Nutrient and Dietary Patterns in Relation to the Pathogenesis of Postmenopausal Osteoporosis—A Literature Review

Postmenopausal women tend to be susceptible to primary osteoporosis due to its association with oestrogen deficiency. There is emerging evidence that an unhealthy dietary pattern drives an increase in the risk of postmenopausal osteoporosis (PO), whereas a healthy dietary pattern may decrease its occurrence. In this narrative literature review, we sought to review the role of nutrient and dietary patterns in the pathogenesis of PO. Therefore, we searched and reported all research articles from 2001 to May 2020 in Web of Science, Cinahl and Scopus that have researched a relationship between nutrient and/or dietary patterns and postmenopausal osteoporosis. Nutrients such as calcium, phosphorus, magnesium and vitamin D have been proven to be beneficial for bone health. Meanwhile, for the dietary patterns, foods such as dairy products especially milk, fibre and protein-rich foods, e.g., meat were directly linked to a positive association with bone mineral density (BMD). Likewise, fruits, vegetables and probiotic and prebiotic foods were reported for its positive relationship with BMD. Therefore, aside from physical activity, nutrition and diet in adequate proportions are suggested to be an important tool for ameliorating osteoporosis and bone health issues in older age.


Introduction
Osteoporosis is a major public health concern with the ageing populations [1]. Worldwide, 8.9 million fractures occur annually which results in an osteoporotic fracture every 3 s [2].
Postmenopausal osteoporosis is a condition on the rise amongst aged women as the world demography experiences marked ageing of the population. Globally, New Zealand is amongst one of the most affected by the burden of the disease. Postmenopausal osteoporosis is characterized by increased low-grade inflammation contributing to low bone mass and degradation of bone mineral content resulting in bone loss and/or fractures [1,2].
Although the pathogenesis of osteoporosis is multifactorial, key drivers include oestrogen deficiency, poor dietary habits, chronic inflammation, smoking, excessive alcohol consumption and sedentary lifestyle. However, diet regulates the composition and function of the human gut microbiota with recent evidence suggesting that the gut microbiome plays essential roles in the host energy homeostasis, immune system enablement and metabolic function and health [3].
Menopausal hormone replacement therapy (HRT) has been employed in the treatment of menopausal treatments. However, its risks have also been documented which include increased occurrence of breast cancer, stroke, venous thromboembolism (VTE) and risk of coronary artery disease but the "timing hypothesis" has been suggested for a possible amelioration if administered early in menopause [4].
Nutraceuticals, also known as alternative pharmaceuticals products made from plants and foods which have medicinal properties, are non-hormonal natural therapies or approach to menopausal symptoms. These include phytoestrogenic plants or isoflavones, antioxidants, dietary supplements and fortified dairy products [5].
Nutrition and lifestyle changes are essential in promoting health and in the prevention of metabolic diseases such as osteoporosis. Many nutrients are known to interact with each other thereby influencing their bioavailability and absorption [3]. Several key nutrients are known to affect bone mineral content (BMC) and bone mineral density (BMD). These nutrients, however, occur together in foods and dietary patterns, therefore the need to study the diet in its entirety. Unhealthy dietary patterns are known to be associated with some chronic diseases such as diabetes and cardiovascular disease [4]. Likewise, nutrients such as calcium and vitamin D are well-established as nutritional drivers in the maintenance of normal bone metabolism. Additionally, nutrients such as potassium, zinc, magnesium, iron, copper, vitamin C and vitamin K are micronutrients rich in fruits and vegetables that are beneficial for bone metabolism. However, the overall effects of dietary choices on bone health are not well understood and therefore need further research and discussion.
There are two main holistic methodologies used in describing and quantifying nutrient and/or dietary patterns/habits: 1. The a posteriori (data-driven) dietary pattern approach, i.e., the use of statistical methods such as principal component analysis (PCA) or factor analysis, reduced rank regression (RRR), cluster analysis and partial least square to generate dietary patterns from data collected; and 2. The a priori dietary pattern approach, i.e., the use of created or predefined dietary indexes on the basis of existing knowledge in nutrition usually complying with dietary guidelines and recommendations [5].
The aim of this review was to investigate and discuss the reported relationships observed between nutrient and dietary patterns and bone health status (BMD, bone biomarkers and fracture risks) in postmenopausal women.

