Efficacy of Turmeric Extract in Prevention of Post-menopausal Osteoporosis

描述(申请人提供)：确定一种有效抑制骨吸收的膳食补充剂可能为预防绝经后骨质疏松症提供一种特别有吸引力的方法。绝经后骨质疏松症是一种发病率极高的疾病，基本上是不可逆转的，但通过抑制骨吸收的早期干预很容易预防。芬克博士的实验室最近利用关节炎动物模型进行的研究表明，含有姜黄素的姜黄素提取物(C-CTE)对炎症相关的骨吸收具有有效的抑制作用。由于相同的炎症途径在关节炎和绝经期中介导骨丢失，我们假设C-CTES在预防绝经后骨质疏松症(PMO)方面可能具有类似的效果。为解决这一假设，将在临床前试验中检验C-CTE的疗效，该试验利用两种互补的绝经期骨丢失模型：(1)手术绝经(去卵巢大鼠)，这是FDA授权的评估PMO药物干预措施的模型；(2)新描述的自然绝经模型(VCD诱导的大鼠卵泡闭锁)，更接近人类围绝经期过渡和自然绝经早期，这是一种根据目前的护理标准很少得到治疗的加速骨丢失时期。标准的分析终点将包括骨密度的变化、骨转换的生化标记物、通过microCT评估的骨微结构的结构变化，以及绝经后骨丢失部位骨吸收破骨细胞形成的组织学评估。拟议中的研究利用了首席研究员芬克博士和她的NCCAM资助的实验室的专业知识，他们在临床前模型中初步发现了姜黄提取物的骨骼保护作用，并与其合作者帕特里夏·霍耶博士(Dr.Patricia Hoyer)进行了研究。霍耶博士是NIA资助的研究人员，最初描述了VCD诱导的自然更年期新模型，后来又描述了这种模型的特征。在这里获得的证据支持(或驳斥)姜黄膳食补充剂预防和/或治疗骨质疏松症的有效性，将(1)开始帮助指导公众使用姜黄补充剂来保护骨骼健康，(2)帮助设计临床前试验，比较具有良好特征的化学复杂的姜黄提取物在治疗骨质疏松症中的疗效并确定其作用机制，以及(3)为未来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.