Parametric study of control mechanism of cortical bone remodeling under mechanical stimulus

The control mechanism of mechanical bone remodeling at cellular level was investigated by means of an extensive parametric study on a theoretical model described in this paper. From a perspective of control mechanism, it was found that there are several control mechanisms working simultaneously in bone remodeling which is a complex process. Typically, an extensive parametric study was carried out for investigating model parameter space related to cell differentiation and apoptosis which can describe the fundamental cell lineage behaviors. After analyzing all the combinations of 728 permutations in six model parameters, we have identified a small number of parameter combinations that can lead to physiologically realistic responses which are similar to theoretically idealized physiological responses. The results presented in the work enhanced our understanding on mechanical bone remodeling and the identified control mechanisms can help researchers to develop combined pharmacological-mechanical therapies to treat bone loss diseases such as osteoporosis.

Clinicopathological Correlation of Primary Malignant Bone Tumors—An Observational Study

Background: Primary malignant tumors arising from bone are uncommon but important malignant neoplasms which account for 0.2% of all primary cancers in adults and approximately 5% of all childhood malignancies. Aim: No comprehensive surveillance data about primary malignant bone tumors is available from this region of West Bengal in the literature. An attempt is undertaken to correlate clinicopathological findings, both histological & cytological features of primary bone tumours. Method: This observational study of clinical presentation was corroborated with cytology and histopathology of 67 cases of primary malignant bone tumors in 2005-2007 in a tertiary health care centre. Results: Among the primary malignant tumors, 39 cases (58.20%) were male and 28 (41.80%) were female. Sixty one lesions (91%) were located in the long bones and 6 (9%) involving flat and short bones. Osteosarcomas are found to be the predominant primary malignant bone tumors (44.77%), followed by Ewing’s sarcomas (20.89%), chondrosarcomas (13.43%), high grade giant cell tumor, and plasmacytoma (5.97%). Predilection for male (M: F 2:1) found in both osteosarcoma and chondrosarcoma, but it was reverse in cases of Ewing’s sarcomas. Conclusion: Osteosarcoma is the most common around knee joint and chondrosarcoma is frequent in long bones in this region. We made an attempt to correlate FNAC findings with the histopathology and it was seen that overall sensitivity of FNAC of primary malignant bone tumors was 56.71%.

Biodegradation of Polymethylmethacrylate Bone Cement May Not Be a Serious Issue in Total Hip Arthroplasty—Retrieval Study for Knoop Hardness and Young’s Modulus

Introduction: To investigate a long-term in vivo deterioration of polymethylmethacrylate (PMMA) bone cement over time, we evaluated retrieved PMMA cement in terms of chemical elements presenting in the cement using energy dispersive analysis of X-rays;Knoop hardness;and the Young’s modulus using scanning acoustic microscopy. Materials and Methods: For mechanical evaluation, we could neglect the influences of entrapped air bubbles or blood by the use of small specimens. The study was based on thirteen cement samples (six used in the acetabulum and seven in the femur) derived from eight patients (age at revision surgery: mean 72.5, range 68 to 79). All of these samples were Simplex-P?cement. They were functioning well at least ten years after the previous surgery. Duration until revision surgery was ranged 12 to 25 years (average, 17.4 years). The reason for revision was aseptic mechanical loosening. Twenty samples of Simplex-Preg;cement were served by manually mixing as a control. Results: The average of the hardness of the cement was 17.0 ± 1.2 (range, 13.4-20.6). In the control, the hardness was 17.8 ± 1.5 (range, 14.0-24.6). There was no significant difference between these values. The mean of Young’s modulus of the cement was 5.61 ± 0.19 GPa (range, 5.09-6.10). In the control, the modulus was 6.04 ± 0.13 GPa (range, 5.68-6.45). Although the modulus was significantly less than that of the control, there was only 7% decrease in average between twelve and twenty-five years in vivo. Conclusions: Our results suggest that long-term implantation and functional loading in vivo may not be the limiting factor in the mechanical integrity of the bone cement.