The Relationship between Nutrient Patterns and Postmenopausal Osteoporosis
Research shows there is a relation between nutrient patterns and postmenopausal osteoporosis; however, results from studies are heterogeneous and therefore no conclusive nutrient pattern has been proposed. To date, only two studies have explored the relationship between nutrient patterns and bone health exclusively in postmenopausal women.
The first study by Karamati et al., 2014 indicated that a nutrient pattern (NP1) high in folate, fiber, vitamin B6, potassium, vitamin A, vitamin C, β-carotene, vitamin K, magnesium, copper and manganese was positively associated with lumbar spine BMD. These nutrients are particularly rich in fruits and vegetables. These antioxidant micronutrients are important for the formation and maintenance of bone cells and the structure required for normal bone metabolism. However, they failed to find any correlation with the well-known nutrients that are important for bone health in their NP2 which was high in vitamin B2, protein, calcium, phosphorus, zinc, vitamin B12, vitamin D and low in vitamin E. The explanation was that although protein intake levels have been associated with bone health benefits, the influence of protein intakes generally depends on a balanced whole diet in terms of acid-producing potential. Acid/base balance is important to avoid urinary calcium loss with acid-forming foods such as processed meat, shellfish and pastries. The NP3 with high intakes of dietary fats and low intakes of carbohydrate, vitamin B1 and fiber was likewise not correlated with BMD [6].
The second study by Ilesanmi-Oyelere et al., 2019 found a positive association between NP1 (characterised by high riboflavin, phosphorus, calcium, sugars, potassium, vitamin B6, carbohydrate and magnesium) and lumbar spine, femoral neck and whole-body BMD. These nutrients are particularly rich in eggs, lean meats, milk, milk products and some fruits and vegetables. NP2 (high in dietary fats, vitamin E, alpha and beta carotene) was negatively associated with BMD while NP3 (also characterised by high fat, protein, zinc and cholesterol with low intakes of alpha and beta carotene and vitamin C) was not associated with BMD at all sites (Table 1). BMD = bone mineral density; BMC = bone mineral content; LS = lumbar spine; FN = femoral neck; DXA = dual energy X-ray absorptiometry; NP = nutrient pattern.

Dietary Pattern Analyses and Bone Health in Postmenopausal Osteoporosis
Generating dietary patterns with correlated foods are important to investigate diet due to the complexity and interaction of various nutrients and foods. Studies have used dietary patterns generated from foods to give a view of the association between dietary intakes and BMD/BMC, bone biomarkers, osteoporosis and fractures ( Table 2).
Traditional Western-style diets that are characterised by processed foods high in salt, fats and sugar have been researched and positively associated with osteoporosis as is evidenced in six studies that explored dietary patterns and bone health status [10][11][12][13][14]. Similarly, energy-dense foods such as white rice, wheat and grains have been associated with the risk of fractures during postmenopause [15]. These patterns of foods have therefore been labelled "unhealthy" and are known to drive the risk of many metabolic diseases including osteoporosis and consequently fractures.

Dietary Patterns Score/index and Bone Health in Postmenopausal Osteoporosis
Some studies have used the dietary pattern score/index in association with BMD/BMC, bone biomarkers and fractures in postmenopausal women as is shown in Table 3. The Mediterranean score indicates compliance with the Mediterranean diet. A traditional Mediterranean diet is rich in the intake of vegetables, fruit, nuts and olive oil but low in saturated fats, moderately high intake of fish, low to moderate intake of dairy and lesser intake of meat and poultry as well as moderate intake of wine [22][23][24]. In general, the Mediterranean diet score/index was directly associated with BMD and inversely associated with fracture risk [22,23]. Meanwhile, the Healthy Eating Index (HEI) that measures the quality of diet and how well a particular set of foods aligns with the dietary guidelines for Americans has been reported as having no significant association for both the HEI 2005 and 2010 [25,26] On the other hand, the Dietary Inflammatory Index (DII) that assesses the inflammatory potential of a diet was inversely associated with BMD as was shown by two separate studies from the United States of America and Iran [25,26], these indicating the relationship between inflammation and bone degeneration.

Discussion
In this review, we discussed various studies on the relationship between nutrient and dietary patterns and BMD/BMC, bone biomarkers and fractures in postmenopausal women. Studies on the nutrient patterns and BMD, although conducted in different communities and settings, indicate the importance of phosphorus, riboflavin, potassium, calcium, magnesium, vitamin B6, vitamin D, protein, fiber, vitamin K and folate from fruits and vegetables as well as milk intake [6][7][8].
Dietary patterns help elaborate the health attributes of food groups; in factor or cluster analysis as a combination of foods and in the reduced rank regression (RRR) analysis method to represent groups of food with health outcomes. It is not surprising that foods such as low-fat dairy, legumes, nuts, olive oil, fish, fruits and vegetables have emerged in this study as important for the prevention of non-communicable diseases such as osteoporosis and fractures. Similarly, Mediterranean-based dietary patterns have been reported to be directly associated with calcium absorption and therefore bone health status in men [31]. Although data-driven dietary patterns are known not to be reproducible and comparable across studies with the explanation that subjectivity of the approach or the fact that real habits of dietary intake across populations differ [5]. Data-driven dietary patterns, however, have the advantage of assessing the real dietary/food patterns in the populations.
On the other hand, processed and/or refined foods such as French fries, hamburgers, biscuits and cookies, and carbonated drinks known as the Western (unhealthy) food patterns, have frequently been inversely correlated with BMD and bone parameters both in children and aged adults. Sweet foods, coffee and tea have also been reported to be inversely correlated with BMD/BMC [18]. Similarly, foods high in sugar such as added sugar fruit drinks, chocolate, and confectionery and high-fat foods such as processed meat, French fries, mayonnaise and desserts [17] were all negatively correlated with BMD and/or BMC. Investigations on starchy-foods (rice) patterns have shown that a high intake of rice in foods was associated with a higher risk of osteoporosis [11,13]. Our nutrient and dietary-based investigation into the pathogenesis of osteoporosis in postmenopausal women showed the importance of an adequate and balanced diet.
Overall, the choice of foods is important for optimum health during aging and a "healthy" diet rich in vegetables and milk or a Mediterranean style diet may be beneficial for bone health in comparison to a Western-style traditional dietary pattern. The implementation of policies for an increase in the dietary intake of vegetables, fruits, non-refined grains and low-fat milk is warranted from childhood to adulthood.