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. ? ? ?
