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Isoflavone intervention and its impact on bone mineral density in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials

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Abstract

Summary

Due to estrogen deficiency, postmenopausal women may suffer from an imbalance in bone metabolism that leads to bone fractures. Isoflavones, a type of phytoestrogen, have been suggested to improve bone metabolism and increase bone mass. Therefore, isoflavones are increasingly recognized as a promising natural alternative to hormone replacement therapy for postmenopausal women who face a heightened risk of osteoporosis and are susceptible to bone fractures.

Purpose

This study aimed to evaluate the efficacy of isoflavone interventions on bone mineral density (BMD) in postmenopausal women by means of systematic review and meta-analysis.

Methods

The electronic database searches were performed on PubMed, Embase, Scopus, and Cochrane Library databases, covering literature up to April 20, 2023. A random-effects model was used to obtain the main effect estimates, with a mean difference (MD) and its 95% confidence interval (CI) as the effect size summary. The risk of bias assessment was conducted using the Risk of Bias 2 (RoB2) tool.

Results

A total of 63 randomized controlled trials comparing isoflavone interventions (n = 4,754) and placebo (n = 4,272) were included. The results indicated that isoflavone interventions significantly improved BMD at the lumbar spine (MD = 0.0175 g/cm2; 95% CI, 0.0088 to 0.0263, P < 0.0001), femoral neck (MD = 0.0172 g/cm2; 95% CI, 0.0046 to 0.0298, P = 0.0073), and distal radius (MD = 0.0138 g/cm2; 95% CI, 0.0077 to 0.0198, P < 0.0001) in postmenopausal women. Subgroup analysis showed that the isoflavone intervention was effective for improving BMD when the duration was ≥ 12 months and when the intervention contained genistein of at least 50 mg/day.

Conclusion

This systematic review and meta-analysis suggests that isoflavone interventions, especially those containing genistein of at least 50 mg/day, can effectively enhance BMD in postmenopausal women.

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Data availability

All data used to support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Jeremiah MP, Unwin BK, Greenawald MH, Casiano VE (2015) Diagnosis and management of osteoporosis. Am Fam Physician 92:261–268

    PubMed  Google Scholar 

  2. WHO Scientific Group on the Prevention and Management of Osteoporosis (2003) Prevention and management of osteoporosis: report of a WHO scientific group. World Health Organization

    Google Scholar 

  3. Boschitsch EP, Durchschlag E, Dimai HP (2017) Age-related prevalence of osteoporosis and fragility fractures: real-world data from an Austrian Menopause and Osteoporosis Clinic. Climacteric J Int Menopause Soc 20:157–163. https://doi.org/10.1080/13697137.2017.1282452

    Article  CAS  Google Scholar 

  4. Cheng C-H, Chen L-R, Chen K-H (2022) Osteoporosis due to hormone imbalance: An overview of the effects of estrogen deficiency and glucocorticoid overuse on bone turnover. Int J Mol Sci 23:1376. https://doi.org/10.3390/ijms23031376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Center JR, Nguyen TV, Schneider D et al (1999) Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet Lond Engl 353:878–882. https://doi.org/10.1016/S0140-6736(98)09075-8

    Article  CAS  Google Scholar 

  6. Feldstein A, Elmer PJ, Orwoll E et al (2003) Bone mineral density measurement and treatment for osteoporosis in older individuals with fractures: a gap in evidence-based practice guideline implementation. Arch Intern Med 163:2165–2172. https://doi.org/10.1001/archinte.163.18.2165

    Article  PubMed  Google Scholar 

  7. Rondanelli M, Faliva MA, Barrile GC et al (2021) Nutrition, physical activity, and dietary supplementation to prevent bone mineral density loss: A food pyramid. Nutrients 14:74. https://doi.org/10.3390/nu14010074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Body J-J, Bergmann P, Boonen S et al (2011) Non-pharmacological management of osteoporosis: a consensus of the Belgian Bone Club. Osteoporos Int 22:2769–2788. https://doi.org/10.1007/s00198-011-1545-x

    Article  PubMed  PubMed Central  Google Scholar 

  9. Reginster JY, Neuprez A, Beaudart C et al (2014) Antiresorptive drugs beyond bisphosphonates and selective oestrogen receptor modulators for the management of postmenopausal osteoporosis. Drugs Aging 31:413–424. https://doi.org/10.1007/s40266-014-0179-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tu KN, Lie JD, Wan CKV et al (2018) Osteoporosis: A review of treatment options. Pharm Ther 43:92–104

