Bone metabolism in male patients with type 2 diabetes

Few reports are available on bone turnover in type 2 diabetes. Impaired bone turnover in type 2 diabetes appears to result from decreased bone formation. Studies also suggest that poor glycaemic control in type 2 diabetes may contribute to osteopaenia. The aim of this study was to investigate biochemical markers of bone turnover in males with poorly controlled type 2 diabetes and look for correlations with glycaemic control and gonadal and hypophyseal hormonal axis. Consecutive male patients with poorly controlled type 2 diabetes and attending the internal medicine department during a period of 6 months were enrolled. The patients were receiving oral hypoglycaemic agents (metformin or sulphonylureas or both). None of the patients had any evidence of macroangiopathy, nephropathy or neuropathy. Only two patients had proliferative retinopathy. Serum osteocalcin, crosslaps (C-telopeptide, CTx), parathyroid hormone (PTH), testosterone, oestrogen, prolactin, follicle-stimulating hormone (FSH) and luteinising hormone (LH) were measured in 35 patients and 35 controls. The mean age of the study population was 53.7 (10.3) years (range: 50.2–57.3) and the mean disease duration was 8.6 (6.0) years (range: 6.5–10.7). No differences between patients and controls were observed in serum calcium, phosphorus, creatinine, albumin, PTH, CTx, oestrogen, testosterone, LH, FSH, prolactin and urinary calcium. Patients had lower serum levels of osteocalcin than controls with a significant statistical difference [15.3 (4.1) vs 18.3 (5.3), p=0.012]. There was a negative significant statistical correlation between CTx levels and HbA1c (r=–0.41, p< 0.05). Our study suggested that bone formation is altered in type 2 diabetes and that bone turnover is affected by glycaemic control status.     

Running has a negative effect on bone metabolism and proinflammatory status in male aged rats

Animal models for male osteoporosis are scarce. This study aimed at identifying the impact of different living conditions on bone structure and metabolism as well as the inflammatory status in a rat model of age-related male osteoporosis. Bone mineral density, bone histomorphometric data, ex vivo osteoclast generation, and bone metabolism serum marker as well as intracellular cytokine expressions were evaluated in 23-month-old male Sprague-Dawley rats subjected to different housing conditions from the age of 5 months. Running rats were housed individually and were exercised voluntarily in running wheels attached to their cages. Dieting rats were housed individually, too, but were fed to pair weight with the running rats. Walking rats were exercised mildly by use of a treadmill (800m/day, 5 days a week) and social rats were kept as four in a cage and fed ad libitum. Whereas no marked differences could be found for bone mineral density, trabecular bone volume as well as trabecular bone surface were diminished in walking rats. The ex vivo osteoclast generation assay revealed no significant differences between groups. Osteoblasts of running rats were not only decreased in number, but displayed also a lower activity as indicated by decreased serum osteocalcin levels. Osteoclast activity was increased in the same group as indicated by elevated CTX (c-terminal telopeptide of type I collagen) levels. Additionally, production of tumor necrosis factor (TNF)-alpha and interferone (IFN)-gamma by CD8(+) T cells was elevated in running rats. In conclusion, running has a negative effect on bone metabolism and proinflammatory status in male aged rats.     