The Twelve Chinese Zodiac Scripts of Ancient Luo Yue Stone Inscriptions and the Oracle Bone:A Comparative Study

The 12 animal calendars of the Chinese zodiac are the essence and source of Chinese civilization,and have been deeply rooted in the production,life,and social activities of various ethnic groups in China since ancient times.The ancient Luo Yue stone inscription1 is a popular ancient script from four to six thousand years ago,and 17,496 characters have been found,which is the earliest script found on the Chinese land so far.A comparative study of Chinese zodiac characters2 between the ancient Luo Yue stone inscriptions and the oracle bone through paleographic conformation reveals that the two characters have the same and similar characteristics.Therefore,this paper intends to further investigate the kinship between the two,and to conduct a preliminary exploration of the origin,development,and evolution of the zodiac by combining recent human archaeological data,emerging molecular anthropological data,historical literature,and data from the Chinese Civilization Exploration Project,in an attempt to show the integration and dependence of Chinese civilization,the pluralistic pattern of Chinese culture,and the Chinese nation for thousands of years.

Demineralized Bone Matrix Fibers plus Allograft Bone for Multilevel Posterolateral Spine Fusion: A Game Changer?

Introduction: While autograft bone is the gold standard for multilevel posterolateral lumbar fusion, bone substitutes and graft extenders such as allograft bone, ceramics and demineralized bone matrix (DBM) have been used to avoid the morbidity and insufficient quantity associated with harvesting autologous bone. The primary objective of this retrospective study was to determine whether, in patients with increased risk of operative nonunion related to multilevel fusion, adding DBM fibers to mineralized bone allograft resulted in better fusion than using allograft alone. The secondary objectives were to evaluate how adding DBM fibers affects functional disability, low back pain, intraoperative blood loss and the nonunion rate. Methods: This retrospective study involved a chart review of consecutive patients who underwent multilevel lumbar spinal fusion and were operated on by a single surgeon. The patients were divided into two groups: 14 patients received mineralized bone allograft (control group) and 14 patients received a combination of mineralized bone allograft and DBM (experimental group). Patients were reviewed at a mean of 16.4 ± 2.2 months after surgery at which point CT scans were analyzed to determine whether fusion had occurred;Oswestry disability index (ODI) and pain were also evaluated. Results: A mean of 5 levels [min 2, max 13] were fused in these patients. Posterolateral fusion as defined by the Lenke classification was not significantly different between groups. The experimental DBM group had a significantly better composite fusion score than the control group (P Discussion: Adding DBM fibers to allograft bone during multilevel posterolateral spinal fusion was safe and produced better composite fusion than using allograft only as an autograft extender.

超高龄椎体压缩骨折患者经皮椎体后凸成形术后脊柱局部后凸的矫正效果

背景:经皮椎体后凸成形是治疗骨质疏松性椎体压缩骨折的常用术式,然而,目前尚无研究证实经皮椎体后凸成形手术能否有效矫正超高龄(年龄≥80岁)骨质疏松性椎体压缩骨折患者的脊柱局部后凸。目的:探究经皮椎体后凸成形对超高龄骨质疏松性椎体压缩骨折患者脊柱局部后凸的矫正效果。方法:选择2016年3月至2022年8月于北京大学人民医院脊柱外科接受经皮椎体后凸成形治疗的单节段骨质疏松性椎体压缩骨折患者为研究队列,收集患者住院及门诊随访资料,按照年龄将患者分为高龄组(60-79岁,n=126)、超高龄组(≥80岁,n=52)。根据性别、体质量指数、基础疾病(高血压、糖尿病、心血管疾病)、骨折节段、有无术前椎体内裂隙征,采用倾向性评分匹配对两组患者进行1:2匹配,比较两组患者的腰椎CT值、骨水泥注入量、手术前后椎体高度、术前椎体塌陷率、手术前后Cobb角、Cobb角恢复率、术后骨水泥距椎体前缘距离、骨水泥矢状位填充位置、骨水泥接触上下椎板、骨水泥距椎板距离、骨水泥分布评分、骨水泥渗漏、椎体再骨折情况。结果与结论:①倾向性评分匹配后,共115例患者完成匹配,其中高龄组71例、超高龄组44例,两组患者的性别、体质量指数、高血压比率、糖尿病比率、心血管疾病比率、骨折节段、术前椎体内裂隙征比率基线资料比较均无显著性意义(P>0.05),超高龄组术后Cobb角低于高龄组(P<0.05),两组患者的腰椎CT值、骨水泥注入量、手术前后椎体高度、术前椎体塌陷率、术前Cobb角、Cobb角恢复率、术后骨水泥距椎体前缘距离、骨水泥矢状位填充位置、骨水泥接触上下椎板、骨水泥距椎板距离、骨水泥分布评分、骨水泥渗漏比率、椎体再骨折比率比较差异均无显著性意义(P>0.05)。②结果表明,经皮椎体后凸成形能够有效矫正超高龄骨质疏松性椎体压缩骨折患者的脊柱局部后凸。

