Role of fos and src in cadmium-induced decreases in bone mineral content in mice

Cadmium decreases bone mineral in mice and stimulates osteoclast formation and activity in cell culture. Bones from fos-deficient mice contain very few osteoclasts; src-/- bones contain osteoclasts that fail to activate. Fos-/- and src-/- mice develop osteopetrotic bones and their teeth do not erupt. These mice were used to determine if cadmium requires c-Fos or c-Src and secondarily functional osteoclasts to decrease bone mineral content. Mice heterozygous for fos deficiency were mated to produce fos-/- and fos+/o (wild-type) offspring. Pups were divided into four groups: fos+/o, Cd-; fos+/o, Cd+; fos-/-, Cd-; and fos-/-, Cd+. Cd+ pups received daily sc injections (50 microg Cd/kg) on days 17-20 and Cd in drinking water thereafter (10 ppm, days 21-27; 20 ppm, days 27-50). An analogous protocol was followed mating mice heterozygous for src deficiency. For acute exposures, 50-day-old mice were placed on a low-calcium diet and given two sequential 100 microg Cd doses by gavage, and feces were monitored for excretion of bone calcium. Continuous exposure results demonstrate that cadmium (1) significantly decreased bone calcium content (14-15%) and concentration (12-13%) in both fos+/o and fos-/- mice, (2) doubled multinucleated osteoclast-like cell number in fos-/- bones, and (3) stimulated tooth eruption in 40% of fos-/- mice. Cd gavage stimulated bone calcium excretion in both fos+/o and fos-/- mice. In contrast, cadmium had no effect on bones or teeth in src-/- mice. Results indicate that cadmium can decrease bone mineral via a c-Fos-independent pathway; however, c-Src is required for cadmium to stimulate bone remodeling and tooth eruption pathways.     

Statin lipid-lowering drugs and bone mineral density

BACKGROUND: HMG Co-A reductase inhibitors (statin lipid-lowering drugs) have been associated with a reduced rate of fractures in some studies, but not in others. We examined the relationship between statin use and bone density among postmenopausal women. METHODS: We conducted a cross-sectional survey at one academic medical center. Postmenopausal women who underwent bone densitometry and agreed to a telephone interview were surveyed about osteoporosis risk factors, use of hormone replacement therapy and osteoporosis medications and statin exposure. We then developed linear regression models adjusting for known counfounders to assess the relationship between statin use and bone mineral density (BMD). RESULTS: Of 339 women studied, 162 were current or past users of statins, and 177 were not. Statin users and non-users were similar with respect to age, race, prior fracture history, the presence of medical conditions associated with osteoporosis, use of medications for osteoporosis, use of tobacco and use of oral glucocorticoids. Statin users had significantly higher body mass index (BMI) and rates of thiazide use, and were more likely to abstain from alcohol. After adjusting for important confounders, we found that statin use was associated with a significantly higher t-score at the total hip (-0.53 +/- 0.17) compared with non-users (-0.83 +/- 0.18; p = 0.02). At the lumbar spine, there was a trend toward higher t-scores in statin users (-0.91 +/- 0.24) compared with non-users (-1.21 +/- 0.23; p = 0.08). CONCLUSIONS: These results support the hypothesis that statin use is associated with higher BMD. While it is unclear whether their relationship is causal, further controlled studies examining bone formation and resorption would help determine the clinical implications of these findings.     

Management of bone mineral density in HIV-infected patients

Introduction: Loss of bone mineral density is an emerging problem in persons living with HIV infection. Earlier and more rapid bone demineralization has been attributed not only to the high prevalence of traditional risk factors, but also to specific HIV-related factors. The aim of this guidance is to stimulate an appropriate management of osteoporosis in this population, to identify patients at risk and to better manage them.

Areas covered: Appropriate screening of HIV-infected subjects to identify those at risk for bone fractures is described, as well as the recommended interventions. American and European recommendations in HIV-infected and non-infected populations were considered. As the etiology of bone loss is multifactorial, many factors have to be addressed. Overall, recommendations on traditional risk factors are the same for HIV-infected and non–HIV-infected subjects. However, we should consider some specific factors in the HIV-infected population, including an appropriate antiretroviral therapy in patients with low bone mineral density, and probably novel strategies that could provide an additional benefit, such as anti-inflammatory drugs, although data supporting this approach are scant.