睾酮与雄性大鼠骨质疏松关系的实验研究

目的　探讨睾酮在男性骨质疏松中所起的作用及机理。方法　采用１５ 周龄雄性ＳＤ大鼠去睾后作为骨质疏松动物模型，随机分为２ 组：正常对照组（Ｎ）、去睾模型组（ＯＰ） ，术后２８ 周统一处死，行血尿生化、骨密度（ＢＭＤ）、骨生物力学及病理检查。结果　与正常组比较，模型组大鼠血清睾酮水平明显下降（Ｐ＜０ ．０１），雌二醇水平增高，但无显著差异（ Ｐ＞ ０．０５）。生化检查结果示模型组大鼠骨形成指标血清碱性磷酸酶显著降低（ Ｐ＜ ０ ．０５）；骨吸收指标———２４ 小时尿羟脯氨酸浓度／肌酐与尿钙／ 肌酐显著增高（ Ｐ＜０ ．０５）。应用ＤＥＸＡ 与ＳＰＡ法分别测定大鼠全身及股骨中点ＢＭＤ，发现模型组大鼠均明显下降（ Ｐ＜ ０．０５） 。骨生物力学测定发现，反映模型组大鼠的股骨整骨强度的指标———最大受力负荷及反映股骨整骨能承受的最大形变的指标———最大挠度均显著下降（ Ｐ＜ ０ ．０５） 。骨形态计量学测定发现模型组大鼠骨小梁体积、骨表面面积／ 体积比、平均骨小梁厚度显著下降（Ｐ＜０ ．０１），说明模型组大鼠骨小梁普遍变薄变细甚至断裂穿孔。据此，雄性大鼠去势２８ 周后已经形成了雄激素缺乏而引起的骨质疏松症。由此推断雄激素在体内不仅可转换为雌     

甲状旁腺激素及其拟似剂治疗骨质疏松症的研究进展

甲状旁腺激素(PTH)目前已作为一种促骨合成药物,用于骨质疏松症的临床治疗。它所发挥的生物学效应取决于其作用模式和剂量,即间断小剂量使用能增加骨形成,而大剂量持续使用则加速骨吸收使骨量减少。PTH对骨代谢调节的确切机制尚未阐明,大量研究工作力图从各个层面寻找PTH治疗骨质疏松的效应模式及机制,以便使其更安全有效地应用于临床,本文对目前的研究进展作综述。     

血管生成在骨代谢及骨质疏松症中的作用研究进展

目前,骨质疏松症(OP)的防治主要集中于抑制骨吸收,但其局限性已显现。近年文献报道,血管生成与OP关系密切,而且发现血管生成与骨代谢间存在特定的"耦合"关系。血管生成,尤其是H型血管,可能通过影响骨形成、骨吸收及骨重塑进程的方式,在OP发生、发展及防治过程中发挥着重要的调节作用。本文重点梳理血管生成与骨代谢和OP之间的...     

Understanding the mechanisms of senile osteoporosis: new facts for a major geriatric syndrome

Knowledge of the underlying mechanisms of osteoporosis in older adults has significantly advanced in recent years. There is an acute loss of bone mineral density in the peri-menopausal period, followed by a more gradual and progressive decline, which is also seen in men. Markedly increased bone resorption leads to the initial fall in bone mineral density. With increasing age, there is also a significant reduction in bone formation. This is mostly due to a shift from osteoblastogenesis to predominant adipogenesis in the bone marrow. This study reviews new evidence on the pathophysiology of senile osteoporosis, with emphasis upon the mechanism of action of current osteoporosis treatments. New potential treatments are also considered, including therapeutic approaches to osteoporosis in elderly people that focus on the pathophysiology and potential reversal of the adipogenic shift in bone.     

多项骨代谢指标与老年男性骨质疏松关系的研究

目的：探讨与老年男性骨质疏松发生有关的骨代谢指标变化特点及意义。方法：采用放射免疫分析法对58例老年男性骨质疏松和37例骨量减少患者进行血清白细胞介素1β（IL－1β）,胰岛素样生长因子II（IGF－II）,甲状旁腺素中段（PTH－M）和25－羟基维生素D（25－OH－D）的含量和骨密度检测,同时与青中年和老年健康人进行比较。结果：老年男性骨质疏松和骨量减少患者IL－1β和PTH－M水平不同程度高于对照组（P＜0．01）,IGF－II和25－OH－D水平均较对照组明显降低（P＜0．01）,随着年龄增长的病情加重,两组患者骨密度均明显低于青中年对照组（P＜0．01）,老年男性骨质疏松组骨密度明显低于骨量减少组（P＜0．05）,结论：细胞因子等骨代谢指标紊乱是造成老年男性以骨吸收大于骨形成为特点的骨质疏松症的重要。     

