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

Plain Language Summary

Women who are post-menopause are at a higher risk of osteoporosis due to lower levels of the hormone oestrogen. Oestrogens promote bone building and limit breakdown. In addition, oestrogen protects the bones against oxidative stress, which can cause further bone breakdown. Polyphenols, which are naturally occurring chemicals found in fruits and vegetables, may prevent oxidative stress and subsequent bone breakdown. This systematic review and meta-analysis of 21 randomised control trials aimed to determine the effect of polyphenol supplementation on post-menopausal bone density. The results showed that polyphenol supplementation had no effect on bone density in the spine, leg, hip, or across the whole body. If polyphenol supplementation extended beyond 2 years, there was evidence of an improvement in spinal bone density. Supplementation also increased one biomarker associated with bone building and decrease one associated with its breakdown. It was concluded that polyphenol use is not recommended to improve bone health in postmenopausal women. This study could be used by healthcare professionals to understand polyphenol supplementation is ineffective for the prevention of osteoporosis and other lifestyle modifications should be considered.

Expert Review

Reviewer: Chloe Steele

10th Apr 2024

Conflict of interest

None

Take home message

Postmenopausal women are susceptible to decreased BMD due to lower oestrogen levels and oxidative stress.
Although polyphenols have an antioxidant effect, supplementation does not seem to affect bone mineral density in postmenopausal women.
Post-menopausal women should consider other lifestyle modifications to reduce the risk of osteoporosis.

Evidence category

A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)

Summary review

Introduction

Postmenopausal, low oestrogen levels can decrease osteoclastic activity, increase osteoclastic apoptosis, and make bones more susceptible to oxidative stress, which in turn increases osteoclastogenesis and decreases osteoblastogenesis.
Polyphenols from fruits and vegetables can have an antioxidant effect. They have been shown in vitro to enhance osteoblastic activity through effects on endothelial function and have been associated with a lower risk of fractures.
This systematic review and meta-analysis aimed to evaluate the effect of polyphenol supplementation on postmenopausal bone mineral density (BMD).

Methods

21 randomised control trials were included.
The primary outcome assessed the effect of polyphenols on BMD.
The secondary outcome assessed the effect of polyphenols on bone turnover markers; deoxypyridinoline, osteocalcin, alkaline phosphatase, and pyridinoline.
18 studies reported on lumbar BMD, 12 on femoral neck BMD, and 7 on total body BMD.
Study durations ranged from 3-36 months

Results

Polyphenols did not affect BMD of the 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), or whole body (sMD: −0.12, 95% CI [−0.42 to 0.17], p = 0.41). However, a sub-analysis based on studies longer than 24 months showed that lumbar BMD was improved (sMD: 1.00, 94% CI [0.19 to 1.81], p=0.02).
Treatment duration did not affect femoral neck BMD, total hip BMD, or whole-body BMD.
Polyphenols did not affect deoxypyridinoline or osteocalcin levels, however they did increase bone specific alkaline phosphatase (sMD: 1.27, 95% CI [1.13 to 1.42], p < 0.0001) and decrease pyridinoline (sMD: −0.58, 95% CI [−0.77 to −0.39], p < 0.0001).
There was high heterogeneity amongst the studies and 14 showed high or unclear risk of bias.

Conclusion

Polyphenol use is not recommended as the sole preventative therapy for postmenopausal osteoporosis.

Clinical practice applications

A polyphenol rich diet is not recommended to improve BMD and fracture risk in postmenopausal women.
Other lifestyle modifications with more robust research should be recommended instead.

Considerations for future research

Future studies would be interesting in women in perimenopause to determine if life stage affects efficacy of polyphenols.

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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], = 0.16), femoral neck (sMD: 0.16, 95% CI [-0.23 to 0.55], = 0.42), total hip (sMD: 0.05, 95% CI [-0.14 to 0.24], = 0.61), and whole body (sMD: -0.12, 95% CI [-0.42 to 0.17], = 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], < 0.0001) and a decrease in pyridinoline (PD) levels (sMD: -0.58, 95% CI [-0.77 to -0.39], < 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.