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Inpatient zoledronic acid (IP-ZA) administered during the initial fracture hospitalization significantly improves the osteoporosis treatment rate. Clinical outcomes of IP-ZA after hip fracture remain uncertain. Here we report a cohort study that emulated a randomized controlled trial using real-world data and evaluated the risk of all-cause-mortality and radiologically confirmed subsequent new fractures among patients hospitalized for a hip fracture who had received IP-ZA as compared with propensity-matched controls. A total of 654 patients who had received IP-ZA and 6877 controls (for whom anti-osteoporosis treatment was indicated but no IP-ZA started during index hospitalization) were included in the study. The primary cohort comprised 652 IP-ZA patients (IP-ZA group) and 1926 matched controls (untreated group), with 71.7% female 92.1% White participants, with a mean age of 80.9 years. Cumulative all-cause mortality over the 24-month follow-up for the IP-ZA group was 12.3% and 20.7% for the untreated group (hazard ratio [HR], 0.62; 95% CI, 0.49-0.78, p < .001). A total of 585 (89.7%) patients in IP-ZA group received only a single dose of ZA during the 24 months, and the death rate of this single dose group was 13.3%, which was significantly lower than that of the untreated group (HR, 0.70; 95% CI, 0.55-0.89, p = .003). Rates of radiologically confirmed cumulative subsequent new vertebral fractures were 2.0% in the IP-ZA group and 5.4% in the untreated group (HR, 0.40; 95% CI, 0.22-0.71, p = .001). A similarly lower rate of new vertebral fractures was seen in the single dose subgroup (1.9% vs 5.4%; HR, 0.44; 95% 0.24-0.82, p = .008). IP-ZA, administered during the initial hospitalization for hip fracture, was associated with lower all-cause-mortality and risk of radiologically confirmed subsequent new vertebral fractures, and thus offers a mechanism to narrow the treatment gap in patients having sustained a hip fragility fracture., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Patients who sustain a hip fracture are known to be at imminent refracture risk. Their complex multidisciplinary rehabilitation needs to include falls prevention and anti-osteoporosis medication (AOM) to prevent such fractures. This study aimed to determine which hospital-level organizational factors predict prescription of post-hip fracture AOM and refracture risk. A cohort of 178 757 patients aged ≥60 yr who sustained a hip fracture in England and Wales (2016-2019) was examined and followed for 1 yr. Patient-level hospital admission datasets from 172 hospitals, the National Hip Fracture Database, and mortality data were linked to 71 metrics extracted from 18 hospital-level organizational reports. Multilevel models determined organizational factors, independent of patient case-mix, associated with (1) AOM prescription and (2) refracture (by ICD10 coding). Patients were mean (SD) 82.7 (8.6) yr old, 71% female, with 18% admitted from care homes. Overall, 101 735 (57%) were prescribed AOM during admission, while 50 354 (28%) died during 1-yr follow-up, 12 240 (7%) refractured. Twelve organizational factors were associated with AOM prescription, for example, orthogeriatrician-led care compared to traditional care models (odds ratio [OR] 4.65 [95% CI, 2.25-9.59]); AOM was 9% (95% CI, 6%-13%) more likely to be prescribed in hospitals providing routine bone health assessment to all patients. Refracture occurred at median 126 d (IQR 59-234). Eight organizational factors were associated with refracture risk; hospitals providing orthogeriatrician assessment to all patients within 72 h of admission had an 18% (95% CI, 2%-31%) lower refracture risk, weekend physiotherapy provision had an 8% (95% CI, 3%-14%) lower risk, and where occupational therapists attended clinical governance meetings, a 7% (95% CI, 2%-12%) lower risk. Delays initiating post-discharge community rehabilitation were associated with a 15% (95% CI, 3%-29%) greater refracture risk. These novel, national findings highlight the importance of orthogeriatrician, physiotherapist, and occupational therapist involvement in secondary fracture prevention post hip fracture; notably, fracture risk reductions were seen within 12 mo of hip fracture., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Objectives: Evaluate differences between blood transfusion and complication rates among fragility hip fracture patients treated with locally injected (Local) versus intravenous (IV) tranexamic acid (TXA)., Methods: Design: Retrospective comparative cohort., Setting: Tertiary referral orthopaedic specialty hospital; Level I trauma center., Patient Selection Criteria: Patients aged 50 years and over who underwent surgical treatment for a proximal femur fragility fracture (Orthopedic Trauma Association/Arbeitsgemeinschaft für Osteosynthesefragen 31A and 31B). Between March 2018 and April 2022 with or without the use of local TXA during wound closure or IV TXA., Outcome Measures and Comparisons: Postoperative blood transfusion, venous thromboembolism, surgical site infections, and 30-day readmissions compared between those who received IV TXA, Local TXA, and controls that did not receive any TXA., Results: Seven hundred forty-six patients (258 received IV TXA, 252 received Local TXA, and 236 controls that did not receive any TXA) were studied. Both Local and IV TXA groups received fewer blood transfusion versus controls. IV TXA was associated with a transfusion rate reduction of 12% compared with Local TXA ( P < 0.001). Regression analysis indicated that IV TXA reduced the odds of a postoperative blood transfusion by 48% compared with Local TXA ( P = 0.017). There were no differences in complication rates among the groups; however, patients receiving IV TXA had a significantly lower 30-day readmission rate (5%) than the control (13.9%) or Local (13.8%) TXA groups ( P = 0.001)., Conclusions: IV TXA significantly reduced the risk of postoperative transfusion compared with controls and patients receiving Local TXA. There was no increased risk of complications, and a lower 30-day readmission was observed for the IV TXA group. IV TXA seems to be a safe and effective way to reduce postoperative blood transfusion in patients with fragility hip fractures., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There is no high-quality, evidence-based protocol for the treatment of postoperative fatigue syndrome (POFS) after total joint arthroplasty (TJA) or fracture surgery with Chinese herbal medicine (CHM)., Purpose: The purpose of this study was to explore the efficacy of CHM in the treatment of POFS after TJA or hip fracture surgery (HFS)., Methods: We searched six databases to obtain randomized controlled trials (RCTs) of CHM for the treatment of POFS after TJA or HFS. The retrieval time limit was from the establishment of each database to August, 2022. According to the Cochrane Handbook for Systematic Reviews version 5.1, we used RevMan 5.3 to evaluate the quality of the studies. Stata 14.0 software was used to merge and analyze the data. The weighted mean difference (WMD) was the effect estimate for statistical analysis. We also performed subgroup analyses according to different types of surgeries., Results: A total of 11 RCTs were included in this study, comprising 430 cases in the CHM group and 432 cases in the control group (CG). The meta-analysis results showed that there was no significant difference in the Brief Profile of Mood States (BPOMS) score (WMD=0.08, 95% confidence interval (CI): -0.29 to 0.45, P=0.688), Christensen Fatigue scale (CHFS) score (WMD = 0.15, 95% CI: -0.09 to 0.39, P=0.214) or Identity-Consequence Fatigue Scale (ICFS) score (WMD=-0.40, 95% CI: -1.84 to 1.05, P=0.589) between the CHM group and the CG on the first postoperative day. The use of CHM significantly reduced the BPOMS score (WMD=-0.85 and WMD=-3.01, respectively), CHFS score (WMD=-1.01 and WMD= -1.45, respectively), and ICFS score (WMD=-3.51 and WMD=-5.26) on postoperative days 3 and 7. Compared with the CG, the CHM group had significantly increased serum transferrin and IgG levels on postoperative days 3 and 7. The subgroup analysis results suggested that the application of CHM in HFS patients improved fatigue symptoms on postoperative days 3 and 7, while the application of CHM to treat POFS in TJA patients had great inconsistency in the evaluation of different indicators., Conclusion: The application of CHM improved the fatigue status of POFS patients after TJA or HFS and increased the levels of transferrin and IgG in serum, which is conducive to promoting the postoperative rehabilitation process of patients. The subgroup analysis results showed that the application of CHM to intervene in POFS in HFS patients had obvious benefits., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Bisphosphonates are commonly prescribed to mitigate the effects of osteoporosis, a condition associated with an increased risk of fracture. However, despite their success, there has been growing concern regarding the long-term use of bisphosphonates because of the increased risk of atypical subtrochanteric fractures of the femur (AFFs). The objective of this study was to describe a cohort of patients with AFFs and evaluate the risk of evolving to non-union, the time of consolidation associated with the location of the fracture, the time of use of the drug, and the implant involved in its treatment., Methods: This retrospective study recruited patients between June 2008 and May 2018. We identified patients with AFFs according to the task force criteria and a history of bisphosphonate use. We included all patients older than 65 years, with long-term use of bisphosphonates, AFF criteria according to the task force, and a follow-up of 12 months or longer. We studied the following variables: the time of use of bisphosphonates, localization of the fracture according to Hyodo et al., implant use, and fracture healing time, considering the presence of bone callus observed in two radiologic projections, which were measured in weeks., Results: Between June 2008 and May 2018, 72 patients met the task force criteria for AFFs. A total of 67 patients were included in this study. From this total, 37 were in the proximal region of the femur and 31 corresponded to the diaphyseal region. Univariate and multivariate analyses showed statistical significance in the time of bone healing compared with the different locations of the fracture along the femur., Conclusion: According to our study, the localization of AFFs in patients with a history of bisphosphonate use influences the duration of bone healing., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023. Published by Elsevier Ltd.)

