Clinical significance of zoledronic acid in combination with calcium tablets and calcitriol for hip biomechanics and bone mineral density after total hip replacement: a prospective randomized controlled trial

Clinical significance of zoledronic acid in combination with calcium tablets and calcitriol for hip biomechanics and bone mineral density after total hip replacement: a prospective randomized controlled trial | 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 Clinical significance of zoledronic acid in combination with calcium tablets and calcitriol for hip biomechanics and bone mineral density after total hip replacement: a prospective randomized controlled trial 贞东 徐, 庄 杜, 清 里, 辛 王, 紫 王, 华 邵, 宇通 胡, 莫真 刘 This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4213460/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: To investigate the effects of zoledronic acid (ZA) combined with calcium tablets and calcitriol on bone mineral density (BMD), hip function after total hip arthroplasty (THA). Methods: 50 elderly patients with THA from January 2022 to December 2022 were included in this study. The ZA group was given ZA combined with calcium tablets and calcitriol, while the control group was only given calcium tablets and calcitriol. The preoperative and postoperative BMD, bone metabolism-related indexes, Harris score, incidence of prosthesis loosening and hip biomechanics between the two groups were compared. Results: There were no significant differences in age, sex, Body Mass Index. Postoperative systemic BMD and periprosthetic BMDin ZA group were higher than those in the control group. The BMD in Gruen zones 1, 6 and 7 at postoperative 6 months, Gruen zones 1, 2, 4, 6 and 7 at postoperative 1 year was significantly higher than that in the control group. Postoperative 1 year, the 25-hydroxyvitamin D, procollagen 1 intact N-terminal and Harris score in ZA group were higher than those in control group, the β-type Ⅰ collagen carboxy-terminal peptide was lower. Acetabular height and acetabular deviation in ZA group were significantly better than those in control group at postoperative 1 year. Only 2 cases of prosthesis loosening in control group. Conclusion: ZA can effectively restore the loss of BMD, maintain the biomechanical stability of the hip, and reduce the incidence of prosthesis loosening. It is an effective method to prevent osteoporosis after THA. Trial registration: This study has been registered in the Chinese Clinical Registry (registration No.: ChiCTR2200065144, date: January 2022) total hip arthroplasty osteoporosis zoledronic acid bone mineral density bone metabolism biomechanics Figures Figure 1 1. Introduction Total hip arthroplasty (THA) is an important method in the treatment of femoral head necrosis and femoral neck fracture. Studies have pointed out that 73% of patients with osteoporosis who receive THA have not been diagnosed with osteoporosis before, resulting in insufficient postoperative anti-osteoporosis treatment[ 1 ]. After THA surgery, the incidence of postoperative revision, prosthesis loosening and periprosthetic fracture in osteoporosis patients can be as high as 14%, 20.2% and 12.3%[ 2 ]. Therefore, active anti-osteoporosis in patients with osteoporosis after THA is critical for long-term prognosis. Zoledronic acid (ZA), a third-generation bisphosphonate, is a first-line anti-osteoporosis drug in clinical practice. It has a high affinity for mineralized bone and can selectively act on bone to inhibit osteoclast activity and induce osteoclast apoptosis, thereby inhibiting bone resorption and improving bone density, thereby reducing revision rate and prolonging the service life of prosthetics. Reduces the risk of recurrent fractures[ 3 – 6 ]. It has been reported that a single injection of ZA can effectively improve bone mineral density (BMD) for at least 12 months[ 7 ] and has a positive effect on male BMD[ 8 ]. In another study, ZA was injected into postmenopausal osteoporosis patients every year for three years, and it was found that the bone mineral density of the patients continued to improve, and the fractures of the vertebral body, hip and other parts were significantly reduced and continued to decrease, indicating the significance of ZA in osteoporosis patients[ 9 ]. However, the changes of hip biomechanics after THA have not been fully understood, and the effect of ZA on hip biomechanics after THA is rarely studied. Therefore, this study was a prospective controlled study to investigate the effects of ZA combined with calcium tablets on hip function, biomechanics, bone mineral density and bone metabolism after total hip arthroplasty. 2. Materials and methods 2.1 Selection criteria Inclusion criteria: (1) total hip replacement; (2) Complete clinical data; (3) Age ≥ 65 years old. Exclusion criteria: (1) Failure to complete follow-up; (2) Failure to complete treatment as required; (3) Previous major hip diseases; (4) Other major diseases of the limbs or long-term bed rest; (5) Mental disorders; (6) Peripheral neuropathy. Shedding criteria:(1) The subject voluntarily withdraws the informed consent at any time; (2). The subjects were found to have seriously violated the admission criteria after random enrollment; (3) Discontinue study therapy but continue to follow up as required by the study: any clinical adverse events, laboratory abnormalities, or other medical conditions occur that may no longer benefit the subject from continued treatment; (4) Other reasons that the researcher believes that the study cannot be continued. 2.2 Patients According to the inclusion and exclusion criteria, a total of 50 elderly patients who underwent THA in our hospital from January 2022 to December 2022 were included in this study. All patients were randomly divided into ZA group and control group, with 25 cases in each group. Randomization was carried out by computer random selection. This study is in line with the Declaration of Helsinki 2013 edition and has been approved by the Ethics Committee of our hospital, 123. This study has been registered in the Chinese Clinical Registry (registration No., ChiCTR2200065144), and the informed consent of patients has been obtained and signed. 2.3 Drugs and surgery All patients were orally administered calcium tablets and calcitriol after surgery. Patients in ZA group received 5mg ZA injection on the 2nd day after surgery, once a year. All patients were monitored for the use of calcium tablets and calcitriol by outpatient follow-up or telephone follow-up. All procedures are performed by the same experienced joint surgeon. THA was performed within a specified period. The posterior articular capsule was cut with a T-shaped incision to expose the femoral neck, and 1cm cortical bone remained at the proximal end. The femoral head was removed and acetabular plasty was performed, and the acetabulum was reduced to an appropriate size with an acetabular file extending 45° and 15° forward. The proximal pulp cavity of the femur was filled-down to an appropriate size by keeping the abducting angle and the forward angle, the test mold was placed, and appropriate non-cement-type standard stem and artificial femoral head were installed. The artificial joint was reduced. After checking the range of motion and stability of the joint without active bleeding, the operative area was rinsed with normal saline, drainage was placed, and sutures were made layer by layer. 2.4 Assessments 2.4.1 Bone mineral density The systemic BMD and periprosthetic BMD were tested by dual-energy X-ray absorptiometry, and the BMD around the prosthesis was measured in different regions of interest, and the mean value was taken as periprosthetic BMD. The systemic BMD and periprosthetic BMD were measured before surgery, 6 months and 12 months after surgery. 2.4.2 Bone metabolism related indexes Bone metabolism-related indexes (including 25 hydroxyvitamin D, procollagen 1 intact N-terminalz (P1NP), osteocalcin (OCN) and β-type Ⅰ collagen carboxy-terminal peptide (β-CTX)) were measured before and 12 months after surgery. 2.4.3 Harris Score Patients are scored by the same physician according to the Harris score scale, with a total score of 100. A higher score indicates a better quality of life for patients. 2.4.4 evaluation At 1 week and 1 year after surgery, anteroposteric x-rays of the pelvis and anteroposteric and lateral X-rays of both hips were taken. The height and deviation of the acetabulum were measured according to the images. Acetabular height: the vertical distance from the acetabular center of rotation to the teardrop line; Acetabular deviation: The vertical distance between the center of rotation of the acetabulum and the tear drop perpendicular. The diagnostic criteria of prosthesis loosening were as follows: stalk sinking indicated by X-ray, zona pellucida between bone cement and prosthesis > 3mm, 2 or more holes around the stalk, defect of the inner wall of the proximal end of the prosthesis, defect of the lateral bone of the distal end of the prosthesis, displacement of the socket to the medial or lateral side of the prosthesis > 5mm, the upper margin of the prosthesis continuous light or increased light. 2.5 Statistical analysis SPSS26.0 statistical software was used for statistical analysis. All measurement data were tested for normal distribution. The measurement data conforming to normal distribution were represented by mean ± standard deviation, and the difference between the two groups of measurement data was analyzed by T-test. For counting data or rank data, n (%) was used, and Chi-square test was used to analyze the difference between the two groups. For the multiple time point repeated measurement data of BMD, the repeated measurement design analysis of variance was used. After the interaction, the independent effect was further analyzed, and the multiple weight ratio was corrected by Bonferroni. Bilateral test, α = 0.05. 3. Outcome 3.1 Patient demographics There were 25 patients in ZA group and control group, respectively. In the ZA group, there were 11 males and 14 females, aged 77.4 ± 6.9 years (68 ~ 88 years), body mass index (BMI) 25.0 ± 3.7 (kg/m2). In the control group, there were 12 males and 13 females, aged 78.9 ± 6.6 years (66 ~ 88 years). BMI was 26.4 ± 3.4 (kg/m2). There were 13 cases of left hip joint, 12 cases of right hip joint in ZA group, 9 cases and 16 cases in control group. There were 11 fracture cases and 14 f avascular necrosis cases in ZA group, 9 cases and 16 cases in control group. There were no significant differences in age, BMI, sex, surgical site and primary disease between the two groups. (Table 1 ) Table 1 Patient demographics ZA group (n = 25) Control group (n = 25) Age (years) 77.4 ± 6.9 78.9 ± 6.6 Sex, male/female 11/14 12/13 BMI (kg/m2) 25.0 ± 3.7 26.4 ± 3.4 Operative site, left/right 13/12 9/16 primary disease, fracture/AVN 11/14 9/16 ZA: zoledronic acid, BMI: body mass index, AVN: avascular necrosis. 