Treatment with denosumab reduces second hip fracture risk in elderly patients with femoral neck fractures

Treatment with denosumab reduces second hip fracture risk in elderly patients with femoral neck fractures | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Treatment with denosumab reduces second hip fracture risk in elderly patients with femoral neck fractures Yuzhu Wang, Kunming Pan, Xiaoyu Li, Qianzhou Lv, Yunchao Shao, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6569056/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Oct, 2025 Read the published version in BMC Musculoskeletal Disorders → Version 1 posted 10 You are reading this latest preprint version Abstract Background The issue of second hip fracture following surgery for a hip fracture has recently been the focus of increased research attention. The purpose of our study was to evaluate the effect of denosumab on the risk of second hip fracture following first hip fracture surgery in the elderly Chinese population. Methods This was a retrospective observation study in which patients aged 65 years and older suffering from osteoporotic femoral neck fractures between 1 January 2020 and 31 December 2021 were included. The patients were divided into two groups: denosumab group and control group. Propensity score matching (PSM) was performed to adjust between-group differences. Second hip fracture was defined as the time to the first occurrence following first hip fracture. Results A total of 259 patients were included in the analysis. After PSM, the risk of second hip fracture was significantly reduced in the denosumab group when compared with that in the control group (8.8% vs. 29.7%, hazard ratio (HR) = 0.292, 95%CI = 0.133–0.643, P <0.001). The incidence of second hip fracture was significantly lower in female patients and patients aged 65–84 years in the denosumab group than that in the control group (5.3% vs. 29.8%, HR = 0.293, 95%CI = 0.126–0.680, P = 0.002; 6.2% vs. 22.8%, HR = 0.241, 95%CI = 0.079–0.740, P = 0.007; respectively). Conclusions Denosumab reduced the risk of second hip fracture in elderly patients, with this reduction being especially marked in female patients and those aged 65–84 years. Patients who received denosumab following first hip fracture had a lower incidence of second hip fractures, thus emphasizing the importance of the prompt initiation of antiosteoporosis treatment in elderly patients following hip fracture. denosumab second hip fracture elderly patients femoral neck fracture osteoporotic fracture Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Current projections indicate a global increase in the number of hip fractures, from 1.26 million in 1990 to 4.5 million by 2050, with approximately half of these occurring in Asia, a region of particular concern which includes China [ 1 ]. Hip fracture, including femoral neck and intertrochanteric fractures, is the most devastating type of osteoporotic fracture, which can be attributed to the elevated risk of morbidity, mortality, disability and subsequent hip fracture, as well as the significant societal healthcare expenditures it engenders [ 2 – 7 ]. The majority of these injuries occur in the elderly population as a result of low-energy falls and may involve either direct or indirect mechanisms [ 2 , 8 ]. Direct mechanisms encompass a fall onto the greater trochanter or forced external rotation of the lower extremity, which exerts pressure on the femoral neck against the posterior lip of the acetabulum. Indirect mechanisms arise from the occurrence of muscle forces which surpass the capacity of the femoral neck. Therefore, it is imperative that surgeons are able to recognize specific fracture patterns and patient characteristics that indicate the use of particular implants and methods for the effective management of such injuries. Denosumab is a fully human monoclonal antibody that functions as an inhibitor of receptor activator of nuclear factor-κB ligand, a key mediator of osteoclast development, function, and survival [ 9 ]. In the second and third phases of the trial, denosumab rapidly decreased bone resorption markers and increased bone mineral density (BMD) at all skeletal sites measured in comparison with the placebo [ 10 – 11 ]. In the multicentre, randomized, double-blind, placebo-controlled, phase 3 FREEDOM trial, denosumab treatment for a period of up to 10 years was associated with low rates of adverse events, a low fracture incidence when compared with that observed during the original trial, and continued increases in BMD without plateau in postmenopausal women with osteoporosis [ 12 ]. In the FREEDOM study, the incidence of hip fracture in subjects (1.2%) who received a placebo was lower than in the Fracture Intervention Trial-I (2.2%) and the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly trials (2.5%) [ 13 – 14 ]. However, the effect of denosumab on the incidence of second hip fracture in elderly Chinese individuals afflicted with femoral neck fractures after first hip fracture surgery remains to be scarcely reported. In addition, in order to develop a comprehensive understanding of the factors related to second hip fracture, it is essential to conduct a detailed investigation into the impact of gender and age in patient populations. In this study, we evaluated the incidence of second hip fracture in elderly patients suffering from osteoporotic femoral neck fractures following first hip fracture surgery who were simultaneously administered denosumab and assessed the relationship between denosumab and second hip fracture with regard to gender and age. Methods A retrospective observational study was conducted at a single centre, with elderly patients suffering from primary femoral neck fractures owing to low-energy trauma who had undergone the internal fixation or hip arthroplasty from January 2020 to December 2021 being enrolled. A total of 267 patients were included in the study according to the inclusion and exclusion criteria. The patients participating in the study were divided into two groups, categorized on the basis of whether they received denosumab treatment following hip fracture surgery: denosumab group and non-denosumab group (control group). The administration of denosumab was conducted via subcutaneous injection, with a dosage of 60 mg per each injection, administered twice per year, over a period of three years. Inclusion criteria were as followed: (1) patients aged 65 years and older; (2) patients suffering from primary femoral neck fractures caused by low-energy trauma who undergo internal fixation or hip arthroplasty; (3) willingness to undertake the subsequent telephone follow-up. Exclusion criteria included: (1) patients with multiple fractures; (2) receiving other antiosteoporosis medications prior to denosumab treatment; (3) tumor patients; (4) immune system diseases including thyroid dysfunction, systemic lupus erythematosus, and rheumatoid arthritis; (5) reluctance to engage with telephone communications made in follow-up. The study population comprised patients who had been diagnosed with a fragility hip fracture, and for whom three years of follow-up data were available for the objective of evaluating the incidence of second hip fracture following primary hip fracture surgery. Follow-up time was defined as the number of days from the index fracture event to the occurrence of second hip fracture or the most recent appointment, whichever occurred first. The following demographic and clinical characteristics were collected: gender (female or male), age, body mass index (BMI), American Society of Anesthesiologist (ASA) classification, anesthesia (general anesthesia or spinal anesthesia), site of fracture (left or right), surgical types (internal fixation or hip arthroplasty), comorbid diseases (hypertension, diabetes, stroke, heart attack, chronic obstructive pulmonary disease (COPD), anxiety/depression, dementia, and Parkinson’s disease). Statistical analysis In order to adjust for differences between the groups, propensity score matching (PSM) was employed, using propensity scores (PSs) in order to reflect the probability of each patient. These scores were derived through multiple logistic regression analysis, with the analysis based on the patients’ characteristics and clinical risk factors, including gender, age, BMI, ASA, anesthesia, site of fracture, surgical types, hypertension, diabetes, stroke, COPD, anxiety/depression, dementia, and Parkinson’s disease. In this study, a width measurement of 0.2 calipers was used for the implementation of the matching process. The equilibrium of variables among the groups was evaluated through the calculation of standardized mean differences (SMDs), with a cut-off value of 0.10, in the overall population as well as the propensity score-matched population. In instances of normal distribution, continuous variables were expressed as the mean ± standard deviation (SD). For non-normal distribution, continuous variables were expressed as the median with the interquartile range (IQR). The determination of significant differences between groups was achieved through the implementation of two statistical tests: Student t test or Mann-Whitney U test. Categorical variables were expressed as frequencies or percentages and were tested using the chi-square test or the Fisher exact test, as appropriate. Multiple imputation was performed to replace the missing data for baseline variables. Kaplan-Meier survival curve analysis was performed in order to assess the cumulative incidence according to different groups, and the differences were then compared between the denosumab group and the control group by means of the log-rank test. The hazard ratios (HRs) and confidence intervals (CIs) were calculated using Cox proportional hazards models. All statistical analyses were conducted using the SPSS (version 27.0) software (IBM, 187 Chicago, IL, USA) and the R (version 4.3.2) statistical software. All results were deemed to be statistically significant at a significance level of P < 0.05 (2-tailed). Results Baseline characteristics A total of 267 patients were included