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Resveratrol Prevents Bone Density Loss in Patients With Type 2 Diabetes

By Prof. Gene Bruno, MS, MHS, RH(AHG), Huntington University of Health Sciences

Patients with type 2 diabetes (T2DM) have an increased risk of fracture, and researchers are continually searching for strategies to help prevent bone loss and reduce fracture risk. One potentially promising strategy is the use of resveratrol.

Preclinical Research on Resveratrol for Bone Health Animal studies have shown that resveratrol prevents bone loss, reduces mineral density due to immobilization, older age, and ovariectomy,1-4 and causes bone healing and repair after surgical procedures or trauma.5-6 It promoted osteoblastogenesis, antagonized osteoclasts in vitro,7-9 and potentiated vitamin D receptor activity.10

A Human Clinical Trial on Resveratrol for Bone Health Given these positive preclinical results, a double-blind randomized placebo-controlled trial11 was conducted to investigate the effects of resveratrol on bone mineral density (BMD) and on calcium metabolism biomarkers in T2DM patients. A total of 192 T2DM outpatients were randomized to receive resveratrol 500 mg/day (Resv500 arm), resveratrol 40 mg/day (Resv40 arm) or placebo for six months. BMD, bone mineral content (BMC), serum calcium, phosphorus, alkaline phosphatase, and 25-hydroxy vitamin D were measured at baseline and after six months. The results were that, 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/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. In conclusion, supplementation with 500 mg resveratrol prevented bone density loss in patients with T2DM, in particular, in those with unfavorable conditions at baseline.


  1. Durbin SM, et al. Resveratrol supplementation preserves long bone mass, microstructure, and strength in hindlimb-suspended old male rats.  Bone Miner. Metab. 2014;32:38–47.
  2. Tresguerres IF, et al. Resveratrol as anti-aging therapy for age-related bone loss. Rejuvenation Res. 2014;17:439–445.
  3. Karimian E, et al. Resveratrol treatment delays growth plate fusion and improves bone growth in female rabbits. PLoS ONE. 2013;8:e67859.
  4. Zhao H, et al. Long-term resveratrol treatment prevents ovariectomy-induced osteopenia in rats without hyperplastic effects on the uterus.  J. Nutr. 2014;111:836–846.
  5. Casarin RC, et al. Resveratrol improves bone repair by modulation of bone morphogenetic proteins and osteopontin gene expression in rats.  J. Oral. Maxillofac. Surg. 2014;43:900–906.
  6. Wang HD, et al. Treatment with resveratrol attenuates sublesional bone loss in spinal cord-injured rats.  J. Pharmacol. 2013;170:796–806.
  7. Ornstrup MJ, et al. Resveratrol increases osteoblast differentiation in vitro independently of inflammation.  Tissue Int. 2016;99:155–163.
  8. Kupisiewicz K, et al. Potential of resveratrol analogues as antagonists of osteoclasts and promoters of osteoblasts.  Tissue Int. 2010;87:437–449.
  9. Zhao L, et al. Effects of dietary resveratrol on excess-iron-induced bone loss via antioxidative character.  Nutr. Biochem. 2015;26:1174–1182.
  10. Dampf Stone A, Batie SF, Sabir MS. Resveratrol potentiates vitamin D and nuclear receptor signaling.  Cell. Biochem. 2015;116:1130–1143.
  11. Bo S, Gambino R, Ponzo V, Cioffi I, Goitre I, Evangelista A, Ciccone G, Cassader M, Procopio M. Effects of resveratrol on bone health in type 2 diabetic patients. A double-blind randomized-controlled trial. Nutr Diabetes. 2018 Sep 20;8(1):51.

Professor Gene Bruno, MS, MHS, the Provost for Huntington College of Health Sciences, is a nutritionist, herbalist, writer and educator. For more than 37 years he has educated and trained natural product retailers and health care professionals, has researched and formulated natural products for dozens of dietary supplement companies, and has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications. He can be reached at gbruno@hchs.edu.