Expert opinion: Some personal opinions are highlighted on the management of bone health in HIV-infected subjects, mainly on the use of FRAX^® score and DXA scans. In addition, the need to implement new strategies to delay demineralization is remarked upon.     

甲状腺功能减退对妊娠妇女骨代谢及骨密度的影响

目的 探讨甲状腺功能减退(甲减)对妊娠妇女骨代谢及骨密度(BMD)的影响.方法 选取82例妊娠中期甲减患者作为甲减组,同期50例妊娠中期产检正常的妇女作为对照组.采用超声骨密度仪测定并比较跟骨部位的BMD值,同时检测并比较两组血钙(Ca)、血磷(P)、碱性磷酸酶(ALP)、总Ⅰ型前胶原氨基端延长肽(TPⅠNP)、Ⅰ型胶原羧基端肽 β特殊序列(CTX-β)等骨代谢指标,促甲状腺激素(TSH)、游离甲状腺素(FT4)、游离三碘甲状腺原氨酸(FT3)等甲状腺功能指标.采用Pearson线性相关分析各指标之间的相关性.结果 甲减组跟骨BMD值较对照组显著降低[(1.08±0.16比0.96±0.15)g·cm-2],骨质疏松的发生率(6.0%比18.3%)则显著升高(t=4.347,P=0.000;χ2=3.985,P=0.046).与对照组比较,甲减组血清Ca[(2.22±0.14比2.54±0.16)mmol·L-1]、ALP[(63.92±10.32比69.53±11.24)U·L-1]明显降低,P[(1.43±0.23比1.18±0.17)mmol·L-1]、TPⅠNP[(56.32±12.52比47.06±11.86)μg·L-1]、CTX-β[(0.32±0.12比0.21±0.07)pg·L-1]明显升高(t=12.062,P=0.000;t=7.148,P=0.000;t=2.929,P=0.004;t=4.204,P=0.000;t=6.650,P=0.000).TSH与跟骨BMD值及Ca、ALP呈负相关(r=-0.58,-0.51,-0.45,P<0.05),与TPⅠNP、CTX-β呈正相关(r=0.48,0.44,P<0.05),FT3、FT4与跟骨BMD值、Ca、ALP呈正相关(r=0.43,0.40,0.41;0.51,0.44,0.48,P<0.05),与TPⅠNP、CTX-β呈负相关(r=-0.47,-0.50;-0.46,-0.51,P<0.05).结论 甲减可影响妊娠妇女骨代谢,降低骨密度,导致骨量丢失、骨折风险增加,临床上应加强对妊娠妇女的甲状腺功能筛查.     

依那西普对类风湿关节炎患者骨代谢生化指标、骨密度的影响

目的:研究类风湿关节炎患者接受依那西普(etanercept,ETN)治疗52周后血清骨代谢生化指标、骨密度改变。方法:39例患者分为对照组(MTX7.5 mg/周逐渐加量至15 mg/周,3例患者于第8周时最大剂量为20 mg/周);治疗组17例(MTX用法同前,其中2例患者于第8周时最大剂量为20 mg/周,ETN:25 mg,每周2次,皮下注射)。于治疗前、12周、26周、52周分别检测骨保护素(OPG)、血清骨钙素(OC)、降钙素(CT)、甲状腺旁素(iPTH)。并行腰椎及股骨不同部位骨密度(BMD)测定。结果:2组在治疗前血清OPG水平即有显著降低,对照组随着治疗时间的持续而进一步降低。治疗组在治疗26周后出现升高,2组比较有统计学差异(P<0.01);而血清iPTH在治疗前2组均有显著升高,对照组随着治疗时间的持续而进一步升高。治疗组在治疗12周后出现升高,2组比较有统计学差异(P<0.01);2组患者腰椎、股骨颈、股骨沃德三角BMD比较有统计学意义(P<0.01)。结论:应用依那西普治疗类风湿关节炎能减少骨丢失、有效改善患者骨质疏松。     

