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Interleukin-1β induces cyclic AMP formation in isolated human osteoblasts: a signalling mechanism that is not related to enhanced prostaglandin formation 白细胞介素-1β诱导分离的人成骨细胞形成环状AMP:一种与增强前列腺素形成无关的信号传导机制
Pub Date : 1994-01-01 DOI: 10.1016/S0169-6009(08)80212-7
Eva Bornefalk , Sverker Ljunghall , Anna G. Johansson , Kenneth Nilsson , Östen Ljunggren

Interleukin-1 (IL-1) is a potent stimulator of bone resorption. Induction of osteoclastic bone resorption by various endocrine or paracrine factors is mediated via the osteoblasts. We have therefore investigated the effects of 1L-1β on cell signalling in isolated human osteoblasts. Special interest was focused on prostaglandin synthesis, since indomethacin, an inhibitor of prostaglandin synthesis, partly inhibits IL-1-induced bone resorption. IL-1β, at and above 0.3 pM, dose dependently stimulated PGE2 formation in isolated human osteoblasts, with half maximal stimulation, EC50, at 3 pM. Treatment with the calcium ionophore A23187 (1 μM), or with forskolin (30 μM), also stimulated PGE2 formation in human osteoblasts. The time-course for IL-1β-induced PGE2 formation was similar to that of forskolin, with a significant increase in the formation of PGE2 seen after 1 h. In contrast, A23187-induced PGE2 formation was seen within minutes. IL-1β stimulated the accumulation of cyclic AMP in isolated human osteoblasts incubated for 15 min. This increase in cyclic AMP formation was not secondary to PGE2 formation since it was not blocked by the addition of indomethacin (1 μM). Pretreatment with the phosphodiesterase inhibitor IBMX did not augment IL-lβ-induced PGE2 formation, nor did the protein kinase A inhibitor Rp-cAMPs inhibit IL-1β-induced PGE2 formation, suggesting that cyclic AMP does not mediate the stimulatory effect of IL-1 on PGE2 formation. We conclude that IL-1β enhances the formation of cyclic AMP as well as PGE2 in primary cultures of isolated human osteoblasts.The IL-1β-induced cyclic AMP formation is, however, not related to the enhanced prostaglandin formation. The findings implicate that both cyclic AMP- and PGE2-formation in osteoblasts might be involved as independent mediators of IL-1β-induced bone resorption.

白细胞介素-1 (IL-1)是骨吸收的有效刺激物。各种内分泌或旁分泌因子诱导破骨细胞骨吸收是通过成骨细胞介导的。因此,我们研究了11l -1β对分离的人成骨细胞信号传导的影响。特别的兴趣集中在前列腺素的合成,因为吲哚美辛,一种前列腺素合成抑制剂,部分抑制il -1诱导的骨吸收。在0.3 pM及以上,IL-1β剂量依赖性地刺激离体人成骨细胞中PGE2的形成,在3pm时达到最大刺激的一半,EC50。钙离子载体A23187 (1 μM)或福斯olin (30 μM)也能刺激人成骨细胞中PGE2的形成。il -1β诱导PGE2形成的时间过程与forskolin相似,在1 h后PGE2的形成明显增加。相比之下,a23187诱导的PGE2形成在几分钟内。IL-1β刺激分离的人成骨细胞中环状AMP的积累,培养15分钟。这种环状AMP形成的增加不是继发于PGE2的形成,因为它不会被添加吲哚美辛(1 μM)阻断。磷酸二酯酶抑制剂IBMX预处理不能增强IL-1β诱导的PGE2的形成,蛋白激酶A抑制剂Rp-cAMPs也不能抑制IL-1β诱导的PGE2的形成,这表明环AMP不能介导IL-1对PGE2形成的刺激作用。我们得出的结论是,IL-1β增强了分离的人成骨细胞原代培养中环AMP和PGE2的形成。然而,il -1β诱导的环状AMP形成与前列腺素形成的增强无关。研究结果表明,成骨细胞中环AMP-和pge2的形成可能作为il -1β诱导骨吸收的独立介质参与。
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引用次数: 4
Effects of endurance exercise on bone histomorphometric parameters in intact and ovariectomized rats 耐力运动对完整和去卵巢大鼠骨组织形态学参数的影响
Pub Date : 1994-01-01 DOI: 10.1016/S0169-6009(08)80058-X
E.I. Barengolts, P.V. Lathon, D.J. Curry, S.C. Kukreja

