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Zoledronic Acid Ameliorates the Bone Turnover Activity and Periprosthetic Bone Preservation in Cementless Total Hip Arthroplasty.

ABSTRACT: The administration of zoledronic acid (ZA) to patients who received cementless total hip arthroplasty (THA) has been reported to reduce bone turnover markers (BTMs) and increase bone mineral density (BMD). The effects of two-dose ZA versus placebo on cementless THA patients were analyzed in this five-year extension study. Alkaline phosphatase (ALP), osteocalcin (OC), procollagen 1 intact N-terminal propeptide (P1NP), serum calcium, renal function, radiological findings, and functional outcomes were compared in 49 patients, and the periprosthetic BMD of seven Gruen zones were compared in 19 patients. All the patients had normal renal function and calcium levels at their final follow-up. The mean ALP level in the ZA group was significantly lower at the fifth year, mean OC levels were significantly lower at the second and fifth year, and mean P1NP levels were significantly lower from 6 weeks to 5 years as compared with the control group. Fifth-year BMD levels were not found to be different between the ZA and control groups. The BMD Change Ratios in the ZA group were significantly increased in Gruen zone 6 at 1, 2, and 5 years. Our study results suggest that short-term ZA treatment with a subsequent 4-year drug holiday may inhibit serum BTMs and provide periprosthetic bone preservation at five years without adverse events.

SUBMITTER: Hsu AHS

PROVIDER: S-EPMC9030653 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Zoledronic Acid Ameliorates the Bone Turnover Activity and Periprosthetic Bone Preservation in Cementless Total Hip Arthroplasty.

Hsu Allen Herng Shouh AHS Yen Chun-Hsien CH Kuo Feng-Chih FC Wu Cheng-Ta CT Huang Tsan-Wen TW Cheng Juei-Tang JT Lee Mel S MS

Pharmaceuticals (Basel, Switzerland) 20220330 4

The administration of zoledronic acid (ZA) to patients who received cementless total hip arthroplasty (THA) has been reported to reduce bone turnover markers (BTMs) and increase bone mineral density (BMD). The effects of two-dose ZA versus placebo on cementless THA patients were analyzed in this five-year extension study. Alkaline phosphatase (ALP), osteocalcin (OC), procollagen 1 intact N-terminal propeptide (P1NP), serum calcium, renal function, radiological findings, and functional outcomes w ...[more]

PMID: 35455417

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Project description:BackgroundAlthough the loss of bone mineral density (BMD) after total hip arthroplasty (THA) is a known problem, it remains unresolved. This study prospectively examined the effect of zoledronic acid (ZA) on bone turnover and BMD after cementless THA.MethodsBetween January 2010 and August 2011, 60 patients who underwent cementless THA were randomly assigned to receive either ZA infusion or placebo (0.9% normal saline only) postoperatively. ZA was administered at 2 day and 1 year postoperatively. Periprosthetic BMD in seven Gruen zones was assessed preoperatively and at given time points for 2 years. Serum markers of bone turnover, functional scales, and adverse events were recorded.ResultsEach group contained 27 patients for the final analysis. The loss of BMD across all Gruen zones (significantly in zones 1 and 7) up to 2 years postoperatively was noted in the placebo group. BMD was significantly higher in the ZA group than in the placebo group in Gruen zones 1, 2, 6, and 7 at 1 year and in Gruen zones 1, 6, and 7 at 2 years (p < 0.05). Compared with baseline measures of BMD, the ZA group had increased BMD in zones 1, 2, 4, 5, 6, and 7 at 1 year and in zones 1, 4, 6, and 7 at 2 years (p < 0.05). Serum bone-specific alkaline phosphatase and N-telopeptide of procollagen I levels were significantly increased at 6 weeks in the placebo group and decreased after 3 months in the ZA group. A transient decrease in osteocalcin level was found at 6 months in the ZA group. Functional scales and adverse events were not different between the two groups.ConclusionsThe loss of periprosthetic BMD, especially in the proximal femur (zones 1 and 7), after cementless THA could be effectively reverted using ZA. In addition, bone turnover markers were suppressed until 2 years postoperatively following ZA administration.Trial registrationChang Gung Memorial Hospital Protocol Record 98-1150A3, Prevention of Periprosthetic Bone Loss After Total Hip Replacement by Annual Bisphosphonate Therapy, has been reviewed and will be made public on ClinicalTrials.gov.Trial registration numberNCT02838121 . Registered on 19 July, 2016.