3.2 Bone metabolism related indicators There was no significant difference in the special sequence of 25-hydroxyvitamin D, P1NP and β-CTX between ZA group and control group before operation (P = 0.623, P = 0.619, P = 0.733). One year after surgery, 25 hydroxyvitamin D and P1NP in ZA group were significantly increased compared with control group (54.96 ± 5.46 vs. 44.72 ± 5.76 nmol/L, P < 0.001; 0.40 ± 0.11 vs. 0.31 ± 0.13 µg/L, P = 0.010), β-CTX was significantly decreased (0.31 ± 0.10vs. 0.38 ± 0.09ng/ml, P = 0.012), and these differences were statistically significant. There were no significant differences in OCN between the two groups before and one year after surgery (P = 0.082, P = 0.395). (Table 2 ) 3.3 Function outcomes There was no significant difference in preoperative Harris scores between the two groups (P = 0.570). At 1 year after surgery, the Harris score of ZA group was significantly higher than that of control group (78.72 ± 6.06 vs. 73.56 ± 6.23, P = 0.005), and the difference was statistically significant. (Table 2 ) Table 2 Bone metabolism related indicators and function outcomes 25-hydroxyvitamin D P1NP OCN β-CTX Harris scores Preoperative ZA group 49.01 ± 5.14 0.32 ± 0.12 16.78 ± 3.52 0.40 ± 0.12 50.40 ± 5.66 Control group 48.22 ± 5.14 0.30 ± 0.13 18.61 ± 3.79 0.42 ± 0.11 49.48 ± 5.72 P value 0.623 0.619 0.082 0.733 0.570 Postoperative 1 year ZA group 54.96 ± 5.46 0.40 ± 0.11 16.40 ± 2.90 0.31 ± 0.10 78.72 ± 6.06 control group 44.72 ± 5.76 0.31 ± 0.13 17.33 ± 4.63 0.38 ± 0.09 73.56 ± 6.23 P value < 0.001 0.010 0.395 0.012 0.005 ZA: zoledronic acid, P1NP: procollagen 1 intact N-terminal, OCN: osteocalcin, β-CTX: β-type Ⅰ collagen carboxy-terminal peptide, P < 0.05 considered as significant. 3.4 Bone mineral density There were no significant differences in preoperative systemic BMD and periprosthetic BMD between the two groups (P = 0.664, P = 0.209). At 6 months and 1 year after surgery, systemic BMD and periprosthetic BMD in ZA group were higher than those in control group (1.22 ± 0.15 vs. 1.08 ± 0.14 g/cm3, P = 0.002; 1.03 ± 0.12 vs. 0.95 ± 0.15 g/cm3, P = 0.042; 1.25 ± 0.15 vs. 1.02 ± 0.12 g/cm3, P < 0.001; 1.10 ± 0.10 vs. 0.92 ± 0.14 g/cm3, P < 0.001), these differences were statistically significant (Table 3 ). BMD in different regions of interest around the prosthesis showed no significant difference between the two groups before surgery. 6 months after surgery, BMD in Gruen zones 1, 6 and 7 in ZA group was significantly higher than that in control group (P < 0.001, < 0.001, P < 0.001). At 1 year after surgery, bone mineral density in Gruen zones 1, 2, 4, 6, 7 in ZA group was significantly higher than that in control group (P < 0.001, P = 0.025, P < 0.001 P < 0.001, P < 0.001), these differences were statistically significant. (Table 4 ) Table 3 Systemic BMD and periprosthetic BMD Systemic BMD Periprosthetic BMD Preoperative Postoperative 6 months Postoperative 1 year Preoperative Postoperative 6 months Postoperative 1 year ZA group 1.13 ± 0.11 1.22 ± 0.15 1.25 ± 0.15 1.01 ± 0.14 1.03 ± 0.12 1.10 ± 0.10 Control group 1.12 ± 0.14 1.08 ± 0.14 1.02 ± 0.12 1.06 ± 0.16 0.95 ± 0.15 0.92 ± 0.14 P value 0.664 0.002 < 0.001 0.209 0.042 < 0.001 ZA: zoledronic acid, BMD: bone mineral density, P < 0.05 considered as significant. Table 4 BMD in different regions of interest around the prosthesis Gruen zone 1 Gruen zone 2 Gruen zone 3 Gruen zone 4 Gruen zone 5 Gruen zone 6 Gruen zone 7 Preoperative ZA group 0.63 ± 0.08 1.19 ± 0.10 1.29 ± 0.11 1.48 ± 0.11 1.42 ± 0.11 1.10 ± 0.11 0.84 ± 0.11 Control group 0.63 ± 0.07 1.20 ± 0.08 1.31 ± 0.16 1.48 ± 0.09 1.42 ± 0.09 1.10 ± 0.07 0.83 ± 0.06 P value 0.884 0.673 0.563 0.922 0.910 0.951 0.631 Postoperative 6 months ZA group 0.68 ± 0.09 1.20 ± 0.11 1.30 ± 0.11 1.49 ± 0.11 1.41 ± 0.11 1.19 ± 0.10 0.93 ± 0.10 Control group 0.58 ± 0.07 1.19 ± 0.09 1.29 ± 0.15 1.47 ± 0.09 1.41 ± 0.08 1.05 ± 0.07 0.79 ± 0.06 P value < 0.001 0.728 0.925 0.437 0.840 < 0.001 < 0.001 Postoperative 1 year ZA group 0.72 ± 0.09 1.23 ± 0.12 1.31 ± 0.11 1.57 ± 0.12 1.44 ± 0.12 1.28 ± 0.10 1.02 ± 0.10 Control group 0.50 ± 0.07 1.16 ± 0.08 1.28 ± 0.15 1.41 ± 0.09 1.40 ± 0.09 1.03 ± 0.07 0.77 ± 0.06 P value < 0.001 0.025 0.344 < 0.001 0.137 < 0.001 < 0.001 ZA: zoledronic acid, P < 0.05 considered as significant. 3.5 Imaging outcomes There was no significant difference in acetabular height and acetabular deviation between the two groups at 1 week after surgery (P = 0.874, P = 0.266). At 1 year after surgery, the acetabular height and deviation in the ZA group were higher than those in the control group (17.16 ± 2.79 vs. 14.01 ± 2.19, P < 0.001; 33.80 ± 3.50 vs. 29.21 ± 3.93, P < 0.001). The acetabular height and acetabular deviation of ZA group 1 year after surgery had no significant difference compared with 1 week after surgery (P = 0.076, P = 0.123), while the acetabular height and acetabular deviation of the control group 1 year after surgery were lower than that of 1 week after surgery (P < 0.001, P < 0.001). (Table 5 ) Table 5 Imaging outcomes Acetabular height Acetabular deviation Postoperative 1 week Postoperative 1 year P value Postoperative 1 week Postoperative 1 year P value ZA group 17.24 ± 2.86 17.16 ± 2.79 0.076 34.52 ± 3.24 33.80 ± 3.50 0.123 Control group 17.10 ± 3.54 14.01 ± 2.19 < 0.001 35.65 ± 3.84 29.21 ± 3.93 < 0.001 P value 0.874 < 0.001 0.266 < 0.001 ZA: zoledronic acid, P < 0.05 considered as significant. 4. Discussion Continuous reduction of periprosthetic BMD after THA is a common problem in patients with osteoporosis. However, anti-osteoporosis treatment after THA has not received effective attention, resulting in revision surgery for some postoperative patients due to loosening of prostheses or periprosthetic fractures, increasing the burden of patients. For patients with osteoporosis, the application of calcium and calcitriol alone cannot effectively increase the BMD of the hip[ 10 ]. ZA is a new class of drugs for the treatment of osteoporosis and calcium metabolic diseases. It has a long action time and can be combined with bone matrix to inhibit osteoclast activity and bone absorption[ 11 – 13 ]. Early intravenous application of ZA can effectively improve BMD, reduce P1NP and β-CTX levels in osteoporosis patients, and prevent fragility fractures. In a Mata analysis, the authors noted that bisphosphonates appeared to reduce early peri-femoral bone resorption after primary cementless THA, and found that the drug effect persisted in the major load-bearing areas (Gruen zones 6 and 7)[ 14 ]. ZA can effectively improve the periprosthetic BMD (Gruen zones 1, 2, 4, 6 and 7) after THA and extend the use time of the implant[ 15 ]. In 2019, zhou et al also reported that ZA significantly inhibited the bone mass loss of Gruen zones 1, 2, 4, 6 and 7 after THA surgery, which could effectively improve the periprosthetic BMD[ 3 ]. Scott et al. 's study pointed out that ZA can significantly improve BMD loss in Gruen zones 1, 4, 6 and 7 at 1 and 2 years after THA[ 16 ]. In 2017, Huang et al. pointed out that ZA can effectively restore the loss of periprosthetic BMD after cementless THA, especially the proximal femur (Gruen zones 1 and 7). And bone turnover markers (bone-specific alkaline phosphatase and n-terminal peptide of type I procollagen) were inhibited after ZA administration until 2 years after surgery[ 17 ]. In this study, the systemic BMD and periprosthetic BMD of ZA group after surgery were significantly better than those of the control group. As for BMD of various periprosthesis zones, the BMD of Gruen zones 1, 2, 4, 6 and 7 of ZA group one year after surgery was significantly higher than that of the control group, which was similar to the results of previous relevant studies and further confirmed that ZA can effectively improve systemic BMD and periprosthetic BMD, while calcium and vitamin supplementation alone cannot effectively prevent osteoporosis. In conclusion, the application of ZA after THA is an effective method to prevent osteoporosis. ZA also affects bone metabolism related indicators (e.g., 25-hydroxyvitamin D, P1NP, OCN and β-CTX). The bone metabolism related indicator can reflect the changes of bone metabolism in the whole body, help to judge the type of bone turnover, distinguish primary and secondary osteoporosis, and suggest whether treatment is effective, as well as the risk of bone loss and fracture to a certain extent. The deficiency of 25 hydroxyvitamin D will lead to the decrease of serum calcium, and then lead to osteoporosis[ 18 , 19 ]. P1NP and osteocalcin are indicators reflecting the ability of OCN, and when their levels increase, the body's osteogenic activity is more active[ 20 – 23 ]. β-CTX is an indicator of the activity of human osteoclasts, and its clinical significance is to show the degree of osteoclast absorption of bone. Studies have shown that bone specific alkaline phosphatase and N-terminal peptide of type I procollagen were significantly improved when ZA was given after THA until 2 years after surgery[ 17 ]. In this study, we made a comparative analysis of these four bone metabolism indicators. At one year after surgery, 25 hydroxyvitamin D and P1NP in ZA group were significantly higher than those in control group, and β-CTX specific sequences was significantly lower than those in control group. This is similar to previous research. When applying ZA, we need to pay attention to the safety of ZA. After 6 weeks of administration of ZA, the serum calcium level will decrease, etc., so we need to pay attention to giving patients calcium supplements[ 17 ]. Increased creatinine may also occur after the application of ZA, which requires close attention to patients' kidney function[ 17 ]. In addition, with the long-term application of ZA, jaw necrosis is the most serious complication, and atypical femoral fracture also exists, which requires close attention[ 24 , 25 ]. The purpose of THA is to relieve the pain symptoms of patients with hip lesions, and at the same time restore the biomechanical structure of hip joint, rebuild the biomechanical structure of hip joint, and restore the function of hip joint[ 26 , 27 ]. A delayed bone resorption process called "stress shielding" occurs in the proximal region of the femur, which is related to the biomechanical characteristics of the bone implant structure and the stiffness difference between the prosthesis and the surrounding bone. The stress shielding tends to be stable at one year after surgery[ 28 ]. In our study, the improvement of HHS indicates the positive effect of ZA on the functional recovery of osteoporosis patients after THA. On the one hand, it inhibits the bone loss around the prosthesis caused by stress shielding and enhances the fixation and stability of the implant. On the other hand, it improves the bone density of the whole body and helps improve the quality of life of osteoporosis patients[ 29 ]. Maintaining the acetabular height after THA is of great