Resveratrol promotes bone mass in ovariectomized rats and the SIRT1 rs7896005 SNP is associated with bone mass in women during perimenopause and early postmenopause

Objective: This study aimed to examine the effects of SIRT1 agonist resveratrol on bone mass in ovariectomized (OVX) rats and the SIRT1 single-nucleotide polymorphism (SNP) rs7896005 on bone mass in women during menopause and early postmenopause. Methods: An animal experiment was conducted on rats that were sham-operated (SHAM), OVX or OVX and different administered doses of resveratrol. Serum markers and femur microstructure and staining were assessed. A cross-sectional study was conducted in women undergoing menopause. SIRT1 protein and SIRT1 SNP rs7896005 were evaluated. Results: OVX rats administered resveratrol, especially high doses, showed lower bone loss than OVX rats. Serum osteoprotegerin (OPG) and femur SIRT1, beta-catenin and bone mineral density (BMD) were significantly increased, whereas receptor activator of NF-kappa B ligand (RANKL) was significantly decreased. Serum SIRT1 levels were significantly lower in women with low bone mass (p < 0.01). Women with the CA genotype of rs7896005 had lower bone mass than those with the CC genotype. The A allele showed a significant negative effect on bone loss risk (odds ratio = 3.48; p = 0.025). Conclusions: Resveratrol stimulated SIRT1 expression and Wnt/beta-catenin signaling to promote bone mass in rat femurs. Among women in perimenopause and early postmenopause, SIRT1 protected bone mass, and the A allele of SIRT1 rs7896005 was a risk factor for reduced bone mass.