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Hamidian Shirazi M, Mollaei A, Ramezani A, Hamidian Shirazi A, Hejazi N. The Probable Impact of Soy Isoflavones in Bone Fracture Downturn: A Systematic Review. JNFS 2024; 9 (1) :160-172
URL: http://jnfs.ssu.ac.ir/article-1-611-en.html
Department of Veterinary, Beyza branch, Islamic Azad University, Beyza, Iran
Keywords: Isoflavones, Bone, Fracture
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The Probable Impact of Soy Isoflavones in Bone Fracture Downturn: A Systematic Review


Maryam Hamidian Shirazi; MSc 1,2, Alireza Mollaei; DVM 3, Atena Ramezani; PhD 4,  
Amirreza Hamidian Shirazi; DVM, MPH 3,5 & Najmeh Hejazi; PhD *2

1 Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran; 2 Department of Community Nutrition, School of Nutrition and Food Science, Shiraz University of Medical Sciences, Shiraz, Iran; 3 Department of Veterinary, Beyza branch, Islamic Azad University, Beyza, Iran; 4 Diabetes Research Center, Mazandaran University of Medical Sciences, Sari, Iran; 5 University of Applied Science and Technology.
ARTICLE INFO ABSTRACT
SYSTEMATIC REVIEW Background: There is a direct relationship between taking soy isoflavones and higher bone density, but there is a paucity of studies examining the relationship between flavonoid consumption and fracture risk. This study aimed to assess the bone fracture and its relationship to soy product intake by performing a systematic review. Methods: Scopus, PubMed, and Web of science were searched to find studies on the effect of soy isoflavones on bone fracture, without any time and language of publication restrictions. Key words of SoyMilk, soymilk, soybeans, soybean, soy, soya, Isoflavones, Isoflavone, ipriflavone, equol, genistein, daidzein, glycitin, fractures, and broken bone were used. Results: From a total of 1675 articles, 27 studies (cross-sectional studies (n=1), case-control studies (n=1), cohort (n=11), and randomized control trials (n=14)) were identified, and their quality was assessed. Eighteen studies highlighted mainly positive results in preventive influence of soy bone fractures. Two papers reported a positive effect was observed in men with cancer. No significant association was found between soy intake and bone prevention fracture in eight distinct papers. Conclusion: Intake of soy isoflavones can make a significant preventive effect on bone fracture; however, the results of some studies are controversial.  Therefore, it is necessary to survey more studies to identify the relationship between isoflavones and bone fracture.
Keywords: Isoflavones; Bone; Fracture
Article history:
Received: 3 Apr 2022
Revised: 28 Jul 2022
Accepted: 28 Aug 2022
*Corresponding author:
najmehhejazi@gmail.com
Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.