奥美拉唑对去势大鼠骨密度和骨代谢的影响

目的：观察质子泵抑制剂奥美拉唑对去势雌性大鼠骨密度和骨代谢的影响,为临床合理应用质子泵抑制剂提供依据。方法：8月龄SD雌性大鼠,分成假手术组（Sham+NS组）、假手术给药组（Sham+OMZ组）、去势组（OV+NS组）、去势给药组（OV+OMZ组）。去势组大鼠行去卵巢手术建模,假手术组同等部位切除部分脂肪。给药组大鼠按体质量30 mg·kg^-1·d^-1灌胃奥美拉唑,非给药组按2 mL·d^-1生理盐水灌胃。以双能X线吸收法（DXA）检测骨密度;酶联免疫吸附法检测血清中骨代谢标志物TRAP、CTX-1、PINP、BALP、OC浓度;qRT-PCR法检测股骨骨髓细胞OPG、RANKL、c-FOS、NFATc1的mRNA表达水平以及R/O值。结果：去势组较假手术组骨密度降低、TRAP、CTX-1、PINP、OC浓度升高、R/O值升高,去势给药组较去势组骨密度降低、TRAP、CTX-1、PINP、OC浓度升高、R/O值升高。结论：质子泵抑制剂奥美拉唑可能诱导去势雌性大鼠体内的RANKL表达量相对增加,R/O值升高,进而通过OPG/RANK/RANKL信号通路使得破骨细胞活动相对增强,骨吸收代谢加快,加速骨质疏松进程。     

Effects of denosumab on bone mineral density and bone turnover in postmenopausal women

Osteoporosis is a degenerative bone disease affecting approximately 10 million American adults. Several options are available to prevent development of the disease or slow and even stop its progression. Nonpharmacologic measures include adequate intake of calcium and vitamin D, exercise, fall prevention, and avoidance of tobacco and excessive alcohol intake. Current drug therapy includes bisphosphonates, calcitonin, estrogen or hormone therapy, selective estrogen receptor modulators, and teriparatide. Denosumab, a receptor activator of nuclear factor-K B ligand (RANKL) inhibitor, was recently approved by the United States Food and Drug Administration for treatment of postmenopausal osteoporosis. Patients treated with denosumab experienced significant gains in bone mineral density, rapid reductions in markers of bone turnover, and a reduced risk for new vertebral fracture. Compared with placebo, patients receiving denosumab 60 mg subcutaneously once every 6 months experienced gains in bone mineral density of 6.5-11% when treated for 24-48 months. One trial demonstrated the superiority of denosumab compared with alendronate, but the differences were small. The most common adverse reactions to denosumab include back pain, pain in extremities, musculoskeletal pain, and cystitis. Serious, but rare, adverse reactions include the development of serious infections, dermatologic changes, and hypocalcemia. The recommended dosing of denosumab is 60 mg every 6 months as a subcutaneous injection in the upper arm, upper thigh, or abdomen. Although beneficial effects on bone mineral density and fracture rate have been established in clinical trials, the risks associated with denosumab must be evaluated before therapy initiation. Of concern is the risk of infection, and denosumab should likely be avoided in patients taking immunosuppressive therapy or at high risk for infection. Therefore, bisphosphonates will likely remain as first-line therapy. Denosumab should be considered in patients unable to tolerate or who have adherence issues or contraindications to other therapies.     

仙珍骨宝抗骨质疏松的大鼠骨密度研究

目的进一步探讨仙尼骨宝的抗骨质疏松作用。方法取3月龄雄性SD大鼠作为制备对象,随机分为3组,分别为对照组6例,骨质疏松组6例,治疗组6例。所有受试大鼠均饲养90d,行麻醉并处死,取各鼠的胫骨作为骨密度的测量骨。结果骨质疏松组大鼠平均股骨密度明显低于对照组,治疗组平均股骨密度明显高于对照组(P<0.05),但与对照组无显著差异(P>0.05);股骨中段和远段,骨质疏松组平均股骨密度明显低于对照组,治疗组平均股骨密度明显高于对照组(P<0.05),但与对照组无显著差异(P>0.05);股骨近段三组经统计学比较无显著差异(P>0.05)。结论仙珍骨宝对于动物体的骨质疏松具有较好的抵抗作用,可有效改善骨密度降低的问题,提高骨强度。     

肾移植患者骨密度分析研究

目的探讨肾移植受者与正常人群骨密度(BMD)的差异.方法选取肾移植受肾者53例为移植组(男23例,女30例),正常体检人群115例为对照组(男64例,女51例).以双能X线吸收法测定腰椎、左股骨颈和全髋BMD,比较不同性别移植组和对照组BMD和骨质疏松发生率.结果男性移植组仅左股骨颈BMD明显低于同性别对照组(P＜0....     

