A systematic review and meta-analysis of the effects of isoflavone formulations against estrogen-deficient bone resorption in peri- and postmenopausal women

Abstract

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 estrogendeficient 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 metaanalysis. 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.