture risk.*

Iran/160 postmenopausal women

*DII - Dietary Inflammatory Index; BMD - Bone Mineral Density.*

60.6 years)

**Authors/design of the study**

Salari-Moghaddam A et al. 2018/cross sectional study

Ruiz-Canela M. et al. 2015/cross sectional study

**Authors/design of the study**

Veronese N et al. 2017/longitudinal cohort study

Orchard T et al. 2016/ cross sectional study

Correa-Rodríguez M et al. 2018/cross sectional study

Shivappa N et al. 2015/ cross sectional

study

**Table 2.**

*Osteoporosis and Dietary Inflammatory Index DOI: http://dx.doi.org/10.5772/intechopen.96772*


*DII and its correlation with carcinomas and other diseases.*

*IWHS - Iowa Women's Health Study; CRC – colorectal carcinoma; WHI - Women's Health Initiative; MASHAD - Mashhad Stroke and Heart Atherosclerotic Disorder; PREDIMED - Prevención con Dieta Mediterránea.*

**Table 2.**

*Osteoporosis - Recent Advances, New Perspectives and Applications*

**DII Objectives Main results**

To examine association between DII (quintile) and CRC

To analyze the association between the DII and the risk of pancreatic cancer

To investigate relationship between DII and risk of developing prostate cancer

To investigate association between DII and CRC and its interaction with polymorphisms of inflammatory

genes

To examine the association of DII with increased risk for CRC in WHI

To examine the association of DII with increased risk of endometrial cancer

To examine the association of DII with increased risk for hepatocellular cancer

To quantify the possible inflammatory effect of diet on the occurrence of depression and anxiety

Significantly higher risk for CRC in the 5th quintile (high DII)

Subjects in the 2nd, 3rd, 4th and

th quintiles had increased risk for pancreatic cancer

Men who had followed a proinflammatory diet were more at risk at developing prostate cancer

High DII diets are associated with increased risk of CRC association differed on the genotype of the cytokines

Consumption of more DII diet was associated with increased risk of CRC, especially proximal colon

Consumption of more DII diet was associated with increased risk of endometrial cancer

Consumption of more DII diet was associated with increased risk for hepatocellular cancer

Significant association between 3rd and 4th quartiles of DII score with severe depression level

5

DII based on 37 nutrient parameters

DII based on 45 nutrient parameters

DII dependent on each publication/ DII is ranged between 18 and 36 nutrient parameters

DII based on 37 nutrient parameters

DII based on 45 nutrient parameters

DII based on 45 nutrient parameters

DII based on 45 nutrient parameters

DII based on 65 nutrient parameters

**Ethnicity/ participants**

United States (lowa)/34,703 postmenopausal women of the IWHS

Italy/326 patients with pancreatic carcinoma and 652 controls (median age

63 years)

Italy, Jamaica, France, Mexico, Iran, Canada/age span 40-94/\*depending on publication

Spain/424 male participants and 401 control/age span

United States/161808 postmenopausal women

Italy/454 women/age span 18-79

participants/age span 43-84 years

Iran/7083 adults of the MASHAD cohort study (age span 35-65

Italy/258

years)

39-60

**Authors/design of the study**

Shivappa N et al. 2014/prospective cohort

Shivappa N et al. 2015/case-control

Mohseni R et al. 2018/ meta-analysis

Zamora-Ros R et al. 2014/ case-control

Tabung FK et al. 2014/prospective

Schivappa N et al. 2016/case control

Schivappa N et al. 2015/case control

Ghazizadeh H et al. 2020/cross sectional

study

study

study

study

study

study

**34**

*Association between dietary inflammatory indeks with chronic diseases and cancers.*


#### **Table 3.**

*Association between dietary inflammatory index (DII) with bone mineral density and fracture risk.*

Proper nutrition based on the anti-inflammatory pyramid and changes in poor eating habits is a long-term strategy for preventing inflammation and developing osteoporosis. The level of inflammation can be measured and monitored using several biomarkers, including pro-and anti-inflammatory cytokines. The main proinflammatory cytokines are tumor necrosis factor (TNF), interleukin (IL) -1, L-6 and interferon (IFN). Anti-inflammatory cytokines are IL-4 and IL-10. C-reactive protein (CRP), and the more recently highly sensitive C-reactive protein (hs-CRP), are clinical markers of inflammation that were used in the study that investigated the association between different conditions and levels of inflammation [37].

Proinflammatory cytokines such as TNF-α, NF-κB, IL-1, and IL-6 are key mediators of the osteoclast differentiation and bone resorption. Bone resorption and bone loss due to chronic inflammation and increased proinflammatory cytokines is found in patients with periodontitis [38], pancreatitis [39] and rheumatoid arthritis [40]. It is also been established that upregulated proinflammatory cytokines are primary mediators of osteopenia or osteoporosis. These proinflammatory cytokines stimulate osteoclast activity through the regulation of the RANKL/RANK/OPG pathway [41]. The assorted increase within the event of osteoarthritis in obese human subjects is another evidence that chronic inflammation influences bone metabolism.

