严重骨质疏松患者全膝关节置换术疗效分析

目的：探讨严重骨质疏松患者在进行人工全膝关节置换术时的特点和围手术期处理方法。方法：2005年至2007年期间,我科进行伴有严重骨质疏松症的人工全膝关节置换术患者共计36例41膝,其中单膝关节置换31例,双膝置换5例。所有病例入院前均采用双光能X线骨密度仪（DEXA）检测骨密度。所有病例均采用后稳定型膝关节假体。患者在术前给予钙尔奇D片及鲑鱼降钙素等抗骨质疏松治疗1月,术后继续给予抗骨质疏松治疗2~3月。结果：术后切口均一期愈合,无并发症。所有病例随访时间36~60个月,平均49个月。膝关节功能评分（HSS评分法）术前平均为37.2±6.4分,术后平均评分94.6±8.8分,随访期间未见假体早期松动影像学改变,骨密度复查较术前有明显改善。结论：对于伴有严重骨质疏松的病例,骨质已受到不同程度的破坏,进行假体选择的个体化,手术操作的精细化以及术后康复治疗具体化等对临床疗效至关重要。     

Notch Signaling in Osteocytes Differentially Regulates Cancellous and Cortical Bone Remodeling

Notch receptors play a role in skeletal development and homeostasis, and Notch activation in undifferentiated and mature osteoblasts causes osteopenia. In contrast, Notch activation in osteocytes increases bone mass, but the mechanisms involved and exact functions of Notch are not known. In this study, Notch1 and -2 were inactivated preferentially in osteocytes by mating Notch1/2 conditional mice, where Notch alleles are flanked by loxP sequences, with transgenics expressing Cre directed by the Dmp1 (dentin matrix protein 1) promoter. Notch1/2 conditional null male and female mice exhibited an increase in trabecular bone volume due to an increase in osteoblasts and decrease in osteoclasts. In male null mice, this was followed by an increase in osteoclast number and normalization of bone volume. To activate Notch preferentially in osteocytes, Dmp1-Cre transgenics were crossed with Rosa^Notch mice, where a loxP-flanked STOP cassette is placed between the Rosa26 promoter and Notch1 intracellular domain sequences. Dmp1-Cre^+/−;Rosa^Notch mice exhibited an increase in trabecular bone volume due to decreased bone resorption and an increase in cortical bone due to increased bone formation. Biomechanical and chemical properties were not affected. Osteoprotegerin mRNA was increased, sclerostin and dickkopf1 mRNA were decreased, and Wnt signaling was enhanced in Dmp1-Cre^+/−;Rosa^Notch femurs. Botulinum toxin A-induced muscle paralysis caused pronounced osteopenia in control mice, but bone mass was preserved in mice harboring the Notch activation in osteocytes. In conclusion, Notch plays a unique role in osteocytes, up-regulates osteoprotegerin and Wnt signaling, and differentially regulates trabecular and cortical bone homeostasis.     

The effect of dehydroepiandrosterone administration on intestinal calcium absorption in ovariectomized female rats

[Purpose] Dehydroepiandrosterone (DHEA) administration reportedly recovers osteoporosis, a bone disorder associated with bone deficiency in postmenopausal women. However, the physiological mechanism of DHEA in osteoporosis remains elusive, especially in terms of intestinal calcium absorption. Therefore, we investigated the effect of DHEA administration on calcium absorption in ovariectomized (OVX) female rats using an estrogen receptor antagonist.[Methods] Female Sprague-Dawley rats (n=23, 6 weeks old) were randomized into three groups: OVX control group (OC, n=7), OVX with DHEA treatment group (OD, n=8), and OVX with DHEA inhibitor group (ODI, n=8) for 8 weeks.[Results] Intestinal calcium accumulation, as well as the rate of absorption, demonstrated no significant differences during the experimental period among investigated groups. The bone mineral density (BMD) of the tibia at the proximal metaphysis was higher in the OD group than that in the OC group (p<0.05); however, BMD of the ODI group showed no significant difference from investigated groups. Furthermore, the BMD of the tibia at the diaphysis did not significantly differ among these groups.[Conclusion] We revealed that DHEA administration does not involve intestinal Ca absorption, although this treatment improves BMD levels in OVX rats. These observations indicate that the effect of DHEA on the bone in postmenopausal women is solely due to its influence on bone metabolism and not intestinal calcium absorption.     