Project description:Antiresorptive denosumab is known to improve the quality and strength of cortical bone in the proximal femurs of osteoporotic women, but its efficacy in preventing periprosthetic bone loss and reducing femoral stem migration has not been studied in women undergoing cementless total hip arthroplasty. We conducted a single-center, randomized, double-blinded, placebo-controlled trial of 65 postmenopausal women with primary hip osteoarthritis and Dorr type A or B proximal femur anatomy. The patients randomly received subcutaneous injections of denosumab 60?mg or placebo once every 6 months for 12 months, starting 1 month before surgery. The primary endpoint was the change in bone mineral density (BMD) of the proximal femur (Gruen zone 7) at week 48, and the secondary endpoint was stem subsidence measured by radiostereometric analysis (RSA) at week 48. Exploratory endpoints included changes in BMDs of the contralateral hip, lumbar spine and distal radius, serum levels of bone turnover markers, walking speed, walking activity, patient-reported outcome measures, and radiographic assessment of stem osseointegration. The participants underwent vertebral-fracture assessment in an extension safety study at 3 years. Denosumab significantly decreased bone loss in the medial femoral neck (zone 7) and increased periprosthetic BMD in the greater trochanteric region (zone 1) and lesser trochanteric region (zone 6). Denosumab did not reduce temporary femoral stem migration. The migration occurred mainly during the settling period (0 to 12 weeks) after implantation of the prosthesis. All of the stems osseointegrated, as evaluated by RSA and radiographs. There were no intergroup differences in functional recovery. Discontinuation of denosumab did not lead to any adverse events. In conclusion, denosumab increased periprosthetic BMD in the clinically relevant regions of the proximal femur, but the treatment response was not associated with any reduction of initial stem migration. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Project description:Mortality related to femoral neck fractures remains a challenging health issue, with a high mortality rate at 1 year of follow-up. Three modifiable factors appear to be under control of the surgeon: the choice of the implant, the use of cement and the timing before surgery. The aim of this research project was to study the impact on mortality each of these risk factors play during the management of femoral neck fractures. A large retrospective epidemiological study was performed using a national database of the public healthcare system. The inclusion criteria were patients who underwent joint replacement surgery after femoral neck fracture during the years 2015 to 2017. All data points were available for at least 2 years after the fracture. The primary outcome was mortality within 2 years following the surgery. We evaluated the association between mortality and the type of the implant hemiarthroplasty (HA) versus total hip arthroplasty (THA), cemented versus non cemented femoral stem as well as the timing from fracture to surgical procedure. A multivariate analysis was performed including age, gender, comorbidities/autonomy scores, social category, and obesity. We identified 96,184 patients who matched the inclusion criteria between 2015 and 2017. 64,106 (66%) patients underwent HA and 32,078 (33.4%) underwent THA. After multivariate analysis including age and comorbidities, patients who underwent surgery after 72 h intra-hospital had a higher risk of mortality: Hazard Ratio (HR) = 1.119 (1.056-1.185) p = 0.0001 compared to the group who underwent surgery within 24 h. THA was found to be a protective factor HR = 0.762 (0.731-0.795) p < 0.0001. The use of cement was correlated with higher mortality rate: HR = 1.107 (1.067-1.149) p < 0.0001. Three key points are highlighted by our study in the reduction of mortality related to femoral neck fracture: the use of hemiarthroplasty a surgery performed after 48 h and the use of cement for femoral stem fixation adversely affect mortality risk.