significance for maintaining the stability of the hip joint and preventing the unequal length of the lower limbs. The reduction of the acetabular height is related to the inward and downward movement of the rotation center, which can affect the postoperative recovery of patients. At the same time, maintaining acetabular deviation after THA is of great significance to further strengthen the stability of hip joint, reduce the wear of prosthesis on surrounding bone, improve hip joint motion, and increase the degree of extension[ 30 , 31 ]. The selection of prostheses with appropriate parameters and installation Angle, and the maintenance of appropriate acetabular height, may be beneficial to further improve the hip function of patients after THR. In addition, postoperative improvement of the bone strength around the prosthesis can effectively maintain the stability of the prosthesis, thus reducing the postoperative changes in acetabular height and acetabular deviation. In this study, there was no significant difference in acetabular height and acetabular deviation between the two groups before surgery. At 1 year after surgery, the acetabular height and acetabular deviation in the ZA group were significantly higher than those in the control group. This suggests that the application of ZA after THA has some significance in maintaining the biomechanics of hip joint, which may be related to the improvement of periprosthetic BMD. The abnormal biomechanics after THA results in increased compression of the prosthesis on surrounding bone and increased stress, which can accelerate bone loss and lead to decreased periprosthetic BMD, which in turn can lead to weaker stability of the prosthesis, forming a vicious cycle. Therefore, stopping the vicious cycle by increasing the periprosthetic BMD is an option. In this study, only 2 cases of prosthesis loosening occurred in the control group, which failed to form a meaningful statistical analysis. The stability of early implants is mainly based on implant design and cortical structure. ZA acts on bone trabeculae, promotes bone integration and bone growth after a few weeks to a few months, and can reduce the incidence of prosthesis loosening[ 28 ]. Therefore, in the future, we will further extend the follow-up time and maintain the injection of ZA in the second and third years. To further observe the effect of ZA on prosthesis loosening after THA. In studies on the use of bisphosphonate and aseptic loosening after THA, postoperative bisphosphonate treatment can reduce osteoclast activity, thereby improving the implant-host bone integration process and lasting implant fixation, thereby reducing the risk of aseptic loosening[ 32 ]. In addition, studies have pointed out that bisphosphonates can significantly improve the revision rate after THA, and that the positive effect of bisphosphonates is obvious only when treatment begins after the initial THA[ 33 ]. There are also some limitations in this study, mainly focusing on follow-up time and sample size, but the results of this study are similar to those of previous studies, and the results are more convincing. In the future, we will further expand the sample size and increase the follow-up time to further confirm the clinical and radiographic findings after the application of ZA. In addition, in the study, some patients lacked the results of blood calcium and renal function at a certain time before or after surgery, so we did not include the results of blood calcium and renal function in the statistical analysis, which are related to the adverse results of ZA application. Therefore, we will further improve this part in the subsequent study. 5. Conclusion In conclusion, the application of ZA after THA can effectively improve the periprosthetic BMD (Gruen zones 1, 2, 4, 6, 7), maintain the stability of the prosthesis, and reduce the biomechanical changes of hip joint and the incidence of prosthesis loosening, which may be an effective method to prevent osteoporosis after total hip arthroplasty. Abbreviations zoledronic acid ZA bone mineral density BMD total hip arthroplasty THA procollagen 1 intact N-terminalz P1NP osteocalcin OCN β-type Ⅰ collagen carboxy-terminal peptide β-CTX body mass index BMI Declarations Competing of interests Zhendong Xu, Zhuang Du, Qing Li, Xin Wang, Zi Wang, Hua Shao, Yutong Hu, Mozhen,Lu declare that they have no conflict of interests. Acknowledgements The authors are grateful to the patients and their family members for their participation. Thanks for all doctors and nursing staff involved in the study. Funding This work was supported by project 2022JJ13SN085. Consent for publication Patients sign informed consent forms for the release of their data and photos. Availability of data and materials The datasets generated and analyzed during the current study are not publicly available because they were part of patients’ records but are available as a de-identified data sheet from the correspond- ing author upon reasonable request. Authors’ contributions ZX, QL, ML and YH set up the conception and designed the research. ZX, XW, ZW, ZD collected and interpreted patient’s clinical information. ZX, ZD and YH drafted the manuscript. ZX, YH and ML critically reviewed, revised the manuscript and supervised the study. All authors revised the paper critically for intellectual content and approved the final version. All authors agree to be accountable for the work and to ensure that any questions relating to the accuracy and integrity of the paper are investigated and properly resolved. Ethics approval and consent to participate All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Ethical approval was obtained from the Ethics Committee of Dalian Central Hospital (YN2024-003-01). References Delsmann MM, Strahl A, Muhlenfeld M , et al. High prevalence and undertreatment of osteoporosis in elderly patients undergoing total hip arthroplasty. Osteoporos Int. 2021;32(8):1661-8. doi: 10.1007/s00198-021-05881-y. Zhou X, Chen M, Yu W , et al. Uncemented versus cemented total hip arthroplasty for displaced femoral neck fractures in elderly patients with osteoporosis: A retrospective analysis. J Int Med Res. 2020;48(8):300060520944663. doi: 10.1177/0300060520944663. Zhou W, Liu Y, Guo X , et al. Effects of zoledronic acid on bone mineral density around prostheses and bone metabolism markers after primary total hip arthroplasty in females with postmenopausal osteoporosis. Osteoporos Int. 2019;30(8):1581-9. doi: 10.1007/s00198-019-05005-7. Jia F, Ruan L, Du C , et al. The nanoformula of zoledronic acid and calcium carbonate targets osteoclasts and reverses osteoporosis. Biomaterials. 2023;296:122059. doi: 10.1016/j.biomaterials.2023.122059. Treurniet S, Bevers M, Wyers CE , et al. Bone Microarchitecture and Strength Changes During Teriparatide and Zoledronic Acid Treatment in a Patient with Pregnancy and Lactation-Associated Osteoporosis with Multiple Vertebral Fractures. Calcif Tissue Int. 2023;112(5):621-7. doi: 10.1007/s00223-023-01066-3. M U, Ethiraj P, Nazar SM , et al. Does Zoledronic Acid Provide a Good Clinical Outcome in Patients With Chronic Back Pain Associated With Vertebral Osteoporosis? Cureus. 2023;15(1):e33328. doi: 10.7759/cureus.33328. Reid IR, Brown JP, Burckhardt P , et al. Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med. 2002;346(9):653-61. doi: 10.1056/NEJMoa011807. Liang BC, Shi ZY, Wang B , et al. Intravenous Zoledronic Acid 5 mg on Bone Turnover Markers and Bone Mineral Density in East China Subjects with Newly Diagnosed Osteoporosis: A 24-month Clinical Study. Orthop Surg. 2017;9(1):103-9. doi: 10.1111/os.12307. Black DM, Delmas PD, Eastell R , et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356(18):1809-22. doi: 10.1056/NEJMoa067312. Fu GT, Lin LJ, Sheng PY , et al. Efficiency of Zoledronic Acid in Inhibiting Accelerated Periprosthetic Bone Loss After Cementless Total Hip Arthroplasty in Osteoporotic Patients: A Prospective, Cohort Study. Orthop Surg. 2019;11(4):653-63. doi: 10.1111/os.12513. Cheng YT, Liao J, Zhou Q , et al. Zoledronic acid modulates osteoclast apoptosis through activation of the NF-kappaB signaling pathway in ovariectomized rats. Exp Biol Med (Maywood). 2021;246(15):1727-39. doi: 10.1177/15353702211011052. Kameda Y, Aizawa M, Sato T , et al. Zoledronic Acid-Loaded beta-TCP Inhibits Tumor Proliferation and Osteoclast Activation: Development of a Functional Bone Substitute for an Efficient Osteosarcoma Treatment. Int J Mol Sci. 2021;22(4). doi: 10.3390/ijms22041889. Tai TW, Su FC, Chen CY , et al. Activation of p38 MAPK-regulated Bcl-xL signaling increases survival against zoledronic acid-induced apoptosis in osteoclast precursors. Bone. 2014;67:166-74. doi: 10.1016/j.bone.2014.07.003. Zhao X, Hu D, Qin J , et al. Effect of bisphosphonates in preventing femoral periprosthetic bone resorption after primary cementless total hip arthroplasty: a meta-analysis. J Orthop Surg Res. 2015;10:65. doi: 10.1186/s13018-015-0206-8. Gao J, Gao C, Li H , et al. Effect of zoledronic acid on reducing femoral bone mineral density loss following total hip arthroplasty: A meta-analysis from randomized controlled trails. Int J Surg. 2017;47:116-26. doi: 10.1016/j.ijsu.2017.08.559. Scott DF, Woltz JN, Smith RR. Effect of zoledronic acid on reducing femoral bone mineral density loss following total hip arthroplasty: preliminary results of a prospective randomized trial. J Arthroplasty. 2013;28(4):671-5. doi: 10.1016/j.arth.2012.08.007. Huang TW, Wang CJ, Shih HN , et al. Bone turnover and periprosthetic bone loss after cementless total hip arthroplasty can be restored by zoledronic acid: a prospective, randomized, open-label, controlled trial. BMC Musculoskelet Disord. 2017;18(1):209. doi: 10.1186/s12891-017-1577-2. Morrison RJM, Bunn D, Gray WK , et al. VASO (Vitamin D and Arthroplasty Surgery Outcomes) study - supplementation of vitamin D deficiency to improve outcomes after total hip or knee replacement: study protocol for a randomised controlled feasibility trial. Trials. 2017;18(1):514. doi: 10.1186/s13063-017-2255-2. Nawabi DH, Chin KF, Keen RW , et al. Vitamin D deficiency in patients with osteoarthritis undergoing total hip replacement: a cause for concern? J Bone Joint Surg Br. 2010;92(4):496-9. doi: 10.1302/0301-620X.92B3.23535. Xu Y, Shen L, Liu L , et al. Undercarboxylated Osteocalcin and Its Associations With Bone Mineral Density, Bone Turnover Markers, and Prevalence of Osteopenia and Osteoporosis in Chinese Population: A Cross-Sectional Study. Front Endocrinol (Lausanne). 2022;13:843912. doi: 10.3389/fendo.2022.843912. Roomi AB, Mahdi Salih AH, Noori SD , et al. Evaluation of Bone Mineral Density, Serum Osteocalcin, and Osteopontin Levels in Postmenopausal Women with Type 2 Diabetes Mellitus, with/without Osteoporosis. J Osteoporos. 