Causal impact of DNA methylation on refracture in elderly individuals with osteoporosis - a prospective cohort study.

BACKGROUND: Osteoporotic vertebral compression fractures (OVCF) in the elderly increase refracture risk post-surgery, leading to higher mortality rates. Genome-wide association studies (GWAS) have identified susceptibility genes for osteoporosis, but the phenotypic variance explained by these genes has been limited, indicating the need to explore additional causal factors. Epigenetic modifications, such as DNA methylation, may influence osteoporosis and refracture risk. However, prospective cohorts for assessing epigenetic alterations in Chinese elderly patients are lacking. Here, we propose to conduct a prospective cohort study to investigate the causal network of DNA polymorphisms, DNA methylation, and environmental factors on the development of osteoporosis and the risk of refracture. METHODS: We will collect vertebral and peripheral blood from 500 elderly OVCF patients undergoing surgery, extract DNA, and generate whole genome genotype data and DNA methylation data. Observation indicators will be collected and combined with one-year follow-up data. A healthy control group will be selected from a natural population cohort. Epigenome-wide association studies (EWAS) of osteoporosis and bone mineral density will be conducted. Differential methylation analysis will compare candidate gene methylation patterns in patients with and without refracture. Multi-omics prediction models using genetic variants and DNA methylation sites will be built to predict OVCF risk. DISCUSSION: This study will be the first large-scale population-based study of osteoporosis and bone mineral density phenotypes based on genome-wide data, multi-time point methylation data, and phenotype data. By analyzing methylation changes related to osteoporosis and bone mineral density in OVCF patients, the study will explore the feasibility of DNA methylation in evaluating postoperative osteoporosis intervention effects. The findings may identify new molecular markers for effective anti-osteoporosis treatment and inform individualized prevention and treatment strategies. TRIAL REGISTRATION: chictr.org.cn ChiCTR2200065316, 02/11/2022.

Orthogeriatric co-managements lower early mortality in long-lived elderly hip fracture: a post-hoc analysis of a prospective study.

OBJECTIVE: To evaluate the clinical effectiveness of orthogeriatric co-management care in long-lived elderly hip fracture patients (age ≥ 90). METHODS: Secondary analysis was conducted in long-lived hip fracture patients between 2018 to 2019 in 6 hospitals in Beijing, China. Patients were divided into the orthogeriatric co-management group (CM group) and traditional consultation mode group (TC group) depending on the management mode. With 30-day mortality as the primary outcome, multivariate regression analyses were performed after adjusting for potential covariates. 30-day mobility and quality of life were compared between groups. RESULTS: A total of 233 patients were included, 223 of whom completed follow-up (125 in CM group, 98 in TC group). The average age was 92.4 ± 2.5 years old (range 90-102). The 30-day mortality in CM group was significantly lower than that in TC group after adjustments for (2.4% vs. 10.2%; OR = 0.231; 95% CI 0.059 ~ 0.896; P = 0.034). The proportion of patients undergoing surgery and surgery performed within 48 h also favored the CM group (97.6% vs. 85.7%, P = 0.002; 74.4% vs. 24.5%, P < 0.001; respectively). In addition, much more patients in CM group could walk with or without aids in postoperative 30 days than in the TC group (87.7% vs. 60.2%, P < 0.05), although differences were not found after 1-year follow-up. And there was no significant difference in total cost between the two groups (P > 0.05). CONCLUSIONS: For long-lived elderly hip fracture patients, orthogeriatric co-management care lowered early mortality, improved early mobility and compared with the traditional consultation mode.

The effectiveness of percutaneous endoscopic decompression compared with open decompression and fusion for lumbar spinal stenosis: protocol for a multicenter, prospective, cohort study.