    Google Scholar 

  11. Cosman F (2014) Anabolic and antiresorptive therapy for osteoporosis: Combination and sequential approaches. Curr Osteoporos Rep 12:385–395. https://doi.org/10.1007/s11914-014-0237-9

    Article  PubMed  Google Scholar 

  12. Chen JS, Sambrook PN (2012) Antiresorptive therapies for osteoporosis: a clinical overview. Nat Rev Endocrinol 8:81–91. https://doi.org/10.1038/nrendo.2011.146

    Article  CAS  Google Scholar 

  13. Levin VA, Jiang X, Kagan R (2018) Estrogen therapy for osteoporosis in the modern era. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 29:1049–1055. https://doi.org/10.1007/s00198-018-4414-z

    Article  CAS  Google Scholar 

  14. Marjoribanks J, Farquhar C, Roberts H et al (2017) Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev 2017:CD004143. https://doi.org/10.1002/14651858.CD004143.pub5

    Article  PubMed Central  Google Scholar 

  15. Wu L, Ling Z, Feng X et al (2017) Herb medicines against osteoporosis: Active compounds & relevant biological mechanisms. Curr Top Med Chem 17:1670–1691. https://doi.org/10.2174/1568026617666161116141033

    Article  CAS  PubMed  Google Scholar 

  16. Geller SE, Studee L (2006) Soy and red clover for mid-life and aging. Climacteric 9:245–263. https://doi.org/10.1080/13697130600736934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Barańska A, Kanadys W, Bogdan M, et al (2022) The role of soy isoflavones in the prevention of bone loss in postmenopausal women: A systematic review with meta-analysis of randomized controlled trials. J Clin Med 11. https://doi.org/10.3390/jcm11164676

  18. Kanadys W, Barańska A, Błaszczuk A et al (2021) Effects of soy isoflavones on biochemical markers of bone metabolism in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials. Int J Environ Res Public Health 18:5346. https://doi.org/10.3390/ijerph18105346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Harahap IA, Suliburska J (2022) An overview of dietary isoflavones on bone health: The association between calcium bioavailability and gut microbiota modulation. Mater Today Proc 63:S368–S372. https://doi.org/10.1016/j.matpr.2022.03.549

    Article  CAS  Google Scholar 

  20. Wong WW, Lewis RD, Steinberg FM et al (2009) Soy isoflavone supplementation and bone mineral density in menopausal women: a 2-y multicenter clinical trial. Am J Clin Nutr 90:1433–1439. https://doi.org/10.3945/ajcn.2009.28001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ye Y-B, Tang X-Y, Verbruggen MA, Su Y-X (2006) Soy isoflavones attenuate bone loss in early postmenopausal Chinese women. Eur J Nutr 45:327–334. https://doi.org/10.1007/s00394-006-0602-2

    Article  CAS  PubMed  Google Scholar 

  22. Arcoraci V, Atteritano M, Squadrito F et al (2017) Antiosteoporotic activity of genistein aglycone in postmenopausal women: Evidence from a post-hoc analysis of a multicenter randomized controlled trial. Nutrients 9:179. https://doi.org/10.3390/nu9020179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Moher D, Shamseer L, Clarke M et al (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 4:1. https://doi.org/10.1186/2046-4053-4-1

    Article  PubMed  PubMed Central  Google Scholar 

  24. Rohatgi A (2022) Web based tool to extract data from plots, images, and maps. WebPlotDigitizer: Version 4.6. Pacifica, California, USA. https://automeris.io/WebPlotDigitizer

  25. Sterne JAC, Savović J, Page MJ et al (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 366:l4898. https://doi.org/10.1136/bmj.14898

    Article  PubMed  Google Scholar 

  26. Schünemann HJ, Higgins JPT, Vist GE, Glasziou P, Akl EA, Skoetz N, Guyatt GH (2019) Cochrane Handbook for Systematic Reviews of Interventions. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (eds) Completing ‘Summary of findings’ tables and grading the certainty of the evidence, 2nd edn. Wiley, Chichester, pp 375–402

    Google Scholar 

  27. Deeks JJ, Higgins JPT, Altman D (2019) Cochrane Handbook for Systematic Reviews ofInterventions. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (eds) Analysing data and undertaking meta-analyses, 2nd edn. Wiley, Chichester, pp 241–284