2022;2022:1437061. doi: 10.1155/2022/1437061. Sun Y, Xiao Y, Chen L , et al. Application value of serum osteocalcin and bone mineral density detection in middle-aged and elderly healthy physical examination. Minerva Med. 2021;112(6):829-31. doi: 10.23736/S0026-4806.20.06710-5. Miyaoka D, Imanishi Y, Yano M , et al. Effects of burosumab on osteocalcin and bone mineral density in patient with 15-year history of nonremission tumor-induced osteomalacia initially treated with conventional therapy: Case report. Bone Rep. 2020;13:100736. doi: 10.1016/j.bonr.2020.100736. Curraj E, Gonzalez Rodriguez E. [Side effects of osteoporosis treatments: how to explain them to patients?]. Rev Med Suisse. 2023;19(823):746-51. doi: 10.53738/REVMED.2023.19.823.746. Khan M, Cheung AM, Khan AA. Drug-Related Adverse Events of Osteoporosis Therapy. Endocrinol Metab Clin North Am. 2017;46(1):181-92. doi: 10.1016/j.ecl.2016.09.009. Ardestani MM, Amenabar Edwards PP, Wimmer MA. Prediction of Polyethylene Wear Rates from Gait Biomechanics and Implant Positioning in Total Hip Replacement. Clin Orthop Relat Res. 2017;475(8):2027-42. doi: 10.1007/s11999-017-5293-x. Li J, McWilliams AB, Jin Z , et al. Unilateral total hip replacement patients with symptomatic leg length inequality have abnormal hip biomechanics during walking. Clin Biomech (Bristol, Avon). 2015;30(5):513-9. doi: 10.1016/j.clinbiomech.2015.02.014. Hsu AHS, Yen CH, Kuo FC , et al. Zoledronic Acid Ameliorates the Bone Turnover Activity and Periprosthetic Bone Preservation in Cementless Total Hip Arthroplasty. Pharmaceuticals (Basel). 2022;15(4). doi: 10.3390/ph15040420. Liu Y, Xu JW, Li MY , et al. Zoledronic Acid for Periprosthetic Bone Mineral Density Changes in Patients With Osteoporosis After Hip Arthroplasty-An Updated Meta-Analysis of Six Randomized Controlled Trials. Front Med (Lausanne). 2021;8:801282. doi: 10.3389/fmed.2021.801282. Mahmood SS, Mukka SS, Crnalic S , et al. Association between changes in global femoral offset after total hip arthroplasty and function, quality of life, and abductor muscle strength. A prospective cohort study of 222 patients. Acta Orthop. 2016;87(1):36-41. doi: 10.3109/17453674.2015.1091955. Little NJ, Busch CA, Gallagher JA , et al. Acetabular polyethylene wear and acetabular inclination and femoral offset. Clin Orthop Relat Res. 2009;467(11):2895-900. doi: 10.1007/s11999-009-0845-3. Pegios VF, Kenanidis E, Tsotsolis S , et al. Bisphosphonates' use and risk of aseptic loosening following total hip arthroplasty: a systematic review. EFORT Open Rev. 2023;8(11):798-808. doi: 10.1530/EOR-22-0121. Prieto-Alhambra D, Lalmohamed A, Abrahamsen B , et al. Oral bisphosphonate use and total knee/hip implant survival: validation of results in an external population-based cohort. Arthritis Rheumatol. 2014;66(11):3233-40. doi: 10.1002/art.38789. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-4213460","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":288366188,"identity":"05404bfb-63d2-4c58-91f6-0373c02b85e8","order_by":0,"name":"贞东 徐","email":"","orcid":"","institution":"Dalian Municipal Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"贞东","middleName":"","lastName":"徐","suffix":""},{"id":288366189,"identity":"866d96b1-dcb1-4361-9b85-9279e0d3e2d5","order_by":1,"name":"庄 杜","email":"","orcid":"","institution":"Dalian Municipal Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"庄","middleName":"","lastName":"杜","suffix":""},{"id":288366190,"identity":"3743c55b-5b14-4526-85c1-2a1939b50332","order_by":2,"name":"清 里","email":"","orcid":"","institution":"Dalian Municipal Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"清","middleName":"","lastName":"里","suffix":""},{"id":288366191,"identity":"4f9a4d5d-6e12-4143-a072-05d1befee474","order_by":3,"name":"辛 王","email":"","orcid":"","institution":"Dalian Municipal Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"辛","middleName":"","lastName":"王","suffix":""},{"id":288366192,"identity":"22fb12d4-27cf-4446-8e8a-0beb52879dbf","order_by":4,"name":"紫 王","email":"","orcid":"","institution":"Dalian Municipal Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"紫","middleName":"","lastName":"王","suffix":""},{"id":288366193,"identity":"a5b0334a-bba6-46ac-80a5-342c4c5f5939","order_by":5,"name":"华 邵","email":"","orcid":"","institution":"Dalian Municipal Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"华","middleName":"","lastName":"邵","suffix":""},{"id":288366194,"identity":"02945710-03df-4369-8deb-02258b1b718a","order_by":6,"name":"宇通 胡","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvUlEQVRIiWNgGAWjYBACAxCRUCHBw8/MfPgBsVoYGz6csZGRbGdLMyBaS+PMtjQbg/M8ChJEaTGXyDF/zNt2mMf4MA9Qf41NNEEtljNyDJt5zh3mMTvMe+ABw7G03AaCDrsB0lIG0sKXYMDYcJhYLWxAhzXzGEgQraVxRlsajwEz0VrOPCucAQxkHonDwEBOIMovx5M3fABGpT1//+HDDz7U2BDWwsDAgRSBCYSVgwD7A+LUjYJRMApGwcgFAE2gQIS83JakAAAAAElFTkSuQmCC","orcid":"","institution":"The Second Affiliated Hospital of Soochow University","correspondingAuthor":true,"prefix":"","firstName":"宇通","middleName":"","lastName":"胡","suffix":""},{"id":288366195,"identity":"50ee3ebe-accd-4a1e-975d-2a0c77fd81b0","order_by":7,"name":"莫真 刘","email":"","orcid":"","institution":"3、The First Affiliated Hospital of Dalian Medical University","correspondingAuthor":false,"prefix":"","firstName":"莫真","middleName":"","lastName":"刘","suffix":""}],"badges":[],"createdAt":"2024-04-03 14:32:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4213460/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4213460/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":54315588,"identity":"7b95991d-937f-49fc-b4e6-ebc9921da08a","added_by":"auto","created_at":"2024-04-08 17:44:44","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":144199,"visible":true,"origin":"","legend":"\u003cp\u003eBone mineral density Changes in Gruen zones in the ZA group and control group. Preop: preoperative, Postoperative.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4213460/v1/f6475cbe581ee465a260522b.png"},{"id":58420992,"identity":"d904b215-0685-40e4-9036-d39ec396ade5","added_by":"auto","created_at":"2024-06-15 15:15:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":848599,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4213460/v1/34f0a23d-ffa6-4f5f-adc7-31520dd53a9d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical significance of zoledronic acid in combination with calcium tablets and calcitriol for hip biomechanics and bone mineral density after total hip replacement: a prospective randomized controlled trial","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eTotal hip arthroplasty (THA) is an important method in the treatment of femoral head necrosis and femoral neck fracture. Studies have pointed out that 73% of patients with osteoporosis who receive THA have not been diagnosed with osteoporosis before, resulting in insufficient postoperative anti-osteoporosis treatment[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. After THA surgery, the incidence of postoperative revision, prosthesis loosening and periprosthetic fracture in osteoporosis patients can be as high as 14%, 20.2% and 12.3%[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Therefore, active anti-osteoporosis in patients with osteoporosis after THA is critical for long-term prognosis. Zoledronic acid (ZA), a third-generation bisphosphonate, is a first-line anti-osteoporosis drug in clinical practice. It has a high affinity for mineralized bone and can selectively act on bone to inhibit osteoclast activity and induce osteoclast apoptosis, thereby inhibiting bone resorption and improving bone density, thereby reducing revision rate and prolonging the service life of prosthetics. Reduces the risk of recurrent fractures[\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. It has been reported that a single injection of ZA can effectively improve bone mineral density (BMD) for at least 12 months[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] and has a positive effect on male BMD[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In another study, ZA was injected into postmenopausal osteoporosis patients every year for three years, and it was found that the bone mineral density of the patients continued to improve, and the fractures of the vertebral body, hip and other parts were significantly reduced and continued to decrease, indicating the significance of ZA in osteoporosis patients[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, the changes of hip biomechanics after THA have not been fully understood, and the effect of ZA on hip biomechanics after THA is rarely studied. Therefore, this study was a prospective controlled study to investigate the effects of ZA combined with calcium tablets on hip function, biomechanics, bone mineral density and bone metabolism after total hip arthroplasty.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Selection criteria\u003c/h2\u003e \u003cp\u003eInclusion criteria: (1) total hip replacement; (2) Complete clinical data; (3) Age\u0026thinsp;\u0026ge;\u0026thinsp;65 years old. Exclusion criteria: (1) Failure to complete follow-up; (2) Failure to complete treatment as required; (3) Previous major hip diseases; (4) Other major diseases of the limbs or long-term bed rest; (5) Mental disorders; (6) Peripheral neuropathy. Shedding criteria:(1) The subject voluntarily withdraws the informed consent at any time; (2). The subjects were found to have seriously violated the admission criteria after random enrollment; (3) Discontinue study therapy but continue to follow up as required by the study: any clinical adverse events, laboratory abnormalities, or other medical conditions occur that may no longer benefit the subject from continued treatment; (4) Other reasons that the researcher believes that the study cannot be continued.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Patients\u003c/h2\u003e \u003cp\u003eAccording to the inclusion and exclusion criteria, a total of 50 elderly patients who underwent THA in our hospital from January 2022 to December 2022 were included in this study. All patients were randomly divided into ZA group and control group, with 25 cases in each group. Randomization was carried out by computer random selection.\u003c/p\u003e \u003cp\u003e This study is in line with the Declaration of Helsinki 2013 edition and has been approved by the Ethics Committee of our hospital, 123. This study has been registered in the Chinese Clinical Registry (registration No., ChiCTR2200065144), and the informed consent of patients has been obtained and signed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Drugs and surgery\u003c/h2\u003e \u003cp\u003eAll patients were orally administered calcium tablets and calcitriol after surgery. Patients in ZA group received 5mg ZA injection on the 2nd day after surgery, once a year. All patients were monitored for the use of calcium tablets and calcitriol by outpatient follow-up or telephone follow-up. All procedures are performed by the same experienced joint surgeon. THA was performed within a specified period. The posterior articular capsule was cut with a T-shaped incision to expose the femoral neck, and 1cm cortical bone remained at the proximal end. The femoral head was removed and acetabular plasty was performed, and the acetabulum was reduced to an appropriate size with an acetabular file extending 45\u0026deg; and 15\u0026deg; forward. The proximal pulp cavity of the femur was filled-down to an appropriate size by keeping the abducting angle and the forward angle, the test mold was placed, and appropriate non-cement-type standard stem and artificial femoral head were installed. The artificial joint was reduced. After checking the range of motion and stability of the joint without active bleeding, the operative area was rinsed with normal saline, drainage was placed, and sutures were made layer by layer.