羟乙膦酸钠对支睾丸大鼠骨代谢的影响

目的：通过骨组织形态计量学方法观察药物羟乙磷酸钠对去睾丸大量代谢的影响。方法：30只3．5月龄SD雄性大鼠,随机分成基础对照组,年龄对照组,去睾丸组和去睾丸后加羟乙膦酸钠组,前3组每日生理盐水5ml,kg^-1,羟乙膦酸钠（邦得林）组每日36mg.kg^-1,灌胃90d,实验结束,取胫骨近心端行不脱钙骨制片进行骨组织形态计量学分析。结果：去睾丸90d大鼠的骨量与年龄对照组相比明显下降（骨小梁面积百分率降低了50％）,羟乙膦酸钠用药组骨量明显高于去睾丸组（骨小梁面积百分率增加了92％）,达到年龄对照组的水平,但未达到基础对照组的水平,结论：羟乙膦酸钠能防止大鼠去睾丸引起的骨丢失,但未能完全克服增相关的骨丢失。     

阿仑膦酸钠和甲状旁腺素对糖皮质激素性骨丢失的作用

目的比较并探讨甲状旁腺素和阿仑膦酸钠治疗糖皮质激素性骨质疏松(GIOP)的疗效和作用机制。方法动物实验:将40只9月龄雄性SD大鼠分为对照组:0.9%氯化钠注射液皮下注射;糖皮质激素(GC)组:甲泼尼龙琥珀酸钠2.5mg/kg·d皮下注射;GC+双膦酸盐组:甲泼尼龙琥珀酸钠2.5mg/kg·d皮下注射+阿仑膦酸钠4mg/kg·d灌胃;GC+甲状旁腺激素(PTH)组:甲泼尼龙琥珀酸钠2.5mg/kg·d皮下注射+rPTH80μg/kg·d皮下注射。所有动物喂养3个月后处死。采用双能X线骨密度仪检测大鼠腰椎和股骨骨密度,用骨形态计量学方法分析大鼠股骨力学参数,收集外周血检测抗酒石酸酸性磷酸酶和骨钙素。细胞实验:将原代培养大鼠成骨细胞分为对照组;GC组:地塞米松(Dex)10-5mol/L;阿仑膦酸钠(ALN)组:ALN10-7mol/L;PTH组:人重组PTH1-3410-7mol/L;GC+ALN组:Dex10-5M+ALN10-7mol/L;GC+PTH组:Dex10-5mol/L+PTH10-7mol/L;分别采用MTT、碱性磷酸酶活性检测和茜素红染色法观察各组成骨细胞的增殖、分化和矿化情况;采用Real-timePCR检测各组成骨细胞FGF23和SOST基因表达情况。结果动物实验结果显示,GC组大鼠腰椎骨密度(0.232±0.021)和股骨骨密度(0.203±0.018)较各自对照组(0.247±0.03和0.226±0.037)明显降低(P<0.05);GC+ALN组股骨骨密度(0.224±0.03)和GC+PTH组腰椎骨密度(0.271±0.018)较GC组明显升高(P<0.05)。与对照组相比,GC组骨小梁容积、骨形成率、矿化沉积率和血BGP明显降低(P<0.05),破骨细胞表面积和血TRAP5b明显升高(P<0.05)。GC+PTH组骨小梁容积显著增加(P<0.05),GC+ALN组骨小梁容积与对照组持平。与GC组相比,GC+PTH组骨形成率和血BGP明显升高(P<0.05),GC+ALN组矿化沉积率升高(P<0.01),破骨细胞表面积和血TRAP5b降低(P<0.05)。细胞实验结果显示,GC可降低成骨细胞的增殖率和碱性磷酸酶活性,减少矿化结节形成(P<0.05),GC+PTH和GC+ALN使碱性磷酸酶活性升高至对照组水平,但PTH能著抑制矿化,ALN促进矿化。Realtime-PCR结果提示经GC干预后骨硬化蛋白(SOST)和纤维生长因子23(FGF23)表达显著升高(P<0.05),PTH抑制SOST表达(P<0.01),ALN抑制SOST和FGF23的表达(P<0.05)。结论过量GC可增加SOST和FGF23表达,与糖皮质激素性骨质疏松的骨形成降低和骨矿化受损有关。PTH和ALN可提高骨量,改善骨强度;PTH可降低SOST表达,促进骨形成;ALN可降低FGF23表达,促进骨矿化。     