This study aimed to assess the impact of drug adherence and treatment duration for denosumab on mortality risk after hip fracture surgery. Lower all-cause mortality risk was associated with drug intervals of 7 months or less and longer treatment duration. The study highlights the importance of proper denosumab administration., Purpose: Prescription of anti-osteoporotic medications (AOMs) after osteoporotic hip fracture may increase bone mineral density (BMD) and decrease mortality risk. However, few studies have been conducted on drug adherence and treatment duration for denosumab, a popular choice among AOMs. This study aimed to assess the impact of denosumab adherence and treatment duration on the mortality risk of hip fracture patients after surgery., Methods: We conducted a cohort study using nationwide population data from National Health Insurance Research Database (NHIRD) in Taiwan. Patients newly diagnosed with osteoporosis and hip fracture between 2008 and 2019 who used denosumab after surgery were included. We assessed drug adherence, treatment duration, and other parameters associated with patient outcomes., Results: A total of 21,316 patients diagnosed with osteoporotic hip fractures were included. Compared with a > 7-month drug interval for denosumab, an interval of ≤ 7 months led to lower all-cause mortality risk (hazard ratio (HR): 0.60, 95% confidence interval (CI): 0.57 ~ 0.64). Patients with denosumab treatment for over 1, 2, and 3 years had lower all-cause mortality risk (HR&CI: 0.68 (0.64 ~ 0.73), 0.48 (0.43 ~ 0.53), 0.29 (0.26 ~ 0.33)) than those with treatment duration < 1 year. Analysis after excluding short-term death yielded similar results. Analysis of causes of death also showed that good adherence and longer duration were associated with reduced mortality due to cancer and cardiovascular disease., Conclusion: Better drug adherence and longer duration of denosumab treatment are associated with lower all-cause mortality risk among hip fracture patients after surgery. Our study highlights the benefits of a proper time interval of denosumab administration. These findings provide important insight into management of osteoporotic hip fractures and may inform clinical practice and development of guidelines., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Objectives: To examine the relationship between anticoagulant and antiplatelet drugs and surgical blood loss for geriatric patients undergoing cephalomedullary nail fixation of extracapsular proximal femur fractures., Design: Multicenter, retrospective, cohort study using bivariate and multivariable regression analyses., Setting: Two Level-1 trauma centers., Patients: One thousand four hundred forty-two geriatric (ages 60-105 years) patients undergoing isolated primary intramedullary fixation of nonpathologic extracapsular hip fractures from 2009 to 2018 including 657 taking an antiplatelet drug alone (including aspirin), 99 taking warfarin alone, 37 taking a direct oral anticoagulant (DOAC) alone, 59 taking an antiplatelet drug and an anticoagulant, and 590 taking neither., Intervention: Cephalomedullary nail fixation., Main Outcome Measurements: Blood transfusion and calculated blood loss., Results: More patients taking antiplatelet drugs required a transfusion than controls (43% vs. 33%, P < 0.001), whereas patients taking warfarin or DOACs did not (35% or 32% vs. 33%). Median calculated blood loss was increased in patients taking antiplatelet drugs (1275 mL vs. 1059 mL, P < 0.001) but not in patients taking warfarin or DOACs (913 mL or 859 mL vs. 1059 mL). Antiplatelet drugs were independently associated with an odds ratio of transfusion of 1.45 [95% confidence interval (CI), 1.1-1.9] in contrast with 0.76 (95% CI, 0.5-1.2) for warfarin and 0.67 (95% CI, 0.3-1.4) for DOACs., Conclusions: Geriatric patients taking warfarin (incompletely reversed) or DOACs lose less blood during cephalomedullary nail fixation of hip fractures than those taking aspirin. Delaying surgery to mitigate anticoagulant-related surgical blood loss may be unwarranted., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Anaemia and blood transfusion are associated with poor outcomes after hip fracture. We evaluated the efficacy of intravenous iron and tranexamic acid in reducing blood transfusions after hip fracture surgery., Methods: In this double-blind, randomised, 2 × 2 factorial trial, we recruited adults hospitalised for hip fractures in 12 medical centres in France who had preoperative haemoglobin concentrations between 9·5 and 13·0 g/dL. We randomly allocated participants (1:1:1:1), via a secure web-based service, to ferric derisomaltose (20 mg/kg intravenously) and tranexamic acid (1 g bolus followed by 1 g over 8 h intravenously at inclusion and 3 g topically during surgery), iron plus placebo (normal saline), tranexamic acid plus placebo, or double placebo. Unmasked nurses administered study drugs; participants and other clinical and research staff remained masked to treatment allocation. The primary outcome was the percentage of patients transfused during hospitalisation (or by day 30). The primary analysis included all randomised patients. This study is registered on ClinicalTrials.gov (NCT02972294) and is closed to new participants., Findings: Of 413 patients (51-104 years old, median [IQR] 86 [78-91], 312 [76%] women, 101 [24%] men), 104 received iron plus tranexamic acid, 103 iron plus placebo, 103 tranexamic acid plus placebo, and 103 double placebo between March 31, 2017 and June 18, 2021 (study stopped early for efficacy after the planned interim analysis done on the first 390 patients included on May 25, 2021). Data for the primary outcome were available for all participants. Among patients on double placebo, 31 (30%) were transfused versus 16 (15%) on both drugs (relative risk 0·51 [98·3% CI 0·27-0·97]; p=0·012). 27 (26%) participants on iron (0·81 [0·50-1·29]; p=0·28) and 28 (27%) on tranexamic acid (0·85 [0·54-1·33]; p=0·39) were transfused. 487 adverse events were reported with similar event rates among the groups; among prespecified safety endpoints, severe postoperative anaemia (haemoglobin <8 g/dL) was more frequent in the double placebo group. Main common adverse event were sepsis, pneumonia, and urinary infection, with similar rates among all groups., Interpretation: In patients hospitalised for hip fracture surgery with a haemoglobin concentration 9·5-13·0 g/dL, preoperative infusion of ferric derisomaltose plus tranexamic acid reduced the risk of blood transfusion by 50%. Our results suggest that combining treatments from two different pillars improves patient blood-management programmes. Either treatment alone did not reduce transfusion rates, but we might not have had the power to detect it., Funding: French Ministry of Health, HiFIT trial., Competing Interests: Declaration of interests SL or his institution has received grants, personal fees, and non-financial support from Pharmocosmos, Vifor Pharma, Masimo, and Pfizer outside the submitted work. LR received a grant and personal fee from NEWCLIP TECHNIC, outside the submitted work. ER received personal fees and non-financial support from Vifor Pharma and Pfizer outside the submitted work. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: This study aimed to examine the impacts of DOACs compliance and prescribing preferences on clinical outcomes in elderly hip fracture patients with isolated calf deep vein thrombosis (ICDVT)., Methods: We conducted a retrospective cohort study that evaluated 702 patients who underwent surgical treatment combined with ICDVT in an academic university hospital between January 2016 and October 2021. DOACs compliance was investigated through telephone and outpatient follow-up, and ICDVT clinical outcomes were collected 30 and 90 days post-discharge, respectively. Variables of interest were collected through the electronic medical record system, and data were analyzed after adjusting for predictors of non-completely dissolved (CD) of ICDVT., Results: The DOACs compliance survey revealed that 375 (53.42%) patients were fully adherent, 270 (38.46%) were fairly adherent, and 57 (8.12%) were poorly adherent. Approximately 62% of patients had ICDVT dissipation within 30 days after discharge, reaching 94% within 90 days. DOACs QD/BID regimen is often based on economic status, activity capacity, discharge destination and post-operative weight-bearing activities (p<0.05).The mechanism of injury, ASA classification, surgical technique and timing of ICDVT formation were significantly correlated with DOACs 14/28 days regimen (p<0.05).Multivariate analysis revealed that rural patients [OR 1.518 (95% CI, 1.117-2.236)], pre-operative ICDVT[OR 2.816 (95% CI, 1.862-4.259)] and thrombus length [OR 1.157 (95% CI, 1.263-1.821)] were ICDVT risk factors for non-CD. Furthermore, DOACs fair compliance [OR 0.087 (95% CI, 0.042-0.178)], DOACs full compliance [OR 0.283 (95% CI, 0.139-0.579)], and hospitalization duration [OR 0.793 (95% CI, 0.694-0.907)] were ICDVT protective factors for CD., Conclusion: Better compliance with DOACs benefits early ICDVT dissipation, but final clinical outcomes have to be validated with longer follow-up periods. When managing elderly patients with hip fractures, indications for anticoagulation should be considered and individualized protocols should be used., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Wang et al.)

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are indicated in patients with or without type 2 diabetes mellitus atherosclerotic cardiovascular disease, chronic kidney disease, or heart failure. Postmarket surveillance data have identified many safety signals which warrants further investigation. We aimed to compare the safety of SGLT-2i and glucagon-like peptide-1 receptor agonists (GLP-1RA). Using the Veterans Health Administration nationwide database, patients with type 2 diabetes mellitus who were newly initiated on a SGLT-2i or GLP-1RA between April 1, 2013 and September 1, 2020 were identified. The primary outcome was the incidence of any amputation, below-knee amputation (BKA), all clinical fractures, hip fracture, Fournier gangrene, acute pancreatitis, diabetic ketoacidosis (DKA), serious urinary tract infections (UTIs), and venous thromboembolism (VTE). All outcomes were compared between the treatment groups. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs) for the comparative analysis. A total of 70,694 propensity-matched new users of SGLT-2i and GLP-1RA were identified. The use of SGLT-2 inhibitors, compared with GLP-1RA, was not associated with an increased rate of any amputation (aHR 1.02, 95% confidence interval [CI] 0.82 to 1.27), BKA (aHR 1.05, 95% CI 0.84 to 1.32), all clinical fractures (aHR 0.94, 95% CI 0.86 to 1.03), hip fractures (aHR 0.82, 95% CI 0.50 to 1.32), DKA (aHR 1.66, 95% CI 0.97 to 2.85), VTE (aHR 1.02, 95% CI 0.80 to 1.30), acute pancreatitis (aHR 1.02, 95% CI 0.80 to 1.30), and Fournier gangrene (aHR 0.92 95% CI 0.61 to 1.38). Lower rates of serious UTIs were observed in the SGLT-2i group than in the GLP-1RA group (aHR 0.74, 95% CI 0.64 to 0.84). This real-world study found that SGLT-2i use compared with GLP-1RA did not increase the rate of amputation, BKA, clinical fractures, hip fracture, Fournier gangrene, acute pancreatitis, DKA, serious UTIs, and VTE in veteran patients., Competing Interests: Declaration of Competing Interest Dr. Patil reports administrative support was provided by Salem Veterans Affair Medical Center. The remaining authors have no conflicts of interest to declare., (Published by Elsevier Inc.)

Background: Teriparatide is an effective anabolic agent used in the treatment of severe osteoporosis. In addition, it is also used to promote fracture healing. The purpose of this double-blind randomized controlled trial was to evaluate the influence of weekly teriparatide administration on bone formation in hip fracture patients., Methods: The control group (n = 41) was composed of patients treated with normal saline other than teriparatide, and the teriparatide group (n = 51) consisted of patients who received weekly teriparatide. Bone turnover markers, C-terminal telopeptide (CTx) and osteocalcin (OC), were assessed through blood tests at the initial hospital visit and 3-month, 6-month, and 1-year follow-ups. Dual-energy X-ray absorptiometry was performed 5 days postoperatively and at 1-year postoperative follow-up. The degree of fracture union was evaluated by comparing the radiographic union scoring system for hips using Radiographic Union Score for Hip (RUSH) scores between the two groups at 3 months, 6 months, and 1 year after surgery., Results: Evaluation of the rate of change in bone mineral density over 1 year showed that the lumber bone mineral density increased by more than 7% in the experimental group. The control group did not show a difference between the CTx and OC at 6 months, but the difference between the CTx and OC values was large at 6 months in the experimental group. The mean RUSH score was significantly different between the control group and the experimental group: 12.105 and 15.476, respectively ( p = 0.004), at 3 months and 18.571 and 22.389, respectively, at 6 months ( p = 0.006)., Conclusions: Weekly use of teriparatide improved fracture healing, bone formation, and clinical outcomes at 1 year after hip fracture surgery by the anabolic window effect., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2023 by The Korean Orthopaedic Association.)