in this study, with 107 patients in the denosumab group and 160 patients in the control group meeting the inclusion criteria. During the 3-year follow-up period, 8 patients were lost, and 259 patients were included in the final analysis. Of these, 104 patients were treated with denosumab, while 155 patients did not receive denosumab ( Figure 1 ). The baseline characteristics of the patients are shown in Table 1 . Before matching, the proportion of males in the denosumab group was significantly lower than that observed in the control group. PSM was used, resulting in 91 patients receiving denosumab and 91 patients not receiving denosumab. The PSM resulted in a balance of baseline characteristics between the groups; all of the baseline variables had SMD values of less than 0.1 ( Table 1 and Figure 2 ). Table 1. Baseline characteristics before and after matching. Before PSM After PSM Denosumab group Control group P SMD Denosumab group Control group P SMD N 104 155 91 91 Age, years M ( IQR ) 79(12) 80(14.5) 0.963 0.018 81(13.5) 79(12) 0.470 0.087 Gender, n (%) ＜0.001 1.000 Female 97(93.3) 106(68.4) 0.993 84(92.3) 84(92.3) 0.000 Male 7(6.7) 49(31.6) -0.993 7(7.7) 7(7.7) 0.000 BMI (kg/m 2 ) M ( IQR ) 21.7(4.5) 21.5(5.5) 0.854 -0.009 21.5(4.9) 21.8(4.8) 0.961 0.017 ASA, n (%) 0.993 0.738 1 37(35.6) 54(34.8) 0.015 34(36.6) 36(38.7) 0.044 2 61(58.7) 92(59.4) -0.014 55(59.1) 51(54.8) -0.086 3 6(5.8) 9(5.8) -0.002 4(4.3) 6(6.5) 0.088 Anesthesia, n (%) 0.057 0.854 Spinal anesthesia 78(75.0) 131(84.5) -0.220 75(80.7) 74(79.6) -0.027 General anesthesia 26(25.0) 24(15.5) 0.220 18(19.4) 19(20.4) 0.027 Site of fracture, n (%) 0.801 0.657 Left hip 50(48.1) 77(49.7) -0.021 47(51.6) 44(48.4) -0.050 Right hip 54(51.9) 78(50.3) 0.021 44(48.4) 47(51.6) 0.050 Surgical types, n (%) 0.696 0.844 Internal fixation 18(17.3) 24(15.5) 0.048 15(16.5) 16(51.6) 0.022 Hip replacement 86(82.7) 131(84.5) -0.048 76(83.5) 75(82.4) -0.022 Comorbid diseases Hypertension, n (%) 40(38.5) 61(39) 0.885 -0.018 41(44.1) 37(39.8) 0.552 -0.088 Diabetes, n (%) 14(13.5) 30(19.4) 0.216 -0.173 14(15.1) 14(15.1) 1.000 0.000 Stroke, n (%) 10(9.6) 10(6.5) 0.350 0.107 7(7.5) 6(6.5) 0.774 -0.044 Heart attack, n (%) 16(15.4) 24(15.5) 0.983 -0.013 13(14.3) 13(14.3) 1.000 0.000 COPD, n (%) 2(1.9) 2(1.3) 1.000 0.046 1(1.1) 2(2.2) 1.000 0.074 Anxiety/Depression, n (%) 3(2.9) 1(0.7) 0.358 0.134 1(1.1) 1(1.1) 1.000 0.000 Dementia, n (%) 3(2.9) 2(1.3) 0.650 0.095 2(2.2) 2(2.2) 1.000 0.000 PD, n (%) 5(4.8) 8(5.2) 0.898 -0.015 5(5.5) 5(5.5) 1.000 0.000 Abbreviations: BMI, body mass index; ASA, American society of anesthesiologists; COPD, chronic obstructive pulmonary disease; PD, Parkinson’s disease; SMD, standardized mean difference. Clinical outcomes After PSM, the 3-year cumulative incidence of second hip fracture occurred in 8.8% of patients in the denosumab group and 29.7% of patients in the control group (HR = 0.292, 95%CI = 0.133-0.643, P ＜0.001; Figure 3 ). As demonstrated in the findings of this study, patients in the denosumab group had a significantly lower incidence of second hip fracture (1.1%) in comparison with those in the control group within one year postoperatively (11.0%; P = 0.005). Moreover, a lower incidence of second hip fracture (2.2%) was exhibited by patients in the denosumab group when compared with the control group within two years postoperatively (15.4%; P = 0.002). The details of second hip fracture events are presented in Table 2 . Table 2 Second hip fracture events after first hip fracture surgery. Denosumab group Control group P value Unmatched N=155 N=104 Cumulative 1-year refracture, n (%) 4(3.8) 14(9.0) 0.108 Cumulative 2-year refracture, n (%) 4(3.8) 24(15.5) 0.003 Cumulative 3-year refracture, n (%) 12(11.5) 48(31.0) ＜0.001 Propensity score matching 91 91 Cumulative 1-year refracture, n (%) 1(1.1) 10(11.0) 0.005 Cumulative 2-year refracture, n (%) 2(2.2) 14(15.4) 0.002 Cumulative 3-year refracture, n (%) 8(8.8) 27(29.7) ＜0.001 Effect of denosumab on second hip fracture risk with gender and age According to the existing literature reports, female gender and advanced age in the elderly population have been identified as risk factors for subsequent fragility fracture [15]. Therefore, these two factors were selected for analysis in this study. After PSM, female patients had a significantly lower risk of second hip fracture when they were treated with denosumab compared with those not treated with denosumab (5.3% vs. 29.8%, HR = 0.293, 95%CI = 0.126-0.680, P = 0.002). For male patients, denosumab treatment did not result in a reduction in the incidence of second hip fracture when compared with the cohort that did not receive such treatment, and the difference in the risk of second hip fracture between the two groups was not statistically significant (14.3% vs. 28.6%, HR = 0.205, 95%CI = 0.020-2.061, P =0.140). Similarly, in patients aged 65-84 years, denosumab treatment was also associated with a reduced risk of second hip fracture in comparison with those not treated with denosumab (6.2% vs. 22.8%, HR = 0.241, 95%CI = 0.079-0.740, P = 0.007). For patients aged 85+ years, denosumab treatment reduce the incidence of second hip fracture in comparison with patients not receiving such treatment, but the difference in the risk of second hip fracture between the two groups was not statistically significant (15.4% vs. 41.2%, HR = 0.521, 95%CI = 0.168-1.619, P = 0.250; Figure 4, 5 and 6 ). Comparison of medical costs and outcomes for patients with and without denosumab The present study revealed that there was no statistically significant difference between patients with and without denosumab in terms of total medical costs or length of hospital stay. There were no statistically significant differences in the mortality rates between the denosumab group and the control group within one year or two years postoperatively. However, a lower mortality rate was observed in patients in the denosumab group compared to the control group within three years postoperatively (23.6% vs. 30.8%, P = 0.023; Table 3 ). It is therefore imperative that surgeons give priority to the prompt administration of antiosteoporosis treatment for patients with osteoporotic hip fractures. Table 3 Medical costs and outcomes of patients with and without denosumab treatment after first hip fracture surgery. Total (n=182) Denosumab group (n=91) Control group (n=91) P value Total costs (thousand US $) Median (IQR) 7.20(4.62) 7.24(4.90) 7.21(4.53) 0.860 Length of hospital stay(day) Median (IQR) 6.0(4.0) 5.9(5.5) 7.0(6.0) 0.445 Cumulative 1-year mortality, n (%) 9(4.9) 5(5.5) 4(4.4) 0.732 Cumulative 2-year mortality, n (%) 23(12.6) 12(13.2) 11(12.1) 0.823 Cumulative 3-year mortality, n (%) 43(23.6) 15(16.5) 28(30.8) 0.023 Discussion In this study, we found that denosumab treatment decreased the incidence of second hip fracture in elderly patients afflicted with osteoporotic femoral neck fractures following first hip fracture surgery, a finding that was particularly evident among female patients and those within the age range of 65-84 years. Osteoporosis increases fracture risk, particularly in older adults. Previous studies showed that denosumab reduced refracture rates among older adults with spinal or hip fractures 16-18 . In a research report, Martina Behanova et al. observed a higher risk of subsequent hip fracture in women receiving denosumab treatment [19]. Although denosumab is frequently prescribed for the treatment of osteoporosis, further investigation is required into its efficacy in reducing the risk of second hip fracture in elderly Chinese patients. A review of the literature suggests that denosumab may be an effective antiosteoporosis drug for the prevention of periprosthetic proximal femoral bone loss due to stress shielding following total hip arthroplasty (THA). However, there remains a paucity of real-world data concerning the impact of denosumab administration on elderly patients in China. However, despite almost five years of general use, several questions merit exploration: Does denosumab reduce the incidence of second hip fracture in elderly Chinese patients suffering femoral neck fractures following first hip fracture surgery? And do the benefits of denosumab outweigh the risks? In this study, we discovered that patients in the denosumab group demonstrated a significantly reduced risk of second hip fracture in comparison with the control group following PSM (HR = 0.292, 95%CI = 0.133-0.643, P ＜0.001). However, a recent large retrospective study of hip-fractured patients in Austria revealed that 54145 hip-fractured patients who were treated with denosumab had a higher cumulative incidence of subsequent hip fractures and a higher risk of developing such fractures when compared to patients who did not undergo antiresorptive treatment [19] . Similarly, Bergman J et al. reported that, among patients with any clinical fracture, the rate of subsequent hip fracture was higher in bisphosphonate users than in nonusers following the first six months of treatment [20]. However, this rate difference decreased over time. A potential explanation for this phenomenon is that the median follow-up period was insufficiently prolonged to demonstrate a reduction in the risk of fractures. It is also possible that the initiation of therapy occurred among patients exhibiting a high fracture risk profile. Therefore, further randomized studies with a larger sample size are expected to explore this issue. In the subgroup analysis, we determined the association between denosumab and second hip fracture risk with regard to gender and age. In our study population, however, no statistically significant difference in the incidence of second hip fracture was observed between the denosumab and control groups in male patients, which was partly attributed to the relatively small sample size of patients (denosumab group: N = 7; control group: N = 7). As demonstrated in the preceding nationwide and single-centre studies, female patients are subject to a heightened risk of sustaining a second hip fracture [21-22]. In our study, among female patients the denosumab group had a