Postal code: 7153675500
Tel: +98 71 37251004

Introduction
Bone with frequent renovation during the lifespan is an active tissue (Shetty et al., 2016). Bone renovation contains two stages including formation of new bone tissue and reabsorption of the old bone tissue (Eastell and Szulc, 2017). During growth, the amount of new bone tissue formation surpasses that of reabsorption of old bone tissue, but with age, this trend is reversed. Augmented and non-stop bone reabsorption in aging causes osteoporosis. Osteoporosis is categorized by decreased bone mass related to augmented bone fragility and vulnerability to fracture (Shetty et al., 2016).
Pelvic fractures increase the financial burden by 20 percent due to long-term care of the elderly and in some cases even death (Bunout et al., 2006). Isoflavone soy is classified as phytoestrogens, because of its similarity with estrogen herbal mixtures that can attach to estrogen receptors, and performs the same function as estrogen (Taku et al., 2011). Isoflavones are found in abundance in soy, so in the case of estrogen deficiency (menopause), they can prevent bone loss and bone fracture (Taku et al., 2011, Zhang et al., 2005, Zheng et al., 2016).
Soybean production and dietary consumption have increased within Western nations with postulated health benefits by increasing bone health, especially in women (Xiao, 2008). There has also been an association between the use of phytoestrogens and increased bone density (Greendale et al., 2002, Zhang et al., 2005); however, studies in Caucasian people are incomplete due to lower habitual consumption of phytoestrogens. 
In a study in Shanghai, the average soy isoflavone intake in postmenopausal women was 38 mg / day, which was associated with a reduction in bone fractures (Zhang et al., 2005). Even though genetic factors affect the peak bone mass, regimen is one of the risk factors for osteoporosis (Chan et al., 2011). Natto is a kind of fermented soybean that is taken. This food is rich in menaquinone-7and comprises 100 times more menaquinone-7 than numerous types of cheese (Katsuyama et al., 2002). Based on the present evidence, the consequences of epidemiological studies are still controversial about the effect of soy isoflavone on bone fraction. To the best of the authors’ knowledge, this systematic review is the first to survey the effect of soy isoflavone on preventing bone fraction in patients. Bone fracture, especially in menopause women is an important problem worldwide, so in this systematic review, literature was searched to investigate the probable effect of soy isoflavones on bone fracture to reveal the positive effect of soy products on ameliorating fracture of bone in human to help them enjoy their life better. Thus, the main aim of this study was to survey the efficiency of soy isoflavone on fraction in patients by searching randomized controlled trials (RCTs), cohort studies, and case report studies. The study also aimed to examine which type, quantity, and duration of soy isoflavone is more effective for preventing bone fraction.
The influence of isoflavones on bone metabolism
Phytoestrogens are derivatives of plant compounds that have both antiestrogenic and estrogenic properties. Soy contains large amounts of isoflavones with a structure of 17 b-estradiol. Isoflavones bind to estrogen-binding receptors and function similarly to estrogen (Kuiper et al., 1997). Genistein and daidzine are key isoflavones found in soy (Anderson et al., 1999). 
 Isoflavones are involved in the formation of the bone tissue by binding to osteoblast receptors through a genomic mechanism involved in inhibiting the function of nuclear estrogen receptors (Blair et al., 1996). Its receptor osteoprotein (OPG) and receptor activator of nuclear factor kappa beta (RANKL) are involved in tissue analysis and hemostatic bone resorption. Postmenopausal women receiving genistein have lower sRANKL levels, indicating a possible mechanism of the phytoestrogens in the bone (Marini et al., 2008). Excessive consumption of animal protein increases the urinary excretion of calcium which is effective in the process of osteoporosis, while this trend has not been observed in the consumption of soy protein (Breslau et al., 1988). 
Materials and Methods
Search strategy: Systematic search of studies was performed in PubMed, Scopus, and ISI web of science from the initial record up to July 2021 by means of the MESH terms and keywords compromising: Soy Milk” “soymilk” or “Soybeans” or “soybean” or “soy” or “soya” or "Isoflavones" or "Isoflavone" or "ipriflavone" or "equol" or “genistein OR “daidzein” OR “glycitin” AND “Fracture” or “fractures” or “broken bone” to find the pertinent studies for this study by two independent reviewers (Hamidian Shirazi M and  Hejazi  M). Also, to confirm that all relevant articles were included, the reviewers evaluated the reference lists of the studies. For screening the studies, all the articles were imported to the Endnote X9 (Bld 12062). Then, duplicated articles were omitted and the suitability of the remaining essays was evaluated based on the title, abstract, and full text.
Search strategies  exist as the supplementary file (the search was processed by the Web of science as: (“Soy Milk” or soymilk or Soybeans or soybean or soy or soya or "Isoflavones" or "Isoflavone" or "ipriflavone" or "equol" or genistein OR daidzein OR glycitin) AND (Fracture or fractures or “broken bone”), by PubMed as: (((((SOY[Title/Abstract]) OR ("Soy Foods"[Mesh] OR "Soy Milk"[Mesh] OR "Soybeans"[Mesh] OR "Soybean Proteins"[Mesh])) OR ((((("Isoflavones"[Mesh]) OR "Genistein"[Mesh]) OR "Equol"[Mesh]))) OR ((((((isoflavone*[Title/Abstract]) OR Genistein*[Title/Abstract]) OR Equol*[Title/Abstract]) OR ipriflavone*[Title/Abstract]) OR daidzein*[Title/Abstract]) OR glycitin[Title/Abstract]))) AND ((("Fractures, Bone"[Mesh]) OR bone* fracture*[Title/Abstract]) OR bone* broken[Title/Abstract]), and by scopus as: (“Soy Milk” or soymilk or Soybeans or soybean or soy or soya or "Isoflavones" or "Isoflavone" or "ipriflavone" or "equol" or genistein OR daidzein OR glycitin) AND (Fracture or fractures or “broken bone”)).
Eligibility criteria: The articles were selected based on inclusion and exclusion criteria. The inclusion criteria were clinical trial studies, observational studies, case reports, cohort patients of all ages with fractions in a database, international journals, and domestic scientific journals. The exclusion criteria comprised books, theses, research reports, animal studies, such as red clover or synthetic isoflavones, curments with isoflavones from origins other than soy, and review articles.
Data extraction: Associated data on the effect of soyisoflavone consumption on bone fracture were extracted by two reviewers (Hamidian Shirazi M and  Hejazi  M). The information was extracted from the selected articles and collected in a sheet containing the first authors’ name, article’s name, publication year, study design (parallel or crossover), intervention duration, blinding, randomization, number of participants in each group, form of treatment (e.g., isoflavones, soy, or soy milk), dosage of isoflavones, and the substance used as placebo.
Study quality: The Jadad Quality Assessment (Peterson et al., 2011) Scale was used to assess the quality of interventional studies. This scale consisted of three variables including randomization methods (1 point), blinding (1 point), and inclusion of participants (1 point) for a total score of 3 points. Studies that received 3 points or more were identified as high quality (Clark et al., 1999). On the other hand, Newcastle-Ottawa Quality scale was used to assess quality of observational studies. Papers were evaluated based on selection (4 questions), outcome (3 questions), and comparability (1 question) for a total score of 10 points. In this scale, studies obtaining 3-10, 3-6, and 0-3 points were ranked as high, moderate, and low quality (Penson et al., 2013, Piekarz and Ward, 2007) (Tables 2 and 3).
Study selection: First, by studying titles and abstracts of articles based on inclusion and exclusion criteria, the papers were reviewed (Figure 1), and then the articles on the effect of soy isoflavones on bone fraction were excluded from this study.
Results
After studying the related articles, the titles and abstracts were cautiously screened to find the effect of soy isoflavones on bone fraction (Figure 1). The researchers investigated 1675 articles in Scopus (n=861), Web of science (n=703), and PubMed (n=111). After omitting duplicates (n=502), the remaining articles (n=1046) were screened. Full texts of 102 articles were assessed and 3 studies were not available; moreover, 99 studies were excluded based on the criteria or had nothing to do with the subject of the study, so 27 articles were selected. The articles contained cross-sectional studies (n=1), case-control studies (n=1), cohort (n=11), and randomized control trials (n=14). All the studies showed the effect of soy isoflavone on the bone fraction. Based upon the jadad Scale among 12 interventional studies, eight studies were identified as high quality and four studies as low quality. Among observational studies, 11 studies were categorized as and the others as low quality.
Outcome characteristics of participants with bone fracture: The baseline characteristics of the studies are displayed in Table 1. The studies were printed from 1997 to 2020. The geographic place of each study was different. In 23 studies, the study population consisted of females and mostly postmenopausal and also in 5 studies, they were both sexes. The age range of participants in the studies was between 6 months and 75 years. The length of time of the studies was different, ranging from 1 month to 10 years. The amounts of soy product were different (36mg/day to 200mg/day).
Effect of soy isoflavones on bone fracture: In 18 out of 27 studies, the preventive effect of soy and other soy products was observed on bone fractures. In 2 studies, only a positive effect was observed in men with cancer, and no effect was seen in women with cancer. In 8 studies, there was no association between other soy products and bone fractures.

