Efficacy of Turmeric Extract in Prevention of Post-menopausal Osteoporosis

描述（由申请人提供）：确定一种有效抑制骨吸收的膳食补充剂可以为预防绝经后骨质疏松症提供一种特别有吸引力的方法，骨质疏松症是一种患病率极高的疾病，本质上是不可逆转的，但通过早期干预抑制骨吸收很容易预防。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，含有姜黄素的姜黄提取物（C-CTEs）是炎症相关骨吸收的有效抑制剂。由于相同的炎症途径介导关节炎和绝经期骨质流失，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。为了验证这一假设，C-CTE的有效性将在临床前试验中进行检验，利用两种互补的绝经期骨质流失模型(1)手术绝经（切除卵巢的大鼠），fda授权的PMO药物干预评估模型(2)新描述的自然绝经模型（vcd诱导的大鼠卵泡闭锁），更接近于人类的围绝经期过渡和早期自然绝经。一段加速骨质流失的时期，在目前的护理标准下很少得到治疗。分析的标准终点将包括骨矿物质密度的变化，骨转换的生化标志物，通过微ct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。拟议的研究利用了主要研究者Funk博士和她的nccam资助的实验室的专业知识，他们在临床前模型中首次发现了姜黄提取物的骨骼保护作用，以及他们的合作研究者Patricia Hoyer博士，nia资助的研究人员，她首先描述并后来描述了新的vcd诱导的自然绝经模型。这里获得的证据支持（或反驳）姜黄膳食补充剂在骨质疏松症预防和/或治疗方面的功效，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，比较姜黄化学复合物提取物治疗PMO的功效，并确定其作用机制。(3)为今后临床试验的设计提供必要的信息。

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.