Since the introduction of the inflammatory diet index, numerous studies have related this method to bone health (**Table 3**). All the investigations represented in **Table 3** have analyzed relationship between DII and BMD or fracture risk and results are inconclusive. In a study of Rodrigez et al., association between DII and obesity in young adults was found, with no implication for bone health. Even though, there are rising evidences that in elderly women fat tissue can compromise bone structure and quality. Accordingly, some clinical data showed that obesity is not always protective against osteoporosis. This is supported by the fact that in obesity BMD values are usually falsely increased due to fat deposition and incorrect positioning during bone densitometry scanning [42, 43]. More adequate interpretation of the bone mass has been given by NMR imaging, which revealed decreased values of the trabecular bone volume in elderly women, due to bone marrow infiltration with fat. Given the fact that postmenopausal women have more bone marrow fat in the forearm bones, their trabecular bone volume is deteriorated, which could lead to bone fracture [42]. Replacement of the osteoblasts with adipocytes due to aging or hormones deprivation can also occur as a result of immobilization or physical inactivity. The results of the experimental studies suggest that obesity is epigenetic factor, which can compromise new bone formation in a male offspring of fat mothers. The possible mechanism that prevents bone formation includes systemic inflammation and activation of the RANK/RANKL/OPG system [21, 22]. Pro-inflammatory cytokines, such as TNF-α, activate NF-κB from fat cells in obesity, which could affect bone metabolism in a manner of enhanced bone resorption mediated by osteoclasts and sRANKL [21, 22].

#### **3. Conclusion**

Considering everything, it is clear that further clinical randomized studies are needed to better understand the influence of DII on bone mineral density. Of utmost importance are prospective studies that will follow up dietary habits (DII) along with concentrations of the bone remodeling markers as dynamic indicators of the bone metabolism.

Special attention should be given to obese patients who are at one hand prone to osteoporosis due to increased production of the proinflammatory cytokines from

**37**

*Osteoporosis and Dietary Inflammatory Index DOI: http://dx.doi.org/10.5772/intechopen.96772*

has a positive impact on bone health.

"The authors declare no conflict of interest."

RANK receptor activator of nuclear factor κB

DEXA dual- energy X-ray absorptiometry

TRAP tartrate-resistant acid phosphatase

bALP bone-specific alkaline phosphatase

WHO World Health Organization

BMD bone mineral density SD standard deviations

CTx C-terminal telopeptide NTx N-terminal telopeptide

NFκB nuclear factor-kappa B NMR nuclear magnetic resonance

TNF-α tumor necrosis factor alpha DII Dietary Inflammatory Index

**Acknowledgements**

**Conflict of interest**

**Appendix and nomenclature**

OPG osteoprotegerin

IL-6 interleukin 6 IL-4 interleukin 4 IL-10 interleukin 10 CRP C-reactive protein

IFN interferon

Welfare.

the fat tissue and, on the other hand, lower concentrations of the vitamin D in serum [38]. DII and bone remodeling markers should be followed in patients who lose and gain weight to better understand the influence of the inflammatory diet on bone metabolism and to answer the question, whether an anti-inflammatory diet

The chapter was published from the funds of the Rijeka City Department of Health and Social Welfare and the Municipality of Kostrena Department of Health

sRANKL solubile receptor activator of nuclear factor κ-Β ligand

*Osteoporosis and Dietary Inflammatory Index DOI: http://dx.doi.org/10.5772/intechopen.96772*

the fat tissue and, on the other hand, lower concentrations of the vitamin D in serum [38]. DII and bone remodeling markers should be followed in patients who lose and gain weight to better understand the influence of the inflammatory diet on bone metabolism and to answer the question, whether an anti-inflammatory diet has a positive impact on bone health.

#### **Acknowledgements**

*Osteoporosis - Recent Advances, New Perspectives and Applications*

tion influences bone metabolism.

resorption mediated by osteoclasts and sRANKL [21, 22].