significantly reduced risk of second hip fracture when compared with the control group, thereby suggesting the imperative for the initiation of antiosteoporosis drug treatment as soon as possible after a primary hip fracture. With regard to the role of age, a constant increase in the incidence of second hip fractures was observed with advancing age, irrespective of gender [22], while some studies reported a decrease in the oldest age groups, i.e. those aged 85 and over or 90 and above [23-24]. In the present study, the difference in the risk of second hip fracture between the denosumab and control groups was not statistically significant in patients aged 85 and over, while the denosumab group demonstrated a reduced incidence of second hip fracture in comparison to the control group (15.4% vs. 41.2%, P = 0.031). The results of the subgroup analysis aligned with the primary outcomes, thereby validating a lower risk of second hip fracture associated with denosumab treatment. Furthermore, denosumab reduced the 3-year cumulative mortality rate, which is also definitely reflective of the importance of antiosteoporosis medications in elderly patients following primary hip fracture surgery. Our study was subject to several limitations. First, this was a single-centre, nonrandomized study with a small sample size. Despite the implementation of PSM to adjust for imbalances between the groups, unmeasured confounding factors could not be balanced. Our findings of this study require further validation through subsequent investigations with a larger sample size or a multicentre study. Second, the elderly patients included in this study were exclusively those with osteoporotic hip fractures. Therefore, it is conceivable that the research findings are not indicative of the refracture and mortality rates of patients suffering from high-energy traumatic or pathological fractures. In addition, this study did not document the bone mineral density (BMD) of the patients, which was due to the fact that many of them did not regularly monitor their BMD at the institute. Thus, it is imperative that medical professionals advise their patients to undergo regular BMD tests and adhere to antiosteoporosis treatment regimens, with a view to evaluating the efficacy of such treatment. Conclusion Denosumab decreased the risk of second hip fracture in elderly patients suffering from osteoporotic femoral neck fractures following first hip fracture surgery; the treatment especially decreased the risk of second hip fracture in female patients and those aged 65-84 years. Therefore, physicians and surgeons should highlight the importance of the prompt initiation of antiosteoporosis treatment in elderly patients following osteoporotic hip fractures. Abbreviations BMI Body Mass Index ASA American Society of Anesthesiologists COPD Chronic Obstructive Pulmonary Disease PD Parkinson’s disease SMD Standardized Mean Difference. BMD Bone Mineral Density PSM Propensity Score Matching Declarations Ethics approval and consent to participate This study was approved by the Medical Ethics Committee of Zhongshan Hospital Fudan University, Shanghai, China (No. B2024-479R). Prior to participation, informed consent was obtained from each patient or their legal guardian. All procedures were carried out in accordance with the pertinent guidelines and the Declaration of Helsinki, thereby ensuring that ethical principles were adhered to throughout the study. The dissemination of information from all participants was considered to constitute an act of consent, having obtained written consent from all individuals involved. Should a request be made for such documentation, consent will be provided for the consent form to be reviewed. To the best of the present author's knowledge, there have been no other published reports dedicated to these patients. Clinical trial number Not applicable. Consent for publication Not applicable. Availability of data and material The relevant datasets, along with the analytical methods employed in the present study, are available upon reasonable request from the corresponding author. Funding This study was supported by grants from the National Key Research and Development Program of China (2024YFC3044700) and the Science and Technology Innovation Action Program of the Shanghai Science and Technology Commission (23ZR1480300). Competing interests It is declared by the authors that there are no conflicts of interest with respect to the research, authorship, and/or publication of this article. Authors' contributions The study was designed by Y.W., Y.S., and L.C.; the data were analyzed by Y.W., K.P; Q.L., and X.L.; the preparation of the manuscript was the responsibility of Y.W., and L.C. All authors have read and approved the final version of this manuscript. Acknowledgements I would like to express my sincere gratitude to L Cao and KM Pan for their invaluable assistance in the collection of data. I would like to express my profound gratitude to YC Shao and QZ Lv for their assistance with the English writing. Thanks to Xiaoyu Li for his assistance in providing references. The present study would like to express its gratitude to all those who have offered assistance and support throughout the research process. 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Cite Share Download PDF Status: Published Journal Publication published 30 Oct, 2025 Read the published version in BMC Musculoskeletal Disorders → Version 1 posted Editorial decision: Revision requested 31 Jul, 2025 Reviews received at journal 14 Jul, 2025 Reviewers agreed at journal 05 Jul, 2025 Reviews received at journal 09 May, 2025 Reviewers agreed at journal 09 May, 2025 Reviewers invited by journal 07 May, 2025 Editor invited by journal 06 May, 2025 Editor assigned by journal 05 May, 2025 Submission checks completed at journal 05 May, 2025 First submitted to journal 01 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6569056","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":454545861,"identity":"6a29855a-2018-43a6-a4c5-c35525ec7518","order_by":0,"name":"Yuzhu Wang","email":"","orcid":"","institution":"zhongshan hospital fudan university","correspondingAuthor":false,"prefix":"","firstName":"Yuzhu","middleName":"","lastName":"Wang","suffix":""},{"id":454545864,"identity":"4d6bca1f-1df8-4cfe-a476-48daa1a90b89","order_by":1,"name":"Kunming Pan","email":"","orcid":"","institution":"zhongshan hospital fudan university","correspondingAuthor":false,"prefix":"","firstName":"Kunming","middleName":"","lastName":"Pan","suffix":""},{"id":454545865,"identity":"95fba958-bc77-48fe-bafc-9e569dacca9e","order_by":2,"name":"Xiaoyu Li","email":"","orcid":"","institution":"zhongshan hospital fudan university","correspondingAuthor":false,"prefix":"","firstName":"Xiaoyu","middleName":"","lastName":"Li","suffix":""},{"id":454545866,"identity":"c11b2bff-57ee-402d-bfdc-f6bf5d64932b","order_by":3,"name":"Qianzhou Lv","email":"","orcid":"","institution":"zhongshan hospital fudan university","correspondingAuthor":false,"prefix":"","firstName":"Qianzhou","middleName":"","lastName":"Lv","suffix":""},{"id":454545867,"identity":"63f9ec6a-5482-4b9f-8e5c-beb6284ee0dd","order_by":4,"name":"Yunchao Shao","email":"","orcid":"","institution":"zhongshan hospital fudan university","correspondingAuthor":false,"prefix":"","firstName":"Yunchao","middleName":"","lastName":"Shao","suffix":""},{"id":454545868,"identity":"81e8aa7d-c268-431c-ae3a-517cb549eee6","order_by":5,"name":"Lu Cao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIie3QMWvCQBTA8RcCdnnx1ieB5iu8IgSHkn6VyIGTlEKhOElAiKOrX6Nbx5MbuohdC110cXIQnNz6rqDQ4WLHgvcfjhvul9w9gFDov7aGe1nRbQngBiC+SEoYnAm5838h9kTgMlFTa6BffzxkVbLYHN96YzWB+PAExaOP0HJQCvmK2bR1N1kSkYVWOgf97CMMQ3akxdkuT6Na3iIkRjD9ykfUzpEVZhXmnaOQzMrFGgn9/MUQGMwpEcIyirSJ0Oe2NOVKMxvsurd0Xm1Up8jaS9RML9b7l0ImhncysbG6fZ/YA44KL3GZ8y6qTis3nP9V1PTlUCgUutq+AeXfSb8E1uyuAAAAAElFTkSuQmCC","orcid":"","institution":"zhongshan hospital fudan university","correspondingAuthor":true,"prefix":"","firstName":"Lu","middleName":"","lastName":"Cao","suffix":""}],"badges":[],"createdAt":"2025-05-01 04:23:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6569056/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6569056/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12891-025-09264-w","type":"published","date":"2025-10-30T15:58:13+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82604483,"identity":"ab9ddf2e-d0de-480a-aefd-4753d87485b4","added_by":"auto","created_at":"2025-05-13 09:57:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":229637,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the study.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6569056/v1/9af6243148c587b9879df415.png"},{"id":82604517,"identity":"50153525-e988-498b-9525-4ff33948d9b6","added_by":"auto","created_at":"2025-05-13 09:57:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":553916,"visible":true,"origin":"","legend":"\u003cp\u003eStandardized mean differences.\u003c/p\u003e\n\u003cp\u003eAbbreviations: COPD, chronic obstructive pulmonary disease; BMI, body mass index; PD, Parkinson’s disease.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6569056/v1/efbcfc6946bef877b0306fa3.png"},{"id":82604490,"identity":"4f1bc0b4-48cd-4875-b013-2d53c094835f","added_by":"auto","created_at":"2025-05-13 09:57:06","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":182948,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curve for second hip refracture within 36 months after first hip fracture surgery.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-6569056/v1/4bcd99371a66221ce351c491.png"},{"id":82604489,"identity":"fd855a68-8c0e-4ed3-b24c-539dcd87ed33","added_by":"auto","created_at":"2025-05-13 09:57:06","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":496946,"visible":true,"origin":"","legend":"\u003cp\u003eIncidence of second hip fracture within 36 months in gender and age subgroups between the denosumab group and the matched control group.