糖尿病对骨代谢影响的基础研究进展

近年来,一系列临床研究及动物实验结果表明,糖尿病与骨质疏松症的发生及发展进程密切相关,糖尿病可通过不同的分子机制对骨代谢产生不良影响。相关的机制研究表明糖尿病通过脂肪因子、晚期糖基化终末产物、骨硬化蛋白、胰岛素、胰岛素生长因子-1、促炎因子、骨髓脂肪组织及胰高血糖素样肽1等因素直接或间接地参与和诱导了骨质疏松症的形成和发展。本研究就糖尿病对骨代谢影响的基础研究,糖尿病性骨质疏松症的分子机制进行综述。     

巨噬细胞影响骨质疏松性骨折骨愈合的研究进展

骨质疏松性骨折愈合缓慢,预后差。募集的巨噬细胞极化为促炎M1型巨噬细胞及抑炎M2型巨噬细胞,两种亚型的动态平衡影响骨折愈合速度和预后。但在原发性骨质疏松性骨折及继发性骨质疏松性骨折中,M1型和M2型巨噬细胞极化失衡,严重影响骨折愈合。研究表明,通过一些生物学方法重建巨噬细胞极化平衡,如生物医用仿生材料和外泌体携载miRNA治疗等,可有效改善巨噬细胞表型极化,减少骨吸收,促进成骨分化,加速骨质疏松性骨折骨愈合。因此,笔者从巨噬细胞在骨折愈合过程中的作用、巨噬细胞极化失衡导致骨质疏松性骨折延迟愈合及重建巨噬细胞极化平衡加速骨质疏松性骨折骨愈合等方面,就巨噬细胞对骨质疏松性骨折骨愈合影响的研究进展进行综述,为临床治疗骨质疏松性骨折提供新的思路。     

Primary osteoliposarcoma of bone

Summary Radiologic and pathoanatomic findings in two patients with the very rare primary osteoliposarcoma of bone are reported. In one case, there was a manifestation on the left femoral shaft which led to pathologic fracture. Amputation of the femur was followed by a 2.5-year tumor-free interval. In the second case, there was a manifestation in the region of the right upper part of the ilium. After radiation and cytostatic therapy, pronounced intratumoral ossifications occurred and the patient's condition was good up to exitus lethalis 3 years after diagnosis. Osteoliposarcoma thus shows a markedly more favorable prognosis than the osteosarcoma and rather corresponds to that of a liposarcoma. Typical clinical and radiologic symptoms are lacking.     

骨代谢指标测定在骨质疏松诊治中的应用价值

目的 比较妇女绝经前后骨代谢指标的变化，研究各指标在骨质疏松症治疗后的变化率，对各指标在骨质疏松症诊治中的应用作出初步评价。方法 48例绝经前妇女、48例绝经后妇女测定10项骨代谢指标．45例绝经后骨质疏松症患者．治疗前、治疗6个月后分别测定10项骨代谢指标，观察其变化率。12名绝经后妇女，每两个月测定10项骨代谢指标。共观察一年。结果 绝经后妇女骨代谢指标明显升高，绝经后骨质疏松症患者经抗吸收治疗后．大部分骨代谢指标明显降低，血清骨形成指标比尿骨吸收指标长期个体内的变异要小。结论 绝经后骨质疏松症患者骨转换加快，部分血清骨代谢指标优于尿骨代谢指标，尤以血清骨形成指标N—mid骨钙素和血清骨吸收指标CTX为优。     

Handgrip Strength is an Independent Predictor of Distal Radius Bone Mineral Density in Postmenopausal Women

Several cross-sectional studies have reported a positive correlation between muscle strength and local bone mineral density. However, very few studies have evaluated the possible role of confounding variables, which may be substantial as both bone mineral density and muscle strength are multifactorial variables. We studied 140 postmenopausal women who underwent their first osteodensitometry in our hospital. Of these, 102 women affected neither by bone diseases apart from primary osteoporosis nor treated with drugs affecting bone mass were selected. Distal radius bone mineral density of the non-dominant arm was assessed by dual photon absorptiometry. Handgrip strength was measured by a handheld dynamometer. The following factors influencing bone mass were also considered: age, years since menopause, years of cyclic ovarian activity, body weight, body height, body mass index, and both calcium and alcohol dietary intake. Statistical evaluation was performed by stepwise multiple regression analysis. This showed that only two variables were independently related to bone mineral density: handgrip strength (which was the best bone density predictor among the studied independent variables) and years since menopause. R² value was 0.43 (F=38.04, p<0.001). All the other variables studied were not significantly related to bone density when the effects of both strength and years since menopause were considered. In conclusion, the data showed that handgrip strength was a strong independent predictor of distal radius bone mineral density in postmenopausal women. Clinical assessment of osteoporosis risk factors, including muscle strength, is recommended: although it is not an adequate substitute for bone densitometry, it can help clinicians to identify the risk groups at which to direct bone density measurement. Received: 1 October 1999 / Accepted: 29 May 2000     