Considering everything, it is clear that further clinical randomized studies are needed to better understand the influence of DII on bone mineral density. Of utmost importance are prospective studies that will follow up dietary habits (DII) along with concentrations of the bone remodeling markers as dynamic indicators of

Special attention should be given to obese patients who are at one hand prone to osteoporosis due to increased production of the proinflammatory cytokines from

Proper nutrition based on the anti-inflammatory pyramid and changes in poor eating habits is a long-term strategy for preventing inflammation and developing osteoporosis. The level of inflammation can be measured and monitored using several biomarkers, including pro-and anti-inflammatory cytokines. The main proinflammatory cytokines are tumor necrosis factor (TNF), interleukin (IL) -1, L-6 and interferon (IFN). Anti-inflammatory cytokines are IL-4 and IL-10. C-reactive protein (CRP), and the more recently highly sensitive C-reactive protein (hs-CRP), are clinical markers of inflammation that were used in the study that investigated the association between different conditions and levels of inflammation [37]. Proinflammatory cytokines such as TNF-α, NF-κB, IL-1, and IL-6 are key mediators of the osteoclast differentiation and bone resorption. Bone resorption and bone loss due to chronic inflammation and increased proinflammatory cytokines is found in patients with periodontitis [38], pancreatitis [39] and rheumatoid arthritis [40]. It is also been established that upregulated proinflammatory cytokines are primary mediators of osteopenia or osteoporosis. These proinflammatory cytokines stimulate osteoclast activity through the regulation of the RANKL/RANK/OPG pathway [41]. The assorted increase within the event of osteoarthritis in obese human subjects is another evidence that chronic inflamma-

Since the introduction of the inflammatory diet index, numerous studies have related this method to bone health (**Table 3**). All the investigations represented in **Table 3** have analyzed relationship between DII and BMD or fracture risk and results are inconclusive. In a study of Rodrigez et al., association between DII and obesity in young adults was found, with no implication for bone health. Even though, there are rising evidences that in elderly women fat tissue can compromise bone structure and quality. Accordingly, some clinical data showed that obesity is not always protective against osteoporosis. This is supported by the fact that in obesity BMD values are usually falsely increased due to fat deposition and incorrect positioning during bone densitometry scanning [42, 43]. More adequate interpretation of the bone mass has been given by NMR imaging, which revealed decreased values of the trabecular bone volume in elderly women, due to bone marrow infiltration with fat. Given the fact that postmenopausal women have more bone marrow fat in the forearm bones, their trabecular bone volume is deteriorated, which could lead to bone fracture [42]. Replacement of the osteoblasts with adipocytes due to aging or hormones deprivation can also occur as a result of immobilization or physical inactivity. The results of the experimental studies suggest that obesity is epigenetic factor, which can compromise new bone formation in a male offspring of fat mothers. The possible mechanism that prevents bone formation includes systemic inflammation and activation of the RANK/RANKL/OPG system [21, 22]. Pro-inflammatory cytokines, such as TNF-α, activate NF-κB from fat cells in obesity, which could affect bone metabolism in a manner of enhanced bone

**36**

**3. Conclusion**

the bone metabolism.

The chapter was published from the funds of the Rijeka City Department of Health and Social Welfare and the Municipality of Kostrena Department of Health Welfare.

#### **Conflict of interest**

"The authors declare no conflict of interest."

#### **Appendix and nomenclature**


### **Author details**

Olga Cvijanović Peloza1 \*, Sandra Pavičić Žeželj2 , Gordana Kenđel Jovanović2 , Ivana Pavičić3 , Ana Terezija Jerbić Radetić1 , Sanja Zoričić Cvek1 , Jasna Lulić Drenjak4 , Gordana Starčević Klasan1 , Ariana Fužinac Smojver5 and Juraj Arbanas1

1 Department of Anatomy, Medical Faculty of the University of Rijeka, Rijeka, Croatia

2 Department of Health Ecology, Medical Faculty of the University of Rijeka, Rijeka, Croatia

3 Clinic of Internal Medicine, CHC Rijeka, Rijeka, Croatia

4 Department of Physiotherapy, Faculty of Health Studies of the University of Rijeka, Rijeka, Croatia

5 Department of Basic Medical Sciences, Faculty of Health Studies of the University of Rijeka, Rijeka, Croatia

\*Address all correspondence to: olga.cvijanovic@uniri.hr

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**39**

*Osteoporosis and Dietary Inflammatory Index DOI: http://dx.doi.org/10.5772/intechopen.96772*

[1] Prentice A. Diet, nutrition and prevention of osteoporosis. Pub Health bone mineral density and the rate of bone loss in elderly women. Am J Clin

[12] Gaffney-Stomberg E, Insogna KL, Rodriguez NR, Kerstetter JE. Increasing

[13] Zaidi, Mone & Buettner, Christoph & Sun, Li & Iqbal, Jameel. (2012). Minireview: The Link Between Fat and Bone: Does Mass Beget Mass?. Endocrinology. 153. 2070-2075. 10.1210/

[14] Magni P., Dozio E., Galliera E., Ruscica M., Corsi M. (2010) Molecular aspects of adipokine–bone interactions.

