Risk factors for subsequent fractures in hip fracture patients: a nested case-control study.

BACKGROUND: The risk factors for subsequent fractures following an initial hip fracture are not entirely understood. This study examined the clinical characteristics of hip fracture patients to identify potential risk factors associated with a higher risk of experiencing subsequent fractures. METHODS: We conducted a nested case-control study using data from the Chinese PLA General Hospital Hip Fracture Cohort between January 2008 and March 2022. The cases were individuals who experienced subsequent fractures following an initial hip fracture. Each case was matched with up to 2 controls who did not develop subsequent fractures. Important clinical factors were compared across groups, including traditional fracture risk factors and potential risk factors (e.g., comorbidities, falls risk, physical impairment, calcium or vitamin D use, and anti-osteoporosis medications). Conditional logistic regression analyses were used to evaluate the impact of these clinical features as potential risk factors for subsequent fractures. RESULTS: A total of 96 individuals who suffered from subsequent fractures were matched with 176 controls. The median time between the initial hip fracture and the subsequent fracture was 2.1 years. The overall proportion of patients receiving anti-osteoporosis treatment after initial hip fracture was 25.7%. In the multivariable regression analysis, living in a care facility (OR = 3.78, 95%CI: 1.53-9.34), longer hospital stays (OR = 1.05, 95%CI: 1.00-1.11), and falls after discharge (OR = 7.58, 95%CI: 3.37-17.04) were associated with higher odds of subsequent fractures. CONCLUSIONS: This study showed that living in a care facility, longer hospital stays, and falls after discharge may be independent risk factors for repeat fractures following an initial hip fracture. These findings could be used to identify and manage patients at high risk of subsequent fractures.

Evolution of Musculoskeletal Electronics.

The musculoskeletal system, constituting the largest human physiological system, plays a critical role in providing structural support to the body, facilitating intricate movements, and safeguarding internal organs. By virtue of advancements in revolutionized materials and devices, particularly in the realms of motion capture, health monitoring, and postoperative rehabilitation, "musculoskeletal electronics" has actually emerged as an infancy area, but has not yet been explicitly proposed. In this review, the concept of musculoskeletal electronics is elucidated, and the evolution history, representative progress, and key strategies of the involved materials and state-of-the-art devices are summarized. Therefore, the fundamentals of musculoskeletal electronics and key functionality categories are introduced. Subsequently, recent advances in musculoskeletal electronics are presented from the perspectives of "in vitro" to "in vivo" signal detection, interactive modulation, and therapeutic interventions for healing and recovery. Additionally, nine strategy avenues for the development of advanced musculoskeletal electronic materials and devices are proposed. Finally, concise summaries and perspectives are proposed to highlight the directions that deserve focused attention in this booming field.

Effect of denosumab on glucose metabolism in postmenopausal osteoporotic women with prediabetes: a study protocol for a 12-month multicenter, open-label, randomized controlled trial.

BACKGROUND: Participants with prediabetes are at a high risk of developing type 2 diabetes (T2D). Recent studies have suggested that blocking the receptor activator of nuclear factor-κB ligand (RANKL) may improve glucose metabolism and delay the development of T2D. However, the effect of denosumab, a fully human monoclonal antibody that inhibits RANKL, on glycemic parameters in the prediabetes population is uncertain. We aim to examine the effect of denosumab on glucose metabolism in postmenopausal women with osteoporosis and prediabetes. METHODS: This is a 12-month multicenter, open-label, randomized controlled trial involving postmenopausal women who have been diagnosed with both osteoporosis and prediabetes. Osteoporosis is defined by the World Health Organization (WHO) as a bone mineral density T score of ≤ - 2.5, as measured by dual-energy X-ray absorptiometry (DXA). Prediabetes is defined as (i) a fasting plasma glucose level of 100-125 mg/dL, (ii) a 2-hour plasma glucose level of 140-199 mg/dL, or (iii) a glycosylated hemoglobin A1c (HbA1c) level of 5.7-6.4%. A total of 346 eligible subjects will be randomly assigned in a 1:1 ratio to receive either subcutaneous denosumab 60 mg every 6 months or oral alendronate 70 mg every week for 12 months. The primary outcome is the change in HbA1c levels from baseline to 12 months. Secondary outcomes include changes in fasting and 2-hour blood glucose levels, serum insulin levels, C-peptide levels, and insulin sensitivity from baseline to 12 months, and the incidence of T2D at the end of the study. Follow-up visits will be scheduled at 3, 6, 9, and 12 months. DISCUSSION: This study aims to provide evidence on the efficacy of denosumab on glucose metabolism in postmenopausal women with osteoporosis and prediabetes. The results derived from this clinical trial may provide insight into the potential of denosumab in preventing T2D in high-risk populations. TRIAL REGISTRATION: This study had been registered in the Chinese Clinical Trials Registry. REGISTRATION NUMBER: ChiCTR2300070789 on April 23, 2023. https://www.chictr.org.cn .