    Google Scholar 

  28. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634. https://doi.org/10.1136/bmj.315.7109.629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wan X, Wang W, Liu J, Tong T (2014) Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 14:135. https://doi.org/10.1186/1471-2288-14-135

    Article  PubMed  PubMed Central  Google Scholar 

  30. Higgins JPT, Li T, Deeks JJ (2019) Cochrane Handbook for Systematic Reviews of Interventions. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (eds) Choosing effect measures and computing estimates of effect, 2nd edn. Wiley, Chichester, pp 143–176

    Google Scholar 

  31. Agnusdei D, Adami S, Cervetti R et al (1992) Effects of ipriflavone on bone mass and calcium metabolism in postmenopausal osteoporosis. Bone Miner 19(Suppl 1):S43-48. https://doi.org/10.1016/0169-6009(92)90865-b

    Article  PubMed  Google Scholar 

  32. Melis GB, Paoletti AM, Bartolini R et al (1992) Ipriflavone and low doses of estrogens in the prevention of bone mineral loss in climacterium. Bone Miner 19:S49–S56. https://doi.org/10.1016/0169-6009(92)90866-C

    Article  CAS  PubMed  Google Scholar 

  33. Passeri M, Biondi M, Costi D et al (1992) Effect of ipriflavone on bone mass in elderly osteoporotic women. Bone Miner 19(Suppl 1):S57-62. https://doi.org/10.1016/0169-6009(92)90867-d

    Article  PubMed  Google Scholar 

  34. Kovács AB (1994) Efficacy of ipriflavone in the prevention and treatment of postmenopausal osteoporosis. Agents Actions 41:86–87. https://doi.org/10.1007/BF01986400

    Article  PubMed  Google Scholar 

  35. Maugeri D, Panebianco P, Russo MS et al (1994) Ipriflavone-treatment of senile osteoporosis: results of a multicenter, double-blind clinical trial of 2 years. Arch Gerontol Geriatr 19:253–263. https://doi.org/10.1016/0167-4943(94)00571-0

    Article  CAS  PubMed  Google Scholar 

  36. Valente M, Bufalino L, Castiglione GN et al (1994) Effects of 1-year treatment with ipriflavone on bone in postmenopausal women with low bone mass. Calcif Tissue Int 54:377–380. https://doi.org/10.1007/BF00305522

    Article  CAS  PubMed  Google Scholar 

  37. Agnusdei D, Gennari C, Bufalino L (1995) Prevention of early postmenopausal bone loss using low doses of conjugated estrogens and the non-hormonal, bone-active drug ipriflavone. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 5:462–466. https://doi.org/10.1007/BF01626609

    Article  CAS  Google Scholar 

  38. Ushiroyama T, Okamura S, Ikeda A, Ueki M (1995) Efficacy of ipriflavone and 1α vitamin D therapy for the cessation of vertebral bone loss. Int J Gynecol Obstet 48:283–288. https://doi.org/10.1016/0020-7292(94)02280-C

    Article  CAS  Google Scholar 

  39. Melis GB, Paoletti AM, Cagnacci A (1996) Ipriflavone prevents bone loss in postmenopausal women. Menopause 3:27

    Article  Google Scholar 

  40. Adami S, Bufalino L, Cervetti R et al (1997) Ipriflavone prevents radial bone loss in postmenopausal women with low bone mass over 2 years. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 7:119–125. https://doi.org/10.1007/BF01623686

    Article  CAS  Google Scholar 

  41. Agnusdei D, Bufalino L (1997) Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcif Tissue Int 61(Suppl 1):S23-27. https://doi.org/10.1007/s002239900381

    Article  CAS  PubMed  Google Scholar 

  42. Agnusdei D, Crepaldi G, Isaia G et al (1997) A double blind, placebo-controlled trial of ipriflavone for prevention of postmenopausal spinal bone loss. Calcif Tissue Int 61:142–147. https://doi.org/10.1007/s002239900312

    Article  CAS  PubMed  Google Scholar 

  43. de Aloysio D, Gambacciani M, Altieri P et al (1997) Bone density changes in postmenopausal women with the administration of ipriflavone alone or in association with low-dose ERT. Gynecol Endocrinol Off J Int Soc Gynecol Endocrinol 11:289–293. https://doi.org/10.3109/09513599709152548

    Article  Google Scholar 

  44. Gambacciani M, Ciaponi M, Cappagli B et al (1997) Effects of combined low dose of the isoflavone derivative ipriflavone and estrogen replacement on bone mineral density and metabolism in postmenopausal women. Maturitas 28:75–81. https://doi.org/10.1016/s0378-5122(97)00059-5