Bone remodelling in osteoporosis

Bone remodelling, a highly regulated succession of events, is the temporal sequence of osteoclastic bone resorption and osteoblastic bone formation. Bone loss with age and in osteoporotic patients is due to a desequilibrium between both processus. Bone histomorphometry was the method used to measure these events. Its shows clearly that, with age, the quantity of bone formed in one remodelling unit (so called mean wall thickness) decreases. In osteoporotic women, compared to control women of the same age the amount of bone formed is also decreased. Concordant data on this point have been obtained in different laboratories. By contrast, the cellular mechanism underlying this decreased amount of bone formed is largely controversial: a decreased osteoblast recruitment or life span or capacity to synthetise collagen have been suggested. Bone loss with age is associated with an increase in the amount of bone resorbed. This observation is the result of an indirect measurement founded on the distance between trabeculae. As the decreased bone formation, this processus is exaggerated in postmenopausal osteoporosis. The respective importance of decreased bone formation and increased bone resorption is however difficult to assess. Some osteoporotic patients have increased bone resorption surfaces compared to control women on their bone biopsy; however, it does not seem that these patients form a definite subgroup of osteoporotic patients as the extent of resorption surfaces changes with time in an untreated osteoporotic. In conclusion, the observed changes in bone remodelling in osteoporotic postmenopausal women are an exaggeration of those observed during ageing. These changes should be a basis for a coherent therapy of bone loss in osteoporotic patients.     

抗酒石酸酸性磷酸酶测定及在骨质疏松症诊断中的应用

目的：建立抗酒石酸酸性磷酸酶测定方法及在原发性骨质疏松症诊断中的临床应用。方法：以1－萘酚磷酸为基质,测定肝素抗凝血抗酒石酸,氟化物抑制酸性磷酸酶,并以双能X线骨密度仪测定戎腰椎2－4的骨密度,结果：抗酒石酸酸性磷酸酶测定方法在本地区老年妇女的参考值为2．9－5．3U／L,该方法的平均批内和批间变异分别为2．7％和5．0％,骨质疏松症该酶活性明显高于健康对照组（P＜0．001）,并与骨密度测定呈显著的相关性（r=0.82),结论：抗酒石酸性磷酸酶测定方法简便,快速,是早期原发性骨质疏松症的筛选,诊断及观察疗效的敏感指标。     

葡萄糖对大鼠骨髓破骨细胞骨吸收功能的影响

目的 观察葡萄糖对大鼠骨髓破骨细胞骨吸收功能的影响,探讨糖尿病骨质疏松的发病机制.方法 用巨噬细胞集落刺激因子、RANKL诱导大鼠骨髓单个核细胞分化为破骨细胞,同时给予不同浓度的葡萄糖(0、5.5、15、25 mmol/L)干预,通过观察骨吸收陷窝数量和面积比及破骨细胞膜表面整合索αvβ3(CD61)表达水平分析葡萄糖对破骨细胞骨吸收功能的影响.结果 (1)高糖(25 mmoL/L)组培养7 d骨吸收陷窝数量和面积比与其他3组相比明显增多(P＜0.05或P＜0.01).(2)高糖组破骨细胞膜表面CD61表达量及平均荧光强度3 d时与其他3组相比均明显上调(P＜0.05或P＜0.01);5、7 d时与对照组(0 mmol/L)相比明显上调(P＜0.05).结论 高糖可增强破骨细胞的骨吸收功能,这可能是糖尿病骨质疏松的发病机制之一.     