BACKGROUND: Lumbar spinal stenosis (LSS) is one of the most frequent indications for spine surgery. Open decompression and fusion surgery was the most common treatment and used to be regarded as the golden standard treatment for LSS. In recent years, percutaneous endoscopic decompression surgery was also used for LSS. However, the effectiveness and safety of percutaneous endoscopic decompression in the treatment of LSS have not been supported by high-level evidence. Our aim is to 1) compare the effectiveness of percutaneous endoscopic decompression surgery and open decompression and fusion for the treatment of LSS. 2) Investigate the prognosis risk factors for LSS. 3) Evaluate the influence of percutaneous endoscopic decompression for the stability of operative level, and degeneration of adjacent level. METHODS: It's a prospective, multicenter cohort study. The study is performed at 4 centers in Beijing. This study plans to enroll 600 LSS patients (300 patients in the percutaneous endoscopic decompression group, and 300 patients in the open decompression and fusion group). The demographic variables, healthcare variables, symptom related variables, clinical assessment (Visual analogue score (VAS), Oswestry disability index (ODI), Japanese Orthopaedic Association score (JOA)), and radiological assessment (dynamic X-ray, CT, MRI) will be collected at baseline visit. Patients will follow up at 3, 6, 12 months. The primary outcome is the difference of improvement of ODI between baseline and 12-month follow-up between the two groups. The secondary outcome is the score changes of preoperative and postoperative VAS, the recovery rate of JOA, MacNab criteria, patient satisfaction, degeneration grade of adjacent level, ROM of operative level and adjacent level, complication rate. DISCUSSION: In this study, we propose to conduct a prospective registry study to address the major controversies of LSS decompression under percutaneous spinal endoscopy, and investigate the clinical efficacy and safety of percutaneous endoscopic decompression and open decompression in the treatment of LSS. TRIAL REGISTRATION: This study has been registered on clinicaltrials.gov in January 15, 2020 ( NCT04254757 ). (SPIRIT 2a).

The effectiveness of a co-management care model on older hip fracture patients in China - A multicentre non-randomised controlled study.

BACKGROUND: Clinical guidelines recommend orthogeriatric care to improve older hip fracture patients' outcomes, but few studies have been conducted in China. This study evaluated the effects of an orthogeriatric co-management care model in six Chinese hospitals. METHODS: This non-randomised controlled study was designed as an exploratory trial and was conducted in 3 urban and 3 suburban hospitals. Eligible patients were aged ≥ 65 years with X-ray confirmed hip fracture and admitted to hospital within 21 days of injury. All patients received three times follow-ups within one year (1-month, 4-month and 12-month post admission). Co-management care was implemented in 1 urban hospital, while usual care continued in 5 urban and suburban hospitals. Patient demographics, pre-, peri- and post-operative information, complications and mortality were collected at baseline and follow-ups. The primary outcome was proportion of patients receiving surgery within 48 hours from ward arrival. Secondary outcomes included osteoporosis assessment, in-hospital rehabilitation, length of hospital stay, in-hospital mortality and one-year cumulative mortality. FINDINGS: There were 2,071 eligible patients enrolled (1,110 intervention, 961 control). Compared to usual care, a significantly higher proportion of intervention patients received surgery within 48 hours (75% vs 27%, p<0.0001), osteoporosis assessment (99.9% vs 60.6%, p<0.0001), rehabilitation (99.1% vs 3.9%, p<0.0001) and shorter length of hospital stay (6.1 days vs 12.0 days, p<0.0001). The intervention group saw a significant lower in-hospital mortality rate than the control group (adjusted relative risk 0.021, 95% CI 0.001 to 0.45, P=0.01). One-year cumulative mortality was also significantly reduced in the intervention group (hazard ratio 0.59, 95% CI 0.38 to 0.80, p=0.01). INTERPRETATION: Co-management care of older hip fracture patients resulted in better outcomes, including decreased time to surgery, improved clinical management, and reduced one-year mortality. A randomised controlled trial is needed to provide definitive evidence. FUNDING: The study is supported by Capital's Funds for Health Improvement and Research (2018-1-2071).

[Analysis of complications of osteosarcoma around knee treated by resection and replacement of tumor-type prosthesis].

OBJECTIVE: To summarize the effects and complications of osteosarcoma around knee treated by wide resection and replacement by the tumor-type prosthesis. METHODS: Between July 1997 and July 2004, 117 patients with osteosarcoma around the knee had been treated with wide resection and reconstruction with prosthesis. Alcohol-devitalized tumor bone prosthetic composite were used for reconstruction in 13 patients, and allograft prosthetic composite (APC) were used in 25 patients. All patients accepted 2 cycles of chemotherapy before the surgery. RESULTS: The mean follow-up period was 3.5 years (1 - 8 years). Nine patients had failure of union at the graft-host junction. Fracture of the stem of the prosthesis occurred in 5 patients, late infection was found in 19 patients, and aseptic loosening occurred in 3 patients. Bone fracture occurred in 1 patient and prosthesis sinking occurred in 2 patients. CONCLUSIONS: The tumor-type prosthetic reconstruction offers the best knee function after resection of the tumor around the knee, and recurrence rate can be accepted. However, the tumor-type prosthesis needs further improvement because of the high complication rate.