[15] Cao J. (2011) Effects of obesity on bone metabolism. J Orthop Surg

[16] Jessica K.Black, N.D. The Anti-Inflammation Diet and Recipe Book.

[17] Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence

[18] Kanis JA, Borgstrom F, De Laet C i sur. A meta-analysis of previous fracture and subsequent fracture risk.

[19] Xu J, Lombardi G, Jiao W, Banfi G. Effects of Exercise on Bone Status in Female Subjects, from Young Girls to Postmenopausal Women: An Overview of Systematic Reviews and Meta-Analyses. Sports Med. 2016;46(8):1165- 1182. doi:10.1007/s40279-016-0494-0

[20] Watts NB. Clinical utility of biochemical markers of

of osteoporotic fractures. BMJ

1996;312:1254-1259.

Bone 2004;35:375-382.

Curr Mol Med 10: 522-532.

dietary protein requirements in elderly people for optimal muscle and bone health. J Am Geriatr Soc

Nutr 2003;77:1517-1525.

2009;57(6):1073-1079.

en.2012-1022.

Res 6: 30.

[2] Department of Health and Human Services(HHS), Department of

Agriculture(USDA). Dietary Guidelines

**References**

Nutr 2004; 7: 227-243.

for Americans, 2005.

[3] Antonić Degač K, Capak K, Kaić-Rak A, Kramarić D, Ljubičić M,

Maver H, Mesaroš-Kanjski E, Petrović I., Reiner Ž. Hrvatska prehrambena politika. Ministarstvo zdravstva Republike Hrvatske, Hrvatski

zavod za javno zdravstvo, 1999.

Understanding Nutrition. Eleventh Edition. Belmont USA: Thomson. 2008,

[5] Šatalić Z. Povijest znanosti o prehrani. Medicus 2008;17(1):149-156.

[6] Mandić LM. Znanost o prehrani. Hrana i prehrana u čuvanju zdravlja. Osijek: Prehrambeno-tehnološki fakultet.2007, str.4, 57-91.

[7] Novotny R, Boushey C, Bock MA,

Peck L, Auld G, Bruhn CM, Gustafson D, Gabel K, Jensen JK, Misner S, Read M. Calcium Intake of Asian, Hispanic and White Youth. J Am

Coll Nutr 2003; 22:64-70.

81: 1232S-1239S.

[8] Pravilnik o hrani za posebne prehrambene potrebe 2004, Zagreb, Narodne novine, broj 81 (NN 81/04).

[9] Nieves JW. Osteoporosis: the role of micronutrients. Am J Clin Nutr 2005;

[10] Heaney RP. Nutrition and risk for osteoporosis. In: (Marcus R, Feldman D, Kelsey J, eds), Osteoporosis. San Diego: Academic Press, 1996:p.483-505.

Haynatzka V. Protein intake: effects on

[11] Rapuri PB, Gallagher JC,

[4] Whitney E, Rolfes SR.

str.3,106.

*Osteoporosis and Dietary Inflammatory Index DOI: http://dx.doi.org/10.5772/intechopen.96772*

#### **References**

*Osteoporosis - Recent Advances, New Perspectives and Applications*

**38**

**Author details**

Ivana Pavičić3

Rijeka, Croatia

Rijeka, Rijeka, Croatia

of Rijeka, Rijeka, Croatia

Croatia

Olga Cvijanović Peloza1

Jasna Lulić Drenjak4

and Juraj Arbanas1

\*, Sandra Pavičić Žeželj2

1 Department of Anatomy, Medical Faculty of the University of Rijeka, Rijeka,

2 Department of Health Ecology, Medical Faculty of the University of Rijeka,

4 Department of Physiotherapy, Faculty of Health Studies of the University of

5 Department of Basic Medical Sciences, Faculty of Health Studies of the University

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

, Gordana Starčević Klasan1

, Ana Terezija Jerbić Radetić1

3 Clinic of Internal Medicine, CHC Rijeka, Rijeka, Croatia

\*Address all correspondence to: olga.cvijanovic@uniri.hr

provided the original work is properly cited.

, Gordana Kenđel Jovanović2

, Ariana Fužinac Smojver<sup>5</sup>

,

, Sanja Zoričić Cvek1

,

[1] Prentice A. Diet, nutrition and prevention of osteoporosis. Pub Health Nutr 2004; 7: 227-243.

[2] Department of Health and Human Services(HHS), Department of Agriculture(USDA). Dietary Guidelines for Americans, 2005.

[3] Antonić Degač K, Capak K, Kaić-Rak A, Kramarić D, Ljubičić M, Maver H, Mesaroš-Kanjski E, Petrović I., Reiner Ž. Hrvatska prehrambena politika. Ministarstvo zdravstva Republike Hrvatske, Hrvatski zavod za javno zdravstvo, 1999.