Physical activity is important for maintenance of bone mass. The effects of exercise on bone histomorphometry were studied in 9-month-old intact (INT) and ovariectomized (OVX) rats. The rats were either kept sedentary (SED) or were exercised (EX) on a treadmill at 21 m/min for 1 h/day 5 days/week for 3 months. Bone resorption as well as formation parameters were significantly higher in OVX-SED than in 1NT-SED rats, indicating increased bone turnover in OVX rats. In OVX rats, lower osteoclast perimeter and number, lower labeled perimeter but higher mineral apposition rate (MAR) and bone formation rate (BFR) were associated with higher trabecular bone in OVX-EX compared with OVX-SED rats. In intact rats, trabecular bone mass and osteoclast number and perimeter were not affected by exercise. Labeled perimeter was slightly lower while MAR was higher and BFR was insignificantly higher in INT-EX than in INT-SED rats. Thus, exercise resulted in fewer resorption-formation sites, as indicated by lower labeled perimeter, but higher activity of individual osteoblasts, as indicated by higher MAR, both in estrogen-depleted and estrogen-replete states.

体力活动对维持骨量很重要。研究了运动对9月龄完整(INT)和去卵巢(OVX)大鼠骨组织形态学的影响。这些大鼠要么静止不动(SED),要么以21米/分钟的速度在跑步机上运动(EX),每天1小时,每周5天,持续3个月。OVX- sed大鼠骨吸收和骨形成参数明显高于1NT-SED大鼠,表明OVX大鼠骨转换增加。OVX大鼠与OVX- sed大鼠相比,OVX- ex的破骨细胞周长和数量较低,标记周长较低,但矿物质附着率(MAR)和骨形成率(BFR)较高,与OVX- sed大鼠相比,OVX- ex的骨小梁骨较高。在完整的大鼠中,运动不影响骨小梁骨量、破骨细胞数量和周长。与INT-SED大鼠相比,INT-EX大鼠标记周长略低,MAR较高,BFR无显著性升高。因此,运动导致更少的吸收形成位点,如标记周长较低所示,但个体成骨细胞活性较高,如较高的MAR所示,无论是在雌激素耗尽状态还是雌激素充满状态下。
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引用次数: 47
The effect of 17β-estradiol treatment on the mass and the turnover of bone in ovariectomized rats taking a mild dose of thyroxin 17β-雌二醇对轻度甲状腺素去卵巢大鼠骨质量及骨周转率的影响
Pub Date : 1994-01-01 DOI: 10.1016/S0169-6009(08)80129-8
Motonori Yamaura , Toshitaka Nakamura , Azusa Kanou , Tomoshi Miura , Hiroyuki Ohara , Katsumi Suzuki

We performed the dosing experiment to establish whether estrogen administration has any beneficial effects on the mass and the turnover of bone in ovariectomized rats taking a mild dose of thyroxin. Thirty-five Wistar rats, 28 weeks of age, received ovariectomies (OVX) or sham operations and were divided into five groups. Group I was the sham group, Groups 2–5 were ovariectomized. Group 2 was the OVX-control, Group 3 treated with thyroxin 30 μg/kg/day (T4), Group 4, 17β-estradiol 0.3 mg/kg/week (E2), and Group 5, the combination of T4 and E2. The duration of the experiment was 12 weeks. At the end of the experiment, serum chemistries were measured. Bone minerals in the femur were determined with single photon absorptiometry and bone turnover was assessed histomorphometrically. Alkaline-phosphatase increased in Group 3 (OVX-T4), but it reduced in Groups 4 (OVX-E2) and 5 (OVX-T4 + E2). Bone minerals decreased in Groups 2 (OVX) and 3. In Group 4, it was preserved at the same level as in Group 1. Group 5 showed a significant increase of bone mass compared with Group 1. Eroded surface and osteoid surface increased in Groups 2 and 3 and they were reduced in Groups 4 and 5. Bone volume and mineral apposition rate were at a maximum in Group 5. This study demonstrated that 17β-estradiol was capable of preventing the bone mass decrease by regulating the turnover in ovariectomized rats taking a mild dose of thyroxin. Osteoblast function appeared to be stimulated in combination with 17β-estradiol and thyroxin.