Stem Cell Ophthalmology Treatment Study(SCOTS) for retinal and optic nerve diseases: a case report of improvement in relapsing auto-immune optic neuropathy

We present the results from a patient with relapsing optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study （SCOTS）. SCOTS is an Institutional Review Board ap- proved clinical trial and has become the largest ophthalmology stem cell study registered at the National Institutes of Health to date （www.clinicaltrials.gov Identifier NCT 01920867）. SCOTS utilizes autologous bone marrow-derived stem cells （BMSCs） for treatment of retinal and optic nerve diseases. Pre-treatment and post-treatment comprehensive eye exams of a 54 year old female patient were performed both at the Florida Study Center, USA and at The Eye Center of Columbus, USA. As a consequence of a relapsing optic neuritis, the patient＇s previously normal visual acuity decreased to between 20/350 and 20/400 in the right eye and to 20/70 in the left eye. Significant visual field loss developed bilaterally. The patient underwent a right eye vitrectomy with injection of BMSCs into the optic nerve of the right eyeand retrobulbar, subtenon and in- travitreal injection of BMSCs in the left eye. At 15 months after SCOTS treatment, the patient＇s visual acuity had improved to 20/150 in the right eye and 20/20 in the left eye. Bilateral visual fields improved markedly. Both macular thickness and fast retinal nerve fiber layer thickness were maximally improved at 3 and 6 months after SCOTS treatment. The patient also reduced her mycophenylate dose from 1,500 mg per day to 500 mg per day and required no steroid pulse therapy during the 15-month follow up.

Acetabular revisions using porous tantalum components: A retrospective study with 5-10 years follow-up

AIM To evaluate the clinical and X-ray results of acetabular components and tantalum augments in prosthetic hip revisions.METHODS Fifty-eight hip prostheses with primary failure of the acetabular component were reviewed with tantalum implants. The clinical records and X-rays of these cases were retrospectively reviewed. Bone defect evaluations were based on preoperative CT scans and classified according to Paprosky criteria of Radiolucent lines and periprosthetic gaps; implant mobilization and osteolysis were evaluated by X-ray. An ad hoc database was created and statistical analyses were performed with SPSS software(IBM SPSS Statistics for Windows, version 23.0). Statistical analyses were carried out using the Student's t test for independent and paired samples. A P value of < 0.05 was considered statistically significant and cumulative survival was calculated by the KaplanMeier method.RESULTS The mean follow-up was 87.6 ± 25.6 mo(range 3-120 mo). 25 cases(43.1%) were classified as minor defects, and 33 cases(56.9%) as major defects. The preoperative HHS rating improved significantly from a mean of 40.7 ± 6.1(range: 29-53) before revision, to a mean of 85.8 ± 6.1(range: 70-94) at the end of the follow-up(Student's t test for paired samples: P < 0.001). Considering HHS only at the end of follow-up, no statistically significant difference was observed between patients with a major or minor defect(Student's t test for independent samples: P > 0.05). Radiolucent lines were found in 4 implants(6.9%). Postoperative acetabular gaps were observed in 5 hips(8.6%). No signs of implant mobilization or areas of periprosthetic osteolysis were found in the x-rays at the final follow-up. Only 3 implants failed: 1 case of infection and 2 cases of instability. Defined as the end-point, cumulative survival at 10 years was 95%(for all reasons) and 100% for aseptic loosening of the acetabular component.CONCLUSION The medium-term use of prosthetic tantalum components in prosthetic hip revisions is safe and effective in a wide variety of acetabular bone defects.

