Phytoestrogens are candidate drugs for the treatment of osteoporosis. Many experiments
have been designed to investigate the preventive effects of phytoestrogens for osteoporosis;
however, it is easy for a single dissenting result from animal experiments to mislead clinical
investigations. Herein, we use meta-analysis to assess the evidence for a protective effect of
phytoestrogens on ovariectomized rat models of osteopenia. With respect to osteoporosis, PubMed and
Web of Science were searched from January 2000 to March 2013 for relevant studies of phytoestrogens
in ovariectomized rats. Two reviewers independently selected and assessed the studies. Data were
aggregated using a random effects model. Meta- analysis revealed that the phytoestrogen treatment
group demonstrated a significantly higher femur bone mineral density and trabecular bone and lower
bone turnover markers (serum alkaline phosphatase and serum osteocalcin) compared with the control
ovariectomized group, thus showing a bone protective effect of phytoestrogens in ovariectomized
rats. Subsequent sensitivity analyses indicated that the effect of phytoestrogens on serum alkaline
phosphatase and serum osteocalcin are not robust. Despite the high heterogeneity in the systematic
review of animal experiments, the present results indicated that phytoestrogens may offer the most
potential for the prevention of bone loss by reducing the expected loss of trabecular bone and bone
mineral density. Their effects are likely due to inhibition of bone resorption, but their benefits
on bone formation are still unclear. Further studies are needed to assess the effect of
phytoestrogens on bone formation and the efficacy and safety of individual phytoestrogens.