阿仑膦酸钠对老年男性骨质疏松症骨密度的影响

目的　探讨阿仑膦酸钠对老年男性骨质疏松症腰椎骨密度 (BMD)的影响。　 方法　筛选了 10 0例老年男性骨质疏松患者 ,采用美国GE公司的LUNAREXPERT XL型双能X线骨密度测定仪进行BMD测定。入选的患者腰椎 (L2～ 4 )BMD均低于峰值的 2 5个标准差或以下。随机分成治疗组 5 0例 ,对照组 5 0例。治疗组给予阿仑膦酸钠 10mg·d-1,联合用钙尔奇D 6 0 0mg·d-1;对照组单用钙尔奇D 6 0 0mg·d-1,观察 12月。每 6月做 1次腰椎、髋部的BMD测定。以腰椎 (L2～ 4 )BMD为比较指标。　 结果　治疗组在治疗后 6月和 12月腰椎BMD增加分别为2 10 %和 3 2 0 % ,与治疗前比较有统计学差异 (P <0 0 5和P <0 0 1)。对照组在治疗后 6月和 12月腰椎BMD增加分别为 0 91%和 1 0 6 % ,与治疗前比较无统计学差异。消化道不良事件 2组相似。　 结论 　阿仑膦酸钠使腰椎BMD获显著性的进行性上升     

阿仑膦酸钠治疗男性原发性骨质疏松症临床研究

目的 探讨骨吸收抑制剂阿仑膦酸钠对男性原发性骨质疏松症骨密度和骨转换生化指标的影响.方法 2005年1月至2007年1月前瞻性纳入北京协和医院诊断的20例男性原发性骨质疏松症患者,以20名正常男性为对照.骨质疏松症患者每周服用阿仑膦酸钠70 mg,且每日服用钙尔奇D 1片,疗程为18个月.每6个月采用双能x线骨密度仪测量腰椎和股骨近段骨密度,每3个月测量骨形成指标碱性磷酸酶和骨吸收指标Ⅰ型胶原羧基末端肽.正常男性不予干预,研究开始时和18个月时检查腰椎和股骨近端骨密度.结果 骨质疏松症组治疗前骨密度明显低于正常对照组.阿仑膦酸钠组治疗18个月时,与治疗前比较,腰椎、股骨颈、大转子、全髋和股骨干骨密度值增加6.3%、2.5%、5.8%、3.5%及4.2%(P均<0.05).骨转换生化指标碱性磷酸酶(ALP)和CTX治疗6个月时即显著下降,此后维持在较低水平,治疗18个月后ALP降低33.6%,CTX下降66.7%(P均<0.01).骨吸收指标较骨形成指标下降更明显.患者对阿仑膦酸钠的耐受性良好.正常对照组骨密度和血ALP在18个月期间无明显变化.结论 与对女性骨质疏松症患者疗效相似,阿仑膦酸钠能够明显增加男性原发性骨质疏松症患者的骨密度、降低骨转换生化指标,且安全性良好.     

阿仑膦酸钠治疗老年男性骨质疏松的效果

目的观察阿仑膦酸钠治疗65岁以上男性骨质疏松患者的疗效和安全性。方法采用前瞻性随机研究方法,将80例65岁以上男性OP患者随机分为治疗组和对照组,治疗组给予阿仑膦酸钠治疗,对照组给予维D钙咀嚼片治疗,疗程均为12个月,检测两组患者治疗前后的骨密度(BMD)和肝肾功能及血脂各项指标,评价临床疗效及药物的不良反应,骨痛采用视觉模拟评分法(VAS)对疼痛分级。结果治疗后治疗组患者BMD较治疗前及对照组有明显提高(P0.05),VAS疼痛评分治疗组较对照组明显减低(P0.05);肝肾功能和血脂各项指标治疗组与对照组无明显变化。治疗组临床疗效优良率(92.5%)显著高于对照组(62.5%)。结论阿仑膦酸钠能显著增加腰椎骨BMD,明显减轻疼痛,能有效降低破骨细胞活性,抑制骨破坏,显著提高骨量,而且不影响肝肾功能,具有较好的安全性和依从性,是老年男性OP患者的首选。     