我们进行了剂量实验,以确定雌激素给药是否对服用轻度甲状腺素的去卵巢大鼠的骨质量和骨转换有任何有益的影响。取28周龄Wistar大鼠35只,分别行卵巢切除或假手术,分为5组。1组为假手术组,2 ~ 5组切除卵巢。第2组为ovx对照组,第3组给予甲状腺素30 μg/kg/d (T4),第4组给予17β-雌二醇0.3 mg/kg/周(E2),第5组给予T4和E2联合治疗。试验期为12周。实验结束时,测定血清化学成分。用单光子吸收法测定股骨骨矿物质,用组织形态学法评估骨转换。3组(OVX-T4)碱性磷酸酶升高,4组(OVX-E2)和5组(OVX-T4 + E2)碱性磷酸酶降低。第2组(OVX)和第3组骨矿物质含量下降。第4组与第1组保存水平相同。第5组骨量较第1组显著增加。2、3组侵蚀面和类骨面增多,4、5组减少。骨体积和矿物质附着率在第5组最大。本研究表明,17β-雌二醇能够通过调节轻度甲状腺素切除卵巢大鼠的代谢来防止骨量减少。17β-雌二醇和甲状腺素可刺激成骨细胞功能。
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引用次数: 9
Gender dependent effects of testosterone and 17β-estradiol on bone growth and modelling in young mice 睾酮和17β-雌二醇对幼鼠骨生长和骨模型的性别依赖性影响
Pub Date : 1994-01-01 DOI: 10.1016/S0169-6009(08)80130-4
A. Ornoy , S. Giron , R. Aner , M. Goldstein , B.D. Boyan , Z. Schwartz

This study examined the effects of estrogen (17β-estradiol) and testosterone on the growth of long bones in male and female mice, with and without gonadectomy. Weight and nose-to-tail length were determined at 3 weeks of age at time of gonadectomy, 7 days later at the onset of hormone therapy, and throughout the treatment period. Gonadectomized mice exhibited an initial weight gain during the pretreatment period but length was unaffected. Hormone treatment altered weight gain in surgical and intact animals in a gender- and hormone-dependent manner. Estradiol enhanced weight gain in intact mice, but inhibited weight gain in ovariectomized mice. Lower doses of estradiol increased weight gain in orchiectomized mice at early time points. Testosterone increased weight in intact females and males, but not in gonadectomized mice. Estradiol increased nose-to-tail length in intact females at early time points, but inhibited length in ovariectomized females at later times, and it decreased length in intact males. Testosterone increased length in normal females and normal males. Serum Ca was unaffected by ovariectomy, but orchiectomy resulted in decreased levels. Estradiol reduced serum Ca in gonadectomized animals; serum Ca was increased by estradiol treatment in intact females. Changes in tibial bone weight, ash weight and mineral composition, and relative sizes of epiphyseal and metaphyseal bone were gender-, gonadectomy- and hormone-specific. Bone weight was greater in ovariectomized mice. Ash weight per bone was comparable, but there was an increase in Ca and P content with ovariectomy. Estradiol increased bone weight, ash content, and bone Ca and P in ovariectomized and intact females. Orchiectomy alone did not alter bone weight, ash content, or Ca and P, but orchiectomized mice were sensitive to estradiol; all parameters were increased in the orchiectomized animals treated with estradiol. Analysis of the ash content and Ca and P per mg bone, rather than per bone, demonstrated estradiol and testosterone alter net bone formation, but not the amount of mineral per unit bone. Ovariectomy increased hypertrophic cartilage. While estradiol did not alter tibial area in ovariectomized mice, it caused an increase in intact females. The total amount of growth plate cartilage in ovariectomized animals was decreased by estradiol to levels typical of intact animals due to a greater decrease in the hypertrophic cartilage in the ovariectomized mice, as well as a greater increase in metaphyseal bone area. Testosterone had no effect on these parameters in the females. Orchiectomy decreased the amount of growth plate cartilage, but increased the hypertrophic zone. Estradiol increased growth plate cartilage in intact male mice, but decreased it in orchiectomized mice. This difference was also seen in the hypertrophic zone. Total growth plate cartilage and hypertrophic cartilage were increased by testosterone in intact males, whereas metaphyseal and epip

