Abstract
ObjectivesPatients 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.MethodsIn 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.ResultsAt 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/cm2, 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.ConclusionsSupplementation with 500 mg resveratrol prevented bone density loss in patients with T2DM, in particular, in those with unfavorable conditions at baseline.
Highlights
Introduction Type2 diabetes (T2DM) subjects are at a higher risk for bone fracture due to altered bone cell function and bone remodeling, advanced glycation end-product (AGE)accumulation causing collagen deterioration, and microarchitectural changes[1,2].The list of the healthy properties of the polyphenolic compound resveratrol (3,5,4ʹ-trihydroxy-trans-stilbene), not all confirmed in human studies[3,4,5,6], has recently lengthened after the discovery of the benefits on bone metabolism for this compound[7]
We have investigated the effects of resveratrol at dosages of 40 and 500 mg/day for 6 months on bone mineral density (BMD) and on the circulating concentrations of calcium metabolism biomarkers in these patients by a double-blind randomized placebo-controlled trial
Statistical methods The sample size was originally calculated for another outcome, the reduction of C-reactive protein (CRP): to obtain an effect size of 0.5027, a total sample size of 192 patients was necessary to reach a statistical power of 80% considering an overall type 1 error of 5%24
Summary
Introduction Type2 diabetes (T2DM) subjects are at a higher risk for bone fracture due to altered bone cell function and bone remodeling, advanced glycation end-product (AGE)accumulation causing collagen deterioration, and microarchitectural changes[1,2].The list of the healthy properties of the polyphenolic compound resveratrol (3,5,4ʹ-trihydroxy-trans-stilbene), not all confirmed in human studies[3,4,5,6], has recently lengthened after the discovery of the benefits on bone metabolism for this compound[7]. Animal studies have shown that resveratrol prevents bone loss, reduces mineral density due to immobilization, older age, and ovariectomy[8,9,10,11], and causes bone healing and repair after. Bo et al Nutrition and Diabetes (2018)8:51 surgical procedures or trauma[12,13]. Other preclinical studies reported mixed or negative effects of resveratrol on bone health[18,19,20,21] Despite this substantial preclinical evidence, human data about the effects of resveratrol on bone metabolism are very scarce[22,23]. Resveratrol has shown to increase lumbar spine trabecular volumetric bone mineral density (BMD) in a dose-dependent manner in middle-aged, obese men with metabolic syndrome[23]
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