The pain-related behavior changes correlate with the bone damage in a rat model of rheumatoid arthritis

In view of the extensive bone damage in rheumatoid arthritis, we used a commonly utilized animal model to detect behavioral changes in pain-related and the bone damage during the early disease, and to explore the correlation between bone damage and pain-related behavioral changes. Methods： Arthritis were induced in Sprague-Dawley （SD） male rats by injecting complete Freund＇s adjuvant （CFA） into the tails. Pain-related behavior changes were studied using the Hargreaves, VonFrey, and acetone tests on the 0, 7, 14, day and 28 day after CFA injection. The rats were sacrificed according the same schedule. The bone damage of the right proximal tibia was studied by microCT scan and bone histological slices. Results： Animals developed soft tissue inflammation and polyarthritis on 7 days after CFA injection, and arthritic score proved obvious arthritis were established within the study period. Mechanical hyperalgesia and cold allodynia were present in the affected hind paw from the 7 day through the 28 day, but the heat hyperalgesia and the mechanical allodynia lasted a short time after CFA injection. Trabecular bone number （Tb.N）, Tissue Mineral Content （TMC） and Bone Volume to Tissue Volume （BV/TV） in the proximal tibia by microCT scan were also reduced after induction, especial 14 days after CFA injection. The bone histologicalslices showed the trabecular bone and proteoglycan diminished, the bone damage severity scores became more severely on the 7 day after CFA injection. Using analysis of covariance, these changes had statistical significance compared with baseline. By linear regression analysis demonstrated mechanical hyperalgesia and cold allodynia correlated well with arthritic score, bone damage parameters and bone damage severity scores. Conclusion： Adjuvant-induced arthritis （AA） were observed after CFA injection and lasted within the later experimental period. Pain-related behavioral changes were observed in the early time of AA. Bone damage was also occurred with arthritis development. Pain-related behavioral change correlated well with arthritic score and bone damage parameters

Transplanted bone marrow stromal cells are not cellular origin of hepatocellular carcinomas in a mouse model of carcinogenesis

AIM:To investigate the malignant potential of hepatic stem cells derived from the bone marrow stromal cells (BMSCs) in a mouse model of chemical hepatocarcino- genesis. METHODS:BMSCs from male BALB/c mice were harvested and cultured, then transplanted into female syngenic BALB/ c mice via portal vein. Hepato-carcinogenesis was induced by 6 mo of treatment with diethylnitrosamine (DEN). Six months later, the liver was removed from each treated mouse and evaluated by immunohistochemistry and fluorescence in situ hybridization (FISH). RESULTS:Twenty-six percent of recipient mice survived and developed multiple hepatocellular carcinomas (HCCs). Immunohistochemically, HCC expressed placental form of glutathione-S-transferase (GST-P) and α-fetoprotein, but did not express cytokeratin 19. Y chromosome positive hepatocytes were detected by fluorescent in situ hybridization (FISH) in the liver of mice treated with DEN after BMSCs transplantation while no such hepatocytes were identified in the liver of mice not treated with DEN. No HCC was positive for the Y chromosome by FISH. CONCLUSION:Hepatic stem cells derived from the bone marrow stromal cells have a low malignant potential in our mouse model of chemical hepatocarcingenesis.