    Article  CAS  PubMed  Google Scholar 

  45. Gennari C, Adami S, Agnusdei D et al (1997) Effect of chronic treatment with ipriflavone in postmenopausal women with low bone mass. Calcif Tissue Int 61(Suppl 1):S19-22. https://doi.org/10.1007/s002239900380

    Article  CAS  PubMed  Google Scholar 

  46. Nozaki M, Hashimoto K, Inoue Y et al (1998) Treatment of bone loss in oophorectomized women with a combination of ipriflavone and conjugated equine estrogen. Int J Gynaecol Obstet Off Organ Int Fed Gynaecol Obstet 62:69–75. https://doi.org/10.1016/s0020-7292(98)00068-x

    Article  CAS  Google Scholar 

  47. Potter SM, Baum JA, Teng H et al (1998) Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 68:1375S-1379S. https://doi.org/10.1093/ajcn/68.6.1375S

    Article  CAS  PubMed  Google Scholar 

  48. Ohta H, Komukai S, Makita K et al (1999) Effects of 1-year ipriflavone treatment on lumbar bone mineral density and bone metabolic markers in postmenopausal women with low bone mass. Horm Res 51:178–183. https://doi.org/10.1159/000023354

    Article  CAS  PubMed  Google Scholar 

  49. Alekel DL, Germain AS, Peterson CT et al (2000) Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr 72:844–852. https://doi.org/10.1093/ajcn/72.3.844

    Article  CAS  PubMed  Google Scholar 

  50. Alexandersen P, Toussaint A, Christiansen C et al (2001) Ipriflavone in the treatment of postmenopausal osteoporosisa randomized controlled trial. JAMA 285:1482–1488. https://doi.org/10.1001/jama.285.11.1482

    Article  CAS  PubMed  Google Scholar 

  51. Katase K, Kato T, Hirai Y et al (2001) Effects of ipriflavone on bone loss following a bilateral ovariectomy and menopause: a randomized placebo-controlled study. Calcif Tissue Int 69:73–77. https://doi.org/10.1007/s00223-001-0017-2

    Article  CAS  PubMed  Google Scholar 

  52. Morabito N, Crisafulli A, Vergara C et al (2002) Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo-controlled study. J Bone Miner Res Off J Am Soc Bone Miner Res 17:1904–1912. https://doi.org/10.1359/jbmr.2002.17.10.1904

    Article  CAS  Google Scholar 

  53. Chen Y-M, Ho SC, Lam SSH et al (2003) Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial. J Clin Endocrinol Metab 88:4740–4747. https://doi.org/10.1210/jc.2003-030290

    Article  CAS  PubMed  Google Scholar 

  54. Uesugi T, Toda T, Okuhira T, Chen J-T (2003) Evidence of estrogenic effect by the three-month-intervention of isoflavone on vaginal maturation and bone metabolism in early postmenopausal women. Endocr J 50:613–619. https://doi.org/10.1507/endocrj.50.613

    Article  CAS  PubMed  Google Scholar 

  55. Atkinson C, Compston JE, Day NE et al (2004) The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 79:326–333. https://doi.org/10.1093/ajcn/79.2.326

    Article  CAS  PubMed  Google Scholar 

  56. Harkness LS, Fiedler K, Sehgal AR et al (2004) Decreased bone resorption with soy isoflavone supplementation in postmenopausal women. J Womens Health 2002 13:1000–1007. https://doi.org/10.1089/jwh.2004.13.1000

    Article  Google Scholar 

  57. Kreijkamp-Kaspers S, Kok L, Grobbee DE et al (2004) Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial. JAMA 292:65–74. https://doi.org/10.1001/jama.292.1.65

    Article  CAS  PubMed  Google Scholar 

  58. Lydeking-Olsen E, Beck-Jensen J-E, Setchell KDR, Holm-Jensen T (2004) Soymilk or progesterone for prevention of bone loss–a 2 year randomized, placebo-controlled trial. Eur J Nutr 43:246–257. https://doi.org/10.1007/s00394-004-0497-8

    Article  CAS  PubMed  Google Scholar 

  59. Arjmandi BH, Lucas EA, Khalil DA et al (2005) One year soy protein supplementation has positive effects on bone formation markers but not bone density in postmenopausal women. Nutr J 4:8. https://doi.org/10.1186/1475-2891-4-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Huang H-Y, Yang H-P, Yang H-T et al (2006) One-year soy isoflavone supplementation prevents early postmenopausal bone loss but without a dose-dependent effect. J Nutr Biochem 17:509–517. https://doi.org/10.1016/j.jnutbio.2006.01.003