运动康复联合阿仑膦酸钠对老年骨质疏松患者的干预效果

目的探讨运动康复联合阿仑膦酸钠对老年骨质疏松(OP)患者的干预效果。方法选择老年OP患者240例,根据随机数字法分为对照组和运动康复组,每组120例。对照组给予阿伦磷酸钠治疗,运动康复组给予运动康复联合阿伦磷酸钠治疗,共12个月。干预前后,视觉模拟评分法(VAS)评估疼痛程度,测定骨密度(BMD)和血清总1型胶原氨基端前肽(P1NP)、骨钙素(BGP)、Ⅰ型胶原羧基端肽β特殊序列(CTX)、25-羟基维生素D[25(OH)D]水平。结果干预前,两组VAS评分、腰椎BMD和股骨近端BMD、血清P1NP、BGP、CTX、25(OH)D水平比较差异无统计学意义(P0.05)。干预后,两组VAS评分均明显低于干预前(P0.05),腰椎和股骨近端BMD均明显高于干预前(P0.05),血清P1NP、CTX水平明显低于干预前(P0.05),BGP、25(OH)D水平明显高于干预前(P0.05);运动康复组VAS评分明显低于对照组(P0.05),腰椎和股骨近端BMD明显高于对照组(P0.05),血清P1NP、CTX水平低于对照组(P0.05),BGP、25(OH)D水平明显高于对照组(P0.05)。结论运动康复可提高阿仑膦酸钠对老年OP患者的治疗效果。     

阿仑膦酸钠与舍曲林联合治疗对老年期抑郁症患者骨质量的影响

<正>老年期抑郁患者的药物治疗非常棘手。多数抗抑郁药物都存在加重老年病的副作用,尤其是会造成骨质疏松(OP),OP一旦形成就很难缓解〔1〕。本文拟观察阿仑膦酸钠联用舍曲林对老年期抑郁症患者骨质量的影响。1资料与方法1.1一般资料2012年6月至2013年12月吉林大学第一医院心理科老年抑郁症患者108例,65~82岁,平均68.2岁,符合中国精神障碍诊断和分类方案第三版(CCMD-3)抑郁症的诊     

阿仑膦酸钠联合骨松宝颗粒治疗老年女性骨质疏松的效果

目的 探讨倾向性评分匹配下阿仑膦酸钠联合骨松宝颗粒治疗老年女性骨质疏松(OP)的效果。方法 回顾性分析150例老年女性OP患者临床资料,其中85例采用阿仑膦酸钠治疗为对照组,65例接受阿仑膦酸钠联合骨松宝颗粒治疗为观察组,用倾向性评分匹配分析患者年龄、体重指数(BMI)、病程、合并糖尿病、合并高血压基线资料,采用近邻法进行1∶1匹配,经倾向性评分配比后,最终纳入观察组、对照组各30例。评估两组治疗6个月时的治疗效果,比较两组治疗前、治疗6个月时骨代谢指标[骨钙素(BGP)、Ⅰ型胶原β降解产物(β-CTX)]、骨密度T值(腰椎L1～4、股骨颈),统计两组治疗期间不良反应发生情况。结果 观察组治疗6个月时总体治疗效果优于对照组,且治疗总有效率高于对照组,差异有统计学意义(P<0.05);两组治疗6个月时BGP较治疗前升高,且观察组高于对照组,两组β-CTX水平均较治疗前降低,且观察组低于对照组,差异有统计学意义(P<0.05);两组治疗6个月时腰椎L1～4、股骨颈骨密度T值均较治疗前升高,且观察组高于对照组,差异有统计学意义(P<0.05);治疗期间,两组均无不良反应发生...     

阿仑膦酸钠对糖皮质激素导致骨质疏松防治作用的Meta分析

目的 评价阿仑膦酸钠防治糖皮质激素导致的骨质疏松(GIOP)的有效性和安全性.方法 检索PubMed、EMBASE、Cochrane Library、Web of Science、中国生物医学文献数据库(CBM)、万方数据库,收集有关阿仑膦酸钠与安慰剂比较防治GIOP的随机对照试验(RCT),依据Jadad评分评价纳入RCT的质量,采用RevMan 5.1进行统计分析.结果 纳入7篇文献,共1111例患者.Meta分析显示,与安慰剂相比,阿仑膦酸钠治疗12个月可增加腰椎和股骨颈的骨密度(BMD)[均数差(MD)＝3.35,95％ CI(2.67 ～4.02),P=0.000;MD=1.90,95％ CI(0.89 ～2.92),P=0.000],治疗24个月增加腰椎BMD[MD＝3.91,95％ CI(2.37 ～5.45),P＜0.000],但没有增加股骨颈BMD[MD=1.91,95％ CI(-1.15 ～5.02),P＝0.22].在降低椎骨和非椎骨骨折风险方面与安慰剂相比差异无统计学意义[RR＝1.00,95％ CI (0.49 ～2.07),P=0.99;RR=1.02,95％ CI (0.49～2.14),P=0.95].阿仑膦酸钠与安慰剂相比不良事件发生率的差异无统计学意义[RR =0.97,95％CI (0.90～1.05),P＝0.47].结论 阿仑膦酸钠能增加患者腰椎和股骨颈BMD,且不良反应低,还没有证据表明可以降低骨折风险.今后,尚需要开展大样本RCT观察阿仑膦酸钠对股骨BMD的影响是否与用药时间有关以及进一步探索其能否降低骨折发生率.     