本研究考察了雌激素(17β-雌二醇)和睾酮对雄性和雌性小鼠长骨生长的影响,并对未切除性腺的小鼠进行了研究。在切除性腺时3周龄、激素治疗开始后7天以及整个治疗期间测定体重和鼻尾长度。在预处理期间,去性腺细胞的小鼠表现出最初的体重增加,但长度不受影响。激素治疗以性别和激素依赖的方式改变了手术和完整动物的体重增加。雌二醇促进了完整小鼠的体重增加,但抑制了去卵巢小鼠的体重增加。较低剂量的雌二醇增加了早期切除睾丸小鼠的体重增加。睾酮增加了雌性和雄性的体重,但在去性腺的小鼠中没有。雌二醇在早期增加了未切除卵巢雌性的鼻尾长度,但在后期抑制了未切除卵巢雌性的鼻尾长度,并减少了未切除卵巢雄性的鼻尾长度。睾酮增加了正常女性和正常男性的体长。血清钙不受卵巢切除术的影响,但卵巢切除术导致钙水平下降。雌二醇降低了去性腺动物的血清钙;雌二醇处理可使正常雌性血清钙升高。胫骨骨量、灰分重量和矿物质组成以及骨骺和干骺相对大小的变化与性别、性腺切除术和激素有关。去卵巢小鼠的骨量更大。每骨灰分重比较,但Ca和P含量随卵巢切除而增加。雌二醇增加了卵巢切除和完整女性的骨量、灰分含量和骨钙、磷含量。单独切除睾丸不会改变骨量、灰分含量或钙和磷,但切除睾丸的小鼠对雌二醇敏感;雌二醇治疗后,所有参数均增加。对灰分含量和钙磷含量的分析表明,雌二醇和睾酮会改变骨的形成,但不会改变每单位骨的矿物质含量。卵巢切除术增加了肥大软骨。虽然雌二醇没有改变切除卵巢小鼠的胫骨面积,但它会增加未切除卵巢小鼠的胫骨面积。雌二醇使去卵巢动物的生长板软骨总量减少到正常动物的水平,因为去卵巢小鼠的肥大软骨减少得更多,干骺端骨面积增加得更多。在雌性中,睾酮对这些参数没有影响。睾丸切除术减少了生长板软骨的数量,但增加了肥大带。雌二醇增加了完整雄性小鼠的生长板软骨,但减少了睾丸切除小鼠的生长板软骨。这种差异在肥厚带也可见。睾酮使完整雄鼠生长板软骨和肥大软骨面积增加,而干骺和骨骺面积减少。研究结果首次表明,无论动物是否进行了性腺切除术,雄性和雌性小鼠对雌二醇和睾丸激素都有性别特异性反应。在许多参数中,睾丸切除小鼠对两种性类固醇的反应与雌性相似,这表明雄性性腺是小鼠骨骼对雌二醇和睾酮表现出雄性表型反应所必需的。
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引用次数: 74
1,25-Dihydroxyvitamin D3 receptors in peripheral blood mononuclear cells from patients with primary and secondary hyperparathyroidism 原发性和继发性甲状旁腺功能亢进患者外周血单个核细胞中的1,25-二羟基维生素D3受体
Pub Date : 1994-01-01 DOI: 10.1016/S0169-6009(08)80183-3
Josefina Martínez , José M. Olmos , Angel L.M. de Francisco , José A. Amado , Jose A. Riancho , Jesús González-Macías