[4] Whitney E, Rolfes SR. Understanding Nutrition. Eleventh Edition. Belmont USA: Thomson. 2008, str.3,106.

[5] Šatalić Z. Povijest znanosti o prehrani. Medicus 2008;17(1):149-156.

[6] Mandić LM. Znanost o prehrani. Hrana i prehrana u čuvanju zdravlja. Osijek: Prehrambeno-tehnološki fakultet.2007, str.4, 57-91.

[7] Novotny R, Boushey C, Bock MA, Peck L, Auld G, Bruhn CM, Gustafson D, Gabel K, Jensen JK, Misner S, Read M. Calcium Intake of Asian, Hispanic and White Youth. J Am Coll Nutr 2003; 22:64-70.

[8] Pravilnik o hrani za posebne prehrambene potrebe 2004, Zagreb, Narodne novine, broj 81 (NN 81/04).

[9] Nieves JW. Osteoporosis: the role of micronutrients. Am J Clin Nutr 2005; 81: 1232S-1239S.

[10] Heaney RP. Nutrition and risk for osteoporosis. In: (Marcus R, Feldman D, Kelsey J, eds), Osteoporosis. San Diego: Academic Press, 1996:p.483-505.

[11] Rapuri PB, Gallagher JC, Haynatzka V. Protein intake: effects on bone mineral density and the rate of bone loss in elderly women. Am J Clin Nutr 2003;77:1517-1525.

[12] Gaffney-Stomberg E, Insogna KL, Rodriguez NR, Kerstetter JE. Increasing dietary protein requirements in elderly people for optimal muscle and bone health. J Am Geriatr Soc 2009;57(6):1073-1079.

[13] Zaidi, Mone & Buettner, Christoph & Sun, Li & Iqbal, Jameel. (2012). Minireview: The Link Between Fat and Bone: Does Mass Beget Mass?. Endocrinology. 153. 2070-2075. 10.1210/ en.2012-1022.

[14] Magni P., Dozio E., Galliera E., Ruscica M., Corsi M. (2010) Molecular aspects of adipokine–bone interactions. Curr Mol Med 10: 522-532.

[15] Cao J. (2011) Effects of obesity on bone metabolism. J Orthop Surg Res 6: 30.

[16] Jessica K.Black, N.D. The Anti-Inflammation Diet and Recipe Book.

[17] Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996;312:1254-1259.

[18] Kanis JA, Borgstrom F, De Laet C i sur. A meta-analysis of previous fracture and subsequent fracture risk. Bone 2004;35:375-382.

[19] Xu J, Lombardi G, Jiao W, Banfi G. Effects of Exercise on Bone Status in Female Subjects, from Young Girls to Postmenopausal Women: An Overview of Systematic Reviews and Meta-Analyses. Sports Med. 2016;46(8):1165- 1182. doi:10.1007/s40279-016-0494-0

[20] Watts NB. Clinical utility of biochemical markers of

bone remodeling. Clin Chem 1999;45:1359-1368.

[21] Mundy GR. Osteoporosis and inflammation. Nutr Rev. 2007;65(12 Pt 2):S147-S151. doi:10.1111/j.1753-4887.2007.tb00353.x

[22] Peric Kacarevic, Z., Snajder, D., Maric, A., Bijelic, N., Cvijanovic, O., Domitrovic, R., Radic, R. (2016). High-fat diet induced changes in lumbar vertebra of the male rat offsprings. Acta Histochemica, 118(7), 711-721. doi:10.1016/j.acthis.2016.08.002

[23] Shivappa N, Steck SE, Hurley TG i sur. Designing and developing a literature-derived, population-based dietary inflammatory index. Public Health Nutr. 2014;17(8):1689-1696;

[24] Shivappa N, Herbert JR, Rietzschel ER i sur. Associations between dietary inflammatory index and inflammatory markers in the Asklepios Study. Br J Nutr. 2015;113:665-671;

[25] Ruiz-Canela M, Bes-Rastrollo M, Martínez-González MA. The Role of Dietary Inflammatory Index in Cardiovascular Disease, Metabolic Syndrome and Mortality. Int. J. Mol. Sci. 2016;17(8):1265;

[26] Shivappa, N , Hébert JR, Zucchetto A i sur. Dietary inflammatory index and endometrial cancer risk in an Italian case-control study. Br J Nutr. 2016;115(1):138-146;

[27] Shivappa N, Hébert JR, Polesel J i sur. Inflammatory potential of diet and risk for hepatocellular cancer in a case-control study from Italy. Br J Nutr. 2016;115(2):324-331;

[28] Shivappa N, Prizment AE, Blair CK, Jacobs DR Jr, Steck SE, Hébert JR. Dietary inflammatory index and risk of colorectal cancer in the Iowa Women's Health Study. Cancer Epidemiol Biomarkers Prev. 2014

Nov;23(11):2383-92. doi: 10.1158/1055- 9965.EPI-14-0537. Epub 2014 Aug 25. PMID: 25155761; PMCID: PMC4221503.

