Long-term resveratrol treatment prevents ovariectomy-induced osteopenia in rats without hyperplastic effects on the uterus

Br J Nutr. 2014 Mar 14;111(5):836-46. doi: 10.1017/S0007114513003115. Epub 2013 Sep 30.


Resveratrol (Res), a polyphenol that is abundant in many medicinal plants and is a selective oestrogen receptor modulator, exhibits multiple biological activities. In the present study, we determined whether Res prevents oestrogen deficiency-induced osteopenia and whether Res administration decreases pathological changes in the endometrium and lumen of the uterus compared with oestradiol replacement therapy (ERT). A total of sixty 3-4-month-old female Wistar rats were randomly divided into a sham-operated group (Sham) and five ovariectomy (OVX) subgroups, i.e. OVX rats as a control group (OVX); OVX rats receiving oestradiol valerate (ERT, 0·8 mg/kg); and OVX rats receiving Res 20, 40 and 80 mg/kg. Daily oral administration was initiated at week 2 after OVX for 12 weeks. A dose-response difference was observed in the effects of Res on bone mineral density (BMD) and trabecular microarchitecture. Only at the highest dose, bone loss was almost equivalent to that observed in the ERT group. The dose-response effects of Res on the biochemical parameters (alkaline phosphatase, IL-6, TNF-α and transforming growth factor-β1 concentrations in the serum as well as urinary Ca and P excretion) and the expressions of receptor activator of nuclear factor κB ligand (RANKL) and the RANKL:osteoprotegerin protein ratio in the femur were also observed. Furthermore, the thickening of the endometrium and the infiltration of lymphocytes were prevented in all the three Res-treated groups compared with the ERT group. In conclusion, Res treatment not only improves BMD and trabecular microarchitecture but also does not affect the uterus and Res might be a potential remedy for the treatment of postmenopausal osteoporosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / adverse effects
  • Antioxidants / therapeutic use*
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Biomarkers / urine
  • Bone Density
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use
  • Dietary Supplements* / adverse effects
  • Disease Models, Animal
  • Endometrial Hyperplasia / chemically induced
  • Endometrial Hyperplasia / prevention & control*
  • Endometrium / pathology*
  • Estrogen Replacement Therapy / adverse effects
  • Female
  • Femur / chemistry
  • Femur / immunology
  • Femur / metabolism
  • Femur / pathology
  • Humans
  • Osteoporosis, Postmenopausal / immunology
  • Osteoporosis, Postmenopausal / metabolism
  • Osteoporosis, Postmenopausal / pathology
  • Osteoporosis, Postmenopausal / prevention & control*
  • Osteoprotegerin / metabolism
  • Phytoestrogens / administration & dosage
  • Phytoestrogens / adverse effects
  • Phytoestrogens / therapeutic use*
  • RANK Ligand / metabolism
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Resveratrol
  • Stilbenes / administration & dosage
  • Stilbenes / adverse effects
  • Stilbenes / therapeutic use*
  • Time Factors


  • Antioxidants
  • Biomarkers
  • Bone Density Conservation Agents
  • Osteoprotegerin
  • Phytoestrogens
  • RANK Ligand
  • Stilbenes
  • Tnfrsf11b protein, rat
  • Resveratrol