骨关节炎中软骨骨相互作用的研究进展

<正>近年来随着对骨关节炎（Osteoarthritis,OA）的研究不断深入,人们不再将骨关节炎看作以关节软骨退变、关节间歇狭窄为主的疾病,而是影响关节软骨、软骨下骨、滑膜、韧带、半月板、     

The effects of bone turnover rate on subchondral trabecular bone structure and cartilage damage in the osteoarthritis rat model

The effects of bone turnover rate on subchondral trabecular changes and cartilage destruction were evaluated in an iodoacetate-induced osteoarthritis rat model. Thirty female rats were randomly divided into three groups as the ovariectomized group, the no-treatment group and the bisphosphonate medication group. Arthritis was induced by a single intra-articular iodoacetate injection into the right tibiofemoral joint. Eight weeks after this injection, tibiofemoral joints on both sides were scanned with a micro-CT. Subchondral trabecular indices were measured on both sides of the tibial lateral condyle epiphysis. In the ovariectomized group, the percentage of bone volume, trabecular thickness and trabecular bone pattern factor of the arthritic sides were lower than those of the control sides, while trabecular separation and structure model index of the arthritic sides were higher than those of the control sides (p < 0.05). In the no-treatment group, only trabecular thickness of the arthritic sides was lower than in the control sides (p < 0.05). In the bisphosphonate medication group, trabecular indices were no different between the arthritic and control sides. Articular cartilage destruction and severity of arthritis increased significantly in the order: ovariectomized group < no-treatment group < bisphosphonate medication group (p < 0.05). After osteoarthritis development, severities of subchondral trabecular changes appeared to be strongly affected by bone turnover rate. Furthermore, a correlation was found between cartilage destruction severity and subchondral trabecular change in the intra-articular iodoacetate-injected osteoarthritis rat model.     

The effects of orally administered diacerein on cartilage and subchondral bone in an ovine model of osteoarthritis

OBJECTIVE: An ovine model of osteoarthritis (OA) induced by bilateral lateral meniscectomy (BLM) was used to evaluate in vivo effects of the slow acting antiarthritic drug diacerein (DIA) on degenerative changes in cartilage and subchondral bone of the operated joints. METHODS: Twenty of 30 adult age matched Merino wethers were subjected to BLM in the knee joints and the remainder served as non-operated controls (NOC). Half of the BLM group (n = 10) were given DIA (25 mg/kg orally) daily for 3 mo, then 50 mg/kg daily for a further 6 mo. The remainder of the meniscectomized (MEN) group served as OA controls. Five DIA, 5 MEN, and 5 NOC animals were sacrificed at 3 mo and the remainder at 9 mo postsurgery. One knee joint of each animal was used for bone mineral density (BMD) studies. Osteochondral slabs from the lateral femoral condyle and lateral tibial plateau were cut from the contralateral joint and were processed for histological and histomorphometric examination to assess the cartilage and subchondral bone changes. RESULTS: No significant difference was observed in the modified Mankin scores for cartilage from the DIA and MEN groups at 3 or 9 mo. However, in animals treated with DIA, the thickness of cartilage (p = 0.05) and subchondral bone (p = 0.05) in the lesion (middle) zone of the lateral tibial plateau were decreased relative to the corresponding zone of the MEN group at 3 mo (p = 0.05). At 9 mo subchondral bone thickness in this zone remained the same as NOC but BMD, which included both subchondral and trabecular bone, was significantly increased relative to the NOC group (p = 0.01). In contrast, the subchondral bone thickness of the outer zone of lateral tibial plateau and lateral femoral condyle of both MEN and DIA groups increased after 9 mo, while BMD remained the same as in the NOC. CONCLUSION: DIA treatment of meniscectomized animals mediated selective responses of cartilage and subchondral bone to the altered mechanical stresses induced across the joints by this procedure. While subchondral bone thickness in tibial lesion sites was reduced, cartilage and bone proliferation at the outer joint margins, a region where osteophyte formation occurred, were enhanced, suggesting that DIA supported the processes of repair and endochondral ossification.     

