Effects of soy isoflavone supplements on bone turnover markers in menopausal women: Systematic review and meta-analysis of randomized controlled trials

Introduction: Effects of soy isoflavone supplements on bone turnover markers remain unclear. This up-to-date systematic review and meta-analysis of randomized controlled trials (RCTs) was performed primarily to more completely and precisely clarify the effects on urinary deoxypyridinoline (DPD) and serum bone alkaline phosphatase (BAP) and secondarily to evaluate the effects on other bone turnover markers, compared with placebo in menopausal women. Methods: PubMed, CENTRAL, ICHUSHI, and CNKI were searched in June 2009 for relevant studies of RCTs. Data on study design, participants, interventions, and outcomes were extracted and methodological quality of each included trial was assessed. Results: From 3740 identified relevant articles, 10 (887 participants), 10 (1210 participants), and 8 (380 participants) RCTs were selected for meta-analysis of effects on DPD, BAP, and serum osteocalcin (OC), respectively, using Review Manager 5.0.22. Daily ingestion of an average 56mg soy isoflavones (aglycone equivalents) for 10weeks to 12months significantly decreased DPD by 14.1% (95% CI: -26.8% to -1.5%; P=0.03) compared to baseline (heterogeneity: P<0.00001; I²=93%; random effects model). The overall effect of soy isoflavones on DPD compared with placebo was a significant decrease of -18.0% (95% CI: -28.4% to -7.7%, P=0.0007; heterogeneity: P=0.0001; I²=73%; random effects model). Subgroup analyses and meta-regressions revealed that isoflavone dose and intervention duration did not significantly relate to the variable effects on DPD. Daily supplementation of about 84mg and 73mg of soy isoflavones for up to 12months insignificantly increased BAP by 8.0% (95% CI: -4.2% to 20.2%, P=0.20; heterogeneity: P<0.00001; I²=98%) and OC by 10.3% (95% CI: -3.1% to 23.7%, P=0.13; heterogeneity: P=0.002; I²=69%) compared with placebo (random effects model), respectively. Conclusions: Soy isoflavone supplements moderately decreased the bone resorption marker DPD, but did not affect bone formation markers BAP and OC in menopausal women. The effects varied between studies, and further studies are needed to address factors relating to the observed effects of soy isoflavones on DPD and to verify effects on other bone turnover markers.