A decreased number of calcitriol (1,25(OH)2D3) receptors has been observed in parathyroid glands of uremic animals. In humans, studies carried out in surgically removed parathyroid glands have shown that calcitriol binding is higher in primary than in secondary hyperparathyroidism. Since specific receptors for calcitriol have been described in peripheral blood mononuclear cells (PBMC), we have investigated the specific uptake of 3H-labelled l,25(OH)2D3 in PBMC of 12 women with primary hyperparathyroidism (PHP), 8 women with hyperparathyroidism secondary to chronic renal failure (SH), 9 women with renal transplant (RT), and 23 healthy women. The median dissociation constant (Kd) was similar in all three groups of patients and in healthy women (mean ± S.D. (range): PHP, 1.2 ± 1.0 (0.2–4) × 10−10 M; SH, 0.6 ± 0.4 (0.2–1.2) × 10−10 M; RT, 1.1 ± 0.5 (0.4–1.9) × 10−10 M; controls, 1.0 ± 0.6 (0.3–2.6) × 10−10 M). However, the maximal binding capacity (Nmax) was significantly enhanced in PHP (3.9 ± 1.9 (1.3–7.6) fmol/107 cells vs. 2.3 ± 0.9 (1.1–4.4) fmol/107 cells in controls; P = 0.0006) and decreased in SH (0.8 ± 0.5 (0.2–1.6) fmol/107 cells vs. 2.3 ± 0.9 (1.1–4.4) fmol/107 cells in controls; P = 0.0001), whereas no changes were seen in RT (2.3 ± 0.7 (1.2–3.3) fmol/107 cells vs. 2.3 ± 0.9 (1.1–4.4) fmol/107 cells in controls). In three patients with PHP who were subjected to parathyroidectomy, the calcitriol number came down to normal. Changes of calcitriol receptors in primary and secondary hyperparathyroidism could magnify the consequences of disturbances in serum concentration of calcitriol itself and might play an important role in the development of secondary hyperparathyroidism in uremia.

在尿毒症动物甲状旁腺中观察到骨化三醇(1,25(OH)2D3)受体数量减少。在人类中,手术切除甲状旁腺的研究表明,骨化三醇的结合在原发性甲状旁腺功能亢进患者中高于继发性甲状旁腺功能亢进患者。由于骨化三醇的特异性受体已经在外周血单核细胞(PBMC)中被描述,我们研究了12名原发性甲状旁腺功能亢进(PHP)女性、8名继发于慢性肾功能衰竭(SH)的甲状旁腺功能亢进女性、9名肾移植(RT)女性和23名健康女性的PBMC中3h标记的1,25 (OH)2D3的特异性摄取。三组患者和健康女性的中位解离常数(Kd)相似(平均±sd(范围):PHP, 1.2±1.0 (0.2-4)× 10−10 M;Sh, 0.6±0.4 (0.2-1.2)× 10−10 m;Rt, 1.1±0.5 (0.4-1.9)× 10−10 m;然而,最大结合能力(Nmax)在PHP中显著增强(3.9±1.9 (1.3-7.6)fmol/107细胞,而在对照组中为2.3±0.9 (1.1-4.4)fmol/107细胞;P = 0.0006), SH降低(0.8±0.5 (0.2-1.6)fmol/107细胞,对照组为2.3±0.9 (1.1-4.4)fmol/107细胞;P = 0.0001),而RT未见变化(对照为2.3±0.7 (1.2-3.3)fmol/107细胞,对照为2.3±0.9 (1.1-4.4)fmol/107细胞)。在接受甲状旁腺切除术的3例PHP患者中,骨化三醇数降至正常。原发性和继发性甲状旁腺功能亢进患者骨化三醇受体的变化可放大骨化三醇自身血清浓度紊乱的后果,并可能在尿毒症患者继发性甲状旁腺功能亢进的发生中起重要作用。
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引用次数: 6
Circulating levels of insulin-like growth factor-I and -II, and IGF-binding protein-3 in inflammation and after parathyroid hormone infusion 炎症和甲状旁腺激素输注后胰岛素样生长因子- i和-II及igf结合蛋白-3的循环水平
Pub Date : 1994-01-01 DOI: 10.1016/S0169-6009(08)80128-6
Anna G. Johansson , David J. Baylink , Eva af Ekenstam , Erik Lindh , Subburaman Mohan , Sverker Ljunghall