Articular cartilage repair using dedifferentiated articular chondrocytes and bone morphogenetic protein 4 in a rabbit model of articular cartilage defects

OBJECTIVE: To observe redifferentiation of dedifferentiated chondrocytes after transplantation into the joint, and to evaluate the ability of dedifferentiated chondrocytes transduced with adenovirus containing bone morphogenetic protein 4 (BMP-4) to redifferentiate in vitro and in vivo in a rabbit model of articular cartilage defects. METHODS: Monolayer and pellet culture systems were used to evaluate the redifferentiation of dedifferentiated chondrocytes transduced with BMP-4. A rabbit model of partial-thickness articular cartilage defects was used to evaluate cartilage repair macroscopically and histologically, 6 and 12 weeks after transplantation with first-passage, fifth-passage, or transduced fifth-passage chondrocytes. Histologic grading of the repaired tissue was performed. Expression of BMP-4 and the ability of transplanted cells to recover a chondrocytic phenotype were also assessed. RESULTS: BMP-4--expressing dedifferentiated chondrocytes recovered a chondrocytic phenotype in vitro. After transplantation into the joint, some of the dedifferentiated chondrocytes in the defect sites could undergo redifferentiation and formed matrix that displayed positive toluidine blue staining for glycosaminoglycans. Histologic scores of the regenerative tissue revealed significantly better cartilage repair in rabbits transplanted with BMP-4--expressing cells than in the other treatment groups. Staining with toluidine blue revealed expression of BMP-4 in the cells and in the matrix surrounding the cells. CONCLUSION: Some dedifferentiated chondrocytes can redifferentiate after transplantation into the load-bearing joint. BMP-4 can be used to induce redifferentiation of dedifferentiated chondrocytes in vitro and in vivo, which could help enhance articular cartilage repair.     

Apoptotic chondrocytes from osteoarthrotic human articular cartilage and abnormal calcification of subchondral bone

OBJECTIVE: Osteoarthrosis (OA) is accompanied by altered subchondral bone remodeling. We investigated the role of chondrocytes in the mechanism of abnormal cartilage calcification. METHODS: Knee articular cartilage samples from OA and normal tissue were studied. Macroscopic and microscopic observations, alkaline phosphatase staining for light and electron microscopy (bright and dark fields). TUNEL technique, electron diffraction, and x-ray microanalyses were performed. RESULTS: Chondrocytes from patients displayed a morphology of apoptosis and showed abundant alkaline phosphatase (ALP)-rich matrix vesicles (MV) budding from the plasma membrane with hydroxyapatite microcrystals on their surface. Farther from the cells, hydroxyapatite crystals were detected on the MV surface and increased as they approached the subchondral bone. The concentration of Ca and P and their ratio increased inside the ALP-rich MV in relation to the proximity to subchondral bone. In the OA subchondral bone the ratio Ca/P varied from 3.936 to 0.974. In normal tissue the ratio was very homogeneous (maximum 1.973, minimum 1.781). CONCLUSION: In situ, apoptotic chondrocytes correlate with factors known to be involved in the calcification of the extracellular matrix. This suggests that apoptosis is involved in the abnormal calcification of OA cartilage, and consequently in the altered remodeling of the subchondral bone.     

The role of subchondral bone remodeling in osteoarthritis: reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model

OBJECTIVE: It has been suggested that subchondral bone remodeling plays a role in the progression of osteoarthritis (OA). To test this hypothesis, we characterized the changes in the rat anterior cruciate ligament transection (ACLT) model of OA and evaluated the effects of alendronate (ALN), a potent inhibitor of bone resorption, on cartilage degradation and on osteophyte formation. METHODS: Male Sprague-Dawley rats underwent ACLT or sham operation of the right knee. Animals were then treated with ALN (0.03 and 0.24 microg/kg/week subcutaneously) and necropsied at 2 or 10 weeks postsurgery. OA changes were evaluated. Subchondral bone volume and osteophyte area were measured by histomorphometric analysis. Coimmunostaining for transforming growth factor beta (TGF beta), matrix metalloproteinase 9 (MMP-9), and MMP-13 was performed to investigate the effect of ALN on local activation of TGF beta. RESULTS: ALN was chondroprotective at both dosages, as determined by histologic criteria and collagen degradation markers. ALN suppressed subchondral bone resorption, which was markedly increased 2 weeks postsurgery, and prevented the subsequent increase in bone formation 10 weeks postsurgery, in the untreated tibial plateau of ACLT joints. Furthermore, ALN reduced the incidence and area of osteophytes in a dose-dependent manner. ALN also inhibited vascular invasion into the calcified cartilage in rats with OA and blocked osteoclast recruitment to subchondral bone and osteophytes. ALN treatment reduced the local release of active TGF beta, possibly via inhibition of MMP-13 expression in articular cartilage and MMP-9 expression in subchondral bone. CONCLUSION: Subchondral bone remodeling plays an important role in the pathogenesis of OA. ALN or other inhibitors of bone resorption could potentially be used as disease-modifying agents in the treatment of OA.