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-6569056/v1/522216226c5aa368fc18fd4e.png"},{"id":82604506,"identity":"0fda9354-7629-4a53-a47b-5db6591711ad","added_by":"auto","created_at":"2025-05-13 09:57:07","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":400002,"visible":true,"origin":"","legend":"\u003cp\u003eCumulative incidence of second hip fracture within 36 months following first hip fracture surgery in the denosumab cohort. (A) The cumulative incidence of second hip fracture in female patients; (B) The cumulative incidence of second hip fracture in male patients; (C)The cumulative incidence of second hip fracture in patients aged 65-84 years; (D) The cumulative incidence of second hip fracture in patients aged 85+years.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-6569056/v1/241fe02a5f257937f1359be9.png"},{"id":82604497,"identity":"6cb249ea-f7ff-45fa-80cb-acd5b7f9f0c7","added_by":"auto","created_at":"2025-05-13 09:57:07","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":565975,"visible":true,"origin":"","legend":"\u003cp\u003eHazard ratio of second hip fracture among patients in gender and age subgroups for denosumab group versus matched control group.\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-6569056/v1/60c9a30a33235948f29765ae.png"},{"id":95040009,"identity":"e830897b-ddcf-4bed-8039-ca5b9166e730","added_by":"auto","created_at":"2025-11-03 16:07:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3363999,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6569056/v1/77b4e3b4-693f-4dd4-9045-d1f8e917a613.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Treatment with denosumab reduces second hip fracture risk in elderly patients with femoral neck fractures","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCurrent projections indicate a global increase in the number of hip fractures, from 1.26\u0026nbsp;million in 1990 to 4.5\u0026nbsp;million by 2050, with approximately half of these occurring in Asia, a region of particular concern which includes China [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Hip fracture, including femoral neck and intertrochanteric fractures, is the most devastating type of osteoporotic fracture, which can be attributed to the elevated risk of morbidity, mortality, disability and subsequent hip fracture, as well as the significant societal healthcare expenditures it engenders [\u003cspan additionalcitationids=\"CR3 CR4 CR5 CR6\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The majority of these injuries occur in the elderly population as a result of low-energy falls and may involve either direct or indirect mechanisms [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Direct mechanisms encompass a fall onto the greater trochanter or forced external rotation of the lower extremity, which exerts pressure on the femoral neck against the posterior lip of the acetabulum. Indirect mechanisms arise from the occurrence of muscle forces which surpass the capacity of the femoral neck. Therefore, it is imperative that surgeons are able to recognize specific fracture patterns and patient characteristics that indicate the use of particular implants and methods for the effective management of such injuries.\u003c/p\u003e \u003cp\u003eDenosumab is a fully human monoclonal antibody that functions as an inhibitor of receptor activator of nuclear factor-κB ligand, a key mediator of osteoclast development, function, and survival [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In the second and third phases of the trial, denosumab rapidly decreased bone resorption markers and increased bone mineral density (BMD) at all skeletal sites measured in comparison with the placebo [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In the multicentre, randomized, double-blind, placebo-controlled, phase 3 FREEDOM trial, denosumab treatment for a period of up to 10 years was associated with low rates of adverse events, a low fracture incidence when compared with that observed during the original trial, and continued increases in BMD without plateau in postmenopausal women with osteoporosis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In the FREEDOM study, the incidence of hip fracture in subjects (1.2%) who received a placebo was lower than in the Fracture Intervention Trial-I (2.2%) and the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly trials (2.5%) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, the effect of denosumab on the incidence of second hip fracture in elderly Chinese individuals afflicted with femoral neck fractures after first hip fracture surgery remains to be scarcely reported. In addition, in order to develop a comprehensive understanding of the factors related to second hip fracture, it is essential to conduct a detailed investigation into the impact of gender and age in patient populations.\u003c/p\u003e \u003cp\u003eIn this study, we evaluated the incidence of second hip fracture in elderly patients suffering from osteoporotic femoral neck fractures following first hip fracture surgery who were simultaneously administered denosumab and assessed the relationship between denosumab and second hip fracture with regard to gender and age.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eA retrospective observational study was conducted at a single centre, with elderly patients suffering from primary femoral neck fractures owing to low-energy trauma who had undergone the internal fixation or hip arthroplasty from January 2020 to December 2021 being enrolled. A total of 267 patients were included in the study according to the inclusion and exclusion criteria. The patients participating in the study were divided into two groups, categorized on the basis of whether they received denosumab treatment following hip fracture surgery: denosumab group and non-denosumab group (control group). The administration of denosumab was conducted via subcutaneous injection, with a dosage of 60 mg per each injection, administered twice per year, over a period of three years. Inclusion criteria were as followed: (1) patients aged 65 years and older; (2) patients suffering from primary femoral neck fractures caused by low-energy trauma who undergo internal fixation or hip arthroplasty; (3) willingness to undertake the subsequent telephone follow-up. Exclusion criteria included: (1) patients with multiple fractures; (2) receiving other antiosteoporosis medications prior to denosumab treatment; (3) tumor patients; (4) immune system diseases including thyroid dysfunction, systemic lupus erythematosus, and rheumatoid arthritis; (5) reluctance to engage with telephone communications made in follow-up.\u003c/p\u003e \u003cp\u003eThe study population comprised patients who had been diagnosed with a fragility hip fracture, and for whom three years of follow-up data were available for the objective of evaluating the incidence of second hip fracture following primary hip fracture surgery. Follow-up time was defined as the number of days from the index fracture event to the occurrence of second hip fracture or the most recent appointment, whichever occurred first.\u003c/p\u003e \u003cp\u003eThe following demographic and clinical characteristics were collected: gender (female or male), age, body mass index (BMI), American Society of Anesthesiologist (ASA) classification, anesthesia (general anesthesia or spinal anesthesia), site of fracture (left or right), surgical types (internal fixation or hip arthroplasty), comorbid diseases (hypertension, diabetes, stroke, heart attack, chronic obstructive pulmonary disease (COPD), anxiety/depression, dementia, and Parkinson\u0026rsquo;s disease).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eIn order to adjust for differences between the groups, propensity score matching (PSM) was employed, using propensity scores (PSs) in order to reflect the probability of each patient. These scores were derived through multiple logistic regression analysis, with the analysis based on the patients\u0026rsquo; characteristics and clinical risk factors, including gender, age, BMI, ASA, anesthesia, site of fracture, surgical types, hypertension, diabetes, stroke, COPD, anxiety/depression, dementia, and Parkinson\u0026rsquo;s disease. In this study, a width measurement of 0.2 calipers was used for the implementation of the matching process. The equilibrium of variables among the groups was evaluated through the calculation of standardized mean differences (SMDs), with a cut-off value of 0.10, in the overall population as well as the propensity score-matched population. In instances of normal distribution, continuous variables were expressed as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). For non-normal distribution, continuous variables were expressed as the median with the interquartile range (IQR). The determination of significant differences between groups was achieved through the implementation of two statistical tests: Student \u003cem\u003et\u003c/em\u003e test or Mann-Whitney \u003cem\u003eU\u003c/em\u003e test. Categorical variables were expressed as frequencies or percentages and were tested using the chi-square test or the Fisher exact test, as appropriate. Multiple imputation was performed to replace the missing data for baseline variables.\u003c/p\u003e \u003cp\u003eKaplan-Meier survival curve analysis was performed in order to assess the cumulative incidence according to different groups, and the differences were then compared between the denosumab group and the control group by means of the log-rank test. The hazard ratios (HRs) and confidence intervals (CIs) were calculated using Cox proportional hazards models.\u003c/p\u003e \u003cp\u003eAll statistical analyses were conducted using the SPSS (version 27.0) software (IBM, 187 Chicago, IL, USA) and the R (version 4.3.2) statistical software. All results were deemed to be statistically significant at a significance level of \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 (2-tailed).