In this international study, we examined the incidence of hip fractures, postfracture treatment, and all-cause mortality following hip fractures, based on demographics, geography, and calendar year. We used patient-level healthcare data from 19 countries and regions to identify patients aged 50 years and older hospitalized with a hip fracture from 2005 to 2018. The age- and sex-standardized incidence rates of hip fractures, post-hip fracture treatment (defined as the proportion of patients receiving anti-osteoporosis medication with various mechanisms of action [bisphosphonates, denosumab, raloxifene, strontium ranelate, or teriparatide] following a hip fracture), and the all-cause mortality rates after hip fractures were estimated using a standardized protocol and common data model. The number of hip fractures in 2050 was projected based on trends in the incidence and estimated future population demographics. In total, 4,115,046 hip fractures were identified from 20 databases. The reported age- and sex-standardized incidence rates of hip fractures ranged from 95.1 (95% confidence interval [CI] 94.8-95.4) in Brazil to 315.9 (95% CI 314.0-317.7) in Denmark per 100,000 population. Incidence rates decreased over the study period in most countries; however, the estimated total annual number of hip fractures nearly doubled from 2018 to 2050. Within 1 year following a hip fracture, post-hip fracture treatment ranged from 11.5% (95% CI 11.1% to 11.9%) in Germany to 50.3% (95% CI 50.0% to 50.7%) in the United Kingdom, and all-cause mortality rates ranged from 14.4% (95% CI 14.0% to 14.8%) in Singapore to 28.3% (95% CI 28.0% to 28.6%) in the United Kingdom. Males had lower use of anti-osteoporosis medication than females, higher rates of all-cause mortality, and a larger increase in the projected number of hip fractures by 2050. Substantial variations exist in the global epidemiology of hip fractures and postfracture outcomes. Our findings inform possible actions to reduce the projected public health burden of osteoporotic fractures among the aging population. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Background: Meta-analyses on the use of tranexamic acid (TXA) in intertrochanteric fractures have shown inconsistent results due to variations in inclusion criteria and clinical heterogeneity. To address these limitations, we conducted a rigorous analysis of recent randomized controlled trials (RCTs) with strict inclusion criteria. The aim of this study was to objectively evaluate the effects and safety of intravenous TXA administration in the treatment of geriatric intertrochanteric femoral fractures with intramedullary nailing., Methods: PubMed, Embase, and the Cochrane Library were searched for RCTs published from the database inception to August 2022. The date of total blood loss (TBL), intra-operative blood loss (IBL), hidden blood loss (HBL), transfusion rate, transfusion units, thromboembolic events, and mortality were extracted. Review Manager 5.3 was used for the analysis., Results: A total of six RCTs involving 689 patients were included. Meta-analyses indicated that TXA can significantly reduce TBL (WMD = -232.82; 95% CI -312.81 to -152.84; p < 0.00001), IBL (WMD = -36.33; 95% CI -51.38 to -21.28; p < 0.00001), HBL (WMD = -189.23; 95% CI -274.92 to -103.54; p < 0.0001), transfusion rate (RR = 0.53; 95% CI 0.33 to 0.85; p = 0.008), and transfusion units (WMD = -0.58; 95% CI -0.75 to -0.41; p < 0.01). No increase in thromboembolic events rate (RR = 0.75; 95% CI 0.38 to 1.50; p = 0.42) and mortality (RR = 1.36; 95% CI 0.61 to 3.04; p = 0.45) was observed., Conclusions: Our meta-analysis provides robust evidence supporting the efficacy and safety of intravenous TXA administration in treating geriatric intertrochanteric femoral fractures with intramedullary nailing. TXA significantly reduces blood loss and transfusion requirements without increasing the risk of thromboembolic events or mortality., (© 2023. The Author(s).)

In an analysis of claims data from a city in Japan, male patients and patients with dementia were less likely to receive osteoporosis pharmacotherapy after hip fracture. Treatment initiation rate has improved between 2014 and 2017., Purpose: Older adults with recent hip fractures are at a high risk of recurrent fractures. However, the post-fracture care gap has been reported globally. This study examines factors associated with pharmacotherapy non-initiation within 1 year after hip surgery., Methods: Using medical and long-term care (LTC) claims, and LTC needs certification data in Tsukuba City, Japan, we identified individuals aged 65 years or older who had hip fractures with subsequent surgical procedures between October 1, 2014, and December 31, 2017. Patient (age, sex, dementia, and comorbidities) and health service-related characteristics (fiscal year, type of hospital, number of hospital beds, and admission to recovery phase rehabilitation wards) were examined. The association of these factors with non-pharmacotherapy for osteoporosis within 1 year after hip fracture using multivariable logistic models was analyzed., Results: We identified 275 patients with hip fractures who did not receive pharmacotherapy pre-fracture. Forty percent of them received pharmacotherapy within 1 year of post-fracture. Male sex (odds ratio (OR) = 4.49 [2.14-9.44]) and dementia (OR = 1.90 [1.03-3.52]) were associated with no pharmacotherapy, whereas later fiscal year (OR = 0.64 [0.48-0.87]) and admission to rehabilitation wards (OR = 0.25 [0.14-0.46]) were associated with pharmacotherapy initiation within 1 year of post-fracture. Comorbidities were not associated with the initiation of pharmacotherapy., Conclusion: Pharmacotherapy for osteoporosis was less likely to be initiated after a hip fracture in male patients and patients with dementia. These patients should be considered for pharmacotherapy because they are at high risk of recurrent fractures., (© 2023. The Author(s).)

Hip fractures are strong risk factors for further fractures. However, using the National Hip Fracture Database, we observed that in England and Wales, 64% of patients admitted on oral bisphosphonates were discharged on the same and injectable drug use varies from 0-67% and 0.2%-83.6% were deemed "inappropriate" for bone protection. This variability requires further investigation., Introduction: A key aim for the National Hip Fracture Database (NHFD) is to encourage secondary fracture prevention of the 75,000 patients who break their hip annually in the UK, through bone health assessment and appropriate provision of anti-osteoporosis medication (AOM). We set out to describe trends in anti-osteoporosis medication prescription and examine the types of oral and injectable AOMs being prescribed both before and after a hip fracture., Methods: We used data freely available from the NHFD  www.nhfd.co.uk  to analyse trends in oral and injectable AOM prescription across a quarter of a million patients presenting between 2016 and 2020, and more detailed information on the individual type of AOM prescribed for 63,705 patients from 171 hospitals in England and Wales who presented in 2020., Results: Most patients (88.3%) are not taking any AOM when they present with a hip fracture. Half of all patients (50.8%) were prescribed AOM treatment by the time of discharge, but the proportion deemed 'inappropriate for AOM' varied hugely (0.2-83.6%) in different hospitals. Nearly two-thirds (64.2%) of those previously taking an oral bisphosphonate were simply discharged on the same type of medication. The total number of patients discharged on oral medication fell by over a quarter in these five years. The number discharged on injectables increased by nearly three-quarters to 14.2% over the same period, but remains hugely variable across the country, with rates ranging from 0-67% across different units., Conclusion: A recent hip fracture is a strong risk factor for future fractures. The huge variability in approaches, and in particular the use of injectables, in different trauma units across England and Wales requires further investigation., (© 2023. Crown.)

Background: Tranexamic acid (TXA) has long been the antifibrinolytic hemostatic drug of choice for orthopedic surgery. In recent years, the hemostatic effect of epsilon aminocaproic acid (EACA) has gradually been recognized by orthopedic surgeons and has begun to be used in hip and knee arthroplasty with little mention of the comparison of these two drugs; Therefore, this study compared the efficacy and safety of EACA and TXA in the perioperative period of elderly patients with trochanteric fractures to verify whether EAC could be a "qualified alternative" to TXA and to provide theoretical support for the clinical application of TXA., Methods: Two hundred and forty-three patients who received proximal femoral nail antirotation (PFNA) for trochanteric fractures from January 2021 to March 2022 at our institution were included and divided into the EACA group (n = 146) and the TXA group. (n = 97) determined by the drugs used in the perioperative period The main observations were blood loss and blood transfusion.The second second outcome was blood routine, coagulation, Hospital complications and complications after discharge., Results: The perioperative EACA patients had significantly lower significant blood loss (DBL) than the TXA group (p < 0.0001) and statistically significant lower C-reactive protein in the EACA group than in the TXA group on postoperative day 1 (p = 0.022). Patients on perioperative TXA had better postoperative day one (p = 0.002) and postoperative day five erythrocyte width than the EACA group (p = 0.004). However, there was no statistically significant difference between the two groups in the remaining indicators in both drugs: blood items, coagulation indicators, blood loss, blood transfusion, length of hospital(LOH), total hospital expense, and postoperative complications (p > 0.05)., Conclusion: The hemostatic effects and safety of EACA and TXA in the perioperative application of trochanteric fractures in the elderly are essentially similar, and EACA can be considered for use as an alternative to TXA, increasing the flexibility of physicians to use it in the clinical setting. However, the limited sample size included necessitated a high-quality, large sample of clinical studies and long-term follow-up., (© 2023. The Author(s).)