降钙素治疗老年骨质疏松症的临床研究

目的　观察鲑鱼降钙素对老年骨质疏松症的治疗效果。　方法　将经双能X线骨密度仪 (DEXA)测定确诊为骨质疏松且有临床症状的老年患者 86例分成两组 ,鲑鱼降钙素组 4 6例 ,予以鲑鱼降钙素肌肉注射 ,每天 1次 10 0IU ,连用 3d后 ,改为 5 0IU隔天 1次 ,连用 1个月 ,间歇 1个月后再重复 ,共半年 ,同时加服钙尔奇D每天 1片 ;对照组 4 0例 ,单纯口服钙尔奇D每天 1片 ,疗程半年 ,两组治疗前后均测定 1～ 4腰椎 (L1-4)及股骨近端骨密度 (BMD) ,治疗后记录临床症状。　结果　鲑鱼降钙素组较对照组骨痛症状缓解 (91 3%和 4 7 5 % )效果明显 (P <0 0 1) ,鲑鱼降钙素组腰椎BMD (0 78± 0 12 ) g/cm2 较治疗前 (0 73± 0 10 ) g/cm2 有所升高 (P <0 0 5 ) ,股骨近端BMD变化不明显 ;对照组BMD无明显改变。　结论　鲑鱼降钙素与钙剂联合对治疗老年骨质疏松患者有缓解临床症状及增加腰椎BMD的作用。     

Site-specific bone loss in senescence-accelerated mouse (SAMP6): A murine model for senile osteoporosis

The senescence-accelerated mouse strain P6 (SAMP6) is a model of senile osteoporosis, which possesses many features of senile osteoporosis in humans. So far, little is known about the systemic bone microstructural changes that occur at multiple skeletal sites. In this study, we therefore, investigated site (vertebra, femur and tibia) dependence of bone microstructure and bone mineral density (BMD) in SAMP6 and the normal control mouse (SAMR1) at 5 and 12 months of age using quantitative micro computed tomography (micro-CT) and image analysis software. As compared with SAMR1, the most prominent change in SAMP6 was the reduction of vertebral trabecular bone volume fraction (BV/TV) and trabecular BMD. Moderate decrease of trabecular bone mass was observed in the proximal tibia and distal femur. Increased marrow area and periosteal perimeter were investigated, though the cortical area and cortical thickness had no marked changes in the mid-tibial and mid-femoral cortical bones. These results indicate that bone microstructural properties in SAMP6 are remarkably heterogeneous throughout the skeleton, which is analogous to changes that occur in human bones. These findings further validate the relevance of SAMP6 as a model of senile osteoporosis.     

糖皮质激素诱导骨质疏松机制的研究进展

骨吸收增加是糖皮质激素诱导骨质疏松的原因之一,但近年来的研究证实糖皮质激素通过Wnt、丝裂原活化蛋白激酶、转化生长因子-β等信号途径抑制成骨细胞的增殖、分化;刺激cas-pase-3表达而促进成骨细胞凋亡;抑制胶原合成相关基因的表达而减少胶原合成,同时促进基质胶原蛋白酶的表达,促进胶原分解;激活11β-羟类固醇脱氢酶,促进非活性和活性类固醇之间的转化,增强糖皮质激素的作用,影响成骨细胞的增殖、分化及其功能,从而使骨形成减少导致骨质疏松。     

老年男性骨质疏松症患者口服阿仑膦酸钠的依从性分析

  目的 调查老年男性骨质疏松症患者口服阿仑膦酸钠的依从性,探讨影响服药依从性的相关因素。方法 入选2011年1—6月在解放军总医院门诊确诊骨质疏松症并开始口服阿仑膦酸钠治疗的老年男性患者145例,调查其服该药1年的依从性,根据药物占有率（MPR）分为依从性好组（MPR≥80%）和差组（MPR<80%）,比较两组差异,分析影响依从性的因素。结果 随访到139例患者,其中依从性好者32例（23.02％),依从性差者107例（76.98％);对筛选出的影响服药依从性的因素进行logistic回归分析,结果显示,骨痛(OR值0.69,P=0.043)、无人提醒用药（OR值1.37,P=0.025）、担心药物副作用(OR值1.49,P=0.018)、服药种类＞7种(OR值1.30,P=0.036)、不清楚远期疗效(OR值1.39,P=0.021)为影响服药依从性的因素。结论 老年男性骨质疏松症患者口服阿仑膦酸钠治疗的依从性差;降低服药依从性的因素有：无人提醒服药、担心药物副作用、服药种类＞7种和不清楚远期疗效;骨痛可提高患者服药依从性。     