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eBaseline characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 267 patients were included in this study, with 107 patients in the denosumab group and 160 patients in the control group meeting the inclusion criteria. During the 3-year follow-up period, 8 patients were lost, and 259 patients were included in the final analysis. Of these, 104 patients were treated with denosumab, while 155 patients did not receive denosumab (\u003cstrong\u003eFigure 1\u003c/strong\u003e). The baseline characteristics of the patients are shown in\u003cstrong\u003e Table 1\u003c/strong\u003e. Before matching, the proportion of males in the denosumab group was significantly lower than that observed in the control group. PSM was used, resulting in 91 patients receiving denosumab and 91 patients not receiving denosumab. The PSM resulted in a balance of baseline characteristics between the groups; all of the baseline variables had SMD values of less than 0.1 (\u003cstrong\u003eTable 1 and Figure 2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eTable 1. Baseline characteristics before and after matching.\u003c/p\u003e\n\u003ctable width=\"719\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"124\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" width=\"246\"\u003e\n\u003cp\u003eBefore PSM\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"5\" width=\"350\"\u003e\n\u003cp\u003eAfter PSM\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDenosumab group\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eControl group\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eSMD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDenosumab group\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eControl group\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eSMD\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eN\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e104\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e155\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e91\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e91\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eAge, years \u003cem\u003eM \u003c/em\u003e(\u003cem\u003eIQR\u003c/em\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e79(12)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e80(14.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.963\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.018\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e81(13.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e79(12)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e0.470\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.087\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eGender, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e＜0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e97(93.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e106(68.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.993\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e84(92.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e84(92.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e7(6.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e49(31.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-0.993\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e7(7.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e7(7.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e) \u003cem\u003eM \u003c/em\u003e(\u003cem\u003eIQR\u003c/em\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e21.7(4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e21.5(5.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.854\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-0.009\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e21.5(4.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e21.8(4.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e0.961\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.017\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eASA, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.993\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e0.738\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e37(35.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e54(34.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e34(36.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e36(38.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.044\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e61(58.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e92(59.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-0.014\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e55(59.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e51(54.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-0.086\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e6(5.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e9(5.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-0.002\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e4(4.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e6(6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.088\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eAnesthesia, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.057\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e0.854\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eSpinal anesthesia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e78(75.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e131(84.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-0.220\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e75(80.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e74(79.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-0.027\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eGeneral anesthesia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e26(25.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e24(15.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.220\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e18(19.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e19(20.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.027\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eSite of fracture, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.801\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e0.657\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eLeft hip\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e50(48.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e77(49.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-0.021\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e47(51.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e44(48.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-0.050\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eRight hip\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e54(51.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e78(50.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.021\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e44(48.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e47(51.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.050\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eSurgical types, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.696\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e0.844\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eInternal fixation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e18(17.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e24(15.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.048\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e15(16.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e16(51.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.022\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eHip replacement\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e86(82.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e131(84.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-0.048\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e76(83.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e75(82.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-0.022\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eComorbid diseases\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eHypertension, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e40(38.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e61(39)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.885\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-0.018\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e41(44.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e37(39.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e0.552\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-0.088\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eDiabetes, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e14(13.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e30(19.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.216\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-0.173\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e14(15.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e14(15.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eStroke, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e10(9.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e10(6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.350\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.107\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e7(7.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e6(6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e0.774\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-0.044\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eHeart attack, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e16(15.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e24(15.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.983\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-0.013\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e13(14.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e13(14.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eCOPD, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e2(1.