Evaluating resveratrol as a therapeutic bone agent: preclinical evidence from rat models of osteoporosis.

Resveratrol (RSV) is a naturally occurring plant polyphenol that has potential to attenuate osteoporosis with distinct pathologies. This review evaluates preclinical evidence regarding the efficacy and safety of RSV as a therapeutic bone agent using different rat models. Limitations of these animal models are discussed, and suggestions for strengthening the experimental design of future studies are provided. The ovariectomized rat model of postmenopausal osteoporosis reported that RSV supplementation attenuated estrogen deficiency-induced bone loss and trabecular structural deterioration. RSV safety was indicated by the absence of stimulation of estrogen-sensitive tissue. Providing RSV to rats aged >6 months attenuated age-related bone mass loss and structural deterioration but produced inconsistent effects on bones in rats aged <6 months. The hindlimb-suspension rat model of disuse osteoporosis reported that RSV attenuated bone loss in old rats, but higher doses and longer duration supplementation before mechanical loading were required for younger rats. Limitations common to studies using rat models of osteoporosis include requirements to include animals that are skeletally mature, longer study durations, and to adjust for potential confounding effects due to altered body weight and endocrine function. Strengthening experimental design can contribute to translation of animal results to clinically relevant recommendations for humans.