Resveratrol Boosts Bone Formation in Obese Men

Becky McCall

October 24, 2014

High-dose resveratrol, a polyphenolic compound found naturally in nuts and grapes, stimulates formation or mineralization of new bone in obese men with metabolic syndrome, according to results of a new study recently published online October 16 in the Journal of Clinical Endocrinology and Metabolism.

After only 16 weeks of treatment, dose-dependent increases in bone alkaline phosphatase and lumbar-spine bone-mineral density were evident, report Dr Marie Juul Ørnstrup (Aarhus University Hospital, Denmark) and colleagues.

"We found a significant increase in trabecular bone-mineral density at the lumbar spine in men with metabolic syndrome," Dr Ørnstrup told Medscape Medical News in an interview.

"Blood markers of bone turnover suggested that the increase in bone-mineral density was primarily driven by activation of the bone-forming cells rather than decreased activity of the bone-resorptive cells," she added.

"This study shows that the initial increase in bone alkaline phosphatase is maintained for at least 16 weeks. To my knowledge, no other human studies have yet been published describing effects of resveratrol on bone," Dr Ørnstrup observed.

She and her colleagues now intend to study this further, with a trial in women at risk for osteoporosis or osteopenia planned.

Dose-Dependent Effects of Resveratrol

The findings confirm those of a previous 4-week study by the same researchers on the effects of resveratrol, which showed that it stimulated serum levels of bone alkaline phosphatase in obese nondiabetic men.

Expanding upon this initial study, the Danish researchers set out to investigate whether resveratrol could help men with metabolic syndrome, which has been linked to low-grade inflammation that can cause bone loss.

The randomized, double-blind, placebo-controlled trial examined the effects of resveratrol (Evolva) in 74 middle-aged obese men with metabolic syndrome and a mean body mass index (BMI) of 33.7 kg/m2.

Participants received oral treatment with 1000 mg of resveratrol (high-dose group), 150 mg resveratrol (low-dose group), or placebo daily for 16 weeks. Change in bone alkaline phosphatase was the primary end point. Secondary end points included changes in bone-mineral density, changes in bone geometry, and changes in other biochemical markers of bone turnover, as well as markers of calcium homeostasis.

The participants were instructed to maintain their body weight and lifestyle and to abstain from any changes in intake of nutritional supplements, including calcium and vitamin D, during the study period.

Bone alkaline phosphatase was found to increase dose dependently with resveratrol (R = 0.471, P < .001), with a rise of 16% after 4 weeks in the high-dose resveratrol group compared with placebo, which was maintained through the end of the study.

Trabecular volumetric bone-mineral density at the spine also increased dose-dependently with resveratrol (R = 0.268, P = .036), reaching +2.6% in patients who received high-dose resveratrol compared with placebo (= .043).

In addition, changes in bone alkaline phosphatase and bone-mineral density were positively correlated (R = 0.281, = .027), "supporting a causal relationship," according to the study authors.

"These are encouraging results. In just 4 months on high-dose resveratrol, we saw significant improvements in bone-mineral density at the spine and elevated levels of the bone-formation marker [bone alkaline phosphatase]," Dr Ørnstrup said.

She said they were surprised to find bone-mineral density changes after only 16 weeks of treatment. "Turnover in bone is normally quite low, so we speculate that resveratrol affects mineralization of bone rather than new bone formation."

No Changes to Inflammatory Markers

Resveratrol has demonstrated anti-inflammatory properties in preclinical studies, and the researchers initially believed that if it did increase bone-mineral density, it would be due to these anti-inflammatory effects.

But there were no changes in inflammatory markers during the 16 weeks of the study; coauthor Dr Thomas N Kjær (Aarhus University Hospital) presented these findings last month at the European Association for the Study of Diabetes (EASD) 2014 Meeting in Vienna.

The results suggest that resveratrol might have wider application, according to Dr Ørnstrup.

"As no changes were detected in inflammatory markers, we do consider it possible that resveratrol's effects on bone are not limited only to men with metabolic syndrome."

However, she concluded that additional research would be required to assess whether the bone-protective effects shown in this study would be evident in populations at risk for osteoporosis over the course of long-term treatment.

The authors have reported they have no relevant financial relationships.

J Clin Endocrinol Metab. Published online October 16, 2014. Abstract

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