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e2(1.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.046\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e1(1.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e2(2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.074\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eAnxiety/Depression, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e3(2.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e1(0.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.358\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.134\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e1(1.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e1(1.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003eDementia, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e3(2.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e2(1.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.650\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.095\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e2(2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e2(2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"124\"\u003e\n\u003cp\u003ePD, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e5(4.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e8(5.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.898\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-0.015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e5(5.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e5(5.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: BMI, body mass index; ASA, American society of anesthesiologists; COPD, chronic obstructive pulmonary disease; PD, Parkinson\u0026rsquo;s disease; SMD, standardized mean difference.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter PSM, the 3-year cumulative incidence of second hip fracture occurred in 8.8% of patients in the denosumab group and 29.7% of patients in the control group (HR = 0.292, 95%CI = 0.133-0.643, \u003cem\u003eP\u003c/em\u003e＜0.001; \u003cstrong\u003eFigure 3\u003c/strong\u003e). As demonstrated in the findings of this study, patients in the denosumab group had a significantly lower incidence of second hip fracture (1.1%) in comparison with those in the control group within one year postoperatively (11.0%; \u003cem\u003eP\u003c/em\u003e = 0.005). Moreover, a lower incidence of second hip fracture (2.2%) was exhibited by patients in the denosumab group when compared with the control group within two years postoperatively (15.4%; \u003cem\u003eP\u003c/em\u003e = 0.002). The details of second hip fracture events are presented in \u003cstrong\u003eTable 2\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 \u003c/strong\u003eSecond hip fracture events after first hip fracture surgery.\u003c/p\u003e\n\u003ctable\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"221\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003eDenosumab group\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"110\"\u003e\n\u003cp\u003eControl group\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"99\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"221\"\u003e\n\u003cp\u003eUnmatched\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003eN=155\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"110\"\u003e\n\u003cp\u003eN=104\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"99\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"221\"\u003e\n\u003cp\u003eCumulative 1-year refracture, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e4(3.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"110\"\u003e\n\u003cp\u003e14(9.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"99\"\u003e\n\u003cp\u003e0.108\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"221\"\u003e\n\u003cp\u003eCumulative 2-year refracture, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e4(3.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"110\"\u003e\n\u003cp\u003e24(15.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"99\"\u003e\n\u003cp\u003e0.003\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"221\"\u003e\n\u003cp\u003eCumulative 3-year refracture, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e12(11.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"110\"\u003e\n\u003cp\u003e48(31.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"99\"\u003e\n\u003cp\u003e＜0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"221\"\u003e\n\u003cp\u003ePropensity score matching\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e91\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"110\"\u003e\n\u003cp\u003e91\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"99\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"221\"\u003e\n\u003cp\u003eCumulative 1-year refracture, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e1(1.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"110\"\u003e\n\u003cp\u003e10(11.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"99\"\u003e\n\u003cp\u003e0.005\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"221\"\u003e\n\u003cp\u003eCumulative 2-year refracture, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e2(2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"110\"\u003e\n\u003cp\u003e14(15.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"99\"\u003e\n\u003cp\u003e0.002\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"221\"\u003e\n\u003cp\u003eCumulative 3-year refracture, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"114\"\u003e\n\u003cp\u003e8(8.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"110\"\u003e\n\u003cp\u003e27(29.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"99\"\u003e\n\u003cp\u003e＜0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eEffect of denosumab on second hip fracture risk with gender and age \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAccording to the existing literature reports, female gender and advanced age in the elderly population have been identified as risk factors for subsequent fragility fracture [15]. Therefore, these two factors were selected for analysis in this study. After PSM, female patients had a significantly lower risk of second hip fracture when they were treated with denosumab compared with those not treated with denosumab (5.3% \u003cem\u003evs.\u003c/em\u003e 29.8%, HR = 0.293, 95%CI = 0.126-0.680, \u003cem\u003eP\u003c/em\u003e = 0.002). For male patients, denosumab treatment did not result in a reduction in the incidence of second hip fracture when compared with the cohort that did not receive such treatment, and the difference in the risk of second hip fracture between the two groups was not statistically significant (14.3% \u003cem\u003evs.\u003c/em\u003e 28.6%, HR = 0.205, 95%CI = 0.020-2.061, \u003cem\u003eP\u003c/em\u003e=0.140). Similarly, in patients aged 65-84 years, denosumab treatment was also associated with a reduced risk of second hip fracture in comparison with those not treated with denosumab (6.2% \u003cem\u003evs.\u003c/em\u003e 22.8%, HR = 0.241, 95%CI = 0.079-0.740, \u003cem\u003eP \u003c/em\u003e= 0.007). For patients aged 85+ years, denosumab treatment reduce the incidence of second hip fracture in comparison with patients not receiving such treatment, but the difference in the risk of second hip fracture between the two groups was not statistically significant (15.4% \u003cem\u003evs.\u003c/em\u003e 41.2%, HR = 0.521, 95%CI = 0.168-1.619, \u003cem\u003eP\u003c/em\u003e = 0.250; \u003cstrong\u003eFigure 4, 5 and 6\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComparison of medical costs and outcomes for patients with and without denosumab\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe present study revealed that there was no statistically significant difference between patients with and without denosumab in terms of total medical costs or length of hospital stay. There were no statistically significant differences in the mortality rates between the denosumab group and the control group within one year or two years postoperatively. However, a lower mortality rate was observed in patients in the denosumab group compared to the control group within three years postoperatively (23.6% \u003cem\u003evs.\u003c/em\u003e 30.8%, \u003cem\u003eP\u003c/em\u003e = 0.023; \u003cstrong\u003eTable 3\u003c/strong\u003e). It is therefore imperative that surgeons give priority to the prompt administration of antiosteoporosis treatment for patients with osteoporotic hip fractures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e Medical costs and outcomes of patients with and without denosumab treatment after first hip fracture surgery.\u003c/p\u003e\n\u003ctable\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"88\"\u003e\n\u003cp\u003eTotal\u003c/p\u003e\n\u003cp\u003e(n=182)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"131\"\u003e\n\u003cp\u003eDenosumab group\u003c/p\u003e\n\u003cp\u003e(n=91)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003eControl group\u003c/p\u003e\n\u003cp\u003e(n=91)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"71\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eTotal costs (thousand US $) \u003cem\u003eMedian (IQR)\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"88\"\u003e\n\u003cp\u003e7.20(4.62)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"131\"\u003e\n\u003cp\u003e7.24(4.90)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e7.21(4.53)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"71\"\u003e\n\u003cp\u003e0.860\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eLength of hospital stay(day) Median (IQR)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"88\"\u003e\n\u003cp\u003e6.0(4.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"131\"\u003e\n\u003cp\u003e5.9(5.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e7.0(6.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"71\"\u003e\n\u003cp\u003e0.445\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eCumulative 1-year mortality, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"88\"\u003e\n\u003cp\u003e9(4.