Table 1. Features of the studies on the effect of isoflavones.
Study Location Number Characteristics Sex Age(y) Interventions and groups Study design Outcomes
(Kojima et al., 2020) Japanese
1417
Postmenopausal
Female
15–79
FFQ of natto, tofu, and another soybean
 
Prospective cohort Decrease the risk of hip fracture
(Zheng et al., 2019)



China




N1=4139
N2= 1987
N3=2152


N1= stage 0–III breast cancer patients
N2= pre-/perimenopausal
N3= postmenopausal patients
Female




20-75




Consume soy using Frequency questionnaire
Prospective




 
Decrease the risk of hip fracture



(Nayeem et al., 2019)
America

99

Healthy premenopausal women Female

30-42

Isoflavones (136.6 mg)
and placebo
Clinical trial

Decrease the risk of hip fracture
(Yoshikata et al., 2018)
China

74

Menopause

Female

44–74

Per oral equol-containing supplement, 10 mg/day
A Prospective Observational Study Decrease the risk of hip fracture
(Zhang et al., 2017) China
1050
Elderly
Male/
female
52-83
Validated 79-item food frequency questionnaire Case-control study of Decrease the risk of hip fracture
(Arcoraci et al., 2017)

Italy

121


Postmenopausal


Female


Mean 54.5

With either 1000 mg of calcium and 800 IU vitamin D3  in placebo group and vitamin D3,calcium, and Genistein aglycone (54 mg/day in intervention group Clinical trial


 Decrease the risk of hip fracture

(Myers et al., 2015)
Australia

1188

Postmenopausal

Female

Mean  80.0
 A validated food-frequency questionnaire

Prospective cohort
Decrease the risk of hip fracture
(Baglia et al., 2015)

China

1,587

Breast cancer diagnosis
Male and female 20 - 75

Food frequency questionnaire

Cohort

Decrease the risk of hip fracture
(Dai et al., 2014)
Singapore Chinese
63,257

 
Both pre- and postmenopausal
Male and female 45–74

A validated food-frequency questionnaire

Prospective population-based cohort Decrease the risk of hip fracture
(Lappe et al., 2013)

USA

70

Postmenopausal

Female

Mean age 54.8 Case: genistein (30 mg/days), vitamin K1 (150 μg/days) vitamin D3 (800 IU/days), vitamin K1 (150 μg/days) and polyunsaturated fatty acids (1 g
Controle: calcium

Clinical trial

Decrease the risk of hip fracture
(Tai et al., 2012)

Taiwan


431


Postmenopausal


Female


45-65


00-mg/day isoflavones (aglycone equivalents) (172.5 mg genistein + 127.5 mg daidzein) and600 mg of calcium and 125 IU of vitamin D3 per day Clinical trial


The relative risk of bone fracture and its 95% CI for the isoflavone group were 1.64 (0.74, 3.67)
(Hasnah et al., 2012)

Malaysia

125

Postmenopausal

Female

Mean age 60
A dietary history Questionnaire

A cross-sectional study

A diet without dairy increased the risk of bone fractures
(Lousuebsakul Matthews et al., 2011) Canada



337



Postmenopausal



Female



54-75



Completed a lifestyle and dietary questionnaire and FFQ


Cohort study



BUA measurement related to soy foods intake and history of minor accident fracturesp= 0.25
(Kuhnle et al., 2011)

UK

F=2580

M=4973

 Cancer

Male and female 45–75

Survey of soy intake using a newly developed food composition database

Prospective study cohort

Decrease the risk of hip fracture
(Haron et al., 2010)


Malaysia



21



Postmenopausal



Female



55-65



A glass of milk (114 g) or from a
meal of tempeh (206 g); each containing 130 mg calcium. At each study of Phase and Phase 2 (mid-August), intravenous 42Ca and oral 44Ca
Clinical trial



No effect



(Koh et al., 2009)

Chinese

63,257

Healthy

Male and female 45–74

Using food frequency questionnaire ,  lifestyle factors and questions on medical history

Prospective cohort

Decrease the risk of hip fracture
(Newton et al., 2006)

USA


F=13
M=98

 Healthy


Male and female
50–80


Soy protein comprising 83 mg isoflavones (45.6 mg genistein, 31.7 mg daidzein), aglycone units; the control group comprising 3mg isoflavones Clinical trial


No effect


(Ikeda et al., 2006)

Japan

944

Postmenopausal
Female
20-79
Dietary natto intake was assessed by a FFQ on both occasions

Cohort

Reduced risk
(Bunout et al., 2006)
Chile

100

Elderly with femoral osteoporosis.
Male and female Mean age 70
31 g proteins per and 90 mg
isoflavones, 400 IU vitamin D, 800 mg calcium,  60 ug vitamin K day
Clinical trial

No effect

(Zhang et al., 2005)

USA

75,000

 

Postmenopausal
Female
40-70
FFQ

Cohort

 

May reduce the risk of fracture
(Welch et al., 2005)

UK


F=5,379
M=6,369

Cancer


Male and female
42 -82


Individuals were divided into four groups based on soy consumption and vegetarian status and a food frequency questionnaire was used. Prospective study

Calcaneum BUA in vegetarian men was significantly lower than but in female had no effect
(Harada et al., 2004)

Japan

2035

Elderly

Male and female Mean age 65
An anonymous survey consisting of 12 questions

Clinical trial

Reduced risk

(Kaneki et al., 2001) Japan
105
Postmenopausal
Female
50–84
Examined the influence of Japanese fermented soybean, on serum vitamin K Clinical trial
Reduced risk
(Alexandersen et al., 2001)

Denmark

474

 Postmenopausal

Female

45-75

200 mg 3 r placebo all received 500 mg/d of calcium

Clinical trials

No effect

(Sato et al., 2000) Japan
9
Long-Distance Runners Female
20-24
1350 g of vitamin K2  and 72 mg of soybean isoflavones Clinical trial
Reduced risk
(Reginster et al., 1997)

Denmark

460
Menopause
Female
45-75
IP (200 mg, and 500 g oral calcium everyday

Clinical trial

Reduced risk
(Agnusdei and Bufalino, 1997)