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Assessments\u003c/h2\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003e2.4.1 Bone mineral density\u003c/h2\u003e \u003cp\u003eThe systemic BMD and periprosthetic BMD were tested by dual-energy X-ray absorptiometry, and the BMD around the prosthesis was measured in different regions of interest, and the mean value was taken as periprosthetic BMD. The systemic BMD and periprosthetic BMD were measured before surgery, 6 months and 12 months after surgery.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003e2.4.2 Bone metabolism related indexes\u003c/h2\u003e \u003cp\u003eBone metabolism-related indexes (including 25 hydroxyvitamin D, procollagen 1 intact N-terminalz (P1NP), osteocalcin (OCN) and β-type Ⅰ collagen carboxy-terminal peptide (β-CTX)) were measured before and 12 months after surgery.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003e2.4.3 Harris Score\u003c/h2\u003e \u003cp\u003ePatients are scored by the same physician according to the Harris score scale, with a total score of 100. A higher score indicates a better quality of life for patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003e2.4.4 evaluation\u003c/h2\u003e \u003cp\u003eAt 1 week and 1 year after surgery, anteroposteric x-rays of the pelvis and anteroposteric and lateral X-rays of both hips were taken. The height and deviation of the acetabulum were measured according to the images. Acetabular height: the vertical distance from the acetabular center of rotation to the teardrop line; Acetabular deviation: The vertical distance between the center of rotation of the acetabulum and the tear drop perpendicular.\u003c/p\u003e \u003cp\u003eThe diagnostic criteria of prosthesis loosening were as follows: stalk sinking indicated by X-ray, zona pellucida between bone cement and prosthesis\u0026thinsp;\u0026gt;\u0026thinsp;3mm, 2 or more holes around the stalk, defect of the inner wall of the proximal end of the prosthesis, defect of the lateral bone of the distal end of the prosthesis, displacement of the socket to the medial or lateral side of the prosthesis\u0026thinsp;\u0026gt;\u0026thinsp;5mm, the upper margin of the prosthesis continuous light or increased light.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Statistical analysis\u003c/h2\u003e \u003cp\u003eSPSS26.0 statistical software was used for statistical analysis. All measurement data were tested for normal distribution. The measurement data conforming to normal distribution were represented by mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, and the difference between the two groups of measurement data was analyzed by T-test. For counting data or rank data, n (%) was used, and Chi-square test was used to analyze the difference between the two groups. For the multiple time point repeated measurement data of BMD, the repeated measurement design analysis of variance was used. After the interaction, the independent effect was further analyzed, and the multiple weight ratio was corrected by Bonferroni. Bilateral test, α\u0026thinsp;=\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Outcome","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Patient demographics\u003c/h2\u003e \u003cp\u003eThere were 25 patients in ZA group and control group, respectively. In the ZA group, there were 11 males and 14 females, aged 77.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.9 years (68\u0026thinsp;~\u0026thinsp;88 years), body mass index (BMI) 25.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7 (kg/m2). In the control group, there were 12 males and 13 females, aged 78.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6 years (66\u0026thinsp;~\u0026thinsp;88 years). BMI was 26.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4 (kg/m2). There were 13 cases of left hip joint, 12 cases of right hip joint in ZA group, 9 cases and 16 cases in control group. There were 11 fracture cases and 14 f avascular necrosis cases in ZA group, 9 cases and 16 cases in control group. There were no significant differences in age, BMI, sex, surgical site and primary disease between the two groups. (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient demographics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eZA group (n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl group (n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, male/female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11/14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12/13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperative site, left/right\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13/12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9/16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eprimary disease, fracture/AVN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11/14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9/16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eZA: zoledronic acid, BMI: body mass index, AVN: avascular necrosis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Bone metabolism related indicators\u003c/h2\u003e \u003cp\u003eThere was no significant difference in the special sequence of 25-hydroxyvitamin D, P1NP and β-CTX between ZA group and control group before operation (P\u0026thinsp;=\u0026thinsp;0.623, P\u0026thinsp;=\u0026thinsp;0.619, P\u0026thinsp;=\u0026thinsp;0.733). One year after surgery, 25 hydroxyvitamin D and P1NP in ZA group were significantly increased compared with control group (54.96\u0026thinsp;\u0026plusmn;\u0026thinsp;5.46 vs. 44.72\u0026thinsp;\u0026plusmn;\u0026thinsp;5.76 nmol/L, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; 0.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11 vs. 0.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13 \u0026micro;g/L, P\u0026thinsp;=\u0026thinsp;0.010), β-CTX was significantly decreased (0.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10vs. 0.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09ng/ml, P\u0026thinsp;=\u0026thinsp;0.012), and these differences were statistically significant. There were no significant differences in OCN between the two groups before and one year after surgery (P\u0026thinsp;=\u0026thinsp;0.082, P\u0026thinsp;=\u0026thinsp;0.395). (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Function outcomes\u003c/h2\u003e \u003cp\u003eThere was no significant difference in preoperative Harris scores between the two groups (P\u0026thinsp;=\u0026thinsp;0.570). At 1 year after surgery, the Harris score of ZA group was significantly higher than that of control group (78.72\u0026thinsp;\u0026plusmn;\u0026thinsp;6.06 vs. 73.56\u0026thinsp;\u0026plusmn;\u0026thinsp;6.23, P\u0026thinsp;=\u0026thinsp;0.005), and the difference was statistically significant. (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBone metabolism related indicators and function outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25-hydroxyvitamin D\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP1NP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOCN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eβ-CTX\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHarris scores\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZA group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49.01\u0026thinsp;\u0026plusmn;\u0026thinsp;5.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.78\u0026thinsp;\u0026plusmn;\u0026thinsp;3.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e50.40\u0026thinsp;\u0026plusmn;\u0026thinsp;5.66\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48.22\u0026thinsp;\u0026plusmn;\u0026thinsp;5.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.61\u0026thinsp;\u0026plusmn;\u0026thinsp;3.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e49.48\u0026thinsp;\u0026plusmn;\u0026thinsp;5.72\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.623\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.619\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.082\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.733\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.570\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative 1 year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZA group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54.96\u0026thinsp;\u0026plusmn;\u0026thinsp;5.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.40\u0026thinsp;\u0026plusmn;\u0026thinsp;2.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e78.72\u0026thinsp;\u0026plusmn;\u0026thinsp;6.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003econtrol group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44.72\u0026thinsp;\u0026plusmn;\u0026thinsp;5.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17.33\u0026thinsp;\u0026plusmn;\u0026thinsp;4.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e73.56\u0026thinsp;\u0026plusmn;\u0026thinsp;6.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.395\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eZA: zoledronic acid, P1NP: procollagen 1 intact N-terminal, OCN: osteocalcin, β-CTX: β-type Ⅰ collagen carboxy-terminal peptide, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered as significant.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Bone mineral density\u003c/h2\u003e \u003cp\u003eThere were no significant differences in preoperative systemic BMD and periprosthetic BMD between the two groups (P\u0026thinsp;=\u0026thinsp;0.664, P\u0026thinsp;=\u0026thinsp;0.209). At 6 months and 1 year after surgery, systemic BMD and periprosthetic BMD in ZA group were higher than those in control group (1.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15 vs. 1.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14 g/cm3, P\u0026thinsp;=\u0026thinsp;0.002; 1.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12 vs. 0.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15 g/cm3, P\u0026thinsp;=\u0026thinsp;0.042; 1.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15 vs. 1.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12 g/cm3, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; 1.