Combining single-cell RNA sequencing and population-based studies reveals hand osteoarthritis-associated chondrocyte subpopulations and pathways.

Hand osteoarthritis is a common heterogeneous joint disorder with unclear molecular mechanisms and no disease-modifying drugs. In this study, we performed single-cell RNA sequencing analysis to compare the cellular composition and subpopulation-specific gene expression between cartilage with macroscopically confirmed osteoarthritis (n = 5) and cartilage without osteoarthritis (n = 5) from the interphalangeal joints of five donors. Of 105 142 cells, we identified 13 subpopulations, including a novel subpopulation with inflammation-modulating potential annotated as inflammatory chondrocytes. Fibrocartilage chondrocytes exhibited extensive alteration of gene expression patterns in osteoarthritic cartilage compared with nonosteoarthritic cartilage. Both inflammatory chondrocytes and fibrocartilage chondrocytes showed a trend toward increased numbers in osteoarthritic cartilage. In these two subpopulations from osteoarthritic cartilage, the ferroptosis pathway was enriched, and expression of iron overload-related genes, e.g., FTH1, was elevated. To verify these findings, we conducted a Mendelian randomization study using UK Biobank and a population-based cross-sectional study using data collected from Xiangya Osteoarthritis Study. Genetic predisposition toward higher expression of FTH1 mRNA significantly increased the risk of hand osteoarthritis (odds ratio = 1.07, 95% confidence interval: 1.02-1.11) among participants (n = 332 668) in UK Biobank. High levels of serum ferritin (encoded by FTH1), a biomarker of body iron overload, were significantly associated with a high prevalence of hand osteoarthritis among participants (n = 1 241) of Xiangya Osteoarthritis Study (P-for-trend = 0.037). In conclusion, our findings indicate that inflammatory and fibrocartilage chondrocytes are key subpopulations and that ferroptosis may be a key pathway in hand osteoarthritis, providing new insights into the pathophysiology and potential therapeutic targets of hand osteoarthritis.

Prognostic nutritional index with postoperative complications and 2-year mortality in hip fracture patients: an observational cohort study.

BACKGROUND: The prognostic nutritional index (PNI) has been proposed as a useful prognostic tool in multiple populations. However, its prognostic value has not been fully evaluated in the hip fracture population. We aimed to assess the relationship between PNI and postoperative complications as well as 2-year all-cause mortality in the hip fracture population. MATERIALS AND METHODS: We included patients aged 45 or older who underwent surgery for hip fracture between 2000 and 2022. The baseline serum albumin and total lymphocyte count were used to calculate PNI with the following formula: 10×serum albumin level (g/dl)+0.005×total lymphocyte count (per mm 3 ). Patients were classified into low, medium, and high categories based on tertiles of PNI (≤43.23, 43.23-47.35, and >47.35, respectively). Logistic regression and Cox proportional hazards models were used to calculate the odds ratio (OR) for postoperative compilations and the hazard ratio (HR) for mortality, adjusting for potential confounders. RESULTS: Of 3351 hip patients, 236 (7.04%) developed postoperative complications, and 305 (9.10%) died during the 2-year follow-up. Compared to the low-category patients, the medium-category and high-category patients showed lower odds of postoperative complications (ORs 0.69, 95% CI 0.48-0.98; and 0.61, 95% CI 0.40-0.93, respectively), and lower hazards of 2-year mortality (HRs 0.66, 95% CI 0.49-0.88; and 0.61, 95% CI 0.42-0.88, respectively). These associations were robust across a series of analyses, including subgroup analyses and dose-response sensitivity analyses. CONCLUSION: PNI is an independent predictor of postoperative complications and 2-year all-cause mortality in hip fracture patients. PNI can be used to identify patients who may be at high risk of a poor prognosis.

Denosumab and incidence of type 2 diabetes among adults with osteoporosis: population based cohort study.

