Letter to the Editor Response

Abstract

Background: COPD pathology involves not only the lungs but also extrapulmonary abnormalities. Osteoporosis is one of the most important abnormalities because it may cause vertebral compression fractures and deteriorate pulmonary function. COPD patients have many risk factors for osteoporosis, such as low BMI, decreased activity, systemic inflammation, and use of corticosteroids. Some of these factors have been shown to deteriorate with COPD exacerbations. We previously demonstrated the correlation between emphysema and osteoporosis and between emphysema progression and COPD exacerbations. Thus, the hypothesis that exacerbation causes osteoporosis progression in COPD patients was investigated. Methods: Forty-two COPD patients not on osteoporosis treatment for over 2 years were recruited. During follow-up, exacerbations had been prospectively recorded. Thoracic vertebral bone mineral density (BMD) was measured using chest CT, and the annual change in BMD was calculated. The change was compared between patients with and without a history of exacerbations. Results: The decrease in thoracic vertebral BMD was greater in patients with than in those without a history of exacerbations (median ΔBMD mg/ml?year: –3.78 versus –0.30, p = 0.02). Moreover, multivariate regression analysis showed that exacerbations and baseline PaO2 were independent predictors of the BMD decrease (R2 = 0.20, p = 0.007, and R2 = 0.09, p = 0.03, respectively) after adjustment for baseline age, smoking status, and airflow limitation. Conclusions: This is the first longitudinal study to demonstrate that COPD exacerbations are independently associated with osteoporosis progression. Osteoporosis progression should be evaluated in COPD patients, especially in those with a history of frequent exacerbations.     

驱动基因在肺癌骨转移中的研究进展

骨是肺癌常见的血行转移部位之一，其发生率为30%~40%，好发于脊柱和躯干近端，包括脊柱、股骨、肋骨和胸骨等。肺癌骨转移患者中位生存期为6~10月，治疗后1年生存率为40%~50%。骨转移分子机制的研究对治疗具有重要的指导意义。研究显示肺癌原发灶和骨转移灶驱动基因表达存在异质性，然而肺癌驱动基因在肺癌骨转移中的作用以及对骨微环境的的影响机制尚不明确。本文就肺癌骨转移分子机制研究进展进行综述，着重对常见肺癌驱动基因在肺癌骨转移中的作用及对骨微环境的影响进行阐述。     

Calcium and vitamin D supplementation and loss of bone mineral density in women undergoing breast cancer therapy

An unintended consequence of breast cancer therapies is an increased risk of osteoporosis due to accelerated bone loss. We conducted a systematic review of calcium and/or vitamin D (Ca ± D) supplementation trials for maintaining bone mineral density (BMD) in women with breast cancer using the “before–after” data from the Ca ± D supplemented comparison group of trials evaluating the effect of drugs such as bisphosphonates on BMD. Whether Ca ± D supplements increase BMD in women undergoing breast cancer therapy has never been tested against an unsupplemented control group. However, results from 16 trials indicate that the Ca ± D doses tested (500–1500 mg calcium; 200–1000 IU vitamin D) were inadequate to prevent BMD loss in these women. Cardiovascular disease is the main cause of mortality in women with breast cancer. Because calcium supplements may increase cardiovascular disease risk, future trials should evaluate the safety and efficacy of Ca ± D supplementation in women undergoing breast cancer therapy.     