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"131\"\u003e\n\u003cp\u003e5(5.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e4(4.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"71\"\u003e\n\u003cp\u003e0.732\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eCumulative 2-year mortality, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"88\"\u003e\n\u003cp\u003e23(12.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"131\"\u003e\n\u003cp\u003e12(13.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e11(12.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"71\"\u003e\n\u003cp\u003e0.823\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"227\"\u003e\n\u003cp\u003eCumulative 3-year mortality, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"88\"\u003e\n\u003cp\u003e43(23.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"131\"\u003e\n\u003cp\u003e15(16.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e28(30.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"71\"\u003e\n\u003cp\u003e0.023\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we found that denosumab treatment decreased the incidence of second hip fracture in elderly patients afflicted with osteoporotic femoral neck fractures following first hip fracture surgery, a finding that was particularly evident among female patients and those within the age range of 65-84 years.\u003c/p\u003e\n\u003cp\u003eOsteoporosis increases fracture risk, particularly in older adults. Previous studies showed that denosumab reduced refracture rates among older adults with spinal or hip fractures\u003csup\u003e16-18\u003c/sup\u003e. In a research report, Martina Behanova et al. observed a higher risk of subsequent hip fracture in women receiving denosumab treatment [19]. Although denosumab is frequently prescribed for the treatment of osteoporosis, further investigation is required into its efficacy in reducing the risk of second hip fracture in elderly Chinese patients. A review of the literature suggests that denosumab may be an effective antiosteoporosis drug for the prevention of periprosthetic proximal femoral bone loss due to stress shielding following total hip arthroplasty (THA). However, there remains a paucity of real-world data concerning the impact of denosumab administration on elderly patients in China. However, despite almost five years of general use, several questions merit exploration: Does denosumab reduce the incidence of second hip fracture in elderly Chinese patients suffering femoral neck fractures following first hip fracture surgery? And do the benefits of denosumab outweigh the risks?\u003c/p\u003e\n\u003cp\u003eIn this study, we discovered that patients in the denosumab group demonstrated a significantly reduced risk of second hip fracture in comparison with the control group following PSM (HR = 0.292, 95%CI = 0.133-0.643, \u003cem\u003eP\u003c/em\u003e＜0.001). However, a recent large retrospective study of hip-fractured patients in Austria revealed that 54145 hip-fractured patients who were treated with denosumab had a higher cumulative incidence of subsequent hip fractures and a higher risk of developing such fractures when compared to patients who did not undergo antiresorptive treatment \u003csup\u003e[19]\u003c/sup\u003e. Similarly, Bergman J et al. reported that, among patients with any clinical fracture, the rate of subsequent hip fracture was higher in bisphosphonate users than in nonusers following the first six months of treatment [20]. However, this rate difference decreased over time. A potential explanation for this phenomenon is that the median follow-up period was insufficiently prolonged to demonstrate a reduction in the risk of fractures. It is also possible that the initiation of therapy occurred among patients exhibiting a high fracture risk profile. Therefore, further randomized studies with a larger sample size are expected to explore this issue.\u003c/p\u003e\n\u003cp\u003eIn the subgroup analysis, we determined the association between denosumab and second hip fracture risk with regard to gender and age. In our study population, however, no statistically significant difference in the incidence of second hip fracture was observed between the denosumab and control groups in male patients, which was partly attributed to the relatively small sample size of patients (denosumab group: N = 7; control group: N = 7). As demonstrated in the preceding nationwide and single-centre studies, female patients are subject to a heightened risk of sustaining a second hip fracture [21-22]. In our study, among female patients the denosumab group had a significantly reduced risk of second hip fracture when compared with the control group, thereby suggesting the imperative for the initiation of antiosteoporosis drug treatment as soon as possible after a primary hip fracture. With regard to the role of age, a constant increase in the incidence of second hip fractures was observed with advancing age, irrespective of gender [22], while some studies reported a decrease in the oldest age groups, i.e. those aged 85 and over or 90 and above [23-24]. In the present study, the difference in the risk of second hip fracture between the denosumab and control groups was not statistically significant in patients aged 85 and over, while the denosumab group demonstrated a reduced incidence of second hip fracture in comparison to the control group (15.4% \u003cem\u003evs.\u003c/em\u003e 41.2%, \u003cem\u003eP\u003c/em\u003e = 0.031). The results of the subgroup analysis aligned with the primary outcomes, thereby validating a lower risk of second hip fracture associated with denosumab treatment. Furthermore, denosumab reduced the 3-year cumulative mortality rate, which is also definitely reflective of the importance of antiosteoporosis medications in elderly patients following primary hip fracture surgery.\u003c/p\u003e\n\u003cp\u003eOur study was subject to several limitations. First, this was a single-centre, nonrandomized study with a small sample size. Despite the implementation of PSM to adjust for imbalances between the groups, unmeasured confounding factors could not be balanced. Our findings of this study require further validation through subsequent investigations with a larger sample size or a multicentre study. Second, the elderly patients included in this study were exclusively those with osteoporotic hip fractures. Therefore, it is conceivable that the research findings are not indicative of the refracture and mortality rates of patients suffering from high-energy traumatic or pathological fractures. In addition, this study did not document the bone mineral density (BMD) of the patients, which was due to the fact that many of them did not regularly monitor their BMD at the institute. Thus, it is imperative that medical professionals advise their patients to undergo regular BMD tests and adhere to antiosteoporosis treatment regimens, with a view to evaluating the efficacy of such treatment.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eDenosumab decreased the risk of second hip fracture in elderly patients suffering from osteoporotic femoral neck fractures following first hip fracture surgery; the treatment especially decreased the risk of second hip fracture in female patients and those aged 65-84 years. Therefore, physicians and surgeons should highlight the importance of the prompt initiation of antiosteoporosis treatment in elderly patients following osteoporotic hip fractures.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBMI \u0026nbsp; \u0026nbsp;Body Mass Index\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eASA \u0026nbsp; \u0026nbsp;American Society of Anesthesiologists\u003c/p\u003e\n\u003cp\u003eCOPD \u0026nbsp; Chronic Obstructive Pulmonary Disease\u003c/p\u003e\n\u003cp\u003ePD \u0026nbsp; \u0026nbsp; \u0026nbsp;Parkinson’s disease\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSMD \u0026nbsp; \u0026nbsp;Standardized Mean Difference.\u003c/p\u003e\n\u003cp\u003eBMD \u0026nbsp; \u0026nbsp;Bone Mineral Density\u003c/p\u003e\n\u003cp\u003ePSM \u0026nbsp; \u0026nbsp; Propensity Score Matching\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Medical Ethics Committee of Zhongshan Hospital Fudan University, Shanghai, China (No. B2024-479R). Prior to participation, informed consent was obtained from each patient or their legal guardian. All procedures were carried out in accordance with the pertinent guidelines and the Declaration of Helsinki, thereby ensuring that ethical principles were adhered to throughout the study. The dissemination of information from all participants was considered to constitute an act of consent, having obtained written consent from all individuals involved. Should a request be made for such documentation, consent will be provided for the consent form to be reviewed. To the best of the present author's knowledge, there have been no other published reports dedicated to these patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe relevant datasets, along with the analytical methods employed in the present study, are available upon reasonable request from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by grants from the National Key Research and Development Program of China (2024YFC3044700) and the Science and Technology Innovation Action Program of the Shanghai Science and Technology Commission (23ZR1480300).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIt is declared by the authors that there are no conflicts of interest with respect to the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was designed by Y.W., Y.S., and L.C.; the data were analyzed by Y.W., K.P; Q.L., and X.L.; the preparation of the manuscript was the responsibility of Y.W., and L.C. All authors have read and approved the final version of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eI would like to express my sincere gratitude to\u0026nbsp;L Cao and KM Pan for their invaluable assistance in the collection of data. I would like to express my profound gratitude to YC Shao and QZ Lv for their assistance with the English writing. Thanks to Xiaoyu Li for his assistance in providing references. The present study would like to express its gratitude to all those who have offered assistance and support throughout the research process.