Gender differences in the distribution of bone mass in the third lumbar vertebra and its age-related changes

骨密度測量可有效預測日後發生骨折 之風險。目前脊椎骨之骨密度測量，一般 是以正面方式測量，測量之部位包括脊椎 體(vertebral body, VB)及其後方之脊突等 (posterior segment, PS)，唯脊椎骨之骨質疏 鬆壓迫性骨折，幾全發生在VB 。若VB 與PS 之骨量分佈產生變異，正面測量只能 測得總量(VB 與PS 之和)將降低其預測骨 折風險之能力。本研究以側面測量方式， 分別測量VB 與PS 之骨量，在65 位男性 及112 女性觀察年齡、停經及性別對VB 佔骨總量比率之影響。結果顯示在停經年 齡前，女性之比率(mean±SEM: 39.1±0.9%) 較同齡男性(50.0±1.7%)為低(p<0.0001)。在 停經年齡之後，女性隨老化VB 佔總骨量 之比率逐年減少(每年0.22%,　p=0.0001)， 但在男性則與年輕時無異。此外，本研究 也顯示總骨量在男性均隨年齡減少，但各 年齡層之男性均較女性為多。是以女性在 總骨量己較男性為少之狀況下，在停經後 因VB 內之海綿骨較多，損耗較快，反而 有更低之VB 所佔總量比率，不利於抗壓 之需求。此因素應是停後女性易有壓迫性 骨折之原因之一。此外，因男女性之骨量 分佈狀況不同，以傳統正面方式測量骨密 度時，宜考量性別及年齡因素，才能準確 評估脊椎體壓迫性骨折之風險。Compression fractures occur mainly at the vertebral body. Variations in the distribution of bone mass in a vertebra, if undefined, may bias the ability of the acquired bone mineral density values, which was usually measured posteroanteriorly, to predict the risk of fractures. To evaluate the effects of age and gender on the distribution of bone mineral content in the third lumbar vertebrae. We performed a cross sectional study on the distribution of bone mineral content in the third lumbar vertebrae. The bone mineral content of the whole L3 including the L3 vertebral body and the posterior segment was measured using a lateral approach with a dual energy x-ray absorptiometer on 177 healthy Taiwanese adults including 65 men, and 55 premenopausal and 57 postmenopausal women. The proportion of bone mineral content (BMC) in the vertebral body was significantly lower in premenopausal women than in age-matched men (39.1±0.9% vs. 50.0±1.7%, P< 0.0001). Furthermore, while postmenopausal women showed a decreased proportion of BMC in the vertebral body with increased age (about -0.0022 per year, p=0.0001), premenopausal women and men showed a sustained proportion. Thus, the proportion of BMC distributed in the body of L3 vertebrae was lower in women than in men. The discrepancy of this parameter between the genders was even larger with increased ages

Studies on the mechanism(s) of action of estrogen and environmental estrogens on the cell growth of osteoblast