OBJECTIVE: To estimate the effect of denosumab compared with oral bisphosphonates on reducing the risk of type 2 diabetes in adults with osteoporosis. DESIGN: Population based study involving emulation of a randomized target trial using electronic health records. SETTING: IQVIA Medical Research Data primary care database in the United Kingdom, 1995-2021. PARTICIPANTS: Adults aged 45 years or older who used denosumab or an oral bisphosphonate for osteoporosis. MAIN OUTCOME MEASURES: The primary outcome was incident type 2 diabetes, as defined by diagnostic codes. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals, comparing denosumab with oral bisphosphonates using an as treated approach. RESULTS: 4301 new users of denosumab were matched on propensity score to 21 038 users of an oral bisphosphonate and followed for a mean of 2.2 years. The incidence rate of type 2 diabetes in denosumab users was 5.7 (95% confidence interval 4.3 to 7.3) per 1000 person years and in oral bisphosphonate users was 8.3 (7.4 to 9.2) per 1000 person years. Initiation of denosumab was associated with a reduced risk of type 2 diabetes (hazard ratio 0.68, 95% confidence interval 0.52 to 0.89). Participants with prediabetes appeared to benefit more from denosumab compared with an oral bisphosphonate (hazard ratio 0.54, 0.35 to 0.82), as did those with a body mass index ≥30 (0.65, 0.40 to 1.06). CONCLUSIONS: In this population based study, denosumab use was associated with a lower risk of incident type 2 diabetes compared with oral bisphosphonate use in adults with osteoporosis. This study provides evidence at a population level that denosumab may have added benefits for glucose metabolism compared with oral bisphosphonates.

Preoperative Anemia and Risk of In-hospital Postoperative Complications in Patients with Hip Fracture.

Purpose: To evaluate the impact of preoperative anemia on postoperative complications after hip fracture surgery. Patients and Methods: We conducted a retrospective study including hip fracture patients at a teaching hospital between 2005 and 2022. We defined preoperative anemia as the last hemoglobin measurement level before surgery < 130 g/L for men and < 120 g/L for women. The primary outcome was a composite of in-hospital major complications, including pneumonia, respiratory failure, gastrointestinal bleeding, urinary tract infection, incision infection, deep venous thrombosis, pulmonary embolism, angina pectoris, arrhythmia, myocardial infarction, heart failure, stroke, and death. Secondary outcomes were cardiovascular events, infection, pneumonia, and death. We used multivariate negative binomial or logistic regression to evaluate the impact of anemia and its severity, categorized as mild (90-130 g/L for men, 90-120 g/L for women) or moderate-to-severe (< 90 g/L for both) anemia on outcomes. Results: Of the 3540 included patients, 1960 had preoperative anemia. 188 anemic patients experienced 324 major complications, while 63 non-anemic patients had 94 major complications. The risk of major complications was 165.3 (95% CI, 149.5-182.4) and 59.5 (95% CI, 48.9-72.3) per 1000 persons in anemic and non-anemic patients, respectively. Anemic patients were more likely to have major complications than non-anemic patients (adjusted incidence rate ratio (aIRR), 1.87; 95% CI, 1.30-2.72), which was consistent in mild (aIRR, 1.77; 95% CI, 1.22-2.59) and moderate-to-severe (aIRR, 2.97; 95% CI, 1.65-5.38) anemia. Preoperative anemia also increased the risk of cardiovascular events (aIRR, 1.96; 95% CI, 1.29-3.01), infection (aIRR, 1.68; 95% CI, 1.01-2.86), pneumonia (adjusted odds ratio (aOR), 1.91; 95% CI, 1.06-3.57), and death (aOR, 3.17; 95% CI, 1.06-11.89). Conclusion: Our findings suggest that even mild preoperative anemia is associated with major postoperative complications in hip fracture patients. This finding highlights considering preoperative anemia as a risk factor in surgical decision-making for high-risk patients.

Lowering Serum Urate With Urate-Lowering Therapy to Target and Incident Fracture Among People With Gout.

OBJECTIVE: Gout is associated with a higher risk of fracture; however, findings on the associations of hyperuricemia and urate-lowering therapy (ULT) with the risk of fracture have been inconsistent. We examined whether lowering serum urate (SU) levels with ULT to a target level (i.e., <360 µmoles/liter) reduces the risk of fracture among individuals with gout. METHODS: We emulated analyses of a hypothetical target trial using a "cloning, censoring, and weighting" approach to examine the association between lowering SU with ULT to the target levels and the risk of fracture using data from The Health Improvement Network, a UK primary care database. Individuals with gout who were age 40 years or older and for whom ULT was initiated were included in the study. RESULTS: Among 28,554 people with gout, the 5-year risk of hip fracture was 0.5% for the "achieving the target SU level" arm and 0.8% for the "not achieving the target SU level" arm. The risk difference and hazard ratio for the "achieving the target SU level" arm was -0.3% (95% confidence interval [95% CI] -0.5%, -0.1%) and 0.66 (95% CI 0.46, 0.93), respectively, compared with the "not achieving the target SU level" arm. Similar results were observed when the associations between lowering SU level with ULT to the target levels and the risk of composite fracture, major osteoporotic fracture, vertebral fracture, and nonvertebral fracture were assessed. CONCLUSION: In this population-based study, lowering the SU level with ULT to the guideline-based target level was associated with a lower risk of incident fracture in people with gout.