A comprehensive study of long-term skeletal changes after spinal cord injury in adult rats

Spinal cord injury（SCI）-induced bone loss represents the most severe osteoporosis with no effective treatment.Past animal studies have focused primarily on long bones at the acute stage using adolescent rodents. To mimic chronic SCI in human patients, we performed a comprehensive analysis of long-term structural and mechanical changes in axial and appendicular bones in adult rats after SCI. In this experiment, 4-month-old Fischer 344 male rats received a clinically relevant T13 contusion injury. Sixteen weeks later, sublesional femurs, tibiae,and L4 vertebrae, supralesional humeri, and blood were collected from these rats and additional non-surgery rats for micro-computed tomography（m CT）, micro-finite element, histology, and serum biochemical analyses.At trabecular sites, extreme losses of bone structure and mechanical competence were detected in the metaphysis of sublesional long bones after SCI, while the subchondral part of the same bones showed much milder damage. Marked reductions in bone mass and strength were also observed in sublesional L4 vertebrae but not in supralesional humeri. At cortical sites, SCI induced structural and strength damage in both sub- and supralesional long bones. These changes were accompanied by diminished osteoblast number and activity and increased osteoclast number and activity. Taken together, our study revealed site-specific effects of SCI on bone and demonstrated sustained inhibition of bone formation and elevation of bone resorption at the chronic stage of SCI.

Five-year outcomes of immediate implant placement for mandibular molars with and without chronic apical periodontitis:A retrospective study

BACKGROUND Most physicians consider molars with chronic apical periodontitis(CAP)lesions as contraindications for immediate implant placement.At the patient’s request,we perform immediate implant placement of the mandibular molars with CAP in clinical practice.AIM To retrospectively analyze and compare the 5-year outcomes of immediate implant placement of the mandibular molars with CAP and those without obvious inflammation.METHODS The clinical data of patients with immediate implant placement of the mandibular molars in the Department of Oral and Maxillofacial Surgery,the Affiliated Hospital of Qingdao University,from June 2015 to June 2017 were collected.The patients were divided into CAP(n=52)and no-CAP(n=45)groups.Changes in bone mineral density and bone mass around implants were analyzed 5 years after implant restoration.RESULTS At 5 years after implantation,the peri-implant bone mineral density was 528.2±78.8 Hounsfield unit(HU)in the CAP group and 562.6±82.9 HU in the no-CAP group(P=0.126).Marginal bone resorption around implants did not differ significantly between the two groups,including buccal(P=0.268)or lingual(P=0.526)resorption in the vertical direction or buccal(P=0.428)or lingual(P=0.560)resorption in the horizontal direction.Changes in the peri-implant jump space did not differ significantly between the two groups,including the buccal(P=0.247)or lingual(P=0.604)space in the vertical direction or buccal(P=0.527)or lingual(P=0.707)space in the horizontal direction.The gray value of cone-beam computed tomography measured using Image J software can reflect the bone mineral density.In the CAP area,the gray values of the bone tissue immediately and 5 years after implant placement differed significantly from those of the surrounding bone tissue(P<0.01).CONCLUSION The results of this study suggest that immediate implant placement of the mandibular molars with CAP can achieve satisfactory 5-year clinical results,without significant differences in the complications,survival rate,or bone tissue condition from the no-CAP mandibular molars.

