Protective effect and possible mechanisms of resveratrol in animal models of osteoporosis: A preclinical systematic review and meta‐analysis

Abstract Resveratrol (RES) has extensively been utilized to treat osteoporosis (OP) in animal models. However, the anti‐OP effects of RES have not been tested during clinical application due to the lack of evidence and poor knowledge of the underlying mechanisms. Moreover, there is little preclinical evidence to support the use of RES in the management of OP. In the present paper, we conducted a preclinical systematic review and meta‐analysis to assess the efficacy of RES in animal OP models. The potential mechanisms underlying the efficacy of RES against OP were summarized. The online databases PubMed, CNKI, EMBASE, Wanfang, Web of Science, Chinese Biomedical Literature, Cochrane Library, and Chinese VIP were retrieved from inception to December 2021. The CAMARADES 10‐item quality checklist was utilized to assess the risk of bias of the included studies. STATA 12.0 software was employed to analyze the data. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Thirteen studies containing 248 animals were included yielding a mean risk of bias score of 5.54 (range 4–7). The pooled estimates showed that the administration of RES could significantly elevate the bone mineral density (BMD) both at femur (SMD = 2.536; 95% CI = 1.950–3.122; p < 0.001) and lumbar spine (SMD = 1.363; 95% CI = 0894–1.832; p < 0.001), bone volume over total volume (BV/TV) (SMD = 2.543; 95% CI = 2.023–3.062; p < 0.001), trabecular linear density (Tb.N) (SMD = 2.724; 95% CI = 2.186–3.262; p < 0.001) and trabecular thickness (Tb.Th) (SMD = 1.745; 95% CI = 1.294–2.196; p < 0.001), while serum phosphorus (S‐P) (SMD = −2.168; 95% CI = −2.753 to −1.583; p < 0.001) and trabecular separation (Tb.Sp) (SMD = −2.856; 95% CI = −4.218 to −1.494; p < 0.001) were significantly reduced in animal OP models. No significant change in serum calcium (S‐Ca) (SMD = −2.448; 95% CI = −5.255–0.360; p = 0.087) was observed after RES treatment. Furthermore, RES could significantly improve the bone biomechanical indexes: bone maximum load (BML) (SMD = 2.563; 95% CI = 1.827–3.299; p < 0.001) and connectivity density (Conn.D) (SMD = 1.512; 95% CI = 0.909–2.116; p < 0.001) and decrease the structural model index (SMI) (SMD = −2.522; 95% CI = −3.243 to −1.801; p < 0.001). Overall, the present study revealed that RES has huge prospects as a medicine or dietary supplement for the clinical treatment of OP. High‐quality studies with stringent designs and larger sample sizes are warranted to substantiate our conclusion.