    Article  CAS  PubMed  Google Scholar 

  61. Wu J, Oka J, Higuchi M et al (2006) Cooperative effects of isoflavones and exercise on bone and lipid metabolism in postmenopausal Japanese women: a randomized placebo-controlled trial. Metabolism 55:423–433. https://doi.org/10.1016/j.metabol.2005.10.002

    Article  CAS  PubMed  Google Scholar 

  62. Evans EM, Racette SB, Van Pelt RE et al (2007) Effects of soy protein isolate and moderate exercise on bone turnover and bone mineral density in postmenopausal women. Menopause N Y N 14:481–488. https://doi.org/10.1097/01.gme.0000243570.78570.f7

    Article  Google Scholar 

  63. Marini H, Minutoli L, Polito F et al (2007) Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Ann Intern Med 146:839–847. https://doi.org/10.7326/0003-4819-146-12-200706190-00005

    Article  PubMed  Google Scholar 

  64. Wu J, Oka J, Ezaki J et al (2007) Possible role of equol status in the effects of isoflavone on bone and fat mass in postmenopausal Japanese women: a double-blind, randomized, controlled trial. Menopause N Y N 14:866–874. https://doi.org/10.1097/gme.0b013e3180305299

    Article  Google Scholar 

  65. Zhang G, Qin L, Shi Y (2007) Epimedium-derived phytoestrogen flavonoids exert beneficial effect on preventing bone loss in late postmenopausal women: a 24-month randomized, double-blind and placebo-controlled trial. J Bone Miner Res Off J Am Soc Bone Miner Res 22:1072–1079. https://doi.org/10.1359/jbmr.070405

    Article  CAS  Google Scholar 

  66. Brink E, Coxam V, Robins S et al (2008) Long-term consumption of isoflavone-enriched foods does not affect bone mineral density, bone metabolism, or hormonal status in early postmenopausal women: a randomized, double-blind, placebo controlled study. Am J Clin Nutr 87:761–770. https://doi.org/10.1093/ajcn/87.3.761

    Article  CAS  PubMed  Google Scholar 

  67. Marini H, Bitto A, Altavilla D et al (2008) Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: a follow-up study. J Clin Endocrinol Metab 93:4787–4796. https://doi.org/10.1210/jc.2008-1087

    Article  CAS  PubMed  Google Scholar 

  68. Marini H, Minutoli L, Polito F et al (2008) OPG and sRANKL serum concentrations in osteopenic, postmenopausal women after 2-year genistein administration. J Bone Miner Res Off J Am Soc Bone Miner Res 23:715–720. https://doi.org/10.1359/jbmr.080201

    Article  CAS  Google Scholar 

  69. Powles TJ, Howell A, Evans DG et al (2008) Red clover isoflavones are safe and well tolerated in women with a family history of breast cancer. Menopause Int 14:6–12. https://doi.org/10.1258/MI.2007.007033

    Article  PubMed  Google Scholar 

  70. Atteritano M, Mazzaferro S, Frisina A et al (2009) Genistein effects on quantitative ultrasound parameters and bone mineral density in osteopenic postmenopausal women. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 20:1947–1954. https://doi.org/10.1007/s00198-009-0883-4

    Article  CAS  Google Scholar 

  71. Kenny AM, Mangano KM, Abourizk RH et al (2009) Soy proteins and isoflavones affect bone mineral density in older women: a randomized controlled trial. Am J Clin Nutr 90:234–242. https://doi.org/10.3945/ajcn.2009.27600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Radhakrishnan G, Rashmi, Agarwal N, Vaid NB (2009) Evaluation of isoflavone rich soy protein supplementation for ostmenopausal therapy. Pak J Nutr 8:1009–1017. https://doi.org/10.3923/pjn.2009.1009.1017

    Article  CAS  Google Scholar 

  73. Vupadhyayula PM, Gallagher JC, Templin T et al (2009) Effects of soy protein isolate on bone mineral density and physical performance indices in postmenopausal women–a 2-year randomized, double-blind, placebo-controlled trial. Menopause N Y N 16:320–328. https://doi.org/10.1097/gme.0b013e3181844893