Intramedullary nailing versus plating fixation for the treatment of midshaft clavicular fractures: A meta-analysis of randomized controlled trials.

PURPOSE: This study was to test the hypothesis that intramedullary (IM) nailing fixation of midshaft clavicle fractures could result in better clinical outcomes and lower complications rates than plating fixation. METHODS: PubMed, Embase, and the Cochrane Library database were used to search all English language published randomized controlled trials (RCTs) of midshaft clavicle fractures using plating versus IM nailing. The characteristics of the study participants were collected. Outcomes of postoperative shoulder functional measurements, operative data and complications rates were meta-analyzed. RESULTS: Eight hundred and ninety-five patients in ten RCTs and three quasi-RCTs were involved in the meta-analysis. The results of meta-analysis of these studies showed that the functional outcome evaluated by the Constant Shoulder and Disabilities of the Arm, Shoulder and Hand (DASH) scores after accepting IM nailing was significantly better than that of plating fixation at one year post-operatively (P < 0.01), with the heterogeneity of 43% and 91%, respectively. Sensitivity analyses of the pooled results of Constant and DASH scores displayed that the functional advantage of IM nailing fixation comes from the subgroup of locked IM nailing. Further, regarding the operative statistics, operative time, blood loss and wound length were significantly less in the IM nailing group than the plating group (P < 0.001). The rates of infection, major complications and complications-related revision surgery were significantly higher in the plating group than the IM nailing group; however, there were no significantly statistical differences in other complications, e.g., nonunion, refracture after hardware removal, implant failure, symptomatic hardware, etc. (P > 0.05). CONCLUSION: The observations in this review suggested that IM nailing, especially locked IM nailing, could provide better shoulder functional outcome at one-year follow-up. Moreover, IM nailing fixation could effectively reduce operative time, blood loss, rates of infection, major complications, and revision surgery than plating. Further high-quality clinical trials with large samples and consistent designs are still needed to verify the long-term functional advantage of locked and unlocked IM nailing for midshaft clavicle fractures. LEVEL OF EVIDENCE: Level II.

Angiotensin receptor blockade is associated with increased risk of giant cell arteritis.

OBJECTIVES: Angiotensin II is implicated in GCA pathology. We examined whether the use of angiotensin receptor blockers (ARBs) is associated with GCA risk compared with angiotensin-converting enzyme inhibitors (ACEis) or other antihypertensives. METHODS: We performed a matched cohort study including adults who were initiators of antihypertensives in UK primary care data between 1995 and 2019. Treatment-naïve individuals without prior GCA or PMR were categorized into three groups-ARB initiators, ACEi initiators, or other antihypertensive initiators (beta-blockers, calcium channel blockers, diuretics or alpha-adrenoceptor blockers)-and followed for up to 5 years. Incident GCA was defined using validated Read codes, with age of onset ≥50 years and two or more glucocorticoid prescriptions. Inverse probability-weighted Cox models were used to model outcome risk, adjusting for lifestyle parameters, comorbidities and comedications. RESULTS: Among >1 million new starters of antihypertensives (81 780 ARBs, 422 940 ACEis and 873 066 other antihypertensives), the incidence rate of GCA per 10 000 patient-years was 2.73 (95% CI 2.12, 3.50) in the ARB group, 1.76 (95% CI 1.25, 2.39) in the ACEi group and 1.90 (95% CI 1.37, 2.56) in the other antihypertensives group. The hazard of GCA was higher in ARB initiators [hazard ratio (HR) 1.55; 95% CI 1.16, 2.06] than initiators of ACEis, but similar between initiators of other antihypertensives and ACEis (HR 1.08; 95% CI 0.87, 1.35). CONCLUSIONS: Initiation of ARBs is associated with a higher risk of GCA compared with ACEis or other antihypertensives. Mechanistic studies of angiotensin receptor biology will provide further clarity for our findings.

Novel slide compression anatomic plates of the femoral neck for treating unstable femoral neck fracture: A biomechanical study.