Investigating the Effects of Motion Streaks on pQCT-Derived Leg Muscle Density and Its Association With Fractures

Lower peripheral quantitative computed tomography (pQCT)-derived leg muscle density has been associated with fragility fractures in postmenopausal women. Limb movement during image acquisition may result in motion streaks in muscle that could dilute this relationship. This cross-sectional study examined a subset of women from the Canadian Multicentre Osteoporosis Study. pQCT leg scans were qualitatively graded (1–5) for motion severity. Muscle and motion streak were segmented using semi-automated (watershed) and fully automated (threshold-based) methods, computing area, and density. Binary logistic regression evaluated odds ratios (ORs) for fragility or all-cause fractures related to each of these measures with covariate adjustment. Among the 223 women examined (mean age: 72.7?±?7.1 years, body mass index: 26.30?±?4.97?kg/m²), muscle density was significantly lower after removing motion (p?<?0.001) for both methods. Motion streak areas segmented using the semi-automated method correlated better with visual motion grades (rho?=?0.90, p?<?0.01) compared to the fully automated method (rho?=?0.65, p?<?0.01). Although the analysis-reanalysis precision of motion streak area segmentation using the semi-automated method is above 5% error (6.44%), motion-corrected muscle density measures remained well within 2% analytical error. The effect of motion-correction on strengthening the association between muscle density and fragility fractures was significant when motion grade was?≥3 (p interaction <0.05). This observation was most dramatic for the semi-automated algorithm (OR: 1.62 [0.82,3.17] before to 2.19 [1.05,4.59] after correction). Although muscle density showed an overall association with all-cause fractures (OR: 1.49 [1.05,2.12]), the effect of motion-correction was again, most impactful within individuals with scans showing grade 3 or above motion. Correcting for motion in pQCT leg scans strengthened the relationship between muscle density and fragility fractures, particularly in scans with motion grades of 3 or above. Motion streaks are not confounders to the relationship between pQCT-derived leg muscle density and fractures, but may introduce heterogeneity in muscle density measurements, rendering associations with fractures to be weaker.     

In vitro cultivation of rat bone marrow mesenchymal stem cells and establishment of pEGFP/Ang-1 transfection method

ObjectiveTo obtain the bone marrow mesenchymal stem cells (BMSCs), complete phenotypic identification and successfully transfect rat BMSCs by recombinant plasmid pEGFP/Ang-1.MethodsBMSCs were isolated from bone marrow using density gradient centrifugation method and adherence screening method, and purified. Then the recombinant plasmid pEGFP/Ang-1 was used to transfect BMSCs and the positive clones were obtained by the screen of G418 and observed under light microscopy inversely. Green fluorescent exhibited by protein was enhanced to measure the change time of the expression amount of Ang-1.ResultsBMSCs cell lines were obtained successfully by adherence screening method and density gradient centrifugation. Ang-1 recombinant plasmid was transfected smoothly into rat BMSCs, which can express Ang-1 for 3 d and decreased after 7 d.ConclusionsAdherence screening method and density gradient centrifugation can be effective methods to obtain BMSCs with high purity and rapid proliferation. Besides, the expression of transfected recombinant plasmid pEGFP/Ang-1 in rat BMSCs is satisfactory.     

镉染毒对大鼠骨生物力学性能的影响

目的: 探讨镉对大鼠股骨和腰椎生物力学性能的影响。方法: 24只8周龄雄性SD大鼠随机分成4组，分别背部皮下注射生理盐水0.5ml（对照组）和0.1mg/kg bw(低剂量组)，0.5mg/kg bw（中剂量组），1.5mg/kg bw（高剂量组）CdCl2，每周称体重，并根据体重调整注射量。染毒后第12周，收集全血、腰椎及股骨，分别用于血镉测定、骨镉测定、骨密度测定及生物力学测定。结果: 染毒组大鼠体内血镉及骨镉水平明显高于对照组，差异有统计学意义（P < 0.05）；中、高剂量染毒组大鼠骨密度较对照组显著下降（P < 0.05）；染毒组大鼠股骨和腰椎生物力学性能较对照组有不同程度的的降低，其中高剂量染毒组大鼠股骨生物力学性能的下降和对照组相比有显著差异（P < 0.01）；中剂量和高剂量染毒组大鼠腰椎生物力学性能和对照组相比差异有统计学意义（P < 0.01）。结论: 镉能影响大鼠股骨和腰椎的生物力学性能，并且腰椎生物力学性能的改变要早于股骨。