[29] Mohseni R, Abbasi S, Mohseni F, Rahimi F, Alizadeh S. Association between Dietary Inflammatory Index and the Risk of Prostate Cancer: A Meta-Analysis. Nutr Cancer. 2019;71(3):359- 366. doi: 10.1080/01635581.2018.1516787. Epub 2018 Oct 1. PMID: 30273060.

[30] Shivappa N, Bosetti C, Zucchetto A, Serraino D, La Vecchia C, Hébert JR. Dietary inflammatory index and risk of pancreatic cancer in an Italian case-control study. Br J Nutr. 2015 Jan 28;113(2):292-8. doi: 10.1017/ S0007114514003626. Epub 2014 Dec 17. PMID: 25515552; PMCID: PMC4470878.

[31] Zamora-Ros R, Shivappa N, Steck SE, Canzian F, Landi S, Alonso MH, Hébert JR, Moreno V. Dietary inflammatory index and inflammatory gene interactions in relation to colorectal cancer risk in the Bellvitge colorectal cancer case-control study. Genes Nutr. 2015 Jan;10(1):447. doi: 10.1007/s12263-014-0447-x. Epub 2014 Dec 9. PMID: 25488145; PMCID: PMC4259879.

[32] Tabung FK, Steck SE, Ma Y, Liese AD, Zhang J, Caan B, Hou L, Johnson KC, Mossavar-Rahmani Y, Shivappa N, Wactawski-Wende J, Ockene JK, Hebert JR. The association between dietary inflammatory index and risk of colorectal cancer among postmenopausal women: results from the Women's Health Initiative. Cancer Causes Control. 2015 Mar;26(3):399- 408. doi: 10.1007/s10552-014-0515-y. Epub 2014 Dec 31. PMID: 25549833; PMCID: PMC4334706.

[33] Fowler ME, Akinyemiju TF. Meta-Analysis of the Association Between Dietary Inflammatory Index (DII) and Cancer Outcomes. Int J Cancer. 2017(prihvaćen manuskript. doi:10.1002/ijc.30922).

**41**

*Osteoporosis and Dietary Inflammatory Index DOI: http://dx.doi.org/10.5772/intechopen.96772*

[34] Wood L, Shivappa N, Berthon BS i sur. Dietary inflammatory index is related to asthma risk, lung function and systemic inflammation in asthma. Clin Exp Allergy. 2015;45:177-183;

30, Issue 2, 2002, pages 340-346, ISSN

[41] Khosla S. Minireview: the OPG/ RANKL/RANK system. Endocrinology. 2001 Dec;142(12):5050-5055. doi: 10.1210/endo.142.12.8536. PMID:

Mechanisms of disease: is osteoporosis the obesity of bone? Nat Clin Pract Rheumatol. 2006 Jan;2(1):35-43. doi: 10.1038/ncprheum0070. PMID:

[43] Vanlint S. Vitamin D and Obesity. Nutrients. 2013; 5(3):949-956. https://

[42] Rosen CJ, Bouxsein ML.

doi.org/10.3390/nu5030949

8756-3282.

11713196.

16932650.

[35] Salari-Moghaddam A, Keshteli AH, Afshar H, Esmaillzadeh A, Adibi P. Association between dietary

inflammatory index and psychological profile in adults. Clin Nutr. 2019 Oct;38(5):2360-2368. doi: 10.1016/j. clnu.2018.10.015. Epub 2018 Oct 27.

[37] Nanri A, Moore MA, Kono S. Impact of C-reactive protein on disease risk and its relation to dietary factors. Asian Pac J

[36] Ghazizadeh, H., Yaghooti-Khorasani, M., Asadi, Z. et al. Association between Dietary Inflammatory Index (DII®) and depression and anxiety in the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) Study population. BMC Psychiatry 20, 282 (2020). https://doi.org/10.1186/

PMID: 30415907.

s12888-020-02663-4

12562878.

12759887.

Cancer Prev 2007;8:167-177.

[38] Van Dyke TE, Serhan CN. Resolution of inflammation: a new paradigm for the pathogenesis of periodontal diseases. J Dent Res. 2003 Feb;82(2):82-90. doi: 10.1177/154405910308200202. PMID:

[39] Mann ST, Stracke H, Lange U, Klör HU, Teichmann J. Alterations of bone mineral density and bone metabolism in patients with various grades of chronic pancreatitis.