    Article  Google Scholar 

  74. Alekel DL, Van Loan MD, Koehler KJ et al (2010) The soy isoflavones for reducing bone loss (SIRBL) study: a 3-y randomized controlled trial in postmenopausal women. Am J Clin Nutr 91:218–230. https://doi.org/10.3945/ajcn.2009.28306

    Article  CAS  PubMed  Google Scholar 

  75. Zhang X, Li S-W, Wu J-F et al (2010) Effects of ipriflavone on postmenopausal syndrome and osteoporosis. Gynecol Endocrinol Off J Int Soc Gynecol Endocrinol 26:76–80. https://doi.org/10.3109/09513590903184159

    Article  CAS  Google Scholar 

  76. Cho S-H, Jang J-H, Yoon JY et al (2011) Effects of a safflower tea supplement on antioxidative status and bone markers in postmenopausal women. Nutr Res Pract 5:20–27. https://doi.org/10.4162/nrp.2011.5.1.20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Choquette S, Riesco É, Cormier É et al (2011) Effects of soya isoflavones and exercise on body composition and clinical risk factors of cardiovascular diseases in overweight postmenopausal women: a 6-month double-blind controlled trial. Br J Nutr 105:1199–1209. https://doi.org/10.1017/S0007114510004897

    Article  PubMed  Google Scholar 

  78. Levis S, Strickman-Stein N, Ganjei-Azar P et al (2011) Soy isoflavones in the prevention of menopausal bone loss and menopausal symptoms: a randomized, double-blind trial. Arch Intern Med 171:1363–1369. https://doi.org/10.1001/archinternmed.2011.330

    Article  CAS  PubMed  Google Scholar 

  79. Shedd-Wise KM, Alekel DL, Hofmann H et al (2011) The soy isoflavones for reducing bone loss study: 3-Yr Effects on pQCT bone mineral density and strength measures in postmenopausal women. J Clin Densitom 14:47–57. https://doi.org/10.1016/j.jocd.2010.11.003

    Article  PubMed  PubMed Central  Google Scholar 

  80. Tousen Y, Ezaki J, Fujii Y et al (2011) Natural S-equol decreases bone resorption in postmenopausal, non-equol-producing Japanese women: a pilot randomized, placebo-controlled trial. Menopause N Y N 18:563–574. https://doi.org/10.1097/gme.0b013e3181f85aa7

    Article  Google Scholar 

  81. Gui J-C, Brašić JR, Liu X-D et al (2012) Bone mineral density in postmenopausal Chinese women treated with calcium fortification in soymilk and cow’s milk. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 23:1563–1570. https://doi.org/10.1007/s00198-012-1895-z

    Article  CAS  Google Scholar 

  82. Tai TY, Tsai KS, Tu ST 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. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 23:1571–1580. https://doi.org/10.1007/s00198-011-1750-7

    Article  CAS  Google Scholar 

  83. Chi X-X, Zhang T (2013) The effects of soy isoflavone on bone density in north region of climacteric Chinese women. J Clin Biochem Nutr 53:102–107. https://doi.org/10.3164/jcbn.13-37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Chilibeck PD, Vatanparast H, Pierson R et al (2013) Effect of exercise training combined with isoflavone supplementation on bone and lipids in postmenopausal women: a randomized clinical trial. J Bone Miner Res Off J Am Soc Bone Miner Res 28:780–793. https://doi.org/10.1002/jbmr.1815

    Article  CAS  Google Scholar 

  85. Lappe J, Kunz I, Bendik I 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. Eur J Nutr 52:203–215. https://doi.org/10.1007/s00394-012-0304-x

    Article  CAS  PubMed  Google Scholar 

  86. Orsatti FL, Nahas EAP, Nahas-Neto J et al (2013) Efeito do treinamento contrarresistência e isoflavona na densidade mineral óssea em mulheres na pós-menopausa. Rev Bras Cineantropometria Desempenho Hum 15:726–736. https://doi.org/10.5007/1980-0037.2013v15n6p726

    Article  Google Scholar 

  87. Clifton-Bligh PB, Nery M-L, Clifton-Bligh RJ et al (2015) Red clover isoflavones enriched with formononetin lower serum LDL cholesterol-a randomized, double-blind, placebo-controlled study. Eur J Clin Nutr 69:134–142. https://doi.org/10.1038/ejcn.2014.207