晚期糖化终末产物在去卵巢大鼠骨质疏松发病中的作用及氨基胍防治效果

目的　探讨晚期糖化终末产物 (AGEs)在去卵巢大鼠骨质疏松发病中的作用及氨基胍防治效果。方法　选用 1 0月龄大鼠通过卵巢切除诱导骨质疏松并用氨基胍防治其骨量丢失 ,测定其骨密度及骨胶原中 AGEs的含量及血、尿生化指标。结果　卵巢切除大鼠骨密度 (0 .2 0 7g/cm2 ± 0 .0 1 6 g/cm2 )明显低于假手术大鼠 (0 .2 36 g/cm2 ± 0 .0 1 0 g/cm2 ) (P<0 .0 1 ) ,而骨胶原 AGEs含量 (59.86 RU/mg胶原± 3.1 3 RU/mg胶原 )明显高于假手术组大鼠 (53.83RU/mg胶原± 5.46RU/mg胶原 ) (P<0 .0 1 )。卵巢切除大鼠血清雌激素 (4.50 pg/ml± 1 .73pg/ml)与假手术组(8.45 pg/ml± 2 .90 pg/ml)比较明显降低 (P<0 .0 2 ) ,2 4 h尿钙、尿钙与肌酐比值、尿磷、尿磷与肌酐比值均有升高趋势。卵巢切除大鼠给予氨基胍后骨密度 (0 .2 2 1 g/cm2± 0 .0 1 7g/cm2 )明显升高 (P<0 .0 5) ,骨胶原中 AGEs含量 (51 .2 3RU/mg胶原± 7.46RU/mg胶原 )明显降低 (P<0 .0 1 ) ,血清雌激素 (8.59pg/ml± 3.0 1 pg/ml)明显升高 (P<0 .0 1 ) ,2 4 h尿钙、尿钙与肌酐比值降低 ,2 4 h尿羟脯氨酸升高 ,与手术组比较有显著差异 (P<0 .0 5)。结论　卵巢切除后 ,雌激素的降低和 AGEs的增加是导致骨质疏松的主要原因。而氨基胍通过降低体内 AGE     

老年人腰椎和髋部骨密度测定T评分的一致性比较

目的 探讨老年人腰椎和髋部双能X线骨密度(DEXA)测定T评分的一致性及髋部骨密度(BMD)T评分在骨质疏松诊断中的意义。方法 在排除患有影响骨量的疾病及使用影响骨代谢药物者后，选择60-89岁老年人260(其中男123人，女137人)例作为为研究对象。受检者均接受问卷调查、胸腰段脊椎正侧位X线摄片，DEXA测定2-4腰椎(L2-4)椎体前后位和左髋部BMD(若左髋部发生过骨折或存有明显病变则改测右髋部)，并进行有关统计分析。结果 老年男性各年龄组L2-4 BMD T评分比髋部要高(P＜0．01或P＜0.05)；老年女性除在65—69岁、85—89岁年龄组腰椎BMD T评分比髋部要高(P＜0．01和P＜0.05)外，其余各组则差异无显著性。按照WHO标准，以髋部、腰椎和同时以髋部、腰椎BMD T评分为依据，在123例男性中，分别有19、6、5人被诊断为骨质疏松症；在137例女性中，则分别有35、17、14人被诊断为骨质疏松症；单以腰椎和同时以髋部、腰椎BMD T评分为依据所检出的骨质疏松症患者人数均少于单以髋部BMD T评分为依据者(P＜0．01)。结论 在老年人尤其是老年男性，其腰椎BMD T评分明显高于髋部，腰部BMD T评分在骨质疏松诊断中的意义更为重要。     