Objectives: To compare the efficacy of different dosages of intravenous (IV) tranexamic acid (TXA) in the treatment of traumatic hip fractures against that of the control group of no TXA., Data Sources: This study used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to perform a network meta-analysis on the use of TXA for the treatment of hip fractures. The study team used Ovid MEDLINE, Cochrane Reviews, Scopus, Embase, and Web of Science databases to perform the search. Studies that were published in English between the years 2010 and 2020 were selected., Study Selection/data Extraction: For inclusion in this study, selected articles were required to be randomized controlled trials with at least 1 control group that had no antifibrinolytic intervention to serve as a control, and IV formulations of TXA were used as part of the treatment group. Furthermore, all study participants must have undergone surgical intervention for traumatic hip fractures. Studies that did not immediately meet criteria for inclusion were saved for a review by the full investigating team and were included based on consensus., Data Synthesis: All statistical analyses conducted for this study were performed using R software (R Foundation for Statistical Computing, Vienna, Austria). Network meta-analyses were conducted with a frequentist approach with a random-effects model using the netmeta package version 0.9-6 in R. The frequentist equivalent to surface under the cumulative ranking probabilities, termed " P score," was used to rank different treatments., Conclusion: The use of TXA in the surgical management of traumatic hip fractures reduces the number of transfusions and perioperative blood loss, with minimal to no increased incidence of thrombotic events when compared with those in controls. When comparing formulations, no route of administration is clearly superior in reducing perioperative blood loss., Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Postoperative delirium (POD) is a common complication along with poor prognosis in geriatric intertrochanteric fracture (ITF) patients. However, the prevention and treatment of POD remain unclear. Previous studies have confirmed that POD is essentially a consequence of neuro-inflammatory responses. Dexamethasone is a glucocorticoid with comprehensive anti-inflammatory effects, while a high dose of dexamethasone correlates with many side effects or even adverse consequences. Thus, this prospective study aims to discuss whether a single preoperative low-dose dexamethasone can reduce the impact of POD on geriatric ITF patients with internal fixation surgery., Methods: Between June 2020 and October 2022, there were 219 consecutive ITF patients assessed in our department. Of the 219 ITF patients, 160 cases who met the inclusion and exclusion criteria were finally enrolled and randomly allocated to the dexamethasone group and the placebo group (80 geriatric ITF patients in each group) in this prospective study. The patients in the dexamethasone group received intravenous 10 mg (2 ml) dexamethasone while the patients in the placebo group received intravenous 2 ml saline in 30 min before being sent to the operating room, respectively. The baseline characteristics, surgical information, incidence and severity of POD as the efficacy-related outcomes, and infection events and hyperglycemia as safety-related outcomes (adverse events), were collected and analyzed between the two groups. The severity of POD was evaluated by Memorial Delirium Assessment Scale (MDAS) score., Results: There were no differences in baseline characteristics and surgical information between the dexamethasone group and the placebo group. The dexamethasone group had a lower incidence of POD than the placebo group within the first 5 days after surgery [(9/80, 11.3% vs. 21/80, 26.3%, RR = 0.83, 95% CI 0.71-0.97, P = 0.015]. The dexamethasone group had lower MDAS scores (Mean ± SD) than the placebo group [13.2 ± 1.0 (range 11 to 15) vs. 15.48 ± 2.9 (range 9 to 20), P = 0.011, effect size = 0.514]. There were no differences in infection events and hyperglycemia between the two groups., Conclusions: A single preoperative low-dose dexamethasone may reduce the incidence and severity of POD in geriatric ITF patients with internal fixation surgery., Trial Registration: ChiCTR2200055281., (© 2023. The Author(s).)

Background: Hip fracture patients face a patient safety threat due to medication discrepancies and adverse drug reactions when they have a combination of high age, polypharmacy and several care transitions. Consequently, optimised pharmacotherapy through medication reviews and seamless communication of medication information between care settings is necessary. The primary aim of this study was to investigate the impact on medication management and pharmacotherapy. The secondary aim was to evaluate implementation of the novel Patient Pathway Pharmacist intervention for hip fracture patients., Methods: Hip fracture patients were included in this nonrandomised controlled trial, comparing a prospective intervention group (n = 58) with pre-intervention controls who received standard care (n = 50). The Patient Pathway Pharmacist intervention consisted of the steps: (A) medication reconciliation at admission to hospital, (B) medication review during hospitalisation, (C) recommendation for the medication information in the hospital discharge summary, (D) medication reconciliation at admission to rehabilitation, and (E) medication reconciliation and (F) review after hospital discharge. The primary outcome measure was quality score of the medication information in the discharge summary (range 0-14). Secondary outcomes were potentially inappropriate medications (PIMs) at discharge, proportion receiving pharmacotherapy according to guidelines (e.g. prophylactic laxatives and osteoporosis pharmacotherapy), and all-cause readmission and mortality., Results: The quality score of the discharge summaries was significantly higher for the intervention patients (12.3 vs. 7.2, p < 0.001). The intervention group had significantly less PIMs at discharge (- 0.44 (95% confidence interval - 0.72, - 0.15), p = 0.003), and a higher proportion received prophylactic laxative (72 vs. 35%, p < 0.001) and osteoporosis pharmacotherapy (96 vs. 16%, p < 0.001). There were no differences in readmission or mortality 30 and 90 days post-discharge. The intervention steps were delivered to all patients (step A, B, E, F = 100% of patients), except step (C) medication information at discharge (86% of patients) and step (D) medication reconciliation at admission to rehabilitation (98% of patients)., Conclusion: The intervention steps were successfully implemented for hip fracture patients and contributed to patient safety through a higher quality medication information in the discharge summary, fewer PIMs and optimised pharmacotherapy., Trial Registration: NCT03695081., (© 2023. The Author(s).)

Introduction: Hip fracture patients, who are often frail, continue to be a challenge for healthcare systems with a high postoperative mortality rate. While beta-blocker therapy (BBt) has shown a strong association with reduced postoperative mortality, its effect in frail patients has yet to be determined. This study's aim is to investigate how frailty, measured using the Orthopedic Hip Frailty Score (OFS), modifies the effect of preadmission beta-blocker therapy on mortality in hip fracture patients., Methods: This retrospective register-based study included all adult patients in Sweden who suffered a traumatic hip fracture and subsequently underwent surgery between 2008 and 2017. Treatment effect was evaluated using the absolute risk reduction (ARR) in 30-day postoperative mortality when comparing patients with (BBt+) and without (BBt-) ongoing BBt. Inverse probability of treatment weighting (IPTW) was used to reduce potential confounding when examining the treatment effect. Patients were stratified based on their OFS (0, 1, 2, 3, 4 and 5) and the treatment effect was also assessed within each stratum., Results: A total of 127,305 patients were included, of whom 39% had BBt. When IPTW was performed, there were no residual differences in observed baseline characteristics between the BBt+ and BBt- groups, across all strata. This analysis found that there was a stepwise increase in the ARRs for each additional point on the OFS. Non-frail BBt+ patients (OFS 0) exhibited an ARR of 2.2% [95% confidence interval (CI) 2.0-2.4%, p < 0.001], while the most frail BBt+ patients (OFS 5) had an ARR of 24% [95% CI 18-30%, p < 0.001], compared to BBt- patients within the same stratum., Conclusion: Beta-blocker therapy is associated with a reduced risk of 30-day postoperative mortality in frail hip fracture patients, with a greater effect being observed with higher Orthopedic Hip Frailty Scores., (© 2023. The Author(s).)

Background: Age-associated multimorbidity and polypharmacy, predispose individuals to falls and consequent hip fractures. We examined the impact of polypharmacy (≥ 4 drugs daily), including anticholinergic agents, on hospital length of stay (LOS), mobility within 1-day of hip surgery and pressure ulcers in adults ≥ 60 years admitted with hip fractures., Methods: In this retrospective observational study, information on medications at admission was obtained to calculate the total number of drugs taken, including those imposing an anticholinergic burden (ACB). Associations between variables were examined by logistic regression; adjusted for age, sex, co-morbidities, pre-fracture functional limitations and alcohol consumption., Results: There were 787 women and 318 men of similar mean age (± SD): 83.1 years (± 8.6) and 82.5 years (± 9.0), respectively. Compared to patients with an ACB score = 0 and taking < 4 drugs daily, those with an ACB score ≥ 1 and taking ≥ 4 drugs daily had greater risk of prolonged LOS (≥ 2 weeks), OR 1.8 (1.2-2.7); failure to mobilise within 1-day of surgery, OR 1.9 (1.1-3.3); and pressure ulcers, OR 3.0 (95% CI 1.2-7.9). LOS was further prolonged by failure to mobilise within 1-day of surgery and/or pressure ulcers. Those with either an ACB score ≥ 1 or the use of ≥ 4 drugs daily had intermediate risks., Conclusions: Anticholinergic agents and polypharmacy in patients with hip fractures are associated with longer LOS in hospital, further accentuated by failure to mobilise within 1-day after surgery and pressure ulcers. This study provides further evidence of the impact of polypharmacy, including those with an ACB, on adverse health outcomes and lends support to reduce potentially inappropriate prescribing., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The development of a pelvic wound infection in the presence of hardware after open reduction and internal fixation presents a clinical dilemma and there is little literature to aid in decision-making. The purpose of this study was to describe the possibility of debridement, antibiotic pearls and retention of the implant (DAPRI) procedure to eradicate the infection., Methods: Tumor-like debridement, antibiotic pearls and retention of the implant (DAPRI) aimed to remove the biofilm allowing a higher and prolonged local antibiotic concentration by using calcium sulfate antibiotic-added beads. Wound status, radiological signs of bone healing, gait and functional activity of the patient were evaluated., Results: Seven patients underwent this technique. The mean follow up time was nine months (range: 6 -16 months). Complete wound healing was achieved in all the patients with no major complications. Average time of bony union was 4.3 months (range: 3-6 months) with no need for implant removal., Conclusion: The DAPRI technique might represent a safe and more conservative treatment for management of early fracture-related infections (FRI) of the pelvis and acetabulum., Competing Interests: Declaration of Competing Interest Authors had nothing to disclose about conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Denosumab is an effective antiresorptive drug commonly prescribed for the treatment of osteoporosis. However, some patients do not respond well to denosumab treatment. The aim of this study was to evaluate the factors underlying treatment nonresponses to denosumab in elderly patients following hip fracture. This retrospective study included 130 patients treated with denosumab after osteoporotic hip fracture between March 2017 and March 2020. The patients were categorized as denosumab nonresponders if they had a T-score <-3 that persisted between dual-energy X-ray absorptiometry scans, a >3% decrease in bone mineral density (BMD), or an incident fracture on denosumab therapy. We examined the baseline characteristics associated with blunted BMD responses and compared the groups following denosumab treatment for 12 months. Of 130 patients with baseline data, 105 patients (80.8%) were considered responders. No difference in baseline vitamin D, calcium, BMI, age, gender, prior fracture history, or bisphosphonate use was observed between responders and nonresponders. A longer interval between denosumab injections was associated with suboptimal BMD response at both spine and total hip (p<0.001 and p=0.04, respectively). The overall L-BMD and H-BMD were significantly increased compared with pretreatment levels after denosumab treatment (5.7% and 2.5%, respectively). This study revealed that nonresponse was not strongly associated with certain baseline variables and it appears that the reponders and nonresponders were reasonably comparable in this study population. The results of our study highlight the importance of timely denosumab administration when using this drug for osteoporosis management. Physicians should keep these results in mind in clinical practice so that they can improve utilization of 6-month denosumab.