Metabolism. 2003 May;52(5):579-585. doi: 10.1053/meta.2003.50112. PMID:

[40] Romas E, Gillespie MT, Martin TJ. Involvement of receptor activator of NFκB ligand and tumor necrosis factor-α in bone destruction in rheumatoid arthritis, Bone, Volume

*Osteoporosis and Dietary Inflammatory Index DOI: http://dx.doi.org/10.5772/intechopen.96772*

*Osteoporosis - Recent Advances, New Perspectives and Applications*

Nov;23(11):2383-92. doi: 10.1158/1055- 9965.EPI-14-0537. Epub 2014 Aug 25. PMID: 25155761; PMCID: PMC4221503.

[29] Mohseni R, Abbasi S, Mohseni F, Rahimi F, Alizadeh S. Association between

[30] Shivappa N, Bosetti C, Zucchetto A, Serraino D, La Vecchia C, Hébert JR. Dietary inflammatory index and risk of pancreatic cancer in an Italian case-control study. Br J Nutr. 2015 Jan 28;113(2):292-8. doi: 10.1017/ S0007114514003626. Epub 2014 Dec 17. PMID: 25515552; PMCID: PMC4470878.

Dietary Inflammatory Index and the Risk of Prostate Cancer: A Meta-Analysis. Nutr Cancer. 2019;71(3):359- 366. doi: 10.1080/01635581.2018.1516787. Epub 2018 Oct 1. PMID: 30273060.

[31] Zamora-Ros R, Shivappa N, Steck SE, Canzian F, Landi S,

gene interactions in relation to colorectal cancer risk in the Bellvitge colorectal cancer case-control study. Genes Nutr. 2015 Jan;10(1):447. doi: 10.1007/s12263-014-0447-x. Epub 2014 Dec 9. PMID: 25488145; PMCID:

[32] Tabung FK, Steck SE, Ma Y, Liese AD, Zhang J, Caan B, Hou L, Johnson KC, Mossavar-Rahmani Y, Shivappa N, Wactawski-Wende J, Ockene JK, Hebert JR. The association between dietary inflammatory index and risk of colorectal cancer among postmenopausal women: results from the Women's Health Initiative. Cancer Causes Control. 2015 Mar;26(3):399- 408. doi: 10.1007/s10552-014-0515-y. Epub 2014 Dec 31. PMID: 25549833;

PMCID: PMC4334706.

doi:10.1002/ijc.30922).

[33] Fowler ME, Akinyemiju TF. Meta-Analysis of the Association Between Dietary Inflammatory Index (DII) and Cancer Outcomes. Int J Cancer. 2017(prihvaćen manuskript.

PMC4259879.

Alonso MH, Hébert JR, Moreno V. Dietary inflammatory index and inflammatory

bone remodeling. Clin Chem

[21] Mundy GR. Osteoporosis and inflammation. Nutr Rev. 2007;65(12 Pt 2):S147-S151.

doi:10.1111/j.1753-4887.2007.tb00353.x

[22] Peric Kacarevic, Z., Snajder, D., Maric, A., Bijelic, N., Cvijanovic, O., Domitrovic, R., Radic, R. (2016). High-fat diet induced changes in lumbar vertebra of the male rat offsprings. Acta Histochemica, 118(7), 711-721. doi:10.1016/j.acthis.2016.08.002

[23] Shivappa N, Steck SE, Hurley TG i sur. Designing and developing a literature-derived, population-based dietary inflammatory index. Public Health Nutr. 2014;17(8):1689-1696;

[24] Shivappa N, Herbert JR, Rietzschel ER i sur. Associations between dietary inflammatory index and inflammatory markers in the Asklepios Study. Br J

[25] Ruiz-Canela M, Bes-Rastrollo M, Martínez-González MA. The Role of Dietary Inflammatory Index in Cardiovascular Disease, Metabolic Syndrome and Mortality. Int. J. Mol. Sci.

[26] Shivappa, N , Hébert JR, Zucchetto A i sur. Dietary inflammatory index and endometrial cancer risk in an Italian case-control study. Br J Nutr.

[27] Shivappa N, Hébert JR, Polesel J i sur. Inflammatory potential of diet and risk for hepatocellular cancer in a case-control study from Italy. Br J Nutr.

[28] Shivappa N, Prizment AE, Blair CK, Jacobs DR Jr, Steck SE, Hébert JR. Dietary inflammatory index and risk of colorectal cancer in the Iowa Women's Health Study. Cancer Epidemiol Biomarkers Prev. 2014

Nutr. 2015;113:665-671;

2016;17(8):1265;

2016;115(1):138-146;

2016;115(2):324-331;

1999;45:1359-1368.