p38丝裂原活化蛋白激酶信号途径在鼠破骨细胞生成和骨吸收中的作用

目的研究p38丝裂原活化蛋白激酶(p38MAPK)信号途径在甲状旁腺素相关肽(PTHrP)诱导的破骨细胞生成和骨吸收中的作用。方法取小鼠骨髓细胞,在PTHrP(45ng/ml)的刺激下,在不同试验组中分别入0.1、1.0及10μmol/L的p38MAPK抑制剂Fr167653,继续培养6d。抗酒石酸染色,进行破骨细胞计数。在小鼠颅骨部位注射PTHrP建立骨吸收和高钙血症动物模型。每日给予p38MAPK抑制剂Fr16765330mg/kg,每日2次,X线片观察骨吸收面积,组织学检查计算单位面积内破骨细胞数目,采集血样观察全血内游离钙水平。结果PTHrP刺激下,大量破骨细胞生成(118.9±28.3)个/孔;加入0.1μmol/LFr167653可以部分抑制破骨细胞的生成(79.6±28.0)个/孔,加入10μmol/LFr167653几乎全抑制了破骨细胞生成(7.4±0.4)个/孔,每日给予Fr16765330mg/kg,每日2次,可以明显抑制骨吸收,表现为X线片上骨吸收面积减少,单位面积内破骨细胞数目减少,但是并不能有效地抑制高钙血症。结论抑制p38MAPK信号途径可以抑制破骨细胞的分化和局部骨吸收。     

人骨髓基质干细胞的分子表型特征及微环境依赖向内皮分化的能力

目的 :探讨人骨髓基质干细胞的分子表型特征及与成熟内皮共培养时向内皮分化的能力。方法 :采用密度梯度离心法分离培养人骨髓基质干细胞 ,用荧光激活细胞分选法分析其CD34、CD10 5和CD16 6表达率 ,用免疫荧光细胞化学法观察与成熟兔主动脉内皮共培养的人骨髓基质干细胞Flk -1和vWF蛋白表达 ,并分析anti VEGF抗体对骨髓基质干细胞Flk -1表达的影响。结果 :分离培养的骨髓基质干细胞CD34表达率为 (4 .16± 0 . 16 ) % ,与阴性对照 (4. 0 6± 0 . 2 3) %相比无统计学差异 ,CD10 5表达率为(90 .2 0± 2 . 35 ) % ,CD16 6表达率为 (82. 30± 3. 2 2 ) % ,均明显高于阴性对照 (n =6 ,P <0 .0 5 ) ;与成熟内皮细胞共培养 5d时 ,vWF染色仍为阴性 ,但部分骨髓基质干细胞开始表达Flk -1;anti VEGF抗体呈浓度依赖地抑制Flk- 1阳性骨髓基质干细胞计数 (n =6 ,P <0 .0 5 )。结论 :与成熟内皮共培养的骨髓基质细胞具有微环境依赖向内皮细胞分化的能力。     

Bone marrow transplantation or chemotherapy as post-remission treatment of adult acute myelogenous leukemia

Summary We compared three consolidation regimens in patients with acute myelogenous leukemia in first remission. Thirty-four patients received only intensive consolidation chemotherapy (SIC); 28 patients were scheduled to undergo an autologous bone marrow transplant (auto-BMT) and 44 patients an allogeneic BMT (allo-BMT). Twenty-seven of them were referred in first remission for allo-BMT. Nineteen patients achieved a complete remission after salvage treatment. All other patients obtained a remission after one or two courses of a standard combination of cytosine arabinoside and daunorubicin. Except for the patients who were referred in remission, all patients received intermediate dose cytosine arabinoside and amsacrine as a first consolidation treatment. The median ages of the three groups were 48 (SIC), 39 (auto-BMT) and 33 years (allo-BMT). Two patients relapsed before auto-BMT and 1 before allo-BMT. The median interval from the date of complete remission to the auto- or allo-BMT was 3 months. In total, 80% of the patients of the SIC group relapsed, compared to 50% of the patients belonging to the auto-BMT group and 35% of the 44 patients who were scheduled to receive an allo-BMT. The overall median disease-free survival was 14 months, 30% of the patients being alive and disease-free at 3 years. The disease-free survival rate at three years was 25% for the SIC group, 30% for the allo-BMT group and 40% for the ABMT group (P=0.45). Our study shows no benefit for bone marrow transplantation over intensive consolidation treatment. However, large randomized trials are required to define the real value of these treatment modalities.