Background: (1) To evaluate the prescription rate of anti-osteoporosis medication, and (2) to identify factors associated with patients not receiving anti-osteoporosis medication or, when prescribed, not persisting with medication 1 year after hip fracture treatment., Methods: We retrospectively reviewed the medical records of all fragility hip fracture patients admitted to the orthopedic unit of the Faculty of Medicine Siriraj Hospital, Mahidol University, between July 1, 2016, and December 31, 2019. We identified patients who did not receive anti-osteoporosis medication both 6 months and 1 year after fracture treatment. Patients who did not receive the medication 1 year after their treatment were enrolled and interviewed using a no-treatment questionnaire., Results: In total, 530 patients with fragility hip fractures were eligible (mean age, 79.0 years), and most (74.5%) were women. Only 148 patients (31.6%) received anti-osteoporosis medication 1 year after hip fracture. Logistic regression analysis identified predictors for not receiving the medication: male sex (OR 1.8; 95% CI 1.1-3.0), Charlson comorbidity index score ≥ 5 (OR 1.5; 95% CI 1.0-2.3), and secondary school education or below (OR 2.0; 95% CI 1.2-3.3). The main reason for not receiving the medication was that healthcare providers neither discussed nor initiated pharmacological treatment for osteoporosis (48.2%). When the medication was prescribed, non-persistence primarily stemmed from transportation difficulties that resulted in patients missing follow-ups (50.0%)., Conclusions: Improved physician attitudes toward anti-osteoporosis medications might enhance the treatment rate. Developing a follow-up team and facilitating access to medications (eg, courier delivery to patients) would promote therapy compliance., Trial Registrations: The protocol for the first phase and second phase was approved by the Siriraj Institutional Review Board of the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand (COA no. Si 180/2021) and for the second phase, patients-informed consent forms used in the cross-sectional component were approved by the Siriraj Institutional Review Board of the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand (COA no. Si 180/2021). The research was registered with the Thai Clinical Trials Registry (TCTR number: 20210824002). The study was conducted in accordance with the Declaration of Helsinki. Each patient (or a relative/caregiver) provided informed consent in writing or by telephone to participate in this second study phase., (© 2023. The Author(s).)

Objective: To evaluate the effect of warfarin on blood transfusion and postoperative complications in a low-energy hip fracture population compared with a non-anticoagulated comparison group., Design: Multicenter Retrospective Cohort., Setting: Three Urban Level I Academic Trauma Centers., Patients: Acute, low-energy, native hip fractures in patients 55 years of age or older on chronic warfarin anticoagulation, propensity score matched 1:2 to non-anticoagulated hip fracture patients meeting all other inclusion criteria., Main Outcome Measurements: Transfusion and postoperative complication rates., Results: Two hundred ten anticoagulated hip fracture patients were matched to 420 nonanticoagulated patients. A higher proportion of patients required blood transfusion in the warfarin cohort (52.4% vs. 43.3%, P < 0.001), attributable mostly to the subgroup of patients undergoing arthroplasty. Warfarin patients had higher incidence of overall 90-day complications (47% vs. 38%, P = 0.039) and readmissions (31.4% vs. 8.9%, P < 0.001). Day of surgery international normalized ratio (INR) did not influence transfusions or complications among warfarin patients. Warfarin patients undergoing surgery within 24 hours had no difference in transfusions and had fewer complications compared with those undergoing surgery after 24 hours. On multivariable logistic regression analysis, warfarin use and day of surgery INR were not predictors of transfusion or complications., Conclusions: Patients on warfarin experienced longer time to surgery and higher incidence of overall transfusion and postoperative complications within 90 days of surgery. However, warfarin use and day of surgery INR was not independently associated with transfusions or complications. The reason for poorer outcomes in warfarin patients remains a topic of further investigation., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Health records of patients hospitalized for osteoporotic fracture were analyzed. Prior to the index hospital admission, most patients were not receiving any antiosteoporotic treatment. During the index hospitalization visit, 25.5% of patients received antiosteoporotic treatment. The most common treatment regimens were active vitamin D 3 , bisphosphonates, and teriparatide., Purpose: To examine the real-world treatment patterns and factors associated with receipt of treatment among Japanese patients with osteoporotic fracture., Methods: We retrospectively analyzed health records of patients who were hospitalized for osteoporotic fracture between February 2016 and February 2018 in Japan. The type and duration of treatment with antiosteoporotic medications prescribed during hospital stays and after discharge were examined using descriptive statistics. Demographic and clinical factors (e.g., age, previous diagnoses, Charlson Comorbidity Index scores) associated with osteoporotic treatment were explored using multivariable logistic regression., Results: A total of 112,275 patient medical records were evaluated, including 56,574 records from patients with hip fracture, 26,681 records from patients with vertebrae fracture, and 29,020 patients with non-vertebral non-hip fractures. Prior to the index hospital admission, most patients (91.7%, n = 102,919) were not receiving any antiosteoporotic treatment. For those receiving treatment, active vitamin D 3 (51.1%, n = 4778) and bisphosphonates (47.5%, n = 4441) were the most common. During the index hospitalization visit, 25.5% (n = 28,678) of patients received treatment for their fracture, including active vitamin D 3 (n = 17,074), bisphosphonates (n = 10,007), and teriparatide (n = 4561). Upon discharge, 41.5% (n = 46,536) of patients returned to their home and 34.3% (n = 38,542) of patients were transferred to a different hospital or medical care facility. Variables associated with receipt of treatment at follow-up included older age, previous diagnoses of osteoporosis and fracture, and higher Charlson Comorbidity Index scores., Conclusion: Despite osteoporotic fracture being a major health concern within older Japanese populations, treatment with antiosteoporotic medication regimens remains generally low., (© 2023. The Author(s).)

Introduction: Although the use of venous thromboembolism (VTE) chemoprophylaxis has markedly reduced VTE rates after hip fracture surgery, few studies have directly compared the efficacy of different anticoagulant agents in this setting. The purpose of this study was to compare outcomes of Lovenox, Eliquis, or Coumadin as VTE prophylaxis after hip fracture surgery., Methods: The PearlDiver MHip national database was queried for patients older than 60 years undergoing first-time hip fracture surgery with no concurrent pelvic or distal femoral fractures. Prescriptions for Lovenox, Eliquis, or Coumadin were identified. Univariate and multivariate analyses of patient characteristics, 90-day incidences of VTE, adverse events, and readmissions were compared. Odds ratios (ORs) were calculated, and significance was set at P < 0.01 based on Bonferroni adjustment., Results: A total of 11,384 patients were identified, with the Lovenox used for 6835 patients (60.0%), Eliquis for 1092 patients (9.6%), and Coumadin for 3457 patients (30.4%). The prevalence of 90-day VTE in the Lovenox, Eliquis, and Coumadin groups was 3.1%, 3.8%, and 5.0%, respectively (P < 0.001). Multivariate analyses adjusting for demographic and comorbidity profiles were conducted with Lovenox as the referent. Those on Eliquis had significantly lower transfusions (OR 0.52, P = 0.005), but similar rates of other outcomes including VTE (P > 0.01). Conversely, patients on Coumadin had significantly greater odds of any adverse event (OR 1.18, P < 0.001) and VTE (OR 1.58, P < 0.001)., Discussion: In evaluating Lovenox, Eliquis, and Coumadin as VTE chemoprophylactic agents after hip fracture surgery in anticoagulant-naïve patients, Lovenox and Eliquis had similar 90-day VTE, whereas patients on Coumadin had greater odds of 90-day VTE. Interestingly, patients on Eliquis had nearly two-fold lower odds of transfusions compared with patients on Lovenox. Although consensus on the optimal VTE prophylactic agent after hip fracture surgery does not exist, Eliquis and Lovenox may be comparable options and seem to be more effective than Coumadin., Competing Interests: Dr. Rubin or an immediate family member declares potential conflict of interest with the AAOS, Arthroplasty Today, Covatec, DePuy, Johns Hopkins University Press, the Journal of Arthroplasty, Reconstructive Review, and SLACK Incorporated. Dr. Grauer or an immediate family member declares potential conflict of interest with the Lumbar Spine Research Society and the North American Spine Society. Dr. Bernstein or an immediate family member declares potential conflict of interest with the American Association of Hip and Knee Surgeons, AAOS, and DePuy. None of the following authors or any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this article: Dr. Joo, Dr. Modrak, Park and Dr. Brand., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Objectives: To analyze the effect of intravenous tranexamic acid (TXA) on blood transfusion requirements in adult patients undergoing hip fracture surgery. Secondary aim was to evaluate the safety by assessing thromboembolic events., Data Sources: Cochrane Central Register of Controlled Trials, Medline, PubMed, and Embase were searched for randomized controlled trials published in English from 2010., Study Selection: Studies eligible for inclusion were randomized controlled trials that analyzed the use of intravenous TXA on blood transfusion requirement in hip fracture surgery., Data Extraction: Titles and abstracts were screened and assessed for eligibility by 2 independent reviewers. Quality and risk of bias was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach and the Cochrane risk-of-bias tool (RoB2)., Data Synthesis: Meta-analysis with random and fixed effect models was performed. Risk ratio (RR) was calculated for dichotomous outcomes and estimated with a 95% confidence interval (CI). For continuous data, the risk difference (RD) was estimated with a 95% CI., Results: A total of 13 trials involving 1194 patients were included. Pooled results showed that patients in the TXA group had significantly lower transfusion requirements (RR 0.50, 95%CI 0.30-0.84, P = 0.009). Similar findings were observed in the subcohort of patients with transfusion threshold of Hb < 8g/dL, (RR 0.42, 95%CI 0.31-0.56, P < 0.0001). This risk reduction was not observed in the subcohort of patients with transfusion threshold of Hb 8.1-10g/dL who received TXA (RR 0.77, 95%CI 0.51-1.18, P = 0.23) and no statistically significant differences were found for total thromboembolic events (RR 0.01, 95%CI -0.02-0.04, P = 0.47)., Conclusion: This meta-analysis demonstrated that intravenous TXA reduced blood transfusion rates and did not increase the risk of thromboembolic events., Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Polypharmacy is a common problem amongst the elderly population. The complexity of the drug regimen refers not only to a simple medication count, but also to the number of daily doses, frequency, and special instructions given for their use. Medication regimen complexity may affect health outcomes, including an increase in hospitalization rates, drug non-adherence, and mortality rates., Aim: To assess whether the admission medication regimen complexity index score is associated with rehabilitation outcomes in hip fracture patients; secondary- to assess whether changes in the medication regimen complexity index scores during rehabilitation are associated with rehabilitation outcomes., Method: A retrospective study of 336 hip fracture patients admitted to a post-acute rehabilitation hospital. Primary rehabilitation outcome was assessed via the discharge functional independence measure score. Secondary outcomes included functional independence measure score changes, length of stay and discharge destination., Results: Patients with low admission medication regimen complexity index scores attained significantly higher admission and discharge motor functional independence measure scores (40.1 vs. 37.1, p = 0.044; 57.1 vs. 52.9, p = 0.014, respectively), a higher motor functional independence measure score effectiveness (36.1 vs. 31.3, p = 0.030) and a higher rate of favorable motor functional independence measure effectiveness score (58.1% vs. 42.0%, p = 0.004). A multiple linear regression analysis revealed that the admission medication regimen complexity index score was not associated with the discharge functional independence measure score (standardized coefficient = - 0.058; p = 0.079)., Conclusion: A high medication regimen complexity which usually implies severe comorbidity should not be considered a barrier for the rehabilitation of older patients., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Type 2 diabetes (T2D) is associated with increased risk of fractures. However, it is unclear whether current osteoporosis treatments reduce fractures in individuals with diabetes. The aim of the study was to determine whether presence of T2D influences the efficacy of antiresorptive treatment for osteoporosis using the Foundation for the National Institutes of Health (FNIH)-American Society for Bone and Mineral Research (ASBMR)-Study to Advance Bone Mineral Density (BMD) as a Regulatory Endpoint (SABRE) cohort, which includes individual patient data from randomized trials of osteoporosis therapies. In this study we included 96,385 subjects, 6.8% of whom had T2D, from nine bisphosphonate trials, two selective estrogen receptor modulator (SERM) trials, two trials of menopausal hormone therapy, one denosumab trial, and one odanacatib trial. We used Cox regression to obtain the treatment hazard ratio (HR) for incident nonvertebral, hip, and all fractures and logistic regression to obtain the treatment odds ratio (OR) for incident morphometric vertebral fractures, separately for T2D and non-DM. We used linear regression to estimate the effect of treatment on 2-year change in BMD (n = 49,099) and 3-month to 12-month change in bone turnover markers (n = 12,701) by diabetes status. In all analyses, we assessed the interaction between treatment and diabetes status. In pooled analyses of all 15 trials, we found that diabetes did not impact treatment efficacy, with similar reductions in vertebral, nonvertebral, all, and hip fractures, increases in total hip and femoral neck BMD, and reductions in serum C-terminal cross-linking telopeptide (CTX), urinary N-telopeptide of type I collagen/creatinine (NTX/Cr) and procollagen type 1 N propeptide (P1NP) (all interactions p > 0.05). We found similar results for the pooled analysis of bisphosphonate trials. However, when we considered trials individually, we found a few interactions within individual studies between diabetes status and the effects of denosumab and odanacatib on fracture risk, change in BMD or bone turnover markers (BTMs). In sum, these results provide strong evidence that bisphosphonates and most licensed antiresorptive drugs are effective at reducing fracture risk and increasing BMD irrespective of diabetes status. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Background and Objectives: The majority of research on the effects of osteoporosis drugs has measured the bone mineral density (BMD) of the spine and femur through dual-energy X-ray absorptiometry (DEXA) and compared and analyzed the effects of the drugs through changes in the BMD values. This study aims to compare osteoclast and sclerostin expression in osteocytes after risedronate therapy by obtaining femoral heads from patients with hip fractures. Materials and Methods: We obtained the femoral heads of 10 female patients (age: ≥65 years) who received risedronate therapy for at least 1 year through hip arthroplasty during 2019−2021 (risedronate group). Meanwhile, 10 patients who had never received osteoporosis treatment were selected as controls using propensity scores with age, body mass index, and bone density as covariates (control group). While the osteoclast count was evaluated using tartrate-resistant acid phosphatase (TRAP) staining, the sclerostin expression in osteocytes was assessed using immunohistochemistry. Moreover, Western blotting and polymerase chain reaction (PCR) were performed for receptor activation of nuclear factor kappa-Β ligand (RANKL), RANK, osteoprotegerin (OPG), sclerostin, and bone morphogenetic protein-2 (BMP2). Results: TRAP staining revealed significantly more TRAP-positive cells in the control group (131.75 ± 27.16/mm2) than in the risedronate group (28.00 ± 8.12/mm2). Moreover, sclerostin-positive osteocytes were expressed more in the control group (364.12 ± 28.12/mm2) than in the risedronate group (106.93 ± 12.85/mm2). Western blotting revealed that the expressions of RANKL, RANK, sclerostin, and BMP2 were higher in the control group than in the risedronate group (p < 0.05). Furthermore, RANK, sclerostin, and OPG protein levels were higher in the control group than in the risedronate group. Conclusions: In this study, the risedronate group demonstrated lower osteoclast activity and sclerostin expression in osteocytes in the femoral head than the control group.