動情素(estrogen)在生理病理上 有其特殊意義，對於骨骼也具有保 護作用，但其需透過何種機制來進 行則尚未完全清楚。環境動情素 (environmental estrogens) 包括有去污 劑、殺蟲劑、其他工業化學物如多 氯聯苯(hydroxy-PCBs)、2,3,4-TCB、 4-OH-alkyl-phenols、多環芳香烴類化 合物等，以及緣自植物的phytosterol esters，已知其中某些物質會與細胞 核類固醇受體交互作用而影響到性 分化現象。雖然目前對於環境動情 素在內分泌及生殖系統的影響有較 多的研究，但這些賀爾蒙樣物質對 於骨代謝系統的影響也是不容忽 視，而有關此方面的研究並不多。 在本研究計劃中，我們發現動情素 樣物質會促進初級培養成骨細胞 (primary culture of rat osteoblast-like cells) 及人類成骨細胞株(MG-63 cells)增 生，此作用會被ICI182,780 (動情素 拮抗劑)對抗。動情素樣物質亦會促 進成骨細胞ERK1/2蛋白磷酸化及誘 導二型環氧酵素(cyclooxygenase-2)表 現。MAP kinase 抑制劑PD98059 會對 抗動情素樣物質引起的二型環氧酵 素及細胞增生表現。這些結果顯示 MAP kinase 系中之ERK1/2 參與動情 素樣物質引起的二型環氧酵素及細 胞增生表現過程。It has been found that estrogen had protective effects on bone, but the mechanisms of action have not been fully established. Environmental estrogens include the detergents, pesticide, chlorinated insecticides, polycyclic aromatic hydrocarbons and phytosterol esters, and some of these compounds have recently been reported to modulate sexual differentiation by interacting with nuclear steroid receptors. There is an ongoing scientific debate concerning the potential threat of environmental estrogenic pollutants to animal and human health. So far, the focus has been on endocrinological system and reproductive organs, but environmental estrogens have far more widespread actions like as bone system. Nevertheless, the literatures about the action of these substances on the bone system are rare. In our study, we found that environmental estrogens were capable of increasing the proliferation in primary culture of rat osteoblast-like cells and human osteoblast-like cell line (MG-63), which could be blocked by estrogen antagonist (ICI182,780). Moreover, these environment estrogens could also trigger the phosphorylation of ERK1/2 and could induce the protein expression of cyclooxygenase-2 (COX-2) in osteoblasts. MAP kinase inhibitor PD98059 was capable of inhibiting the expression of COX-2 and cell proliferation induced by these environmental estrogens. These results indicate that the MAP kinase pathway may be involved in environment estrogens-induced COX-2 expression and cell proliferation in osteoblast

The mechanism(s) of effect of phytoestrogens on the cell proliferation and inflammatory factors release

植物動情素(phytoestrogens)是一種天然來源的植物化學物。一般來說其 可分類為isoflavones、 coumestans及 lignans等類。它們之所以被稱為植物 動情素是因其化學結構類似於內生性動情素(endogenous estrogens)，且也 會結合到動情素受體-及對於動情素受體-有較高的親和力)，因而 具有表現動情素樣活性(estrogen-like activity)之能力。相較於其它系統， 植物動情素對於免疫系統方面的研究是比較少的。本研究計畫即計畫 以巨噬細胞及腎絲球環間膜細胞實驗模式來探討植物動情素影響細 胞生長及對於發炎媒介物質的合成及釋放作用，以及可能之分子機 制，並且研究動情素受體在其中的角色，進而評估其對於免疫系統可 能具有的病理生理學意義。本年度我們的試驗結果發現植物動情素 -sitosterol、 resveratrol 及genistein在低劑量範圍會促進巨噬細胞及腎絲 球環間膜細胞增生。-sitosterol、 resveratrol 及genistein 亦具有促進巨噬 細胞及腎絲球環間膜細胞對於COX-2蛋白及mRNA表現的能力，且可觀 察到前列腺素PGE2釋放增加；但並不會影響COX-1蛋白表現。而這些 植物動情素的作用會受到動情素拮抗劑ICI182780的部份拮抗。因此， 植物動情素對於免疫系統可能具有某種程度的影響。Phytoestrogens are naturally occurring plant compounds that are present primarily in soybeans as isoflavones and in flaxseed as lignans. These plant chemicals display estrogen-like activity because of their structural similarity to human estrogens and exhibit high affinity binding for the estrogen receptor beta. Few, if any, studies have been made on the impact of these phytoestrogens on the immune system. The aims of this study, therefore, are twofold. The first goal is to verify the effects of phytoestrogens on the modulation of the cell proliferation and release of inflammatory mediators in macrophages and glomerular mesangial cell. The role of estrogen receptor in these responses is also investigated. Second, we try to investigate the possible molecular mechanism(s) involving in the effect of phytoestrogens on the macrophages and glomerular mesangial cell. In this year’s works, we found that low concentration range (3-100 nM) of phytoestrogens (-sitosterol, resveratrol and genistein) were capable of increasing cell proliferation and inducing the cyclooxygenase-2 protein and mRNA expression in macrophage and glomerular mesangial cell line, which could be partially inhibited by selective estrogen receptor antagonist ICI182780. The expression of COX-1 protein did not affected by these phytoestrogens. These results imply that there are some influences by phytoestrogens in immune system