    Article  CAS  PubMed  Google Scholar 

  88. Thorup AC, Lambert MN, Kahr HS et al (2015) Intake of Novel Red Clover Supplementation for 12 Weeks Improves Bone Status in Healthy Menopausal Women. Evid-Based Complement Altern Med ECAM 2015:689138. https://doi.org/10.1155/2015/689138

    Article  Google Scholar 

  89. Lambert MNT, Thybo CB, Lykkeboe S et al (2017) Combined bioavailable isoflavones and probiotics improve bone status and estrogen metabolism in postmenopausal osteopenic women: a randomized controlled trial. Am J Clin Nutr 106:909–920. https://doi.org/10.3945/ajcn.117.153353

    Article  CAS  PubMed  Google Scholar 

  90. Li L, Sun M, Sun J et al (2019) The effect of dried beancurd on bone mineral density in postmenopausal Chinese women: A 2-Year randomized controlled trial. Calcif Tissue Int 105:573–581. https://doi.org/10.1007/s00223-019-00604-2

    Article  CAS  PubMed  Google Scholar 

  91. Warriner AH, Patkar NM, Curtis JR et al (2011) Which fractures are most attributable to osteoporosis? J Clin Epidemiol 64:46–53. https://doi.org/10.1016/j.jclinepi.2010.07.007

    Article  PubMed  PubMed Central  Google Scholar 

  92. Greendale GA, Sowers M, Han W et al (2012) Bone mineral density loss in relation to the final menstrual period in a multiethnic cohort: results from the Study of Women’s Health Across the Nation (SWAN). J Bone Miner Res Off J Am Soc Bone Miner Res 27:111–118. https://doi.org/10.1002/jbmr.534

    Article  Google Scholar 

  93. Riggs BL, Khosla S, Melton LJ (1998) A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J Bone Miner Res 13:763–773. https://doi.org/10.1359/jbmr.1998.13.5.763

    Article  CAS  PubMed  Google Scholar 

  94. Ji MX, Yu Q (2015) Primary osteoporosis in postmenopausal women. Chronic Dis Transl Med 1:9–13. https://doi.org/10.1016/j.cdtm.2015.02.006

    Article  PubMed  PubMed Central  Google Scholar 

  95. Nardi A, Ventura L, Rossini M, Ramazzina E (2010) The importance of mechanics in the pathogenesis of fragility fractures of the femur and vertebrae. Clin Cases Miner Bone Metab 7:130–134

    PubMed  PubMed Central  Google Scholar 

  96. Tanaka S, Adachi T, Kuroda T et al (2014) New simulation model for bone formation markers in osteoporosis patients treated with once-weekly teriparatide. Bone Res 2:14043. https://doi.org/10.1038/boneres.2014.43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Kenkre JS, Bassett J (2018) The bone remodelling cycle. Ann Clin Biochem 55:308–327. https://doi.org/10.1177/0004563218759371

    Article  CAS  PubMed  Google Scholar 

  98. Wei P, Liu M, Chen Y, Chen D-C (2012) Systematic review of soy isoflavone supplements on osteoporosis in women. Asian Pac J Trop Med 5:243–248. https://doi.org/10.1016/S1995-7645(12)60033-9

    Article  CAS  PubMed  Google Scholar 

  99. Hirattanapun E, Koonrungsesomboon N, Teekachunhatean S (2018) Variability of isoflavone content in soy milk products commercially available in Thailand. J Health Sci Med Res 36:117–126

    Article  Google Scholar 

  100. Wu Z, Liu L (2022) The protective activity of genistein against bone and cartilage diseases. Front Pharmacol 13:1016981. https://doi.org/10.3389/fphar.2022.1016981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Nikander E, Metsä-Heikkilä M, Ylikorkala O, Tiitinen A (2004) Effects of phytoestrogens on bone turnover in postmenopausal women with a history of breast cancer. J Clin Endocrinol Metab 89:1207–1212. https://doi.org/10.1210/jc.2003-031166

    Article  CAS  PubMed  Google Scholar 

  102. Liu J, Ho SC, Su Y et al (2009) Effect of long-term intervention of soy isoflavones on bone mineral density in women: a meta-analysis of randomized controlled trials. Bone 44:948–953. https://doi.org/10.1016/j.bone.2008.12.020

    Article  CAS  PubMed  Google Scholar 

  103. Sansai K, Na Takuathung M, Khatsri R et al (2020) Effects of isoflavone interventions on bone mineral density in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 31:1853–1864. https://doi.org/10.1007/s00198-020-05476-z