**40**

[34] Wood L, Shivappa N, Berthon BS i sur. Dietary inflammatory index is related to asthma risk, lung function and systemic inflammation in asthma. Clin Exp Allergy. 2015;45:177-183;

[35] Salari-Moghaddam A, Keshteli AH, Afshar H, Esmaillzadeh A, Adibi P. Association between dietary inflammatory index and psychological profile in adults. Clin Nutr. 2019 Oct;38(5):2360-2368. doi: 10.1016/j. clnu.2018.10.015. Epub 2018 Oct 27. PMID: 30415907.

[36] Ghazizadeh, H., Yaghooti-Khorasani, M., Asadi, Z. et al. Association between Dietary Inflammatory Index (DII®) and depression and anxiety in the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) Study population. BMC Psychiatry 20, 282 (2020). https://doi.org/10.1186/ s12888-020-02663-4

[37] Nanri A, Moore MA, Kono S. Impact of C-reactive protein on disease risk and its relation to dietary factors. Asian Pac J Cancer Prev 2007;8:167-177.

[38] Van Dyke TE, Serhan CN. Resolution of inflammation: a new paradigm for the pathogenesis of periodontal diseases. J Dent Res. 2003 Feb;82(2):82-90. doi: 10.1177/154405910308200202. PMID: 12562878.

[39] Mann ST, Stracke H, Lange U, Klör HU, Teichmann J. Alterations of bone mineral density and bone metabolism in patients with various grades of chronic pancreatitis. Metabolism. 2003 May;52(5):579-585. doi: 10.1053/meta.2003.50112. PMID: 12759887.

[40] Romas E, Gillespie MT, Martin TJ. Involvement of receptor activator of NFκB ligand and tumor necrosis factor-α in bone destruction in rheumatoid arthritis, Bone, Volume

30, Issue 2, 2002, pages 340-346, ISSN 8756-3282.

[41] Khosla S. Minireview: the OPG/ RANKL/RANK system. Endocrinology. 2001 Dec;142(12):5050-5055. doi: 10.1210/endo.142.12.8536. PMID: 11713196.

[42] Rosen CJ, Bouxsein ML. Mechanisms of disease: is osteoporosis the obesity of bone? Nat Clin Pract Rheumatol. 2006 Jan;2(1):35-43. doi: 10.1038/ncprheum0070. PMID: 16932650.

[43] Vanlint S. Vitamin D and Obesity. Nutrients. 2013; 5(3):949-956. https:// doi.org/10.3390/nu5030949

**43**

**Chapter 4**

**Abstract**

**1. Introduction**

quality of life for those affected.

Disease

*and Rajeev Aurora*

Osteoporosis: A Multifactorial

A great achievement of modern medicine is the increased lifespan of the human

population. Unfortunately, the comorbidities of aging have created a large economic and health burden on society. Osteoporosis is the most prevalent age-related disease. It is characterized by uncoupled bone resorption that leads to low bone mass, compromised microarchitecture and structural deterioration that increases the likelihood of fracture with minimal trauma, known as fragility fractures. These fractures lead to disproportionally high mortality rate and a drastic decline in quality of life for those affected. While estrogen loss is one known trigger of osteoporosis, a number of recent studies have shown that osteoporosis is a multifactorial condition in both humans and rodent models. The presence or absence of certain factors are likely to determine which subset of the population develop osteoporosis. In this chapter, we review the factors that contribute to osteoporosis with an

emphasis on its multifactorial nature and the therapeutic consequences.

gut microbiome, metabolism, osteoimmunology, therapy, T-cells

using a fracture risk assessment tool score or FRAX score [5, 6].

**Keywords:** osteoporosis, postmenopausal osteoporosis, aging, mineral homeostasis,

Osteoporosis (OP) is the most prevalent metabolic bone disease that affects half the women and one third of men, typically, in the sixth and seventh decade of life [1, 2]. OP is characterized by uncoupled bone resorption that leads to low bone mass, compromised microarchitecture and structural deterioration that increases the likelihood of fractures with minimal trauma, known as fragility fractures. These fractures lead to disproportionally high mortality rate and a drastic decline in

OP is diagnosed by an X-ray (typically by dual energy X-ray absorptiometry or DEXA) scan to measure bone mineral density (BMD) [3]. Two scores are returned: a Z-score and a T-score [4]. The T-score is normalized BMD by sex and age, whereas the Z-score also accounts for weight and ethnicity. Both scores report standard deviations (σ) of BMD from mean. A T-score of −1 is normal (within 1 σ of mean), whereas less than −1 to −2.5 indicates osteopenia. A patient with T-scores less than −2.5 is considered osteoporotic. Additional factors to BMD such as smoking, family history of fractures, the diagnosis of rheumatoid arthritis, alcohol consumption and glucocorticoid use many be considered to predict the probability of fracture

*Di Wu, Anna Cline-Smith, Elena Shashkova* 

#### **Chapter 4**
