Locally Administered Clodronate in the Prevention of Aseptic Implant Loosening

Study Overview
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Brief Summary
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Periprosthetic bone-loss after total hip arthroplasty (THA), detected as an early migration of the prosthesis, may predict later loosening. The investigators hypothesized that by reducing bone resorption after THA with bisphosphonates, it might be possible to achieve better early fixation of the implant. Nineteen patients suffering arthrosis were recruited to a prospective, double-blinded, randomized, placebo-controlled clinical pilot trial. Patients were operated with an uncemented Bimetric stem with tantalum markers, the acetabular cup and liner were chosen by the surgeon. The femoral proximal intramedullary canal was rinsed with 1mM (millimole) clodronate, that was done by adding the clodronate to the 1000 ml 0.9% NaCl (sodium chloride) in nine patients and rinsing solution was the pure 0.9% NaCl for 10 patients. These rinsing packages were labeled only with the code from the pharmacy of the hospital. These patients were followed for two years using radiostereometric analysis (RSA), dual energy x-ray absorptiometry (DXA) and the Harris hip score (HHS). The purpose of the investigator's study was to examine whether the local intraoperative administration of clodronate could reduce periprosthetic bone loss and further stem migration after primary THA.

Official Title
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Could the Intra-operative Clodronate Rinsing Improve the Integration of the Femoral Stem in a Prospective, Double-blinded, Randomized, Placebo-controlled Clinical RSA-study

Conditions
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Hip Arthrosis

Intervention / Treatment
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* Drug: Clodronate
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: hip arthrosis and a primary THA was planned Exclusion Criteria: renal insufficiency hypercalcemia malignant tumors contemporaneously treatment with another bisphosphonate or aminoglycoside

Ages Eligible for Study
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Maximum Age: 73 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
Interventional Model Description: In this prospective, double-blinded, randomized, placebo-controlled clinical trial with two years follow-up period the investigators rinsed the proximal intramedullary cavity of the femur with either clodronate (60 mg clodronate in 1000 ml saline) or saline (1000 ml saline) prior to the application of the femoral stem.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Clodronate<br>1 mM clodronate (60 mg in 1000 ml saline) was used intraoperatively during total hip arthroplasty: before installation of the prosthesis, the rinsing was performed with pulsatile lavage using the clodronate solution. The time for rinsing was about one minute. | Drug: Clodronate<br> <br> |
| Placebo Comparator: Saline<br>1000 ml saline was used intraoperatively during total hip arthroplasty: before installation of the prosthesis, the rinsing was performed with pulsatile lavage using the saline solution. The time for rinsing was about one minute. | Drug: Saline<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal total point motion (MTPM) - migration of the femoral stem | It represents the length of the translation vector of the point in a rigid body that has the greatest motion. It can only have positive values, and is not normally distributed. The reason for using MTPM is that in many cases, motion implies a biological effect of some kind and this effect is liable to be greatest at the point of maximum motion. The parameter has been measured by RSA-methods, which is an accurate method of determining the migration and wear of orthopaedic implants: it determine the precise location of two distinct objects relative to each other in three dimension such as the relative position of the femoral component and the proximal femur. In radiostereometric analysis the position in space of the original object is reconstructed from a two dimensional x-ray film using tantalum beads. Movement between segments is then calculated by localizing each segment in a coordinate system. Lower values represent a better outcome. | 0 to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone mineral density (BMD) in 7 Gruen zones | BMD was measured by dual-energy X-ray absorptiometry, DXA. In clinical use, precision errors are < 5 %. To evaluate the horizontal linear distribution of the BMD, seven Gruen zones, peri-prosthetic sub-regions of interest, ROI (region of interest) were calculated by the software on the anteroposterior view of the proximal femur. The value of BMD is g/cm2 and it estimates the strength of the bone. Higher values/lesser decrease in values represent a better outcome. | 0 to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RSA, DXA, Bisphosphonates, Migration of stem, Aseptic loosening of prosthesis