Italy

149


Elderly, osteoporotic women

Female


65–79


IP (200 mg, and 1 g oral calcium everyday


Clinical trial

Reduced risk


Table 2. Jadad scale quality assessment for RCTs.
Quality Total An account of all patients Blinding Randomization Study
High 5 1 2 2 (Nayeem et al., 2019)
High 4 0 2 2 (Arcoraci et al., 2017)
High 5 1 2 2 (Lappe et al., 2013)
High 5 1 2 2 (Tai et al., 2012)
Low 3 1 1 1 (Haron et al., 2010)
High 5 1 2 2 (Newton et al., 2006)
Low 3 1 1 1 (Bunout et al., 2006)
Low 3 1 1 1 (Kaneki et al., 2001)
High 5 1 2 2 (Alexandersen et al., 2001)
Low 3 1 1 1 (Sato et al., 2000)
High 4 0 2 2 (Reginster et al., 1997)
High 4 0 2 2 (Agnusdei and Bufalino, 1997)
Table 3. Newcastle-Ottawa quality assessment for cohort, case control, and cross sectional studies.
Quality Total Outcome Comparability Selection Study
Good 7 3 1 3 (Kojima et al., 2020)
Fair 6 2 1 3 (Zheng et al., 2019)
Fair 5 2 1 2 (Yoshikata et al., 2018)
Good 6 2 1 3 (Zhang et al., 2017)
Good 6 2 1 3 (Myers et al., 2015)
Good 6 3 1 2 (Baglia et al., 2015)
Good 6 2 1 3 (Dai et al., 2014)
Fair 5 2 0 3 (Hasnah et al., 2012)
Good 6 2 1 3 (Lousuebsakul Matthews et al., 2011)
Good 6 2 1 3 (Kuhnle et al., 2011)
Good 6 2 1 3 (Koh et al., 2009)
Good 6 2 1 3 (Ikeda et al., 2006)
Good 6 2 1 3 (Zhang et al., 2005)
Good 7 3 1 3 (Welch et al., 2005)
Fair 5 2 1 2 (Harada et al., 2004)
Discussion
This study provided a summary of soy isoflavone and its products on bone fracture. By reviewing 27 articles, the relationship between the consumption of soy isoflavone and the risk of bone fractures in individuals was assessed. Results revealed that the intake of soy isoflavones caused a significant preventive effect on bone fracture. Bone repair, which is caused by various diseases and factors, is a complex function that interacts with the cells. Osteoblasts play a role in bone synthesis and collagen deposition outside the cell. Inflammatory cells such as neutrophils, macrophages, and eosinophil go to the fracture site and cause inflammation (Claes et al., 2012). This process leads to absorption of the osteoblasts. Peroxidases also penetrate the affected area. On the other hand, peroxidases  and fibroblasts play a role in the extracellular matrix biosynthesis (DeNichilo et al., 2015).  Soy-derived peroxidase also builds bone tissue and collagen I and it is also effective in controlling inflammation and regenerating the extracellular matrix (Barker et al., 2021).
In the view of quality, 8 interventional studies had high quality, which makes it possible to draw a causal link between bone fracture prevention and soy isoflavone intake. Moreover, 11 out of 15 studies had high quality and showed beneficial effects for bone fracture prevention.
Soy products reduce the risk of bone fractures in postmenopausal women (Zhang et al., 2005). They also increased bone mineral density (BMD) (Abdi et al., 2016). Soy isoflavones might affect the bone by decreasing bone resorption while motivating bone formation (Arjmandi and Smith, 2002). Soy products stimulate the osteoblastic formation of osteoprotegerin, which prevents bone resorption (Viereck et al., 2002). They also have a function and structure similar to tamoxifen, which can be effective in reducing bone loss after menopause (George et al., 2020). Soy isoflavones, with their antioxidant effect, suppress angiogenesis by inhibiting the protein tyrosine kinase and cell growth by interfering with signal transmission. Isoflavones are also thought to inhibit aromatase and 5α reductase and induce estrogen synthesis (George et al., 2020).
Soy also increases the production of insulin-like growth factor 1, an indicator recognized to increase osteoblastic activity related to bone formation (Arjmandi and Smith, 2002).The amount of IGF-I in both sexes decreases with age, which intensifies in menopause (George et al., 2020). IGF-I, like growth hormone, stimulates bone formation (George et al., 2020). It may also increase the production of 1,25 (OH)2 vitamin D by regulating 1α-hydroxylase activity (George et al., 2020). Soy consumption in postmenopausal women has caused a reduction in urinary excretion of bone indicators (Nikander et al., 2004). Menaquinone-7 (MK-7) enables osteocalcin γ -carboxylation (Shetty et al., 2016), and mineralization (Bruge et al., 2011). In a study in the Caucasus, MK-7  consumption was effective in preventing bone fractures in postmenopausal women (Knapen et al., 2013). Thus, soy products prevent bone fractures by preserving bone mass and bone microarchitecture (Rønn et al., 2016). Soy products can decrease bone loss (Wong et al., 2009) and provoke bone formation (Ma et al., 2008b, Marini et al., 2007); this association was not found in 8 studies. This can be attributed to different types of isoflavones in different soy products (Kojima et al., 2020). Isoflavone aglycones in unfermented soy products, such as tofu, are absorbed faster and have more bioavailability than other soy products (Izumi et al., 2000). The phytoestrogens in soy reduce the process of bone loss (Ma et al., 2008a). The effect of soy in avoiding osteoporosis in men has not been determined (Newton et al., 2006). The exact mechanism of genistein in men is unknown (Piekarz and Ward, 2007). Genistein prevents bone loss by increasing the activity of osteoblasts in male rodents (Khalil et al., 2005). Decreased testosterone is observed in men with age (Orwoll et al., 2006), since testosterone helps maintain bone health in men (Amin et al., 2006). Therefore, isoflavones can be effective in preventing bone fractures in older men and soy products, due to the mentioned properties, can be effective in preventing bone fractures.
Opposing effects
 Isoflavones have structures similar to estrogens, so they increase the risk of breast cancer in susceptible individuals or general survival from breast cancer (Qiu and Jiang, 2019, Touillaud et al., 2019).
Limitation
This review study had some limitations.  Each study had different interventions, evaluating different results, which made impossible to compare the results. Also, confounding factors such as age, BMI, and dietary calcium intake were not investigated.
Conclusion
Various diseases and factors that affect bone fractures mainly affect the quality of life of people. Therefore, the results of this review revealed that soy consumption may have a beneficial effect on preventing bone fraction. More studies with a longer time of intervention on a larger sample size are recommended to approve these results.
Acknowledgement
The authors would like to thank Shiraz University of Medical Sciences, Shiraz, Iran, Center for Development of Clinical Research of Nemazee Hospital, and Shiraz Medical School Library.
Funding
No funding
Author contributions
Hamidian Shirazi M, Mollaei M, Hamidian Shirazi A and Hejazi N. contributed to the research concept; Hamidian Shirazi M, Hejazi N and Ramezani A searched databases, screened articles, and extracted data. All authors contributed to the writing and revision of the manuscript. All authors have read and agreed to the published version of the manuscript.
Conflict of interest
No conflict of interest is declared.
Reference
Abdi F, Alimoradi Z, Haqi P & Mahdizad F 2016. Effects of phytoestrogens on bone mineral density during the menopause transition: a systematic review of randomized, controlled trials. Climacteric. 19 (6): 535-545.
Agnusdei D & Bufalino L 1997. Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcified tissue international. 61 (1): S23-S27.
Alexandersen P, et al. 2001. Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial. Journal of the American Medical Association (JAMA). 285 (11): 1482-1488.
Amin S, et al. 2006. Estradiol, testosterone, and the risk for hip fractures in elderly men from the Framingham Study. American journal of medicine. 119 (5): 426-433.
Anderson JJ, Anthony M, Messina M & Garne SC 1999. Effects of phyto-oestrogens on tissues. Nutrition research reviews. 12 (1): 75-116.
Arcoraci V, et al. 2017. Antiosteoporotic activity of genistein aglycone in postmenopausal women: Evidence from a post-hoc analysis of a multicenter randomized controlled trial. Nutrients. 9 (2): 179.
Arjmandi BH & Smith BJ 2002. Soy isoflavones’ osteoprotective role in postmenopausal women: mechanism of action. Journal of nutritional biochemistry. 13 (3): 130-137.
Baglia ML, et al. 2015. Soy isoflavone intake and bone mineral density in breast cancer survivors. Cancer causes control. 26 (4): 571-580.
Barker AJ, et al. 2021. Plant-derived soybean peroxidase stimulates osteoblast collagen biosynthesis, matrix mineralization, and accelerates bone regeneration in a sheep model. Bone reports. 101096.
Blair HC, Jordan SE, Peterson TG & Barnes S 1996. Variable effects of tyrosine kinase inhibitors on avian osteoclastic activity and reduction of bone loss in ovariectomized rats. Journal of cellular biochemistry. 61 (4): 629-637.