甲状腺功能亢进患者骨密度与骨代谢指标的临床观察

目的观察甲状腺功能亢进患者骨密度（BMD）与骨代谢指标的改变。方法应用双能X线测定仪（DXA）检测86例甲状腺功能亢进患者BMD和髋关节强度指数（FSI）,同时测定血清骨钙素（BGP）、总Ⅰ型前胶原氨基端延长肽（PINP）和B-胶原降解产物（B-Crosslaps）。结果甲状腺功能亢进患者并发骨质疏松发生率20．9％,并发骨量减少占40．7％,与对照组比较,甲状腺功能亢进忠者BMD和FSI明显低于对照组（P〈0．05）,骨代谢指标BGP、PINP和B-Crosslaps明显升高（P〈0．05,P〈0．01）。结论甲状腺功能亢进时反映成骨细胞活性的BGP和PINP和反映破骨细胞活性的8-CrossLaps均明显升高,且以破骨指标升高明显,呈高转换型骨质疏松。     

Genistein inhibits osteolytic bone metastasis and enhances bone mineral in nude mice

In this study, the effective activity of genistein on osteolytic bone metastasis and bone mineral was investigated. Female BALB/c-nu/nu mice were injected with estrogen receptor-negative human breast cancer cells, MDA-MB-231, into left cardiac ventricle to form osteolytic bone metastases, and administered genistein subcutaneously after radiologically small but defined osteolytic metastases had been observed (protocol 1), simultaneously with cancer cells inoculation (protocol 2) and prophylactically 7 days before inoculation of cancer cells (protocol 3). In all protocols, genistein (10mg/kg/day) markedly reduced the number and volume of osteolytic bone metastases assessed by radiography and the number of osteoclasts. Furthermore, histomorphometrical analysis revealed that genistein markedly increased trabecular area (Tb.Ar%), trabecular thickness (Tb.Th) and trabecular number (Tb.N), and decreased trabecular separation (Tb.Sp). These results thus demonstrate that genistein could inhibit osteolytic bone metastases, suppress bone resorption, increase bone mass and improve bone microstructure in bone metastases of breast cancer.     

骨质疏松和骨性关节炎大鼠动物模型骨密度和骨组织结构的变化

目的 采用大鼠切除双侧卵巢(Ovariectomy,OVX)制作骨质疏松症(Osteoporosis,OP)模型,切断右膝前交叉韧带制作骨性关节炎(Osteoarthritis,OA)模型,观察动物模型股骨骨密度和骨组织结构的变化.方法 3月龄Sprague-Dawley大鼠40只,分成双侧卵巢切除组(OVX,G1),基础对照组1(OVX+假手术,G2),右膝前交叉韧带切断组(OA,G3),基础对照组2(OA +假手术,G4),共4组,每组10只.所有的大鼠在术后6个月后处死.处死前10 d和4 d分别皮下注射盐酸四环素和钙黄绿素行荧光双标记.取大鼠右股骨.用双能X线骨密度仪(DEXA,Luner-DPXIQ)测量股骨近段骨密度.取股骨远段进行硬组织包埋、切片,用半自动图象分析仪分析及松质骨骨形态计量学软件处理.结果 OVX组与OVX+假手术组比较,BMD和骨量BV/TV显著减少,提示造模成功.OA组与OA +假手术组比较, BMD和骨量BV/TV无变化.结论 在本研究SD大鼠切除双侧卵巢制作OP模型,饲养6个月,股骨骨量降低.SD大鼠切断右膝前交叉韧带制作OA模型,饲养6个月,股骨骨量无改变.     

骨密度测量的临床应用与质量控制

在骨质疏松症临床与科研中,骨密度是检测骨量的主要手段。近年来由于检查仪器的发展,常采用单光子骨密度仪、双能x线骨密度仪、定量CT扫描法、周围骨CT扫描法和定量超声波骨扫描仪进行骨量定量检查。不管采用哪种方法,     