Introduction: The use of tranexamic acid (TXA) in hip fracture surgery remains inconclusive. The aim of the present meta-analysis was to assess the role of TXA use in hip fracture surgery, and attempt to disclose possible factors which might influence TXA efficacy and safety., Materials and Methods: A systematic computerized literature search was conducted to retrieve all randomized controlled trials (RCTs) and cohort studies regarding TXA use in hip fracture surgery. Overall efficacy and safety were evaluated. Then, subgroup and meta-regression analyses were conducted to disclose the influence of geographic area, fracture type, administration route, frequency and dosage of TXA, blood transfusion threshold, and follow-up duration on the overall effect., Results: Thirty-four RCTs and 11 cohort studies were included. Patients receiving TXA had a significant decrease in the need for blood transfusion, reduced total, intra-operative and post-operative blood loss, a decrease in pre- and postoperative hemoglobin difference, without increasing thromboembolic events risk. Subgroup analysis showed that topical TXA had a lower transfusion rate compared with controls, yet the result did not reach statistical significance. Also, TXA had similar efficacy and safety profiles in patients with different frequency and dosage of TXA., Conclusion: Current evidence indicated that intravenous administration of TXA could significantly reduce blood transfusion and blood loss without increasing risk of thromboembolic events. The frequency and dosage of TXA might not alter the beneficial effect. The application of topical TXA should be cautious., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The purpose of this study was to analyze the association between the preoperative and postoperative use of antidepressant and benzodiazepine and all-cause mortality in elderly hip fracture patients., Methods: Patients who underwent surgical treatment for hip fracture over 65 years old were classified into Past-user, Current-user, and Non-users for each period according to use history for antidepressants or benzodiazepines. And, for the subgroup analysis, patients were classified by presence of past history for psychiatric medication. A multivariable-adjusted Cox proportional hazards model was used to investigate the effects of antidepressants and benzodiazepines on all-cause mortality., Results: A total of 15,576 patients were included in this study. Past users of antidepressants and benzodiazepines were 5699 (36.59%) patients and 11,319 (72.67%) patients, respectively. Current users of antidepressants and benzodiazepines were 2888 (18.54%) patients and 6287 (40.36%) patients, respectively. There were no statistically significant differences in the adjusted hazard for death compared to the non-users for both the past and the current users (p > 0.05). In the subgroup analysis, there were 12,502 once-users and 3074 never-users according to psychiatric medication. Current uses of antidepressants and benzodiazepine in the once-user did not increase adjusted hazard for death compared to the non-users (p>0.05). However, current uses of antidepressants by never-users increased the adjusted hazard for death compared to the non-user (adjusted hazard ratio, 1.31; 95% CI, 1.08-1.59; p = 0.007)., Conclusions: No association was observed between the uses of antidepressants and benzodiazepines after hip fracture and mortality risk in elderly patients who received psychiatric medication before hip fracture. However, the use of these medications was associated with increased all-cause mortality risk in patients who had no history of psychiatric medication before hip fracture., Level of Evidence: III, retrospective cohort study., Competing Interests: Declaration of competing interest Jun-Il Yoo, Suk-Yong Jang, Yonghan Cha, Joon-Hyeok Gwak, Jung-Taek Kim, Chan Ho Park, and Won-Sik Choy declare that they have no conflict of interest., (Copyright © 2021 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Anti-osteoporosis treatment following hip fractures may reduce the overall mortality rate. However, the effects of different drugs on mortality is still unclear. This population-based cohort study aimed to identify the degree of reduced mortality after various anti-osteoporosis regimens following hip fracture surgery. We conducted this cohort study to identify patients with newly diagnosed osteoporosis and hip fractures from 2009 to 2017 using the Taiwan National Health Insurance Research Database (NHIRD). The subsequent use of anti-osteoporosis medication following hip fracture surgery was collected and analyzed. National death registration records were retrieved to determine mortality. A total of 45,226 new cases of osteoporotic hip fracture were identified. Compared with patients who did not receive further treatment, patients who had ever used oral bisphosphonates (alendronate and risedronate, hazard ratio [HR] 0.81; 95% confidence interval [CI], 0.78-0.84), ibandronate (HR 0.76; 95% CI, 0.67-0.86), zoledronic acid (HR 0.70; 95% CI, 0.64-0.76), and denosumab (HR 0.64; 95% CI, 0.60-0.68) showed lower all-cause mortality rates. Patients treated with bisphosphonates had a lower mortality risk than those treated with selective estrogen receptor modulators (HR 0.81; 95% CI, 0.75-0.87). Patients treated with zoledronic acid showed a lower mortality risk than those treated with oral bisphosphonates (HR 0.89; 95% CI, 0.82-0.97). However, patients receiving denosumab and zoledronic acid did not show a significant difference in mortality (HR 0.94; 95% CI, 0.85-1.03). Different anti-osteoporosis treatments for postsurgical patients were associated with different levels of decline in mortality. Generally, longer durations of drug use were associated with lower mortality. © 2022 American Society for Bone and Mineral Research (ASBMR)., (© 2022 American Society for Bone and Mineral Research (ASBMR).)

Purpose: Early initiation of anti-osteoporosis medications (AOMs) is recommended for patients on long-term glucocorticoid (GC) therapy. This study aimed to examine whether physicians prescribe AOMs as soon as GC therapy is initiated, and whether a delay in AOM initiation affects hip and vertebral fracture incidence, using the nationwide health insurance claims database of Japan (NDBJ)., Methods: Patients aged ≥50 years who were prescribed GC (≥5 mg/day prednisolone or equivalent) for ≥90 days and who were followed for AOM use and hip and vertebral fracture events for the subsequent 1080 days in 2012-2018 were selected from NDBJ. Delay in AOM initiation was defined as the number of days without AOMs following GC therapy initiation. Associations between delay in AOM initiation and hip and vertebral fracture risk were evaluated by Cox proportional hazards regression., Results: In total, 92,143 women and 94,772 men were included in the analysis, of which only 39.3% of women and 28.5% of men received AOMs within 90 days from GC therapy initiation. Approximately, 15% of hip fractures and 30% of vertebral fractures occurred before AOM initiation in patients with delayed AOM initiation. HRs of both fractures were significantly greater in patients with a longer delay in AOM initiation (p value for trend<0.001). After excluding patients who had fractures before AOM initiation, the magnitude of HRs significantly decreased, and HR trends for hip fracture became insignificant., Conclusions: Delayed initiation of AOMs may result in increased fracture events, which may be reduced by early initiation of AOMs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To investigate the effect of biologic therapy on risk of fracture in selected rheumatic and autoimmune diseases., Methods: The PubMed, Cochrane library, and EMBASE databases were systematically searched from the inception dates to June 4, 2021. Randomized clinical trials (RCTs) comparing biological disease-modifying antirheumatic drugs (bDMARDs) with non-bDMARDs or placebo in patients with five selected rheumatic and autoimmune diseases were included. Meta-analyses were conducted to calculate the odds ratio (OR) with 95 % confidence intervals (CIs) for major osteoporotic fracture, hip fracture, osteoporotic non-vertebral fracture, and total fracture., Results: A total of 100 RCTs involving 51,413 participants fulfilled the inclusion criteria. In patients with psoriasis (Ps), and psoriatic arthritis (PsA), compared with placebo or non-bDMARDs therapy, the risk of major osteoporotic fracture (OR, 0.34 [95 %Cl, 0.15-0.76], p = 0.009), hip fracture (OR, 0.22 [95 %Cl, 0.05-0.89], p = 0.03), and osteoporotic non-vertebral fracture (OR, 0.26 [95 %Cl, 0.10-0.62], p = 0.003) were significantly decreased with the use of bDMARDs. In patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), systemic lupus erythematosus (SLE), and inflammatory bowel diseases (IBD), the risk of fracture were not changed with biologic treatment., Conclusions: The existing evidence from RCTs indicated the use of bDMARDs was associated with a low risk of major osteoporotic fracture, hip fracture, and osteoporotic non-vertebral fracture in patients with Ps and PsA. There are still urgent needs for studies regarding the actions of biologic therapies on the risk of bone fractures in systemic inflammatory diseases., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Hip fractures among older people are a major public health issue, which can impact quality of life and increase mortality within the year after they occur. A recent observational study found an increased risk of hip fracture in subjects who were new users of tramadol compared with codeine. These drugs have somewhat different indications. Tramadol is indicated for moderate to severe pain and can be used for an extended period; codeine is indicated for mild to moderate pain and cough suppression., Objective: In this observational study, we compared the risk of hip fracture in new users of tramadol or codeine, using multiple databases and analytical methods., Methods: Using data from the Clinical Practice Research Datalink and three US claims databases, we compared the risk of hip fracture after exposure to tramadol or codeine in subjects aged 50-89 years. To ensure comparability, large-scale propensity scores were used to adjust for confounding., Results: We observed a calibrated hazard ratio of 1.10 (95% calibrated confidence interval 0.99-1.21) in the Clinical Practice Research Datalink database, and a pooled estimate across the US databases yielded a calibrated hazard ratio of 1.06 (95% calibrated confidence interval 0.97-1.16)., Conclusions: Our results did not demonstrate a statistically significant difference between subjects treated for pain with tramadol compared with codeine for the outcome of hip fracture risk., (© 2022. The Author(s).)