To compare the biomechanical stability of slide compression anatomic plates of the femoral neck, cannulated compression screws and dynamic hip screws with derotation screws for stabilizing unstable femoral neck fractures (Pauwels angle = 70°). Pauwels III femoral neck fractures were created on 45 Sawbones femurs and randomly assigned to three implant groups (1:1:1). The biomechanical stability of all Sawbones in each treatment group was evaluated with three tests. First, in the static loading test, the load-displacement curve, vertical stiffness (load/vertical displacement [N/mm]) and 5 mm failure load were recorded. Second, in the incremental cyclic loading test (700, 1000, and 1400 N), the cyclic-displacement curve and the displacement of the fragments were recorded. Third, in the torsion test, the torsional rigidity, maximum torque, and torsional angle corresponding to the maximum torque were recorded. The static compression test showed that slide compression anatomic place-femoral neck (SCAP-FN) had the largest vertical stiffness (275 ± 11 N/mm, p < 0.01) and 5 mm failure load (1232 ± 156, p < 0.01). The cyclic loading test showed that SCAP-FN had the lowest change in displacement after 30000 cycles of loading. The torsional stiffness and the maximum torque followed the order SCAP-FN > dynamic hip screw systems (DHS) + derotational screw (DS) > CCS, and the torsional angle corresponding to the maximum torque followed the order SCAP-FN < DHS + DS < CCS. The SCAP-FN construct provides stiffness and stability compared with other standard fixation techniques (3CS and DHS + DS). The fixation strategy of SCAP-FN might be sufficient for clinical use, indicating studies in the human body are warranted.

Using observational study data as an external control group for a clinical trial: an empirical comparison of methods to account for longitudinal missing data.

BACKGROUND: Observational data are increasingly being used to conduct external comparisons to clinical trials. In this study, we empirically examined whether different methodological approaches to longitudinal missing data affected study conclusions in this setting. METHODS: We used data from one clinical trial and one prospective observational study, both Norwegian multicenter studies including patients with recently diagnosed rheumatoid arthritis and implementing similar treatment strategies, but with different stringency. A binary disease remission status was defined at 6, 12, and 24 months in both studies. After identifying patterns of longitudinal missing outcome data, we evaluated the following five approaches to handle missingness: analyses of patients with complete follow-up data, multiple imputation (MI), inverse probability of censoring weighting (IPCW), and two combinations of MI and IPCW. RESULTS: We found a complex non-monotone missing data pattern in the observational study (N = 328), while missing data in the trial (N = 188) was monotone due to drop-out. In the observational study, only 39.0% of patients had complete outcome data, compared to 89.9% in the trial. All approaches to missing data indicated favorable outcomes of the treatment strategy in the trial and resulted in similar study conclusions. Variations in results across approaches were mainly due to variations in estimated outcomes for the observational data. CONCLUSIONS: Five different approaches to handle longitudinal missing data resulted in similar conclusions in our example. However, the extent and complexity of missing observational data affected estimated comparative outcomes across approaches, highlighting the need for careful consideration of methods to account for missingness in this setting. Based on this empirical examination, we recommend using a prespecified advanced missing data approach to account for longitudinal missing data, and to conduct alternative approaches in sensitivity analyses.

Peptic Ulcer Disease and Risk of Hip Fracture: A General Population-based Cohort Study.

AIMS: Previous studies reported proton pump inhibitor (PPI) use may increase the risk of fracture; however, the findings may be susceptible to indication bias because peptic ulcer disease (PUD), 1 major indication for PPIs, may affect skeletal health. Determining whether PUD would increase hip fracture risk may help identify high-risk populations and explore risk factors. METHODS: We conducted a cohort study using data from The Health Improvement Network (THIN) in the United Kingdom. THIN contains patient information such as disease diagnosis and medicine prescriptions. Up to 5 non-PUD individuals (n = 138 265) were matched to each case of incident PUD (n = 27 653) by age, sex, and body mass index. We examined the association between PUD and hip fracture by a multivariable Cox proportional hazard model. We repeated the same analysis among individuals with incident PUD and gastroesophageal reflux disease (GERD) (n = 27 160), another disease with similar indication for PPIs, as a positive control exposure. RESULTS: Over a mean of 5.6 years of follow-up, hip fracture occurred in 589 individuals with PUD and 2015 individuals without PUD (3.8 vs 2.6/1000 person-years), with a multivariable-adjusted hazard ratio (HR) being 1.44 (95% confidence interval [CI], 1.31-1.58). The association persisted among subgroups stratified by sex and age. In positive control exposure analysis, the hip fracture risk was also higher in PUD than GERD (3.8 vs 2.4/1000 person-years; multivariable-adjusted HR = 1.65; 95% CI, 1.45-1.7). CONCLUSIONS: This general population-based cohort study suggests, after controlling for acid-lowering medication and other potential risk factors, PUD is independently associated with an increased risk of hip fracture.