3D氨基质子转移加权成像联合弥散加权成像鉴别良、恶性骨与软组织肿瘤

目的探讨3D氨基质子转移加权成像(APTWI)、弥散加权成像(DWI)及二者联合鉴别良、恶性骨与软组织肿瘤的价值。方法前瞻性对96例骨盆或下肢骨与软组织肿瘤患者采集平扫MRI、APTWI及DWI。分别基于APTWI及DWI获得偏移量为3.5 ppm的非对称性磁化传递率(MTRasym)图及表观弥散系数(ADC)图,测量病灶MTRasym(3.5 ppm)最大值(MTRasym_(max))、均值(MTRasym_(mean))及最小值(MTRasym_(min)),以及ADC最大值(ADC_(max))、均值(ADC_(mean))及最小值(ADC_(min));比较良、恶性肿瘤各参数差异,绘制受试者工作特征曲线,计算曲线下面积(AUC),评估APTWI、DWI及二者联合的鉴别诊断效能。结果96例中,良性41例、恶性55例。恶性肿瘤MTRasym(MTRasym_(max)、MTRasym_(mean)和MTRasym_(min))均明显高于,而ADC(ADC_(max)、ADC_(mean)和ADC_(min))均明显低于良性肿瘤(P均<0.05)。MTRasym_(max)和ADC_(min)鉴别良、恶性肿瘤的AUC分别为0.791和0.873,差异无统计学意义(P=0.122);二者联合的AUC为0.944,高于单一项(P<0.001、P=0.041)。结论APTWI联合DWI鉴别良、恶性骨与软组织肿瘤的效能较高。

牙种植同期植骨术围术期高血压的相关危险因素

目的:探索牙种植同期植骨术中,围术期高血压的特点及相关危险因素。方法:对北京大学口腔医院某门诊科室2021年9月至2022年8月的728例牙种植及植骨术患者进行回顾性队列研究,分析研究对象围术期高血压与性别、年龄、手术时长、植骨术式4种暴露因素的关联性。结果:牙种植同期植骨术中,收缩压平均波动幅度为9.93%±6.63%(最大值50.41%),舒张压平均波动幅度为12.45%±8.79%(最大值68.75%),平均动脉压平均波动幅度为10.02%±6.61%(最大值为49.48%)。围术期高血压的发病率为26.77%。男性、年龄≥60岁、手术时长>60 min是围术期高血压的危险因素(P<0.05),相对危险度(95%CI)分别为1.74(1.21~2.50)、2.35(1.54~3.58)和1.65(1.15~2.38)。引导性骨再生术、上颌窦内提升术、上颌窦外提升术3种植骨术式围术期高血压发病率差异无统计学意义(P>0.05),但不同植骨方式下围术期高血压的影响因素不同。引导性骨再生术围术期高血压的危险因素为男性、年龄≥60岁和手术时长>60 min(P<0.05);上颌窦内提升术围术期高血压的危险因素为年龄≥60岁(P<0.05);而对于上颌窦外提升术,男性、年龄≥60岁、手术时长>60 min都不是围术期高血压的危险因素(P>0.05)。结论:牙种植同期植骨术中存在一定的围术期高血压风险,男性、年龄≥60岁和手术时间>60 min对围术期高血压的影响程度与植骨方式有关。

下肢骨搬运治疗患者参与自身健康照护体验与需求的质性研究

目的了解下肢骨搬运治疗患者参与自身健康照护过程中的体验与需求,为制订基于患者诉求的健康照护参与方案提供参考。方法2023年2-3月,采用描述性现象学研究方法,对在广东省某三级甲等医院创伤骨科行下肢骨搬运术治疗的12例患者进行半结构式访谈,运用Colaizzi 7步分析法进行资料分析。结果共提炼归纳出参与态度差异化(主动参与、被动接受)、参与过程存在障碍(角色思维固化、疾病负担制约、信息困境感知、医疗环境限制)、呈现多维度的参与需求(信息支持需求、情感支持需求、过渡期护理需求)3个主题。结论下肢骨搬运治疗患者参与自身健康照护过程中尚存在较多问题,医护人员应帮助其纠正角色认知偏差,提高其自我倡权意识和参与能力,关注其参与过程的障碍因素,优化多元支持系统,以促进患者围术期和过渡期自身健康照护的有效参与。