北京海淀部分人群骨质疏松流行病学及相关危险因素研究

目的:探讨当前北京市海淀区部分人群骨质疏松相关危险因素。方法:选择我院2018年1月至6月的346例体检人群,采用双能X线吸收仪进行髋部骨密度检查,统计受检者身高、体重和体重指数,并通过自制问卷调查获取既往基础病史、药物使用史及日常生活习惯等相关信息。统计骨质疏松患病率,并筛查其相关危险因素。结果:当前人群的总体骨质疏松患病率为26.8%,女性达35.3%;骨量异常人群占69.5%。对于全部人群,高龄、饮用咖啡和碳酸饮料是骨质疏松危险因素(OR 1.098,95%CI1.072-1.125;OR 3.576,95%CI 1.302-9.826;OR 5.407,95%CI 1.317-22.202)。对于男性,年龄、激素使用和饮用咖啡是骨质疏松危险因素(OR 1.103,95%CI 1.065-1.142;OR 127.924,95%CI 10.045-999.999;OR 11.863,95%CI 2.969-47.400)。对于女性,年龄是骨质疏松的危险因素(OR 1.088,95%CI 1.059-1.117)。结论:当前北京市海淀区部分中老年人群具有较高的骨质疏松患病率,高龄和不良生活习惯是骨质疏松的相关危险因素,高体重是骨质疏松的保护因素。超过60岁的中老年人,特别是高危人群,应及早进行骨密度筛查、健康宣教、抗骨质疏松综合性治疗。     

补骨脂素对乳鼠颅骨成骨细胞分化成熟的影响

骨质疏松症是一种全身性骨骼疾病,其特点是骨量低、骨微结构恶化、骨脆性增加、易骨折。为了改善骨质疏松,需要寻找合成代谢和口服药物的副作用最小的替代药物。补骨脂素是从中草药中提取的香豆素衍生物。然而,补骨脂素在成骨细胞功能中的作用及其分子机制尚不清楚。本研究发现,补骨脂素通过上调成骨细胞特异性标志基因(包括icollagen,骨钙素和骨唾液蛋白)的表达,增强碱性磷酸酶的活性,以剂量依赖的方式促进小鼠原代成骨细胞的成骨分化。本研究同时证明补骨脂素能上调BMP2和BMP4基因的表达,提高磷酸化smad1/5/8蛋白水平,激活BMP报告基因(12xbe-oc-luc)的活性以及增强BMP信号直接靶基因osx的表达。BMP2和BMP4基因的缺失消除了补骨脂素对成骨细胞标志基因col1、alp、oc和bsp表达的促进作用。结果表明,补骨脂素通过激活BMP信号促进成骨细胞分化,提示补骨脂素可能是治疗骨质疏松等骨丢失相关疾病的一种潜在的合成代谢剂。     

Osteoclast response to low extracellular sodium and the mechanism of hyponatremia-induced bone loss

