Prevention of Periprosthetic Bone Loss After Total Hip Replacement by Annual Bisphosphonate Therapy

Study Overview
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Brief Summary
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Periprosthetic bone loss caused by stress-shielding effect, a phenomenon of bone atrophy under mechanical unloading after THR implantation, further compromises the longevity of implant. The prospective randomized study is aimed to investigate the periprosthetic bone loss after primary total hip replacements.

Detailed Description
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This study is a prospective, randomized, open-label clinical trial. The study will be performed in patients after obtaining informed consent. Group assignment is by drawing a sealed envelops based on random table. (1) Group 1: Experimental group 30 cases, Aclasta® (Zoledronic acid 5mg/100ml) is given intravenously on the 4th postoperative day and one year after the total hip replacement, (2) Group 2: Control group, 30 cases, no bisphosphonate is given to the patients. Only the unilateral coxarthrosis will be recruited for the study. Patients will be analyzed with (1) DXA study (2) Clinical assessment (Harris hip score and SF-12) (3) X-ray (4) serum marker of bone turnover. Patients will be scheduled for specified examinations preoperatively, postoperatively 6 weeks, 3 months, 6 months, 12 months, and 24 months.

Official Title
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Investigation on the Prevention of Periprosthetic Bone Loss After Total Hip Replacement by Annual Bisphosphonate Therapy: A Prospective Randomized Clinical Trial

Conditions
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Prevention of BMD Loss After THR, Serum Markers of Bone Turnover, Functional Outcomes

Intervention / Treatment
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* Drug: Aclasta
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female,between 35 and 85 years of age Indicated for Total hip replacement for various hip diseases Has preoperative DXA study within 3 months before the total hip replacement procedure or willing to receive preoperative DXA study as a baseline comparison Signed written informed consent Standard transgluteal approach for total hip replacement using Zimmer Triology Cup and Versys Fiber Metal Taper Stem with metal to highly cross-linked polyethylene bearing surface Exclusion Criteria: Any prior use of intravenous bisphosphonate within the last 2 years Uncontrolled seizure disorders associated with falls A history of invasive malignancy of any organ system, treated or untreated, within the past five years; excluding, basal cell or squamous cell carcinoma of the skin, colonic polyps with non-invasive malignancy which have been removed Carcinoma in situ of the uterine cervix History of osteogenesis imperfecta, multiple myeloma, or Paget's disease Active primary hyperparathyroidism History of iritis or uveitis Self-reported history of diabetic nephropathy or retinopathy AST or ALT more than twice the upper limit of normal Alkaline phosphatase more than twice the upper limit of normal Serum calcium 2.75 mmol/L (11.0 mg/dL) Baseline renal insufficiency (calculated creatinine clearance 35 ml/min) History of hypersensitivity to bisphosphonates Use of any investigational drug(s) and/or devices within 30 days prior to randomization Any medical or psychiatric condition which, in the Investigator's opinion, would preclude the participant from adhering to the Protocol or completing the trial per protocol Use of hip protectors With implant or prosthesis on the contralateral hip joint

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aclasta<br>Aclasta IV once annual for 2 years | Drug: Aclasta<br>* Aclasta once annually for 2 years<br>|
| Placebo Comparator: Placebo<br>Placebo group | Drug: Placebo<br>* No IV aclasta<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| bone mineral density [g/cm2] of the 7 Gruen zones | bone mineral density measured by dual energy x-ray absorptiometry | 5 years | 
| bone mineral density change relative to the baseline values of the 7 Gruen zones | bone mineral density measured by dual energy x-ray absorptiometry | 5 years | 
| implant loosening or migration | check the implant position by serial standard X ray follow-up | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum alkaline phosphatase |  | 5 years | 
| serum calcium level |  | 5 years | 
| serum phosphate level |  | 5 years | 
| serum osteocalcin level |  | 5 years | 
| serum N-telopeptide procollagen level |  | 5 years | 
| serum creatinine level | renal function and glomerular filtration rate | 5 years | 
| serum alanine aminotransferase level | liver function | 5 years | 
| serum aspartate aminotransferase level | liver function | 5 years | 
| harris hip score | hip function measurement | 5 years | 
| short form-12 | life quality measurement | 5 years | 
| University of California Los Angeles Activity Score | functional and activity evaluation, 10 point scale | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bisphosphonate, Total hip replacement, functional outcomes, bone mineral density