老年男性慢性阻塞性肺疾病患者骨代谢与骨密度的关系

目的　探讨老年男性慢性阻塞性肺疾病 (COPD)患者继发性骨代谢与骨密度 (BMD)变化的原因、临床特点及相互关系。方法　根据COPD肺功能诊断标准将 5 0例老年男性稳定期单纯COPD患者分为中度组和重度组 ,另设老年男性健康对照组 3 0例。检测并分析血气分析 ,BMD ,骨矿含量 (BMC) ,与骨吸收和骨形成有关的血、尿骨代谢生化指标的变化。结果　中、重度组患者的BMD和BMC较健康对照组明显降低 (P <0 .0 5或 0 .0 1) ,其中 ,重度组BMD、BMC的降低与氧分压降低明显相关 (r =0 .48～ 0 .5 3 ,P <0 .0 1)。骨吸收指标中尿钙 /肌酐比值明显升高 (P <0 .0 1) ;骨形成指标血清Ⅰ型前胶原羧基端前肽 ,碱性磷酸酶 ,骨钙素 ,2 5 (OH)D3 和雌二醇均明显升高 (P <0 .0 1或 0 .0 5 )。结论　根据WHO有关骨质疏松 (OP)诊断标准 ,多数老年男性COPD患者主要表现为骨量减低 ,很少发生OP ,这可能与机体代偿性对抗OP发生有关。其骨代谢特点与高转换Ⅰ型OP相似 ,与原发性老年男性Ⅱ型OP不同。治疗原发病 ,改善COPD患者缺氧状态可能是一种重要的防治方法。     

辛伐他汀对骨质疏松大鼠骨形成作用研究

目的　探讨他汀类药物对绝经后骨质疏松症骨形成的刺激作用和药理机制。方法　 54只 SD雌鼠随机分为 3组 :去势后给药实验组 ,去势组和对照组 ,观察术后 4、1 0和 1 6 w骨形成指标 :骨钙素 (BGP) ,骨特异碱性磷酸酶 (骨 AKP)和总碱性磷酸酶 (总 AKP) ;骨吸收指标 :尿呲啶醚 (PYD)和脱氧呲啶醚 (DPD)。同步用 IBAS计算机全自动图像分析系统对不脱钙骨组织动态观测骨形态计量学参数。结果　给药实验组在去势后 4～ 1 6 w BGP和骨 AKP明显高于单纯去势组 (分别为 P<0 .0 0 1和 P<0 .0 5) ,而尿 PYD和 DPD两组间无显著差异 (P>0 .0 5)。骨形成表面(FS)和骨小梁体积 (TBV) ,骨小梁平均厚度 (MTT)较去势组明显升高 ,尤其是 TBV和 FS(分别为 P<0 .0 0 1和 P<0 .0 1 ) ,这种差异在第 1 0周最为显著。随着给药时间的延长 (第 1 6周 ) MAR逐渐增加 (P<0 .0 0 1 )。 RS与去势组比较在所有实验周均无差异。结论　辛伐他汀可刺激骨质疏松大鼠成骨细胞活跃增生 ,促进骨形成与骨转换速率 ,并可使骨质疏松症骨组织形态改善。     