BACKGROUND Numerous randomized controlled trials (RCTs) have evaluated pharmacological therapies for osteoporosis. The aim of this Bayesian network meta-analysis was to compare the efficacy and safety of pharmacological therapies for osteoporosis patients. MATERIAL AND METHODS The electronic databases of PubMed, Embase, and Cochrane Library were systematically searched for eligible RCTs from their inception up to January 2021. The primary endpoints were all fractures, vertebral fractures, and non-vertebral fractures, while the secondary endpoints were fractures at hip or peripheral locations, bone mineral density (BMD) at various sites, and potential adverse events. RESULTS We included 79 RCTs reporting a total of 108 797 individuals in the final quantitative analysis. The results of network analysis indicated that romosozumab (92.1%) was the most effective in reducing the risk for all fractures, with the best therapeutic effects on vertebral fracture (97.2%) and non-vertebral fracture (88.0%). Romosozumab (92.5%) provided better therapeutic effects for the reduction of hip fracture. The best treatment agents for improving whole-body BMD (100.0%), spine BMD (95.7%), hip BMD (92.4%), femoral neck BMD (86.7%), and trochanter BMD (95.5%) were alendronate, strontium ranelate, ibandronate, risedronate, and ibandronate, respectively. Finally, the use of bazedoxifene was associated with the highest incidence of any upper-gastrointestinal event, nasopharyngitis, and back pain, while risedronate was associated with higher incidence of abdominal pain and dyspepsia. CONCLUSIONS This study found that romosozumab yielded the best effects for preventing fracture risk, while abaloparatide was the most effective in reducing the risk of vertebral fracture and non-vertebral fracture.

Background: The use of tramadol among osteoarthritis (OA) patients has been increasing rapidly around the world, but population-based studies on its safety profile among OA patients are scarce. We sought to determine if tramadol use in OA patients is associated with increased risks of all-cause mortality, cardiovascular diseases (CVD), venous thromboembolism (VTE), and hip fractures compared with commonly prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) or codeine., Methods: Using administrative health datasets from British Columbia, Canada, we conducted a sequential propensity score-matched cohort study among all OA patients between 2005 and 2013. The tramadol cohort (i.e., tramadol initiation) was matched with four comparator cohorts (i.e., initiation of naproxen, diclofenac, cyclooxygenase-2 [Cox-2] inhibitors, or codeine). Outcomes are all-cause mortality, first-ever CVD, VTE, and hip fractures within the year after the treatment initiation. Patients were followed until they either experienced an event, left the province, or the 1-year follow-up period ended, whichever occurred first. Cox proportional hazard models were used to estimate hazard ratios after adjusting for competing risk of death., Results: Overall, 100,358 OA patients were included (mean age: 68 years, 63% females). All-cause mortality was higher for tramadol compared to NSAIDs with rate differences (RDs/1000 person-years, 95% CI) ranging from 3.3 (0.0-6.7) to 8.1 (4.9-11.4) and hazard ratios (HRs, 95% CI) ranging from 1.2 (1.0-1.4) to 1.5 (1.3-1.8). For CVD, no differences were observed between tramadol and NSAIDs. Tramadol had a higher risk of VTE compared to diclofenac, with RD/1000 person-years (95% CI) of 2.2 (0.7-3.7) and HR (95% CI) of 1.7 (1.3-2.2). Tramadol also had a higher risk of hip fractures compared to diclofenac and Cox-2 inhibitors with RDs/1000 person-years (95% CI) of 1.9 (0.4-3.4) and 1.7 (0.2-3.3), respectively, and HRs (95% CI) of 1.6 (1.2-2.0) and 1.4 (1.1-1.9), respectively. No differences were observed between tramadol and NSAIDs for all events., Conclusions: OA patients initiating tramadol have an increased risk of mortality, VTE, and hip fractures within 1 year compared with commonly prescribed NSAIDs, but not with codeine., (© 2022. The Author(s).)