Genetically predicted vitamin K levels and risk of osteoarthritis: Mendelian randomization study.

OBJECTIVE: Osteoarthritis (OA) is a progressive disease for which there is no disease modifying therapy. Vitamin K levels and vitamin K antagonism have been associated with risk and progression of OA which may have direct implications for clinical management, but these observational findings are susceptible to confounding. We aimed to estimate the causal association between vitamin K and OA risk using Mendelian randomisation (MR). METHODS: We used data from the largest genome-wide association study (GWAS) of OA to date (up to 826,690 individuals) to estimate the effect of genetically predicted vitamin K level (instrumented using four variants derived from a GWAS of 2,138 individuals) on risk of all OA types, knee, hip, spine, hand OA, and total joint replacement. We employed the inverse-variance weighted method for the primary analysis and, in a series of sensitivity analyses, adjusted for sub-genome wide significant instruments and tested for potential bias from pleiotropy. RESULTS: We showed that genetically predicted vitamin K levels were not causally associated with risk of OA overall (OR 0.98 per unit increase in log-transformed vitamin K1; 95%CI 0.96-1.01), knee (OR 0.98; 0.92-1.03), hip (OR 0.97; 0.88-1.07), spine (OR 0.97; 0.90-1.04), hand OA (OR 0.97; 0.91-1.04) or joint replacement (OR 0.96; 0.89-1.04). Results were similar across all sensitivity analyses. CONCLUSION: We found little evidence of a causal association between genetically predicted vitamin K and OA risk. Larger genetic and interventional studies of vitamin K are required to confirm our findings.

Denosumab and Risk of Community-acquired Pneumonia: A Population-based Cohort Study.

CONTEXT: Recent meta-analyses of randomized controlled trials have raised concerns that denosumab might increase the risk of infection. However, data of denosumab on the risk of community-acquired pneumonia are sparse. OBJECTIVE: This work aimed to examine the risk of community-acquired pneumonia in individuals receiving denosumab compared to those receiving alendronate. METHODS: We conducted a propensity score-matched cohort study with a UK primary care database (IQVIA Medical Research Database). We examined the relation of denosumab to community-acquired pneumonia using a Cox proportional hazard model. The study participants were osteoporotic patients older than 45 years who were initiators of denosumab or alendronate from August 1, 2010, to September 17, 2020. The outcome measure was community-acquired pneumonia. RESULTS: Patients treated with denosumab (n = 933) were compared with those treated with alendronate (n = 4652). In the matched population, the mean (SD) age was 77 (11) years, 89% were women, and about half of the study population had a history of major osteoporotic fracture. Over 5 years of follow-up, the incidence of community-acquired pneumonia per 1000 person-years was 72.0 (95% CI, 60.1-85.7) in the denosumab group and 75.1 (95% CI, 69.4-81.2) in the alendronate group. The hazard of community-acquired pneumonia was similar between denosumab and alendronate users (hazard ratio [HR] 0.96; 95% CI, 0.79-1.16). The results remained consistent in a series of sensitivity analyses, with HR ranging from 0.82 (95% CI, 0.65-1.04) to 0.99 (95% CI, 0.81-1.21). CONCLUSION: Denosumab does not significantly increase the susceptibility of community-acquired pneumonia and could possibly be safely used for the management of osteoporosis.

Chronic kidney disease and risk of postoperative cardiovascular events in elderly patients receiving hip fracture surgery.

