The Effects of Polyphenols on Bone Metabolism in Postmenopausal Women: Systematic Review and Meta-Analysis of Randomized Control Trials

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Abstract
Osteoporosis is a condition favored by the postmenopausal decline in estrogen levels and worsened by oxidative stress (OS). Polyphenols are natural compounds abundantly found in fruits and vegetables, and they exert antioxidant and hormonal effects that could be useful in osteoporosis prevention, as suggested by epidemiological studies showing a lower incidence of fractures in individuals consuming polyphenol-rich diets. The aim of our meta-analysis is to evaluate the effects of polyphenols on bone mineral density (BMD, primary endpoint) and bone turnover markers (BTMs, secondary endpoint) in postmenopausal women. Twenty-one randomized control trials (RCTs) were included in our analysis after in-depth search on PubMed, EMBASE, and Scopus databases. We found that supplementation with polyphenols for 3–36 months exerted no statically significant effects on BMD measured at lumbar spine (sMD: 0.21, 95% CI [−0.08 to 0.51], p = 0.16), femoral neck (sMD: 0.16, 95% CI [−0.23 to 0.55], p = 0.42), total hip (sMD: 0.05, 95% CI [−0.14 to 0.24], p = 0.61), and whole body (sMD: −0.12, 95% CI [−0.42 to 0.17], p = 0.41). Subgroup analysis based on treatment duration showed no statistical significance, but a significant effect on lumbar BMD emerged when studies with duration of 24 months or greater were analyzed separately. On the other hand, we found a significantly slight increase in bone-specific alkaline phosphatase (BALP) levels (sMD: 1.27, 95% CI [1.13 to 1.42], p < 0.0001) and a decrease in pyridinoline (PD) levels (sMD: −0.58, 95% CI [−0.77 to −0.39], p < 0.0001). High heterogeneity among studies and unclear risk of bias in one third of the included studies emerged. A subgroup analysis showed similar effects for different duration of treatment and models of dual-energy X-ray absorptiometry (DXA) scanner. More robust evidence is needed before recommending the prescription of polyphenols in clinical practice.

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