    Article  CAS  Google Scholar 

  104. Hu Q, Long C, Wu D et al (2020) The efficacy and safety of ipriflavone in postmenopausal women with osteopenia or osteoporosis: A systematic review and meta-analysis. Pharmacol Res 159:104860. https://doi.org/10.1016/j.phrs.2020.104860

    Article  CAS  PubMed  Google Scholar 

  105. Shams-White MM, Chung M, Fu Z et al (2018) Animal versus plant protein and adult bone health: A systematic review and meta-analysis from the National Osteoporosis Foundation. PLoS One 13:e0192459. https://doi.org/10.1371/journal.pone.0192459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Qiu S, Ma Y, Jiang C (2020) Isoflavone combined with exercise on bone mineral density in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials. J Chin Med Assoc JCMA 83:678–685. https://doi.org/10.1097/JCMA.0000000000000365

    Article  PubMed  Google Scholar 

  107. Lambert MNT, Hu LM, Jeppesen PB (2017) A systematic review and meta-analysis of the effects of isoflavone formulations against estrogen-deficient bone resorption in peri- and postmenopausal women. Am J Clin Nutr 106:801–811. https://doi.org/10.3945/ajcn.116.151464

    Article  CAS  PubMed  Google Scholar 

  108. Ricci E, Cipriani S, Chiaffarino F et al (2010) Soy isoflavones and bone mineral density in perimenopausal and postmenopausal Western women: a systematic review and meta-analysis of randomized controlled trials. J Womens Health 2002 19:1609–1617. https://doi.org/10.1089/jwh.2010.2021

    Article  Google Scholar 

  109. Ma D-F, Qin L-Q, Wang P-Y, Katoh R (2008) Soy isoflavone intake increases bone mineral density in the spine of menopausal women: meta-analysis of randomized controlled trials. Clin Nutr Edinb Scotl 27:57–64. https://doi.org/10.1016/j.clnu.2007.10.012

    Article  CAS  Google Scholar 

  110. Akhlaghi M, Ghasemi Nasab M, Riasatian M, Sadeghi F (2020) Soy isoflavones prevent bone resorption and loss, a systematic review and meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr 60:2327–2341. https://doi.org/10.1080/10408398.2019.1635078

    Article  CAS  PubMed  Google Scholar 

  111. Taku K, Melby MK, Takebayashi J et al (2010) Effect of soy isoflavone extract supplements on bone mineral density in menopausal women: meta-analysis of randomized controlled trials. Asia Pac J Clin Nutr 19:33–42

    CAS  PubMed  Google Scholar 

  112. Song F, Khan KS, Dinnes J, Sutton AJ (2002) Asymmetric funnel plots and publication bias in meta-analyses of diagnostic accuracy. Int J Epidemiol 31:88–95. https://doi.org/10.1093/ije/31.1.88

    Article  PubMed  Google Scholar 

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Acknowledgements

This research work was partially supported by Chiang Mai University, and by CMU Proactive Researcher, Chiang Mai University [grant number 844/2566].

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand

    Ratchanon Inpan, Mingkwan Na Takuathung, Wannachai Sakuludomkan, Nahathai Dukaew, Supanimit Teekachunhatean & Nut Koonrungsesomboon

  2. Clinical Research Center for Food and Herbal Product Trials and Development (CR-FAH), Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand

    Ratchanon Inpan, Mingkwan Na Takuathung, Wannachai Sakuludomkan, Nahathai Dukaew, Supanimit Teekachunhatean & Nut Koonrungsesomboon

  3. Office of Research Administration, Chiang Mai University, Chiang Mai, 50200, Thailand

    Ratchanon Inpan

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Contributions

Conceptualization: NK, MN, ST. Methodology: NK, RI, MN, WS, ND. Validation: RI, MN. Formal analysis: RI, WS. Investigation: RI, MN. Writing – original draft: RI, NK. Writing – review & editing: MN, ST, WS. Visualization: RI, NK. Supervision: NK, ST. Project administration: NK.

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Correspondence to Nut Koonrungsesomboon.

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Ratchanon Inpan, Mingkwan Na Takuathung, Wannachai Sakuludomkan, Nahathai Dukaew, Supanimit Teekachunhatean, and Nut Koonrungsesomboon declare that they have no conflict of interest.

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Inpan, R., Na Takuathung, M., Sakuludomkan, W. et al. Isoflavone intervention and its impact on bone mineral density in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Osteoporos Int 35, 413–430 (2024). https://doi.org/10.1007/s00198-023-06944-y

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