类风湿性关节炎与骨质疏松症和骨密度关系的孟德尔随机化分析

背景:许多临床研究观察表明类风湿性关节炎与骨质疏松症和骨密度之间存在密切关系,但类风湿性关节炎与骨质疏松症和骨密度之间是否存在因果遗传尚不清楚。目的:采用两样本孟德尔随机化研究方法评估类风湿性关节炎与骨质疏松症和骨密度之间潜在的因果关系,从遗传学的角度对潜在的机制提供有意义的见解,为早期预防骨质疏松症、改善疾病的发生发展提供参考。方法:从全基因组关联研究(GWAS)公开数据库中筛选出与类风湿性关节炎相关的(P<5×10^(-8))单核苷酸多态性位点作为工具变量。研究结局主要包括骨质疏松症、5个不同部位的骨密度,包括全身骨密度、腰椎骨密度、股骨颈骨密度、足跟骨密度以及前臂骨密度。逆方差加权法为该研究评估因果效应的主要分析方法,文章采用加权中位数法、简单中位数法、加权中值方法和MR-Egger回归用于补充说明,以比值比(OR)和95%可信区间(95%CI)评价类风湿性关节炎与骨质疏松症及骨密度风险之间的因果关系,使用类风湿性关节炎Cochran’s Q检验异质性,利用MR-Egger-intercept检验是否存在水平多效性。结果与结论:①逆方差加权法结果表明遗传预测的类风湿性关节炎与骨质疏松症呈正相关(OR=1.123,95%CI:1.077-1.171,P=4.02×10^(-8)),异质性检验表明单核苷酸多态性位点不存在异质性(P=0.388),MR-Egger-intercept检验未检测到水平多效性(P=0.571),敏感性分析显示研究结果没有产生偏倚。②类风湿性关节炎与5个部位的骨密度之间不存在因果关系显示如下:全身骨密度(OR=1.000,95%CI:0.988-1.012,P=0.925)、腰椎骨密度(OR=0.999,95%CI:0.982-1.016,P=0.937)、股骨颈骨密度(OR=1.001,95%CI:0.986-1.016,P=0.866)、足跟骨密度(OR=0.996,95%CI:0.989-1.004,P=0.419)、前臂骨密度(OR=1.063,95%CI:0.970-1.031,P=0.996)。MR-Egger-intercept分析未检测到潜在的水平多效性(全身骨密度:P=0.253;腰椎骨密度:P=0.638;股骨颈骨密度:P=0.553;足跟骨密度:P=0.444;前臂骨密度:P=0.079)。③类风湿性关节炎可能通过慢性炎症与骨的形成、骨溶解和吸收之间的相互作用导致骨质疏松症,此外,糖皮质激素的使用和类风湿性关节炎患者身体内的自身抗体(如抗瓜氨酸蛋白抗体)阳性也与骨质疏松症存在相关性。④未来研究需重点关注类风湿性关节炎患者全身免疫水平的系统性炎症指标、糖皮质激素的规范使用以及定期进行骨质疏松症风险筛查。

他汀类药物与骨密度:一项药物靶向孟德尔随机化分析

背景:观察性研究表明他汀类药物可能对骨密度具有保护作用,这使其成为潜在的骨质疏松症治疗药物之一。目的:通过孟德尔随机化方法来评估药物靶点介导的脂质表型与骨密度之间的因果关系。方法:从IEU Open GWAS数据库获取了与他汀类药物相关的单核苷酸多态性以及骨密度相关数据。主要分析方法是逆方差加权法,同时也使用了加权中位数法、简单中位数法、加权中值方法和MR-Egger回归法。使用β值和95%CI来评估他汀类药物与骨密度之间的因果关系;另外,进行敏感性分析以验证结果的可靠性,使用Cochran’s Q检验来评估异质性,使用MR-Egger截距检验是否存在水平多效性。使用留一法分析确定是否有单个或多个单核苷酸多态性影响了结果。结果与结论:他汀类药物作用靶点——3-羟基-3-甲基戊二酰辅酶A还原酶介导的低密度脂蛋白胆固醇与足跟定量超声骨密度(β=-0.086,95%CI:-0.117至-0.055,P=5.42×10^(-8))和全身骨密度(β=-0.193,95%CI:-0.288至-0.098,P=7.35×10^(-5))呈显著相关。该研究结果支持了他汀类药物对骨密度的保护作用。这些发现不仅加深了对胆固醇相关基因和骨骼健康关系的理解,还揭示了改善骨密度的潜在治疗靶点。