Breslau NA, Brinkley L, Hill KD, PAK CY & Metabolism 1988. Relationship of animal protein-rich diet to kidney stone formation and calcium metabolism. Journal of clinical endocrinology. 66 (1): 140-146.
Bruge F, Bacchetti T, Principi F, Littarru GP & Tiano L 2011. Olive oil supplemented with menaquinone-7 significantly affects osteocalcin carboxylation. British journal of nutrition. 106 (7): 1058-1062.
Bunout D, et al. 2006. Effect of a nutritional supplementation on bone health in Chilean elderly subjects with femoral osteoporosis. Journal of the American College of Nutrition. 25 (3): 170-177.
Chan R, Woo J & Leung J 2011. Effects of food groups and dietary nutrients on bone loss in elderly Chinese population. journal of nutrition, health aging. 15 (4): 287-294.
Claes L, Recknagel S & Ignatius A 2012. Fracture healing under healthy and inflammatory conditions. Nature reviews rheumatology. 8 (3): 133-143.
Clark HD, et al. 1999. Assessing the quality of randomized trials: reliability of the Jadad scale. Controlled clinical trials. 20 (5): 448-452.
Dai Z, et al. 2014. Adherence to a vegetable-fruit-soy dietary pattern or the Alternative Healthy Eating Index is associated with lower hip fracture risk among Singapore Chinese. Journal of nutrition, health aging. 144 (4): 511-518.
DeNichilo MO, et al. 2015. Peroxidase enzymes regulate collagen extracellular matrix biosynthesis. American journal of pathology. 185 (5): 1372-1384.
Eastell R & Szulc P 2017. Use of bone turnover markers in postmenopausal osteoporosis. lancet diabetes endocrinology. 5 (11): 908-923.
George KS, et al. 2020. Is soy protein effective in reducing cholesterol and improving bone health? Food function. 11 (1): 544-551.
Greendale GA, et al. 2002. Dietary soy isoflavones and bone mineral density: results from the study of women's health across the nation. American journal of epidemiology. 155 (8): 746-754.
Harada A, et al. 2004. Japanese orthopedists’ interests in prevention of fractures in the elderly from falls. Osteoporosis international. 15 (7): 560-566.
Haron H, et al. 2010. Absorption of calcium from milk and tempeh consumed by postmenopausal Malay women using the dual stable isotope technique. International journal of food sciences. 61 (2): 125-137.
Hasnah H, Amin I & Suzana S 2012. Bone health status and lipid profile among post-menopausal malay women in Cheras, Kuala Lumpur. Malaysian journal of nutrition. 18 (2).
Ikeda Y, et al. 2006. Intake of fermented soybeans, natto, is associated with reduced bone loss in postmenopausal women: Japanese Population-Based Osteoporosis (JPOS) Study. Journal of nutrition. 136 (5): 1323-1328.
Izumi T, et al. 2000. Soy isoflavone aglycones are absorbed faster and in higher amounts than their glucosides in humans. Journal of nutrition. 130 (7): 1695-1699.
Kaneki M, et al. 2001. Japanese fermented soybean food as the major determinant of the large geographic difference in circulating levels of vitamin K2: possible implications for hip-fracture risk. Nutrition research reviews. 17 (4): 315-321.
Katsuyama H, Ideguchi S, Fukunaga M, Saijoh K & Sunami S 2002. Usual dietary intake of fermented soybeans (Natto) is associated with bone mineral density in premenopausal women. Journal of nutritional science vitaminology. 48 (3): 207-215.
Khalil D, et al. 2005. Soy isoflavones may protect against orchidectomy-induced bone loss in aged male rats. Calcified tissue international. 76 (1): 56-62.
Knapen M, Drummen N, Smit E, Vermeer C & Theuwissen E 2013. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporosis International. 24 (9): 2499-2507.
Koh W-P, et al. 2009. Gender-specific associations between soy and risk of hip fracture in the Singapore Chinese Health Study. American journal of epidemiology. 170 (7): 901-909.
Kojima A, et al. 2020. Natto intake is inversely associated with osteoporotic fracture risk in postmenopausal Japanese women. Journal of nutrition. 150 (3): 599-605.
Kuhnle GG, et al. 2011. Association between dietary phyto-oestrogens and bone density in men and postmenopausal women. ritish journal of nutrition. 106 (7): 1063-1069.
Kuiper G, et al. 1997. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors α and β. Endocrinology. 138 (3): 863-870.
Lappe J, et al. 2013. Effect of a combination of genistein, polyunsaturated fatty acids and vitamins D3 and K1 on bone mineral density in postmenopausal women: a randomized, placebo-controlled, double-blind pilot study. European journal of nutrition. 52 (1): 203-215.
Lousuebsakul Matthews V, Knutsen SF, Beeson WL & Fraser GE 2011. Soy milk and dairy consumption is independently associated with ultrasound attenuation of the heel bone among postmenopausal women: the Adventist Health Study―2. Nutrition research reviews. 31 (10): 766-775.
Ma D, Qin L, Wang P & Katoh R 2008a. Soy isoflavone intake increases bone mineral density in the spine of menopausal women: meta-analysis of randomized controlled trials. Clinical nutrition. 27 (1): 57-64.
Ma D, Qin L, Wang P & Katoh R 2008b. Soy isoflavone intake inhibits bone resorption and stimulates bone formation in menopausal women: meta-analysis of randomized controlled trials. European journal of clinical nutrition. 62 (2): 155-161.
Marini H, et al. 2007. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Annals of internal medicine. 146 (12): 839-847.
Marini H, et al. 2008. OPG and sRANKL serum concentrations in osteopenic, postmenopausal women after 2year genistein administration. Journal of bone mineral research. 23 (5): 715-720.
Myers G, et al. 2015. Tea and flavonoid intake predict osteoporotic fracture risk in elderly Australian women: a prospective study. American journal of clinical nutrition. 102 (4): 958-965.
Nayeem F, Chen N-W, Nagamani M, Anderson KE & Lu L-JWJNR 2019. Daidzein and genistein have differential effects in decreasing whole body bone mineral density but had no effect on hip and spine density in premenopausal women: A 2-year randomized, double-blind, placebo-controlled study.  68: 70-81.
Newton K, et al. 2006. Soy protein and bone mineral density in older men and women: a randomized trial. Maturitas. 55 (3): 270-277.
Nikander E, Metsä-Heikkilä M, O Y & Tiitinen A 2004. Effects of phytoestrogens on bone turnover in postmenopausal women with a history of breast cancer. Journal of clinical endocrinology & metabolism. 89 (3): 1207-1212.
Orwoll E, et al. 2006. Testosterone and estradiol among older men. Journal of clinical endocrinology metabolism. 91 (4): 1336-1344.
Penson DF, Krishnaswami S, Jules A, Seroogy JC & McPheeters ML 2013. Evaluation and treatment of cryptorchidism, https://europepmc. org/article/NBK/nbk115847.
Peterson J, Welch V, Losos M & Tugwell P 2011. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Hospital Research Institute. 2 (1): 1-12.
Piekarz AV & Ward WE 2007. Effect of neonatal exposure to genistein on bone metabolism in mice at adulthood. Pediatric research. 61 (1): 48-53.
Qiu S & Jiang C 2019. Soy and isoflavones consumption and breast cancer survival and recurrence: a systematic review and meta-analysis. European journal of nutrition. 58 (8): 3079-3090.
Reginster J-Y, et al. 1997. Design for an ipriflavone multicenter European fracture study. Calcified tissue international. 61 (1): S28-S32.
Rønn SH, Harsløf T, Pedersen SB & Langdahl BL 2016. Vitamin K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture at the tibia in postmenopausal women. European journal of endocrinology. 175 (6): 541-549.
Sato T, et al. 2000. Effect of vitamin K2 (menaquinone-7) and soybean isoflavone supplementation on serum undercarboxylated osteocalcin in female long-distance runners. Food science technology research. 6 (4): 288-290.
Shetty S, Kapoor N, Bondu JD, Thomas N & Paul TV 2016. Bone turnover markers: Emerging tool in the management of osteoporosis. Indian journal of endocrinology metabolism. 20 (6): 846.
Tai T, et al. 2012. The effect of soy isoflavone on bone mineral density in postmenopausal Taiwanese women with bone loss: a 2-year randomized double-blind placebo-controlled study. Osteoporosis International. 23 (5): 1571-1580.
Taku K, Melby MK, Nishi N, Omori T & Kurzer MS 2011. Soy isoflavones for osteoporosis: an evidence-based approach. Maturitas. 70 (4): 333-338.
Touillaud M, et al. 2019. Use of dietary supplements containing soy isoflavones and breast cancer risk among women aged> 50 y: a prospective study. American journal of clinical nutrition. 109 (3): 597-605.
Viereck V, et al. 2002. Phytoestrogen genistein stimulates the production of osteoprotegerin by human trabecular osteoblasts. Journal of cellular biochemistry. 84 (4): 725-735.
Welch A, et al. 2005. Calcaneum broadband ultrasound attenuation relates to vegetarian and omnivorous diets differently in men and women: an observation from the European Prospective Investigation into Cancer in Norfolk (EPIC–Norfolk) population
study. Osteoporosis international. 16 (6): 590-596.