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10 vs. 0.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14 g/cm3, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), these differences were statistically significant (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). BMD in different regions of interest around the prosthesis showed no significant difference between the two groups before surgery. 6 months after surgery, BMD in Gruen zones 1, 6 and 7 in ZA group was significantly higher than that in control group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, \u0026lt;\u0026thinsp;0.001, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). At 1 year after surgery, bone mineral density in Gruen zones 1, 2, 4, 6, 7 in ZA group was significantly higher than that in control group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, P\u0026thinsp;=\u0026thinsp;0.025, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001 P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), these differences were statistically significant. (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSystemic BMD and periprosthetic BMD\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eSystemic BMD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003ePeriprosthetic BMD\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePreoperative\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePostoperative 6 months\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePostoperative 1 year\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePreoperative\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePostoperative 6 months\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePostoperative 1 year\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZA group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.664\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.209\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.042\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eZA: zoledronic acid, BMD: bone mineral density, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered as significant.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBMD in different regions of interest around the prosthesis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGruen zone 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGruen zone 2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGruen zone 3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGruen zone 4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGruen zone 5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGruen zone 6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eGruen zone 7\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZA group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.84\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.884\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.673\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.563\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.922\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.910\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.951\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.631\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative 6 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZA group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.79\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.728\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.925\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.437\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.840\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative 1 year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZA group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.77\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.344\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.137\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eZA: zoledronic acid, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered as significant.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Imaging outcomes\u003c/h2\u003e \u003cp\u003eThere was no significant difference in acetabular height and acetabular deviation between the two groups at 1 week after surgery (P\u0026thinsp;=\u0026thinsp;0.874, P\u0026thinsp;=\u0026thinsp;0.266). At 1 year after surgery, the acetabular height and deviation in the ZA group were higher than those in the control group (17.16\u0026thinsp;\u0026plusmn;\u0026thinsp;2.79 vs. 14.01\u0026thinsp;\u0026plusmn;\u0026thinsp;2.19, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; 33.80\u0026thinsp;\u0026plusmn;\u0026thinsp;3.50 vs. 29.21\u0026thinsp;\u0026plusmn;\u0026thinsp;3.93, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The acetabular height and acetabular deviation of ZA group 1 year after surgery had no significant difference compared with 1 week after surgery (P\u0026thinsp;=\u0026thinsp;0.076, P\u0026thinsp;=\u0026thinsp;0.123), while the acetabular height and acetabular deviation of the control group 1 year after surgery were lower than that of 1 week after surgery (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eImaging outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eAcetabular height\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eAcetabular deviation\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePostoperative 1 week\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePostoperative 1 year\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePostoperative 1 week\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePostoperative 1 year\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZA group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.24\u0026thinsp;\u0026plusmn;\u0026thinsp;2.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.16\u0026thinsp;\u0026plusmn;\u0026thinsp;2.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.076\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e34.52\u0026thinsp;\u0026plusmn;\u0026thinsp;3.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e33.80\u0026thinsp;\u0026plusmn;\u0026thinsp;3.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.123\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.10\u0026thinsp;\u0026plusmn;\u0026thinsp;3.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.01\u0026thinsp;\u0026plusmn;\u0026thinsp;2.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35.65\u0026thinsp;\u0026plusmn;\u0026thinsp;3.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e29.21\u0026thinsp;\u0026plusmn;\u0026thinsp;3.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.874\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.266\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eZA: zoledronic acid, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered as significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eContinuous reduction of periprosthetic BMD after THA is a common problem in patients with osteoporosis. However, anti-osteoporosis treatment after THA has not received effective attention, resulting in revision surgery for some postoperative patients due to loosening of prostheses or periprosthetic fractures, increasing the burden of patients.\u003c/p\u003e \u003cp\u003eFor patients with osteoporosis, the application of calcium and calcitriol alone cannot effectively increase the BMD of the hip[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. ZA is a new class of drugs for the treatment of osteoporosis and calcium metabolic diseases. It has a long action time and can be combined with bone matrix to inhibit osteoclast activity and bone absorption[\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Early intravenous application of ZA can effectively improve BMD, reduce P1NP and β-CTX levels in osteoporosis patients, and prevent fragility fractures.\u003c/p\u003e \u003cp\u003eIn a Mata analysis, the authors noted that bisphosphonates appeared to reduce early peri-femoral bone resorption after primary cementless THA, and found that the drug effect persisted in the major load-bearing areas (Gruen zones 6 and 7)[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. ZA can effectively improve the periprosthetic BMD (Gruen zones 1, 2, 4, 6 and 7) after THA and extend the use time of the implant[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In 2019, zhou et al also reported that ZA significantly inhibited the bone mass loss of Gruen zones 1, 2, 4, 6 and 7 after THA surgery, which could effectively improve the periprosthetic BMD[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Scott et al. 's study pointed out that ZA can significantly improve BMD loss in Gruen zones 1, 4, 6 and 7 at 1 and 2 years after THA[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In 2017, Huang et al. pointed out that ZA can effectively restore the loss of periprosthetic BMD after cementless THA, especially the proximal femur (Gruen zones 1 and 7). And bone turnover markers (bone-specific alkaline phosphatase and n-terminal peptide of type I procollagen) were inhibited after ZA administration until 2 years after surgery[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, the systemic BMD and periprosthetic BMD of ZA group after surgery were significantly better than those of the control group. As for BMD of various periprosthesis zones, the BMD of Gruen zones 1, 2, 4, 6 and 7 of ZA group one year after surgery was significantly higher than that of the control group, which was similar to the results of previous relevant studies and further confirmed that ZA can effectively improve systemic BMD and periprosthetic BMD, while calcium and vitamin supplementation alone cannot effectively prevent osteoporosis. In conclusion, the application of ZA after THA is an effective method to prevent osteoporosis.\u003c/p\u003e \u003cp\u003eZA also affects bone metabolism related indicators (e.g., 25-hydroxyvitamin D, P1NP, OCN and β-CTX). The bone metabolism related indicator can reflect the changes of bone metabolism in the whole body, help to judge the type of bone turnover, distinguish primary and secondary osteoporosis, and suggest whether treatment is effective, as well as the risk of bone loss and fracture to a certain extent. The deficiency of 25 hydroxyvitamin D will lead to the decrease of serum calcium, and then lead to osteoporosis[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. P1NP and osteocalcin are indicators reflecting the ability of OCN, and when their levels increase, the body's osteogenic activity is more active[\u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. β-CTX is an indicator of the activity of human osteoclasts, and its clinical significance is to show the degree of osteoclast absorption of bone. Studies have shown that bone specific alkaline phosphatase and N-terminal peptide of type I procollagen were significantly improved when ZA was given after THA until 2 years after surgery[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, we made a comparative analysis of these four bone metabolism indicators. At one year after surgery, 25 hydroxyvitamin D and P1NP in ZA group were significantly higher than those in control group, and β-CTX specific sequences was significantly lower than those in control group. This is similar to previous research.