Our recent animal and human studies revealed that chronic hyponatremia is a previously unrecognized cause of osteoporosis that is associated with increased osteoclast numbers in a rat model of the human disease of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). We used cellular and molecular approaches to demonstrate that sustained low extracellular sodium ion concentrations ([Na(+)]) directly stimulate osteoclastogenesis and resorptive activity and to explore the mechanisms underlying this effect. Assays on murine preosteoclastic RAW 264.7 cells and on primary bone marrow monocytes both indicated that lowering the medium [Na(+)] dose-dependently increased osteoclast formation and resorptive activity. Low [Na(+)], rather than low osmolality, triggered these effects. Chronic reduction of [Na(+)] dose-dependently decreased intracellular calcium without depleting endoplasmic reticulum calcium stores. Moreover, we found that reduction of [Na(+)] dose-dependently decreased cellular uptake of radiolabeled ascorbic acid, and reduction of ascorbic acid in the culture medium mimicked the osteoclastogenic effect of low [Na(+)]. We also detected downstream effects of reduced ascorbic acid uptake, namely evidence of hyponatremia-induced oxidative stress. This was manifested by increased intracellular free oxygen radical accumulation and proportional changes in protein expression and phosphorylation, as indicated by Western blot analysis from cellular extracts and by increased serum 8-hydroxy-2'-deoxyguanosine levels in vivo in rats. Our results therefore reveal novel sodium signaling mechanisms in osteoclasts that may serve to mobilize sodium from bone stores during prolonged hyponatremia, thereby leading to a resorptive osteoporosis in patients with SIADH.     

VD缺乏相关疾病及其合理补充的临床意义

：众所周知,人体内维生素D水平与少年佝偻病和老年骨质疏松直接相关。最近大量流行病学证据还表明,维生素D（VD）缺乏是多种自身免疫性疾病,癌症,心血管疾病,抑郁症,老年痴呆症,感染性疾病,肌肉骨骼功能下降等的危险因素之一。另外,胰岛素抵抗,高血压和高胆固醇血症也与维生素D缺乏有关。因此,合理补充维生素D可以降低多种疾病风险,并对心血管疾病的风险有益。本文系根据已有的研究结论,阐述维生素D水平与多种临床疾病之间的关联,并对人体血清VD浓度合理监测及合理补充的临床意义做一综述。     

丁酸梭菌在医学领域中的研究进展

肠道益生菌是定植于人体肠道内,能产生确切健康功效从而改善宿主微生态平衡,对宿主发挥有益作用的一类活性微生物总称。最近越来越多的研究表明肥胖、糖尿病、肠易激综合征、骨质疏松等与肠道菌群密切相关,而丁酸梭菌由于能够促进其他有益菌（乳杆菌、双歧杆菌）生长,具有其他有益生菌没有的特性,受到越来越多研究者的重视。本文通过综述近几年有关丁酸梭菌与神经、内分泌、消化等系统中部分疾病的关系,总结了丁酸梭菌可能具有的治疗机制,并将其与益生菌在治疗骨质疏松症时所发挥的机制进行对比,以展望丁酸梭菌可能具有治疗骨质疏松的潜力。     

Bisphosphonate-loaded bone cement: Background,clinical indications and future perspectives

Bisphosphonates represent an established treatment against bone resorption and osseous loss. Local application could help increase bone mineral density while minimizing their systemic use side-effects. Bone cement, used on a large scale in orthopedic surgery and a historically successful drug carrier, could represent an effective scaffold. The aim of this review was to investigate the alterations produced on the cement’s structure and properties by this mixture, as well as its antiosteoporotic and antitumor effect. After a thorough research of articles, title screening and duplicate removal we retained 51 papers. Two independent authors performed abstract and full-text reading, finally leaving 35 articles included in this review. In the current literature, acrylic and calcium phosphate bone cement have been used as carriers. A combination with nitrogen-containing bisphosphonates, e.g., zoledronic acid, provokes modifications in terms of setting time prolongation and mechanical strength decline within acceptable levels, on the condition that the drug’s quantity stays beneath a certain plateau. Bisphosphonates in bone cement seem to have a powerful anti-osteoclastic and osteogenic local impact as well as a direct cytotoxic effect against several neoplastic lesions. Further investigation on the subject is required, with specifically designed studies focusing on this method’s advantages and potential clinical applications.