Wong WW, et al. 2009. Soy isoflavone supplementation and bone mineral density in menopausal women: a 2-y multicenter clinical trial. American journal of clinical nutrition. 90 (5): 1433-1439.
Xiao CW 2008. Health effects of soy protein and isoflavones in humans. Journal of nutrition. 138 (6): 1244S-1249S.
Yoshikata R, Myint KZY & Ohta H 2018. Effects of equol supplement on bone and cardiovascular parameters in middle-aged Japanese women: A prospective observational study. Journal of alternative complementary medicine. 24 (7): 701-708.
Zhang X, et al. 2005. Prospective cohort study of soy food consumption and risk of bone fracture among postmenopausal women. Archives of internal medicine. 165 (16): 1890-1895.
Zhang Z-q, et al. 2017. Association between diet inflammatory index and osteoporotic hip fracture in elderly Chinese population. Journal of the American medical directors association. 18 (8): 671-677.
Zheng N, et al. 2019. Soy food consumption, exercise, and body mass index and osteoporotic fracture risk among breast cancer survivors: The Shanghai breast cancer survival study. JNCI cancer spectrum. 3 (2): pkz017.
Zheng X, Lee S-K & Chun OK 2016. Soy isoflavones and osteoporotic bone loss: a review with an emphasis on modulation of bone remodeling. Journal of medicinal food. 19 (1): 1-14.