阿仑膦酸钠联合钙尔奇D对骨质疏松症患者疼痛和骨密度的影响

目的:探讨阿仑膦酸钠联合钙尔奇D对骨质疏松症患者疼痛和骨密度的影响。方法:选取2013年9月至2016年9月期间我院确诊治疗的骨质疏松症患者100例,依据随机双盲法分为联合组和常规组,每组50例,常规组患者给予常规饮食、运动等指导和300~600 mg·d~(-1)钙尔奇D口服治疗,每天1次,持续6个月,联合组患者在此基础上给予70 mg阿仑膦酸钠口服治疗,每周1次,持续6个月,采用视觉模拟评分法(VAS)评估疼痛程度,采用酶联免疫吸附法(ELISA)检测血清骨钙素(BGP)、碱性磷酸酶(ALP)、尿脱氧吡啶酚(DPD),采用Oswestry功能障碍指数问卷表(ODI)评估生活质量,随访6个月,统计分析所有患者临床疗效、治疗前后血清BGP、ALP、DPD水平、骨密度(腰椎L1~4、大粗隆)、疼痛和治疗前、治疗后1、3、6个月的生活质量及治疗期间不良反应发生情况。结果:联合组患者治疗有效率明显高于常规组,差异有统计学意义(P<0.05);联合组患者治疗后VAS得分明显低于常规组,前者治疗后腰椎L1~4、大粗隆骨密度明显高于后者,差异有统计学意义(P<0.05);联合组患者治疗后血清BGP水平明显高于常规组,前者治疗后血清ALP、DPD水平明显低于后者,差异有统计学意义(P<0.05);联合组患者治疗后1、3、6个月的ODI得分明显低于常规组,差异有统计学意义(P<0.05);联合组和常规组患者治疗期间均无明显的不良反应发生。结论:阿仑膦酸钠联合钙尔奇D治疗可有效提高骨质疏松症患者的治疗疗效,缓解患者的疼痛症状,改善患者的骨密度及骨代谢,有利于提高患者的生活质量,且具有良好的安全性。     

甲亢患者的骨密度改变

目的 观察甲亢患者的ＢＭＤ改变及病程、ＴＴ３、年龄和性别对其改变的影响。方法 用单光子骨密度仪测量了１２９例未治甲亢患者桡骨ＢＭＤ。结果 甲亢组的桡骨ＢＭＤ低于正常对照组（Ｐ〈０．０１）,ＢＭＤ减低发生率为２４．８０％。多元线性回归分析表明９０例女性甲亢患者的桡骨ＢＭＤ与病程及年龄呈负相关,而与ＴＴ３无关;３９例男性甲亢患者的桡骨ＢＭＤ与病程呈负相关,而与ＴＴ３和年龄无关。结论 甲 对骨质改变有重     

产次与绝经后妇女股骨近端骨密度的关系

目的探讨产次与绝经后妇女股骨近端骨密度(BMD)的关系.方法调查180名健康绝经后妇女年龄、产次、绝经时间,并测量身高、体重、左侧股骨近端(Neck、Ward三角、Troch)BMD.结果随着产次的增加,股骨近端各部位BMD逐渐下降,产3次,产4次,产次≥5次各组股骨近端各部位BMD显著低于产1次和产2次组(P＜0.01).多因素分析显示产次与股骨近端各部位BMD呈显著负相关(P＜0.01),绝经年限与Neck和Troch部位BMD呈显著负相关(P＜0.01).结论产次影响绝经后妇女股骨近端各部位BMD,随着产次的增加,股骨近端各部位BMD逐渐下降.     

中西药结合治疗绝经后骨质疏松临床疗效观察

目的观察中西药结合治疗绝经后骨质疏松的临床疗效。方法227例确诊患者随机分为3组：中西药组、中药组和西药组。各组给予不同的治疗药物,为期6个月。检测骨代谢相关指标及性激素水平。结果各组治疗后BMD、血清骨代谢相关指标和性激素水平均有所上升,尿中骨代谢相关指标均有所下降。其中中西药组治疗前后各指标值最大,差异具有显著性意义（P〈0.05）。结论中西药结合治疗绝经后骨质疏松疗效确切。     

绝经后妇女椎体骨折与骨密度的关系

目的探讨绝经后妇女骨质疏松性椎体骨折与骨密度(BMD)的关系。方法对骨质疏松性椎体骨折的绝经后妇女280例(骨折组)和无椎体骨折的绝经后妇女280例(对照组)行胸腰椎正侧位X线摄片,并用双能X线骨密度测量仪(DEXA)检测腰椎(L2~L4)和左髋部BMD和T值。结果骨折组腰椎及髋部BMD和T值均低于对照组(P<0.01)。随着年龄的增加,两组BMD均逐渐下降。结论绝经后妇女的骨质疏松性椎体骨折与腰椎BMD下降相关;随着年龄的增加,椎体骨折的危险性增加;对绝经后妇女应重视BMD和胸腰椎X线片检查。