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Objectives  Patients with type 2 diabetes (T2DM) are at increased fracture risk. Resveratrol has shown beneficial effects on bone health in few studies. The aim of this trial was to investigate the effects of resveratrol on bone mineral density (BMD) and on calcium metabolism biomarkers in T2DM patients.    Methods  In this double-blind randomized placebo-controlled trial 192 T2DM outpatients were randomized to receive resveratrol 500 mg/day (Resv500 arm), resveratrol 40 mg/day (Resv40 arm) or placebo for 6 months. BMD, bone mineral content (BMC), serum calcium, phosphorus, alkaline phosphatase, and 25-hydroxy vitamin D were measured at baseline and after 6 months.    Results  At follow-up, calcium concentrations increased in all patients, while within-group variations in alkaline phosphatase were higher in both resveratrol arms, and 25-hydroxy vitamin D increased in the Resv500 arm only, without between-group differences. Whole-body BMD significantly decreased in the placebo group, while whole-body BMC decreased in both the placebo and Resv40 arms. No significant changes in BMD and BMC values occurred in the Resv500 arm. The adjusted mean differences of change from baseline were significantly different in the Resv500 arm vs placebo for whole-body BMD (0.01 vs −0.03 g/cm 2 ,  p  = 0.001), whole-body BMC (4.04 vs −58.8 g,  p  < 0.001), whole-body T-score (0.15 vs −0.26), and serum phosphorus (0.07 vs −0.01 µmol/L,  p  = 0.002). In subgroup analyses, in Resv500 treated-patients BMD values increased to higher levels in those with lower calcium and 25-hydroxy vitamin D values, and in alcohol drinkers.    Conclusions  Supplementation with 500 mg resveratrol prevented bone density loss in patients with T2DM, in particular, in those with unfavorable conditions at baseline.

Effects of resveratrol on bone health in type 2 diabetic patients. A double-blind randomized-controlled trial