Efficacy of Turmeric Extract in Prevention of Post-menopausal Osteoporosis

姜黄提取物预防绝经后骨质疏松症的功效

• 批准号: 7131181
• 负责人: JANET L FUNK
• 金额: $ 22.65万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7131181
• 关键词: bone; model; osteoporosis; prevention

DESCRIPTION (provided by applicant): The identification of a dietary supplement that effectively inhibits bone resorption could offer a particularly attractive approach to the prevention of postmenopausal osteoporosis, a disease with extremely high prevalence that is essentially irreversible yet readily preventable by early interventions that inhibit bone resorption. Recent studies by Dr. Funk's laboratory using an animal model of arthritis have revealed that curcuminoid-containing turmeric extracts (C-CTEs) are potent inhibitors of inflammation associated-bone resorption. Because the same inflammatory pathways mediate bone loss in arthritis and in menopause, we have hypothesized that C-CTEs may be similarly efficacious in the prevention of postmenopausal osteoporosis (PMO). To address this hypothesis, the efficacy of a C-CTE will be examined in preclinical trials utilizing 2 complementary models of menopausal bone loss (1) surgical menopause (oophorectomized rats), an FDA-mandated model for the evaluation of pharmaceutical interventions for PMO and (2) a newly described model of natural menopause (VCD-induced follicular atresia in rats) that more closely resembles the peri-menopausal transition and early natural menopause in humans, a period of accelerated bone loss rarely treated under current standards of care. Standard endpoints of analysis will include changes in bone mineral density, biochemical markers of bone turnover, structural changes in the bone microarchitecture as assessed by microCT, and histologic assessment of bone-resorbing osteoclast formation at sites of menopausal bone loss. The proposed studies take advantage of the expertise of the principle investigator, Dr. Funk, and her NCCAM-funded laboratory who made the initial discovery of the bone protective effects of turmeric extracts in a preclinical model as well that of its co-investigator, Dr. Patricia Hoyer, an NIA-funded researcher who first described and later characterized the novel VCD-induced model of natural menopause. Evidence obtained here supporting (or refuting) the efficacy of turmeric dietary supplements in osteoporosis prevention and/or treatment will (1) begin to help guide the public's use of turmeric supplements for the preservation of bone health, (2) aid in the design of preclinical trials comparing the efficacy and identifying the mechanism of action of well characterized chemically complex turmeric extracts in the treatment of PMO, and (3) provide necessary information for the design of future clinical trials.

描述（由申请人提供）：有效抑制骨吸收的膳食补充剂的鉴定可以为预防绝经后骨质疏松症提供特别有吸引力的方法，这种疾病患病率极高，基本上是不可逆转的，但可以通过抑制骨吸收的早期干预措施轻松预防吸收。 Funk 博士的实验室最近使用关节炎动物模型进行的研究表明，含有类姜黄素的姜黄提取物 (C-CTE) 是与骨吸收相关的炎症的有效抑制剂。由于相同的炎症途径会介导关节炎和绝经期的骨质流失，因此我们假设 C-CTE 在预防绝经后骨质疏松症 (PMO) 方面可能同样有效。为了解决这一假设，将在临床前试验中使用两种互补的绝经期骨质流失模型来检验 C-CTE 的功效（1）手术绝经（卵巢切除大鼠），这是 FDA 授权的模型，用于评估 PMO 的药物干预和(2) 一种新描述的自然绝经模型（VCD 诱导的大鼠卵泡闭锁），更接近于围绝经期过渡和早期自然绝经人类更年期是骨质流失加速的时期，在目前的护理标准下很少得到治疗。标准分析终点包括骨矿物质密度的变化、骨转换的生化标志物、通过 microCT 评估的骨微结构的结构变化，以及绝经期骨质流失部位骨吸收破骨细胞形成的组织学评估。拟议的研究利用了首席研究员 Funk 博士和她的 NCCAM 资助实验室的专业知识，该实验室在临床前模型中初步发现了姜黄提取物的骨保护作用，其共同研究员 Funk 博士也同样如此。帕特里夏·霍耶 (Patricia Hoyer) 是一位 NIA 资助的研究人员，她首先描述了 VCD 诱导的自然绝经模型，后来又对其进行了描述。这里获得的支持（或反驳）姜黄膳食补充剂在预防和/或治疗骨质疏松症方面功效的证据将（1）开始帮助指导公众使用姜黄补充剂来保持骨骼健康，（2）帮助设计临床前试验比较了特征明确的化学复合姜黄提取物在治疗 PMO 中的功效并确定其作用机制，(3) 为未来临床试验的设计提供必要的信息。