Volume 9, Issue 1 (Feb 2024)                   JNFS 2024, 9(1): 160-172 | Back to browse issues page

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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
Abstract:   (1125 Views)
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
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Type of article: review article | Subject: public specific
Received: 2022/04/3 | Published: 2024/02/21 | ePublished: 2024/02/21

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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