In order to assess if the anabolic action of PTH is related to changes in circulating levels of insulin-like growth factor-I and -II (IGF-I and -II), and IGF binding protein 3 (IGFBP-3), 24 h of PTH infusion was performed in healthy women and in patients with rheumatoid arthritis (RA), a state where both bone metabolism and PTH secretion is influenced by the inflammatory activity. The patients with RA had lower basal levels of both IGF-I and -II than the healthy controls (P < 0.05). In neither group did the IGFs change after 24 h of PTH administration, while IGFBP-3 was significantly increased in the healthy controls (4600 ± 1200 to 5750 ± 2200 μg/l, P < 0.05). IGFBP-3 was not affected by PTH infusion in patients with RA when the disease had high activity, but when inflammation had subsided they responded with a similar increase in IGFBP-3 as the control group and basal IGF-I and -II levels were normalised. Since IGFBP-3 can enhance the anabolic action of IGF-I, increased IGFBP-3 levels after PTH infusion may reflect a mechanism by which PTH is anabolic for bone. Inflammation may inhibit bone formation via decreased serum levels of IGFs and blocked IGFBP-3 response to PTH.

为了评估PTH的合成代谢作用是否与胰岛素样生长因子- i和-II (IGF- i和-II)以及IGF结合蛋白3 (IGFBP-3)循环水平的变化有关,在健康女性和类风湿关节炎(RA)患者中进行了24小时的PTH输注,在这种状态下骨代谢和PTH分泌都受到炎症活动的影响。RA患者IGF-I和-II的基础水平均低于健康对照组(P <0.05)。PTH给药24 h后,两组IGFs均无变化,而健康对照组IGFBP-3显著升高(4600±1200 ~ 5750±2200 μg/l);0.05)。当RA患者病情高活跃时,PTH输注对IGFBP-3没有影响,但当炎症消退时,IGFBP-3的反应与对照组相似,基础IGF-I和-II水平恢复正常。由于IGFBP-3可以增强IGF-I的合成代谢作用,PTH输注后IGFBP-3水平升高可能反映了PTH对骨的合成代谢机制。炎症可能通过降低血清IGFs水平和阻断IGFBP-3对甲状旁腺激素的反应来抑制骨形成。
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引用次数: 41
Calendar of forthcoming events 即将举行的活动日历
Pub Date : 1994-01-01 DOI: 10.1016/S0169-6009(08)80064-5
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引用次数: 0
The effect of fluoridated drinking water on axial bone mineral density — a population-based study 含氟饮用水对轴向骨密度的影响——一项基于人群的研究
Pub Date : 1994-01-01 DOI: 10.1016/S0169-6009(08)80184-5
Heikki Kröger , Esko Alhava , Risto Honkanen , Marjo Tuppurainen , Seppo Saarikoski