INTRODUCTION: The long-term risk of cardiovascular events caused by chronic kidney disease (CKD) is well described in the general population. Less is known concerning the risk of postoperative cardiovascular events in geriatric hip fracture patients with CKD. METHODS: This study involved patients at least 65 years of age who received surgery for acute hip fracture between January 2000 and April 2016. We identified CKD patients with a baseline diagnosis of CKD or an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 at admission. Each CKD patient was matched, for age, gender, fracture type, and year of admission, with 4 control non-CKD patients. The primary endpoint was a compositepostoperative cardiovascular events, including pulmonary embolism, angina pectoris, myocardial infarction, heart failure, arrhythmia, stroke, and death. Conditional logistic regression was used to evaluate the association between CKD and the outcome after adjusting for potential confounders including age, gender, fracture type, body mass index, preexisting comorbidities, history of cardiovascular events, and the Charlson Comorbidity Index (CCI). RESULTS: Three hundred and seventy-five CKD patients were matched with 1,438 non-CKD patients. The mean age of the CKD patients was 81.9 ± 7.0 (mean ± SD), 69.9% were females, and 59.2% had an intertrochanteric fracture. Compared to non-CKD patients, CKD patients had a higher proportion of preexisting comorbidities, including hypertension, coronary heart disease, heart failure, and type 2 diabetes (all p < 0.05). The risk of postoperative cardiovascular events was 125.3 per 1000 persons (95%CI, 91.8-158.8) in CKD patients and 64.7 per 1000 persons (95%CI, 52.0-77.4) in non-CKD patients. A 1.96-fold risk of cardiovascular events after hip fracture surgery was found in CKD patients than those without CKD (adjusted OR, 1.96; 95%CI, 1.23-3.12). CONCLUSION: Patients with CKD were more likely to have cardiovascular events after hip fracture surgery than those without CKD. Appropriate preoperative cardiovascular risk assessment and corresponding preventive and therapeutic measures should be given to this vulnerable population to mitigate such complications.

Allopurinol Initiation and All-Cause Mortality Among Patients With Gout and Concurrent Chronic Kidney Disease : A Population-Based Cohort Study.

BACKGROUND: Two recent randomized clinical trials of escalating doses of allopurinol for the progression of chronic kidney disease (CKD) reported no benefits but potentially increased risk for death. Whether the risk could occur in patients with gout and concurrent CKD remains unknown. OBJECTIVE: To examine the relation of allopurinol initiation, allopurinol dose escalation, and achieving target serum urate (SU) level after allopurinol initiation to all-cause mortality in patients with both gout and CKD. DESIGN: Cohort study. SETTING: The Health Improvement Network U.K. primary care database (2000 to 2019). PARTICIPANTS: Patients aged 40 years or older who had gout and concurrent moderate-to-severe CKD. MEASUREMENTS: The association between allopurinol initiation and all-cause mortality over 5-year follow-up in propensity score (PS)-matched cohorts was examined. Analysis of hypothetical trials were emulated: achieving target SU level (<0.36 mmol/L) versus not achieving target SU level and dose escalation versus no dose escalation for mortality over 5-year follow-up in allopurinol initiators. RESULTS: Mortality was 4.9 and 5.8 per 100 person-years in 5277 allopurinol initiators and 5277 PS-matched noninitiators, respectively (hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.93]). In the target trial emulation analysis, the HR of mortality for the achieving target SU level group compared with the not achieving target SU level group was 0.87 (CI, 0.75 to 1.01); the HR of mortality for allopurinol in the dose escalation group versus the no dose escalation group was 0.88 (CI, 0.73 to 1.07). LIMITATION: Residual confounding cannot be ruled out. CONCLUSION: In this population-based data, neither allopurinol initiation, nor achieving target SU level with allopurinol, nor allopurinol dose escalation was associated with increased mortality in patients with gout and concurrent CKD. PRIMARY FUNDING SOURCE: Project Program of National Clinical Research Center for Geriatric Disorders.

Risk of post-operative cardiovascular event in elderly patients with pre-existing cardiovascular disease who are undergoing hip fracture surgery.

PURPOSE: To evaluate the association between pre-existing cardiovascular disease (CVD) and the risk of developing post-operative cardiovascular event among elderly patients who underwent hip fracture surgery. METHODS: We performed an observational study among patients with acute hip fracture aged at least 65 years and who received surgical intervention. Hip fracture patients with pre-existing CVD were matched for age, gender, fracture type, and year of admission with patients without pre-existing CVD. The primary endpoint was post-operative cardiovascular events, and patients were followed until discharge from hospital. Conditional logistic regression was used to determine the association between pre-existing CVD and post-operative cardiovascular event after adjusting for potential confounders including age, body mass index, time from fracture to surgery, pre-existing comorbidities, and the Charlson Comorbidity Index (CCI). RESULTS: The study matched 858 pairs of patients with and without pre-existing CVD. Post-operative cardiovascular events developed in 40 and 14 patients with and without pre-existing CVD (44.6 versus 16.3 per 1000 persons), respectively. Compared to patients without pre-existing CVD, patients with any pre-existing CVD were more likely to develop post-operative cardiovascular events, with a crude odds ratio (OR) of 2.857 [95% confidence interval (CI), 1.554 to 5.251] and multivariable adjusted OR of 2.850 (95% CI, 1.318 to 7.139), respectively. CONCLUSION: In elderly patients who received hip fracture surgery, patients with pre-existing CVD are at a higher risk of developing post-operative cardiovascular events. Appropriate screening for this vulnerable population is recommended to prevent the risk of post-operative complications.