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' information (optional)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Pharmacy, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai 200032, China.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003eDepartment of Orthopedics, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai 200032, China.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCauley JA, Chalhoub D, Kassem AM, Fuleihan Gel H. Geographic and ethnic disparities in osteoporotic fractures. Nat reviews Endocrinol. 2014;10(6):338\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFlorschutz AV, Langford JR, Haidukewych GJ, Koval KJ. Femoral neck fractures: current management. J Orthop Trauma. 2015;29(3):121\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHu F, Jiang C, Shen J, Tang P, Wang Y. Preoperative predictors for mortality following hip fracture surgery: a systematic review and meta-analysis. Injury. 2012;43(6):676\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJohansson H, Siggeirsd\u0026oacute;ttir K, Harvey NC, et al. Imminent risk of fracture after fracture. Osteoporos Int. 2017;28(3):775\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCui Z, Feng H, Meng X, et al. Age-specific 1-year mortality rates after hip fracture based on the populations in mainland China between the years 2000 and 2018: a systematic analysis. Archives Osteoporos. 2019;14(1):55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilson JM, Boissonneault AR, Schwartz AM, Staley CA, Schenker ML. Frailty and Malnutrition Are Associated With Inpatient Postoperative Complications and Mortality in Hip Fracture Patients. J Orthop Trauma. 2019;33(3):143\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSi L, Winzenberg TM, Jiang Q, Chen M, Palmer AJ. Projection of osteoporosis-related fractures and costs in China: 2010\u0026ndash;2050. Osteoporos Int. 2015;26(7):1929\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJohnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int. 2006;17(12):1726\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYasuda H, Shima N, Nakagawa N, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA. 1998;95(7):3597\u0026ndash;602.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLewiecki EM, Miller PD, McClung MR, et al. Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD. J Bone Miner Res. 2007;22(12):1832\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCosman F, Crittenden DB, Adachi JD, et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016;375(16):1532\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBone HG, Wagman RB, Brandi ML, et al. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. lancet Diabetes Endocrinol. 2017;5(7):513\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBlack DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356(18):1809\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBlack DM, Cummings SR, Karpf DB, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fract Intervention Trial Res Group Lancet (London England). 1996;348(9041):1535\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSriruanthong K, Philawuth N, Saloa S, Daraphongsataporn N, Sucharitpongpan W. Risk factors of refracture after a fragility fracture in elderly. Archives Osteoporos. 2022;17(1):98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang CF, Lin SM, Hsu JC, Kosik RO, Chan WP. Antiresorptive injections in older adult patients with prior osteoporotic fractures: a real-world observational study. Archives Osteoporos. 2025;20(1):25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZou J, Zhang Y, Niu J, et al. A Real-world Study of Denosumab For Reducing Refracture Risk after Percutaneous Vertebral Augmentation. Orthop Surg. 2024;16(8):1849\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTai TW, Tsai YL, Shih CA et al. Refracture risk and all-cause mortality after vertebral fragility fractures: Anti-osteoporotic medications matter. J Formos Med Assoc.122 Suppl 1: S65\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBehanova M, Reichardt B, Stamm TA, Zwerina J, Klaushofer K, Kocijan R. Treatment Effects of Bisphosphonates and Denosumab on Survival and Refracture from Real-World Data of Hip-Fractured Patients. Calcif Tissue Int. 2019;105(6):630\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBergman J, Nordstr\u0026ouml;m A, Nordstr\u0026ouml;m P. Bisphosphonate use after clinical fracture and risk of new fracture. Osteoporos Int. 2018;29(4):937\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee YK, Ha YC, Choi HJ, et al. Bisphosphonate use and subsequent hip fracture in South Korea. Osteoporos Int. 2013;24(11):2887\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRyg J, Rejnmark L, Overgaard S, Brixen K, Vestergaard P. Hip fracture patients at risk of second hip fracture: a nationwide population-based cohort study of 169,145 cases during 1977\u0026ndash;2001. J Bone Miner Res. 2009;24(7):1299\u0026ndash;307.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNymark T, Lauritsen JM, Ovesen O, R\u0026ouml;ck ND, Jeune B. Short time-frame from first to second hip fracture in the Funen County Hip Fracture Study. Osteoporos Int. 2006;17(9):1353\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLawrence TM, Wenn R, Boulton CT, Moran CG. Age-specific incidence of first and second fractures of the hip. J bone joint Surg Br volume. 2010;92(2):258\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"denosumab, second hip fracture, elderly patients, femoral neck fracture, osteoporotic fracture","lastPublishedDoi":"10.21203/rs.3.rs-6569056/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6569056/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe issue of second hip fracture following surgery for a hip fracture has recently been the focus of increased research attention. The purpose of our study was to evaluate the effect of denosumab on the risk of second hip fracture following first hip fracture surgery in the elderly Chinese population.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis was a retrospective observation study in which patients aged 65 years and older suffering from osteoporotic femoral neck fractures between 1 January 2020 and 31 December 2021 were included. The patients were divided into two groups: denosumab group and control group. Propensity score matching (PSM) was performed to adjust between-group differences. Second hip fracture was defined as the time to the first occurrence following first hip fracture.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 259 patients were included in the analysis. After PSM, the risk of second hip fracture was significantly reduced in the denosumab group when compared with that in the control group (8.8% \u003cem\u003evs.\u003c/em\u003e 29.7%, hazard ratio (HR)\u0026thinsp;=\u0026thinsp;0.292, 95%CI\u0026thinsp;=\u0026thinsp;0.133\u0026ndash;0.643, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001). The incidence of second hip fracture was significantly lower in female patients and patients aged 65\u0026ndash;84 years in the denosumab group than that in the control group (5.3% \u003cem\u003evs.\u003c/em\u003e 29.8%, HR\u0026thinsp;=\u0026thinsp;0.293, 95%CI\u0026thinsp;=\u0026thinsp;0.126\u0026ndash;0.680, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002; 6.2% \u003cem\u003evs.\u003c/em\u003e 22.8%, HR\u0026thinsp;=\u0026thinsp;0.241, 95%CI\u0026thinsp;=\u0026thinsp;0.079\u0026ndash;0.740, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007; respectively).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eDenosumab reduced the risk of second hip fracture in elderly patients, with this reduction being especially marked in female patients and those aged 65\u0026ndash;84 years. Patients who received denosumab following first hip fracture had a lower incidence of second hip fractures, thus emphasizing the importance of the prompt initiation of antiosteoporosis treatment in elderly patients following hip fracture.\u003c/p\u003e","manuscriptTitle":"Treatment with denosumab reduces second hip fracture risk in elderly patients with femoral neck fractures","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-13 09:57:00","doi":"10.21203/rs.3.rs-6569056/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-31T08:55:44+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-14T12:29:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"164923496169595661976054547524399110796","date":"2025-07-05T04:03:50+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-10T02:36:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"213515245781419940384429602243664943964","date":"2025-05-10T02:14:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-07T08:12:06+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-05-06T04:38:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-05T08:46:47+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-05T08:42:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Musculoskeletal Disorders","date":"2025-05-01T04:15:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7d8f2e0f-ad2c-42c4-b5f9-df838f485824","owner":[],"postedDate":"May 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-03T16:02:24+00:00","versionOfRecord":{"articleIdentity":"rs-6569056","link":"https://doi.org/10.1186/s12891-025-09264-w","journal":{"identity":"bmc-musculoskeletal-disorders","isVorOnly":false,"title":"BMC Musculoskeletal Disorders"},"publishedOn":"2025-10-30 15:58:13","publishedOnDateReadable":"October 30th, 2025"},"versionCreatedAt":"2025-05-13 09:57:00","video":"","vorDoi":"10.1186/s12891-025-09264-w","vorDoiUrl":"https://doi.org/10.1186/s12891-025-09264-w","workflowStages":[]},"version":"v1","identity":"rs-6569056","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6569056","identity":"rs-6569056","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}