Resveratrol Increases Bone Mineral Density and Bone Alkaline Phosphatase in Obese Men: A Randomized Placebo-Controlled Trial

Context: Metabolic syndrome (MetS) is associated with low-grade inflammation, which may harmfully affect bone. Resveratrol (RSV) possesses anti-inflammatory properties, and rodent studies suggest bone protective effects. Objective: This study sought to evaluate effects of RSV treatment on bone in men with MetS. Setting and Design: The study was conducted at Aarhus University Hospital as a randomized, double-blinded, placebo-controlled trial assessing changes in bone turnover markers, bone mineral density (BMD), and geometry. Participants: The study population comprised 74 middle-aged obese men with MetS recruited from the general community, of which 66 completed all visits. Mean age of participants was 49.3 +/- 6.3 years and mean body mass index was 33.7 +/- 3.6 kg/m(2). Intervention: Oral treatment with 1.000 mg RSV (RSVhigh), 150mg RSV (RSVlow), or placebo daily for 16 weeks. Main Outcome Measure: Prespecified primary endpoint was change in bone alkaline phosphatase(BAP). Results: BAP increased dose dependently with RSV (R = 0.471, P <.001), resulting in a significantly greater increase in BAP in the RSVhigh group compared with placebo at all time-points (week 4, 16.4 +/- 4.2%, P <.001; week 8, 16.5 +/- 4.1%, P <.001; week 16, 15.2 +/- 3.7%, P <.001). Lumbar spine trabecular volumetric bone mineral density (LS vBMD(trab)) also increased dose dependently with RSV (R = 0.268, P =.036), with a significant increase of 2.6 +/- 1.3% in the RSVhigh group compared with placebo (P =.043). In addition, changes in BAP and LS vBMD(trab) were positively correlated (R = 0.281, P =.027). No consistent changes were detected in bone density at the hip. Conclusions: Our data suggest that high-dose RSV supplementation positively affects bone, primarily by stimulating formation or mineralization. Future studies of longer duration comprising populations at risk of osteoporosis are needed to confirm these results.