Bone mineral density (BMD) of the spine and femoral neck was measured in a random stratified sample of 3222 perimenopausal women aged 47–59 years. A total of 969 women had used fluoridated drinking water (1.0–1.2 mg/l) for over 10 years. These women were compared with 2253 women with low levels of fluoride in drinking water (<0.3 mg/l). BMD of the spine was significantly higher in the fluoride group than in the non-fluoride group (1.138 ±0.165 vs. 1.123 ± 0.156 g/cm2, P = 0.026). Femoral neck BMDs did not differ between the groups. When the BMD values were adjusted for confounding factors (age, weight, menopausal status, calcium intake, physical activity level, deliveries, alcohol consumption and estrogen use), the differences between the groups increased (P < 0.001 for the spine and P = 0.004 for the femoral neck, respectively). There was no significant difference between the groups in the prevalence of self-reported fractures sustained during 1980–1989. We propose that the fluoridation of drinking water has a slight increasing effect on axial BMD in women in low fluoride areas.

对3222名47-59岁围绝经期妇女随机分层取样,测量脊柱和股骨颈骨密度(BMD)。共有969名妇女使用含氟饮用水(1.0-1.2毫克/升)超过10年。将这些妇女与2253名饮用水中氟化物含量较低(0.3毫克/升)的妇女进行比较。氟化物组脊柱骨密度显著高于非氟化物组(1.138±0.165比1.123±0.156 g/cm2, P = 0.026)。两组间股骨颈骨密度无差异。当将混杂因素(年龄、体重、绝经状态、钙摄入量、体力活动水平、分娩、饮酒和雌激素使用)纳入BMD值后,组间差异增大(P <脊柱为0.001,股骨颈为P = 0.004)。在1980-1989年期间,两组间自我报告的骨折发生率无显著差异。我们认为,饮用水氟化对低氟地区妇女轴向骨密度的影响略有增加。
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引用次数: 44
Effect of cyclosporine A on normal human osteoblasts in vitro 环孢素A对体外正常人成骨细胞的影响
Pub Date : 1994-01-01 DOI: 10.1016/S0169-6009(08)80172-9
M. Nàcher, J. Aubia, S. Serrano, M.L.I. Mariñoso, J. Hernández, J. Bosch, A. Díez, J.M. Puig, J. Lloveras

Cyclosporin-A (CsA) inhibits in vitro proliferation of non-human tumour-cloned osteoblasts. Our aims were to study the direct effect of CsA on proliferation of normal human osteoblast (NHOb) cultures and to ascertain whether CsA-treated patients' sera (CsATPS) may exert effects on the osteoblast which differ from the direct effects of CsA. We studied tritiated thymidine ([3H]thymidine) incorporation in NHOb cultures incubated with (a) increasing CsA concentrations (1.2 to 4800 ng/ml), (b) the same concentrations as in the previous experiment but with the addition of 20% fetal calf serum (FCS) or 20% normal human serum (NHS), (c) 40% NHS or 40% CsATPS. Results at 96 h in (a) CsA inhibited [3H]thymidine uptake from 300 ng/ml, in (b) CsA inhibited [3H]thymidine uptake from 2400 ng/ml for cultures with FCS and 4800 ng/ml for cultures with NHS, in (c) CsATPS produced [3H]thymidine uptake inhibition compared with NHS. Conclusion: CsA alone inhibited [3H]thymidine incorporation in NHOb from concentrations similar to therapeutic concentrations. With FCS or NHS, inhibition was produced at higher concentrations. CsATPS inhibited at CsA concentrations lower than those of the two previous experiments.

