Resveratrol可加強肥胖男性患者的骨骼形成


  【24drs.com】根據線上發表於10月16日臨床內分泌與代謝期刊的研究結果,高劑量resveratrol這種自然存在於堅果和葡萄的多酚化合物,對於有代謝症候群的肥胖男性,可刺激新骨形成或礦化。
  
  Marie Juul Ornstrup醫師(丹麥Aarhus大學醫院)等人報告指出,僅僅治療16週之後,很明顯地,骨鹼性磷酸酶及腰椎脊柱骨密度增加,且與劑量相關。
  
  Ornstrup醫師表示,我們發現有代謝症候群的男性,腰椎的骨小樑骨密度顯著增加;她指出,骨代謝的血液標誌顯示,骨密度增加主要是由成骨細胞活性而驅動,而不是減少溶骨細胞活性。
  
  Ornstrup醫師觀察發現,這篇研究顯示,骨鹼性磷酸酶最初增加後維持至少16週,就我所知,沒有其他已發表的人類研究論及resveratrol對骨骼的影響。
  
  她和研究夥伴將要進一步探討,計畫針對有骨質疏鬆或骨質減少風險的婦女進行試驗。
  
  這次的研究結果確認了該研究團隊之前探討resveratrol之效果的4週研究,當時顯示它可刺激肥胖非糖尿病男性的骨鹼性磷酸酶血清值。
  
  丹麥研究者根據該初步研究擴大規模,希望探討resveratrol是否可幫助有代謝症候群的男性,這類患者被認為與可能引起骨質流失的低度發炎有關。
  
  這次的隨機雙盲安慰劑控制試驗檢視了resveratrol (Evolva)用於74名中年肥胖、平均身體質量指數(BMI)為33.7 kg/m2且有代謝症候群之男性的效果。
  
  這些研究對象接受每天口服1000 mg的resveratrol (高劑量組)或150 mg resveratrol (低劑量組)或安慰劑,為期16週。主要研究終點是骨鹼性磷酸酶之變化,次要終點包括:骨密度之變化、骨骼幾何形狀變化、骨代謝之其他生化標記變化,以及鈣穩態之標記。
  
  這些研究對象被告知在研究期間要維持體重與生活形態,避免變更營養補充品如鈣和維他命D的攝取習慣。
  
  發現骨鹼性磷酸酶之增加與resveratrol劑量有關(R = 0.471,P < .001),高劑量resveratrol組在4週後比安慰劑組上升16%,且維持到研究結束。
  
  脊柱的骨小樑密度也隨resveratrol之劑量增加而增加(R=0.268,P=.036),高劑量resveratrol組比安慰劑組增加達2.6% (P=.043)。
  
  此外,骨鹼性磷酸酶和骨密度之變化是正相關(R=0.281,P=.027),根據作者指出,這支持了因果關係。
  
  Ornstrup醫師表示,這些結果令人鼓舞,在僅用4個月的高劑量resveratrol者,我們發現脊柱骨密度有顯著改善,成骨標記(骨鹼性磷酸酶)也上升。
  
  她表示,對於僅治療16週即發現骨密度之變化令人驚訝,骨代謝一般是相當低,所以我們推測resveratrol影響骨骼礦化而非新骨形成。
  
  在臨床前研究中,Resveratrol顯示有抗發炎性質,研究者最初相信,如果它確實增加骨密度,可能是因為這些抗發炎效果。
  
  但是,共同作者、Thomas N Kjer (Aarhus 大學醫院)、上個月在歐洲糖尿病研究協會(EASD)2014年會發表這些結果時表示,在這16週的研究期間,發炎標記沒有變化。
  
  根據Ornstrup醫師表示,這些結果認為resveratrol或許可以有更廣泛的應用。因為發炎標記沒有變化,我們認為可能是resveratrol對於骨骼的影響將不限於有代謝症候群的男性。
  
  不過,她結論指出需要更多研究,以探討這項研究顯示的骨骼保護效果對於有骨質疏鬆風險者之長期治療是否也有明顯改善。
  
  資料來源:http://www.24drs.com/professional/list/content.asp?x_logon=W&x_idno=7127&x_classno=0
  

Resveratrol Boosts Bone Formation in Obese Men

By Becky McCall
Medscape Medical News

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 Ornstrup (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 Ornstrup 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 Ornstrup 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 (P = .043).

In addition, changes in bone alkaline phosphatase and bone-mineral density were positively correlated (R = 0.281, P = .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 Ornstrup 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 Kjar (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 Ornstrup.

"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.

    
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