 
Type of article: review article | Subject: public specific
Received: 2022/04/3 | Published: 2024/02/21 | ePublished: 2024/02/21

References
1. Abdi F, Alimoradi Z, Haqi P & Mahdizad F 2016. Effects of phytoestrogens on bone mineral density during the menopause transition: a systematic review of randomized, controlled trials. Climacteric. 19 (6): 535-545.
2. Agnusdei D & Bufalino L 1997. Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcified tissue international. 61 (1): S23-S27.
3. Alexandersen P, et al. 2001. Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial. Journal of the American Medical Association (JAMA). 285 (11): 1482-1488.
4. Amin S, et al. 2006. Estradiol, testosterone, and the risk for hip fractures in elderly men from the Framingham Study. American journal of medicine. 119 (5): 426-433.
5. Anderson JJ, Anthony M, Messina M & Garne SC 1999. Effects of phyto-oestrogens on tissues. Nutrition research reviews. 12 (1): 75-116.
6. Arcoraci V, et al. 2017. Antiosteoporotic activity of genistein aglycone in postmenopausal women: Evidence from a post-hoc analysis of a multicenter randomized controlled trial. Nutrients. 9 (2): 179.
7. Arjmandi BH & Smith BJ 2002. Soy isoflavones’ osteoprotective role in postmenopausal women: mechanism of action. Journal of nutritional biochemistry. 13 (3): 130-137.
8. Baglia ML, et al. 2015. Soy isoflavone intake and bone mineral density in breast cancer survivors. Cancer causes control. 26 (4): 571-580.
9. Barker AJ, et al. 2021. Plant-derived soybean peroxidase stimulates osteoblast collagen biosynthesis, matrix mineralization, and accelerates bone regeneration in a sheep model. Bone reports. 101096.
10. Blair HC, Jordan SE, Peterson TG & Barnes S 1996. Variable effects of tyrosine kinase inhibitors on avian osteoclastic activity and reduction of bone loss in ovariectomized rats. Journal of cellular biochemistry. 61 (4): 629-637.
11. Breslau NA, Brinkley L, Hill KD, PAK CY & Metabolism 1988. Relationship of animal protein-rich diet to kidney stone formation and calcium metabolism. Journal of clinical endocrinology. 66 (1): 140-146.
12. Bruge F, Bacchetti T, Principi F, Littarru GP & Tiano L 2011. Olive oil supplemented with menaquinone-7 significantly affects osteocalcin carboxylation. British journal of nutrition. 106 (7): 1058-1062.
13. Bunout D, et al. 2006. Effect of a nutritional supplementation on bone health in Chilean elderly subjects with femoral osteoporosis. Journal of the American College of Nutrition. 25 (3): 170-177.
14. Chan R, Woo J & Leung J 2011. Effects of food groups and dietary nutrients on bone loss in elderly Chinese population. journal of nutrition, health aging. 15 (4): 287-294.
15. Claes L, Recknagel S & Ignatius A 2012. Fracture healing under healthy and inflammatory conditions. Nature reviews rheumatology. 8 (3): 133-143.
16. Clark HD, et al. 1999. Assessing the quality of randomized trials: reliability of the Jadad scale. Controlled clinical trials. 20 (5): 448-452.
17. Dai Z, et al. 2014. Adherence to a vegetable-fruit-soy dietary pattern or the Alternative Healthy Eating Index is associated with lower hip fracture risk among Singapore Chinese. Journal of nutrition, health aging. 144 (4): 511-518.
18. DeNichilo MO, et al. 2015. Peroxidase enzymes regulate collagen extracellular matrix biosynthesis. American journal of pathology. 185 (5): 1372-1384.
19. Eastell R & Szulc P 2017. Use of bone turnover markers in postmenopausal osteoporosis. lancet diabetes endocrinology. 5 (11): 908-923.
20. George KS, et al. 2020. Is soy protein effective in reducing cholesterol and improving bone health? Food function. 11 (1): 544-551.
21. Greendale GA, et al. 2002. Dietary soy isoflavones and bone mineral density: results from the study of women's health across the nation. American journal of epidemiology. 155 (8): 746-754.
22. Harada A, et al. 2004. Japanese orthopedists’ interests in prevention of fractures in the elderly from falls. Osteoporosis international. 15 (7): 560-566.
23. Haron H, et al. 2010. Absorption of calcium from milk and tempeh consumed by postmenopausal Malay women using the dual stable isotope technique. International journal of food sciences. 61 (2): 125-137.
24. Hasnah H, Amin I & Suzana S 2012. Bone health status and lipid profile among post-menopausal malay women in Cheras, Kuala Lumpur. Malaysian journal of nutrition. 18 (2).
25. Ikeda Y, et al. 2006. Intake of fermented soybeans, natto, is associated with reduced bone loss in postmenopausal women: Japanese Population-Based Osteoporosis (JPOS) Study. Journal of nutrition. 136 (5): 1323-1328.
26. Izumi T, et al. 2000. Soy isoflavone aglycones are absorbed faster and in higher amounts than their glucosides in humans. Journal of nutrition. 130 (7): 1695-1699.
27. Kaneki M, et al. 2001. Japanese fermented soybean food as the major determinant of the large geographic difference in circulating levels of vitamin K2: possible implications for hip-fracture risk. Nutrition research reviews. 17 (4): 315-321.
28. Katsuyama H, Ideguchi S, Fukunaga M, Saijoh K & Sunami S 2002. Usual dietary intake of fermented soybeans (Natto) is associated with bone mineral density in premenopausal women. Journal of nutritional science vitaminology. 48 (3): 207-215.
29. Khalil D, et al. 2005. Soy isoflavones may protect against orchidectomy-induced bone loss in aged male rats. Calcified tissue international. 76 (1): 56-62.
30. Knapen M, Drummen N, Smit E, Vermeer C & Theuwissen E 2013. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporosis International. 24 (9): 2499-2507.
31. Koh W-P, et al. 2009. Gender-specific associations between soy and risk of hip fracture in the Singapore Chinese Health Study. American journal of epidemiology. 170 (7): 901-909.
32. Kojima A, et al. 2020. Natto intake is inversely associated with osteoporotic fracture risk in postmenopausal Japanese women. Journal of nutrition. 150 (3): 599-605.
33. Kuhnle GG, et al. 2011. Association between dietary phyto-oestrogens and bone density in men and postmenopausal women. ritish journal of nutrition. 106 (7): 1063-1069.
34. Kuiper G, et al. 1997. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors α and β. Endocrinology. 138 (3): 863-870.
