Systematic review and meta-analysis of the bone protective effect of phytoestrogens on osteoporosis in ovariectomized rats

Nutr Res. 2014 Jun;34(6):467-77. doi: 10.1016/j.nutres.2014.05.003. Epub 2014 May 17.


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.

Keywords: Bone histomorphometric parameters; Bone mineral density; Bone turnover markers; Meta-analysis; Osteoporosis; Ovariecomized rat; Phytoestrogens.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Alkaline Phosphatase / blood
  • Animals
  • Bone Density / drug effects*
  • Bone Resorption / prevention & control
  • Bone and Bones / drug effects*
  • Databases, Factual
  • Female
  • Osteocalcin / blood
  • Osteogenesis / drug effects
  • Osteoporosis / prevention & control*
  • Ovariectomy
  • Phytoestrogens / pharmacology*
  • Rats


  • Phytoestrogens
  • Osteocalcin
  • Alkaline Phosphatase