Trends in Comorbidities and Postoperative Complications of Geriatric Hip Fracture Patients from 2000 to 2019: Results from a Hip Fracture Cohort in a Tertiary Hospital.

OBJECTIVE: To describe the secular trends in comorbidities and postoperative complications of geriatric hip fracture patients from the Chinese People's Liberation Army General Hospital Hip Fracture Cohort between 2000 and 2019. METHODS: We included 2,805 hip fracture patients aged 65 years or older and received surgical treatment from 25 January 2000 to 19 December 2019. Demographic characteristics, comorbidities, postoperative complications, length of hospital stay, and the time to surgery were extracted and examined in each 5-year period based on the admission year, namely 2000-2004, 2005-2009, 2010-2014, and 2015-2019. Categorical data were analyzed by chi-squared or Fisher's exact test, with ordinal data by row mean scores difference test and continuous data by one-way analysis of variance. Trends in comorbidities and postoperative complications were examined by the Cochran-Armitage trend test. RESULTS: The average age of the included population was 79.1 ± 7.3 years (mean ± standard deviation), and 69.1% were female. From 2000 to 2019, the proportion of females increased from 59.8% to 73.0% (P for trend <0.05). Hypertension (51.8%), type 2 diabetes (23.6%), coronary heart disease (20.9%), stroke (18.7%), and arrhythmia (11.2%) were the most prevalent five comorbidities. The proportion of hypertension was 27.0%, 45.4%, 53.0%, and 57.2% in each 5-year period with an increasing trend (P for trend <0.05). The proportion of type 2 diabetes was 9.8%, 22.8%, 23.5%, and 26.0% in each 5-year period (P for trend <0.05). Similar increasing trends were found in myocardial infarction, arrhythmia, and tumor. On the contrary, the proportion of patients with major postoperative complications decreased from 2000 to 2019, with 23.0%, 14.6%, 6.5%, and 5.6% in each 5-year period (P for trend <0.05). For each specific postoperative complication, i.e. pneumonia, cardiovascular event, respiratory failure, and in-hospital death, similar decreasing trends were found (all P for trend <0.05). CONCLUSION: This descriptive analysis sheds light on the fact that the health status of the hip fracture population tends to shift gradually. Improving concepts and practices of clinical interventions may help reduce postoperative complications, whereas challenges in the management of comorbidities increase.

Association Between Gut Microbiota and Symptomatic Hand Osteoarthritis: Data From the Xiangya Osteoarthritis Study.

OBJECTIVE: Systemic inflammatory factors have been implicated in symptomatic hand osteoarthritis (OA). Gut microbiome dysbiosis promotes systemic inflammation. The aim of this study was to examine the association between the gut microbiome and the presence of symptomatic hand OA in a population-based study. METHODS: Study participants were subjects of the Xiangya Osteoarthritis Study, a community-based observational study conducted in the Hunan Province of China. Symptomatic hand OA was defined as the presence of both symptoms and radiographic OA in the same hand. The gut microbiome was analyzed using 16S ribosomal RNA gene sequencing in stool samples. We examined the relation of α-diversity, ß-diversity, relative abundance of taxa, and potential bacterial functional pathways to symptomatic hand OA. RESULTS: A total of 1,388 participants (mean age 61.3 years, 57.4% women) were included in the study, of whom 72 had symptomatic hand OA (prevalence of symptomatic hand OA 5.2%). Beta-diversity of the gut microbiome, but not α-diversity, was significantly associated with the presence of symptomatic hand OA (P = 0.003). Higher relative abundance of the genera Bilophila and Desulfovibrio as well as lower relative abundance of the genus Roseburia was associated with symptomatic hand OA. Most functional pathways (i.e., those annotated in the KEGG Ortholog hierarchy) that were observed to be altered in participants with symptomatic hand OA belonged to the amino acid, carbohydrate, and lipid metabolic pathways. CONCLUSION: This large, population-based study provides the first evidence that alterations in the composition of the gut microbiome were observed among study participants who had symptomatic hand OA, and a low relative abundance of Roseburia but high relative abundance of Bilophila and Desulfovibrio at the genus level were associated with prevalent symptomatic hand OA. These findings may help investigators understand the role of the microbiome in the development of symptomatic hand OA and could contribute to potential translational opportunities.