\u003c/p\u003e \u003cp\u003eWhen applying ZA, we need to pay attention to the safety of ZA. After 6 weeks of administration of ZA, the serum calcium level will decrease, etc., so we need to pay attention to giving patients calcium supplements[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Increased creatinine may also occur after the application of ZA, which requires close attention to patients' kidney function[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In addition, with the long-term application of ZA, jaw necrosis is the most serious complication, and atypical femoral fracture also exists, which requires close attention[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe purpose of THA is to relieve the pain symptoms of patients with hip lesions, and at the same time restore the biomechanical structure of hip joint, rebuild the biomechanical structure of hip joint, and restore the function of hip joint[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. A delayed bone resorption process called \"stress shielding\" occurs in the proximal region of the femur, which is related to the biomechanical characteristics of the bone implant structure and the stiffness difference between the prosthesis and the surrounding bone. The stress shielding tends to be stable at one year after surgery[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In our study, the improvement of HHS indicates the positive effect of ZA on the functional recovery of osteoporosis patients after THA. On the one hand, it inhibits the bone loss around the prosthesis caused by stress shielding and enhances the fixation and stability of the implant. On the other hand, it improves the bone density of the whole body and helps improve the quality of life of osteoporosis patients[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Maintaining the acetabular height after THA is of great significance for maintaining the stability of the hip joint and preventing the unequal length of the lower limbs. The reduction of the acetabular height is related to the inward and downward movement of the rotation center, which can affect the postoperative recovery of patients. At the same time, maintaining acetabular deviation after THA is of great significance to further strengthen the stability of hip joint, reduce the wear of prosthesis on surrounding bone, improve hip joint motion, and increase the degree of extension[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. The selection of prostheses with appropriate parameters and installation Angle, and the maintenance of appropriate acetabular height, may be beneficial to further improve the hip function of patients after THR. In addition, postoperative improvement of the bone strength around the prosthesis can effectively maintain the stability of the prosthesis, thus reducing the postoperative changes in acetabular height and acetabular deviation.\u003c/p\u003e \u003cp\u003eIn this study, there was no significant difference in acetabular height and acetabular deviation between the two groups before surgery. At 1 year after surgery, the acetabular height and acetabular deviation in the ZA group were significantly higher than those in the control group. This suggests that the application of ZA after THA has some significance in maintaining the biomechanics of hip joint, which may be related to the improvement of periprosthetic BMD. The abnormal biomechanics after THA results in increased compression of the prosthesis on surrounding bone and increased stress, which can accelerate bone loss and lead to decreased periprosthetic BMD, which in turn can lead to weaker stability of the prosthesis, forming a vicious cycle. Therefore, stopping the vicious cycle by increasing the periprosthetic BMD is an option.\u003c/p\u003e \u003cp\u003eIn this study, only 2 cases of prosthesis loosening occurred in the control group, which failed to form a meaningful statistical analysis. The stability of early implants is mainly based on implant design and cortical structure. ZA acts on bone trabeculae, promotes bone integration and bone growth after a few weeks to a few months, and can reduce the incidence of prosthesis loosening[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Therefore, in the future, we will further extend the follow-up time and maintain the injection of ZA in the second and third years. To further observe the effect of ZA on prosthesis loosening after THA. In studies on the use of bisphosphonate and aseptic loosening after THA, postoperative bisphosphonate treatment can reduce osteoclast activity, thereby improving the implant-host bone integration process and lasting implant fixation, thereby reducing the risk of aseptic loosening[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In addition, studies have pointed out that bisphosphonates can significantly improve the revision rate after THA, and that the positive effect of bisphosphonates is obvious only when treatment begins after the initial THA[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere are also some limitations in this study, mainly focusing on follow-up time and sample size, but the results of this study are similar to those of previous studies, and the results are more convincing. In the future, we will further expand the sample size and increase the follow-up time to further confirm the clinical and radiographic findings after the application of ZA. In addition, in the study, some patients lacked the results of blood calcium and renal function at a certain time before or after surgery, so we did not include the results of blood calcium and renal function in the statistical analysis, which are related to the adverse results of ZA application. Therefore, we will further improve this part in the subsequent study.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eIn conclusion, the application of ZA after THA can effectively improve the periprosthetic BMD (Gruen zones 1, 2, 4, 6, 7), maintain the stability of the prosthesis, and reduce the biomechanical changes of hip joint and the incidence of prosthesis loosening, which may be an effective method to prevent osteoporosis after total hip arthroplasty.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003ezoledronic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eZA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003ebone mineral density\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eBMD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003etotal hip arthroplasty\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eTHA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eprocollagen 1 intact N-terminalz\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eP1NP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eosteocalcin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eOCN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026beta;-type Ⅰ collagen carboxy-terminal peptide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026beta;-CTX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003ebody mass index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting of interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZhendong\u0026nbsp;Xu,\u0026nbsp;Zhuang Du, Qing Li, Xin Wang, Zi\u0026nbsp;Wang, Hua Shao, Yutong Hu, Mozhen,Lu declare that they have no conflict of interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors are grateful to the patients and their family members for their participation. Thanks for all doctors and nursing staff involved in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by project 2022JJ13SN085.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients sign informed consent forms for the release of their data and photos.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are not publicly available because they were part of patients\u0026rsquo; records but are available as a de-identified data sheet from the correspond- ing author upon reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZX, QL, ML and YH set up the conception and designed the research. ZX, XW, ZW, ZD collected and interpreted patient\u0026rsquo;s clinical information. ZX, ZD and YH drafted the manuscript. ZX, YH and ML critically reviewed, revised the manuscript and supervised the study. All authors revised the paper critically for intellectual content and approved the final version. All authors agree to be accountable for the work and to ensure that any questions relating to the accuracy and integrity of the paper are investigated and properly resolved.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Ethical approval was obtained from the Ethics Committee of Dalian Central Hospital (YN2024-003-01).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDelsmann MM, Strahl A, Muhlenfeld M\u003cem\u003e, et al.\u003c/em\u003e High prevalence and undertreatment of osteoporosis in elderly patients undergoing total hip arthroplasty. Osteoporos Int. 2021;32(8):1661-8. doi: 10.1007/s00198-021-05881-y. \u003c/li\u003e\n\u003cli\u003eZhou X, Chen M, Yu W\u003cem\u003e, et al.\u003c/em\u003e Uncemented versus cemented total hip arthroplasty for displaced femoral neck fractures in elderly patients with osteoporosis: A retrospective analysis. J Int Med Res. 2020;48(8):300060520944663. doi: 10.1177/0300060520944663. \u003c/li\u003e\n\u003cli\u003eZhou W, Liu Y, Guo X\u003cem\u003e, et al.\u003c/em\u003e Effects of zoledronic acid on bone mineral density around prostheses and bone metabolism markers after primary total hip arthroplasty in females with postmenopausal osteoporosis. Osteoporos Int. 2019;30(8):1581-9. doi: 10.1007/s00198-019-05005-7. \u003c/li\u003e\n\u003cli\u003eJia F, Ruan L, Du C\u003cem\u003e, et al.\u003c/em\u003e The nanoformula of zoledronic acid and calcium carbonate targets osteoclasts and reverses osteoporosis. Biomaterials. 2023;296:122059. doi: 10.1016/j.biomaterials.2023.122059. \u003c/li\u003e\n\u003cli\u003eTreurniet S, Bevers M, Wyers CE\u003cem\u003e, et al.\u003c/em\u003e Bone Microarchitecture and Strength Changes During Teriparatide and Zoledronic Acid Treatment in a Patient with Pregnancy and Lactation-Associated Osteoporosis with Multiple Vertebral Fractures. Calcif Tissue Int. 2023;112(5):621-7. doi: 10.1007/s00223-023-01066-3. \u003c/li\u003e\n\u003cli\u003eM U, Ethiraj P, Nazar SM\u003cem\u003e, et al.\u003c/em\u003e Does Zoledronic Acid Provide a Good Clinical Outcome in Patients With Chronic Back Pain Associated With Vertebral Osteoporosis? Cureus. 