老年男性骨质疏松症患者骨密度和生化指标的变化

目的：了解老年男性骨质疏松症患者骨密度和骨代谢生化指标变化的特点。方法：对30例老年男性骨质疏松症患者进行腰椎（L2－4）骨密度（BMD）、骨矿含量（BMC）、血和尿骨代谢生化指标的测定,并与对照组进行比较。结果：骨质疏松（OP）组的BMD和BMC均显著小于对照组,分别比对照组下降21．6％和25％;OP组骨形成指标血清碱性磷酸酸（ALP）和C端骨钙素（BGP）明显高于对照组,分别上升25．4％和222％;骨吸收指标尿羟脯氨酸与肌酐的比值（HOP／Cr)和Ⅰ型胶原N－末端肽与肌酐的比值（INTX／Cr)明显高于对照组,分别上升22．6％和223％。OP组血清T水平明显低于对照组,两组血清25－羟维生素D3（25－OH－D3）均在正常低限或低于正常水平。结论：腰椎（L2－4）BMD和BMC是诊断男性骨质疏松症的主要依据;老年男性骨质疏松症患者一部分人属于骨代谢高转换型;雄激素对老年男性骨量的维持起重要作用;老年男性维生素D缺乏质疏松症发生的重要基础。     

Comparison of the effect of alendronate on lumbar bone mineral density and bone turnover in men and postmenopausal women with osteoporosis

The purpose of the present study was to compare the effect of alendronate treatment on lumbar bone mineral density (BMD) and bone turnover in men and postmenopausal women with osteoporosis. Sixty men with primary or secondary osteoporosis and 318 women with postmenopausal osteoporosis were treated with alendronate. The primary end points were lumbar BMD and urinary cross-linked N-terminal telopeptides of type I collagen (NTX) and serum alkaline phosphatase (ALP) levels. The secondary end point was the incidence of vertebral and nonvertebral fractures. Forty-seven (78.3%) men and 254 (79.9%) women who could complete the 12-month trial were analyzed. The mean ages of men and postmenopausal women were 69.1 and 70.4 years, respectively. Both men and postmenopausal women showed higher levels of urinary NTX as compared with normal range of premenopausal women. Alendronate treatment decreased urinary NTX level by 39.2% in men and 45.4% in postmenopausal women at 3 months and serum ALP level by 17.8 and 21.0%, respectively, at 12 months. Following reduction in bone turnover markers, lumbar BMD increased 5.8 and 7.6% in men and postmenopausal women, respectively, at 12 months. Reduction in urinary NTX level and increase in lumbar BMD were smaller in men than in postmenopausal women. The incidence of vertebral and nonvertebral fractures was 10.6 and 8.5%, respectively, in men and 8.3 and 7.5%, respectively, in postmenopausal women, with no significant difference in these incidences between them. These results suggested that alendronate treatment effectively increased lumbar BMD from baseline in men with primary or secondary osteoporosis following reduction in bone turnover, although its efficacy did not appear to be greater than in postmenopausal women with osteoporosis. We have no funding sources; we have no conflict of interest.     

老年妇女不同骨骼部位的骨丢失及其对诊断骨质疏松症的评价

目的评价老年妇女随增龄骨骼各部位骨丢失和骨质疏松症（ＯＰ）的发生率。方法采用扇形束双能Ｘ线骨密度仪测量３６１例老年妇女腰椎正侧位、股骨和桡骨的骨密度。结果６０～６４岁组各部位骨量比峰值骨量平均减少（２８．３±７．４）％,Ｗａｒｄ＇ｓ区和腰椎侧位中间区减少最多（分别减少４４．７％和３５．９％）,桡骨远端中段和股骨颈骨丢失率最少（分别丢失２０．６％和２１．６％）。７０岁以前的老年妇女腰椎侧位是诊断ＯＰ的敏感部位,随年龄增长股骨和桡骨的ＯＰ检出率迅速增高。结论老年妇女不同骨骼部位骨丢失方式和丢失率存在明显差别。测量的部位不同ＯＰ检出率不同,随年龄增长ＯＰ检出率也不同。