Project description:BackgroundPeriprosthetic fractures are a devastating complication of total hip arthroplasty (THA) and are associated with significantly higher mortality rates in the postoperative period. Given the strain that periprosthetic fractures place on the patient as well as the healthcare system, identifying and optimizing medical comorbidities is essential in reducing complications and improving outcomes.MethodsAll THA with primary indications of osteoarthritis from 2007 to 2020 were queried from the National Surgical Quality Improvement Program database. Demographic data, preoperative laboratory values, medical comorbidities, hospital course, and acute complications were collected and compared between patients with and without readmission for a periprosthetic fracture. A multivariate logistic regression analysis was performed to determine associated independent risk factors for periprosthetic fractures after index THA.ResultsThe analysis included 275,107 patients, of which 2539 patients were readmitted for periprosthetic fractures. Patients with postoperative fractures were more likely to be older (>65 years), females, BMI >40, and increased medical comorbidities. Preoperative hypoalbuminemia, hyponatremia, and abnormal estimated glomerular filtration rates were independent risk factors for sustaining a periprosthetic fracture and readmission within 30 days. Modifiable patient-related factors of concurrent smoking and chronic steroid use at the time of index THA were also independent risk factors for periprosthetic fractures. Inpatient metrics of longer length of stay, operative time, and discharge to rehab predicted postarthroplasty fracture risk. Readmitted fracture patients subsequently had increased risks of developing a surgical site infection, urinary tract infection, and requiring blood transfusions.ConclusionsPatients with hypoalbuminemia, hyponatremia, and abnormal estimated glomerular filtration rate are at increased risk for sustaining periprosthetic fractures after THA. Preoperative optimization with close monitoring of metabolic markers and modifiable risk factors may help not only prevent acute periprosthetic fractures but also associated infection and bleeding risk with fracture readmission.

Project description:Introduction: Periprosthetic bone mineral density (BMD) loss following total hip arthroplasty (THA) may threaten the survival of the implant, especially in patients with osteoporosis. Zoledronic acid (ZA) is the representative of the third generation of bisphosphonates, which were effective in reducing bone loss in conditions associated with accelerated bone turnover. The aim of this study was to evaluate the efficacy and safety of ZA in patients with osteoporosis after THA. Methods: Randomized controlled trials (RCTs) associated with ZA and THA were searched from the MEDLINE, PubMed, EMBASE, Wanfang database, and the Web of Science (August 2021). Other methods, such as hand search and email request were also tried. The methodological quality was assessed by the Risk of Bias (RoB) 2.0. Relevant data were abstracted from the included RCTs and authors were contacted when necessary. Results: In this study, six RCTs involving a total of 307 patients were finally included and analyzed. The pooled data demonstrated that significantly less periprosthetic BMD loss in Gruen zone seven had occurred in the ZA-treated patients than in the control patients at 3 months (mean difference [MD] = 4.03%; 95% CI: 0.29-7.76%; P = 0.03), 6 months (MD = 7.04%; 95% CI: 2.12-11.96%; P = 0.005), and 12 months (MD = 7.12%; 95% CI: 0.33-13.92%; P = 0.04). The Harris Hip Score (HHS) was also significantly increased in ZA group at 6 and 12 months after operation (P = 0.03 and P = 0.02, respectively). Influenza-like symptom was found related to the usage of ZA [relative risk (RR) = 7.03, P < 0.0001]. Conclusion: A meta-analysis of six RCTs suggested that ZA was beneficial in maintaining the periprosthetic BMD in patients with osteoporosis at 6 and 12 months after THA. In addition, the HHS was significantly improved in patients treated with ZA. However, the short length of follow-up of the available studies resulted in the lack of analyses regarding the survival of implants including the rate of aseptic loosing, periprosthetic fracture, and revision. It still needs to be determined in research with longer follow-up period. Clinical Trial Registration: Researchregistry.com, identifier: reviewregistry1087.

Dataset Information

Zoledronic Acid Ameliorates the Bone Turnover Activity and Periprosthetic Bone Preservation in Cementless Total Hip Arthroplasty.

Publications

Zoledronic Acid Ameliorates the Bone Turnover Activity and Periprosthetic Bone Preservation in Cementless Total Hip Arthroplasty.

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