2023;15(1):e33328. doi: 10.7759/cureus.33328. \u003c/li\u003e\n\u003cli\u003eReid IR, Brown JP, Burckhardt P\u003cem\u003e, et al.\u003c/em\u003e Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med. 2002;346(9):653-61. doi: 10.1056/NEJMoa011807. \u003c/li\u003e\n\u003cli\u003eLiang BC, Shi ZY, Wang B\u003cem\u003e, et al.\u003c/em\u003e Intravenous Zoledronic Acid 5 mg on Bone Turnover Markers and Bone Mineral Density in East China Subjects with Newly Diagnosed Osteoporosis: A 24-month Clinical Study. Orthop Surg. 2017;9(1):103-9. doi: 10.1111/os.12307. \u003c/li\u003e\n\u003cli\u003eBlack DM, Delmas PD, Eastell R\u003cem\u003e, et al.\u003c/em\u003e Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356(18):1809-22. doi: 10.1056/NEJMoa067312. \u003c/li\u003e\n\u003cli\u003eFu GT, Lin LJ, Sheng PY\u003cem\u003e, et al.\u003c/em\u003e Efficiency of Zoledronic Acid in Inhibiting Accelerated Periprosthetic Bone Loss After Cementless Total Hip Arthroplasty in Osteoporotic Patients: A Prospective, Cohort Study. Orthop Surg. 2019;11(4):653-63. doi: 10.1111/os.12513. \u003c/li\u003e\n\u003cli\u003eCheng YT, Liao J, Zhou Q\u003cem\u003e, et al.\u003c/em\u003e Zoledronic acid modulates osteoclast apoptosis through activation of the NF-kappaB signaling pathway in ovariectomized rats. Exp Biol Med (Maywood). 2021;246(15):1727-39. doi: 10.1177/15353702211011052. \u003c/li\u003e\n\u003cli\u003eKameda Y, Aizawa M, Sato T\u003cem\u003e, et al.\u003c/em\u003e Zoledronic Acid-Loaded beta-TCP Inhibits Tumor Proliferation and Osteoclast Activation: Development of a Functional Bone Substitute for an Efficient Osteosarcoma Treatment. Int J Mol Sci. 2021;22(4). doi: 10.3390/ijms22041889. \u003c/li\u003e\n\u003cli\u003eTai TW, Su FC, Chen CY\u003cem\u003e, et al.\u003c/em\u003e Activation of p38 MAPK-regulated Bcl-xL signaling increases survival against zoledronic acid-induced apoptosis in osteoclast precursors. Bone. 2014;67:166-74. doi: 10.1016/j.bone.2014.07.003. \u003c/li\u003e\n\u003cli\u003eZhao X, Hu D, Qin J\u003cem\u003e, et al.\u003c/em\u003e Effect of bisphosphonates in preventing femoral periprosthetic bone resorption after primary cementless total hip arthroplasty: a meta-analysis. J Orthop Surg Res. 2015;10:65. doi: 10.1186/s13018-015-0206-8. \u003c/li\u003e\n\u003cli\u003eGao J, Gao C, Li H\u003cem\u003e, et al.\u003c/em\u003e Effect of zoledronic acid on reducing femoral bone mineral density loss following total hip arthroplasty: A meta-analysis from randomized controlled trails. Int J Surg. 2017;47:116-26. doi: 10.1016/j.ijsu.2017.08.559. \u003c/li\u003e\n\u003cli\u003eScott DF, Woltz JN, Smith RR. Effect of zoledronic acid on reducing femoral bone mineral density loss following total hip arthroplasty: preliminary results of a prospective randomized trial. J Arthroplasty. 2013;28(4):671-5. doi: 10.1016/j.arth.2012.08.007. \u003c/li\u003e\n\u003cli\u003eHuang TW, Wang CJ, Shih HN\u003cem\u003e, et al.\u003c/em\u003e Bone turnover and periprosthetic bone loss after cementless total hip arthroplasty can be restored by zoledronic acid: a prospective, randomized, open-label, controlled trial. BMC Musculoskelet Disord. 2017;18(1):209. doi: 10.1186/s12891-017-1577-2. \u003c/li\u003e\n\u003cli\u003eMorrison RJM, Bunn D, Gray WK\u003cem\u003e, et al.\u003c/em\u003e VASO (Vitamin D and Arthroplasty Surgery Outcomes) study - supplementation of vitamin D deficiency to improve outcomes after total hip or knee replacement: study protocol for a randomised controlled feasibility trial. Trials. 2017;18(1):514. doi: 10.1186/s13063-017-2255-2. \u003c/li\u003e\n\u003cli\u003eNawabi DH, Chin KF, Keen RW\u003cem\u003e, et al.\u003c/em\u003e Vitamin D deficiency in patients with osteoarthritis undergoing total hip replacement: a cause for concern? J Bone Joint Surg Br. 2010;92(4):496-9. doi: 10.1302/0301-620X.92B3.23535. \u003c/li\u003e\n\u003cli\u003eXu Y, Shen L, Liu L\u003cem\u003e, et al.\u003c/em\u003e Undercarboxylated Osteocalcin and Its Associations With Bone Mineral Density, Bone Turnover Markers, and Prevalence of Osteopenia and Osteoporosis in Chinese Population: A Cross-Sectional Study. Front Endocrinol (Lausanne). 2022;13:843912. doi: 10.3389/fendo.2022.843912. \u003c/li\u003e\n\u003cli\u003eRoomi AB, Mahdi Salih AH, Noori SD\u003cem\u003e, et al.\u003c/em\u003e Evaluation of Bone Mineral Density, Serum Osteocalcin, and Osteopontin Levels in Postmenopausal Women with Type 2 Diabetes Mellitus, with/without Osteoporosis. J Osteoporos. 2022;2022:1437061. doi: 10.1155/2022/1437061. \u003c/li\u003e\n\u003cli\u003eSun Y, Xiao Y, Chen L\u003cem\u003e, et al.\u003c/em\u003e Application value of serum osteocalcin and bone mineral density detection in middle-aged and elderly healthy physical examination. Minerva Med. 2021;112(6):829-31. doi: 10.23736/S0026-4806.20.06710-5. \u003c/li\u003e\n\u003cli\u003eMiyaoka D, Imanishi Y, Yano M\u003cem\u003e, et al.\u003c/em\u003e Effects of burosumab on osteocalcin and bone mineral density in patient with 15-year history of nonremission tumor-induced osteomalacia initially treated with conventional therapy: Case report. Bone Rep. 2020;13:100736. doi: 10.1016/j.bonr.2020.100736. \u003c/li\u003e\n\u003cli\u003eCurraj E, Gonzalez Rodriguez E. [Side effects of osteoporosis treatments: how to explain them to patients?]. Rev Med Suisse. 2023;19(823):746-51. doi: 10.53738/REVMED.2023.19.823.746. \u003c/li\u003e\n\u003cli\u003eKhan M, Cheung AM, Khan AA. Drug-Related Adverse Events of Osteoporosis Therapy. Endocrinol Metab Clin North Am. 2017;46(1):181-92. doi: 10.1016/j.ecl.2016.09.009. \u003c/li\u003e\n\u003cli\u003eArdestani MM, Amenabar Edwards PP, Wimmer MA. Prediction of Polyethylene Wear Rates from Gait Biomechanics and Implant Positioning in Total Hip Replacement. Clin Orthop Relat Res. 2017;475(8):2027-42. doi: 10.1007/s11999-017-5293-x. \u003c/li\u003e\n\u003cli\u003eLi J, McWilliams AB, Jin Z\u003cem\u003e, et al.\u003c/em\u003e Unilateral total hip replacement patients with symptomatic leg length inequality have abnormal hip biomechanics during walking. Clin Biomech (Bristol, Avon). 2015;30(5):513-9. doi: 10.1016/j.clinbiomech.2015.02.014. \u003c/li\u003e\n\u003cli\u003eHsu AHS, Yen CH, Kuo FC\u003cem\u003e, et al.\u003c/em\u003e Zoledronic Acid Ameliorates the Bone Turnover Activity and Periprosthetic Bone Preservation in Cementless Total Hip Arthroplasty. Pharmaceuticals (Basel). 2022;15(4). doi: 10.3390/ph15040420. \u003c/li\u003e\n\u003cli\u003eLiu Y, Xu JW, Li MY\u003cem\u003e, et al.\u003c/em\u003e Zoledronic Acid for Periprosthetic Bone Mineral Density Changes in Patients With Osteoporosis After Hip Arthroplasty-An Updated Meta-Analysis of Six Randomized Controlled Trials. Front Med (Lausanne). 2021;8:801282. doi: 10.3389/fmed.2021.801282. \u003c/li\u003e\n\u003cli\u003eMahmood SS, Mukka SS, Crnalic S\u003cem\u003e, et al.\u003c/em\u003e Association between changes in global femoral offset after total hip arthroplasty and function, quality of life, and abductor muscle strength. A prospective cohort study of 222 patients. Acta Orthop. 2016;87(1):36-41. doi: 10.3109/17453674.2015.1091955. \u003c/li\u003e\n\u003cli\u003eLittle NJ, Busch CA, Gallagher JA\u003cem\u003e, et al.\u003c/em\u003e Acetabular polyethylene wear and acetabular inclination and femoral offset. Clin Orthop Relat Res. 2009;467(11):2895-900. doi: 10.1007/s11999-009-0845-3. \u003c/li\u003e\n\u003cli\u003ePegios VF, Kenanidis E, Tsotsolis S\u003cem\u003e, et al.\u003c/em\u003e Bisphosphonates\u0026apos; use and risk of aseptic loosening following total hip arthroplasty: a systematic review. EFORT Open Rev. 2023;8(11):798-808. doi: 10.1530/EOR-22-0121. \u003c/li\u003e\n\u003cli\u003ePrieto-Alhambra D, Lalmohamed A, Abrahamsen B\u003cem\u003e, et al.\u003c/em\u003e Oral bisphosphonate use and total knee/hip implant survival: validation of results in an external population-based cohort. Arthritis Rheumatol. 2014;66(11):3233-40. doi: 10.1002/art.38789. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"total hip arthroplasty, osteoporosis, zoledronic acid, bone mineral density, bone metabolism, biomechanics","lastPublishedDoi":"10.21203/rs.3.rs-4213460/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4213460/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e To investigate the effects of zoledronic acid (ZA) combined with calcium tablets and calcitriol on bone mineral density (BMD), hip function after total hip arthroplasty (THA).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e 50 elderly patients with THA from January 2022 to December 2022 were included in this study. The ZA group was given ZA combined with calcium tablets and calcitriol, while the control group was only given calcium tablets and calcitriol. The preoperative and postoperative BMD, bone metabolism-related indexes, Harris score, incidence of prosthesis loosening and hip biomechanics between the two groups were compared.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e There were no significant differences in age, sex, Body Mass Index. Postoperative systemic BMD and periprosthetic BMDin ZA group were higher than those in the control group. The BMD in Gruen zones 1, 6 and 7 at postoperative 6 months, Gruen zones 1, 2, 4, 6 and 7 at postoperative 1 year was significantly higher than that in the control group. Postoperative 1 year, the 25-hydroxyvitamin D, procollagen 1 intact N-terminal and Harris score in ZA group were higher than those in control group, the β-type Ⅰ collagen carboxy-terminal peptide was lower. Acetabular height and acetabular deviation in ZA group were significantly better than those in control group at postoperative 1 year. Only 2 cases of prosthesis loosening in control group.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e ZA can effectively restore the loss of BMD, maintain the biomechanical stability of the hip, and reduce the incidence of prosthesis loosening. It is an effective method to prevent osteoporosis after THA.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration:\u003c/strong\u003e This study has been registered in the Chinese Clinical Registry (registration No.: ChiCTR2200065144, date: January 2022)\u003c/p\u003e","manuscriptTitle":"Clinical significance of zoledronic acid in combination with calcium tablets and calcitriol for hip biomechanics and bone mineral density after total hip replacement: a prospective randomized controlled trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-08 17:44:16","doi":"10.21203/rs.3.rs-4213460/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"14e512ed-808d-4d28-b727-c166f7632e15","owner":[],"postedDate":"April 8th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-15T15:07:31+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-08 17:44:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4213460","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4213460","identity":"rs-4213460","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}