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. 2017 Sep;106(3):801-811. doi: 10.3945/ajcn.116.151464. Epub 2017 Aug 2.


Background: Age-related estrogen deficiency leads to accelerated bone resorption. There is evidence that, through selective estrogen receptor modulation, isoflavones may exert beneficial effects against estrogen-deficient bone loss. Isoflavone aglycones show higher bioavailability than their glycosidic counterparts and thus may have greater potency.Objective: To summarize evidence, we executed a systematic review and meta-analysis examining isoflavone therapies and bone mineral density (BMD) loss in peri- and postmenopausal women.Design: We systematically searched EMBASE and PubMed for randomized controlled trials (RCTs) evaluating isoflavone therapies for treating BMD loss at the lumbar spine and femoral neck in estrogen-deficient women. Separate meta-analyses were carried out with the use of random-effects models for the lumbar spine and femoral neck for all studies providing isoflavones as aglycones.Results: Twenty-six RCTs (n = 2652) were included in the meta-analysis. At the lumbar spine, isoflavone treatment was associated with a significantly (P < 0.00001) higher weighted mean difference (WMD) of BMD change of 0.01 (95% CI: 0.01, 0.02) than the control. For the femoral neck (18 RCTs, n = 1604), isoflavone treatment showed a significantly (P < 0.01) higher WMD of BMD change of 0.01 (95% CI: 0.00, 0.02) compared with the control. When isolating studies that provide isoflavone aglycones in their treatment arm, the average effect was further significantly increased at the spine (5 RCTs, n = 682) to 0.04 (P < 0.00001; 95% CI: 0.02, 0.05) and femoral neck (4 RCTs, n = 524) to 0.03 (P < 0.05; 95% CI: 0.00, 0.06) compared with the control. This protective effect against bone loss disappeared when only studies with formulations comprising predominantly isoflavone glycosides were included.Conclusions: Isoflavone treatments exert a moderately beneficial effect against estrogen-deficient bone loss in women. The effect appears dependent on whether isoflavone treatments are in aglycone form; we conclude that beneficial effects against bone loss may be enhanced for isoflavone aglycones.

Keywords: bone; estrogen deficiency; isoflavone; osteopenia; osteoporosis.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Biological Availability
  • Bone Density / drug effects*
  • Bone Density Conservation Agents / pharmacology
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Resorption / etiology
  • Bone Resorption / metabolism
  • Bone Resorption / prevention & control*
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism*
  • Estrogens / deficiency
  • Female
  • Glycosides / pharmacology
  • Glycosides / therapeutic use*
  • Humans
  • Isoflavones / pharmacology
  • Isoflavones / therapeutic use*
  • Menopause
  • Middle Aged
  • Osteoporosis / etiology
  • Osteoporosis / metabolism
  • Osteoporosis / pathology
  • Osteoporosis / prevention & control*
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use


  • Bone Density Conservation Agents
  • Estrogens
  • Glycosides
  • Isoflavones
  • Plant Extracts