环孢素a (CsA)抑制非人肿瘤克隆成骨细胞体外增殖。我们的目的是研究CsA对正常人成骨细胞(NHOb)增殖的直接影响,并确定CsA治疗的患者血清(CsATPS)是否可能对成骨细胞产生不同于CsA直接作用的影响。我们研究了氚化胸腺嘧啶([3H]胸腺嘧啶)与NHOb培养物的结合(a)增加CsA浓度(1.2至4800 ng/ml), (b)与先前实验中相同的浓度,但添加20%胎牛血清(FCS)或20%正常人血清(NHS), (c) 40% NHS或40% CsATPS。结果在96 h时(a) CsA抑制了300 ng/ml胸腺嘧啶的[3H]摄取,(b) CsA抑制了FCS培养物对[3H]胸腺嘧啶的摄取(2400 ng/ml), NHS培养物对[3H]胸腺嘧啶的摄取(4800 ng/ml), (c)与NHS相比,CsATPS产生了[3H]胸腺嘧啶摄取抑制。结论:CsA单独抑制NHOb中[3H]胸苷的掺入,其浓度与治疗浓度相似。使用FCS或NHS,在较高浓度下产生抑制作用。CsATPS对CsA浓度的抑制作用低于前两个实验。
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引用次数: 28
Bone mineralization in children and adolescents with a milk allergy 牛奶过敏儿童和青少年的骨矿化
Pub Date : 1994-01-01 DOI: 10.1016/S0169-6009(08)80181-X
Richard C. Henderson, Patrick R.L. Hayes

To evaluate the correlation between dietary calcium intake and mineralization of the immature skeleton 55 children and adolescents aged 5–14 years (mean, 9.5 years) with a positive radioallergosorbent test (RAST) for serum antibodies to cow's milk protein were evaluated. Bone mineral density (BMD) in the lumbar spine and proximal femurs were measured by dual energy X-ray absorptiometry. BMD at each site for each subject was converted to an age-adjusted Z score based on our own series of 95 normal pediatric controls. Calcium intake was determined using a detailed food frequency questionnaire administered by a nutritionist during a 30–40-min interview. Dietary adjustments to the condition varied and resulted in a wide range of calcium intakes. Calcium supplements were taken by 22% of the subjects and were included in the determination of daily calcium intake. The group of 55 subjects was divided into quartiles based on calcium intake (mean ± S.E mg calcium/day): Group 1, 409 ± 21, Group 2, 663 ± 16, Group 3, 950 ± 32, Group 4, 1437 ± 124. Bone density Z scores in the proximal femur serially increased across the calcium intake groups (mean ± S.E.): Group 1, −0.16 ± 0.31; Group 2, 0.05 ± 0.33; Group 3, 0.44 ± 0.24; Group 4, 0.79 ± 0.41 (P = 0.03). A similar pattern was found with lumbar spine BMD Z scores: Group 1, −0.16 ± 0.27; Group 2,0.10 ± 0.21; Group 3,0.18 ± 0.20; Group 4,0.30 ± 0.25 (P = 0.05). These data add further to the evidence that dietary calcium intake is important for optimal mineralization of the growing skeleton.

为了评估膳食钙摄入量与未成熟骨骼矿化之间的相关性,我们对55名5-14岁(平均9.5岁)的儿童和青少年进行了评估,这些儿童和青少年的放射过敏原吸收试验(RAST)对牛奶蛋白的血清抗体呈阳性。采用双能x线骨密度仪测定腰椎及股骨近端骨密度(BMD)。每个受试者的每个部位的骨密度根据我们自己的95名正常儿童对照,转换为年龄调整后的Z评分。在30 - 40分钟的访谈中,营养学家通过详细的食物频率问卷来确定钙的摄入量。对这种情况的饮食调整各不相同,导致钙摄入量的变化很大。22%的受试者服用了钙补充剂并被纳入了每日钙摄入量的测定。根据钙摄取量(平均±S.E mg钙/天)将55名受试者分为四分位数:1组409±21,2组663±16,3组950±32,4组1437±124。各钙摄入组股骨近端骨密度Z评分依次升高(平均值±S.E.): 1组,−0.16±0.31;第二组,0.05±0.33;第三组,0.44±0.24;第4组,0.79±0.41 (P = 0.03)。腰椎BMD Z评分也有类似的规律:1组,−0.16±0.27;第二组0.10±0.21;第三组:0.18±0.20;第4组,0.30±0.25 (P = 0.05)。这些数据进一步证明,膳食钙的摄入对生长中的骨骼的最佳矿化很重要。
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引用次数: 55
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Bone and mineral
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