35. Lappe J, et al. 2013. Effect of a combination of genistein, polyunsaturated fatty acids and vitamins D3 and K1 on bone mineral density in postmenopausal women: a randomized, placebo-controlled, double-blind pilot study. European journal of nutrition. 52 (1): 203-215.
36. Lousuebsakul Matthews V, Knutsen SF, Beeson WL & Fraser GE 2011. Soy milk and dairy consumption is independently associated with ultrasound attenuation of the heel bone among postmenopausal women: the Adventist Health Study―2. Nutrition research reviews. 31 (10): 766-775.
37. Ma D, Qin L, Wang P & Katoh R 2008a. Soy isoflavone intake increases bone mineral density in the spine of menopausal women: meta-analysis of randomized controlled trials. Clinical nutrition. 27 (1): 57-64.
38. Ma D, Qin L, Wang P & Katoh R 2008b. Soy isoflavone intake inhibits bone resorption and stimulates bone formation in menopausal women: meta-analysis of randomized controlled trials. European journal of clinical nutrition. 62 (2): 155-161.
39. Marini H, et al. 2007. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Annals of internal medicine. 146 (12): 839-847.
40. Marini H, et al. 2008. OPG and sRANKL serum concentrations in osteopenic, postmenopausal women after 2‐year genistein administration. Journal of bone mineral research. 23 (5): 715-720.
41. Myers G, et al. 2015. Tea and flavonoid intake predict osteoporotic fracture risk in elderly Australian women: a prospective study. American journal of clinical nutrition. 102 (4): 958-965.
42. Nayeem F, Chen N-W, Nagamani M, Anderson KE & Lu L-JWJNR 2019. Daidzein and genistein have differential effects in decreasing whole body bone mineral density but had no effect on hip and spine density in premenopausal women: A 2-year randomized, double-blind, placebo-controlled study. 68: 70-81.
43. Newton K, et al. 2006. Soy protein and bone mineral density in older men and women: a randomized trial. Maturitas. 55 (3): 270-277.
44. Nikander E, Metsä-Heikkilä M, O Y & Tiitinen A 2004. Effects of phytoestrogens on bone turnover in postmenopausal women with a history of breast cancer. Journal of clinical endocrinology & metabolism. 89 (3): 1207-1212.
45. Orwoll E, et al. 2006. Testosterone and estradiol among older men. Journal of clinical endocrinology metabolism. 91 (4): 1336-1344.
46. Penson DF, Krishnaswami S, Jules A, Seroogy JC & McPheeters ML 2013. Evaluation and treatment of cryptorchidism, https://europepmc. org/article/NBK/nbk115847.
47. Peterson J, Welch V, Losos M & Tugwell P 2011. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Hospital Research Institute. 2 (1): 1-12.
48. Piekarz AV & Ward WE 2007. Effect of neonatal exposure to genistein on bone metabolism in mice at adulthood. Pediatric research. 61 (1): 48-53.
49. Qiu S & Jiang C 2019. Soy and isoflavones consumption and breast cancer survival and recurrence: a systematic review and meta-analysis. European journal of nutrition. 58 (8): 3079-3090.
50. Reginster J-Y, et al. 1997. Design for an ipriflavone multicenter European fracture study. Calcified tissue international. 61 (1): S28-S32.
51. Rønn SH, Harsløf T, Pedersen SB & Langdahl BL 2016. Vitamin K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture at the tibia in postmenopausal women. European journal of endocrinology. 175 (6): 541-549.
52. Sato T, et al. 2000. Effect of vitamin K2 (menaquinone-7) and soybean isoflavone supplementation on serum undercarboxylated osteocalcin in female long-distance runners. Food science technology research. 6 (4): 288-290.
53. Shetty S, Kapoor N, Bondu JD, Thomas N & Paul TV 2016. Bone turnover markers: Emerging tool in the management of osteoporosis. Indian journal of endocrinology metabolism. 20 (6): 846.
54. Tai T, et al. 2012. The effect of soy isoflavone on bone mineral density in postmenopausal Taiwanese women with bone loss: a 2-year randomized double-blind placebo-controlled study. Osteoporosis International. 23 (5): 1571-1580.
55. Taku K, Melby MK, Nishi N, Omori T & Kurzer MS 2011. Soy isoflavones for osteoporosis: an evidence-based approach. Maturitas. 70 (4): 333-338.
56. Touillaud M, et al. 2019. Use of dietary supplements containing soy isoflavones and breast cancer risk among women aged> 50 y: a prospective study. American journal of clinical nutrition. 109 (3): 597-605.
57. Viereck V, et al. 2002. Phytoestrogen genistein stimulates the production of osteoprotegerin by human trabecular osteoblasts. Journal of cellular biochemistry. 84 (4): 725-735.
58. Welch A, et al. 2005. Calcaneum broadband ultrasound attenuation relates to vegetarian and omnivorous diets differently in men and women: an observation from the European Prospective Investigation into Cancer in Norfolk (EPIC–Norfolk) population study. Osteoporosis international. 16 (6): 590-596.
60. Wong WW, et al. 2009. Soy isoflavone supplementation and bone mineral density in menopausal women: a 2-y multicenter clinical trial. American journal of clinical nutrition. 90 (5): 1433-1439.
61. Xiao CW 2008. Health effects of soy protein and isoflavones in humans. Journal of nutrition. 138 (6): 1244S-1249S.
62. Yoshikata R, Myint KZY & Ohta H 2018. Effects of equol supplement on bone and cardiovascular parameters in middle-aged Japanese women: A prospective observational study. Journal of alternative complementary medicine. 24 (7): 701-708.
63. Zhang X, et al. 2005. Prospective cohort study of soy food consumption and risk of bone fracture among postmenopausal women. Archives of internal medicine. 165 (16): 1890-1895.
64. Zhang Z-q, et al. 2017. Association between diet inflammatory index and osteoporotic hip fracture in elderly Chinese population. Journal of the American medical directors association. 18 (8): 671-677.
65. Zheng N, et al. 2019. Soy food consumption, exercise, and body mass index and osteoporotic fracture risk among breast cancer survivors: The Shanghai breast cancer survival study. JNCI cancer spectrum. 3 (2): pkz017.
66. Zheng X, Lee S-K & Chun OK 2016. Soy isoflavones and osteoporotic bone loss: a review with an emphasis on modulation of bone remodeling. Journal of medicinal food. 19 (1): 1-14.

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