Results from real-world evidence (RWE) from the largest healthcare region in Sweden show low uptake of antiresorptive (AR) treatment, but beneficial effect in those receiving treatment, especially for the composite outcome of hip fracture or death. For RWE studies, Sweden is unique, with virtually complete coverage of electronic medical records (EMRs) and both regional and national registries, in a universal publicly funded healthcare system. To our knowledge, there is no previous RWE study evaluating the efficacy of AR treatment compared to no AR treatment after fragility fracture, including data on parenteral treatments administered in hospital settings. The Stockholm Real World Management (STORM) study cohort was established in the healthcare region of Stockholm to retrospectively assess the effectiveness of AR treatment after first fragility fracture using the regional EMR system for both hospital and primary care. Between 2012 and 2018, we identified 69,577 fragility fracture episodes among 59,078 patients, men and women, 50 years and older. Of those, 21,141 patients met inclusion and exclusion criteria (eligible cohort). From these, the final matched study cohort comprised 9840 fragility fractures (cases receiving AR treatment [n = 1640] and controls not receiving AR treatment [n = 8200]). Propensity scores were estimated using logistic regression models with AR treatment as outcome and confounders as independent variables followed by analysis using Cox proportional hazard models. Real world evidence from Sweden's largest healthcare region, comprising a quarter of the Swedish population, show that only 10% of patients receive AR treatment within 1 year after a fragility fracture. Factors associated with not receiving treatment include having a diagnosis of cardiovascular disease. In those treated, AR have positive effects particularly on the composite of fracture and death (any fracture/death and hip fracture/death) in individuals matched for all major confounders. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Background: Since 2011, Taiwan's National Health Insurance Administration (NHIA) issued a regulation on the reimbursement to anti-osteoporosis medications (AOMs). This study aimed to evaluate the impact of this regulation in reimbursement on the utilization of AOMs, clinical outcomes and associated medical expenditures of patients with incident hip fractures., Methods: By using the National Health Insurance Research Database (NHIRD), patients with incident hip fracture from 2006 to 2015 were identified as our study cohort. Patients younger than 50 years old or prescribed with AOMs within one year prior to incident fracture were excluded. Outcomes of interest were quarterly estimates of the proportion of patients who received bone mineral density (BMD) examination, who were prescribed AOMs, as well as who encountered subsequent osteoporotic fracture-related visits and associated medical expenditures. Particularly, age- and gender specific estimates were reported. An interrupted time series study design with segmented regression model was used to quantitatively explore the impact of the changes of the reimbursement criteria on the level (immediate) and trend (long-term) changes of these outcomes., Results: Our study enrolled 118 493 patients with incident hip fracture with those patients aged older than 80 years old accounting for the largest proportion. A significantly decreased trend of AOMs prescription rates was observed immediately post regulation except for female aged between 65 and 80, while the long-term pattern showed no significant difference. However, the percentage of patients encountered subsequent osteoporotic fracture-related visit was not statistically different between pre- and post-regulation periods. Noteworthy, the policy regulation was associated with an increasing trend of osteoporotic fracture associated medical expenditures, especially for patients older than 80 years old., Conclusion: The regulation on the reimbursement for AOMs decreased the prescribing rate of AOMs immediately although the effect did not sustain thereafter. However, higher subsequent osteoporotic fracture-related medical expenditures were introduced, especially among those very old population., (© 2022 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: Early surgery has been consistently demonstrated to reduce complications and mortality in hip fracture patients. There remains no general consensus, however, regarding the optimal time to surgery for hip fracture patients who are on novel oral anticoagulants (NOAC) on admission and its effect on clinical outcomes after surgery. The objective of this review was to assess the effect of preoperative NOAC therapy on time to surgery and postoperative complications in hip fracture patients., Methods: We performed a systematic review of the literature using the PubMed, Embase, and Cochrane Library electronic databases. Relevant articles were identified and included if they: (i) included patients on NOAC therapy on admission who did not undergo reversal; (ii) included a control group of patients not on any anticoagulation; (iii) included time from admission to surgery; and (iv) included one of the following outcomes: blood transfusion, venous thromboembolism (VTE), stroke, readmission, and mortality., Results: Nine studies were included with a total of 4,419 patients. There were 414 NOAC patients and 4,005 non-anticoagulated patients. Six of the nine studies found a significant increase in time to surgery for patients on NOAC therapy. Three of the seven studies that reported rates of blood transfusion found a significantly higher incidence of transfusion in patients on NOACs. None of the studies found a significant difference in VTE and stroke. One of the two studies that reported readmissions showed a higher risk of readmission for patients on NOACs. Eight of the nine included studies found no significant difference in postoperative mortality rates between the NOAC and control groups, with the remaining study finding a higher mortality rate only in patients on NOAC therapy who underwent fixation and not those who underwent arthroplasty., Conclusions: These mixed findings suggest that delay to surgery may not be warranted in the urgent surgical setting of patients on NOAC therapy who sustain hip fractures., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Background: Inadequate postoperative analgesia has been noted in patients with dementia, but this topic has only been studied in hip fractures. This study aimed to examine whether the duration of postoperative analgesia associated with three surgical procedures was shorter in patients with dementia than in those without dementia., Methods: This retrospective observational study was based on a nationwide discharge database of acute care hospitals in Japan and included patients aged ≥ 65 years diagnosed with lung cancer, rectal cancer, or hip fracture, who underwent surgery in 366 hospitals between April 2013 and September 2018. The primary outcome was the incidence of injectable analgesic use during the postoperative hospital stay. The number of person-days of opioid, non-steroidal anti-inflammatory drug, or acetaminophen use was calculated for patients with and without dementia after each surgery using generalized estimating equations to obtain the age-adjusted incidence per 100 person-days., Results: Among the 32,379 patients included, 4828 (14.9%) had dementia. The duration of opioid administration per 100 person-days was 14% shorter in patients with dementia than in those without dementia after open rectal cancer surgery (incidence rate ratio [IRR] 0.86; 95% confidence interval [CI] 0.74-1.00) and 20% shorter in patients with dementia after open lung cancer surgery (IRR 0.80; 95% CI 0.70-0.91). In patients who underwent thoracoscopic lung cancer surgery, laparoscopic rectal cancer surgery, or hip replacement surgery, the duration of opioid administration was shorter in patients with dementia than in those without dementia, but the difference was not statistically significant., Conclusions: The length of postoperative opioid administration after lung and rectal cancer surgery was reduced in patients with dementia, suggesting that the duration of postoperative analgesia in patients with dementia may be insufficient. More careful pain assessment and management of postoperative analgesia in these patients may be necessary., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Bisphosphonates are effective in reducing hip and other fractures. However, concerns about atypical femur fractures (AFFs) have contributed to substantially decreased bisphosphonate use, and hip fracture rates may be increasing. Despite this impact, important uncertainties remain regarding AFF risks including the association between bisphosphonate use and other risk factors such as BMD, age, weight, and race. To address this evidence gap, a cohort study of 196,129 women ≥50 years of age in the Southern California Kaiser Permanente HMO women (with ≥1 bisphosphonate prescription) were studied; the primary outcome was radiographically-adjudicated AFF between 2007 and 2017. Risk factors including bisphosphonate use and race were obtained from electronic health records. Multivariable Cox models were used for analysis. Benefit-risk was modeled for 1-10 years of bisphosphonates to compare fractures prevented vs. AFFs associated. Among 196,129 women, 277 (0.1%) sustained AFFs. After multivariable adjustment, AFF risk increased with longer bisphosphonate duration: hazard ratio (HR) increased from HR = 8.9 (95%CI: 2.8,28) for 3-5 years to HR = 43.5 (13.7138.1) for >8 years. Hip BMD, surprisingly, was not associated with AFF risk. Other risk factors included Asian ancestry (HR = 4.8 (3.6, 6.6)), short stature, overweight, and glucocorticoid use. Bisphosphonate discontinuation was associated with rapid decrease in AFF risk. Decreases in osteoporotic and hip fractures risk during 1-10 years of bisphosphonates far outweighed the increase AFF risk in Caucasians, but less so in Asians. In Caucasians, after 3 years 149 hip fractures were prevented with 2 AFFs associated compared to 91 and 8 in Asians. The evidence for several potential mechanisms is summarized with femoral geometry being the most likely to explain AFF risk differences between Asians and Caucasians. The results from this new study add to the evidence base for AFF risk factors and will help inform clinical decision-making for individual patients about initiation and duration of bisphosphonate therapy and drug holidays., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To determine whether locally injected tranexamic acid (TXA) used in the surgical treatment of fragility hip fractures can lower transfusion rates without increasing the risk of complications., Design: Retrospective comparative cohort., Setting: Tertiary referral orthopaedic specialty hospital, Level I trauma center., Patients/participants: A total of 490 patients (252 patients received TXA) 50 years of age and older who underwent surgery for a low-energy fragility fracture of the proximal femur between March 2018 and February 2020 were included in this study., Intervention: Use of locally injected TXA at the time of wound closure., Main Outcome: The main outcomes of this study were the number of patients requiring postoperative blood transfusions, incidences of venous thromboembolism, and surgical site infections., Results: A statistically significant difference was noted in the frequency of transfusion between patients who received TXA compared with those who did not receive TXA (33% vs. 43%, respectively) (P = 0.034). There were no significant differences in venous thromboembolism incidence (0.4% vs. 0.8% TXA vs. No TXA) (P = 0.526) or infections (0.4% vs. 0.4% TXA vs. No TXA) (P = 0.965). Regression analysis indicated that the use of TXA reduced the need for postoperative blood transfusion by 31% (odds ratio: 0.688, 95% CI: 0.477-0.993, P = 0.045)., Conclusion: Locally injected TXA significantly reduced the need for postoperative transfusion in the surgical treatment of fragility hip fractures. In addition, there was no increased risk of complications in those receiving TXA versus those who did not. Locally injected TXA seems to be both a safe and effective way to reduce postoperative blood transfusions in patients with fragility hip fractures., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: By aggregating the literature, we evaluated the association between use of specific antihypertensive drugs and the risk of hip fractures compared with nonuse., Study Design and Setting: We systematically searched the Pubmed, Embase, and Cochrane databases from inception of each database until July 30, 2020 to identify articles including patients 18 years of age or older reporting on the association between antihypertensive drugs and the risk of hip fracture. Antihypertensive drugs were restricted to thiazides; beta-blockers; calcium-channel blockers; angiotensin-converting enzyme (ACE) inhibitors; and angiotensin receptor blockers. Nonusers encompass all patients that are not using the specific antihypertensive drug that has been reported. Unadjusted odds ratios with 95% confidence intervals (CIs) of the association between antihypertensive drug use and hip fractures were reported. Meta-analysis was performed when a minimum of five studies were identified for each antihypertensive drug class. Quality assessment was done using ROBINS-I tool. The GRADE approach was used to evaluate the certainty of the evidence., Results: Of 962 citations, 22 observational studies were included; 9 studies had a cohort design and 13 studies were case-control studies. No randomized controlled trials were identified. We found very low certainty of evidence that both thiazides (pooled odds ratio: 0.85, 95% CI 0.73 to 0.99, p = 0.04) as well as beta-blockers (pooled odds ratio: 0.88, 95% CI 0.79 to 0.98, p = 0.02) were associated with a reduced hip fracture risk as compared to specific nonuse. One study, reporting on angiotensin receptor blockers, also suggested a protective effect for hip fractures, whereas we found conflicting findings in four studies for calcium-channel blockers and in two studies for ACE inhibitors., Conclusion: Among 22 observational studies, we found very low certainty of evidence that, compared to specific nonuse of antihypertensive drugs, use of thiazides, beta-blockers, and angiotensin receptor blockers were associated with a reduced protective hip fracture risk, while conflicting findings for calcium-channel blockers and ACE inhibitors were found. Given the low quality of included studies, further research -randomized controlled trials- are needed to definitively assess the causal relationship between specific antihypertensive drug classes and (relatively infrequent) hip fractures., Competing Interests: Declaration of Competing Interest N/A., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: The three direct oral anticoagulants (DOAC), rivaroxaban, apixaban and dabigatran have been associated with lower risks of fractures compared to warfarin. However, no large scale studies have explored the associations with the newest DOAC, edoxaban, with fracture risk. The present study aims to elucidate the effects of edoxaban on the risk of hip fracture amongst elderly patients by comparing the incidence of new onset hip fracture between edoxaban and warfarin users in a Chinese population., Methods: This was a retrospective population-based cohort study of patients with edoxaban or warfarin use between January 1st, 2016 and December 31st, 2019 in Hong Kong, China. Patients with less than one-month exposure, medication switching between warfarin and edoxaban, those who died within 30 days after drug exposure, prior human immunodeficiency virus infection, age <50 years old, and those with prior hip fractures were excluded. Propensity score matching (1:2) between edoxaban and warfarin users using the nearest neighbour method was performed based on demographics, prior comorbidities, and use of different medications. The study outcomes were new onset hip fractures, medically attended falls and all-cause mortality., Results: A total of 5014 patients including 579 edoxaban users and 4435 warfarin users (median age: 70 years old [interquartile range (IQR): 62-79], 56.66% males) with a median follow-up of 637.5 (IQR: 320-1073) days were included. In the matched cohort, edoxaban users had significantly lower rates of new onset hip fractures, medically attended falls and all-cause mortality. The protective value of edoxaban use against new onset hip fracture (hazard ratio [HR]: 0.13, 95% confidence interval [CI]: [0.03-0.54], p = 0.0051), medically attended falls (HR: 0.47, [0.29-0.75], p = 0.0018) and all-cause mortality (HR: 0.61, [0.42-0.87], p = 0.0059) in comparison to warfarin use persisted after matching. The significant relationship between edoxaban use and lower fracture risk was preserved in all sensitivity analyses using different approaches using the propensity score., Conclusions: Edoxaban use is associated with lower risks of new onset hip fractures, medically attended falls and mortality risks compared to warfarin after propensity score matching., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This meta-analysis and systematic review investigated the efficacy of bisphosphonates on the incidence of hip fracture (IHF) in patients of different ages with osteoporosis or osteopenia. We searched Web of Science, Embase, the Cochrane Database, and PubMed from inception to January 10, 2021, for trials reporting the effects of bisphosphonates on the IHF. We included only randomized, double-blind, placebo-controlled clinical trials. We pooled data using a random-effects meta-analysis with risk ratios (RRs) and reported 95% CIs. We also used the Cochran Q and I² statistics to assess the heterogeneity in the results of individual studies. The primary endpoints were the total numbers of people in the bisphosphonates and placebo groups and the numbers of IHFs during the follow-up periods. Bisphosphonates reduced the IHF with an overall effect (RR: 0.66; 95% CI: 0.56 to 0.77; zoledronic acid: RR: 0.60; 95% CI: 0.46 to 0.78; risedronate: RR: 0.74; 95% CI: 0.59 to 0.94, and alendronate: RR: 0.61; 95% CI: 0.40 to 0.95). The result of the heterogeneity assessment was I²=0, p=0.97. In all age groups (all ages, ≥55 years old, ≥65 years old), bisphosphonates reduced the IHF. In the ≥55 years old and ≥65 years old age groups, the RR and 95% CI were 0.63 and 0.43 to 0.93, and 0.60 and 0.44 to 0.81, respectively. Bisphosphonate reduced the IHF in the general population and all age groups (≥55 years old and ≥65 years old). Zoledronic acid, risedronate and alendronate reduced the IHF in osteoporosis or osteopenia populations. The association between bisphosphonate and the IHF does not appear to be influenced by age., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2022. No commercial re-use. See rights and permissions. Published by BMJ.)